Neuro Final

Why does recovery usually occur from relapses?

Acute inflammation resolves Nerve membrane remodeling and redistribution of sodium channels Plasticity Partial re-myelination

Classification of alcohol confusional syndromes

Acute intoxication Acute withdrawal (Delirium Tremens) Subacute (Wernicke's Encephalopathy which can become chronic --> Korsakoff's) Chronic (apart from Wernicke-Korsakoff)

Responsible for homeostatic sleep drive

Adenosine

G alpha-i

Adenylyl cyclase is inhibited leading to decrease in cAMP

Adjustment insomnia vs. idiopathic insomnia vs. inappropriate sleep hygiene vs. paradoxical insomnia vs. psychophysiologic insomnia

Adjustment insomnia: acute stressor Idiopathic insomnia: lifelong insomnia Inappropriate sleep hygiene: bad habit Paradoxical insomnia: misperception of very minimal or no sleep (will have a normal sleep study but still feel like they didn't) Psychophysiologic insomnia: rumination and intrusive thoughts

Corneal reflex arc

Afferent portion: CN V Efferent portion: CN VII

What can be used as a quantitative measure of attention span?

Digit span (7 is normal)

What causes cytotoxic edema in infarction?

Oxygen and glucose substrates are not making it to brain cells, Na/K pump is not being fed with ATP = cells will take on solute/water = swelling = cytotoxic edema (extracellular space now <15%) Impairs water diffusion = bright white on diffusion-weighted imaging MRI

Which areas of the CNS receive protopathic (i.e., slow) pain information as part of the anterolateral system?

PAG, reticular formation, and cingulate gyrus

The limbic system connects with posterior or temporal association cortex via the _______

Parahippocampal gyrus

Artery supplying paramedian region of pons (structures supplied)

Paramedian branches of Basilar artery Structures supplied: corticospinal fibers, medial lemniscus, abducens nerve and nucleus, pontine reticular area, PAG

Pathophysiology of cramps

Cramps may be caused either by peripheral motor nerve excitation or by CNS excitation Stretching may inhibit cramps through relief of distortion of nerve endings and/or through Golgi tendon organ activation, which inhibits spinal motor neurons

Organization of neoplasms of the spinal cord

Extradural vs. intradural EXTRADURAL Spinal: vertebral metastases, primary malignant or benign tumors of bone Intraspinal: epidural metastases INTRADURAL Extramedullary: meningioma, Schwannoma, neurofibroma Intramedullary: ependymoma, astrocytoma, glioblastoma

Spinal Schwannoma

Extramedullary Near ventral nerve root, lateral compression of spinal cord

Aphasia in the absence of other symptoms suggest (focal/generalized) brain pathology

Focal

Metal status abnormalities that favor one hemisphere over another suggest....

Focal cerebral diseases: stroke, tumor, hematoma

Status epilepticus

Seizure lasting >30 minutes or recurrent seizures without return to consciousness 8% mortality rate in children, 3% die from seizure itself Treatment: IV lorazepam (repeat dose if no response) --> add fosphenytoin --> loading dose of phenobarbital if seizure continues to induce medical coma

Genetic defect in Myotonic Dystrophy

Gene near centrosome of chromosome 19 codes for myotonic dystrophy protein kinase (dozens to hundreds of CTG repeats) Transcribed mRNA gets trapped within cell's nucleus Autosomal dominant CTG gets longer (more severe disease) in successive generations

Sleep vs. wake NTs

Sleep: GABA Wake: NE, 5HT, Histamine

What happens to ghrelin and leptin levels during sleep deprivation and what effect does this have?

