MED4 - EXAM SET - PART 1

What are the cognitive functions and their specific function?

Specific functions: 1. Memory 2. Visuospatial functions 3. Language 4. Psychomotor functions 5. Attention 6. Executive functions

What is the Facial Feedback hypothesis?

the pattern of muscles during facial expression feeds back into the brain, providing it with information for subjective feel of an emotion Darwin argues that the facial expression of an emotion will intensify it while the suppression of expression will reduce the emotion - in other words, you can alter the intensity of an emotion by altering the intensity of your facial expression

What is the role of the hypothalamus in regulating pain responses?

the responses to pain as a stressor are mediated through the hypothalamus: neuroendocrine changes and some behaviors. Also regulation of pain and overall integration of neuroendocrine and pain responses

How is applied behaviour analysis used?

to improve language and communicative behaviours by using ABA (Applied behavior analysis) techniques to improve language & communicative behaviors use of shaping to build up to more complex behaviours (e.g. in Autism) reinforcement of successive approximations to the desired behaviour - start training simple behaviours and build up gradually to more complex ones

Give some clinical examples of the use of anaesthetics

topical nasal mucosa and wound margins infiltration vicinity of peripheral nerve endings and major nerve trunks in dental practise regional intravenous injection leading to numbing of a larger area of the body in labour/childbirth

What are the stimuli that are able to be detected?

touch, brush, pressure, tickle, temperature (hot, warm, cold), pain able to discriminate

What are the two types of benzodiazepines? Used to treat anxiety

tranquillisers - diazepam (valium)-Treatment of anxiety- but only short term in this case (tolerance/dependence) - chlordiazepoxide (librium)- useful when it comes to treat people coming off - treat withdrawal from alcohol - long duration hypnotics - temazepam - short to intermediate duration

What are the two types of benzodiazepines?

tranquillisers - diazepam (valium) - chlordiazepoxide (librium) - long duration hypnotics - temazepam - short to intermediate duration

What are the types of insomnia?

transient, short term, chronic

what is the main reason for prescribing for analgesic medication ?

treatment of cancer pain i.e. chronic pain for conditions such as arthritis and low back pain

What does a typical hypnogram of adult sleep look like?

typical 8 hour sleep - idealised start off awake fall asleep within ideally 50 minutes go straight into stage 1 long REM sleep go down to stage 2 very rapidly less than 30 minutes from falling asleep then go into stage 3 and 4 sleep spending a lot of time in the slow wave sleep before starting to lighten the sleep then goes back to stage 2 to stage 1 and then to REM takes around 90 minutes for 1 cycle cycle 3 - spending less time in slow wave - sleep is getting lighter and lighter during the 8 hours and spending more time in the REM stage and slow wave sleep is decreasing increae in REM duration during sleep period and its highest in cycle 5

What is the age of onset of Huntington's?

typical age of onset is in mid-life 30-50 years of age however, it is now well recognised can occur at any age from children/teenagers to old age 50% of age of onset relates to CAG repeat number the other 50% relates to other genetic factors (presence of other protective or harmful genes) and potentially environmental factors whatever the age of onset : disease occurs of about 20 years from diagnosis to death

What are the 3 most abundant and well studied opioid receptors?

u, delta and kappa

How does tolerance to morphine work?

u-protein coupled receptors rely on the binding site they have to couple to the G-protein to signal when G protein receptors are exposed repeatedly to as drug, it is desensitised

What are the different electrical activity EEGs can pick up?

alpha (smooth activity of 8-12Hz) beta (irregular activity of 13-30 Hz) theta (intermittent activity of 5-8Hz) delta (regular, synchronous activity of 1-4 Hz) sleep spindles (short bursts of 12-14 Hz) K complexes (sudden sharp waveforms)

What is behaviour therapy?

also known as behaviour modification rooted in the principles of behaviourism - 'we learn from our environment' an action-based approach; relies on experimentally tested principles of learning theory modern approaches have been developed guided by learning theory and applied through innovative techniques in clinical intervention

Where are the sites of action of opioids?

in the spinal cord directly PAG and NRM - drives the inhibitory control pathway

What is the inappropriate effect?

inappropriate or incongruous affect - Most typically occurs in psychotic disorders rather than depressive disorders or in bipolar disorders - occurs across diagnoses but is most typically seen in the context of psychoses where there are symptoms of disorganisation of thought and associated affect the emotional display of the patient is out of keeping with the context within which it occurs; for example, a patient might laugh on hearing some bad news

How can certain medicines help someone to 'chill out'?

increase GABA (inhibitory NT) reduce glutamate (excitatory)

What is behaviour modification designed to do?

increase frequency of existing adaptive behaviours decrease frequency of existing maladaptive behaviours teach new appropriate behaviours - which are adapative

What are the main sites of nociceptor afferent termination?

laminae I and II (the most dorsal laminae)

What information does the cerebellum receive and what does it do?

receives information from the body and assists with the dynamic coordination of movement, balance and posture

What is the treatment of patients with inflammation?

relieve symptoms (pain, swelling, increased temperature) slow or stop the tissue damaging process

Describe repeat instability and anticipation

repeat instability means repeats can expand in subsequent generations an intermediate repeat or a small expansion can increase in size in subsequent generations results in a more severe phenotype in child than in the parent this is known as anticipation

What is REM?

repeated occasions during the night change in EEG and muscle tone decreases dreaming - stage associated with vivid sleep change in heart rate, respiration rate Ocular activity as well can also dream during slow wave - but less vivid and less likely to remember them

Describe triplet repeat instability

repeats can expand due to errors in DNA replication and repair account for normal variation in repeat length beyond a certain size repeats become unstable and more likely to expand full expansion mutations can be inherited from unaffected parents with an intermediate or permutation allele differences in repeat instability observed for maternal vs paternal transmission

What are triplet repeats?

repetitive sequences are common in the genome - often polymorphic (length varies) some repeat sequences lie in genes - changes in length can impact gene function several severe neuromuscular and neurodegenerative disorders associated with changes in repeat length - longer repeats = more severe disease phenotype

What are the functions of the microglia?

resident immune cells - first cells that respond anytime something goes wrong in the brain once activated - they are ramified (retract all their processes), change morphology (become amoeboid) and will become mobile - at this stage, they are actively producing cytokines so up-regulating the pro-inflammatory phenotype produce enzymes and cytokines capable of phagocytosis

What is lacunar stroke?

results from hyaline arteriolosclerosis; this occurs w/hypertension or diabetes small stroke but can be just as deadly

What is an incomplete reflex of vomiting? When does this occur?

retching where the sphincter does not open and nothing is ejected preliminary phase to vomiting

What is the target site for general anaesthetics?

reticular activating system arousal, sleep and wakefulness

What was the intra cranial self-stimulation test conducted? What did it show?

rodent in chamber with a stimulating electrode which fires off if the rodent presses the lever if it is in the hypothalamus and touching the median forebrain bundle, the rodent will continue to press the lever until it dies it will ignore food, hydration linked with motivation and reward pathway

Give an example of a dopamine agonist Why might there be a problem with using dopamine agonists?

ropinirole profile at human D2 - like receptors drugs cannot distinguish between the two receptor types the inhibitory receptors linked to Gi - D2, D3, D4 are all similar in protein structure and the drugs that bind to them

What is the onset/duration of effect of opioids?

route of administration/formulation not important for continual analgesia but essential for as needed-basis of treatment intravenous - 2 minutes. average for most opioids intramuscular - lipophilic drug: 20 minutes oral - normal release 1 hour, sustained 2-4 hours

What needs to be done before you can commence appropriate therapy with someone who has an anxiety disorder?

rule out organic disease

What do the veins look like in a 3D diagram of the brain?

sagittal sinus is running in anterior to posterior direction embedded in the fall is the inferior sagittal sinus directly below it

What are the anatomical terms used to describe the brain?

sagittal view

Are different types of treatment needed for allodynia vs hyperalgesia?

yes Central mechanisms (spinal cord and brain) are different and that means they need different treatment

What is prodrome? What is an aura? What is unilateral throbbing headache usually associated with?What is resolution? What is recovery?

yawning, mood or appetite change (warning phase occurs in 60%) initial visual disturbance - 30 minutes - visual area lost, surrounding area 'shimmers' - 15% of sufferers = Classical migraine + stage 2 unilateral throbbing headache, lasting 4 to 72 hours - photophobia - nausea and vomiting - prostrate - 85% of suffers = Common migraine just stage 2 resolution = usually deep sleep and loss of headache recovery = often get exhaustion

Can seeing fearful faces activate the amygdala?

yes

Can stroke cause dementia?

yes

Do we have a reserve of dopamine?

yes

What are the direct effects of toxins on the peripheral nerves ?

Direct - Diphtheria Indirect - Tetanus/Botulism

What is depression?

Disorder of affect whereby feelings of low mood (sadness) and despair accompany flat affect , loss of interest in daily activities , psychomotor slowing , diverse cognitive symptoms including reduced attention and concentration as well as tendency (bias) towards negative thoughts and evaluations

Diagnostic criteria for multiple sclerosis

Dissemination of multiple CNS inflammatory demyelinating lesion in space and time

What are the standard Huntington disease reports?

If is predictive (has a family member with HD but no symptoms in patient) - Referals only from clinical genetics ○ Referral reason - Diagnostic (Has symptoms of HD) 1. Referrals taken from Neurologists, Specialist Psychiatrists, Care of the Elderly consultants and Clinical Genetics - Predictive (has a family member with HD but no symptoms in patient) 1. Referrals only from Clinical genetics ○ Headline result - Number and Size of the allele(s) repeats detected is reported ○ Interpretation - Whether this confirms a diagnosis of HD or if the patient is likely to develop HD in the future - Advises on addition testing if appropriate ○ Further information - Other relevant testing if no expansion identified - Testing for family members if expansion identified ○ HD allele repeat sizes stated for information

Potential disadvantages of predictive testing for HD

If positive: - Removes hope - Introduces a different type of uncertainty (if and when) - Known risk to offspring - Impact on self/partner/family/friends - Potential problems with insurance/mortagage If negative: - Expectations of a "good" result - "Survivor" guilt

What are sleep spindles?

bursts of rapid, rhythmic brainwave activity during stage 2 sleep separating yourself from your environment from noises, lights separated from awareness of the external environment

What is the function of oligodendrocytes?

myelinate axons

What is white matter?

myelinated axons

How do intracranial pressure receptors mediate nausea? How does the descending inputs from higher centres lead to vomiting?

nausea after head injury or meningitis descending inputs from higher centres arising from the sight or smell of vomit, situations associated with vomiting, psychiatric disorders, or with general stress - thats why when we see stuff , initiates the vomit reflex

How do you assess pain in dementia in patients unable to communicate?

need to asses pain by observation: - facial expression - verbalizations - body movements - changes in interpersonal interactions - changes inactivity patterns or routines - mental status changes

What are the contraindication of benzodiazpines?

Alcohol - causes respiratory depression in combination with alcohol

Pre-disposing factors to pneumococcal meningitis

Immunosuppression, alcohol, diabetes, hyposplenism, myeloma

What is the treatment for Patients with Early onset parkinson's disease and young patients?

Dopamine (D2) agonists leaves the chance to use L-Dopa to be used later in life

How to treat the tremors in parkinson's disease patients?

Muscarinic receptor antagonists

Is corticosteroids effective against acute vomiting ? Are 5-HT3 antagonists effective against Non-chemotherapy vomiting ?

No

Where are opioid receptors found in the brain?

PAG and NRM - Nucleus raphe magnus

What is the symptomology of migraines?

prodrome aura unilateral throbbing headache resolution recovery

What are emotions?

CNS response to certain stimuli output from: - autonomic - hormonal - behavioural - subjective 'feeling' innate and learned elements multiple neural networks involved

What are the possible reasons for parkinson's to occur?

Cell death due to: 1. Oxidative stress 2. Mitochondrial dysfunction 3. Proteasome dysfunction

Does amount of tissue damage determines pain intensity ?

False

What is Broca's aphasia?

"""broken speech"", trouble speaking, halting/jarring speech but you can understand what people are saying

What is Wernicke's aphasia?

"""fluent aphasia"", nothing the person says makes logical sense and you have trouble understanding

Years lived lost due to disability in the world in 2010(DALY)

2. Major depressive disorder 7. anxiety 12. drug use disorders 15. alcohol use disorders 16. schizophrenia 18. bipolar disorder 19. dysthymia (mild depression)

Neuropsychology tests are still appropriate even if tested frequently. F?

False

What is nociceptive pain?

'good' pain sensation associated with the detection of potentially tissue-damaging noxious stimuli primary afferent neurones are sensing the local stimuli that may cause damage to tissue and tells the body to move itself away from the stimuli Pain as an autonomic response - Withdrawal reflex protective - minimize oppurtunity for tissue damage Adaptive , high-threshold pain Early warning system (protective)

What is the limbic system? What position is the limbic system? What circuits does the limbic system contain?

'model' of brain function it is in a transitional position between subcortical nuclei and neo-cortex different circuits connect the functionally related components - amygdala driven circuit, reward circuit, hippocampus circuit

Describe diamorphine or morphine like analagesics

(heroin) - two molecules of morphine combined high lipophilicity = brain penetration rapid broken-down into morphine in the CNS more potent and addictive than morphine is used clinically

What is the neurological manifestation of Huntingtons?

- 10% red brain weight. Enlarged lateral ventricles. Massive reduction in caudate nucleus & putamen (= striatum) due neuronal degen therein

What is mindfulness based therapy(MBCT)?

- Derived from ancient Buddhist & yoga practices - A process that leads to a mental state of non-judgemental awareness and acceptance of the present - The present moment experience include one's sensations , thoughts , bodily states, consciousness and the environment - Self-regulation and orientation toward the present moment helps to counter the effect of stressors

How to Prev, Delay / Reverse Neurodegeneration in Parkinsons

- Foetal neuronal transplantation → stem cells? Promote neuronal reinnervation, nicotine agonists - Neurotrophic immunophilins?- Block a-synuclein aggregation (could be marker not causal protein)? - In PD, degeneration SNc n's causes less DA rel to both direct & indirect pathways. - 2 conseqs - tonic activation direct pathway X longer occurs & indirect pathway is X longer inhib by D2 r activation. Puts balance in fav indirect

Describe huntingtons

- Genetic disorder affect basal ganglia. 0.01%. Onset middle age, death in 20y - Dyskinesia - odd invol movements. Later motor impairment, D, dementia (Not just motor impairment). - Basal Ganglia (BG) dysfunctional . Loss GABA but not dopamine . Increases Basal Ganglia activity - choreic movements - 10% red brain weight. Enlarged lateral ventricles. Massive red in caudate nucleus & putamen (= striatum) due neuronal degeneration therein - Autosomal dom (1 copy of extended gene confers d). HTT C 4. 5 prime - CAG rep sequence encoding polyglutamine tail. - Normal 17-21 CAG reps. Under 35- normal but risk inheritance offspring. 36-39- red penetrance some dev HD. >40 will express disease - Greater Nucleotide reps ~ earlier onset. Accurate genetic test - single gene disorder- Enkephalin containing GABAergic medium spiny neurons degeneration 1st in HD (indirect) then direct pathway (medium spiny GABAergic) substance P containing GABAergic n's, but cholinergic neurons spared. - Initial loss indirect pathway w no opposition of norm activity in direct results in more thalamocortical drive to cortex & uncontrolled xs move (choreiform move) in HD Later stages direct pathway degenerates giving rigidity loss of voluntary movement- Causes:- Cytosolic p expressed in all cells essential for embryonic development. Multiple functions eg neurogenesis, transcription, intracell sig- Huntington p associated w neuronal cytoskeleton & vesicles. Anti-apoptotic p Up-reg transcription of BDNF- Loss of normal function = BDNF loss = apoptosis of GABA neurones increased? - Toxic gain function - mutant HD protein cause protein aggregation by proteasome = protein inclusions, inhibits mitochondrial function, axonal transport & Ca regulation in n's - Treatment-None effective. Some improvement by dec dop funct - Tetrabenazine- VMAT2 inhibitor USA, X UK where antipsychotics treat delusions & violent outburst & antiDs (SSRIs / tricyclics) are used for D- Glutamate antagonists? Short interfering RNA to prevent huntingtin protein expression?

Explain the drug that prevent dopamine metabolism ?

- MAO B inhibitors - Monoamine oxidase - Selegiline - Can give together with L-Dopa (Levodopa) - Catechol-O-methyl transferase COMT Inhibitors Inhibiting dopamine reuptake and have no effect if not used with L-Dopa

What are some features of RAPID EYE MOVEMENT DISORDER ?

- Majoratively seen in OLDER MEN - Do not lose Muscle tone in REM - increases - Act out violent dreams - May injure self or others - 85% develop neurodegenerative disorders - How to diagnose - during REM sleep normally no muscle tone - these patients suddenly gain it back

List the different changes that occurs progressively in parkinson's disease?

- Neurotransmitters & Parkinsonism - Motor impairment --> 1 (5), Psychiatric --> 2, 4. Endocrine ->3 1. Dopamine in striatum ↓ (60-70% = symptoms) 2. Also loss of dopamine in mesolimbic areas- results in mood changes - results in the psychiatric conditions 3. Hypothalamic amines ↓ - endocrine changes eg: Prolactin 4. Cortical noradrenaline & Ach ↓ (cognitive loss)- dementia - prevelant in late stage parkinson's 5. Neuropeptides in striatum ↓ (CCK-8, Substance P, Enkephalins)

Why to construct a family tree ?

- Pedigree analysis to detect a pattern of inheritance - Precise clinical diagnosis, information about others in the family may help in diagnosis - Assess who is at risk in the family may need screening eg: Cancer family history - Can also provide information about social history who is living at home?

Explain amphetamines ?

- Phenylethylamine drugs (Eg: Methamphetamine, dexamphetamine), produce increased wakefullness and concentration in association with decreased fatigue and appetite - Performance enhancing (Sport and War!). Some tolerance - Released monoamines form neuronal storage vesicles and block re-uptake transporters, causing increased synaptic DA, NA and 5HT - Psychological effects include euphoria , increased libido, energy, self-esteem, self-confidence , aggression , excessive feelings of power, Obsession, paranoia - With chronic and/or high doses, amphetamine psychosis can occur - Increased cardiovascular tone; raised blood pressure , tachycardia

What is the primary pathology of Parkinson's disease What is the main dopaminergic pathway that degenerates

- Primary Pathology - loss of pigmented n's in substantia nigra pars compacta Loss of dopamine in 1. Nigrostriatal pathway - Parkinson's d is the main cause - neurons that project from the substantia nigra to the dorsal striatum that degenrate in parkinson's disease - main pathway in which degenerates and produces motor symptoms - loss of motor function

Circuitry of the basal ganglia:

- Striatum receives input from Glutamatergic affs (Corticostriatal & Thalamostriatal) & Dopaminergic affs (Nigrostriatal) - Striatum composed of 90% inhibitory GABAergic medium spiny n's - 2 GABAergic efferents (outputs): Striatonigral (SN) & Striatopallidal (SP) - Direct & indirect pathways have opp roles controlling activity of thalamus to enable planned movements - Striatum sends GABAergic output to globus pallidus & substantia nigra resulting in differential mod movement (d & ind pathways) via thalamus.

What is a migraine ?

- painful, pulsing headache typically lasting 4 hours to 3 days - often unilateral - associated with photophobia

Describe drug dependence syndrome

- strong desire or sense of compulsion to take the substance - difficulties in controlling use (amount, onset, termination) - physical withdrawal state - tolerance - progressive neglect of other interests, increasing time spent obtaining and taking substance -persistence with substance despite detrimental effects: social, cognitive and physical - predisposing factors in the individual are important: genetic, environmental

How to identify Ischaemic strokes on imaging?

- sulci effacement (sulci start to appear blurry) - loss of definition of basal ganglia (caudate nucleus, internal capsule and can be seen on the non-stroke side) - stroke side, putamen cannot be seen clearly - On the intact side of the brain , there is a wedge shaped structure but cant make out the line of containment on side of stroke - loss of definition of basal ganglia structures

What is the area postrema? What is the vestibular system input? What is the vagal input from the pharynx? What is the vagal input and other gastrointestinal afferents from the GI mucosa?

- vomiting center - detects blood chemicals - has no BBB via the vestibulocochlear (8th cranial) nerve - plays a major role in motion sickness b - rich in muscarinic cholinergic and histamine H1 receptors vagal nerve afferents - activated when the pharynx is irritated, leading to gag reflex - the nucleus tracts solitarius has high density of 5-HT and NK1 receptors CN X and other GI afferents - respond to irritation of the GI mucosa by chemotherapy, radiation, distention or acute gastroenteritis via gut 5-HT3 receptors ,

Explain the action of Mirtazapine?

1. Enhances NA and 5-HT transmission 2. Presynaptic Alpha-2 adrenoceptors responsible for inhibiting noradrenaline release are blocked thus promoting Noradrenaline release 3. Pre-synaptic 5-HT2 responsible for inhibiting 5-HT release are also blocked thus promoting 5-HT release

What is aetiology(cause of disease)?

1 Severe , chronic or recurrent depression and severe anxiety - Genetic risk (polygenic)plus environmental stress 2. Mild and moderate depression or anxiety : Environment only , anyone can experience this 3. Post-traumatic disorder - Has to witness directly or indirectly eg: Through a camera , television a horrific trauma

What is the prevalence of depression and anxiety disorders?

1 in 4 of all adults in the UK will have a depression or anxiety disorder at some point in their life 1 in 7 men and 1 in 5 women will have a depression or anxiety disorder in the last 12 months only 1 in 3 adults, 1 in 4 adolescents seek NHS treatment prevalence, severity and treatment seeking all rising, especially in younger women higher rates in migrants, BME groups and men less likely to access treatment they affect all age groups from 5 years of older post-natal depression is commonest complication of pregnancy (10%) 20% of people with long term physical illness

Explain this angiogram ?

1- Middle cerebral artery 2- Anterior cerebral artery 3- On the bottom of the MCA -Aneurysm - this has ruptured and producing bleeding in brain 4- Carotid artery

when does the L-dopa therapy loose its efficacy/control?

4-6 years of treatment

what does the age on onset of huntington's disease depend on?

1. 50% of age of onset related to CAG repeat number 2. The other 50% - related to other genetic factors (presence of other protective or harmful genes) and potentially environmental factors (smoking seems protective , alcohol might be harmful)

What are the three stages of Operant Conditioning? What are Skinner's ABC Contingencies

1. A= Antecedent stimulus - Conditions/Situation in which the behavior occurs - Green light - Red light 2. B= Behaviours (Operants) - Behavioural response - Rat presses lever 3. C= Consequence - What happens as a result of the operant behaviour - Food is given - reinforcement - Shock is given - punishment(which would decrease the frequency of an undesired behaviour)

What is the action of morphine? Explain the concerted approach of morphine ?

1. Acting on the spinal cord to decrease the amount of transmission from the C-fibres terminals into the dorsal horn , is acting co-synaptically in the dorsal horn and mops up any excitability that pass through 2. Binding in the PAG an NRM to activate the descending inhibitory control pathway is not normally very functional unless need to be 3. It drives that pathway to inhibit the spinal cord excitability 4. Concerted approach: preventing ascending messages to brain and harnessing an endogenous inhibitory system to increase the amount of control the brain has over the spinal cord excitability

What are the NICE recommended treatments for 1. Treatment-resistant cases & 2. Frequent chronic migraine migraine with accompanying neck pain

1. Acupuncture or Gabapentin 2. Botulinum toxin Type A

Give two examples of hippocampal disease ?

1. Alzheimer's : Atrophy of hippocampus is early sign and therefore long term memory loss becomes evident 2. Encephalitis :Brain inflammation target the meso temporal lobes

What are the side effects of Tricyclic antidepressants?

1. Anticholinergic side effects (Dry mouth , blurred vision etc) - affects the PNS 2. Cardiovascular effects can be fatal in overdoses

What are symptoms of anxiety disorder?

1. Anxiety - Psychological symptoms are always about the future - fear of what might happen (vs in depression about the loss that has already happened) - Overestimate threat/danger/vulnerability - Underestimate own ability to cope - Underestimate rescue factors/resources eg: chance , help from others 2. Worry - Painful recurrent thoughts about every minor thing 3. Panic - intense fear accompanied by physical symptoms of autonomic arousal over 10 minutes 4. Phobia

What is the mental state examination?

1. Appearance 2. Behaviour 3. Speech 4. Mood 5. Thought 6. Hallucinations - derogatory voices (rare) 7. cognition 8. Insight

What are some other types of depression?

1. Atypical depression - sleep more , worse in evening 2. Seasonal affective disorder - seasonal pattern 3. Adjustment disorder- To life change 4. Bereavement - Missing a person , longing for them 5. Life stress - GPs wait 2 weeks to see if symptoms of depression lift unless severe , risks are high or history of severe depression - 80% of depression in primary care also has substantial anxiety (mixed anxiety and depression)

What is step 3 of the prophylactic (preventative) migraine therapy ?

1. Avoid known patient- specific migraine triggers such as stress or dietary factors 2. Beta blockers , Calcium channel blockers anti-epileptics (caution in pregnancy) or pre-menstrual oestrogen 3. NICE recommends acupunture or gabapentin in treatment-resistant cases 4. Botulinum toxin type A is recommended as an option for adults with frequent chronic migraine , may be useful in patients with accompanying neck pain 5. CGRP receptor antagonists and monoclonal antibodies are the first drugs now approved that are specifically designed for migraine

List the CSF changes in infectious meningitis based on type of organism ?

1. Bacterial: A. Neutrophils increased in peripheral blood and CSF and protein also increases B. Bacterial infection consumes glucose , CSF glucose drops - normal ratio should be >0.5 , CSF glucose drops - With chronic bacterial infection like TB-tuberculosis , very low glucose seen 2. Viral : A. Cryptococcal meningitis - AIDS defining infection - in immunocompromised patients (otherwise rare) B. Summer - Enterovirus in CSF - Inflammatory response Polymorphs like lymphocytes- mononuclear cell infiltrate early infection: neutrophils

Disadvantages of Congenital insensitivity to pain ?

1. Children with this disease often sustain damage in and around the oral cavity (eg: biting off the tip of their tongue) 2. Suffer fractures to bone 3. Have unnoticed infections 4. Suffer burn injuries 5. Acute pain is a protective mechanism

How effective is mindfulness-based cognitive therapy?

1. Clinical trials shown effectiveness of MBCT as a treatment for active depression disorders have shown pre-post reductions in symptoms of depression 2. MBCT effectiveness has been found to be superior to that CBT in chronic/treatment resistant depression 3. Targets "autonomous" relapse processes

What is reduced penetrance?

1. Common in cancer predisposition syndromes 2. Not everyone who inherits the mutation develops cancer in their lifetime 3. This shows reduced penetrance and also variable expression as different members of the family have different types of cancer and one of the sisters does not even have cancer

What are counselling points for diagnostic counselling test ?

1. Confirmation of diagnoses 2. Consider syndromic causes for cardiomyopathy 3. Genes for cardiomyopathy including inheritance pattern 4. Chance of finding mutation 5. Implications for own management - current , future 6. Implications for relatives

Explain the major epigenetic changes ?

1. DNA Methylation - adds methyl groups to the cytosine residue in CpG dinucelotides 2. MicroRNAs - short non-coding TNA molecules - have fundamental role in the regulation of gene expression in disease processes and physiological pahtways

What are the Unwanted effects prolonged use of L-Dopa?

1. Development of choreic movements - Approx 2 years 2. Rapid fluctuation in clinical state "On-Off Effect" - Drug works well and then patients switch back to old symptoms 3. Nausea and Anorexia - Peripheral effect of L-dopa conversion 4 Hypotension - not a major problem 5. Psychotic effects

What are the requirements for genetic counselling?

1. Diagnosis - clinical/genetic tests - on which to base information 2. Family history 3. Estimation of risks - like maybe risk of cancer developing or something else 4. Communication - Diagnosis/risks/management option - To patients/relatives/colleagues

What is the role of the clinical genetic service?

1. Diagnosis of genetic conditions 2. Genetic counselling for families 3. Support and management

What are the disadvantages of CBT, cognitive based therapy?

1. Due to its structured nature , it may not be suitable for people with more complex mental health problems 2. Due to its focus on current problems , possible underlying causes of mental health conditions rooted in the past are not adequately addressed BUT is recent yeards , psychotherapeutic elements have also been adopted , as in functional analytic psychotherapy

What are the cardiovascular effects of propofol ?

1. Effects on BP , tends to cause hypotension (Low blood pressure) 2. Propofol Reduces systemic vascular resistance SVR and can reduce heart rate , particularly in children 3. Reduce SVR , reduces pre load , and dose dependent effect on myocardial contractility - reduces the contractility ( If enough dose given - dose-dependent)

What are some non-pharmacological treatments?

1. Electric = Electroconsvulsive theraphy (ECT)- used to treat severe or treatment resistant depression = Vagal nerve stimulation and Deep brain stimulation - Rarely used for treatment resistant depression 2. Magnetic: = Transcranial magnetic stimulation - depressionn - No anaesthetic , No seizure , targeted Fronto-limbic circuits

How does CBT change cognition and behaviour?

1. Emotional problems stem from maladaptive beliefs and recognising importance of disputing self-defeating beliefs 2. Accepting we have the ability to change maladaptive thoughts and behaviours by counteracting them 3. Neuroimaging research shows that neurally not just psychologically support the effectiveness of CBT-based approaches in the treatment of a range of mental illnesses particularly depression and anxiety 4. Observed post-CBT normalizing changes in brain regions involved in emotion regulation such as amygdalla ,ACC

What does cognitive therapy emphasize and involve?

1. Emphasizes role of negative beliefs in the cause of maintenance of depression , magnification (of negatives) , minimization (of positives) and over-generalization 2. Involves identifying and replacing distorted thoughts and ultimately changing the associated habitual behavior towards them

Signs of meningitis in infants ?

1. Flaccid , floppy - later opisthostonus 2. Bulging fontanelle due to increased ICP 3. Fever and vomiting often the only sign - fitting sometimes 4. Strange cry 5. Convulsions

What is Huntington's disease and what are its signs & symptoms ?

1. Genetic disorder affecting basal ganglia - basal ganglia dysfunction Symptoms : Dyskinesia - Odd involuntary movements Later motor impairement depression Dementia (not just motor impairement) Onset - middle - death in 20 years

Rapid diagnostic test for Meningitis?

1. Gram stain 2. Zn - TB few organism(ZINC-TUBERCULOSIS ORGANISM) 3. PCR - Meningococcal and pneumococcal on EDTA & CSF - HSV/Enteroviruses - TB 4. Antigen agglutination tests - Cryptococcus

How to diagnose Herpes simplex virus ?

1. Haemorrhagic necrosis especially temporal lobes 2. RBCs in a traumatic LP 3. MRI 4. EEG - temporal lobe - very white lots of inflammation - due to water

What is MBCT especially effective in? Mindfullness Based congitive therapy

1. Highly cost-effective due to its group-based approach , reduced demands for clinician time 2. Equivalent to continued medication 3. Especially relevant for most vulnerable people

name the different parts of the Limbic system and their functions?

1. Hippocampus - role of the , Consolidating information - long term memory 2. Amygdala - Responsible for autonomic responses - particularly associated with fear 3. Thalamus - relays sensory and motor signals to cerebral cortex - regulates consciousness , sleep 4. Hypothalamus - regulate ANS and is involved in homeostasis , motor function control , sleep wake cycle , food and water intake regulations 5. Pituitary gland - Secretohormones which help control growth , blood pressure , thyroid metabolism , sexual organ function 6. Cingulate gyrus - Rational cognitive functions which are often informed by how we feel 7. Frontal lobes - involved in higher functions

What is involved in a routine assessment of cognitive function?

1. History of Cognitive deficit 2. Premorbid level of functioning 3. Educational and Occupational history

Signs of raised intracranial pressure? 3 signs of raised ICP

1. Imaging - CT head scan 2. Lumbar puncture 3: A. If no longer history B. Focal neurology , drowsy , fitting C. Papilloedema can be slow in its development - absence of it does not mean you don't have IC - Risk of bleeding (abnormal clotting)

What are some psychological treatments?

1. Improving access to psychological treatment (IAPT) for primary care , clinical psychology and psychotherapy in secondary mental health care 2. Books with facilitator , individual , group , couples , family forms 3. Targeted at specific causes - Bereavement (CRUSE) , Marital (RELATE) , trauma , specific group eg: Women only or by particular form eg: Cognitive behaviour therapy

Discuss variation in expression in terms of "tuberous sclerosis" ?

1. Inherited in autosomal dominant way 2. Variable expression seen - most people have very subtle skin features - might not affect in any major way - but sometimes affects severely especially if tubers in brain - severe developmental delay and may develop seizures that are hard to control

What are environment predisposing factors?

1. Insecure attachment- lack of security in parenting/absence of consistent secure parental figure 2. Childhood sexual abuse 3. Childhood physical abuse 4. Childhood emotional abuse 5. Childhood physical neglect 6. Childhood emotional neglect

What are the theoretical assumptions of Cognitive-behavior therapy?

1. Internal communication is accesible to reflection- can talk about it 2. Emotional problems stem from maladaptive beliefs; Maladaptive beliefs & behaviours can be changed by counteracting them using priniciples of Learning theory etc.

What are Cyt P450s?

1. Involved in drug metabolism and bioactivation 2. Carry out degradation of "xenobiotics" (drugs) in humans 3. This happens mostly in the liver 4. P450s transform drug into soluble molecules that can be excreted 5. Genetic polymorphisms in the Cytp450 enzymes affect drug metabolism and response

Most common questions asked of a neuropsychologist?

1. Is there deterioration in cognitive functioning? 2. Is it generalized or focal ? 3. If focal - which areas of brain implicated ? 4. With which diagnosis is pattern most consistent 5. What are the implications for rehabilitation , independent living ? 6. How can this person best be helped ?

What are the 4 pair of opposite emotions in Plutchik's wheel of emotions?

1. Joy/sadness 2. Affection/Disgust 3. Anger/Fear 4. Expectation/Surprise

Give a summary of Parent of origin effect?

1. Large expansions of the CAG repeat in HTT almost exclusively occur on paternal transmission 2. Large expansions of the CTG repeat in DMPK almost exclusively occur on maternal transmission

What are the environmental precipitating and protective factors?

1. Life events 2. Life difficulties 3. Organic : Alcohol 4. Social support 5. Secure attachment 6. Positive life events

Explain action of Methadone treatment for Opiate abuse ?

1. Long acting synthetic opiate agonist , administered orally for sustained period at dose sufficient to prevent opiate withdrawal 2. Reduces effects of illicit opiate use and decreases opiate craving 3. Patients stabilized on adequate , sustained dosages of methadone can hold jobs avoid crime and violence of the street culture , reduce exposure to HIV by stopping injecting 4. Very low rate of complete cessation of heroin use in methadone patients.