Ghrelin levels increase: increases appetite --> increased uptake of calories --> weight gain Leptin levels decrease (leptin normally functions to reduce appetite, causing weight loss)

The subthalamic nucleus is most heavily interconnected with the:

Globus pallidus (receives input from and projects to)

Lenticular striatum

Smaller vessels which come off at nearly 90 degree angles from the initial segment of the middle cerebral artery to feed deeper structures (caudate nucleus, internal capsule, basal ganglia)

Bilateral ablation of amygdala

Kluver-Bucy Syndrome: 1) fearlessness 2) extreme curiosity 3) rapid forgetfulness 4) hyperorality 5) hypersexuality

If tongue comes out on the L side of the mouth...

L CN XII lesion suspected

L vs R hemisphere tasks

L hemisphere: language (especially L temporal, parietal and frontal lobes), calculation (L parietal lobe) R hemisphere: drawing, denial and neglect syndromes (especially R parietal lobe)

Valproic acid decreases degradation of ____________

Lamotrigine (Lamictal)

____________ and _________ are almost exclusively L hemisphere tasks

Language, calculation

Hemiballism

Large amplitude proximal chorea Relates to structural lesion in contralateral hemisphere (subthalamic nucleus, interconnections b/w striatum, subthalamic nucleus, thalamus, etc.) Primary causes in elderly: vascular, nonketotic hyperglycemia " " in young: infectious, inflammatory

Common size, shape and location for large-vessel infarction in territory of one or more branches of middle cerebral artery

Large, wedge/triangle-shaped, trans-cortical infarction

Affect of hyperglycemia on infarction. Why? What can you do?

Larger area of infarct In ischemic area of tissue, not having as much aerobic metabolism; if you keep feeding glucose in, it will get shunted off to form lactate (appears toxic to tissues) IV insulin to bring down blood sugar quickly

Long-term memory is generally the (first/last) to be affected by pathology

Last (i.e. resilient)

Parkinsonism

Less movement and what movement there is is slow Hypokinesia/akinesia (for example, decreased frequency of blinking from normal) Bradykinesia Rigidity (increased tone, not to be confused with spasticity or paratonia) Stooped posture Small-stepped gait "Rest" tremor

Bilateral or non-localized cognitive tasks

Level of consciousness Attention Psychiatric inventory Orientation Memory Abstraction (frontal lobes)

Cornerstone of PD treatment

Levodopa (L-DOPA): precursor of dopamine that crosses blood brain barrier and can restore dopamine levels and motor function but causes a lot of nausea; still of benefit to virtually all PD patients but now packaged with carbidopa (inhibitor of dopa-decarboxylase, increases concentration of levodopa in circulation that can be taken across BBB)

Give examples of AEDs with with linear and non-linear pharmacokinetics

Linear (clearance remains constant as dose increases): phenobarbital Non-linear (clearance increases with dose): carbamazepine, valproic acid Non-linear (clearance decreases with dose): phenytoin

What determines potency of local anesthetics?

Lipid solubility/protein binding More lipophilic agents are more potent as local anesthetics

Oligoclonal protein bands seen in electrophoresis of cerebrospinal fluid from multiple sclerosis patients indicate presence of what immune process?

Local immunoglobulin synthesis Local B cell responses by a few cells (oligoclonal vs. polyclonal) to a few antigens results in local accumulation of electrophoretically homogeneous immunoglobulin not normally present in CSF.

Parahippocampal gyrus: location, function and clinical implications

Location: grey matter that surrounds hippocampus and delivers input; complex thought associations from Wernicke's area Function: important in memory encoding and retrieval Clinical implications: loss of spatial memory, schizophrenia, seizures, Alzheimer's disease

Genetic defect in Facioscapulohumeral Muscular Dystrophy

Long arm of chromosome 4

Partial complex seizure

Loss of consciousness Duration 1-2 minutes Aura common (30%) Hallmark: automatisms (50-75%) Medial-temporal area

What is responsible for most of the motor abnormalities in PD?