Name some other bedside mental state assessments?

1. MMSE- out of 30 2. MoCA - free- Montreal cognitive assessment - used for dementia patients- out of 30 3. ACEIII, ACEIII remote- addenbrookes cognitive examination- screen for mild dementia- Allows to distinguish between two types of dementia 4. TICS (for telephone interview)

What are the types of depression?

1. Major depression - 2 weeks , more severe 2. Dysthmia - 2 years persistent , mild (2-5 symptoms) 3. Melancholia - Most severe , slowed down/agitated , worse in morning , early morning , weight loss 4. Bipolar depression - Seperate episodes of mania , >4days of elation or irritability, increased energy and acitivity 5. Depression with psychosis

Importance of making a diagnosis?

1. Management of patient - Treatment -Surveillance for complications - Prognosis - planning 2. Identification of "at-risk" relatives - Surveillance 3. Risk of recurrence - Pregnancy options

Explain these MRI Scans

1. Middle - stroke(circled) - in frontal , parietal and even temporal lobe 2. Anterior- anterior cerbral artery stroke is definitely going to be close to midline

10 most frequent neurological disorders?

1. Migraine 2. Stroke 3. Epilepsy 4. Dementia 5. Parkinson's disease 6. Multiple sclerosis 7. Peripheral neuropathies 8. Brain tumors 9. Muscular dystrophies 10. Motor neurone disease

What are other psychological treatments?

1. Mindfulness based congnitive behaviour therapy 2. Behavior therapy 3. Problem solving counselling 4. Interpersonal therapy 5. Eye movement desensitisation and reprocessing (EMDR) 6. Psychodynamic psychotherapy 7. Supportive listening 8. Family and marital therapy

What is local anaesthetic systemic toxicity (LAST) ? What is emergency treatment for local anaesthetic systemic toxicity (LAST) ? What precautions taken to avoid Local anaesthetic systemic toxicity (LAST) ?

1. Na+ channel/Sodium channel induced arrythmia and neurotoxicity - seizures - cardiac arrest (cardiovascular and neurological symptoms) Overdose or accidental intravenous (IV) injection 2. Intra-lipid fat emulsion given as emergency IV - reduces concentration of local anaesthetics in the heart and may have cardioprotective function intracellularly , given alongside resuscitation 3. PRECAUTION: A. Aspirate before injecting slowly B. Know the maximum safe dose

Describe BDNF and Pain ?Mechanism of Fibromyalgia

1. Nervous system injury expression and secretion of BDNF 2. BDNF initiates neuronal repair yet causes pain 3. BDNF reduces inhibitory synaptic transmission in the dorsal horn 4. Noxious (painful) stimulation increases BDNF expression in the spinal dorsal horn and brainstem leading to hyperalgesia and the development of tactile allodynia ( pain in the absence of a painful stimulus) through enhanced BDNF signalling mechanisms 5. Excessive BDNF expression has been implicated in the development of chronic pain in experimental animal models

Describe a carrier test for X-linked condition in childhood What are the downsides of a Carrier test for X-linked condition in childhood ?

1. No medical need to know during childhood - no need for treatment/investigations. Information for reproductive choices in adulthood 2. Potential to influence relationships within the family 3. Takes away the option for the daughter not to know . Invasion of her privacy

Give example for the following: Brain reward pathways do they use ? 1. Drugs that increased dopamine release in Nucleus accumbens 2. Drugs that enhance serotonin (5HT) function: 3. NMDA Antagonists

1. Opiates , nicotine , amphetamine , cocaine , ethanol , cannabis , ecstasy , PCP(Phenylcyclidine) , Barbiturates , Caffeine 2. LSD , Ecstasy 3. PCP(Phenylcyclidine) , Ketamine - Hallucinogenic

What are advanced directives? Pros and cons of feeding tubes to prolong life

1. Particularly important feeding tubes and other measures to prolong life in the very advanced stages of HD 2. Swallowing is affected long before natural end of life - Feeding tube will therefore help prolong life - Revents pressure sores , infections etc - People can still taste food for pleasure Often even if there is medical tendency to prolong life where we can , most patients not want this especially if they have seen a relative affected

Explain coiling?

1. Pass a tiny catheter up through the femoral artery through the carotid artery until you are at the base of the aneurysm - so cannula is in place 2. Fill the aneurysm with wire coils and fill it up so much that bleeding is evntually stops 3. Retract the catheter and aneurysm no longer going to bleed- because blood within it has coagulated

Common causes of encephalitis in UK?

1. Primary infection -HSV1 (Treatable) Enterovirus (Not) Listeria (Treatable) Measles Mumps 2. Post infection: - Chickenpox - Flu A and B - Measles

What are the characteristics of disorders with an emotional component such as psychotic disorders ?

1. Range of symptoms including hallucinations , delusions , catatonia and thought disorders 2. Abnormal or deficient emotional responsiveness leading to disturbed social interaction and diminished ability to learn from punishment 3. Interpersonal behavior is selfish , dominant , manipulative and superficial : Inability to experience deeper feelings of love and indifference to feelings of others , lack of empathy and remorse flat affect , incongruous affect

What are physical symptoms of Meningitis ?

1. Rash petechial/purpuric - due to leakage of blood (usually meningococcal but also streptococcal , HiB sepsis and enteroviral infection -> you get these blood stream infection spots and leakage of blood into the sites - Happens in skin also happens throughout body - kidney , adrenals 2. Meningeal irritation: - Photophobia - Irritation motor roots by inflammation 3. Kerning's sign test - positive due to hamstring spasm - told to raise leg and it causes pain 4. Neck stiffness - unable to put chin on chest 5. Brudzinski's sign - Flexing the patient's neck causes flexion of the patient's hips and knees 6. In mid meningism this may not be present - unable to curl forwards to put nose on knee

Name instances where neuropsychology not likely to be helpful or appropriate?

1. Recently bereaved 2. Florid psychosis 3. Patient severely or terminally Ill 4. Patient has systemic infection 5. Severe behavioral disorders 6. Assessed less than six months ago - can

what is the process of pre-symptomatic testing?

1. Refer to Clinical genetics 2. Review of family history and confirm diagnosis 3. Initial discussion - provide information , explore motivation for test , discuss benefits and disadvantages of test 4. Time for reflection 5. May arrange further appointments 6. Consent and test - arrange plans for results 7. Results session 8. Negotiated follow up and referrals to other specialities as required

What are the three main modes of action of antidepressants?

1. Reuptake inhibition 2. Receptor Blockade- Block the autoreceptors which are receptors on the pre-synaptic neuron which inhibit the release of neurotransmitter from pre-synaptic neuron into the synaptic cleft 3. MAO Enzyme inhibiton - MAO enzyme present both in the pre-synaptic and synaptic cleft - MAO enzymes regulates the amount of neurotransmitter within the presynaptic neuron- So if MAO enzyme is inhibited , then there will be more neurotransmitter available

Describe implications of a diagnostic test in childhood

1. Review of medical and family history - clinical assessment of child 2. Differential diagnosis made 3. Genetic test may be possible to confirm/exclude diagnosis - helpful to guide management of child 4. Confirming a diagnosis information on inheritance pattern and prediction of parent's chance of having another affected child . Identifying mutation may allow testing of future pregnancies.

What are some anxiety disorders?

1. Simple phobias 2. Agrophobia 3. PTSD 4. Generalised Anxiety Disorder - most common , worry for >6 months out of proportion to stress with insomnia , muscle tension with headaches , backaches , autonomic physical symptoms (IBS)

What are the integrative methods in CBT to change patient's negative thoughts/thinking ?

1. Skills training eg: assertiveness 2. Using humor , emotive imagery , role-play 3. Changing one's language 4. Doing cognitive homework - identify your negative thought 5. Disputing irrational thoughts and beliefs 6. Desensitisation - CBT intervention is based on comprehensive formulation of the patient's presenting problems (Needleman )

What are the risks of depression and anxiety disorders?

1. Suicide 2. Self harm 3. Self-Neglect 4. Neglect 5. Exploitation by others 6. Addiction 7. Homicide/infanticide

What is the advantage of neuropsychological testing/Psychometric approach ?

1. Takes into account the natural changes in cognitive function as we age- scores are corrected as your age 2. allows to look at Relationship between different cognitive functions to see if patient has deficit between many of the assessed functions or just one area - Help diagnose the form of brain damage

What is CBT thinking, behaviour and life problems in depression?

1. Thinking in depression - tackle : A. Negative automatic thoughts B. Assumptions C. Schema -rigid beliefs 2. Behaviour in depression - Behavioural activation A. Set tasks to increase confidence and interest each day 3. Tackle life situation - Problem solving A. Define a specific problem eg: marital problem into one or more solvable problem and help the patient to identify a range of solutions

Three stages of epilepsy

1. Tonic phase - body is stiffened 2. Clonic phase - body is shaking movements - called epileptic fits 3. Postictal stupor - person is in a stage of stupor - poorly responsive , limp body

What are the types of insomnia?

1. Transient (2-3 days) - Acute stress - "Jet-lag" 2. Short-term (acute<month) - Situational stress- (Bereavement , conflict at work) - Pain 3. Long-term (chronic>month) - Upto 50% of patients in this group have underlying psychiatric illness -Also chronic alcohol or drug abuse

Describe supervisory attention system

1. Two or more things we could do - but we want to do only one of them - so we have decision process that will decide which of the alternatives to do 2. We choose an action and not inhibit the other behavioral response but give it less strength and more strength to the positive one 3. Time consumption for decision needed 4. This executive system is intentionally demanding 5. Becomes less efficient when we are stressed or anxious , or when we are sleep deprived 6. Also not good when we are trying to do two things at once 7. Basal ganglia builds and rewards and strengthens habits

Potential advantages of predictive testing for HD

1. Uncertainty of gene status removed - If negative: 1. Concerns about self and offspring reduced - If positive: 1. Make plans for the future 2. Arrange surveillance/treatment if any 3. Take part in research 4. Inform children/consider pregnancy options

What is the application of operant conditioning in Behaviour modification?

1. Understand how behaviors are learned and maintained 2. Modify or change behaviours

What are the aims of genetic counselling ?

1. Understand the clinical features of a condition and its management 2. Understand the inheritance of the disorder 3. Understand the options for managing the risks Eg: testing in pregnancy Eg: Screening/Surgical options if cancer predisposition 4. Choose the course of action which seems most appropriate for them - non-directive 5. Make the best possible adjustment to the disorder

Where is TP-PCR used for ? triple primed PCR

1. Used in HD for individuals homozygous for normal alleles on both HD1+HD3 and HD2+HD5 PCRs 2. Particularly important in possible cases of Juvenile HD which can have those large repeats

What are the simple executive function tests?

1. Verbal fluency 2. Sequenced movements 3. Interpratation/Abstraction

What are the changes that can be seen in the neurotransmitters in the brain with Parkinson's? What symptoms do they lead to?

1. dopamine decrease in striatum (60-70% = symptoms) 2. also loss of dopamine in mesolimbic areas 3. hypothalamic amines loss 4. cortical NA and ACh loss 5. neuropeptides in striatum loss (CCK-8, Substance P, Enkephalins) motor impairment - 1,(5) psychiatric - 2,4 endocrine - 3

what are the functions of huntingtons gene? what is huntingtin protein associated with ?

1. essential for embryonic development 2. Multiple functions eg: Neurogenesis , transcription , intracellular signalling 3. Associated with Neuronal cytoskeleton and vesicles 4. Anti-apoptotic protein Up-regulates transcription of BDNF.

MoCA Montreal cognitive assessement test

1.Visuospatial/Executiv e - Trail making task 2. Naming - choose animals that are less frequent to seen 3. Memory 4. Attention 5. Language 6. Abstraction 7. delayed recall - back to the memory questions 8. Orientation

What is the life expectancy after first consultation/diagnosis?

10-15 years

What are the 4 main arteries that supply the brain with blood?

2 vertebral arteries (posterior) 2 carotid arteries (anterior)

What are the core symptoms of depression?

2 weeks of low mood (feels sad, tearful or numb, maybe worse in morning 'diurnal mood variation') loss of interest or pleasure (in every thing) plus 3 or 4 of the following

What is the McGill Pain Questionnaire?

20 groups of words from which the patient picks one word per group to describe his/her pain; usually performed once every 2-4 weeks assesses pain quality and characteristics - sensory- symptoms - affective- Affect the pain on mood of individual and emotional pain - evaluative - How brain is interpreting that pain and overall impact of pain

When do the first symptoms of huntington disease manifest? What is duration of disease?

35-50 years Duration of disease = 15-20 years

Where is the midbrain in a posterior view of brain, dorsal view of midbrain?

4 little bumps - superior colliculi - inferior colliculi

What are the lobes of the brain?

4 lobes frontal - largest - separated from the parietal lobe by the central sulcus parietal - sits on the side and is separated by the occipital lobe by the parieto-occipital sulcus occipital temporal - second largest - contains the amygdala and hippocampus

What is the treatment for a haemorrhage?

45% mortality 30% risk of vasospasm - buildup of blood products within the brain next to vessels that aren't ruptured is going to cause those vessels to react , so they may begin to spasm , they may either become occluded or disruption and blood flow - so you may end up having secondary events in response to haemorrhagic events Treatment most important - bleed must be managed treatment is pain management and surgery to repair the origin of the bleed with clipping or coiling May include lowering blood pressure with labetalol or glyceryl trinitrate (GTN) berry aneurisms are the most likely cause of SAH BERRY ANEURYSMS ARE THE MOST LIKELY CAUSE OF Sub-arachnoid haemorrhage

How many cortical layers are there?

6

Limbic system is transitional between subcortical nuclei and Neo-cortexo How many layers does the neocortex have? How many layers does the deep nuclei have? How may layers does the limbic system have?

6 do not have layers - jumble of nuclei 3

What are the actions of the opioid receptors?

7 transmembrane spanning receptors coupled to G-proteins coupled to Go/Gi proteins - Go = other - Gi = inhibitory inhibit adenyl cyclase and reduce cAMP alter ion channels through G-protein coupling to channels - open K+ channels - close Ca2+ channels

What are symptoms of generalized anxiety disorder?

>6 months of out proportion stress Insomnia Muscle tension with headaches Backaches Autonomic physical symptoms

Describe the circadian rhythm? When does melatonin secretion begin? When is the deepest sleep? When is highest peak in alertness? When is there elevated testosterone?

9pm - melatonin secretion begins 2am - Deepest sleep 6am - cortisol secretion begins 10am - peak in alertness 5pm - greatest cardiovascular and skeletal muscle strength

What do diagnostic negative report show?

<27 CAGs - Not associated with disease 27-35 - Intermediate disease, repeat can increase 36-39 - Likely to be affected but incomplete penetrance >39 CAGs - Likely to be affected

What is tourette's syndrome?

= transient - long term Odd movements - inappropriate behavior cause of tourettes: altered basal ganglia function - only behavioural therapy needed to treat if minor manifestation Treat when necessary with dopamine receptor antagonists - reduce dopamine function

What is systematic desensitisation?

A behavioural therapy designed to gradually reduce phobic anxiety through the principle of classical conditioning- Counter condition their response with something else Ask them a heirachy of events elicits the maladaptive response such as seeing clinic nurse etc. And then construct is a hierarchy of events from least provoking to most provoking and then first present the least provoking and ask them to associate alternative response (Deep muscle relaxation)- while imagining driving to clinic

Are neuronal responses to repeated stimulation of A fibres and C fibres fixed? Plasticity of spinal responses

A fibres - firing is about the same each time - Same response for different stimulus C fibres - repeated firing gets a bigger and bigger response as stimulus is being applied more frequently - therefore it is not fixed and are not always proportional to the intensity of the stimulus applied - These are pain pathways which are not hardwired and are very plastic

Prevention and control of meningitis?

A. Vaccines: - Conjugated Hib and meningococcal group C pneumococcal vaccines protection i <2 yr olds - Men B vaccine - meningococcus B - Elderly also have pneumococcal vaccine - MMR Vaccine for children , mumps can also cause viral meningitis Chemoprophylaxis: - Reduce secondary cases in close contacts and household of patients with meningococcal and Hib disease - Haemophilus Influenzae Type B - Rifampacin or ciprofloxacin clear nasopharyngeal carriage (ceftriaxone)

How are eicosandoids formed?

AA is metabolised by one of two fatty acid COX enzymes synthesis is driven by many different stimuli-including cell damage prostaglandins, thromboxane, leukotrienes

Give a note on Guillan-Bare syndrome ? How to diagnose Guillan Bare syndrome ? How to treat and supportive care ?

ACUTE IMMUNE-MEDIATED POLYNEUROPATHY: ○ Progressive muscle weakness ○ Reduced or absent tendon reflexes ○ From mild weakness to complete paralysis of limb , facial , respiratory and bulbar muscles ○ Autonomic nervous system dysfunction ○ Entirely reversible but needs proper treatment ○ Labs : elevated spinal fluid protein with normal cell count ○ Recognize early (3-7% mortality even if well treated) ○ Supportive care (close respiratory monitoring) ○ Immunotheraphy- (IVIG, Plasma exchange)

What is the pain scale used commonly in nursing homes?

Abbey pain scales

What is plasticity in chronic pain ?

Ability of pain circuits to respond differently under different conditions Can lead to reduced effectiveness of opioids

why is there slower onset of action in inflammed/infected tissues?

Acidemic - acid environment -end up with less of the ionized form of the drug across the extracellular compartment and loss of ionised form - much slower onset of action

What type of approach is behaviour therapy?

Action based approach

Why is congenital insensitivity to pain dangerous?

Acute pain is a protective mechanism - without this, don't know the limits of the body and end up getting injured without realising Children won't learn that they shouldn't do dangerous things Patients with congenital insensitivity to pain tend to die in childhood due to injuries or illnesses going unnoticed e.g. touching a hot kettle

Treatment of listeriosis?

Amoxicillin +/-gentamicin (Cephalosporins - no activity)

What happens with chronic and/or high doses of amphetamines?

Amphetamine psychosis increased CV tone , raised BP , tachycardia

Name the regions that play a key role in emotion processing and regulation?

Amygdala and Anterior Cingulate Cortex

What are some motor neuron disease?

Amyotrophic lateral sclerosis (ALS) - degeneration of UMNs and LMNs primary lateral sclerosis - slow degeneration of the corticospinal tract - begins as weakness and stiffness of the legs that causes balance and walking problems pseudo bulbar palsy - degeneration of the corticobulbar tract - facial paralysis, including the tongue, persistent dribbling, or difficulty with speaking, chewing and swallowing progressive muscular atrophy - degeneration of the LMNs - begins as weakness and stiffness of the hands that spreads to the lower body and muscle lose tone

Name an general anaesthetic drug that is antanalgesia and causes pain ?

Anti-nociception - Hypnotic such as thiopentone

What are the potential for future treatments for Huntington's?

Anti-sense oligonucleotide (ASO) Spino muscular atrophy

Management of meningitis?

Antibiotics Adequate oxygenation Prevention of hypoglycaemia and hyponatraemia Anticonvulsants Decrease intracranial hypertension

Describe Progressive relaxation? Explain psychological method to treat insomnia

Approach to improve sleep 1. Progressive relaxation therapy provides a means for reducing autonomic activity 2. The Bernstein & Borkovec (1973- handbook updated 2000) technique involves tensing specific muscle groups and then releasing the tension 3. Progressive relaxation can be of benefit in the treatment of sleep-onset insomnia

what are most commonest causes of meningoencephalitis that can be caught by travel?

Arbovirus and rabies

Effect of the local anaesthetics on different types of nerve fibres ? Why do patients still feel touch or pressure and feel sick but not anything sharp or painful when given local anaesthetics ?

As the diameter and velocity of the nerve fibers decreases , the sensitivity to the local anaesthetics increases Because we have not necessarily blocked Aalpha and A beta deeply enough Blocked Adelta - won't be able to feel anything sharp or painful - fast pain ○ You may feel sick , because an anaesthetist by giving local anaesthetics is blocking their sympathetic fibres, blocking the Sympathetic nervous system (in their B and C fibres) causes a loss of normal arteriolar tone and they therefore drop their blood pressure - conscious patients when their BP fall they feel sick

What is the Brief Pain Inventory?

Asks patient to rate pain within past 24 hours on graduated scales (0 to 10) with respect to its impact on areas(Pain interference) such as mood, walking ability, and sleep, relationship with others, normal work Assesses pain severity and degree of interference with function using NRS (numeric rating scale)

What is the predictive test/ presymptomatic test ?

Asymptomatic patient Information about the future Not able to predict when symptoms will develop No immediate impact on management May influence life/reproductive choices Not all individuals want to know. Careful protocols for pre-test counselling Results confidential - not disclosed to other family members

Give a note on Myasthenia gravis ? Is it renologically mediated? How is it diagnosed ?

Autoimmune disorder of the neuromuscular junction Ocular or generalized - starts ocular and can generalize after that Renologically mediated disease - Caused by antibodies against acetylcholine receptors (Ach) and these antibodies block the neuromuscular transmission leading to muscle weakness - muscle fatigueability Diagnosed clinically but presence of Ach antibodies help with the diagnosis

Describe the Wechsler Adult intelligence (IQ) Scale? (WAIS-IV)Scores

Average is 90-109 100 IQ is normal irrespective of age

What is mindfulness? What are the 3 related skills that are to be cultivated for awareness to emerge?

Awareness that emerges as a result of cultivating 3 related skills: 1. Intentionally paying attention. 2. Noticing habitual reactions 3. Responding with curiosity & compassion

What is required for the survival of GABAergic neurones?

BDNF brain derived neurotrophic factor

What is the mode of benzodiazepines?

BDXs are positive allosteric modulators on GABAa receptor complex GABAa receptor = ligand gated chloride selective channel BDZ occupy site on GABAa complex (between alpha and theta) conformation change allows GABA to bind GABA binding -> conformational change in GABAa receptor chloride channel greater flow of chloride ions into the neurone hyperpolarisation = inhibition

What are CBT interventions based on ?

Based on a comprehensive formulation of the patient's presenting problems (NEEDLEMAN 1999)

How does adrenaline affect administration of safe doses of local anaesthetics ?

Because adrenaline causes vasoconstriction - less of the drug (lidocaine) is absorbed into the vasculature where you inject it , so safe doses become higher

Why do emotions influence memory ?

Because hippocampus has important connections with amygdala and thalamus

Why does hypoxia , hypercarbia and acidaemia lead to to toxicity ?

Because of reduced protein binding

What principles does behavioural therapy depend upon?

Behaviorism

Why should you not offer benzodiazepines be offered to general anxiety disorder patients for long term or why can it be given only during a crisis?

Benzodiazepines can be offered for short term use only during a crisis because it can lead to addiction

What is the most likely cause of SAH?sub arrachnoid haemorrhage

Berry aneurisms

What is Patient SM ? Urbach-Wiethe disease ?

Bilateral amygdala lesions Normal ability to recognise familiar faces Normal ability to recongnize happy , sad , surprise , digust face Unable to recognize fear face No fear of snakes , horror films and dangerous situations No deficit in other emotions Cannot learn fearful associations - fear conditioning won't work

What are some radiological features of stroke to be aware of? What are the various cerebrovascular pathologies associated with vascular cognitive impairement (VCI) seen?

Blood flow to brain is reduced - hyperperfusion - arteries become stiff - may accumulate plaques When the blood vessels of the brain become basically compromised or begin to be damaged - due to reduction in blood flow can lead to : 1. there are inflammatory responses - leading to BBB breakdown - may cause bleeding in brain (Lobar or deep haemorrhage) within subcortical structures of the brain Smaller bleeds also possible - called microbleeds/microhaemorrhages - isolated in cortical areas 2. Some pathology occuring in blood vessels - produce a variety of phenotypes : 2ND PART OF Q: A. Enlarged perivascular spaces (seen as white stripes that come in through the cortex)- penetrating arterioles that move through the cortex or surrounded by a space filled with cerebral spinal fluid and now has become enlarged When pathology is occuring in these blood vessels - these spaces become enlarged -series of stripes throughout cortex B. Might have smaller strokes - lacunar infarcts or strategic infarcts - located in really important part of brain - this case- thalamus white matter changes: White matter lesions - common in vascular dementia - commonly seen in elderly - they indicate a really high risk of potentially Going on to develop vascular dementia (white matter should appear dark - but here its blurry and white - called white matter hyper intensity) Build up of amyloid plaques within the leptomeningeal arteries of the brain - CEREBRAL AMYLOID ANGIOPATHY(seen as black dots on scan) - Plaques are building up within the blood vessels - generally in cortex combination of these can produce - small vessel disease- term for what's happening to the brain when blood flow and blood vessels are reacting to the situation

Explain blood pressure management in strokes?

Blood pressure management is a consideration acutely as well as longer term as a preventative strategy Anti-coagulants and lipid lowering drugs may also be helpful to reduce risk of re-occurence or secondary stroke events

Routes of infection in meningitis?

Blood-borne (crosses the choroid plexus) Parameningeal suppuration e.g. otitis media, sinusitis Direct spread through defect in dura e.g. post surgery or trauma Direct spread through cribriform plate

What are the different types of brain disease?

Brain Disease: Neurodegenerative - Loss of n's, Disrupted motor funct, May also incl changes in Behaviour Psychiatric - X obvious loss of n's though may show some struc changes. Change in Behaviour and Movement

What is multi-dimensional pain assessment tools?

Brief Pain Inventory McGill Pain Questionnaire Neuropathic Pain Scale Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale HRQoL - Medical Outcomes Study Short-form Health Survey (SF-36) - Pain Disability Index - Roland-Morris Back Pain Disability Questionnaire - Western Ontario MacMaster Osteoarthritis Index (WOMAC)

What is the most widely used pain assessment scale in pain services?

Brief Pain inventory

When do the midbrain dopaminergic neurones show brief phasic bursts of activity?

Brief phases of bursts of activity after - rewarding stimuli like food or sex - stimuli predicting rewards - causes wanting rather than liking (dopamine depleted addicts still want it , less liking for it tho)

How does PCR detect triplet repeat expansions? What is the name of the PCR used to detect Huntington's ?

CAG 'sizing' PCR - primers flanking CAG repeat region - two primer pairs used - HD1 + HD3 - HD2 + HD5 - products seperated by capillary electrophoresis

what CBT is NOT: _____

CBT is NOT: * anti-pharmacotherapy * against discussion of emotions and interpersonal relationships * the same thing as 'the power of positive thinking'

What are CGRP receptor antagonists and monoclonal antibodies against CGRP?

CGRP receptor antagonists (e.g. talcagepant) and monoclonal antibodies against CGRP (e.g. Fremanezumab , galcanezumab) and the CGRP receptor (erenumab) are in development might be more effective with low CVS risk but need injection sc or iv. Fremanezumab is first available on NHS one in phase III of clinical trials

Where are C and A fibres found?

C - terminate in the superficial laminae of the dorsal horn A - relay touch and are found slightly deeper in the dorsal horn

What is the predominant pain fibre?

C-fibres

How do opioids work in tissue damage - chronic pain?

C-fibres are activated and opioid receptors are present Will cause HYPERALGESIA - OSTEOARTHRITIS for someone who has never taken opioids and they have had chronic pain for a long time, it might work but this is hard to prove

How effective is CBT? Is CBT effective in Physical health problems? Is CBT beneficial in Digital formats ?

CBT is particularly effective in 1. Depression : Anxiety disorders , Bipolar disorder , Psychotic disorders , Somatoform disorders , personality disorder , eating disorders 2. Physical health problems eg: Hypochondriacs , Rheumatoid arthritis and chronic pain 3. Yes, Beneficial effects are evident even when delivered through computerised formats

What is CGRP release regulated by? What happens when there is an agonist working on these receptors? What drug is effective?

CGRP release is regulated by 5-HT1D receptors when this is activated by an agonist, it reduces CGRP release triptans

Where is memory formed ?

CA3 and CA1 parts of the circuit are important signs of plasticity and where memory is formed

Which one the COX enzymes is particularly inducible?

COX2 some molecules can irreversibly inhibit COX2

How does CSF enter the venous system?

CSF is circulated up and around the brain --> through the subarachnoid space --> enters the venous circulation through the arachnoid granulations into the sagittal sinus

What is the journey of the CSF around the brain?

CSF is produced in the choroid plexus - starting point is the lateral ventricles - follows arrows - goes through the inter ventricular foramen into the third ventricle - keeps flowing through the narrow channel which is the cerebral aqueduct - comes out into the large opening between the cerebellum and brain stem = fourth ventricle - CSF leaves the fourth ventricle and goes up and around the brain

Effect of rapid metabolism on opioid effects? influences the efficacy and side effects of analgesics including opioids

CYP2D6 ultra-rapid metabolizers Potential for increased production of morphine from codeine More likely to suffer opioid related adverse effects might suffer from lower dose of opioids Serious adverse reactions including respiratory depression, circulatory depression, respiratory arrest, shock and cardiac arrest

Pathology of Parkinson's What is the main pathology of parkinson's?

Can assemble motor plans but unable specify accuracy of programmes, run / seq them - dorsal striato pallidal is key for accuracy and timing of movements - Primary Pathology - loss of pigmented n's in substantia nigra pars compacta

What are the side effects of triptans or 5-HT1D receptor agonists? Why should triptans not be used in ischaemic heart disease?

Cardiovascular risks May cause chest pain due to coronary artery vasoconstriction so contraindicated in ischaemic heart disease

what are the causes of Parkinson's disease?

Causes- Oxidative stress, 15% pts have first-degree relative w PD- Genetic causal factors - familial PD rare (5% of all cases). PARK1 / SNCA gene codes a-synuclein; autosomal dominant early onset PD with Lewy Bodies & marked rigidity. PARK2 codes Parkin which is part of ubiquitin proteosome; autosomal recessive early onset Parkinson's disease restricted Substantia Nigra cell loss no Lewy Bodies good levodopa response. PINK1 & PARK7 gene mutations also cause autosomal recessive forms of PD- Leucine-rich repeat kinase 2 (LRRK2) gene AND SNCA gene mutations occur in sporadic Parkinsonism = risk factors - Drug-induced neurodegeneration - MPTP (environmental toxin) or exposure to pesticides (eg paraquat) - There are experimental methods of producing degeneration of neurons in substantia nigra - 6-hydroxy dopamine- selectively taken up by dopaminergic neurons and interferes with mitochondrial oxidation- cause degeneration of nerve terminals - Drug-induced symptoms - DA antagonists (antipsychotics). Viral encephalitis

What is released during chronic inflammation? What are the cells involved ?

Cells involved : monocytes/macrophages release PGE2/TXA2

What is myotonic dystrophy characterized by and what are its symptoms?

Characterized by myotonic myopathy with associated abnormalities in other organs - Myotonia (often detected as a difficulty in relaxing clenched hands or a hand shake) - Muscular atrophy - Cataracts - Testicular atrophy - Frontal balding - Cardiac conduction defects

What is the course of depression and anxiety disorders?

Childhood depression and anxiety do not necessarily lead to adult depression or anxiety but can lead to other mental health problems Prognosis of depression and anxiety depends on the underlying problem plus added risks from depression and anxiety

What is fibromyalgia?

Chronic pain condition(long term condition) that causes pain all over the body

Explain action of parkinson's disease drug treatment : ROPINIROLE?

Clincially available drugs dont differentiate between D3,2,4 and act on all of them and D3 receptors are prevalant in frontal cortex- side effects

How is a clinical diagnosis made in genetic counselling ?

Clinical history and examination

Phase 1 metabolism of codeine

Codeine has only mild opioid properties , while most of its analgesia and CNS depressant effects are based on its biotransformation to morphine , a reaction catalyZed by CYP2D6 , a cytochrome P450

What is arbovirus infection?

Common cause of encephalitis due to the transmission by vectors (mosquitoes, ticks or sandflies)

Visuoconstructional tasks/ Body image

Copy drawings of cube , flower and house Place numbers and hands on clockface (next slide) BODY IMAGE: Left-right orientation Finger gnosis , Position detection Hemi-inattention

Describe Structures of the basal ganglia

Corpus striatum: Caudate nucleus Lentiformnucleus includes: Putamen Globus pallidus (GP) - Int (Gpi) & Ext (Gpe) Subthalamic nucleus (STN) Substantia nigra (SN):Pars reticulata (SNr) & Pars compacta (SNc)

What is the second theory for migraines? What is the origin? How does the second theory work? How can depression of cortical activity be induced? What might Cortical Spreading Depression cause?what is the cause of aura

Cortical Spreading Depression neuronal origin - primary cause may be in neuronal firing/activity , thus migraine is of neuronal origin blood flow change does not correspond to intracranial artery distribution vasoconstriction spreads from posterior of one hemisphere = neural mediation (depression of cortical neurones in animals) depression of cortical activity can be induced by altering potassium ion concentration may be cause of aura not migraine

Explain the spinobrachial pathway ?

Critical in emotional affective components of pain , links into the amygdala and how much I am suffering that is associated with the painful stimulus

What is the primary type of DA receptors?

D2 in the striatum

What is the difference between D2 and D1 receptors?

D2 receptors are inhibitory - main ones in the Basal Ganglia - coupled to Gi proteins and reduce adenyl cyclase D1 receptors are excitatory - few in the Basal Ganglia - coupled to Gs and elevate adenyl cyclase

Explain neuropathology of Huntingdons disease?

DA neurones are unaffected GABAergic neurons are affected 1. Enkephalin containing GABAergic medium spiny neurons degenerate first in HD (The indirect pathway) - which is most susceptible to repeats of CAG 2. then direct pathway (medium spiny GABAergic) substance P containing GABAergic neurons , 3. but cholinergic neurons & DOPAEMINERGIC spared

What are the dorsal and ventral striato-pallidal circuits?

DORSAL STRIATO-PALLIDAL CIRCUIT: Dopaminergic circuit : 1. goes from substantia nigra to the dorsal striatum (caudate and putamen) 2. Loop goes through the pallidum (Globus pallidus) -> Thalamus -> Motor cortex This loop of structures give rise to skilled and learnt movements movement control is done by cortical striatal loops - controls the timing the accuracy of movements VENTRAL-STRIATO-PALLIDAL CIRCUIT: similar loops between VTA, ventral palladium, thalamus and MD(Different thalamic nucleus called medial-dorsal nucleus) the limbic and prefrontal cortex - important for behavioural cortex - gives

Possible complications of meningitis?

Death, subdural collection / empyema, EMPHYSEMA cerebral vein thrombosis, hydrocephalus (don't absorb CSF properly -> build-up of fluid- if surgical emergency - need to drain CSF or risk of herniation), deafness, convulsions, visual / motor / sensory deficit

How can you test working memory?