Loss of dopaminergic nerve cells in substantia nigra results in striatal dopamine depletion

Spinal muscular atrophy (types)

Lower motor neuron condition 1. Werdnig-Hoffman: autosomal recessive, "floppy baby" in "strap-hanger position" that generally does not make it to 1st birthday 2. Kugelberg-Weilander: teenage-onset, proximal weakness > distal weakness 3. Adult-onset *Generally cause more weakness distally than proximally with exception of Kugelberg-Weilander, which causes more proximal weakness than distal weakness

pKa, % unionized, lipid solubility and protein binding of: Mepivacaine Lidocaine Bupivacaine Tetracaine

Mepivacaine: pKa = 7.6, 39% unionized, low lipid solubility, medium protein binding (fast onset, intermediate potency) Lidocaine: pKa = 7.9, 24% unionized, low lipid solubility, medium protein binding (fast onset, intermediate potency) Bupivacaine: pKa = 8.1, 17% unionized, high lipid solubility, high protein binding (slow onset, high potency) Tetracaine: pKA = 8.5, 7% unionized, high lipid solubility, high protein binding

Describe the addiction and reward center circuit and its clinical implications

Mesolimbic pathway: ventral tegmental area to amygdala and nucleus accumbens Ventral tegmental area (rich in dopaminergic neurons) projects to nucleus accumbens (part of basal ganglia) and amygdala which then projects to limbic cortex *can cause hallucinations and schizophrenia if not functioning properly *IMPLICATED IN ADDICTION *Can inject dopaminergic receptor antagonists to inhibit pathway

The ________________ pathway is implicated in addiction

Mesolimbic: ventral tegmental areas <--> amygdala <--> nucleus accumbens/basal ganglia

GABA-B receptor agonists

Metabotropic K+ channel Baclofen

Drugs for mild vs. moderate dementia symptoms

Mild: aceylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) Moderate: glutamate-oriented -- i.e. blocking of excitotoxic glutamate at glutamate receptors (Memantine/Namenda)

MAC

Minimum Alveolar Concentration: provides a means to compare the POTENCY of various inhalational agents Serves as a guide to determine dose Additive Lower % MAC value = more lipophilic compound = mot potent Halothane: .75 (only need 0.75% halothane in atmosphere to affect 50% of patients) Nitrous Oxide: 105

Lennox-Gastaut Syndrome

Mixed seizure disorder: atypical absence, generalized tonic-clonic, tonic and atonic Onset 1-8 years (peak 3-5) <10% develop normally Generalized slow spike-wave pattern Most commonly arise in patients with infantile spasms (33%) Cognitive slowing, persisting seizures

Secondary stroke prevention

Modifiable atherosclerotic risk factors: Treat HTN (aggressive) Treat diabetes Treat lipids Stop smoking Consider plant-based diet

Golgi tendon reflex

Monitors external tension produced during muscular contraction to prevent tendon damage (it is the inverse of stretch) GTO (sensory receptor) is activated by stretching of tendon, inhibitory neuron is stimulated (motor neuron is hyperpolarized and muscle relaxes); alpha motor neurons are inhibited; antagonist muscles are activated Purpose is to prevent extensive contraction; both tendon and muscle are protected

2 drug types that prolong dopamine in synapse

Monoamine oxidase B (MAO-B) inhibitors: Selegeline, Rasagiline Catechol-ortho-methyl-transferase (COMT) inhibitors: Entacapone, Tolcapone

Strategies of teratogenesis risk reduction

Monotherapy Lowest dose of AED Folate supplementation Prenatal testing Vagal nerve stimulation In women of child-bearing potential, avoid divalproex, carbamazepine, phenobarbital and polypharmacy

Tonic seizure

Sustained muscle contraction EEG: fast activity (15-25 Hz)

Generalized dystonia

Sustained twisting movements involving trunk as well as limbs Disturbed gate Patients tend to get better on tetrabenazine (pre-synaptic dopamine depleter)

Torticollis

A form of focal dystonia that involves turning/twisting of neck Not weakness, just involuntary movement that can be suppressed to a certain extent (better with calm, disappears during sleep, worse when stressed)