Delayed response tasks N-back tasks Digit span

What memory to test , if there is a history of relatively sudden onset or history of head injury Sudden onset dysfunction (Trauma) What should you do?

Determine how long before the head injury the patient's memory is a hazardous function eg: Whether or not they're forgetting things that happened before the event (retrograde amnesia)or after (Post-traumatic amnesia) Check Retrograde amnesia and Post-traumatic amnesia

Describe diagnosis of Parkinsons Disease & Neuronal cell death

Diagnosis: - Positron emission tomography (PET), Single photon emission CT (SPECT) w DAT ligand - Vis & quant dopaminergic n's use radioactive ligands which bind to D transporter p's (DAT)nerve terminals - Loss of DA n terminals show severity of disease - Loss of DA nerve terminals but little changes in post-synaptic dopamine D2 receptors - means of drug treatment by targetting these D2 receptors Neuronal cell death - Lewy bodies - eosinophilic inclusions in n's w core of a-synuclein (aggregate toform fibrils & may contrib to dementia seen 50% Parkinsons) - Substantia nigra, locus coeruleus, X unique to PD also Alzheimer's. Causal or symptomatic(not clear) - Oxidative stress, Mitoch & Proteasome dysfunction

Explain dopamine agonists treatment for parkinson's disease?

Dopamine Agonists - D2 r's are inhibitory - main ones in Basal Ganglia. - D1 r's excitatory - few in Basal Ganglia - Post-synaptic DA r's not altered by PD. - Use D2 r agonists to treat symps esp in early onset, young pts

Describe the role of bromocriptine ? Why should you take special care with bromocriptine ?

Dopamine agonists 1. Stop breast milk production for medical reasons by activating dopamine receptors - reduction in prolactin causes less milk to be produced - Problems usually causes by not having right amount of prolactin 2. Treating non-cancerous tumors in the brain called prolactinomas 3. Treat parkinson's disease (increase dopamine levels) Causes impulsive control disorders(gambling , high sex drive)

How is Huntington's disease different from Parkinson's disease?

Dopaminergic neurones of the striatalnigra pathway aren't that are affected Loss of GABA not dopamine But loss of GABA - Results in increased BG Activity - choreic movements - which are characteristic features of Huntington's disease

can environmental factors cause PD?

Drug-induced neurodegeneration - MPTP (environmental toxin) or exposure to pesticides (eg paraquat)

What are dural reflections?

Dural reflections are where the inner dural layer folds in on itself to protect the brain Falx cerebri - divides the two hemispheres of the brain (joined together by white mater) - dura folds in and sits in between the hemispheres and holds the brain in place Tentorium cerebelli - holds the cerebellum (looks a but like a tent) - contained in its own environment - separates occipital lobe from cerebellum Falx cerebelli - another one found at the back - separates cerebellar hemispheres

What are the steps in the pathophysiology of a stroke?

EXCITOTOXICITY: 1. Failure of ion pumps, cell depolarization Na+, Ca2+ , and water influx and K+ efflux 2. Glutamate release and receptor activation PERI-INFARCT DEPOLARISATION , APOPTOSIS AND INFLAMMATION: 1. Microglia , astrocytes and blood vessels 2. BBB breakdown 3. Influx of leukocytes which allows bad thing from blood to enter brain

What are the symptoms of Parkinson's disease ?

Early stage/onset parkinsons: Poor slow movement(bradykinesia) cardinal symptoms Postural abnorms, Rigid posture, Mask-like expression, Lack / rigidity movement (Akinesia), Tremor Late stages also include: Later stages incl Depression, Dementia & Endocrine dysfunction

What are the mechanisms of disease of Huntington's and Myotonic dystrophy?

Effect of repeat depends on location in gene - coding vs non 1. Huntington's disease- Gain of function of protein - polyglutamine tract expansion 2. In myotonic dystrophy - expansion in non-coding region - 3'UTR- Gain of function of mRNA

what does absence of HTT cause ?

Embryonic death

What is the difference between emotion and mood? What is mood?

Emotion involves brief, intense experiences; mood involves prolonged, low-level experiences mood is a frame of mind or emotional state that is defined by one's internal state rather than external behaviour

What is the James-Lange theory of emotion?

Emotions result from our interpretation of our bodily reactions to stimuli 'we feel sorry because we cry, angry because we strike, afraid because we tremble' emotions are a direct result of the different patterns of physiological response associated with them: they are cognitive responses to information from the periphery Physiological reaction that determines our emotion not our subjective feel

What does CBT cognitive behaviour therapy emphasize on? Theoretical assumptions:

Emphasizes changing and the role of maladapative thoughts Internal communication is accessible to reflection Emotional problems stem from maladaptive beliefs; maladaptive beliefs and behaviours can be changed by counteracting them

What are the 2 causes of depression?

Endogenous or Reactive Secondary to another medical condition such as Parkinson's disease (upto 50% patients suffer from depression) or can be the result of a life event

What does executive function ensure?

Ensures that our behavior is : 1. Involves identifying goals , holding these in mind 2. Monitoring behavior(correcting errors inhibiting alternatives)

What is genomic imprinting?

Epigenetic changes that have been inherited Different expressions depending on whether it has been inherited from mother or father

Genetic components of fibromyalgia?

Epigenetics and microRNAs are involved in chronic pain and fibromylagia Epigenetic changes in genes involved in fibromyalgia including genes related to neuron differentiation and nervous system development , in particular the BDNF gene, a crucial neuromodulator of pain transmission RNA changes in microglia and in dorsal root ganglion neurons also affect the levels of the BDNF gene expression There is now considerable evidence that epigenetic and microRNAs are involved in chronic pain

What are studied and learnt during the Wisconsin Card Sorting Test?

Error correction , Monitoring , attentional flexibility , inhibitory responses, perseverance errors Perseverance errors- also sometimes seen in parkinson's disease patients

What are the acute effects of opiates What are the chronic effects of opiates?

Euphoria , tranquility , miosis drowsiness , itchiness , nausea Anhedonia CONSTIPATION, DEPRESSION , INSOMNIA , DEPENDENCE (in pic) HIV and hepatitis , significant tolerance

Describe tests to test memory ?

Even when doing history taking - can assess remote memory (Autobiographical memory) Recent memory Immediate (working) memory Sudden-onset dysfunction

Language based neuropsychological/Neurological assessment task?

Expressive vs Receptive distinction Language (Aphasia ) EXPRESSIVE: Tasks to use: Repetition of sentence Recitation (eg: months , counting) Naming common objects Handwriting Check for : Dysarthria (articulation) , dysfluency , word-finding difficulty , paraphasias neologisms RECEPTIVE: Tasks to use: Understanding of conversation Reading text Following commands

What is intensity of acute pain related to ?

Extent of injury - Amount of tissue injury

What are the stroke symptoms?

FAST: Facial weakness Arm weakness Speech difficulty Time to call 999

Explain variation in expression with an example?

Family members have different signs of the same disease Very important clinically in autosomal dominant disorders Many family members don't recognize these features to be linked to same condition (here marfan syndrome) because they affects different parts of the body in different ways

How does reduced expression of FAAH enzyme cause pain insensitivity?

Fatty-acid amide hydrolase (FAAH) is an enzyme in the endocannabinoid system - involved in breaking down endocannabinoids When FAAH is reduced, the levels of endocannabinoids in the blood are very high Endocannabinoids modulate pain, mood, inflammation, appetite and cognition results in reduced anxiety

Presentation of encephalitis?

FeverSeizures and / or focal neurological findings CSF pleocytosis EEG findings compatible with encephalitis Abnormal results of neuroimaging

Why does Bipolar disorder go unnoticed?

First episode unobserved before age 30 with a peak incidence between 15-19 years of age - so undiagnosed

What are the implications for independent living?

Fitness and capacity - advice on : 1. Fitness to work or live alone 2. Fitness to care for children 3. Fitness to drive 4. Capacity - to give consent/make decisions (Eg: finances , treatment choices)

What is the reward circuit controlled by? From where do the projections travel IMPORTANT PATHWAY FOR REWARD CIRCUIT? What are the modulatory inputs? What do rewards signals use to drive behaviour?

Fundamental transmitter involved in reward circuit : midbrain dopaminergic neurons ventral tegmental area (VTA-midbrain) to nucleus accumbens(nucleus in ventral striatum) in the median forebrain bundle Broader circuit that involves other brain regions including: - orbitofrontal and medial frontal cortex - ventral striatum - amygdala Whole system uses reward signals which use environmental signals to drive behavior

What is the main inhibitory neurotransmitter of the brain?

GABA

What are the characteristics of granular cells?

GABAergic interneurones huge amount in the cerebellum and some in the cortex

What are the side effects of NSAIDs?

GI upset, GI ulcers and bleeding, increased creatinine, heartburn GI Disturbances: - Dyspepsia - Diarrhoea - Nausea and vomiting - Piroxicam and meloxicam highest risk - Skin reactions

What is the most common anxiety disorder and what are its symptoms?

Generalised anxiety disorder worry for >6 months out of proportion to stress with insomnia , muscle tension with headaches , backaches , autonomic physical symptoms

is it generalized or focal? Global impairement of cognitive function - Diffuse organic brain syndromes ?

Generalised/diffuse/ global - two types: Developmental or acquired Acquired (before 18)- ACUTE ORGANIC BRAIN SYNDROME: Acute or Chronic Acute : Delirium Chronic :Dementia Delirium and Dementia have common presenting symptoms but DELIRIUM 1. HAS SUDDEN ONSET - Found out by history taking 2.Acute illnesses have fluctuation (diurnal) 3.Impaired level of consciousness- Concentration , Mood changes - BUT IN ACUTE MUCH MORE VARIATION Dementia - 1. you have minor symptoms which can gradually get worse(long term ) 2. Not as bad as fluctuations 3. In early stages of dementia - person stays alert

What are the functions of the basal ganglia?

Group sub-cortical, grey matter strucs that part of extra-pyramidal motor systems. X initiate movement, helps plan movement by integrating cortical input & feeding back to cortex, via thalamus through direct (excitatory; enabling movement) & indirect (inhib) pathway (motor loop). - Basal ganglia also prev unwanted movement, is involved in learning movement & ass reward. - Injury / CNS dysfunct basal ganglia can cause abnorm invol movements (dyskinesias) / postures (akinesias) in which pts rigid / struggle move - Programming of Movement. Decide how, when & where to act. Put into Action Learned Motor Plans - Stim move à assemble motor plan --> a) Select motor prog from mem stores b) Assemble app seq motor programmes à execute motor plan

What are the implications for rehabilitation , independent living? How can this person best be helped?

Guide rehabilitation- Should help in setting goals and measuring changes across time 1. Establish deficits and implications for rehabilitation - Is learning likely to be possible - Are they able to use compensatory strategies : Eg: Memory aids - Or better to concentrate on changing the environment ? - Attention limitations 2. Help in realistic goal setting and measurement of change 3. Education , advice , counselling for patients , relatives and staff

Describe TP-PCR Triple prime PCR triplet-primed PCR

HD_TPR can bind to different parts of the CAG Repeat and forms different sized fragments as above diagram denotes H_Tail Primer is used to amplify the fragment - its used to amplify all the copies HD_TPR binds to CAG repeats and is at a limiting concentration - this prevents gradual shortening of product size - PCR is biased to smaller product sizes- so hard to amplify larger repeats One of the ways to manage this is to use limiting amount of TPR that will get used up early in the reaction - HD_Tail will amplify the different repeat sized products Still problems with the PCR - still identifies smaller products more - but limiting amount of TPR used to helps the problems to be reduced Long extension time allows large alleles to be amplified Seperation of products by capillary electrophoresis and Samples with known allele sizes included as control Particularly useful for possible cases of Juvenile HD = which can have large repeats

What is the effect of the Huntington's disease on the brain?

HTT is neurotoxic different cells affected in different way striatum/grey matter affected first however, also widespread cell death through the brain In Scan - Brain shrinking widening of ventricles as atrophy progresses

What does treatment for haemorrhages involve?

Haemorrhage treatment involves managing pain and surgical repair , as well as lowering blood pressure if necessary

What are the range of symptoms that psychotic disorders are characterised by?

Hallucinations , delusions , catatonia and thought disorder

What is the third-wave behavioural and cognitive therapies?

Hayes argued that the history of behavioural and cognitive therapies has taken place in three waves first wave: 'behavioural therapy' characterised by the development of classical and operant conditioning models second wave: 'cognitivism'; mostly expressed by CBT third wave: recent developments including Acceptance and Commitment Therapy; Functional Analytic Psychotherapy; Mindfulness-Based Cognitive Therapy

Most common viral cause of encephalitis?

Herpes simplex virus , sits in the anterior horn cells and invade backwards and cause encephalitis

Use of steroids to treat meningitis? How to avoid deafness in meningitis? Caution of GI Bleeding?

Hib Meningitis (dexamethasone) reduces long-term morbidity - Haemophilus influenzae type B Give prior to antibiotics for beneficial effect and reduce chances of getting neurological disorders particularly deafness High dose steroids can cause GI Bleeding

Why is diamorphine addictive ?

High lipophilicity thus penetrates the brain rapidly and thus more potent

Symptoms of reduced FAAH?

High physical pain threshold, NOT SEEN: extremes of rage, dread, grief, anxiety and fear

Presentation of listeriosis?

Immunocompromised , neonates , >50 Years with rising incidence with age ( >60 yrs) Presents in 5% of healthy human stools 64% of fridges have atleast 1 contaminated food item Meningo-encephalitis, brainstem with ataxia and movement disorders

How do genetics influence drugs?

How fast the drug breaks down in the body How efficacious it is Side effects

name the gene that causes huntington's disease? How does the number of repeat affect the onset the disease?

Huntingtin gene (HTT) - expressed in all cells essential for embryonic development Normal 17-21 CAG reps. Under 35- normal but risk inheritance offspring. 36-39- red penetrance some developmental HD HD. >40 will express disease Greater N reps ~ earlier onset

What does the Huntington gene code for?

Huntington protein (HTT) well preserved function present in almost all living things, therefore likely to have an important function - absence of HTT causes embryonic death however, knocking out all HTT in adults appears to have no effect in animal models mutated HTT has a 'gain of function' effect as it is toxic to certain cell types, especially in the brain

triad of general anaesthesia ?

Hypnosis analgesia and muscle relaxation Opioids most effective anti-nociceptive , analgesics

When should a bedside mental state assessment be done?

IF you think there might be cognitive dysfunction and it will take about 30 mins to complete

Describe COX 2 enzyme What does increased expression of COX 2 enzyme cause ?

INCREASINGLY induced in activated inflammatory cells (IL-1 and TNF-alpha) - induced in response to injury, inactivated cells and release of cytokines responsible for production of prostaglandin mediators of inflammation - Inhibit COX-2 to prevent the inflammatory response and associated pain

How is herpes simplex encephalitis treated ?

IV Aciclovir for 2-3 weeks

Signs and symptoms of pneumococcal meningitis?

Impaired consciousness, neurological signs and seizures Pneumonia and/or otitis media present in less than or equal to 50% Patient present with seizures or unconsciousness - infection causes puss formation , inflammation seizures etc.

How does neurodegeneration occur neurochemically in Parkinson's disease?

In PD, degeneration Substantia nigra neurons causes less DA rel to both direct & indirect pathways. - 2 conseqs - tonic activation direct pathway X longer occurs & indirect pathway is X longer inhib by D2 r activation. Puts balance in fav indirect pathway

Does the blunted effects reflect actual subjective emotional experiences of Schizophrenic patients?

In Schizophrenia , it may not

What is the conclusion of stroop tasks?

In both healthy states of sadness (patients with mood disorders normally) and when in clinical depressive states: The "emotional brain" takes over Supresses the activity of the dorsal cortical areas and thus patients cant perform well in cognitive tasks

What are the factors that determine whether the occasional use becomes addiction ?

Including the drug (Heroin is more addictive) The person The context (social factors)

Symptoms of fibromyalgia?

Increased sensitivity to pain Extreme fatigue Muscle stiffness Difficulty sleeping Problems with mental processes - memory and concentration Headaches IBS Feels similar to osteoarthritis , bursitis and tendinitis , but over the entire body

Action of cocaine ?

Increases Catecholamine neurotransmitter function by preventing re-uptake of dopamine - DA most important in CNS behaviour , High concentration has anaesthetic properties Effects - Euphoria and Excitement , Increased capacity for work (cf amphetamine) High doses - Overactivity of sympathetic system (uptake blockade) , hypertension , tachycardia , hyperpyrexia , dilated pupil , palpatations

Explain action of URB-597 ?

Inhibits free fatty acids hydroxylase(FAAH enzyme) - if you inhibit this enzyme which normally breaks down anandamide - lasts longer - get more dopamine peak for much longer NAC - increases in levels of dopamine

Difference between Inflammatory pain & Neuropathic pain ?

Inflammatory pain is well localised Neuropathic pain is less well localized

What is "man on fire syndrome"?

Inherited erythromelalgia Simple activities (e.g. putting on a sweater) can be described as feeling like hot lava being poured into their bodies

How do TCAs work? How do tricyclic antidepressants work?

Inhibit serotonin and noradrenaline reuptake Eg: Amitryptiline(has benifical effects against pain) - Sedative properties (H1 receptor antagonists)

Describe the national protocol for pre-symptomatic testing - developed with HD families?

Initial discussion - provide information , explore motivation for test Time for reflection Option for further contact - if initiated by the patient Further discussion with another counsellor/doctor , review of information and plan follow-up Option for consultation with psychiatrist/neurologist if they develop more symptoms - not done routinely Test arranged only - on minimum of session three Results session Negotiated follow up - as to what support they can receive and if they test positive - they are put in touch with neurologist for further treatment Test arranged only on minimum of session 3

Route of infection of encephalomyelitis ?

Initial entry and primary site of replication: 1. Respiratory eg: Measles , mumps , VZV , Cryptococcus neoformans 2. GI Tract eg: Poliovirus , other enteroviruses , Listeria monocytogenes 3. Subcutaneous eg: arthropod -borne viruses , Ricketsii , Trypanasomas 4. Mucosa - Herpes simplex virus , VZV 5. Rarely via peripheral nerves eg: rabies and polio or cribiform plate eg: Naeglaria sp (amoebic) Then via blood into the CNS Rarely via peripheral nerves eg: rabies and polio or cribiform plate eg: Naeglaria sp (amoebic)

Explain how huntingtons disease happens?

Initial loss of indirect pathway together with no opposition of the normal acitivity in the direct pathway results in more thalamocortical drive to cortex and uncontrolled excess movement (CHOREIFORM MOVEMENT) in HD 2. Later stages direct pathway degenerates giving rigidity loss of voluntary movement

What is IMMPACT?

Initiative on methods , measurement and Pain assessment in clinical trials: Pain Intensity: - NRS (0-10) - rescue analgesia used physical functioning - BPI pain interference scores emotional functioning - Beck Depression Inventory - Profile of Mood States - depression specifically patient rating of improvement and satisfaction with treatment - Likert scale other symptoms and adverse effects during treatment patient disposition and characteristics - according to CONSORT recommendations - describing number of patients of different ages in a clinical trial

What is the key input and output pathways ?

Input - lateral nucleus Output - Central nucleus

IMPORTNAT POINTS

Inputs from multiple sensory cortices via entorhinal cortex Specialized intra-hippocampal circuits Synaptic plasticity is the basis of memory Disorders of hippocampus involve memory impairement Amygdala is a key emotional processing structure and is important in fear and anxiety

Pre frontal cortex

Inputs to and from key limbic structures Important in decisions about reward and appetitive behavior: People with pre-frontal cortex regions make bad decisions Motivation and regulation of behavior Disorders of the pre-frontal cortex can include psychiatric and personality disorders

What are the Huntington disease allele sizes?

Intermediate alleles(27-35) - very unlikely to be affected but can expand into disease range upon transmission (esp. Paternal)

What is the downside of CTs cans to diagnose stroke?

It can rule out haemorrhage but is less effective at detecting acute ischaemia

What is the problem with lithium ?

It has very narrow therapeutic window - patient on lithium will require initially to make sure plasma concentration are being achieved and don't overdose

What are the symptoms of juveline onset HD?Juvenile onset Huntington's disease

Juvenile onset HD before the age of 20 Symptoms - Rigidity , tremor , postural hypotonia , behavioural disturbance and learning difficulties

When are referrals made for different age groups?

Known/suspected genetic condition or family history of known/suspected genetic condition 1. Pregnancy - family history of disorder - Abnormalities detected on routine screening tests 2. Childhood - diagnosis and follow-up of rare syndromes Family history of inherited cancer/cardiac symptoms 3. Adulthood - any inherited conditions - eg: Neurological , cardiac - Strong family history of cancer - Diagnosis or presymptomatic tests

What are the drugs that can be used for PA and what do they do?

L-DOPA - taken up by amino acid transporter - crosses the BBB - gets into the nerve terminal and is converted by DOPA carboxylase into dopamine - stored in vesicles to enhance synaptic content and restore function selegilline - inhibits MAO B - present on the outer mitochondrial membrane - stop the degradation of dopamine in the cytosol - try and encourage vesicular uptake COMT inhibitors - present in the cytosol - prevents break down of dopamine directly activate the dopamine D2 receptors = bromocriptine severe tremor, post synaptic neurons also receive stratal cholinergic input of ACh and blocking these receptors with muscarinic antagonists can be beneficial

How to prevent L-dopa from acting peripherally where dopamine has functions like kidney?

L-DOPA(Precursor of dopamine) + CARBIDOPA(DOPA Decarboxylase inhibitor) Prevent the Conversion of L-Dopa to Dopamine by DOPA Decarboxylase anywhere outside the BBB Carbidopa prevents the L-dopa to be converted into dopamine in the peripheral nerves but can cross the BBB and thereafter convert into dopamine in dopaminergic neurones and can act anywhere in CNS

What is the drug treatment for Parkinson's disease?

L-dopa(Precursor of Dopamine) given peripherally can cross the BBB as opposed to dopamine which can't cross the BBB

Where can you access CSF?

L3/L5 for a lumbar puncture

What is the gene that causes sporadic parkinsonism and autosomal early parkinson's disease?

LRRK2- Leucine-rich repeat kinase 2 - SNCA gene mutations - SPARODIC PARKINSONISM - RISK FACTORS & AUTOSOMAL EARLY PARKINSONS

What are the HD1 + HD3 results?

Large repeats give smaller peaks Larger products don't amplify in PCR as much as smaller products

What is the foundation for behavioural theory?

Learning theory - Classical and operant conditioning

What is classical conditioning?

Learning through association Conditioned stimulus(learnt or associated stimulus) will soon cause the same response as the unconditioned stimulus But can alter this by for example a fearful CS is followed by relaxing which will modify behaviour

Name the key brain circuit for the process of emotions?

Limbic system

Common non-viral causes of encephalitis?

Listeria monocytogenesLeptospirosisSyphilisLyme diseaseTBVasculitisCarcinomaDrug reactions

what is LAST and how is it avoided

Local anaesthetic systemic toxicity Intra- lipid fat emulsion is given as emergency IV - reduced concentration of local anasthetics in the heart and may have direct cardioprotective function intracellularly - given alongside resucitation

Describe Dopamine Pathways

Loss of dopamine in 1. Nigrostriatal pathway - Parkinson's d is the main cause - neurons that project from the substantia nigra to the dorsal striatum that degenerate in parkinson's disease - main pathway in which degenerates and produces motor symptoms - loss of motor function 2. Mesocortical 3. Mesolimbic pathways - Schizophrenia? 4. Tuberoinfundibular pathway - Prolactin release

What are the causes of Huntington's disease?

Loss of normal function= BDNF loss = apoptosis of GABA neurones increased Toxic gain of function - mutant HD protein causes protein aggregation by proteasome = protein inclusions , inhibits mitochondria function, axonal transport and calcium regulations in neurons

What is the main neurochemical effect of parkinson's disease?

Loss of striatal dopamine

Propofol CNS effects

Loss of verbal contact(within 10 seconds) , atonia (loss of muscle tone), unresponsiveness, loss of brainstem reflexes(corneal reflex lost which you can illicit via the facial and trigeminal nerves), apnoea (decreased breathing) decrease in cerebral metabolic requirement for oxygen, cerebral blood flow and intracranial pressure

Why can infection establish in the CSF? Name the conditions that allow for CNS Infections to be establish in CSF ?

Low protein - no complement to bind to pathogen for phagocytosis Low IgG No lymphatic Blood-brain / CSF barrier( can't get in antibiotics to treat )

How to diagnose meningitis?

Lumbar puncture- most rapid diagnostic tool: 1. If there is inflammatory space in the CSF Sample - CSF with meningitis - Can see lot of WBCs 2. Helps to distinguish between bacterial and viral causes in most cases

What can lead to the 'cheese reaction'? Why are Monoamine Oxidase Inhibitors not used as first line antidepressants? How does

MAOI - foods that contain tyramine = RECOMMENDED TO AVOID (e.g. cheese, soya) reason being that if someone ingests those foods, there is competition for reuptake of tyramine or NA (tyramine will win) there is more NA present within the synaptic cleft -> activate the a1-adrenoceptors -> over activation -> consequences could be hypertensive crisis as there is increased vasoconstriction

What is MBCT effective in? Name Physical illnesses that MBCT is found to be effective in?

MBCT has been found to be effective in a wide range of mental health problem, besides depression, including: - anxiety - bipolar disorder - chronic fatigue syndrome - Parkinson's disease MBCT has also been found to be effective in reducing clinical symptomatology in physical illness, including: cancer, multiple sclerosis, HIV and diabetes Type I and II

Where would a MCA, ACA, PCA stroke be?

MCA(middle cerebral artery ) - mostly likely to have a stroke - most of the parietal lobe, superior aspect of temporal and some of frontal lobe ACA (anterior cerebral artery) - supplies the corpus callosum and medial aspects of the frontal lobe PCA (posterior cerebral artery) - inferior aspect of temporal lobe is affected

What are some types of movement disorders involving basal ganglia?

MOVEMENT Disorders: Upper Motor Neuron Disorders (in cranium or spinal cord): Stroke, Multiple Sclerosis, Amyotrophic lateral sclerosis (ALS) Lower Motor Neuron Disorders (outside brain): Peripheral neuropathy, Myasthenia gravis Involuntary Movement Disorders (basal ganglia): Parkinson's Disease, Huntington's disease, Tremor Cerebellar Disorders: Various tumours

WHat is the leading cause of disability in young adults?

MS - Multiple sclerosis More common in females 2-3:1 Chronic condition

What plays the giant role to drive the inflammatory response in the diseased joint and driving pain of OSTEOARTHRITIS?

Macrophages - chronic inflammation - release PGE2/TXA2

Treatment for viral meningo-encephalitis ?

Mainly supportive○ Supportive: - Ventilatory support - Blood glucose and electrolytes montiored and corrected (hypothalamic involvement) - Anti-epileptics - Control cerebral oedema - ICP - Cooling if extreme hypeRthermia ○ Specific treatment available for common non-viral infectious causes: - Eg: Amoxicillin for listeria - Doxycycline for Q fever, Chlamydia ○ Viral- limited options: - Aciclovir- HSV , VZV and Herpes B - CMV- Ganciclovir (2ns Line foscarnet) - HIV- may improve with antiretrovirla treatment

expressive language Spontaneous speech The boston cookie theft How to diagnose Neurological assessment in patients with possible frontal lobe dysfunction

Making minimal demands on cognitive capacity but very useful if you want to assess their expressive language abilities In those with frontal lobe dysfunction : there will be a scarcity of what they will be able to say

If focal - which areas of brain implicated?

Many eg: in BN lectures of focal damage Alzheimer's vs FTD Because different brain regions being affected at different rates- Different levels of performance on neuropsychological tests Alzheimer's disease: Well preserved personality and social behaviour. Early symptoms : Prominent impairement of episodic memory Later symptoms: visucospatial memory , Dysphasia , Dyspraxia , Dysexecutive syndrome Frontotemporal lobar degeneration: (frontotemporal dementia , semantic dementia , progressive apasias) Early symptoms : Prominent dysexecutive syndrome Coarsening of personality Expressive dysphasia Later symptoms: Memory impairement

How does parent of origin affect what disease you get? PARENT OF ORIGIN EFFECT ?

Maternal transmission : Myotonic dystrophy Type 1 - Large expansions in the CTG repeat occur almost exclusively on MATERNAL TRANSMISSION - Female carriers of unstable repeat sizes (>or equal to 46 CTGs) more likely to have children with larger expansions - Congenital DIABETES MELLITUS 1 OCCURS almost exclusively via the maternal transmission - Expansion occurs in occyte Paternal transmission: HUNTINGTON DISEASE - Large expansions in the CAG repeat occur almost exclusively on PATERNAL TRANSMISSION - Male carriers of unstable repeat sizes (>or equal to 27 CAGs) more likely to have children with larger expansions - Greater risk of Juvenile Onset HD - Expansion occurs during spermatogenesis

What is the Wisconsin Card Sorting Test?

Measures the ability to learn concepts and considered a good measure of frontal lobe functioning

DALYs for different age groups due to different neurological illness

Meningitis has highest DALYs for younger populations Alzheimer's disease and other dementias has highest DALYs for older populations

What are the side effects of the medications used in treatment of huntington's?

Medications can cause side effects which can be difficult to distunguish from symptoms of HD itself e.g. Parkinsonism, dystonia, tardive dyskinesia(difficult to distinguish from chorea) , worsening cognition from the medication

What is the most severe type of depression?

Melancholia

What are trigger factors for migraines?

Mental stress - in 75% of cases refractory errors in glasses chocolate, eggs or fruit - 15% alcohol oral contraceptives time zone shifts physical exertion - 45% - Patient counselling can have a major benefit to establish a self-care approach

What is the key motivation and reward pathway ? Is this the only pathway involved in motivation

Mesolimbic circuit No , Pre-frontal cortex as well

What is key motivation and reward pathway ?

Mesolimbic circuit: Inputs from VTA to nucleus and basal forebrain and frontal lobe Important in reward driven behavior Disorders of mesolimbic circuit may include addictions

What are the first cells to respond to a stroke?

Microglia - retract processes , becomes amoeboid , secretes cytokines and other pro-inflammatory mediators

How to identify sub-arachnoid stroke on imaging?

Midbrain being compressed with build up of blood in the sub-arachnoid space lateral sulcus that seperates the temporal lobe from the parietal lobe 0 lots of blood accumulating there and around the midbrain

How to treat depression in adults?>18 age

Mild depression: 1. Appropriate psychological intervention 2. NICE does not recommend drug treatment unless under certain circumstances eg: Previous history of Moderate/severe depression

How to treat depression in children and young people under 18s?

Mild depression: 1. Appropriate psychological intervention 2. NICE does not recommend drug treatment unless under certain circumstances eg: Previous history of moderate/severe depression Moderate/severe depression: 1. Psychological therapy 2. Combined therapy i.e. Psychological + antidepressants 3. If unresponsive to combined therapy - consider alternative psychological therapy 4. If experiencing side effect to fluoxetine -> Sertraline or citalopram

What is Mindfulness-Based Therapy?

Mindfulness-based cognitive therapy - combines mindfulness techniques with CBT components - Proven beneficial in depressive disorders Mindfulness-based stress reduction Both types can effectively alter the intensity/frequency of unwanted internal and alleviate unpleasant bodily symptoms.

For Routine assessmentof cognitive function what test to use ?

Mini mental state examination is the reference

Is there deterioration in cognitive functioning?

Monitoring changes over time: Change eg: 1. Recovery from head injury 2. Response to treatment Disease progression eg: 1. Neurodegenerative process

Explain the action of morphine/cannabinoids & Amphetamine/Cocaine?

Morphine/Cannabinoids - Inhibit the inhibitory GABA neurones and prevent GABA from inhibiting the dopaminergic neuron in the VTA that goes to NAC- increase release of dopamine Amphetamine/Cocaine - causes release of dopamine at the level of dopamine receptors - increase dopamine produced - elevate dopamine in the reward pathway

Onset of dementia for different age groups

Most common dementia for onset above 65 - Alzheimer's dementia

What are the Motor system components?

Motor cortex integrates information and produces motor signals. Basal ganglia receives sensory & motor cortical info & helps plan movement by feeding back to cortex via thalamus. Cerebellum receives info from body & assists w dynamic co-ord of movement, balance & posture.

What causes "man on fire syndrome"? Inherited erythromelalgia

Mutations in SCN9A gene Nav1.7 channel involved in propagating electrical signals along nerves is hypersensitive to stimulus and normally it regulates pain transmission in nociceptive neurons. The Nav 1.7 molecule is expressed only in sensory and nociceptive neurons These molecules regulate the action potential generation and propagation in neurons Nav1.7 regulates pain transmission

What neurotransmitters are involved in sleep mechanisms?

NA 5-HT ACh

What is the locus ceoruleus?

NA neurone LBs here may contribute to depression and cognitive dysfunction

How can depression be recognised?

NICE reccomends asking 2 screening questions : Holy questions: 1. During the last month, have you been bothered by feeling down , depressed or hopeless 2. During the last month , have you been bothered by having little interest or pleasure in doing things

What are non-pharmacological treatments of insomnia?

NICE- carry this out first - Primary target non-pharmacological inventions gives help to a large number of people in the first week, medication works well by 4th-8th - pharmacological and non-pharmacological are neck and neck to maintain good sleep then non-pharmacological are much better - behavioural changes CBT will help with the other morbidities as well as sleep problems

What is true in all cases of vomiting?

NK1 antagonist will be useful - best single agent therapy - - aprepitant prevent or at least reduce the vomiting reflex Substance P

Is the offset of Anaesthetics by metabolism ?

NO , diffuses away from the site of action Eg: Propofol , Rockuronium

Mecamylamine

Nicotonic acetylcholine receptor antagonist Blocks rewarding actions of nicotine and cue-induced craving Antagonist effects can be overcome by increasing dose of drug

What are the counselling points for presymptomatic test ?

Nature of familial mutation - which cardiomyopathy gene Inheritance and chance of inheriting family mutation Risks associated with mutation : - Implications for own management - screening , early diagnosis , treatment - Options for children/pregnancies

What is Beck's negative 'schema' model? What is beck's negative triad?

Negative thoughts about : - Oneself - The world - The future set of negative schemas that people start from childhood automatic, maladaptive cognition triad results in a vicious cycle people cannot get out of this cycle that easily - negative thinking maintains seen in anxiety disorders and other mental health disorders e.g. psychosis

Name two agents that prevent the risk of neuromuscular paralysis in rocuronium ?

Neostigmine & suggamadex

Name two agents to prevent neuromuscular paralysis effects of rockuronium ?

Neostigmine and Sugammadex

What is parkinson's disease?

Neurodegeneration of the extrapyramidal system where they are unable to perform normal motor function or initiate movement

What is neurophysiological testing?

Neurophysiological tests cover the range of mental processes from simple motor performance to complex reasoning and problem solving Neuropsychologists use scientifically validated objectives tests to evaluate brain functions

Early meningitis infection sign ?

Neutrophils

Describe the implications of predictive testing in childhood for adult onset condition What are the arguments against predictive test in childhood for adult onset conditions ?

No implications for management in childhood - cancer not expected to develop until adulthood . No screening or surgery appropriate in childhood Takes away the option for the daughter not to know - invasion of her privacy

Describe inflammation in the neurones during stroke

No longer any blood flow that is sufficient to provide all of the neurons energy to survive the neurons begin to experience excitotoxicity dying from electrical failure and peri-infarct depolarisations shrunken = microglia respond Also the astrocytes start to depolarize microglia are amoeboid and release cytokines Microglia retracts all its processes - taking an amoeboid phenotype - its releasing cytokines and the cytokines are activating various enzymes that are breaking down the myelin nodes of the oligodendrocytes-further attracting leukocytes to the brain some of the cytokines eat away at the myelin fibres from the oligodendrocytes wrapped around the neurones cytokines area also attracting leukocytes to the brain leukocytes break thorough the tight junctions, entering the brain, releasing their own cytokines and pro-inflammatory mediators Pericytes undergo cell death as well astrocytes are swollen up, retract its processes and thus BBB is open and impede further in the BBB so more leukocytes can get in and the same thing is happening to the pericytes well first and when they die they get shrunken - contribute to BBB disruption

are granular cells only GABAergic?

No they sometimes have spiny stellate granular cells that glutamatergic

What is done in Verbal rating scale (VRS)?

Non mild moderate and severe words - Used for this scale Reduces the number of Possible responses in comparison to above two scales

What are the risk factors of stroke?

Non-modifiable: Age, Gender , Ethnicity, Family History Modifiable: Hypertension , Diabetes, Hyperlipidaemia , Smoking , Obesity , Carotid artery disease

What is the treatment for huntingtons disease? How to treat violent outbursts and depression in Huntington's disease?

None effective Some improvement by decreasing dopamine function - Tetrabenazine Delusions and violent outburst - antipsychotics(Dopamine D2 agonist) Depression - antidepressants (SSRIs) Glutamate antagonists? Short interfering RNA to prevent huntingtin protein expression

What is rapid eye movement disorder? How to diagnose REM Disorder?

Normally no muscle tone during REM Sleep - these patients suddenly gain it back

Why are neonates given meningococcal vaccine/ checked for meningitis?

One of the complications is visual/motor/sensory deficit - long term neurological damage

Name Genes that are associated with Cause of Parkinson's disease?

PARK 1 OR SNCA- codes Alpha-Synuclein PARK2- codes parkin - Autosomal recessive early onset PD PINK 1 and PARK7 - Autosomal recessive forms of PD LRRK2- Leucine-rich repeat kinase 2 - SNCA gene mutations - SPARODIC PARKINSONISM - RISK FACTORS & AUTOSOMAL EARLY PARKINSONS

What are the emotional deficits seen at a neural level in patients with mood disorders?

Overactive ventral paralimbic regions and hypofunctional dorsal-cortical regions; Normalisation of activity in these regions is seen in remission

What is done in CBT?

Overwhelming problems are broken into smaller parts 1. Overwhelming problem is identified at present (might have resulted from earleir experinces) but in CBT approach, we deal with here and now 2. break it down into small parts

How to diagnose viral meningo-encephalitis ?

PCR-replaced biopsy and viral culture but not 100% sensititivity as may not have sufficient virus in that site - CSF (HSV , enterovirus and VZV) - Stool , throat swabs , urine (measles , mumps) - systemic infections excreted in these sites - MRI more sensitive than CT and EEG

What do mast cells release?

PGD2

What are powerful vasodilators?

PGE2, PGI2 and PGD2

How can depression be measured?

PHQ- 9 Symptom checklist Do once every two weeks

What is functional pain ?

Pain where there is NO inflammation or damage to the pain processing pathway , but the nervous system is functioning in a way it was not intended to .

What are some other anxiety disorders?

Panic disorder Health anxiety Obsessive compulsive disorder - recurrent worry over the same threat - action to neutralize threat - eg: recurrent cleaning Social anxiety disorder

Process of infection of meningitis?

Pathogens sit within the nasopharynx Some pathogens break this barrier into the blood Some will have capsules that resist lysis / phagocytosis so are able to get into choroid plexus Pathogen able to get to the Choroid plexus and infect CSF within subarachnoid space where they multiply because no immune system is primed there to kill them

Executive functions

Patient gives estimates for questions asked - has to be within correct range Verbal fluency Sequenced movements Interpretation/abstraction

What is the penumbra?

Penumbra determines window - The longer we wait , the more the brain is going to die how much blood flow decrease is required to cause death in the brain white area - infarct core(<12 ml/100g/min) this is where the stroke happened - blood flow is severely compromised -unable to maintain homeostasis - within 5-10 minutes, all of the tissue is completely dead quickly - Core determines irreversibly damaged tissues benign oligemia (>22mL/100g/min) - blood flow is quite slow but tissue is still able to survive penumbra (12-22mL/100g/min) - Blood flow is low to the extent that tissue is suffering - tissue may die unless treatment/blood flow is restored within few hours - Penumbra represents potentially salvageable tissue - TPA must be administered very quickly in order to recanalised quickly and ensure blood flow to part of the brain that is affected core expansion - expanded to take the penumbra tissue and all the tissue will die

What is PMLS?

Periodic Limb movement during sleep: Repetitive movements of the limbs every 20-40 seconds

Does the DOPA Decarboxylase Inhibitor CARBIDOPA cross the BBB/CNS?

Peripheral inhibitor only active outside the brain as cannot enter CNS - thus not cross the BBB

What is the most common post infectious causes of Neuritis ? What is the most common cause of neuritis ?

Post infectious - Guillan barre syndrome Campylobacter jejuni (commonest)

What is Plutchik's wheel of emotions?

Plutchik suggested that there are 8 basic emotions grouped in 4 pairs of opposites joy/sadness affection/disgust anger/fear expectation/surprise all other emotions are derived from combinations of this array

Genetic effects on the variation of opioid response?

Polymorphisms of mu-opioid receptor gene (OPRM1) OPRM1 A118G SNP ALSO KNOWN AS A118G , N40D or Asn40Asp Having at least one G allele means that a patient consumes more opioids for analgesia after surgery but has higher pain scores than the homozygous 118AA patients

Discuss the phenotypes of drug metabolism in humans ? Allelic variant in CYP isoform ?

Poor metabolizer (PM - 2 non-functional alleles Intermediate metabolizer (IM) - At least 1 reduced functional alleles Extensive metabolizer (EM) - At least 1 functional allele Ultra-rapid metabolizer (UM) - Multiple copies of functional allele and/or allele(two normal functional copies of CYP2D6 gene) that confers increased gene transcription - Even with normal doses of codeine , these individuals may experience the symptoms of morphine overdose which includes extreme sleepiness , confusion and shallows breathing - Nursing mothers may also produce breast milk containing higher than expected levels of morphine that can lead to severe adverse events in their infants

Effect of poor metabolism on codeine effects?(PM) influences the efficacy and side effects of analgesics

Poor metabolizers have decreased activation of CYP2D6-dependent analgesic prodrugs such as codeine Don't get any analgesic benefits from codeine as it isn't metabolized into morphine Same frequency of side effects as normal metabolizers

Explain a predictive test for testing in childhood What are the arguments for predictive testing in childhood ?

Potential to avoid unnecessary investigations if test is negative Test usually performed before investigations need to start but old enough to understand the process

What are the potential benefits and potential problems of Predictive tests?

Potentials benefits: Reduce uncertainty Screening/surgery/treatment to reduce risk of condition Pregnancy options Plan life - careers , finance , sports and hobbies Information for relatives Potential problems: Further uncertainty Financial implications - insurance/mortgages May restrict career choices - eg: army Survivor guilt Information about relatives risk Information about relative's risk

What are practical anaesthesias used for?

Premedication - atropine and benzodiazepine Fast induction - Thiopental (IV) Maintain - Isoflurane (inhalation) Muscular relaxation - neuromuscular blockading drugs (antracurium , pancuronium , suxamethonium) Reduce pain - analgesic (opiate) , Post-operative - analgesic (opiate)

What does myasthenia gravis present with and name a symptom of it ? What is it characterized by? Explain its presentation What is its cause How to treat Myasthenia gravis ?

Presenting with ptosis, diplopia or bulbar symptoms Fluctuating skeletal muscle weakness ("true muscle fatigue") Neuromuscular respiratory failure Spontaneous or precipitated by infection, surgery or medication Requires early diagnosis and respiratory monitoring and often admission to intensive care

Describe age related and incomplete penetrance?

Proportion of individuals affected with the gene who are affected often dependent on age of assessment

What happens if the patient tests positive for HD?

Put in touch with neurologist for further treatment

What to expect from an assessment by a clinical neuropsychologist? What is included in an assessment by a clinical neuropsychologist?

Quantitative statement of : 1. Current Cognitive status 2. Premorbid Cognitive status 3. Likelihood of decline Detailed profile of cognitive functions , Identification of specific deficits or if it's generalized Opinion on differential diagnosis and needs/strengths.

What is the RAT system?

Recognise Assess Treat EPM-UK

How do you test temporal memory? How to assess recency memory?

Recognition test - did you see the items in the card in the set Recency test= Which one of the two items in the test card did you see most recently

What is the model of neural connections associated with sleep-wake cycle?

REM sleep is 'awake' - wave form pattern between REM sleep and awake is similar REM is induced through the actions of activating the pons which is present within the brainstem release of ACh from the pons which stimulates the thalamus information is transmitted up to the cerebral cortex and then REM sleep is induced thalamus is the relay centre and the information travelling from the periphery travels to the higher regions and in the opposite directions Non-REM sleep - want to inhibit the pons do not get release of ACh and not transmit the information to the cerebral cortex via inhibitory relay of information from Raphe nuclei (5-HT) and from the locus coeruleus (NA) = inhibition of pons information from pons is not relayed to thalamus and to cerebral cortex REM sleep is from pons onwards and non-REM sleep is inhibiting this information by inhibition of Raphe nucleus and locus coeruleus

What is the model of neural connections associated with sleep-wake cycle?

REM sleep is 'awake' - wave form pattern between REM sleep and awake is similar REM is induced through the actions of activating the pons which is present within the brainstem release of ACh from the pons which stimulates the thalamus information is transmitted up to the cerebral cortex and then REM sleep is induced thalamus is the relay centre and the information travelling from the periphery travels to the higher regions and in the opposite directions Non-REM sleep - want to inhibit the pons do not get release of ACh and not transmit the information to the cerebral cortex via inhibitory relay of information from Raphe nuclei (5-HT) and from the locus coeruleus (NA) = inhibition of pons information from pons is not relayed to thalamus and to cerebral cortex REM sleep is from pons onwards and non-REM sleep is inhibiting this information by inhibition of Raphe nucleus and locus coeruleus

At which stage of sleep do we dream? How is dreaming different in this stage from other stages?

REM- Stage associated with vivid sleep Slow wave - but less vivid and less likely to remember them

What is congenital insensitivity to pain?

Rare inherited condition in which a person cannot feel and has never felt physical pain

Which is better on memory tests : Recent or Remote memory and why? If you have got Organic brain disorder

Remote memory is usually better than recent memory on memory tests

What are the withdrawal precipitates of opioids? Do all drugs have the same withdrawal effects?

Raving , insomnia , restlessness , diarrhoea , muscle and bone pain and vomiting , cold flashes with goose bumps(Cold turkey) , Kicking movements Major withdrawal symptoms peak 48-72 hours after the last dose and subside after about a week Heroin Withdrawal is less dangerous than alcohol or barbiturate withdrawal - Sudden withdrawal by heavily dependent users in poor health occasionally fatal

What is repeat instability and what does it cause ?

Repeats can be unstable and expand in subsequent generations - Leads to more severe phenotype

What are the warnings/ side effects of COX-2 inhibitors such as celecoxib?

Risk of heart attack , stroke and CV death

What is the risk of immobility and neuromuscular blockades ?

Rocuronium and suxamethonium - Can stop diaphragm and the intercostal muscles from working , thus stop breathing

What drug is being developed to target the endocannabinoid system? Effect? Why was it taken away?

Rimonabant Blocks CB1 cannabinoid receptor Leads to a reduction in appetite Causes serious side psychiatric side effects - suicidal tendencies

What are some other antidepressants to consider?

SNRI- Serotonin-Noradrenaline reuptake inhibitor eg: Duloxetine, Vnlafaxine TCA - antagonise H1 receptor - inhibit the reuptake of 5-HT and NA - targets the muscarinic receptors - consequences = GI problems MAOI - not favoured NaSSA NARI(Noradrenaline reuptake inhibitor) Eg: Reboxetine

What are pharmacological management options for anxiety symptoms of general anxiety disorders?

SSRIs offered as first line option- Sertraline pregabalin - associated with various side effects, dizziness, weight loss - side effects are less favourable - speculate that it inhibits glutamate release

Where is there direct projection from? Where does sensory input projection ?

Sensory input comes from the skin (superior dorsal horn )to the parabrachial nucleus (red pathway) and leaves through the bottom or ventral horn - the nucleus is a part of the limbic system - the limbic brain allows you to have emotions - therefore this pathway up to the parabrachial nucleus affects emotions

What are the descriptors of inflammatory pain ?

Sharp and/or dull Aching Throbbing Well localized

What do you do if one allele is detected in HD1+3 and HD2+5? When is the TP-PCR Used?

Single allele detected: - Patient may be homozygous for this repeat size (i.e. inherited an allele with 17 repeats from each parent - so homozygous for both CAG and CCG) - Patient may have an expansion that is not detectable by this method - so we use Triple Primed PCR

In the treatment of what is progressive relaxation can be of benefit?

Sleep-Onset insomnia

Varenicline (nicotinic ACh) and buprenorphine - (u-Opioid)

Smoking and opioid cessation respectively Some evidence that bupenephrine with opioid receptors can cause addiction to other substances

What do the HD2 and HD5 results show?

So now we have detected two alleles even thought we don know the size We can see the expansion and size of peaks which indicates the level of expansion

what is most difficult for patients in terms of Non-medical treatment?

Social care and social support Main burden for families

What are some widely used behaviour therapy techniques? What are some applications of Behavioural therapy?

Some of the most widely used techniques are: 1. Graded exposure (eg: systematic desensitization) 2. Exposure and response prevention 3. Social skills training (Eg: Applied behaviour analysis) 4. Modelling; behaviour rehearsal 5. Reinforcement , punishment and aversion therapy Such techniques are applied to a range of mental illnesses including: depression & anxiety , anorexia , autism and schizophrenia

What is first affected in huntington's effect on the brain?

Striatum/Grey matter affected first

Name the DALYS lost in different neurological conditions?

Stroke has the highest DALYs and Parkinson's disease has the least 1. Stroke 2. Dementia 3. Migraine 4. Epilepsy 5. Parkinson's disease

Contributions of various neurological disorders to the overall burden from the neurological disorders

Stroke has the highest contribution

What are some tasks that measure cognitive vs affective processing? What are the results of these tests?

Stroop task/Supression task/Response inhibition task Go-NoGO tast When presented with emotional words - patients with emotional disorders+ anxiety disorders which have that emotional element in them - perform worse Depressed patients -depression related words(sad, depressed)- have effect on them Anxiety patients - same with anxious related words People who make mistakes make even more mistakes , and poor performance results if they have depressive symptomology

Why can meningitis cause increased ICP?

Subarachnoid space doesn't have a primed immune system - takes a while for a response to take place Neutrophils are signalled to come and clear infection Tight junctions become leaky, fluid and proteins leak out Composition of CSF changes If too many immune cells are activated, CSF vol increases, leading to an increase in intracranial pressure - raised intracranial pressure

What is the DA projections doing? Explain dopaminergic circuit projections in brain ?

Substantia nigra projects to caudate and putamen the striatum - this is the circuit that is important in voluntary movement and becomes abnormal in disease like parkinson's disease Ventral tegmental area that sends its own dopaminergic projection to another area in the ventral striatum called nucleus accumbens

What is executive dysfunction?

Subtle or overt behavioral and cognitive defects in executive control , often associated with frontal lobe damage

what are the scores of the MMSE? What is the score for someone with mild cognitive impairement? What is the scores for dementia?

Suggested cut off score - 23 23-26 9.7

What controls the Circadian Rhythm in the body and describe it's function?

Suprachiasmatic nucleus (SCN) present in hypothalamus When its dark - SCN encourages production of melatonin to induce tiredness with levels peak between 2am to 4am As daylight approaches , SCN triggers the release of cortisol to induce wakefullness

Causes of aseptic meningitis? Causes of lymphocytic/mononuclear CSF- lymophocytic CSF - MONONUCLEAR CSF

TB-tuberculosis Partially treated bacterial infection Intracranial abscess Spirochaetes (Leptosirosis , Lyme borrlisosi , Syphilis(can cause a type of dementia - young people screened for this) Viral meningo- encephalitis Lymphocytic leukaemia

What is contraindicated in Ischaemic Heart Disease?

TRIPTANS and 5-HT1B and 5-HT1D AGONISTS

Differential response to pharmacological treatment constitutes a major source of patient morbidity and mortality . TRUE?

TRUE

Difference between tactile pathways and pain pathways

Tactile pathways : Inputs arrive at the dorsal horn of the spinal cord Tactile tracts cross in the medulla Pain pathways: noxious Inputs are processed extensively in the dorsal horn of the spinal cord Pain tracts cross in the spinal cord Tactile pathways are crossing the midline at a higher level than the painful inputs

How can virtual reality therapy be used?

Teach them while they are in those fearful situations an alternative response Used for fearful responses and anxiety-related disorders - Eg: PTSD Graded exposure and habituation to a vivid experience without the associated costs of in-vivo exposure

FAMOUS FACES TEST?

Test has to be appropriate to patient's age

What is the oil-gas partition coefficient?

The *larger the coefficient* -> the more anaesthetic is stored in fat -> the *longer the recovery from the anaesthesia* (more hangover effect) to permeate the BBB - better if they are lipid soluble

Describe (MMSE) Mini mental state exam or MoCA? Assessed out of 30 marks

They test current mental state and the areas tested are: 1. level of conscious awareness , attention , orientation in time and space 2. Memory 3. Visuospatial/ Body image 4. Language 5. Executive/frontal functions

Explain the excitatory and inhibitory inputs of the striatum ?

The striatum is composed of GABAergic (inhibitory) medium spiny neurons and receives glutaminergic (excitatory) input from the cortex and dopaminergic input from the substantia nigra

What is naltrexone used for ?

Therapy for opiate addiction and reduces alcohol craving

Are pain pathways hardwired ?

They are not hardwired and they are very plastic and depend on amount of stimulus , the intensity and frequency , you can start to get large responses of spinal neurons of what would be small stimulus

What is the line of treatment for Parkinson's disease?

Treat Symptoms: Enhance DA Function 1. L-Dopa - Carbidopa 2. DA receptor agonists - Bromocriptine, Ropinirole 3. Prev DA metab - MAO B inhibitors - Deprenyl (selegiline)- COMT inhibitors - Entacapone (only effective when used with L DOPA) 4. IncREASE Dopamine release - Amantidine - rarely used 5. Adenosine A2A antagonist - approved add-on therapy with L DOPA (2019) - Muscarinic receptor antagonists - control tremor - Neuronal transplants

What is the monoamine hypothesis of depression?

Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors(MAOIs) heralded as the first generation of antidepressants antihypertensive drug reserpine (depletes NA and 5-HT; monoamine (MOA) antagonist) caused depression in patients not suffering depression before depletion of NA and 5-HT did not lead to depressive symptoms in normal individuals however, patients on antidepressant treatment were vulnerable to replace following depletion of NA and 5-HT CSF in suicidal depressed patients contains reduced amounts of 5-HT signifying reduced levels of 5-HT in the brain

Genetical reason for congenital insensitivity to pain?

Truncated, non-functional Nav1.7 channels

What is the precursor of 5-HT?

Tryptophan

What are projections fibres and what do they connect?

UMNs connect the cortices to other brain structures and spinal cord the pyramidal tracts are a sub-population of UMNs that produce movement

Explain the stroop task(AN INFERENCE MEASURE) ?

Used as a good measure of interference - Name the color - Slower in reading the word , if it's written in different color

Explain the polymerase chain reaction

Used to identify triple repeat expressions

What is the role of the thalamus in regulating pain responses?

VPL is main somatosensory area of thalamus, but other components may also be involved acts as the final relay before sensory signals reach the cortex

Describe Variable Expressivity & Penetrance?

Variable expressivity : Variation in expression - the degree to which as disorder is expressed in an individual is different - different people have different levels of learning disablities for example , mild to severe Penetrance: Penetrance is complete if everybody who inherits the gene variant for that condition goes on to show signs of that condition or incomplete if people develop disorder and lives without showing signs The proportion of individuals with the gene who are affected often dependent on age of assessment

Cannabis

Various preparation of Cannabis Sativa Active agent (THC) mimics effects of small endogenous lipid messengers (Eg: Anandamide) Inhibits wide range of neurotransmitters release and periphery via specific Gi protein-coupled cannabinoid receptors Mild euphoric effect in moderate doses , dysphoric in high doses particularly in naive users. Very low acute toxicity but some concerns about the precipitation of psychosis in chronic heavy users Stimulates appetite through actions on feeding centers in the hypothalamus and possibly gut - Analgesic

Name the thalamic nuclei that are important mediums for pain processing ?

Ventral posterior lateral nucleus & Ventral posterior medial nucleus VPL very important for processing of different noxious inputs

How do you assess pain in children?

Visual analogue scale using types of faces

How is the amygdala involved in fear conditioning?

Visual thalamus send crude information about stick/snake to amygdala and visual cortex for further processing: 1. Amygdala - Processes this information very rapidly and errs danger and automatically and preconsciuosly prepared for fight or flight 2. Visual cortex responds slowly and accurately

Signs that inflammatory processes going on in meningitis ?

WBC increased in Peripheral blood and CSF

What is doing mode and being mode? What are the "modes of mind" according to John Teasdale?

We should be in the BE MODE as opposed to DOING MODE Be in the present mode and allow things to happen to us and treat thoughts as mental events - accept it and let it pass

Treatment significance of 5-HT1b and 5-HT1D receptors

When 5-HT1d receptors are activated by 5-HT or by another drug like a 5-HT1d agonist - attenuate the release of CRGP (they are heteroreceptors) 5-HT1D receptors - are present on blood vessels and modify blood flow and major treatments for migraine attacks is 5-HT1D agonist

What is vasospasm?

When arteries contract and clamp down due to irritation

TONIC (BASE LEVEL FIRING) relating to motivation ?

When base level firing is blocked , for example - Neuro epileptic drug which are dopamine blockers - we see loss of motivation as a side effect - Differences: D1 receptor - rewarding pathway D2- More aversive

What is Quantitative sensory testing?

When patients are assessed for pain - if you do some physical asessment of pain - where you apply different stimuli and see their response - you can see if they exhibit allodynia or hyperalgesia or both

What is large vessel occlusion?

When the blood clot or a plaque cholesterol plaque has formed somewhere in the body and has then travelled to the brain where it lodges itself to one of the large blood vessels that feed the brain

What is lacunar occlusion?

When thrombotic stroke happens in smaller blood vessels - or some of the smaller subcorticular structures in our brain - lacunar occlusion

Does hypoxia , hypercarbia , acidaemia lead to toxicity ? Why do you have a slower onset of action of local anaesthetics in case of inflammed/infected tissues ?

Yes , because it leads to decreased protein binding and therefore toxicity Causes acid environement - acidemia - so end up with less of ionized form of the drug across the extracellular compartment and less of unionized form - get much slower onset of action

Do emotional disorders such as depression affect patients with mood disorders on a neurological level? If yes where

Yes, Prefrontal cortex , amygdala-hippocampus complex thalamus & ventral striatum , basal ganglia and connections among these

What is addiction?

a compulsion to take a substance despite harmful consequences loss of control over intake negative symptoms when access to substance is prevented wanting occurs despite tolerance to liking many factors determine whether occasional use becomes addiction including the drug, the person and the context

What is emotion?

a positive or negative experience that is associated with a particular pattern of physiological activity Emotions are complex systems developed through the course of human evolutionary history that prepare us to act in response to environmental stimuli and challenges

What is operant conditioning?

a type of learning in which behavior is strengthened if followed by a reinforcer or diminished if followed by a punisher

What can injury to or CNS dysfunction of the basal ganglia cause?

abnormal involuntary movements = dyskinesias or postures = akinesias in which the patients may be rigid or struggle to move

What are the emotional deficits observed clinically and behaviourally in psychotic disorders?

abnormal or deficient emotional responsiveness leading to: 1. disturbed social interaction 2.diminished ability to learn from punishment 3. Interpersonal behaviour is selfish, dominant , maipulative and superficial 4. Inability to experience deeper feelings of love and indifference to feelings of others 5. Lack of empathy and remorse 6. Flat affect; incongruous affect

Explain the action of anti-craving medicines acamprosate?

acamprosate: Calcium salt of N-acteyl-homotaurine: Registered for use as adjunct in maintaining abstinence in alcohol-dependent patients - Reduces alcohol consumption in alcohol-preferring rate - Reduces neuronal excitability that occurs during alcohol withdrawal

What is hydrocephalus?

accumulation of cerebral spinal fluid occurs commonly during birth receive a shunt which takes the CSF out and probably deliver it to the stomach

What is the neurovascular unit?

accumulation of the different types of cells that act together in synergy to give a functioning brain

What is the resolution of inflammation?

active process generation of chemicals which signal healing dysfunction of this response may lead to chronic inflammation associated with disease dysfunction may lead to chronic pain

What is qualities of morphine?

acts via a u-receptor analgesia euphoria/dysphoria tolerance (major issue) dependence (not an issue in patients) constipation (40% on oral) anti-tussive - prevent, relieve cough

What does NICE recommend for preventative migraine therapy?

acupuncture or gabapentin in treatment-resistant cases botulinum toxin type A is recommended as an option for adults with frequent chronic migraine

What do opioids work well for?

acute postoperative pain

What is essential that patients discuss with families?

advanced directives they do not kick in until you lose capacity important to ask before you lose capacity - vitally important to have this discussion early and to make the necessary documentation of a patient's wishes Extremely difficult disease with high carer burden

What do you need to consider in the pharmacological management of depression?

adverse effect profile toxicity in overdose interaction with other treatments cost

What is the role of the anterior cingulate cortex (ACC) in emotion regulation?

also part of the limbic system - involved in a form of attention that serves to regulate both cognitive and emotional processing neuroimaging studies show that ACC has two separate subdivision involved in cognitive (dorsal) and emotional (rostral) processing

What is general anaesthetics? General anaesthesia:

alters central neural processing Multimodal or balanced general anaesthesia: Drug induced readily reversible loss of consciousness with decreased response to painful stimuli(anti-nociception) and muscle tone(immobility) with maintenance of physiological stability divided into inhalation and intravenous anaesthetics

How does Sizing PCR give accurate sizing of the CAG repeat (up to ~ 90 CAGs)

amplification across the CAG repeat HD1 primer is fluorescently labelled PCR fragment sizes can be detected by capillary electrophoresis samples with known alleles sizes included as controls

Why does fear activate the amygdala?

amygdala is involved in the automatic, preconscious detection of threat and danger in the environment, to quickly act (fight or flight)

What are the advantages of CBT?

an empirical, 'here and now', approach short term structure collaborative approach - not 'clinician-centred' Therapeutic attention is focussed on the present situation rather than historical or childhood facts; emphasis on current cognitive factors which can be accessed (and measured) in order to change thinking , emotion and behaviour

What is pain?

an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage

What is the definition of pain according to international association for the study of pain , IASP?

an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

What is the clinical use of NSAIDs?

analgesia (acute/post-operative) - short term: aspirin, paracetamol, ibuprofen - longer acting: naproxen, piroxicam - conjunction with opioids for chronic pain decrease in temperature chronic/acute inflammation - Rheumatoid arthritis - gout - high doses needed to treat above two

What are the 4 stages of anaesthesia?

analgesic stage excitement stage surgical anaesthesia stage medullary paralysis stage

What is paracetamol?

analgesic, antipyretic, weak anti-inflammatory metabolised in liver (half life 2-4 hours) mechanism of action is not very clear

What were COX-2 inhibitors be studied for?

analgesic/anti-inflammatory effects in arthritis

What are opioids?

analgesics opium is extracted from poppy juice, contains a number of alkaloids including morphine used socially and medically for 1000 years, produces euphoria, analgesia and sleep endogenous (endorphins, encephalins) or synthetic substances that produce effects similar to morphine which are blocked by naloxone

What is step 1 in treatment of mild and/or occasional attacks? When are they most effective? What are they often used as? What might GPs add to it? What should it be combined with?

analgesics/NSAIDs - paracetamol, ibuprofen, diclofenac - these are the primary therapy - anti-emetics are useful if nausea is troublesome most effective if taken early during attack often used as self-medication as available over the counter GP can add an anti-emetic - domperidone, metoclopramide - to enhance absorption as they accelerate gastric emptying combine with rest and sleep

What are the clinical features of late disease?

anarthric (loss of articulate speech) severe swallowing problems immobile weight loss slowly progressive(later stages might not be able to communicate what they need )

What is the subcortical blood supply?

anterior cerebral artery - between the two hemispheres middle cerebral artery - gives off tiny branches lenticulostriate arteries - caudate, putamen, parts of the thalamus, white matter tracts are fed - no anastamoses - if they become occluded, there is no alternative supply = STROKE could be DEADLY

What is the internal capsule composed of?

anterior limb genu posterior limb - pyramidal fibres

What are some effects of NSAIDs?

anti-inflammatory analgesic antipyretic - reduce fever

What is the normal stimulus response function?

apply non-painful stimulus, hits threshold, anything over threshold gets bigger and bigger (pain) and reaches plateau

What are the processes to emotion? What are he factors of process of emotion ?

appraisal arousal expression action readiness

What can be seen poking out from the arachnoid into the superior sagittal sinus?

arachnoid granulations - chunks of arachnoid mater that protrude up and inserts themselves into the vein - often in close proximity of the sagittal sinus - role: reabsorption of CSF into the venous system

What is the primary auditory cortex?

area of the cortex involved in processing auditory stimuli found right next to Wernicke's area next to the superior temporal gyrus

What is the chemoreceptor trigger zone (CTZ)? Where is it found? What are some receptors that the CTZ has? What is the major output transmitter?

area outside of the BBB which detects chemicals in the blood and can be activated by such chemicals found at the base of the fourth ventricle and has multiple receptors dopamine D2, 5-HT3, opioid, acetylcholine neurokinin - Substance P - whatever the cause or source, substance P is released from the vomiting centre

What are the pathways that are active when we are moving?

areas 1-3 - primary somatosensory cortex - receiving information from the body sends some projections to the motor cortex vast majority of the projections are going posterior to the secondary somatosensory cortices - this is the area that helps us to interpret all the information being received in the primary SC SSC sends projections to the front of the brain areas 8,9,10 - prefrontal cortex - receives information from the SSC and is organising and planning the movement to be executed information is sent to the premotor cortex - areas that organises the movement area 4 - motor cortex - produces the movement

What are drugs used to control nausea and vomiting?

as many neurotransmitters provide input or output at the vomiting centre, various drugs can be effective 5-HT3 antagonists (ONDANSETRON , GRANISETRON) eicosanoid synthesis inhibition [corticosteroids](Dexamethasone) neurokinin1 antagonist [agonist: substance P] (apprepitant , casopitant) dopamine D2 antagonists(metoclopramide , domperidone , haloperidol) muscarinic antagonists(scopolamine) antihistamines(cinzzarizine) histamine H3 antagonist(betahistine : for vertigo nausea) cannabinoid agonists(nabilone) multiple (dopamine , 5HT & muscarinic antagonist (olanzapine))

What is acetylsalicylic acid also known as?

aspirin irreversible inactivation of COX1/2 oral, rapid absorption, 75% metabolism in liver first order elimination, half life = 4 hours myocardial infarction therapy

What are the three types of white matter tracts?

association fibres - exchange information within one hemisphere (ipsilateral) - pair of them commissural fibres - exchange information between hemispheres (contralateral) - cross left to right projection fibres - carry information from the cortex to other regions of the brain and spinal cord - UMNs are projection fibres and the pyramidal tracts are important sub-sets of UMNs that comprise the pyramidal system and produce movement - concerned with movement

What do patients want from an analgesic?

at least 50% pain reduction no worse than mild pain relief from related problems - sleep disturbance, improved mood no side effects those who get better do well - improvements in fatigue, mood and sleep, general measures of function, QoL and ability to work

Where can be basal (ventral) forebrain be seen?

at the bottom of the brain

What is attentional bias/emotional bias?

attention to emotional stimuli cause interference with their performance making them slower or making them more mistakes

What is multiple sclerosis?

autoimmune disease that attacks the myelin and produces symptoms of UMN and LMN syndromes - insulating fat around them is degenerated TINGLING , COORDINATION PROBLEMS , BLURRED VISION , SWALLOWING, DIFFICULTIES SPEAKING most common is the one that alternates between symptomatic and asymptomatic periods

What does MBCT target?

autonomous relapse processes

Describe Huntington's disease

autosomal dominant expansion of a CAG nucleotide repeat in exon 1 of the Huntingtin (HTT) gene HTT is widely expressed, required for normal development CAG-repeats are in the coding region so are translated into polyglutamine tract - acquires novel deleterious function when abnormally expanded = leading to neuronal dysfunction and neurodegeneration

What is myotonic dystrophy type 1?

autosomal dominant expansion of the CTG trinucleotide repeat in the 3'UTR of the DMPK gene

What is Huntington's disease?

autosomal dominant with full penetration with expansion in the disease range trinucleotide repeat disorder - repeating CAG Gene was first to be discovered on chromosome 4

What is preventative migraine therapy? What is given?

avoid known patient-specific migraine triggers such as stress or dietary factors b-blockers - propranolol, metoprolol calcium channel blockers - flunarizine anticonvulsants/antiepileptics - valproate, topiramate (caution in pregnancy) pre-menstrual oestrogen can be effective tricyclic antidepressant - amitriptyline

What are the EEG waveforms during a sleep cycle?

awake - high frequency beta waves - amplitude is fairly low - voltage is low drowsy - alpha waves prominent - amplitude increases stage 1 sleep - theta waves are prominent - slower and smoother stage 2 sleep - spiky, high amplitude sleep spindles = do not appear until 6 months = fewer in older adults (problem with staying asleep) - mixed EEG activity slow wave sleep - stages 3 and 4 - progressively more delta waves - stage 3 = 50% delta waves - stage 4 = more then 50% delta waves - big amplitude, slow cycling REM - rapid eye movement - low voltage - low amplitude - high frequency asymmetrical waves

What are the EEG waveforms during a sleep cycle?

awake - high frequency beta waves - amplitude is fairly low - voltage is low drowsy - alpha waves prominent - amplitude increases stage 1 sleep - theta waves are prominent - slower and smoother stage 2 sleep - spiky, high amplitude sleep spindles = do not appear until 6 months = fewer in older adults (problem with staying asleep) - mixed EEG activity slow wave sleep - stages 3 and 4 sleep - progressively more delta waves - stage 3 = 50% delta waves - stage 4 = more then 50% delta waves - big amplitude, slow cycling - In picture - stage 4 Shown REM - rapid eye movement - low voltage - low amplitude - high frequency asymmetrical waves

When might acute pains go on for a long time?

burns dressings sickle cell(significant times between crisis when no pain experienced flare ups of RA - Rheumatoid arthritis

Why should benzodiazepines not be stopped immeadiately ? what happens if theyre stopped immeadiately?

because some dependence and withdrawal - dont stop drug but lower dose of drug Sudden medication stop = anxiety , insomnia , unsteadiness , seizures

What are the benefits of sleep for memory?

behavioural evidence of benefits of sleep for procedural (skilled based motor types) and declarative memory (learning, conceptual stuff) more benefits seen after longer sleep durations - even 6 minutes naps can improve procedural learning

What is the best single agent therapy and why? What is the most effective for motion sickness? What is most effective for chemotherpy-induced emesis?

best single agent therapy - NK1 receptor antagonism - aprepitant - this is because substance P is the major output transmitter from the vomiting centre - active against most causes motion sickness - H1 and H3 antagonists are effective(betahistine , betahistamine) chemotherapy-induced emesis - can be controlled by a combination of a corticosteroid and dopamine antagonist - 5-HT3 antagonists(ondasetron) are also effective

What support is there for the James-Lange theory?

beta blockers reduce anxiety/subjective fear (i.e. blood pressure or tightening of muscles) also this idea forms the basis for the lie detection industry i.e if people experience anxiety or guilt when they lie, specific patterns of physiological arousal accompanying these emotions should be detectable

How can management of autonomic symptoms of Generalized anxiety disorders be done?

beta-adrenoceptor antagonists (propanolol) reduces autonomic effect do not withdraw abruptly to prevent rebound effects

How thick is the cortex?

between 2-4mm thick when it is unfolded, it can reach 2 meters^2

What are the symptoms of ischaemic stroke - posterior circulation?

bilateral sensory/motor deficits disconjugate eye movement cerebellar dysfunction isolated hemianopia- means not occuring in conjugation with other symptoms of the anterior circulation

What essentially happens when you take morphine or opioids?

binds to receptors in the PAG and NRM it turns off the inhibitory signalling and releasing and excitatory signal

What are local anaesthetics?

block generation and conduction of nerve impulses at local contact site consciousness is maintained Inhibit action potentials in nociceptive nerve fibers and block transmission of pain impulses. examples of lignocaine, bupivacaine

How do SSRIs work? Why does a person initially feel worse after taking SSRIs ?

block reuptake of serotonin bind to 5-HT reuptake transporter - this means more 5-HT is available in the synaptic cleft so more can bind to 5-HT in the post-synaptic membrane - need to achieve an increase in 5-HT (lack of this in people with depression) once given SSRIs, there is more 5-HT available in the synaptic cleft and some will bind to the auto receptor - by activating the receptor, it will prevent the release of 5-HT from the pre-synaptic neurone into the synaptic cleft - this means, initially, a person may feel slightly worse

How was the first theory of migraines disputed?

blood flow changes do not occur in common migraines MRI cerebral blood flow analysis confirmed biphasic changes but wrong pattern there is a 30% decrease in cerebral blood flow and a variable 30% increase cerebral blood flow the aura starts when there is a decrease in cerebral blood flow

What do stroke symptoms depend on?

blood vessel involved size of the lesion region of the brain affected

What is Schachter's two-factor theory for the process of emotion?

both our physiological response AND cognitive appraisal of the situation determines our emotional experience (possibility for misattribution of arousal!) 2 factors: physiological arousal and cognitive label Eg: If you experience racing heart and sweating palms - during exams - then emotion is anxiety - so arousal feedback (bodily reaction) provides the subjective heat for emotion but the quality of emotion is derived from a second factor based on Cognitive appraisal you give it , based on situtational information Emotion depends on how arousal is interpreted by the person experiencing it

Where are opioid receptors found?

brain and spinal cord

What is BDNF?

brain derived neurotrophic factor - regulates neurogenesis, development, dendritic growth, survival and maturation

Just how much white matter is there in the brain?

brain is composed of a huge amount of white matter lateral ventricles and third ventricles can be seen

How does cell apoptosis start in stroke?

calcium in excess causes mitochondrial damage that initiates apoptosis

Which hypnotic can AND cant be used for elderly?

can - Z Drugs such as Zolipidem , Zopiclone Cant - Diazepam (benzodiazpines)

What is Tourette's syndrome?

can appear in minor forms or violent most patients learn to cope with the behaviour and therapy Altered basal ganglia function

What are the arteries that supply the anterior aspect of the brain?

carotid arteries - internal carotid arteries - first branch they give off is the middle cerebral artery - comes through the lateral fissure - feeds the largest part of the brain - parietal lobe, chunk of frontal lobe, little bit of temporal lobe - most common artery to have a stroke in at the top of the Circle of Willis, there are two arteries that go up through the midline - anterior cerebral arteries - curve posteriorly, supplying a lot of the corpus callosum, frontal lobe

What are non-pharmacological treatments of insomnia?

carry this out first gives help to a large number of people in the first week, medication works well by 4th-8th - pharmacological and non-pharmacological are neck and neck to maintain good sleep then non-pharmacological are much better - behavioural changes CBT will help with the other morbidities as well as sleep problems

What is neuropathic pain and what are the different types?

caused by a lesion or disease of the sensory nervous system tissue injury may not be obvious does not have a protective funcion descriptors commonly used - burning, shooting, pins and needles or numbness less well localised UNLIKE INFLAMMTORY PAIN

What are place cells?

cells that respond only when an animal is in a particular place in a familiar environment - found in hippocampus - formation of a spatial map

What is the role of the cerebellum, brain stem, thalamus?

cerebellum - balance, coordination and synchronisation of muscles brain stem - just about everything - midbrain - cerebral peduncles (motor tracts), substantia nigra, red nucleus, tectum (vision and hearing), reticular formation (consciousness) - pons - some direct connections with cortex - medulla oblongata - respiration, heart rate, vomiting and sneezing thalamus - major relay station for sensory information from. body

What structures can be seen in a midline dissection of the brain?

cerebral hemispheres - the CSF looks bright - sulci are filled with CSF corpus callosum - prominent white matter structure but looks darker in the scan ventricles - contain CSF therefore it is white diencephalon - composed of thalamus and hypothalamus midbrain - directly underneath the diencephalon - look for a little channel (cerebral aqueduct)

What are the alternative to opioids?

change drug or route - switch to subcutaneous to epidural morphine (targeting directly to the site) - changes in metabolism (effects of a single injected dose is 6X that of a single oral dose) spinal opioid - epidural/intrathecal give little benefit over subcutaneous good for combination therapy - infusion for chronic pains

What are changes in blood flow driven by which result from what? What does this overall change result in? What does the aura usually involve? What can therapy that prevents the aura still leave?

changes in blood flow driven by change in metabolic demand resulting from neuronal depression are thought to result in the progressive change in MR signal in the occipital cortex aura usually involves a wave of electrical activity starting in the occipital cortex and spreading slowly at 2-3 mm/min associated with visual hallucinations across the visual field that is reproducible in the same individual headache

What do the electrical activity reflect?

changes in neuronal network connectivity, asynchronous vs. synchronous neuronal activity

Where are electrical activities picked up?

changes in the cyclical frequency of electrical signals measured on scalp the electrical signals are reflecting networks of activity some times they are behaving synchronising - firing together sometimes there are large amplitude wave - theta other times they are firing a synchronising - not firing together

Where are electrical activities picked up?

changes in the cyclical frequency of electrical signals measured on scalp the electrical signals are reflecting networks of activity some times they are behaving synchronising - firing together sometimes there are large amplitude wave - theta other times they are firing a synchronising - not firing together

What is seen post an ecephalitis infection

chickenpox Flu A and B Measles

What are the clinical issues with opioids?

choice of opioid - oral morphine is standard tolerance - higher plasma concentration to achieve same pharmacological effect pain sensitivity - chronic pain is not very responsive to opioids route of administration - speed of onset and duration of effect

What can a lesion in Broca's area cause?

choppy, not well organised conjunctions and prepositions messed up inferior frontal gyrus expressive aphasia - failure to formulate

What are the early clinical features in Huntington's?

chorea +/- psychiatric +/- depression anxiety, psychosis frontal lobe features

What are the surface landmarks in the midline section?

cingulate sulcus - runs in anterior to posterior direction - is it parallel to the corpus callosum marginal sulcus - good way to find the central sulcus parieto-occipital sulcus - runs in the midline as well calcarine sulcus - anterior to posterior direction in the midline - location of the visual cortex

What are the different association fibres?

cingulum - connecting the frontal lobes to the temporal lobes (hippocampus) cingulum (parahippocampal) superior longitudinal fasciculus - runs the entire length of the hemisphere - connects frontal to parietal to occipital inferior longitudinal fasciculus - skips out on frontal - connects the temporal to parietal to occipital fasciculus occipito-frontalis - frontal to occipital uncinate fasciculus - U-shaped - connects the frontal to tip of temporal

What can pre-sleep thoughts promote?

cognitive arousal CBT combines previous strategies with: a range of strategies that can prevent or interrupt maladaptive thoughts - thought-blocking and distraction - cognitive restructuring (beliefs and attitudes)

What can pre-sleep thoughts promote?

cognitive arousal CBT combines previous strategies with: a range of strategies that can prevent or interrupt maladaptive thoughts - thought-blocking and distraction - cognitive restructuring (beliefs and attitudes)

How is combination therapy useful?

combination therapy shows additive benefits clinical trials have shown a combination of a NK1 antagonist, a 5-HT3 antagonist and a corticosteroid give 85-90% protection against highly emetic chemotherapy induce emesis for less severe treatments a 5-HT3 antagonist and a corticosteroid give 70-90% protection

What are the non-medical treatments for Huntington's?

complex condition where MDT working is essential for good care SLT - annual speech and swallowing assessments dietetics - regular weights, fortified diet, supplements specialist nurse - to support family, assess for problems, assist with complex social care aspects CPN - may be needed if significant psychiatric issues

What are the clinical features of Huntington's disease?

complex interaction of neurological, psychiatric and cognitive features neurological - chorea (most common) - uncontrolled, irregular movement - dystonia -uncontrolled contraction of muscle - dysarthria - difficulty with speech - dysphagia - difficulty swallowing - Parkinsonism/seizures in juvenile onset cognitive - progressive dementia of frontal lobe type - 'concrete thinking' - loss of empathy - lack of insight - loss of verbal fluency - loss of ability to sequence - cant work out all the steps of the process to acheive task psychiatric - depression - anxiety - psychosis non-neurological features - high metabolic rate and weight loss People with huntington's - grind teeth to overcome oral-facial chorea Limitation of eye movement is also seen - chorea Difficulty in sustaining movement- Huntington's disease - keep tongue out for long Quasi purposeful movement - as if they're on purpose movements Generalized affecting head to toe especially head and neck - affecting speech - affecting swallow - have to liquidize food to eat Can't close eyes and if told to stretch hands straight - can't sustain for long

Why were emotions developed?

complex systems developed through the course of human evolutionary history that prepares us to act in response to environmental stimuli and challenges

What is opioid induced hyperalgesia?

complication increased pain response to painful stimulus - opioids can cause pain in conditions of tissue damage like osteoarthritis

What are the blood vessels like in the brain?

composed of a layer of endothelial cells which fit together tightly when two cells touch, their membranes join together to create a barrier that allows passage only of selected material between the blood and brain - tight junctions basement membrane surrounds the endothelial cells pericytes and astrocytes also play a role in maintaining the BBB

What are non-specific symptoms of stroke?

confusion, drowsiness, dizziness nausea, double vision incontinence

What is the role of the cortex in regulating pain responses?

consciousness of pain, plus the limbic system for emotional response Makes us conscious of pain

What are the main side effects associated with opioids?

constipation, dependence, respiratory depression

Describe COX 1 enzyme

constitutive enzyme most tissues, blood platelets tissue homeostasis

What are the two modes of how action selection is normally achieved?

contention scheduling supervisory attention system

What do the efferent neurones involved in vomiting do? From where does the vomiting centre receive information from?

contraction - diaphragm - abdominal muscles stop respiration increases abdominal pressure - force the contents of the stomach out of the mouth in this reflex arc receives information from - GI tract, cerebral cortex - can be made to induce this reflex by environmental and chemical changes

What happens once L-DOPA crosses into the CNS?

converted into dopamine in all the neurones of the brain (not just in the basal ganglia)

What does the sensory system achieve?

converts a natural stimulus (energy) to action potentials intensity and duration of the stimulus is conveyed

What are the stages of Vomiting/Emesis ?

coordinated involuntary reflex involves powerful sustained contraction of the abdominal, chest wall and diaphragm muscles (which greatly increase intra-gastric pressure) opening of the cardioesophageal sphincter, glottis and jaw Due to build up of pressure cuz of the above events , rapid evacuation of stomach contents up to and out of the mouth breathing suspended and epiglottis closes over the trachea to avoid any inhalation of vomit

What are the different commissural fibres?

corpus callosum - biggest and most prominent - connection point between the two hemispheres - anterior to posterior direction fornix - connects the hippocampus (temporal lobes) to the mamillary bodies (between the cerebral peduncles) - starts laterally, curves over the top of the thalamus and makes connections to the mamillary bodies important for the limbic system and memory processes that involve the hippocampus anterior commissure - small and cannot be seen that well - get prosection right, you can see it crossing back and forth between the two hemispheres (like the corpus callosum) - connects the two amygdalas - important for the limbic system posterior commissure - comes off from superior colliculus - up and over the thalamus - involved in the visual system and regulating movement of the eyes and the cranial nerves

What are the structures of the basal ganglia?

corpus striatum - caudate nucleus - lentiform nucleus = putamen = globus pallidus ~ internal (GPi) ~ external (GPe) sub thalamic nucleus (STN) - only area that has glutamatergic neurones substantia nigra (SN) - pars reticulate (SNr) - pars compacta (SNc)

What are the features of the cortex?

cortex is the top layer of grey matter so sits on top of the white matter

What does cortical spreading depression look like in a patient who suffers migraines during exercise?

cortical depression starts at the posterior pole wave of activity spreading 2-3 mm per minute and the patient reports aura during this part of the recording of the activity Therapy that prevents the aura can still leave the headache

What is the excitement stage?

cortical inhibitory centres depressed increased muscle tone - hyper excitability vomiting - consider anti-emetic temperature control lost - hypothalamus is dampened down alpha-rhythm of EEG desynchronised - since normal brain activity is synchronised - at this stage, neurones are firing randomly respiration increased / irregular

What makes up the pyramidal tracts?

corticospinal and corticobulbar tracts these are controlling our conscious interpretation of movement 1 million nerve fibres with a conduction velocity of 60m/s

What is the impact of depression and anxiety disorders?

cost 1% of UK gross national product - leading reason you or anyone else will retire early from work leading cause of premature death in doctors (suicide) suicide is 2nd leading cause of death in age groups 15-44years (after accidents): 70% due to depression or anxiety disorders suicide is 3 times more likely in men than women, in socially isolated, with physical and mental illness, alcohol and drug problems, recently discharged from mental health wards, previous self-harm (10-fold) and violence 50% of worse outcomes e.g. longer length of stay from in-patient care complicated by depression or anxiety

What is bipolar disorder?

cycle between depressed mood and mania depressed mood - period of at least 2 weeks with core symptoms accompanied by at least 4 other symptoms mania - elevated mood; increased energy; incomprehensible speech, racing thoughts, poor concentration etc. first episode observed before age 30 with a peak incidence between 15-19 years of age in UK, increased incidence observed in ethnic minorities

What are symptoms of UMN syndrome?

damage to the UMNs, more random firing in the lower motor neurones so bulking up of the muscles clonus = UMNs are not properly communicating with the LMNs spasticity - hold their arm and gradually push on it, there would not be any resistance but push really fast and hard, there is resistance classical symptoms = Babinski reflex

What is the proposed mechanisms of action of General anaesthetics ?

dampening down the system - activate the inhibitory NT - inhibit the excitatory NT GABA-a - activate inhibition - activating it = influx of chloride ions from outside to inside - hyperchlorination - this is synonymous to inhibitory effects Excitation 3 - inhibit the excitatory input - inhibit or block these as they are associated with the movement of sodium from the outside of the cell to the inside

What are the types of long term memory?

declarative (explicit) - events and facts non-declarative (implicit) - unconscious knowledge = motor skills = conditioned responses

What are the symptoms of LMN syndrome?

decrease in muscle tone due to muscle atrophy independent muscle fibres will fire so it will look like twitching (recorded with EEG signals)

What is the analgesic stage?

decreased higher cortical function - affecting brain activity consciousness not loss - but thoughts blurred reflexes present smell and pain lost at end of this stage

What is the pathway that the projection neurone (from lamina I) to the thalamus enters?

deep neurons in the spinal cord spino-thalamic pathway - one of the main pain pathways important for spatial discriminatory aspect of pain (tells its painful there and hurts this much) Projection neurones (from lamina I) project to the brain: thalamus

What is the Duchenne smile?

demonstrated the role of specific facial muscles in producing emotions through facial expressions Duchenne smile is a real smile Obtained false smile by electrically stimulating the appropriate facial muscles : view the facial differ in the degree to which they are under voluntary control and that different muscles are associated with the expression of different emotions

What are the subfields of the hippocampus? What is the main input pathway

dentate gyrus - input pathway - theory that it is a pattern separator (familiar and unfamiliar experiences) - sends messages to CA3(via powerful mossy fibre pathway) which sends messages to CA1 (Via schaffer collateral) - then messages are sent to the subicular cortex this forms a loop which has reciprocal connections backwards as well main input pathway is from the temporal lobe (entorhinal cortex --> dentate gyrus)

What is the HPA axis in depression?

depressed patients displayed HPA hyper-activation: increase cortisol in saliva, plasma and urine increase CRH in CSF and in limbic brain region increase size (as well as activity) of the pituitary and adrenal glands impaired negative feedback

What is the burden of long-term pain?

depression sleep disturbances fatigue impaired physical functioning impaired concentration time off work less active

What is the neurobiology of depression?

depression involves dysfunction of a complex network of limbic - striatum - frontal cortex amygdala - anxiety hippocampus - memory deficits reward circuits - anhedonia(lack of pleasure) and motivation - low dopamine frontal lobe - motivation, decision making striatum - motor slowing - extreme depression: Parkinsonism

How can we top down influence of pain?

descending inhibitory control pathway originates in the amygdala and hypothalamus - affects the emotional processing of pain projections to the PAG PAG does not project directly to the spinal cord but to the NRM(Rostral ventromedial medulla) and then projects to the spinal cord this pathway acts to shove down excitation in the spinal cord - survival that allows you to escape a painful situation

What is executive function?

description of psychological processes that underlie flexible goal directed behaviour (e.g. planning behaviour, inhibitory control, attentional flexibility, working memory, monitoring)

What does not work in emesis and nausea?

despite it being an earlier and less severe sign than vomiting, nausea is more difficult to control with even the best anti-emetics this may be because it involves interactions with higher centres and is partly a learned or associative response a combination of anti-emetics and mild sedation (benzodiazepines) can be used to reduce severe nausea corticosteroids are not very effective for control of acute vomiting, and 5-HT3 antagonists are not very effective against non-chemotherapy vomiting

Why do we assess pain?

determine severity and impact of pain evaluating treatment outcome stratifying and personalising treatments screening for undiagnosed pain

What are some unwanted side effects of L-DOPA?

development of choreic movements ~ 2 years (up till 6) rapid fluctuation in clinical state - 'on-off effect' - may need to adjust the dosage or give more tablets nausea and anorexia - peripheral effect hypotension - not a major problem psychotic effects

How do you identify a stroke?

diagnosis is performed on the basis of a neurological examination followed by urgent referral for neuroimaging generally this is via CT which can detect haemorrhage, but is less effective at detecting acute ischemic stroke

What comes from the forebrain (prosencephalon)?

diencephalon - thalamus - hypothalamus telencephalon - basal ganglia and cortex

Where is the midbrain in an inferior view of the brain, ventral view of midbrain?

diencephalon is superior to it midbrain is tucked away/hidden only see 2 bumps poking out

What is the homunculus?

different areas of the brain are specific to certain parts of the body disfigured as the size of each structure corresponds to the amount of brain dedicated to the structure and the density of cells within that region of the brain

What is aphasia?

disruption of language and/or speech

Does pain occur in isolation?

does not occur in isolation in specific human being in psychosocial, economic and cultural contexts that influence the meaning, experience and verbal and non-verbal expression of pain

How do you recognise pain?

does the patient have pain? do other people know the patient has pain?

What are some alternate drugs that can be given for PA? Which onset of PA is this most useful for? Why?

dopamine agonists early onset - still given the option of introducing L-DOPA later

What are the causes of RLS?

dopamine dysfunction - Parkinson's genetics - familial association medications - antidepressants, antipsychotics chronic illness vitamine and mineral deficiencies - B12 - magnesium pregnancy sleep deprivation

What are the causes of Restless leg syndrome?

dopamine dysfunction - Parkinson's genetics - familial association medications - antidepressants, antipsychotics chronic illness vitamine and mineral deficiencies - B12 - magnesium pregnancy - first trimester sleep deprivation

What are the anatomical terms used to describe the midline structures of the brain?

dorsal is against the back (sensory) ventral is tummy side (motor)

What are the social implications of Huntington's?

driving - DVLA notifiable condition - usually cannot drive for long as it affects their judgement work - usually fail to continue to work beyond early stages - related to chorea but also frontal lobe features very high levels of carer strain - incredibly difficult combination of symptoms which go on for many years family dynamic - children at risk

How does instant use, chronic use and repeated use of drugs affect addiction?

drugs of addiction acutely boost dopaminergic signalling chronically they down regulate rewards signals to normal stimuli due to altered gene expression repeated use leads to craving, withdrawal and compulsive use even if they become tolerant to the effects of it without the pleasurable part

What are the roles of the 3 meninges?

dura mater - tough, protective arachnoid mater - holds blood vessels and contains CSF which supplies cortex (baths the brain and keeps it buoyant) - trabeculae pia mater - difficult to see and will follow the contours of the brain

What are the 3 meninges?

dura mater (tough mother) - holds the brain in place arachnoid mater (spider mother) -sits on the surface of the brain - reabsorption of CSF - blood vessels and subarachnoid space pia mater (tender mother) - very delicate

What are the 3 main considerations for the classification of pain?

duration of pain acute vs chronic what is the cause? cancer vs non-cancer what are the pain mechanisms? nociceptive, inflammatory, neuropathic, (dys)function

What is not a good discriminator of pain?

duration of symptoms

What has neuroimaging studies shown in patients with psychotic disorders? What is the neural deficits seen in psychotic patients?

dysregulation in both top-down control via prefrontal regions and bottom-up signals via limbic areas

How can bipolar disorder be diagnosed?

eliminate misdiagnosis of bipolar disorder --> differential diagnosis confirmed by a specialist mental health professional

What is emesis? What is nausea?

emesis - vomiting - protective reflex (to expel ingested toxins) shown in mean and most meal-feeding mammals (rats can't vomit) and is associated with nausea nausea - unpleasant sensation that immediately proceeds vomiting - a cold sweat, pallor, salivation, self absorption, loss of gastric tone, duodenal contractions, and reflux of intestinal contents into the stomach often accompany nausea

What is there to debunk the Canon-Bard theory?

emotional outcome is irrelevant to the subjective awareness of emotion triggered in cortex is emotion merely an aroused system?

What is Frijda's Four-Factor theory?

emotional processes are manifestations of a common underlying process views emotion as a integrated evaluative process which includes all the aforementioned components of emotions i.e. appraisal of situation, physiological arousal, expressive behaviour and action readiness

What is the role of the limbic system in emotion regulation?

emotional states are mediated by a group of peripheral, autonomic, endocrine and motor response reflecting an interplay between higher brain centres and subcortical regions limbic system - key brain circuit for the process of emotion, the 'hub' of emotions

How do amplication across the CAG and the CCG repeat?

enables two normal alleles to be resolved in cases where both alleles have identical numbers of CAG repeats but different numbers of CCG repeats HD2 primer is fluorescently labelled PCR fragment sizes can be detected by capillary electrophoresis can't be used to size the repeat but useful to confirm 2 alleles have been detected

Case definition of encephalitis ?

encephalopathy (altered level of consciousness , cognition behavior or personality persisting for more than 24 hrs) and 2 or more of the following :CSF PLEOCYSTOSISFeverSeizures and / or focal neurological findingsCSF pleocytosisEEG findings compatible with encephalitisAbnormal results of neuroimaging

What are deep neurones good at doing?

encoding allows you to know how much is hurts and where

What are the components of the BBB?

endothelial cells - signalling, secrete chemicals tight junctions - borders of the endothelial cells come together and create pathways basement membrane - made of extracellular proteins e.g. laminin, glycoproteins - holds everything in place pericytes - helps in constriction and dilation - some are potential immune modulators astrocytes - type of glial cell - helping to seal the BBB - end-feet which stretch out and wrap around the blood vessel

How do you treat the symptoms of Parkinson's?

enhance DA function 1. L-DOPA + carbidopa 2. DA receptor agonists (bromocriptine, ropinirole, rotigotine) 3. prevent DA metabolism - MAO B inhibitors - deprenyl (selegilline) - COMT inhibitors - entacapone (only effective when used with L-DOPA) 4. increase DA release - amantidine 5. indirect DA enhancement - adenosine A2A receptor antagonists muscarinic receptor antagonists = control tremor neuronal transplants

What do antidepressants do to the HPA cycle?

enhance the negative feedback and decrease HPA axis hyperactivity

What is windup?

enhanced responses (windup) for a given noxious stimulus are associated with repeated (0.5 Hz) stimulation the capacity of a response getting bigger for a fixed stimulation

What neurones degenerate in Huntington's?

enkephalin containing GABAergic medium spiny neurones degenerate first in HS (neurone 3 in pathway) then direct pathway (neurone 6)

What are Lewy bodies?

eosinophilic inclusions in neurones with core of a-synuclein (aggregate to form fibrils and may contribute to dementia seen in 50% Parkinson patients)

What is the incidence rate of migraines?

episodic 10-15% of people Female:Male 3.5:1 affects 16% of menstruating females 2-3 times more common if a first degree relative has it(LIKELY TO BE GENETIC LINK) No affect on life expectancy and costs the UK Economy

What is the hippocampus key to? In the case of HM, what happened? What does destruction of the hippocampi on both sides leave you with?

episodic memory bilateral hippocampal amygdala entorhinal resections - profound deficit in episodic memory - preserved procedural memory - preserved memory of events before surgery - Anterograde memory (forwards memories of new events of his life) - were completely lost leave you will severe memory loss (permanent severe amnesia)

What is convergence?

essential that something painful is not ignored a single sensory neurone in the CNS can receive inputs from many sensory receptors convergence: multiple receptor fields are overlapping, each with their own sensory nerves going off - Maximizes how successfully the signal is transmitted/Relayed multiple sensory neurones are activated and they converge into the spinal cord increase the response - bigger area activated, bigger the convergence

What are the TP-PCR results?

every peak represents a difference of one CAG size there is a clear end to those peak - this show that in combination with the size of PCR there is not expansion peaks continue until tailing off - Peaks taper off - because larger repeats harder to amplify than smaller - so we can't determine repeat size from this method but can determine that there is a lot of expansion(because there is lot of small peaks)

Give some facts about pain

everyday pain is an almost universal experience usually pain warns us that we have injured ourselves in some way pain usually gets better with time and may not need to be treated pain is an ambiguous perception all pain is affected by how we are feeling at the time pleasurable pain?- exercise

What is cancer pain?

examples - uterine cervical cancer, breast cancer - bone metastases - nerve compression localized features of acute and chronic pain - may be acute on chronic often mixed nociceptive and neuropathic pain usually gets worse over time if untreated unlike other types of pain - cause tumor continues to grow locally

Describe chronic non-cancer pain

examples - chronic back pain, arthritis cause may not be obvious complex, may be nociceptive and neuropathic different treatments may be needed For inflammatory and neuropathic component , different treatment required

Describe acute non-cancer pain

examples - fracture, appendicitis, MI symptom of tissue injury or illness - signs of injury in body usually nociceptive occasionally neuropathic (e.g. sciatica - nociceptive symptoms - but symptoms that individual experiences is neuropathic)

What is the time course of events in a stroke?

excitotoxicity - Disruption or inability of cell to maintain homeostasis - so they fire repetitive action potentials - early, huge impact - core tissue will die - it can spread peri-infarct - when excitotoxicity spreads - much lower impact - Peri-infarct depolarisations refers to the spreading of electrical dysfunction beyond the original core of this ischaemic consult inflammation - Hours , days maybe months - Inflammatory reaction of the brain - impact might not be as large as excitotoxicity - but long lasting Aspects of information that could be both beneficial and detrimental - takes body time to react - first few hours = early pro-inflammatory mediators apoptosis - most delayed(after few of the stroke) and lowest impact - cell that didnt initially die from excitotoxicity but somehow damaged or deprived for a sufficient amount of time - they become aggravated enough to decide that they need to undergo cell death - programmed cell death

What can sleep deprivation do to risky behaviours?

executive functioning is not working as prefrontal lobe is not working e.g. increase in number of road accidents in individuals who have lack of sleep reduction in hand-eye coordination - get clumsy too

What can sleep deprivation do to risky behaviours?

executive functioning is not working as prefrontal lobe is not working e.g. increase in number of road accidents in individuals who have lack of sleep reduction in hand-eye coordination - get clumsy too

What happens to the CTG repeat in myotonic dystrophy?

expansion of the CTG nucleotide repeat in the 3'UTR of the DMPK gene DMPK is expressed mainly in muscle and CNS CTG repeats are transcribed into mRNA, but not translated into protein large mRNA molecules accumulate in the nucleus acquire new toxic function by trapping essential cellular RNA-binding proteins Toxic effect produced by the RNA not the protein

What was Darwin's theory of expression?

expression of emotion is mostly innate, although some expressions require practice before they are fully developed

Describe bradykinin

extremely painful substance de novo synthesis during tissue injury made in vasculature and tissue by activated enzymes acts on the C fibre terminals of the skin via B1(induced locally following periods of sustained inflammation) and B2 receptors - if you block these receptor, there is a strong anti-analgesic mechanism ProstaGlandins make nerve terminals more sensitive to other molecules like bradykinin Prostaglandins sensitize nociceptors - to other stimuli like Bradykinin and lowered pH to enhance that inflammatory response

What is the action of the association fibres?

facilitating cortical communication between different regions of the cortex

What two things can happen as you pass through a synapse?

fail and message is lost facilitated, message gets bigger and bigger

Give examples of how formulation is a factor in the brain dopamine levels?

faster and higher peaks in brain dopamine levels: 1. IV heroin better than methadone by mouth 2. Inhaling cocaine better than chewing coca leaves 3. Smoking cigarettes better than chewing tobacco - also poses lesser health riks

What the feeling of pain?

feeling/perception pain includes psychological component

When can paracetamol be used? What the side-effects of paracetamol ?

few side effects with therapeutic doses regular intake at high doses over long period = increase risk of kidney damage toxic doses: N&V, 24-48hours later fatal liver damage

How can you find the supra marginal gyrus?

find the central sulcus - in the middle of the brain, follow the cingulate sulcus in an anterior to posterior direction and when you can go no further, it pokes straight up which is the marginal sulcus the one directly in front of that is the central sulcus

What is the trans diagnostic emotional signs - flat affect? What are emotional deficit signs?

flat or blunted effect - can occur across different diagnoses including primary depression, schizophrenia and Parkinson's disease - shows lack of emotional responsivity in facial and vocal expression - has been associated with brain dysfunction - in schizophrenia, it may not truly reflect the actual subjective emotional experiences of patients.

What can be employed to prevent, delay or reverse neurodegeneration?

foetal neuronal transplantation --> stem cells? promote neuronal innervation, nicotine agonists neurotrophic immunophilins - strong evidence that a lot of the CNS disorders involve an immune component MAO B inhibitors block a-synuclein aggregation (could be maker not causal protein)?

How can you override pain sensations?

for a short period of time through endogenous inhibitory control stressful situation, override the pain ability has evolved so we can protect ourselves

What evidence is there for MBCT for prevention of depressive relapse?

for more seriously ill patients (history of >3 episodes) MBCT halves chances of relapse(Mindfullness based cognitive therapy) highly cost effective due to its group-based approach; reduced demands for clinician time equivalent to continued medication especially relevant for most vulnerable people

What is the vast majority of the brain called?

forebrain

What are the controls of the brain lobes?

frontal - personality, attention, motivation, planning movement parietal - integrating sensory information, language processing temporal - memory, sensory processing, language comprehension occipital - vision

What does the ophthalmic division of the trigeminal nerve innervate?

frontal and parietal cortex and meninges vascular beds

What are the different types of inhalation anaesthetics?

gas - nitrous oxide volatile liquids - halothane - enflurane - isoflurane - sevoflurane - desflurane

What side are the language barriers on?

generally left side i.e. stroke on the left side - language centres are disrupted 30% of people have it on the right side of the brain

Inflammation due to damage to tissue - what does bradykinin do?

generated de novo and activates the nerve terminals sensory nerve terminals do not just receive information and send it up, it can also release transmitters into the local environment when sensory nerves stimulated, the peptides are released into the local environment (SP, CGRP) this peptide release is called antigenic peptogenic release following activation of the sensory nerve is an important part of the inflammatory response peptides can then promote vasodilation

What is the first line option in depression?

generic selective serotonin reuptake inhibitors (SSRIs)-inhibit 5-HT reuptake citalopram, fluoxetine, paroxetine, sertraline favourable side effect profile and less toxic in overdose

What are the parts of the corpus callosum?

genu - 'knee' - most anterior isthmus - largest part splenium - posterior part

How to prevent opioid abuse and euphoric effect of morphine and diamorphine?

give methadone alongside

What is the main excitatory neurotransmitter of the brain?

glutamate

Where does the striatum receive inputs from?

glutamatergic afferents - corticostriatal - thalamostriatal dopaminergic afferents - nigrostriatal striatum is composed of 90% inhibitory GABAergic medium spiny neurones - contains a variety of neuropeptides other than GABA TWO GABAergic efferents (outputs) - striatonigral (SN) - striatopallidal (SP)

ventricles

goes into the occipital lobe, temporal lobe and frontal lobe hole in the brain is filled with CSF

What is systematic desensitisation based on?

graded exposure and counter-conditioning Entails training the patient in deep muscle relaxation constructing a hierachy of anxiety-provoking situations and presenting each situation seriatim to the imagination of the person in a relaxed , non-anxious state Owing to recent technological advances , can be supplemented or repleaced by real-life exposure - in vivo desensitization

What are the internal connections of hippocampus? What happens if you lose inhibitory neurones? What condition sees the loss of interneurones?

green = excitatory neurones black = inhibitory neurones where the inhibitory neurones touch the excitatory neurones results in computations that the hippocampus does hippocampus does complex computations in order to generate memories if you lose inhibitory neurones, you get dysfunction of the hippocampus some types of epilepsy where the inhibitory interneurones fall out due to various factors can lead to more seizures and having impaired memory

What is the basal ganglia?

group of sub-cortical, grey matter structures that are part of the extra-pyramidal motor systems it does not initiate movement, but helps plan movement by integrating cortical input, and feeding back to the cortex, via the thalamus through a direct (excitatory; enabling movement) and indirect (inhibitory; preventing movement) pathway (motor loop)

Describe contention schedulling

habit based system: 1. We have a number of responses in our repetoire to choose from 2. When we are in a circumstance , whichever behavioural response is the strongest of these is automatically selected by the circumstance we are in 3. When we choose one behavioural response , we inhibit all the other possible responses 4. Go with the flow of the environment or the situation you're put in 5. Much of our behavior falls into this - we are not making choices actively , consciously or a decision about what to do 6. This automatic system allows to do multiple things at a time

What are the disadvantages of benzodiazepines?

hang-over some dependence and withdrawal sudden medication stop --> anxiety, insomnia, unsteadiness, seizures - diazepam is not given in the elderly

What are the disadvantages of benzodiazepines?

hang-over- might interfere with day to day functioning some dependence and withdrawal- dont stop medication immeadiately but lower dose of drug sudden medication stop --> anxiety, insomnia, unsteadiness, seizures - diazepam is not given in the elderly

What are Ekman's six (or seven) basic emotions?

happiness, sadness, anger, fear, disgust, surprise these are 6 biologically programmed primary emotions which are innate and universal

How is the hippocampus lain out in the brain?

head of structure is located in the central lobe moves in posterior direction comes up and over the thalamus moves in anterior direction and connects to some structures in the diencephalon

What are the symptoms of ischaemic stroke - anterior circulation?

hemiplegia/paresis- motor symptoms - loss of ability to move one side of the body - side of body affected is contralateral to the side of brain affected hemisensory loss - sensory deficit hemianopia - loss of vision in the same side of both eyes generally in same side of both eyes dysphasia - difficulty swallowing aphasia - language difficulties

What are the different types of ischaemic and hemorrhagic strokes?

hemorrhagic - intracerebral(10%) (inside the brain) - subarachnoid(5%) (arachnoid space) ischaemic(85%) - embolic(30%) (blood clot formed somewhere in the body and comes from somewhere else in the body and travelled to the brain e.g. DVT) - thrombotic(55%) (when the artery is slowing closing in before it gets plugged)

How is movement organised?

hierarchical fashion by the cortex

What is the most conserved brain?

hindbrain

What does an MRI scan of the temporal lobe show?

hippocampus

What are the components of the limbic system?

hippocampus - lies in the meso- temporal lobe - which is connected by large arc shaped output pathway called the fornix - outward projection of fornix projects to the mammillary body septal nuclei - lies deep in the brain stem - connected to the hippocampus to and fro through the fornix - Important nuclear inputs into the hippocampus thalamic nuclei - anterior and medio-dorsal nucleus of the thalamus - both have a role in memory function amygdala - used in fear in front of hippocampus para hippocampal gyrus - input cortex - lying around the hippocampus - information has to enter here to get into the hippocampus cingulate gyrus - does not have just one function orbitofrontal cortex - has modulatory input - Connected to the limbic cortex

What is the role of the hippocampus, hypothalamus, ventricles, caudate nucleus and putamen?

hippocampus - memory and spatial navigation hypothalamus - hormone synthesis, temperature, hunger, thirst and sleep ventricles - fluid filled cavities that protect and bath the brain caudate nucleus and putamen - (basal ganglia) - planning movement, cognition and emotion

Where does memory formation of new experiences link between? What studies proved this?

hippocampus and original sensory area - changes in plasticity of these circuits - changes in plasticity results in changes in synaptic connections which results in new memories being formed. fMRI studies where you are looking at a visual thing you are remembering, the visual area in the brain lights up as well as the hippocampus - forming connections

What can be seen in a scan of someone with temporal lobe epilepsy?

hippocampus is slightly brighter and smaller scarred focus of seizures and memory problems (associated cognitive deficit - long term memory deficit)

What do the powerful vasodilators(PGE2 , PGI2 , PGD2) synergize with?

histamine = itch bradykinin = pain cause redness and increased blood flow to the site of injury prostaglandins potentiate the action of bradykinin and histamine on blood vessels and peripheral nerves all released together, potentiate together and further activation = robust response to injury = downside is painful process

What are the ventricles?

holes in the brain filled with CSF - anterior horn = frontal lobe - posterior horn = occipital lobe - little horns that go into the temporal lobe

How do you assess pain?

how severe is the pain? - what is the pain score - how is the pain affecting the patient? what type of pain is it? - acute or chronic? - cancer or non-cancer? - nociceptive or neuropathic? are there other factors? - physical? - psychological?

Describe CBT Cognitive behavioral therapy

how we think --> how we feel --> how we behave Based on the principle that behaviour is learnt and can therefore be re-learnt , or reconditioned focusses on the "here and now" (unlike psychoanalytic therapies)

What does the cortex consist of?

huge array of pyramidal neurones mono-synaptic when the PN discharge, they stimulate motor neurones which will release ACh to the SkM = action

What are the neural connections associated with the sleep-wake cycle?

hypothalamic SCN - provides circadian drive pontine (ACh REM-on cells) - increase firing prior to inducing REM sleep raphe/LC (5HT/NA) REM-off cells - decrease firing of pontine cells, inducing non-REM sleep

What are the neural connections associated with the sleep-wake cycle?

hypothalamic SCN - provides circadian drive pontine (ACh REM-on cells) - increase firing prior to inducing REM sleep.pons raphe/LC (5HT/NA) REM-off cells - decrease firing of pontine cells, inducing non-REM sleep

What are the most important causes of nausea and vomiting?

iatrogenic - chemotherapy, radiotherapy, opiates, antibiotics motion sickness and Meniere's disease pregnancy poisoning (e.g. ethanol) gastroenteritis and stimulation of the pharynx meningitis and intracranial haemorrhage - raised pressure Bulimia nervosa

How can Huntington's be diagnosed?

if asymptomatic then a positive gene does not designate onset of the disease, but pre-symptomatic carrier status diagnosis relies on presence of a movement disorder in conjunction with a positive gene test there may be psychiatric prodrome (early symptom), but diagnosis cannot rest on this as this is common especially in those with positive predictive test additionally, imaging does help as changes predate clinical onset also people might not be clearly symptomatic but when measured longitudionally - prodromal stage- can see deterioration in motor skills

What does Lazarus (1968) say about appraisal of emotion?

if the situation is appraised as unfavourable, and coping potential is appraised as low then the emotional state experiences is likely to be sadness or anxiety if favourable though, it will likely produce hope emotions are rarely direction reactions to stimulus qualities; rather, what gives an object emotional impact is its relevance to one's concerns

What is inflammation?

immediate response of the body to a harmful stimulus reduction of inflammation often results in pain relief Heightens awareness of area that's damaged and results in protecting that region Often short lasting and resolves relatively quickly

What is the differential activation hypothesis?

important factors determining whether one's initial depression or anxious state becomes more severe or persistent are: 1. the degree of activation 2. content of maladaptive thinking patterns that become accessible in the depressed (or anxious) state this phenomenon has been referred to as cognitive reactivity

What are eicosanoids?

important role in inflammation generated de novo from phospholipids - arachadonic acid (AA) is the main source

How do you switch between sleep and wakefulness?

in sleep - VLPO neurons activated and induce sleep; inhibit arousal centres in wakefulness - VLPO neurons inhibited, cerebral cortex activated

How do you switch between sleep and wakefulness?

in sleep - VLPO neurons activated and induce sleep; inhibit arousal centres in wakefulness - VLPO neurons inhibited, cerebral cortex activated

What does sleep deprivation lead to?

increased sleep propensity compensated by subsequent increased sleep intensity and/or duration (changes in sleep architecture) - (Sleep propensity) how easily you go to sleep = increases decreased glucose metabolism in prefrontal and parietal cortices (PET studies, 24hr without sleep) - when in slow wave - Increase in tau in blood mood changes, mental health (paranoia, hallucination Freeman et al, 2017) higher level cognitive functioning - attention, short term memory, working memory disrupted perceptual changes (hallucination Freeman et al, 2017) - Psychotic episodes are preceeded by prolonged periods of insomnia increases in risky behaviour as sleep duration reduced to 5 hours (driving stimulations) importantly the effects on cognition may not be recognized by individual

What does sleep deprivation lead to?

increased sleep propensity compensated by subsequent increased sleep intensity and/or duration (changes in sleep architecture) - how easily you go to sleep = increases decreased glucose metabolism in prefrontal and parietal cortices (PET studies, 24hr without sleep) - when in slow wave mood changes, mental health (paranoia, hallucination Freeman et al, 2017) higher level cognitive functioning - attention, short term memory, working memory disrupted perceptual changes (hallucination Freeman et al, 2017) increases in risky behaviour as sleep duration reduced to 5 hours (driving stimulations) importantly the effects on cognition may not be recognised by the individual

What balance is put in favour in PA?

indirect pathway in PA patients degeneration of SNc neurones causes less dopamine release to both direct and indirect pathways two consequences - tonic activation of direct pathway no longer occurs - indirect pathway is not longer inhibited by D2 receptor activation

How do performances on emotional processing(use emotion) tasks vary?

individuals with elevated levels of mood or anxiety tend to perform poorly (slow reaction time and low accuracy) on affective processing tasks in response to emotion-laden stimuli or feedback that triggers emotional reactions Attention goes more readily/directly to negative stimuli rather than neutral stimuli which affects their stimulus

What are the features of a good hypnotic drug?

induce normal sleep - NREM and REM no hangover on waking lack of tolerance - receptor adaptation; enzyme induction - difficult in hypnotics - may encounter dependence syndromes lack of dependence low risk of overdose - i.e. no respiratory depression; no CVS depression increased problem when used with other CNS depressants - e.g. alcohol

What are the features of a good hypnotic drug?

induce normal sleep - NREM and REM(4-5 cycles of this throughout the sleep at night) no hangover on waking lack of tolerance - receptor adaptation; enzyme induction - difficult in hypnotics - may encounter dependence syndromes lack of dependence low risk of overdose -(Increased problem when used with other CNS depressants - ideally want drug that has wider therapeutic window) i.e. no respiratory depression; no CVS depression increased problem when used with other CNS depressants - e.g. alcohol

What are the different intravenous anaesthetics?

inducing agents - thiopental - methohexitone/methohexital - propofol - etomidate benzodiazepines - diazepam, lorazepam, midazolam dissociative anaesthesia - ketamine

What are the stages of anaesthesia?

induction - inhalation or IV agents used - tend to favour inhalation maintenance - mainly provided with volatile agents recovery - monitoring to assure recovery

What is in area 44,45?

inferior frontal gyrus contains Broca's area (another language centre)

What are the areas that the arteries of the brain supply?

inferior posterior cerebellar arteries - posterior cerebellum basilar artery (brain stem) inferior anterior cerebellar arteries - anterior cerebellum superior cerebellar arteries - cerebellum posterior cerebral arteries - medial occipital and inferior temporal lobe hippocampus anterior cerebral arteries (medial frontal and superior parietal lobe, corpus callosum) middle cerebral arteries (lateral temporal and parietal lobes and posterior frontal lobe) - lenticulostriate arteries (subcortical structures)

What other veins can be found in the midline?

inferior sagittal sinus - smaller and runs parallel with the cingulate gyrus internal cerebral vein - takes from the diencephalon, parts of the brain stem and drains it back into the straight sinus

What is the blood gas partition coefficient?

influences speed of induction and recovery from inhalation anaesthetics

What are the two positions of tentorial tumours?

infratentorial - where the cerebellum should be supratentorial - there is an intact cerebellum

How do NSAIDs work?

inhibition of COX glucocorticoids also have an effect in inhibiting the induction of the enzyme

What is the mechanism of action of NSAIDs?

inhibition of COX enzymes reduced generation of eicosanoids

What is the mechanism of local anaesthetics?

inhibits the voltage gated sodium ion channel equilibrium change within the EC fluid the uncharged molecule will find it way inside the cell, it will become charged once inside and will associate with the voltage gated sodium channel this prevents the sodium channel from opening unable to get the influx of sodium ions therefore no APs numbing sensory nerves responsible for pain mechanism

When might pain be obviously complex from?

initial presentation - multiple somatic complaints - negative test results - emotional burdens - unsatisfied with care (patient and GP) - thick notes (passed around specialities) - feeling that there is little to offer - poor therapeutic relationship - lack of collaborative working

What is the direct pathway activation?

initiate movement

What is the journey through the corticobulbar tract?

initiating in places that correspond to the face comes and passes through the internal capsule ends in the lower medulla - terminates in the brain stem and does not go into the spinal cord does provide input to a lot of the muscles that control the movement of the face, neck and some cranial nerves

What does the dorsal horn of the spinal cord receive?

innocuous (Ab-fibre relayed) and noxious (C-fibre relayed) messages

What are the inputs and outputs of the hippocampus?

input - sensory information from throughout cortex via entorhinal cortex -> preforant path to dentate gyrus - modulatory inputs from septal nuclei (ACh), brainstem nuclei (NA, DA, 5HT) influence the overall functioning output - via subiculum and entorhinal cortex to neocortex - via fornix to (1) septal region (2) mammillary bodies, hypothalamus, median forebrain bundles also important connections with amygdala and thalamus

What are the inputs of the amygdala? What are the outputs of the amygdala?

inputs - talks to hippocampus - cortical regions outputs - under stress, it will send signals to the hypothalamus to release stress hormones - it will talk to other autonomic systems to release NA and adrenaline - talks to Periaqueductal Grey in the brainstem - causes freezing reaction in rodents

What is the pre-frontal cortex important for?

inputs to and from key limbic structures important in decisions about reward and appetitive behaviour motivation and regulation of behaviour disorders can include psychiatric and personality disorders

What is insomnia?

insomnia is subjectively defined as 'the perception of insufficient or inadequate sleep for three weeks or more' - insomnia affects >20% of the population at any one time - most insomniacs underestimate the amount of time they sleep - affects sleep onset and maintenance - the cause of insomnia should be treated not the symptom

What is the blood brain barrier?

interface that ensure the circulatory system (blood) is kept separate from the EC fluid/CSF

How does naltroxone reduce alcohol craving ?

interferes with positive reinforcement and possibly-alcohol conditioned cues Blocking endogenous opioid dis-inhibition of GABA neurones in VTA thereby reducing firing of dopamine releasing neurones

What are sleep promoting factors?

interleukin-1 (increased during illness) adenosine levels increased in sleep and decreased in wakefulness caffeine is an adenosine receptor antagonist - reduce 'sleepiness' - reduce the levels of adenosine and stimulate wakefulness

What do the arteries look like on angiograms?

internal carotid - curled up and passing through the carotid canal

What layers are important for movement?

internal granular and internal pyramidal

What is the panic cycle in panic attack?

internal/external trigger e.g. crowded place, caffeine perceived threat anxiety e.g. intense fear either: avoidance and safety behaviour e.g. get out of here, call 999 or: physical/cognitive symptoms e.g. palpitations, breathlessness misinterpretation e.g. I am having a heart attack

What are the major cisterna in the brain?

interpeduncular - between the cerebral peduncles in the midbrain cisterna pontis - between the pons and medulla cisterna magna - biggest pocket - below the cerebellum and medulla - this is an alternative strategy to obtain CSF if lumbar puncture fails

How do you identify intracerebral on imaging?

intracerebral - blood will appear hyperdense - box-shaped appearance(wedge shaped appearance) - sulci effacement (sulci start to appear blurry) - loss of definition of basal ganglia (caudate nucleus, internal capsule and can be seen on the non-stroke side) - stroke side, putamen cannot be seen clearly

What is propofol?

intravenous short acting with onset of action of 30 seconds and rapid recovery decrease blood pressure and IC pressure does NOT provide analgesia accompanied by excitatory phenomena - muscle twitching, yawning, hiccups some anti-emetic effects post recovery

What is thiopental?

intravenous similar propofol - fast acting within 1 minute may cause apnoea, coughing, chest wall spasm, laryngospasm, bronchospasm not commonly used now as better tolerated agents available

What kind of organisation does the homunculus have?

inverted somatotropic organisation feet are the the top and the face and tongue are at the bottom

What is the extrapyramidal system?

involves the basal ganglia, thalamus, cerebellum and a bit of the brain stem - unconscious regulation of movement cortex is communicating with the basal ganglia which projects to the thalamus and back to the cortex = cortical loop of the basal ganglia

What does the limbic system integrate? What key behaviours does it integrate? What other areas is the limbic system linked to?

key behaviours emotions, reward driven activity (feeding and sex), motivation, social behaviours (friend and foe), memory of environment and experience hypothalamus, sensory, motor and frontal regions to achieve this

Give a pathophysiological overview of stroke

ion pumps are the first things to go - depolarise repetitively - sodium and calcium rush into the cells - potassium leaves the cells (build up and spreads causes adjacent cells to depolarise = peri-infarct depolarisation) -As potassium is building up in the extracellular space - so is glutamate - Glutamate is also being released in huge amounts - toxic effects - this stimulates further calcium release - water comes in and you get oedema - glutamate release (major excititory NT - stimulates by potassium) - too much = glutamate toxicity - spread of peri-infarct = spreading to nearby cells calcium in excess - activates enzymes = proteases, DNAses - produce free radicals = destroy DNA, membranes, proteins - mitochondrial damage = initiates apoptosis all of this produces inflammation - downstream effects happening later on microglia - first cells to respond - retract processes, become amoeboid, secrete cytokines and other pro-inflammatory mediators leukocytes - usually not in the brain and stays in the blood - when there is damage, they can enter the brain - Release their own cytokines and pro-inflammatory mediators PERICYTES: - Undergo cell death as well - When they die , the get shrunken , contribute to BBB disruption

yes left sulcal effacement in the left hemisphere the dark spot in the right hemisphere is an old infraction

is this patient having a stroke? what side is it on?

What are the 2 types of stroke?

ischaemic (85%) - blockage that could be cholesterol, fibrin, RBCs hemorrhagic (15%) - bleeding in the brain

Why are sensory receptor fields important?

it allows you to detect where damage is happening e.g. hands - there is a small area over which you can activate sensory nerves and send messages up to the spinal cord - because the receptor fields are quite small, you can pinpoint where the painful stimulus is in the viscera, the fields are larger e.g. stomach - there are large fields therefore cannot tell exactly where the pain is because there are no small receptor fields

What debunked Schachter's theory?

it did not account for other potential sources of emotionally relevant information which may affect one's judgement e.g. awareness of facial expression or feedback from emotional action

What happens to the L-DOPA when it reaches its target neurones? What problem is there? What solution is there? Can the peripheral inhibitor cross the BBB?

it gets converted by the enzyme DOPA decarboxylase into dopamine problem: dopamine is present in the kidneys, precursor to NA in the sympathetic neurones so anywhere in the periphery that we boost L-DOPA, it will also get converted to dopamine and we get peripheral side effects e.g. hypertension, changes in renal blood flow solution: give L-DOPA at the same time as a drug that inhibits DOPA carboxylase - carbidopa prevents dopamine being produced in the periphery (blocks the enzyme) carbidopa cannot get into the CNS itself

Why is lithium a dangerous drug to use?

it has a narrow therapeutic window exceed 1mmol - can be dangerous Thus must ensure patient does not oversdose

What do emotions involve ? What are the components of emotions ?

it involves the following components: cognitive appraisal, physiological arousal, subjective experience (feelings), expressive behaviour and goal-directed activity

How is dopamine prevented from acting forever once it is released into the synapse?

it is taken back up by the dopamine transporter proteins into the nerve terminals and retaken back into the vesicles

What are dysfunctional beliefs and attitudes about sleep scale?

items include:

What is the Kluver-Bucy syndrome? What are some symptoms? When can aspects of this be seen?

large bilateral anterior temporal lobe resections removing amygdala, hippocampus and surrounding temporal lobe very docile - no longer aggressive towards keeper indiscriminate sexual activity loss of ability to visually discriminate edible from inedible a breakdown of visual input to channels drives Aspects of this is seen in severe brain trauma or advanced neurological-degeneration

What do stronger stimuli evoke? What encodes the intensity of the stimulus ?

larger receptive potentials (from stronger stimuli) greater number and higher frequency of action potentials Recruitement: the intensity of the stimulus is also encoded by the size of the responding receptor population and the numbers of fibres activated

Where are the major sulci of the brain located?

lateral - temporal from frontal and parietal lobes central - frontal from parietal lobe parieto-occipital - parietal from occipital lobe precentral - anterior to central sulcus calcarine - visual cortex cingulate - parallel with corpus callosum

What happens to the corticospinal tract once it enters the spinal cord?

lateral corticospinal tract - pyramidal decussation - projections go into the ventral side of the spinal cord (ventral horn) to the interneurones - control muscles of the limbs and digits interneurons - connect with the lower motor neurones - producing the movement that the motor cortex has asked for ventral corticospinal tract - does not cross over = smaller - also projects to the interneurons and LMNs - innervates the trunk

What are the circuits in the amygdala?

lateral nucleus - takes in a lot of sensory information from cortical regions and higher speed subcortical inputs which may serve instantaneous responses to threat - Synaptic plasticity takes place here : processing in this nucleus will attach the feeling of harm when you get a harmful and innocent stimulus paired together = fear conditioning - May serve instantaneous responses to threat CENTRAL NUCLEUS: Affector nucleus of amygdalla , generate most of its output response this way - Has connections with brainstem - Implements response to threat such as autonomic system , hormones , freezing or startle reactions Eg: If amygdala shouts fear - Central nucleus is how the signals are sent to all the brain regions that have to respond VENTRAL STRIATUM FROM BASAL NUCLEUS : Press a lever for a reward - Has connections with the cortical and hippocampal regions

What is the structure of the ventricles?

lateral ventricles - biggest structure at the top - where most of the CSF is produced inter ventricular foramen - tiny hole which connects the lateral ventricles to the third ventricle - roughly in the middle of the brain - connected to the cerebral aqueduct - landmark = thalamus diencephalon - directly underneath is the midbrain midbrain - ventricles becomes very skinny - cerebral aqueduct - through the cerebral aqueduct, it opens up and becomes the fourth ventricle with is located between the cerebellum and brainstem

What are the connections of the ventricles?

lateral ventricles --> interventricular foramen --> third ventricle --> cerebral aqueduct --> fourth ventricle

What cortical layers are different in the sensory and motor areas?

layer 4 and 5

How is the sensory layer different?

layer 4 in the sensory cortex is larger and in the motor cortex is smaller layer 4 is a huge sensory integration zone lots of information arriving in the sensory cortex

How is the motor layer different?

layer 5 in the motor cortex is larger and in the sensory cortex is smaller layer 5 is the main output area pyramidal cells sending projections to the other parts of the brain and the spinal cord- Projection neurons that leave the cortex to take movement information elsewhere.

What are the advantages of benzodiazepines?

lethal dose very high - no loss of consciousness or respiratory depression at normal dose small effect on sleep pattern - induces 'normal' sleep (some effect on REM sleep) do not induce enzymes although tolerance and dependence occurs - less marked than barbiturates few other side effects - notably -> respiratory depression in combination with alcohol

What are advantages of benzodiazepines?

lethal dose very high(wider therapeutic window) - no loss of consciousness or respiratory depression at normal dose small effect on sleep pattern - induces 'normal' sleep (some effect on REM sleep) do not induce enzymes although tolerance and dependence occurs - less marked than barbiturates few other side effects - notably -> respiratory depression in combination with alcohol(contrindication with alcohol)

What can lithium toxicity lead to?

level>1.0 mmol/L: severe diarrhoea Vomiting or anorexia Coarse hand tremor Muscle twitching Dehyrdation Drowsiness Confusion Muscle weakness Slurred speech Ataxia Paraesthesia Nystagmus Vertigo Tinnitus Restlessness Blurred vision Level>2.0mmol/L: Convulsions Renal failure Electrolyte imbalance Hypotension Clouding of consciousness Coma and death

What is the rate limiting step in the synthesis of eicosanoids?

liberation of AA by phospholipase A2 to produce prostaglandins , thromboxanes , leukotrienes

What is the characteristics description of the microglia?

like astrocytes but smaller and fewer processes motile cell - little processes are moving around and senses changes in the environment

What are some key facts about working memory (short term)?

limited capacity (7+/-2) rapid decay without sustained attention prefrontal cortex visual and auditory versions of working memory

What was the fear conditioning experiment? Does conditioning stimulus go away?

linking an innocent tone to an electric shock causes the rat to freeze to a tone alone conditioning stimulus overtime will distinguish - no longer paired with the harmful stimulus so will disappear overtime - extinction

Where does the CSF leave through?

little holes and collects in pockets called cisterna

How is the brain organised?

lobes - 4 lobes

What is LTP? How long can LTP last for? What is LTP dependent on? What is the basis of long-term memory ?

long-lasting change in synaptic function last for minutes, hours, days it is thought to be one of the most important synaptic ways memory is formed dependent on NMDA receptor (glutamate receptor) and Ca Synaptic plasticity - LTP

Why is The Benzodiazepine Lorazepam favored in elderly patients?

lorazepam is favoured in elderly patients- short half life - does not have an effect in the liver or kidney - affects the clearing of the drug and therefore increases the toxicity of the drug Diazepam produces active metabolites oxazepam temazepam that affects the elderly

What is there a loss of in the nerve terminals? What is there little change in, in post synaptic terminals?

loss of DA nerve terminals binding to the D2 receptor would be virtually completely unaltered in severe forms of this disease

What does the primary pathology of Parkinson's look like?

loss of pigmented neurones in the substantial migration par compacta

What are the functions of the astrocytes?

maintain homeostasis - ability to take up excess potassium and glutamate - takes it up and shuttles it along end feet maintain BBB and contribute to blood flow regulation - stop stuff getting into the brain - role in communication between endothelial cells and neurones repair and scarring - scars in the brain are reactive astrocytes

What is the long term treatment for bipolar disorder?

maintenance - continue treatment as above - long term treatment - lithium or sodium valproate - psychological intervention

What does the cortex enable us to do?

make voluntary movement it integrates information and produces motor signals

What is pathological pain?

maladaptive - not protective - Damage to some parts of pain processing pathway or abnormal function of nervous system results from abnormal functioning of the NS disease states caused by damage to the nervous system - (neuropathic pain) or by its abnormal function (dysfunctional pain/nociplastic pain) SPONTANEOUS PAIN , PAIN HYPERSENSITIVITY Eg of neuropathic pain cause : Stroke Low threshold pain

Explain MINI-MENTAL EXAMINATION?

maximum score of 30 Not enough to make diagnosis of dementia and used only as part of comprehensive test

What is the treatment for bipolar disorder?

mania -acute phase - antipsychotics-halperidol , olanzapine, questiapine or riseperidone - if ineffective, try a 2nd antipsychotic - if ineffective, add lithium or sodium valproate Maintenance - long term: - Continue treatment as above - Long term treatment - lithium or sodium valproate - Psychological intervention depression - quetiapine alone - SSRI fluoxetine combined with olanzapine - olanzapine alone - lamotrigine alone

Describe non-cancer pain

many different causes acute or chronic

What are the clinical features of mid disease? mid huntington's disease

marked chorea dystonia falls/declining mobility frontal lobe dementia and loss of verbal fluency swallowing difficulties behavioural issues +/- psychiatric features

What are some key features of executive dysfunction?

may be subtle deficits - some processes which are still intact normal speech, perception, IQ may be normal - go off on a tangent - behave in a reflexive manner loss of goal orientated behaviour - no regulation - driven by the context of seeing those objects stimulus driven behaviour (utilisation behaviour) deficit in initiation of behaviour (apathy) impaired monitoring of responses disinhibition (socially inappropriate)

Inflammation due to tissue damage - how do pH affect this?

measure pH = lower pH (more protons) due to inflammation sensory nerve are activated by low pH (specifically protons) specific receptors on the nerve which respond to those protons and will be activated by that

What is nociceptive stimuli?

mechanics of the pain pathways being activated and not the emotional experience associated with it

What does inheritance of genetic disease depend on?

mechanism of disease dominant recessive

What receptors detect which stimuli?

mechanoreceptors - touch, pressure, vibration proprioceptors - position of body thermoreceptors - warm, cool, hot nociceptors - mechanical, thermal, chemical (inflammatory process that occurs during tissue damage) on the edge of sensory nerves

What does the underside of the human brain look like? Where is the amygdala found?

medial aspect of the temporal lobe

What are the three parts of the brainstem?

medulla oblongata - most inferior pons - bulge in the middle midbrain - hidden

What comes from the midbrain (mesencephalon)?

mesencephalon - tectum (colliculi) - tegmentum - cerebral peduncles

What happens if you get close to a nociceptive stimuli?

message goes up to the brain, reflex response from the spinal cord = move away from stimulus = essential for survival

How is dopamine normally metabolised?

metabolised by MAO into DOPAC and then by COMT these two enzyme operate in series on each others substrates final metabolite is HVA

What comes from the hindbrain (rhombencephalon)?

metenecephalon - pons - cerebellum myelencephalon - medulla oblongata

What does the midbrain look like?

mickey mouse

What is mickeys ear and body?

mickeys ear (VENTRAL SIDE) - cerebral peduncles - shaped like a V - mammillary bodies are sitting in between the cerebral peduncles, it is a part of the motor system mickeys body (DORSAL SIDE) - made up of the superior and inferior colliculi (together called the tectum)

What are mickeys mouth, headband and eyes?

mickeys mouth - cerebral aqueduct - part of the ventricles - inhibiting pain response = periaqueductal mickeys headband - substantia nigra - produce dopamine and will die in Parkinson's disease (head band is not present in patients with Parkinson's) mickeys eyes - red nucleus - tissue is not fixed and is very vascularised

What is the most common type of stroke? What are its symptoms ?

middle cerebral artery territorial infarction hemiplegia , hemisensory less

What is in area 6?

middle frontal gyrus contains the premotor area located more anterior to the motor area

What is potency of inhalation anaesthetics defined as?

minimum alveolar concentration (MAC) inhaled dose that prevents movement to a standard surgical stimulus (skin incision) in 50% of patients < MAC number = more potent anaesthetic > MAC number = less potent anaesthetic

What is another way to potentiate the action of dopamine? What is the primary enzyme involved in metabolising dopamine?

modify its metabolism MAO B

What are the 6 cortical layers of cortex?

molecular - neurones, glial cells, apical dendrites external granular - small pyramidal, granular neurones external pyramidal - small and medium pyramidal cells and granular cells internal granular - mostly stellate neurones, but some pyramidal cells internal pyramidal - large pyramidal neurones, apical and basilar dendrites, projections neurones multiform - small spindle like pyramidal neurones

What can sleep deprivation do to mood?

mood changes - can be more extreme than irritability and aggression individuals who have depression, once it has lifted, insomnia will still be an issue and can still be a precipitator to other conditions (e.g. bipolar, schizophrenia) even with people who are healthy - symptoms such as paranoia can be seen in those have been deprived of sleep

What can sleep deprivation do to mood?

mood changes - can be more extreme than irritability and aggression individuals who have depression, once it has lifted, insomnia will still be an issue and can still be a precipitator to other conditions (e.g. bipolar, schizophrenia) even with people who are healthy - symptoms such as paranoia can be seen in those have been deprived of sleep

What can a minor expansion of the Huntington's cause?

more minor expansion of gene does not cause disease (with current life expectancy) but can be relevant to offspring minor gene expansion can be unstable and can result in further expansion of the gene during gamete formation in the male line

What are the characteristics of the pyramidal cells?

most abundant cell in the cortex (75-85%) also found in other structures e.g. hippocampus glutamatergic (excitatory) major cortical output

When is executive function required?

most of the time, you will not act in this goal-directed way of acting most of the time, you are dependent on your habits EF mode is when you are consciously monitoring on how you are doing some situations where you strongly usually do something - habitual response - but the situation demands you do something else - two things that you need to override what you want to do EF allows you to stop and do something in a different way = flexible

What is cerebral spinal fluid?

mostly water ventricles are filled with CSF we have approx 150mL of CSF that is changes 3 times each day - we produce approximately 500mL of CSF everyday CSF is a colour-less liquid that bathes the brain, assists in circulating substances, it provides cushioning and absorbs shock CSF is produced in the choroid plexus (a group of cells that line the ventricles) and production induces CSF circulation the choroid plexus also acts as a medium of exchange between the extra cellular fluid and the blood stream

How do sensory inputs to the vomiting centre affect what treatment to give?

motion sickness - activity in the vestibular centre - histamine (H1 , M1) association with smell or experiences , emotions, Hypoxia , hypotension , pain , increased intracranial pressure - affects cortical afferent nerves - - benzodiazepines Afferent nerves from periphery (vagal and glossopharyngeal nerves , GI tract disturbances, pharyngeal nerves) - 5-HT3 , D2 , NK1 drug induced, CTZ - e.g. chemotherapy - D2, 5-HT3, M3 , H1 , Opioid , NK1

What is the course of action of the UMNs and LMNs?

motor signals are carried by upper motor neurones to the brain stem and spinal cord within the structures, the UMNs synapse with lower motor neurones LMNs leave the CNS and bring motor signals to the muscles this is the pyramidal system - conscious regulation of movement

What kind of phenomena is pain?

multidimensional phenomena it can be described by pain location, intensity, temporal aspects, quality, impact and meaning

What is the anatomy of the amygdala

multiple sub-nuclei - multiple sensory and limbic inputs - organise emotional responses to stimuli (hormonal, autonomic and behavioural) - both pleasant and harmful - special role in fear

Explain the indirect pathway

multiple synapses and other GABA neurones coming out through the external GP and will eventually make the same connections to the thalamus however, when this pathway is activated, it inhibits the thalamic output to the cortex = break

What are benzodiazepines used for?

muscle relaxation , insomnia , pre-medication , epilepsy , alcohol withdrawal , anxiety

What is Parkinson's? What is the primary cause?

neurodegeneration of the extrapyramidal system (basal ganglia) unable to perform normal motor function loss of dopamine from the nigrostriatal pathway

What are the 2 types of brain disease?

neurodegenerative - loss of neurones - disrupted motor function - may also include changes in behaviour psychiatric - no obvious loss of neurones though may show some structural changes e.g. inappropriate connectivity - change in behaviour

What is the cortex composed of?

neurones

Why is Parkinson's a disease of late onset?

neurones have been undergoing apoptotic loss throughout life but symptoms do not present until you are in your 60s and 70s

How do opioids work in nerve damage?

neuropathic pain states nerve damage to induce pain is due to changes in A fibre function which causes allodynia (touch evoked pain) A fibre driven pain states will not be responsive to opioids because the opioid receptors are not located on A fibre terminals C-fibres - they can cause hyperalgesia

What do the neurones in the trigeminal nerve contain? What less important neuropeptide does it also contain? What is the action of CGRP? What does vasodilation cause?

neuropeptides - CGRP substance P - less powerful vasodilation powerful vasodilator vasodilation of meningeal vessels causes headache and pain

Explain the projection pathways What they are involved in If they are affected in Parkinson's

nigrostriatal - substantia nigra to dorsal striatum - involved in the control of refined, smooth movements - they are affected in Parkinson's ventral tegmental area contains the: mesolimbic - from ventral tegmentum to nucleus accumbens (ventral striatum) - involved in reward and pleasure - unaffected mesocortical - from ventral tegmentum to prefrontal cortex - involved in social behaviour, cognition, emotions - unaffected tuberoinfundibular - from the arcuate nucleus to the median eminence - release of dopamine inhibits prolactin release to stop secretion (endocrine) - unaffected

What are the four clusters which contain dopamine in the brain? Where do they project to?

nigrostriatal pathway mesocortical pathway mesolimbic pathway tuberoinfundibular pathway they project to a brain nuclei

Are sleep mechanisms clearly understood?

no

Is aspirin suitable for long term treatment?

no

Is the basal ganglia part of the pyramidal system?

no

Can dopamine get past the gut barrier and be absorbed into the CSF? What drug can be given that replaces dopamine? Can L-DOPA be transported across the BBB?

no L-DOPA yes

Are opioids effective in chronic pain?

no reduced effects

Is nociception same as pain ?

no as nociception does not have psychological aspect (As in how you feel)

How do you diagnose migraines?

no definitive test or diagnosis careful assessment of patient history elimination of alternative causes of headache- trauma, other drug treatments, rare disorders

What is the medical treatment for Huntington's?

no treatment which is 'disease modifying' and stops the relentless cell death in practice neurology and psychiatry should work in tandem chorea - responds to dopamine blocking drugs - tetrabenazine - neuroleptics psychiatric medications - neuroleptics, antidepressants, anti-anxyolitics, rarely anticholingerics medications can cause side effects which can be difficult to distinguish from symptoms of HD itself e.g. Parkinsonism, dystonia, tar dive dyskinesia, worsening cognition

What are physiological changes during non-REM and REM sleep?

non-REM sleep - steady HR, BP and respiration rate - muscles relaxed REM sleep - greater brain activity - fluctuating HR, BP and respiration rate - Skeletal Muscle profoundly relaxed (though body movements may occur)

What are physiological changes during non-REM and REM sleep?

non-REM sleep - steady HR, BP and respiration rate - muscles relaxed REM sleep - greater brain activity - fluctuating HR, BP and respiration rate - SkM profoundly relaxed (though body movements may occur)

What is the antipyretic effect of NSAIDs?

normal body temperature regulated by hypothalamus fever due to disturbance in hypothalamus thermostat NSAIDs reset thermostat mechanism mainly due to inhibition of prostaglandin production in hypothalamus temperature regulating mechanisms reduce temperature , don't influence Core temperature unless it's been elevated

Describe the Z Drugs?

not benzodiazepines, but bind to benzodiazepine binding site on the GABA-a receptor advantages - short half life (~6 hours) - pharmacokinetics not altered by age - i.e. ok for the elderly - no change in REM - little reported rebound or withdrawal effects - no abuse potential - YET! however - zopiclone has a bitter taste and causes dry mouth

What are Z drugs?

not benzodiazepines, but bind to benzodiazepine binding site on the GABA-a receptor advantages - short half life (~6 hours) - pharmacokinetics not altered by age - i.e. ok for the elderly - no change in REM - little reported rebound or withdrawal effects - no abuse potential - YET! however - zopiclone has a bitter taste and causes dry mouth

Describe nitrous oxide (NO)

not great at dissolving in the blood phase majority of N2O remains gas phase this favours the rapid entry of N2O into the brain to induce anaesthesia N2O promotes rapid induction (and recovery) of anaesthesia

What is the pathway for pain?

noxious stimuli activate nociceptors different fibres - C fibres, A-delta fibres - to the dorsal horn of the spinal cord messages are relayed to the ventral horn and there is withdrawal reflex messages go up to the thalamus and brainstem via the spinothalamic tract where its crossed thalamus = messages to the sensory cortex (conscious of pain)- which also feedbacks to the limbic system(emotional response) Brainstem = respiratory and cardiovascular effects No direct pathway to the limbic system via the parabrachial nucleus If you don't have a brain, no pain because of no affective emotional aspects of pain processing

How does descending inhibitory control of pain work?

noxious stimuli in the periphery activates the C fibres which feeds message to the spinal cord which feeds message to the brain stem and cortex cortex feeds down and thalamus feeds into the PAG which sends excitatory transmitters to inhibit transmission in the spinal cord NRM sends messages down to the spinal cord and release inhibitory transmitters to inhibit transmission in the spinal cord Done to override pain sensations when put in dangerous situation

Where does the somatosensory system receive information from?

numerous body parts - skin, muscle, tendons, ligaments and connective tissue

When are subjective and objective measures used?

objective - only for people with sleep disorders subjective - maybe for different reasons

What is inflammatory pain?

obvious tissue injury or illness pain generated by the release of chemicals from the area of inflammation associated with tissue damage and infiltration of immune cells and can promote repair by causing pain hypersensitivity until healing occurs protective function descriptors commonly used - sharp and/or dull - aching - throbbing well localized Spontaneous pain Tenderness promotes repair (protective)

What is the journey of an intravenous anaesthetic?

once in the blood stream, some of the drug binds to plasma proteins and the rest remains unbound or free drugs is transported initially through venous blood then systemic circulation eventually gaining access to cerebral circulation a partial pressure gradient permits the entry of the anaesthetic to the brain where it then exerts its effect

What is the journey of an inhalation anaesthetic?

once inhaled, the anaesthetic gains access into the alveoli AKA 'windows to the brain' partial pressure is important in driving the anaesthetic from the respiratory pathway to the brain a steady state for maintenance of anaesthesia is required and this is dependent on partial pressures of alveoli, blood and brain need to make sure that these three are at equilibrium during the maintenance phase

Explain the direct pathway

one pathway from the striatum which goes directly to the internal capsule of the Globus pallidus if this pathway is activated, it will enhance the thalamic glutamate output to the cortex and serve as a drive to enhance motor function

What is the uni-dimensional pain assessment scales?

only assess pain intensity useful for acute pain need to asses during movement and at rest - especially coughing Need to assess pain during activity or function. Visual analogue scale (VAS) - Commonly used in clinical trial setting - and useful in routine clinical practice Numerical rating scale (NRS) - used for many types of acute pain Verbal rating scale (VRS) Type of scale less important - ensure all healthcare using same assessment tool

How do opioids increase the descending control from the brain to the spinal cord?

opioid receptors inhibit the GABA neurone - it is stopped from firing so post synaptic neurone can fire how much ever it wants and you can get lot of excitation Opioid recetpors are present on the GABAergic neurone, this allows glutamatergic neurones to be activated, it is firing a lot, releases a lot of glutamate and will cause a big excitation - DISINHIBITION BY OPIOIDS

Why do opioids not work with chronic pain?

opioids are acting at G protein coupled receptors taking more and more, there will be receptor tolerance and the less analgesic they are

What is the direction of travel of the pyramidal tracts?

originate in the primary motor cortex (layer 5) and converge to form the internal capsule before continuing through the midbrain, brain stem and spinal cord

What is the journey of the corticospinal tract?

originates anywhere but the face fibres come together in the internal capsule passing through the cerebral peduncles down the medulla - at this point, there is pyramidal decussation - some remain on the same side - once they have crossed over, they are referred to as lateral and ventral corticospinal tracts - lateral = crosses over - ventral = remains on the same side

Why do SSRIs take 2-4 weeks to work?

over a course of a few weeks, the auto receptor will become desensitised and the receptor will be down regulated therefore this inhibitory mechanism will be reduced and more 5-HT can bind to the 5-HT receptor

What are the causes of PA?

oxidative stress 15% patients have a first-degree relative with PD genetic causal factors - familial PD rare (5% of all cases) PARK1 or SNCA gene codes a-synuclein; autosomal dominant early onset PD with Lewy bodies and marked rigidity PARK2 gene codes Parkin which is part of ubiquitin proteasome; autosomal recessive early onset PD restricted SN cell loss; no LB; good levodopa response PINK1 and PARK7 gene mutations also cause autosomal recessive forms of PD leucine-rich repeat kinase 2 (LRRK2) gene and SNCA gene mutations occur in sporadic Parkinsonism = risk factors drug-induced neurodegeneration - MPTP (environmental toxin) - or exposure to pesticides (e.g. paraquat) drug induced symptoms = DA antagonists (antipsychotics) viral encephalitis

What might cell death be due to?

oxidative stress mitochondrial dysfunction proteasome dysfunction

What are the factors that affect local anaesthetics absorption ?

pKa - lower pKa = greater unionized form = faster onset of action . They don't work as well in inflammed/infected tissue Lipid solubility = Potency = More lipid soluble - more able to cross the phospholipid bilayer = Need less drug Protein binding - Duration of action = More protein bound = larger protein depot = longer duration of action

Why is a complex definition for pain required?

pain and injury are not always linked in the way we would expect under stressful conditions people and animals suffer quite serious injuries without feeling the pain immediately some people experience terrible pain in the absence of an obvious lesion

What is the analgesic effects of NSAIDs?

pain associated with inflammation/tissue damage reduce inflammation (oedema and vasodilation) which causes pain Used arthritis, muscular pain, toothache, headache etc in combination with opioids decrease postoperative pain

What can be said about pain?

pain is unpleasant emotions are important the cause is not always visible

What is chronic pain?

pain lasting for more than 3 months pain lasting after normal healing sometimes no identifiable cause may be no obvious pathologic process intensity unrelated to tissue injury unpredictable time course difficult to treat

What is acute pain?

pain of recent onset and probable limited duration obvious tissue injury (e.g. injury, operation, burn) varying severity intensity related to extent of injury predictable time course treatment usually successful

What is not allowed to pass into the brain?

pathogens and larger molecules (antibodies)

When might single alleles detected?

patient may be homozygous for this repeat size (i.e. inherited an allele with 17 repeats from each parent) patient may have an expansion that is not detectable by this method - because expansion is very large

What are psychotic disorders characterised by?

patients with psychotic disorders such as schizophrenia present with a variety of behavioural and neural deficits reflecting emotional processing and emotional responding disturbances

What activity can be picked up when you are paying attention, staying alert, drowsy?

paying attention, staying alert - beta activation drowsy - alpha activation short bursts of activity (sleep swindles) - do not know about what these brain waves are doing

What activity can be picked up when you are paying attention, staying alert, drowsy?

paying attention, staying alert - beta activation drowsy - alpha activation short bursts of activity(11-16 Hz) (sleep spindles) - do not know about what these brain waves are doing

What is nociception? Is nociception the same as pain ?

perception of pain neural process (mechanism) = C-fibre activation which detect pain component of pain but is not the same thing Because nociception doesn't have psychological aspect (as in how you feel ?)

Will tissue with a blood flow decrease to 16mL/100g/min die?

perhaps, if treatment is not provided

Describe the describing inhibitory control of pain Explain how even with the positive pathway down from the NRM to the spinal cord with functional consequence of inhibition

peripheral stimulus goes to spinal cord goes to thalamus and brain stem regions from the thalamus, there are projections to the PAG and cortex which also projects PAG and the hypothalamus also projects to the PAG PAG is the central controller of the descending inhibitory pathway PAG sends projections to NRM by sending excitatory projections - activates the region - stimulates fibres that project to the spinal cord - level of SC, release inhibitory transmitters - although the pathway is activated, the primary role is inhibition = because the fibres that are stimulated are releasing inhibitory transmitters e.g. serotonin, endogenous opioids - act to dampen down activity in the SC LC(Locus ceruleus) also projects to SC directly and NRM and is also inhibitory

What information is derived from the oil-gas partition coefficient?

permits ease of gas diffusion into the brain through the BBB less anaesthetic will be required to produce anaesthesia linked to MAC - potency (provides information on the pharmacological agents) since halothane is more 'lipid-loving' than NO - less of the anaesthetic will be required to produce anaesthesia

Describe pethidine and fentanyl

pethidine - orally active - does cross the placenta - less potent - short duration - used in labour fentanyl - orally active - highly potent - short duration - used in anaesthesia

Why is herbal medication not favoured?

pharmacokinetics and pharmacogenetics is not well understood with interaction with other drugs

What is the Canon-Bard theory of emotion?

physiological changes (bodily reactions) and subjective feeling of emotional experiences as a response to a stimulus are separate and independent Physical and psychological experience of the emotion happens at the same time , not one causes the others but they act seperate and independent Emotion is merely an aroused system

What evidence is there to debunk James-Lange theory?

physiological changes that accompany a wide variety of emotions are actually very similar and not distinct enough to differentiate them spinal cord injury patients still experience emotions

Where is melatonin produced?

pineal gland associated with light and darkness as well

Where is melatonin produced?

pineal gland associated with light and darkness as well

What can be seen from inside the temporal lobe?

pink = amygdala blue = hippocampus

basal ganglia made up of putamen and caudate nucleus

pink = putamen orange = caudate nucleus

What are the different types of spatial cells represented in the limbic system?

place cells - only fire in a place grid cells - In entorrhoinal cortex border cells - only fire at the edge of the environment

Describe methadone

plasma half life > 24 hours used to reduce opioid abuse physical abstinence syndrome is reduced psychological dependence similar in presence of methadone, morphine/diamorphine does not produce euphoria

How can sleep be measured in a sleep laboratory?

polysomogram electro-encephalogram (EEG) electromyogram (EMG) electrooculogram (EOG)

How can sleep be measured in a sleep laboratory?

polysomogram : Measures quality of sleep using: 1. electro-encephalogram (EEG)- Changes in neuronal activity in networks 2. electromyogram (EMG) - Skeletal muscle movement 3. electrooculogram (EOG) - Eye movement changes during sleep Good standard to diagnose sleep

Where does propofol primarily act in the brain ?

pons and cortex

What are some early and late symptoms of Parkinson's?

poor slow movement - bradykinesia-cardinal symptoms postural abnormalities rigid posture - difficult to initiate movement mask-like expression - cannot respond in a normal way to something that makes you smile lack OR rigidity of movement - akinesia tremor - shaky tremor in hands which stops when the patient tries to initiate movement later stages depression dementia endocrine dysfunction

What is the action of the cingulate cortex?

poorly understood different areas - pain, emotional, vocalisation, bladder function - Used in handling conflicting information - Error monitoring - when you detect error in performance - Arousal - Patients with damaged cingulate cortex present with neurological syndrome - called akinetic mute syndrome - where they have very low levels of activity and arousal area in blue = sub-callosal area - underneath the corpus callosum - appears over active in depression - stimulating electrodes in this area for people with severe depression has seen some positive responses.

What are the issues related to pre-symptomatic testing for Huntington's?

possible to test asymptomatic carriers aged > 18 has to be done through genetic counselling advice high levels of morbidity in those who test gene positive - studies show higher levels of depression, more disabling early symptoms the wish to have children prompts methods of IVF which allow pretty good guarantee of unaffected child without need for test, but expensive and complicated if a treatment becomes available balance of whether to know will change dramatically

What is in area 1-3?

post central gyrus contains the primary somatosensory area

What might a mutation in TRESK K2P associated with? What might this mutation contribute to? What might this potassium channel be linked with more?

potassium channel in spinal neurones it is typically associated with common migraine may contribute to cortical spreading depression and to familial migraine linked more with the aura and not the migraine itself

What is in area 4?

pre central gyrus contains the primary motor area

Where can u-opioid receptors be found?

pre- and post- synaptically

Explain CBTs to treat insomnia ? Explain this psychological methods to treat Insomnia? Cognitive behavioural therapies ?

pre-sleep thoughts promote cognitive arousal CBT combines previous strategies with - A range of strategies that can prevent or interrupt maladaptive thought 1. Thoughts-blocking and distraction 2. Cognitive restructuring (beliefs and attitudes)

What are the several regions that play a role in movement?

prefrontal - planning movement premotor - organising movement primary motor - producing movement primary somatosensory - receiving sensation secondary somatosensory - interpreting sensation

What can be seen in patients with mood disorders?

present with emotional processing deficits in affective tests e.g. Stroop, GoNoGo and functional abnormalities in the corticolimbic circuit (i.e. in prefrontal cortex, amygdala-hippocampus complex, thalamus and ventral striatum, basal ganglia and connections among these) Overactive ventral paralimbic region Hypofunctional dorsal cortical region

What is the prevalence of Parkinson's? How many people around the UK have it? What are the cultural factors of Parkinson's? Is it the most physically disabling disease of the elderly? How many deaths were there globally in 2013?

prevalence - 40-60 years = 0.1% - >60 years = 0.5% - >85 years = 4% approximately 125,000 patients in UK affects all races, both sexes it is the 2nd most common, after osteoarthritis 103,000 deaths globally in 2013

What did Lazarus say about appraisal of emotion?

primary appraisal: evaluation of relevance of current situation to personal wellbeing: 'am I in trouble or am I OK' secondary appraisal: evaluation of capacity for dealing with the situation: i.e. one's coping potential: ;what can be done about it;what is the likelihood that this person will intentionally take their own life in the near future?

Where do the pyramidal tracts originate?

primary motor cortex

What are the medication goals in mirgaines?

primary to provide acute relief to recurrent attacks secondary to introduce effective prophylactic treatment

What is the sleep hygiene checklist?

principles - getting into a regular routine during the day on all activities e.g. making bedroom quieter - more comfortable - having a wind down sleep routine - having a shower = drops body temperature - avoid napping in the day - avoid screens going into bed at a time when you are tired need to have a regular bedtime and regular get up time

What is the sleep hygiene checklist?

principles- getting into a regular routine during the day on all activities e.g. - making bedroom quieter - more comfortable - having a wind down sleep routine - having a shower = drops body temperature - avoid napping in the day - avoid screens going into bed at a time when you are tired need to have a regular bedtime and regular get up time

What happens if there is an absence of reward after stimulus predicting a reward?

produces a drop in neural firing DA neurones in ventral tegmental area (A10) sends axons to nucleus accumbens and other areas of ventral striatum and orbitofrontal cortex - seems to have regulatory effect on the dopaminergic neurons pleasure hotpots in nucleus accumbens and orbitofrontal cortex (Gaba/Opiate) - craving response

What is the basis of the basal ganglia?

programming of movement decide how, when and where to act put into action learned motor plans stimulus to move assemble motor plan - selecte motor programme from memory stores - assemble appropriate sequence of motor programmes execute motor plan Parkinson's disease - can assemble motor plans but unable to specify accuracy of the programmes, run or sequence them

Describe cancer pain

progressive - pain may increase as disease worsens may be mixture of acute and chronic

What is progressive relaxation?

progressive relaxation therapy provides a means for reducing autonomic activity the Bernstein and Borkovec (1973) technique involves tensing specific muscle groups and then releasing the tension progressive relaxation can be of benefit in the treatment of sleep-onset insomnia

What does the neurotrophic hypothesis of depression propose?

proposes that depression is associated with reduced brain BDNF levels antidepressant treatments alleviate depressive behaviour and increases BDNF levels

What are the mediators derived from COX2?

prostaglandins - hyperalgesia = increased response to an already painful stimulus = sensitize nerve terminals and increase responsiveness = increase blood flow, more inflammatory mediators, increase in temperature PGI2 - hyperalgesic , vasodilator , decreases platelet aggregation PGE2 - hyperalgesic , vasodilator PGD2 - Vasodilator , Decrease platelet aggregation TXA2 - Thrombotic , vasoconstrictor

What is the role of the meninges?

protection support network for blood vessels form fluid filled cavity (to cushion and nourish the brain)

Why do opioids work well for acute pain?

protective mechanism high intensity stimulation of C-fibres opioid receptors present on the C fibres inhibit transmission through mechanisms

What are the P's for good sleep hygiene?

psychological - decrease stress, explain about good sleep behaviours physiological - increase relaxation pharmacological - decrease caffeine, decrease alcohol psychiatric - anxiety/depression physical - decrease pain, asthma, etc

What are the P's for good sleep hygiene?

psychological - decrease stress, explain about good sleep behaviours physiological - increase relaxation pharmacological - decrease caffeine, decrease alcohol psychiatric - anxiety/depression physical - decrease pain, asthma, etc

What information does the basal ganglia receive and what does it do?

receives cortical information and helps plan movement by feeding back to the cortex via the thalamus

What is the structure of the putamen and caudate nucleus?

putamen - wedge shaped structure - largest part is lateral and medially it gets smaller caudate nucleus - connected well with the putamen - C-shaped structure which starts anteriorly, curves up and over the thalamus and then curves back around

What are the two most prominent neurones in cortex?

pyramidal cells- most abundant granular cells

What is the internal capsule a part of and what does it pass between?

pyramidal tracts passes between the caudate and putamen

What is the main way in which we produce movement?

pyramidal tracts the cortex integrates information and produces movement

What is the core question in the sleep diary?

question 8 - how did you feel when you woke up this morning? cannot be captured by objective measures any approaches to insomnia, behavioural or pharmacological needs to good score of how you felt you woke up

What is the core question in the sleep diary?

question 8 - how did you feel when you woke up this morning? cannot be captured by objective measures any approaches to insomnia, behavioural or pharmacological needs to good score of how you felt you woke up question 10 - How would you rate last night's sleep ?

What are the different types of sleep disorders?

rapid eye movement disorder - person acts out their dreams restless legs syndrome - an overwhelming need to move ones legs especially at night periodic limb movement of sleep - repetitive movements in the lower limbs that occur about every 20-40 seconds - recognised as brief muscle twitches, jerking movements or up upward flexing of the feet insomnia - difficulty getting to sleep or staying asleep for long enough to feel refreshed the next morning, even though there has been enough excessive daytime sleepiness narcolepsy, cataplexy

What is familial hemiplegic migraine (with aura)? What is familial hemiplegic migraine caused by? What do these mutations result in? What mutation may be in 30% of patients?

rare autosomal dominant disorder 50% of cases causes point mutations in the CACNA1A gene that encodes the pore-forming alpha1A subunit of the P/Q voltage-gated calcium channel (chromosome 19) mutations result in an altered channel conductance and density of expression in vitro in cells lines - changes in permeability mutations in ATP1A2 gene that encodes the Na+/K+ pump (Alpha2) subunit

What are contributing factors of insomnia?

reaction to distress organic cause (e.g. endogenous depression) faulty/poor sleep management chronic distress - pain

Describe halothane

readily dissolves in the blood phase the system has to 'wait' until the entire blood phase gets saturated once the blood phase is saturated, halothane will occupy the gas phase, and then access the brain the action of 'waiting' for halothane to saturate the blood phase before occupying the gas phase = 'long' time to induce anaesthesia (and recovery)

What is the role of the amygdala in emotion appraisal?

receives visual, auditory, taste and smell information and uses it to make a quick and rough evaluation about the potential harm or benefit of a stimulus amygdala mediates both the autonomic expression and the cognitive experience of emotion Amygdala automatically and preconsciously prepares for fight or flight , the visual cortex however responds more slowly and accurately Pre-frontal cortex is part of brain where conscious control will affect what happens - when amygdala perceives threat in environment - following response is purely controlled by amygdala - amygdala hijack - soon guided by fear as major emotion

What are the arousal brain centres (wakefulness)?

regions within the brain that controls wakefulness (arousal) reticular activating centre, brain stem, hypothalamus = involved in wakefulness arousal centres in these centres are stimulated and information is sent across the cortex hypothalamus - controls sleep with sleep and arousal centres

What are the different primary afferent fibres?

relay information to the spinal cord A-alpha(Aalpha) - larger diameter - myelinated - thus conduct quickly - do not relay painful messages - e.g. tell us about position of our joints = proprioceptive A-beta (Abeta) - group 2 - large diameter - myelinated - mechanical stimuli - like dynamic brush - not painful A-delta (Adelta) - Group 3 - smaller in diameter - finely myelinated = slower conduction - Information about temperature that is both painful and non-painful(temperature) stimuli C-fibres(Cfibres) - relay information only about pain - group 4 - if innervating muscle - fine sensory nerve, small, thin - unmyelinated - slowest conduction - Primary fibres involved in relaying pain

Inflammation due to tissue damage - how do mast cells affect this?

release a number of things e.g. serotonin Serotonin is excitatory and pro-inflammatory in the periphery, serotonin can activate the sensory nerve terminals by CGRPs also release cytokines, TNF-alpha, IL-beta and other growth factors from sympathetic nerves and local immune cells

What is inflammatory responses generally accompanied by?

release of prostanoids - mainly PGE2 and PGI2 generated by local tissue and blood vessels

What does the hippocampus look like?

seahorse

What do signals from nociceptor afferents activate in the spinal cord?

second order neurones

How do you test attentional control?

selecting task relevant information : 1. Accentuate attended information 2. Excluding irrelevant information

What do sensory respiratory receptors exhibit?

selectivity to be able to discriminate between different stimuli

What are some selective inhibitors of MAO? MAOIs Does this drug work on its own?

selegiline these drugs can be given together with L-DOPA and carbidopa useful as it extends the therapeutic window of benefit of L-DOPA no - only in combination

What are the two types of declarative memory?

semantic - facts - stored in the tip of the temporal lobe episodic - events that you can later describe - intensely hippocampus dependent

What does sensory-discriminative and emotional-affective component mean?

sensory discriminative - tells you that you have been hurt and where it is emotional affective - which is the association of unpleasant emotions with the nociceptive stimulus - the suffering of pain comes from the bad emotions that are generated by painful sensations

What is the basic circuit of the hippocampus?

sensory information comes from the world through various sensory cortex - visual, somatosensory, auditory it enters and funnels down the entorhinal cortex for processing it sends messages to the dentate gyrus which sends messages to CA3 -> CA1 there is also a direct route from the entorhinal cortex -> CA1 the final most important output is back to the cortical regions Many of these processes are dependent on NMDA glutamate processes

What are the sensory inputs of the amygdala? What are the outputs of the amygdala?

sensory inputs - subcortical sources of sensory and visceral information - specific sensory cortex inputs outputs - stria terminalis > hypothalamus, brainstem, BNST, accumbens - Output path to the brainstem , hypothalamus will be via the stria terminalis - ventral path: hypothalamus, cortex, brainstem

What is the third and current theory of migraines? Which division of the trigeminal nerve has these changes?

sensory nerve activation is the cause migraine = enhanced trigeminovascular neurone activity ophthalmic division

What does the sensory system allow?

sensory receptors and neurones have peripheral receptive fields: a small area over which you can activate the neurone. a single sensory neurone in the CNS can receive inputs from many sensory receptors = convergence- maximizes how successfully the signal is transmitter/relayed converts a natural stimulus (energy) to action potentials intensity and duration of the stimulus is conveyed

What is the hippocampus also connected to? Patients with fornical lesions

septal nuclei this sends signals to and for the hippocampus sets up a particular rhythm of firing = theta rhythm of the hippocampus (fires 8 or 10 times a second) Have memory problems

What are prophylactic (preventative) migraine therapy given for?

severe attacks and/or >2/month

Genetic reason for inherited erythromelalgia (man on fire syndrome) and proxysmal extreme pain disorder ?

severe pain syndromes associated with gain-of-function mutations in SCN9A Sensory neurons expressing either the mutant Nav1.7 channels are hyperexcitable

What happens in sensitized state (chronic pain)? What happens in case of an injury?

shift to the left When you have sensitized state (inflammed/Injured ankle) - peripheral inflammation stimuli that do not normally cause pain are causing it - allodynia (non-painful stimulus becomes painful) above normal threshold, stimuli that cause some pain and now cause maximal pain - hyperalgesia (painful stimulus becomes more painful)

When would you have a short or long CAG repeat?

short CAG repeat sequence - get it at an older age long CAG repeat sequence - get it at a younger age

What are the different types of hypnotics?

short acting (6 hour half life) benzodiazepines or related Z-drugs (e.g. Zopiclone, Zolpidem) barbiturates - NO LONGER USED AS HYPNOTIC (do not prescribe) others: antihistamines - H1 receptor antagonists sedative antidepressants valerian (plant) extracts melatonin/melatonin receptor (MT1/MT2) agonists e.g. agomelatine

What are the different types of hypnotics?

short acting (6 hour half life) benzodiazepines or related Z-drugs (e.g. Zopiclone, Zolpidem) barbiturates - NO LONGER USED AS HYPNOTIC (do not prescribe) others: antihistamines -(Tricyclics Depressants as well have hypnotic effects) H1 receptor antagonists sedative antidepressants valerian (plant) extracts melatonin/melatonin receptor (MT1/MT2) agonists e.g. agomelatine

Describe the sleep cycle in children

shorter cycle in children second time heading down spending less time in slow wave - more difficult to stir waking - REM sleep more aware of what is going on around you

Where does the blood drain in to from the transverse sinus?

sigmoid sinus and then into the external jugular artery sigmoid sinus gets it names because of its distinctive S-shape

What would be seen in a SPECT scan if cocaine was used as a radioactive ligand? In a healthy patient In a patient with severe Parkinson's

since cocaine can be used to bind to the dopamine transporter and block it more binding = redder image in a healthy patient, there is very high binding with the dopamine transporters in the striatum as the disease progresses, the staining gets less red as nerve terminals are dying, neurones are dying and so dopamine transporters are being lost

Why is there not a loss of D2 receptors? Why is this helpful?

since they are post-synaptic, they are on the cells innervated the dopamine neurones, they will stay there and not disappear it we can find a drug that binds to the dopamine D2 receptors, we might be able to restore function

Where can the nucleus accumbens be found in a scan?

sits at the bottom of the basal ganglia

What is the medullary paralysis stage?

situations where things go wrong: loss of respiration EEG waves --> small --> lost death

What are the guidelines for treating insomnia?

sleep hygiene/behaviour - essential first line treatment strategy P's for good sleep hygiene if severe consider referral to sleep clinic with ward or home monitoring --> video sleep behaviour + EEG monitoring; sleep apnoea (mask)

What are the guidelines for treating insomnia? What is the essential first line treatment strategy ?

sleep hygiene/behaviour - essential first line treatment strategy P's for good sleep hygiene: psychological - decrease stress, explain about good sleep behaviours physiological - increase relaxation pharmacological - decrease caffeine, decrease alcohol psychiatric - anxiety/depression physical - decrease pain, asthma, etc if severe consider referral to sleep clinic with ward or home monitoring --> video sleep behaviour + EEG monitoring; sleep apnoea (mask)

What is the surgical anaesthesia stage?

slow synchronised EEG rhythms regular slow breathing medullary centres depressed - brain activity is synchronised and regular reflexes lost pupils dilated - sensitivity to light

What is the characteristic description of oligodendrocytes?

small cells whose processes form individual nodes of myelin around axons

What is allowed to pass into the brain?

small molecules - oxygen, carbon dioxide, glucose or select amino acids

What is a lacunar infarction?

small, strategic strokes in penetrating arteries that feed sub-cortical structures as many as 80% are clinically silent. motor hemiplegia syndrome - infarction in the posterior limb of the internal capsule, basal ganglia or pons 1- stroke in internal capsule 2- stroke in basal ganglia

What are the different parts of a neurone?

soma (cell body) dendrites - where the neurone is receiving the electrical information from other neurones, sends signals down the axon into the terminals which synapses with other neurones axons - coated in myelin (80% fat and lipids = insulator)

What are the descriptive features of the pyramidal cells?

soma is 10-50um (above average) apical dendrite - prominent structure which stretches upwards towards the cortex there are many other dendrites as well major output of the cortex is occurring via the axons which are inferiorly moving dendrites have spines which are the synapses - Thus called spiny pyramidal cells

What are the descriptive features of the granular cells?

soma is <10um (generally smaller) only communicate to cells in the neighbouring area - do not project to elsewhere in the brain smooth stellate can have different types - basket, chandelier, double bouquet spiny stellate (generally glutamatergic)

Why are small peripheral receptor fields/small receptor fields in sensory system important? What feature do sensory receptors and neurons have that allows for precision ?

spatial discrimination Allows to detect some precision the location of painful stimulus you are exposed to and relay information to spinal cord so each spinal cord neuron will be receiving inputs from a discreet areas from the hand for example

What can a lesion in Wernicke's area cause?

speech did not make sense patients had no idea that they were making no sense superior temporal gyrus receptive aphasia - failure to comprehend

What is central sensitisation?

spinal neurones are sensitised to the noxious stimulus

What is the withdrawal reflex?

spinally mediated nociceptive event that results in the withdrawal from the stimulus set up by the pain signals

What is the ascending pain pathways?

spinothalamic tract (STT) from laminae I and V to the thalamus post-synaptic dorsal column (PSDC) pathway spinoreticular tract (SRT) spinomesencephalic pathway

What is the ideal inhalation anaesthetic?

stable over range of temperature not degraded by light odourless analgesic, anti-emetic and muscle relaxation properties minimal respiratory depression minimal cardiovascular effects is excreted completely by the respiratory system not metabolised or no active metabolites

What is the characteristic description of astrocytes?

star shape lots of different processes

Explain the Papez circuit

starts in the cingulate cortex and sends signals down the para hippocampal gyrus into the hippocampus hippocampus sends the output through the fornix to the mammillary bodies this sends it to the anterior thalamus which sends it back to the cingulate cortex

What is potency?

strength of a drug correlate it to the concentration of the drug the more potent the drug is, the stronger the drug is therefore the less drug that is required

What is the leading cause of adult disability?

stroke Ischaemic stroke is most common Importance of rapid diagnosis and treatment is key

What is stroke?

stroke is the acute onset of neurological deficits (lasting for more than 24hours) due to a disturbance in blood supply to the brain approximately 15 million people suffer strokes each year - 1/3 will die and 1/3 will be disabled

What are the different types of meningeal haematoma?

subarachnoid - blood is filling up in the subarachnoid space - brain will be pressed inwards subdural - arachnoids look relatively intact - blood is filling up in the dura epidural - bleeding on the outside of the brain dura = associated with the best outcome - blood is able to escape via the broken bone and so relieve pressure

What does the limbic system sit between?

subcortical nuclei (e.g. hypothalamus) limbic system (e.g. hippocampus) paralimbic (e.g. cingulate) neo-cortex (e.g. frontal lobe)

What kind of experience is pain?

subjective it can be perceived directly only by the sufferer

What is a sleep diary?

subjective measure captures, in a subjective way, that a polysomnogram will not as accurate in a self-report

What do fMRI studies assess?

subliminal presentations of fearful faces (very short duration followed by a visual mask) without conscious detection of the stimulus still activate the amygdala

What are the rewards circuits involved in addiction (rat)? What is one of the main mechanisms of addiction ?

substances such as opioids, cannabinoids, nicotine, GABA (alcohol) receptors of these pathways influence the rewards pathway All these drugs of addiction seems to funnel through a dopaminergic signalling pathway as one of the mechanisms of addiction.

Where might Lewy Bodies be found? Are LBs unique to Parkinson's? Are LBs causal or symptomatic?

substantia nigra locus ceoruleus no, they can also be seen in Alzheimer's do not know

What is nociplastic or (dys)functional pain?

substantial pain but no noxious stimulus and no, or minimal, peripheral inflammatory pathology no neuronal damage (i.e. functional problem) (Problem in transmission in pain transmission pathways) Affects normal peripheral tissues and nerves conditions include fibromyalgia, irritable bowel syndrome, tension type headache, temporomandibular joint disease, interstitial cytisis

What are the surface landmarks that can be seen on the brain?

sulci - fissures between the bumps gyri - bumps lateral sulcus - big and prominent - looks like the brain is folded under here precentral sulcus - deepest and most prominent sulcus that runs in a superior to inferior direction central sulcus - directly behind the precentral parietal-occipital sulcus - separates the parietal and occipital lobes

Where is the higher concentration of opioid receptors found? How to retain A fibres sensation to touch and pressure and inhibit pain transmission ?

superficial laminae of the dorsal horn - around 70% of these are found pre-synaptically on the C fibres - remaining 30% are post-synaptic acting to mop up any excitability to breach the barrier depending on the dose of morphine ,if given spinally , it leaves A fibres response to touch and pressure intact but still reduce pain e.g. epidurals during pregnancy

What is cognitive behaviour therapy?

tackles reasons why depression or anxiety are still present, not what caused them very large database demonstrating effectiveness from randomised controlled trials

What is the venous drainage of the brain?

superior sagittal sinus - covers almost the entire brain in an anterior to posterior direction as you approach the occipital lobe, there is a little junction called the confluence of sinuses - this is where the sagittal sinus comes together with the straight sinus (medial and runs on top or superior to the cerebellum) - and the occipital sinus (bringing blood back from the occipital lobe) - and transverse sinus therefore the superior, straight and occipital meet at the confluence and all the blood drains through the transverse sinus (runs along the top of the cerebellum on the outside - find one on each side of the brain)

What is in area 22 and 41?

superior temporal gyrus 22 contains Wernicke's area which is a language centre 41 contains the primary auditory area

What are the anatomical terms used to describe the head?

superior/dorsal - above inferior/ventral - below anterior/rostral - towards the front posterior/caudal - towards the back medial - towards the midline lateral - away from the midline

What is in area 5,7?

supra marginal gyrus contains the somatosensory association areas (secondary) role in interpreting sensory information arriving in the sensory cortex

What is the body's master clock? Where does it receive information from? How does it induce sleep?

suprachiasmatic nucleus (SCN) also present within the region of the hypothalamus sensitive to light, darkness and responsible for inducing the Circadian rhythm in the body receive projections from the optic nerve - receives information activating the SCN - will induce a sleep drive and information will be radiated to the VLPN and will induce sleep

What is the body's master clock?

suprachiasmatic nucleus (SCN) also present within the region of the hypothalamus sensitive to light, darkness and responsible for inducing the Circadian rhythm in the body receive projections from the optic nerve - receives information activating the SCN - will induce a sleep drive and information will be radiated to the VLPN and will induce sleep

What is the limbic system key for?

survival

Where do prostaglandins come from in the inflammatory response?

sympathetic nerves and local tissue

What is another name for long-term potentiation? What is long-term potentiation? What happens if you give brief, fast bursts of activity? What happens if you give slow stimulation? What is this thought to be important in?

synaptic plasticity larger responses from nerve fibres after a potentiating (give a strong stimulus) and the subsequent stimuli are stronger short burst - start recording again = enhanced response called LTP - after tetanus response is slightly enlarged slow stimulation for a while = depression called LTD (Long term depression) important for memory

How do the neurones normally work?

synthesis of 5-HT in the pre-synaptic neurone 5-HT is packed into vesicles and then when required, the vesicles will fuse with the pre-synaptic nerve terminal exocytosis = release of 5-HT into the synaptic cleft 5-HT is regulated by MAO and COMT which metabolise 5-HT and is broken down into metabolites some of the 5-HT released will bing to the 5-HT receptors in the post-synaptic membrane and a signalling cascade will be sent down and effects are seen via the action of 5-HT reuptake transporter, reuptake of 5-HT into the pre-synaptic neurone and then the whole process happens again

Describe the tactile (touch) pathways

tactile cross in the medulla and inputs arrive in the dorsal horn of the spinal cord central branches of touch afferent fibres ascend in the dorsal columns synapse in the dorsal column nuclei ascend through the brainstem (contralateral) as the medial lemnisus to thalamus thalamus: synapse on cells (ventral posterior medial (VPM) and ventral posterior lateral (VPL) nuclei) send projections to the primary somatosensory cortex (S-I), post central gyrus of parietal lobe

What is the normal 2 neurone network?

take the PAG - GABAergic neurone (inhibitory) - it is not firing but when it arrives onto a cell that is glutamatergic and is firing - when it reaches the glutamate in the end, it causes excitation

What can sodium valproate cause? Why is sodium valproate not used in women of child bearing age?

teratogenesis therefore it is not recommended for women of child bearing age

What is the process that happens when you activate the somato-sensory system?

terminals in skin, sending messages - synaptic endings in the spinal cord deformation of the membrane opening of Na+ and K+ channels receptor (generator) potential local depolarisation of receptive membrane action potential propagated to CNS

Where do A-beta(abeta) fibres terminate and what responses are they sensitive to?

terminate in intermediate lamina (III-IV) of the dorsal horn responses sensitive to glutamate receptor (AMPA receptor) antagonists main transmitter is glutamate

Where do C fibres terminate and what responses are they sensitive to?

terminate in superficial lamina (I-II) of the dorsal horn responses sensitive to glutamate receptor (AMPA and NMDA receptor) and peptide receptor antagonists release glutamate and many other transmitters(peptides and neurotrophins)

What is test interpretation?

test takes into account and stratified by age and level of education

What did Cannon present in 1927?

the sympathetic and parasympathetic parts of the NS act in balance in non-excited states when the balance has been upset, the sympathetic NS prepares the body for specific actions and mobilises emergency and stress resources (i.e. fight or flight response) through increased secretion of epinephrine People might experience bodily changes - but not necessarily experience the emotions

What is action readiness?

the tendency of an emotion to act as an impulse for an action specific to the emotion being experienced

What is periosteum?

the tough membrane that covers the outside of the bone mostly composed of fibroblasts

What are the side effects of aspirin?

therapeutic doses = gastric bleeding (5/6mls blood loss) anti-platelet function (prevents heart attacks) large doses: dizziness, deafness and tinnitus toxic doses: uncompensated respiratory acidosis, ,metabolic acidosis 2nd highest cause of gastric ulcers epidemiological link with encephalitis if given to children with viral infection

What is cognitive therapy?

therapy that teaches people new, more adaptive ways of thinking; based on the assumption that thoughts intervene between events and our emotional reactions Emphasizes role of negative beliefs in the cause and maintenance of depression : mangification (of negatives) minimisation (of positives) and over-generalisation Involves identifying and replacing distorted thoughts and ultimately changing the associated habitual behaviour towards them

What is the science behind depression?

there is a reduction in the volume in some of the structures in the limbic system structural change in the terms of size in these regions of the limbic system in people suffering from depression

How does normal neuronal transmission without opioids occur?

there is an incoming AP to the pre-synaptic ending the AP will cause the vesicles that contain the neurotransmitter to fuse with the pre-synaptic membrane and it will be released opening of the voltage gated calcium ion channels - calcium comes in and the transmitter is released the transmitter binds to the post-synaptic membrane and if it is an excitatory transmitter such as glutamate, it results in the firing of AP post-synaptically

Why do we sleep? Describe the Restorative function of sleep?

there is no consensus there may not be a single answer restoring the body - sleep does not 'restore' the body according to Carlson and older text books it only restores the brain recent evidence several genes up regulated during sleep (those involved in synthesis and maintenance of cell membrane and myeline, immunity) - Cohen study: Less sleep linked with common cold incidences - Orzech et al 2014 study: common incidences of common illnesses in adolescents if less sleep restoring the brain - delta activity during S-W(slow wave) sleep indicates that the brain is indeed resting - REM sleep is also thought to be necessary - sleep deprivation disrupts cognitive functions - genes up regulated involved in brain plasticity and memory consolidation - Tau (which when accumulates forms tangles) in healthy brains cleared during sleep - Increased plaques and tangles in chronic sleep disturbances

Why do we sleep?

there is no consensus there may not be a single answer restoring the body - sleep does not 'restore' the body according to Carlson and older text books it only restores the brain recent evidence several genes up regulated during sleep (those involved in synthesis and maintenance of cell membrane and myeline, immunity) restoring the brain - delta activity during S-W sleep indicates that the brain is indeed resting - REM sleep is also thought to be necessary - sleep deprivation disrupts cognitive functions - genes up regulated involved in brain plasticity and memory consolidation

What keeps us stuck in distress?

therefore, it's not the content of maladaptive thinking that is toxic but how people try to process that content and how people react/behave towards the trigger of that content this is why cognitive therapy is catalytic in the management of mental illness, in conjunction with pharmacotherapy cognitive models of depression (and anxiety) apply to a number of mental illnesses; the assumption being that depressive thinking and anxiety play a contributing role in the development and maintenance of psychopathology

Where are 5-HT1B receptors found? What are heteroreceptors? Where is there an increase of 5-HT and CGRP?

these receptors are found on the blood vessels and directly reduce vasodilation and actions on these blood vessels 5-HT1D heteroreceptors = autoreceptor (neurotransmitter released from the nerve terminal feeds back on itself to decrease its own release) increase in: urine - 5-HT, CGRP CSF - CGRP plasma - CGRP

What are the neuro psychological tests of executive function?

these tests come with norms norms = what is expected of your age and educational level

Why are benzodiazepines only given in crisis?

they are given only for short term use - because of problems associated with tolerance and dependence or addiction

How do benzodiazepines (lorazepam , temazepam , diazepam ) work?

they bind to the GABA receptor-chloride channel complex and inhibit cell excitability

What roles do the direct and indirect pathways have?

they have opposing roles controlling activity of the thalamus to enable planned movements

What are the points to consider on uptake and distribution?

think of two compartments gas phase blood phase how much of the inhalation anaesthetic dissolves in the gas phase? how much of the inhalation anaesthetic dissolves in the blood phase? induction of anaesthesia favours having the anaesthetic in the gas phase thus permitting its entry into the brain

What is the role of the primary auditory cortex?

this area will be receiving auditory information and Wernicke's area helps to process the information = comprehend the language there is a prominent white matter connection to Broca's area called arcuate fasiculis the information is passed onto Broca's area which then puts together what to say there is then a prominent projection to the motor cortex which is able to elicit movement = speech

What is the fear conditioning pathway? What does an fMRI show during a conditioning experiment?

this conditioned response is the basis of how you might become fearful of something that isn't intrinsically feared synaptic plasticity in the amygdala in the lateral nucleus and some other nuclei you get a pairing of the unconditioned stimulus (electric shock) with the conditioned stimulus (innocent tone) = binding together shows activity in the amygdala (increased blood flow)

reading a paragraph silently

this image if from a functional magnetic resonance imaging experiment this technique infers brain activity by measuring changes in oxygenated and deoxygenated blood based on the overview, what task would subject have been asked to perform? Because of activation of Wernickes area which tries to comprehend the language (its lighting up a lot - so really hard text being read ,doign something hard to comprehend) and brocas area - responsible for speech is not being lit up

How do you treat an ischaemic stroke?

thrombolysis with alteplase (tissue plasminogen activator)- clot buster- breaking clot within brain - needs to be given within 3 hours thrombectromy with retriever devices within 6 hours - much safer Patients with high blood pressure or those with strokes covering a large area - not given alteplase

How do you normally regulate excitability?

through a balance between inhibition and excitation GABAergic neurone will receive an input from somewhere and it makes the GABA neurone fibres and it releases GABA the cell that is synapsing onto it will be inhibited as a result, the cell that it terminates on, i.e. glutamatergic, it fires less and so will release less glutamate and there will be less excitation

What is the role of the brainstem in regulating pain responses?

through the (spinoreticular tract) SRT and branches of the STT, nociceptive signals activate brainstem systems giving rise to changes in BP, respiration and orientation toward stimulus (makes us aware that there is stimulus)

What are the symptoms of haemorragic stroke?

thunderclap headache seizures nausea unilateral weakness

What is the 2nd step in treatment of migraines? How are they accessible? How long do they last for? What may it cause/side effects of triptans? What does it not prevent?

triptans - sumatriptan, zolmitriptan etc 5-HT1B and 5-HT1D receptor agonists - cause constriction of cranial blood vessels and subsequent inhibition of neuropeptide (CGRP) - mainstay of selective migraine (and cluster headache therapy), but some cardiovascular risks they are available OTC (18-65 year olds) short acting = poor CNS penetration it may cause chest pain due to coronary artery constriction it will not prevent aura so take during headache attack

Fibromyalgia affects more females than men ? Risk of developing fibromyalgia is 8 times higher in first-degree relatives (eg children , parents or siblings ) of people who have a diagnosis of fibromyalgia ?

true

What kind of drug crosses the BBB the quickest?

unbound, lipid soluble, unionised molecules

What are the symptoms of restless leg syndrome (RLS)?

uncomfortable feeling in the left and feet (itchy, twitchy, throbbing etc.) powerful urge to move the legs to reduce the uncomfortable feeling worsened at night when lying down (or sitting down)

What is restless leg syndrome (RLS)?

uncomfortable feeling in the left and feet (itchy, twitchy, throbbing etc.) powerful urge to move the legs to reduce the uncomfortable feeling worsened at night when lying down (or sitting down)

What does classical conditioning(behavior therapy) allow you to do?

understand how behaviours are learned understand how behaviours are maintained modify of change behaviours

What is classical conditioning useful for?

understanding psychopathology and treating disordered/maladaptive behaviour - conditioning of emotional reactions and physiological responses

What can executive dysfunction be caused by?

unilateral frontal damage - caused by head injury, degenerative disease, stroke, surgery, may include subcortical as well as cortical damage

What are the different movement disorders?

upper motor neuron disorders - stroke - multiple sclerosis - Amyotrophic lateral sclerosis (ALS) lower motor neurone disorders - peripheral neuropathy - polio myelitis - myasthenia gravis involuntary movement disorders - Parkinsonism - Huntington's disease - dystonia - tremor cerebellar disorders - various tumours

What is N-Back task?

used to assess prefrontal function Patients are required to hold information over successive trials

What is the triplet-primed PCR?

uses 3 primers: 1. HD_TPF: binds to specific sequence upstream of the CAG repeat 2. HD_TPR: Binds to repeat sequence (CAG) 3. Has a tail with unique sequence = HD_Tail : Binds to the HD_TPR Tail

How is problem with TP-PCR resolved for larger repeats to be amplified ?

using limiting amounts of TPR which will get used up early in the reaction Long extension time allows the large alleles to be amplified

How can you visualise and quantify dopaminergic neurones? What can you use to bind to the dopaminergic transporter proteins?

using radioactive ligands which bind to dopamine transporter proteins cocaine

How is the immune system affected by how much sleep we get?

vaccination - give someone, builds antibodies, affected by how much sleep you have studies in adults and children - more likely to have infections - colds, sore throats, flu if you have less sleep

What was the original theory of migraines?What are humeral disturbances?When do migraines initially start?

vascular origin - humoral disturbance causes vascular disturbance - VD leads to firstly: intracerebral vasoconstriction = AURA extracerebral vasodilatation = HEADACHE - vascular disturbance leads to PAIN humoral disturbances are abnormal, cerebral blood flow (build up of ions, change in pH) which causes vascular disturbances migraines initially start at the initial phase of vasoconstriction

What can be found in the basal forebrain? What is this structure important for?

ventral striatum sitting underneath he basal ganglia dorsal striatum is important in movement planning ventral striatum is important in emotional planning

What is the sleep centre and how is sleep intitiated?

ventrolateral preoptic nucleus - VLPO inhibit the activity of arousal or wakefulness = sleep is initiated the information radiating across the cerebral cortex will be inhibited by the VLPO and sleep will be initiated

Where are the sleep centres?

ventrolateral preoptic nucleus - VLPO inhibit the activity of arousal or wakefulness = sleep is initiated the information radiating across the cerebral cortex will be inhibited by the VLPO and sleep will be initiated

What are the arteries that supply the posterior aspect of the brain?

vertebral arteries - coming up parallel with the spinal cord - before they come together, they give off the inferior posterior cerebellar artery (going to the cerebellum) - merge together at the junction of the pons and medulla - just after they merge, there is another artery they give off = inferior anterior cerebellar artery - vertebral arteries merge into the basilar artery - the basilar artery sits on top of the pons and has tiny branches which feed a huge portion of the brainstem - as it comes up the basilar artery gives off some more branches - superior cerebellar (supplies the rest of the cerebellum) - posterior cerebral artery (medial aspect of occipital lobe, inferior aspect of temporal lobe, parts of hippocampus and thalamus)

Does cocaine have dependence ?

very little unless, the free base "crack" can be smoked - very rapid experience Little tolerance Little physical dependence But strong psychological dependence

What are choreic movements? Are they easy to treat?

violent, uncontrolled movements no

What are the voluntary and involuntary facial movements?

voluntary facial movements - controlled by the pyramidal motor system, a brain system that includes the motor cortex involuntary facial movements - e.g. genuine smile, are controlled by the extrapyramidal motor system which depends on subcortical areas, brain damage can disrupt either system

What is emesis generated and coordinated by?/ Describe the Central control of emesis Where is this centre found? What does this centre do?

vomiting centre functionally related group of neurones in the medullary reticular formation (not a specific anatomical area) these generate the motor components of the vomiting reflex, and receive inputs that trigger the reflex

What is the suicide risk of depression?

what is the likelihood that this person will intentionally take their own life in the near future? Intention , thinking , behavior , Medical risk and Protective factors

Describe codeine

weak opiate (20% of morphine) little or no addiction? less respiratory depression good anti-tussive

How do you treat pain?

what non-pharmacological treatments can I use? - commonly used in chronic pain - CBT etc issues - accupuncture, individuals can do stuff for themselves what pharmacological treatments can I use? very effective for acute pain not so much for chronic pain

oligodendrocytes

what type of cells form white matter?

What are the effects of opioids on neuronal transmission?

when an agonist binds to the pre-synaptic opioid receptor - it leads to an activation of G-protein which inhibits adenyl cyclase - decreases levels of cAMP - reduces levels of protein kinase in the pre-synaptic level close calcium channels and open potassium channels - pre-synaptic terminal is hyperpolarized, reduce excitability, reduce transmitters released opioid receptors post-synaptically - any transmitters that do get across(will be mopped any excitability), they will arrive on an post-synaptic membrane that is hyperpolarized - reduce AP arriving at the gate(moves neuron away from threshold for action potential) - effective to shut down synaptic channels -moves neurone away from threshold for action potential

What are the connections in the sensorimotor areas made by?

white matter

How is the arrangement of grey and white matter different in the spinal cord compared to the brain?

white matter is found on the outside of the SC grey matter has a unique butterfly shape appearance dorsal = back = sensory ventral = front = motor

What do groups of myelinated axons form?

white matter tracts

What occurs when there is activation of a lipid bilayer?

within it is a voltage gated sodium channel once it is activated by an ion or ligand undergo a conformational change, open, permit the movement of sodium from the EC fluid into the IC fluid influx of Na+ ions initiate a signalling cascade and generate an AP

Are the posterior aspect and anterior aspect of the brain connected?

yes the anterior aspect is connected to the posterior aspect by the posterior communicating artery (Circle of Willis) back up system - if anything goes wrong, blood is able to be provided from other sources huge anastomoses

Do we all have trinucleotide repeats in our bodies?

yes we all have Huntington's gene

Are sleep spindles seen in all stages? Where are sleep spindles most prominently seen?

yes Stage 2

NEVER USE HYPNOTICS UNLESS REALLY NECESSARY FOR SHORT-TERM RELIEF?

yes , to treat the cause of insomnia

Will it be necessary in certain situations to actively induce vomiting? When should this be done? How can vomiting be induced?

yes - aid elimination of swallowed poisons. Only done if : - the poison is likely to be in the stomach - patient is not likely to inhale vomit (i.e respiratory reflexes are unimpaired) in these rare circumstances vomiting can be induce by swallowing an emetic such as ipecacuanha which directly activates CTZ(chemoreceptor trigger zone)

Is MBCT more effective than CBT in treatment of chronic(m>3 episodes)/Treatment resistant depression ?

yes, the more episodes they have , the more effective MBCT is(mindfullness based cognitive therapy)

What are the neurochemical systems that promote arousal ?

○ ACETYL CHOLINE: - Forebrain and brainstem - Active during wakefulness and REM sleep - Low voltage , high frequency firing in EEG - Seen in Basal Forebrain & LDT/PPT ○ NA/NE: - General arousal "fight/flight response" - Seen in Locus coeruleus ○ HISTAMINE: - Promotes wakefullnes; by promoting wakefullness -> reducing REM & NREM - Seen in Tuberomammilary nucleus ○ 5-HT: - Promotes wakefullness and suppresses REM sleep - There is link between serotonin and arousal for wakefullness ○ Dopamine: - Exerts potent wake promoting effects - Produced in Substantia nigra , ventral tegmental area and ventral periaqueductal gray - In Parkinson's disease - Sleep could be problematic - Because dopamine has been found to exert wake promoting effects

How does rockuronium work ?

○ Acetyl choline binds to that receptor and causes sodium influx and propagation of action potential ○ Molecules lie rock uranium- are competitive antagonists at receptors so they prevent acetyl choline from binding and they prevent sodium unflux on the post synaptic membrane and that's how they exert their muscle relaxing effect - they prevent muscle action potential propagation

Propofol practicalities ?

○ Administered "Only" by anaesthetists ○ Smooth induction and emergence from unconsciousness ○ Titratable for anxiolysis(Can be Given in small doses), sedation, anaesthesia ○ Predictable side effect profile ○ Reduces muscle tone in pharynx - Pharyngeal muscle tne being reduced means that it's very easy to insert one of these devices(LMA-Laryngela mask arirway) 10-20 mg of propofol- lead to reduced state of anxiety ; 40-50 mg- cause sedation , eyes would clsoe , may fall into a sleep like state , but still rousable to voice ; 100 mg - general anaesthesia induced with unconsciousness and being unrousable

Rockuronium ?

○ Administered by iv Bolus or infusion ○ Skeletal muscle paralysis in 30 seconds , lasting >30 mins ○ Offset is diffusion of rockuronium away from NMJ (Neuromuscular junction) to plasma - offset of rockuronium as a drug like many of these drugs isnt by metabolism directly , its actually by diffusing away from its site of action ○ Deacetylated in liver and excreted in urine

What are the core principals of genetic counselling?

○ Autonomy of the individual or couple - There might be conflicts of culture/family dynamics ○ Patient's right to full and complete information in a form they understand ○ Preservation of confidentiality - want to share when seeing their own relatives ○ Aimed at facilitative decision making with time to explore all options

Risk factors

○ Most neurological diseases are the result of multifactorial causal influences, each of which on their own would not result in the disease ○ "Risk factors" are positively associated with the development of a disease, but on their own are not sufficient to cause it ○ Case-control studies are mainly used to identify risk factors Odds ratios are used to measure relative risk in exposure groups

What are the symptoms of parkinson's disease ?

○ Bradykinesia- cardinal symptom- (Slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions) ○ At least one of the following: - Muscular rigidity - 4-6 Hz rest tremor - Postural instability not caused by primary visual , vestibular, cerbellar or proprioceptive or proprioceptive dysfunction ○ Several exclusion criteria (for the specialist ) ○ Good symptomatic treatments (dopaminergic system - "disease modifying treatments" yet

Mechanism of action of anaesthetics ?

○ Halothane is very lipid soluble and thus very potent So the theory is that the agents of anaesthesia must be in some way be disrupting the normal process of the lipid-bilayer on neuronal cells ○ We have also found out there are specific cellular receptor targets for anaesthetic agents , ○ Propofol acts at GABA a receptor-trans membrane receptor- They are mainly found in mammalian nervous system in the Cortex, Thalamus, brain stem and throughout the Central Nervous system ○ GABA is a ligand gated ion channel which allows chloride influx when the endogenous ligand which is GABA activates the channel ○ Chloride influx causes hyperpolarisation , it makes the internal parts of the cell wall more negative and causes hyper-polarisation and these GABA receptors normally found post-synaptically in the CNS and they have an inhibitory action ○ Other agents act on GABA receptors (Benzodiasepenes, Diazepam&Midazolam, Alcohol) , by doing so they exert this inhibitory action they inhibit because they make the GABA have a greater affinity for the receptor binding site ○ So When you're propofol binds to the GABA receptor , the affinity for GABA is increased ,you get more chloride influx and more hyper polarisation and therefore it becomes more difficult because that post synaptic membrane is hyperpolarised and it becomes more difficult to propagate an action potential , so you abolish normal action potential propagation ○ Each agent mentioned that acts at the GABAA receptor acts at different degrees on different types of receptor

How to reduce the effects of rockuronium using neostigmine ? How to prevent bradycardia effects of neostigmine ?

○ IF you don't want your rockuronium to last 30 mins , there are ways to speed the offset , Ach physiologically undergoes a process of destruction by Ach Esterase into choline and acetic acid - Drugs like neostigmine is given commonly IV and we give that which is Ach esterase inhibitor so it stops that enzyme from breaking down , you flood the neuromuscular junction and post-synaptic membrane with Ach Molecules and just by flooding the post-synaptic membrane with Ach , you overcome some of the blocking effect of rockuronium , It cant antagonize or be competitively antagonist enough against that amount of Ach , Ach is also a neurotransmitter of the Parasympathetic nervous system - so Ach acts at nicotinic receptors on skeletal muscles , but also acts on PNS fibres as they have parasympathetic muscarinic receptors and if you give neostigmine , you will casue salication , bronchospasm(Construction of Bronchi- Vasular Attack), slow heart beat from the vagus nerve , increase peristalsis and cause diarrhoea - SO WE CO-ADMINISTER: glycopyrronium which is an antagonist specifically at muscarinci Ach receptors so it prevents bradycarida that you would otherwise get from unopposed neostigmine administration

Neuritis and causes ?

○ Inflammation of peripheral nerves - Infectious eg: Leprosy(microbacterial infection directly invades your peripheral nerves) , trypanosomes, CMV, Lyme Neuroborreliosis(Cranial), HSV+VZV (Sensory ganglia) - Post infectious(This is the common) eg: Gullian Bare syndrome (GBS) - After 1. Campylobacter jejuni(commonest) 2. Mycoplasma pneumoniae 3. Herpes Viruses - Toxins: Produces the effect at the peripheral nerves 1. Direct effect- diphtheria 2. Indirect - tetanus/Botulism

encephalitis ?

○ Inflammation of the brain Cerebral irritation/dysfunction can include: - Irritability , altered personality , drowsiness - Ataxia - Excessively brisk tendon reflexes - Signs of cerebral/Brainstem failure eg: Sluggish pupil reflexes - Signs of brain swelling eg: Focal neurological signs - Focal signs based on which sides of brain parts of brain is affected by organism ○ NB signs of meningism may co-exist = meningo-encephalitis

Myelitis

○ Inflammation of the spinal cord- with or without encephalitis - Transverse - acute transection of the cord 1. Vasculitis of anterior spinal artery - Primary infection eg: VZV, TB, Syphilis, Schistosmiasis - Post infectious- Associated with measles , mumps, rubella, upper respiratory infections 2. Direct invasion of cord - VZV or Borrelia , HTLV -1 thoracic cord - Ascending - ascending flaccid paralysis and sensory loss - Anterior horn cells eg: Polio- flaccid paralysis muscle pain no sensory or bladder dysfunction - polio, enterovirus 71, some arboviruses and rabies virus

Propofol- explain mechanism of propofol

○ Lipid emulsion - White in color ○ GRAPH EXPLAINS: - Enters plasma compartment/blood qucikly - Plasma Compartment declines quickly because propafol is slowly diffusing down the concentration gradient into three gropus of tissue 1. Vessel Rich Groups - Heart - Brain or heart - Fast Metabolising , Fast Blood flow;- IF concentration in brain rises above certain threshold - it induces unconsciousness , offset of unconsciouness - similarly when the propafol starts to decrease in the vessel rich group that's not because its been metabolized into something inactive - its actually just started to diffuse down concentration gradient from the vessel rich group into your fat - so the wake up from propafol 2. Skeletal Muscle - Large Tissue Compartment - slightly lower blood flow compared to vessel rich group - slower offset than brain 3. Fat - Slowly then after above two gropus - it leaks into adipose tissue -- fats

How do local anaesthetics work ?

○ Local anaesthetics acts on that sodium channel that causes that depolarization in phase 2 ○ They do that by going from an unionized and lypophilic form (Extracellularly) , cross the lipid membrane , theyre lypophilic and unionized ○ Become ionized intracellularly, casue of change in pH and then they bind to this sodium channel (Black Ball)- in three states- resting , activated and inactivated and they bind the active sodium channel and force it into an inactive state so you can no longer depolarise ○ Sodium channels are blocked in an inactive state - Instead of getting normal depolarization , local anaesthetic prevents from reaching threshold potential where you are able to depolarize rapidly

What are symptoms of meningitis ?

○ Meningism: - Headache global - Neck and Back stiffness - Nausea and vomiting - Photophobia (Non-specifc) ○ Can occur in other conditions: - Other infections eg: UTI, Dysentery - SAH(Sub-arrachnoid Haemmorhage), Malignancy, NSAIDs

What are the ethical issues in genetic s?

○ Non-paternity ○ Confidentiality ○ Health professional's responsibilities to family members ○ Testing of children and adolescents for genetic analysis ○ Next of kin ○ Prenatal testing ○ The "right to know" and the "right not to know" ○ Genetic testing in the context of adoption

Why are the CNS side effects of propofol seen ? Why does Propofol cause atonia ? Why are patients told to take three deep breaths/3 deep breaths before propofol ? Why is oxygen given before doses of anaesthetic agents ?

○ PROPOFOL is acting on these green arousal centres in the medulla and some higher up but theyre very close (Millimetres away from the motor nuclei controlling your descending motor pathways) and they're very close to the brain stem nuclei and also theyre also very close to your respiratory nuclei in the base of the fourth ventricle , the ventral and dorsal respiratory groups ○ So propofol and other agents don't selectively act on just your arousal centres , but the effects of propofol is felt across the brain stem and that is why patients become atonic, they lose their cranial nerve pathways reflexes and they become apnoeic because of their effect on the respiratory centre ○ This is why oxygen is given before are given doses of anaesthetic agents - Take three deep breaths

What are rockuronium practicalities ?

○ Paralysis to facilitate intubation and surgery - they also facilitate us intubating the patient so introducing airways into the patietns lungs in order to assist with their oxygenation during surgery ○ Not an agent of unconsciousness - they help surgeons stop the patients moving and breathing ○ Anaphylaxis risk- so anaesthetists must be able to manage acute crises and critical incidents due to these agents that have anaphylaxis risk

Explain action of sugammadex (IV)?

○ SO ALTERNATIVELY TO GO THROUGH THIS ALL , YOU CAN GIVEN SUGAMmADEX (Which has NEOSTIGMINE AT ITS ROCK CENTRE)INSTEAD of Neostigmine ○ So if Sugammadex given IV , it encapsulates rockuronium and decreases the concentration of free rock uranium in the plasma compartment and so rockuronium from your neuromuscular junction diffuses more quickly down that steeper concentration gradient away from the neuromuscular junction into the plasma ,where its encapsulated by Sugammadex- Speeding up the physiological process of Rockuronium - These are two agents discussed above which prevent neuromuscular paralysis

Epilepsy ?

○ Seizures can be very long or very brief like absence seizures ○ Epilepsy is repeated seizures ○ On EEG , a hypersynchronous neuronal discharge is seen ○ Worldwide problem (0.5-1% of the population) ○ Primary or symptomatic - brain tumor or stroke or some other brain abnormality ○ Often long-term treatment ○ Clinical history is key ○ EEG helpful in younger patients

What are the different prostanoid receptors?

○ The generation of these prostaglandins following increased induction of COX-2 in response to tissue damage results in mediators that can then act at specific receptors and alter the local environement whether through sensory nerves or other immune cells present

What is Neuroepidemiology incidence , prevalance , point prevalance , period prevalance , Lifetime prevalance , genetics , genomics ?

○ The study of the frequency , distribution and mortality of neurological disease ○ Incidence : Measures the rate at which cases occur in a specified population during a specified period (number of new cases occuring per 100000 of the general population per year) ○ Prevalance is defined as proportion of a population that are cases at a point in time (number of existing cases per 1000 of the general population). ○ Point prevalance: Number of cases on a particular day (prevalance day) ○ Period prevalance: Number of cases in a population over a specified period of time ○ Lifetime prevalance: The risk of acquiring the condition at any time ○ Genetics - the study o selected genes to understand inheritance Genomics - the study of the whole genome (23,000 genes) to understand how variations affect health and disease

Absence seizures

○ VERY Difficult to distinguish in normal state During the seizure - They may be vacant , eye roll upward , eyelids flutter , cessation of activity , lack of response , don't pay attention in class because can last very brief periods in class even the patient wont be aware its happening