-Paresis

Weakness

Diagnostic mental status exam components

What is the hardest thing they can do and the easiest thing they cannot? A. Level of consciousness B. Attention: digit span (7 is normal), preservation = inability to shift appropriately from one mental task to another) C. Psychiatric inventory: interview appearance and behavior, thought content (i.e. delusions), thought process (i.e. logical or loose), perceptual distortion (i.e. hallucinations), affect (moment to moment) and mood (more lasting) D. Orientation: person (patient's own name), place and time (in order of difficulty) E. Language function (generally lateralizes to L cerebrum): fluency (quantity of verbal output, regardless of quality), oral comprehension (give motor commands of varying complexity, ask patient to point to objects and don't give nonverbal cues), naming (point to eye, ear, pen, knuckle, collar), repetition (repeat words and phrases of increasing length and complexity; car, baseball, Mississippi River; no ifs ands or buts), reading comprehension (read written words aloud, alternatively ask patient to read a written instruction and perform the task; tests similar functions as verbal comprehension), writing (ask patient to write a complete sentence of their own choosing; needs to have subject, verb and also make sense; tests similar function as oral output) F. Memory: short term memory = digit span; classic recent or intermediate-term memory = provide 3 words for patient to restate after 5 minutes; long-term memory = can be evaluated by retrieving info from personal history such as wedding date and employment history but independent corroboration is needed, as from family member G. Calculation (largely a L hemisphere task): math problem - i.e. add a penny, nickel, dime and quarter; serial-7 subtractions from 100 or serial-3 subtractions from 100) H. Drawing (largely a R hemisphere task mediated by R parietal lobe): ask patient to copy sample picture or diagram (clock, flower in flower pot, house, intersection pentagons) I. Denial and neglect syndromes (indicate damage to R parietal lobe): patient may deny clinically-obvious signs/symptoms, deny ownership of L-sided body parts; fail to attend to the L halves of their visual worlds (i.e. not shaving the left half of their face); tested for with paper and pencil tests (line bisection) J. Abstraction (one of the highest level of cognitive performance, involves frontal lobes and other association areas): "people who live in glass houses shouldn't throw stones" (can have abstract, concrete or incorrect/non-interpretations)

Folstein Mini-Mental State Exam

Widely-used, quantitative, standardized instrument useful for screening for cognitive impairment Can be administered by non-physicians with good reliability Useful for making serial measurements in patients whose diagnoses are already established (NOT USEFUL AS A DIAGNOSTIC TOOL) Analogous in some ways to Glasgow Coma Scale Out of 30 points Mild: >21 Moderate: 10-20 Severe: <9

Flexor/Withdrawal Reflex

Withdrawal in response to a stimulus or pain, stimulates flexors to withdrawal and inhibits extensors to ensure they are unable to prevent flexion and withdrawal POLYSYNAPTIC 1. Sensory neurons conduction action potentials from pain receptors to spinal cord 2. Sensory neurons synapse with excitatory interneurons that are part of withdrawal reflex 3. Collateral branches of sensory neurons also synapse with inhibitory neurons that are part of reciprocal innervation 4. Inhibitory interneurons synapse with alpha motor neurons supplying extensor muscles, causing them to relax and not oppose flexor muscles of withdrawal reflex which are contracting

Long-term potentiation neuron types and pathways

Within hippocampus Neuron types: pyramidal neurons (CA1 and CA3 regions), granule neurons (dentate region) Pathways: 1. Schaffer collateral (CA1) 2. Mossy fiber (CA3) 3. Perforant (dentate) EPSP (not action potential) stimulates NMDA receptor --> LTP

Sleep in pregnancy

Worse during 1st trimester, improves during 2nd trimester, worst during 3rd trimester (i.e. 3rd > 1st > 2nd) Increase in risk for snoring and OSA (particularly with pre-eclampsia), RLS/PLMD, nocturnal leg cramps, EDS (excessive daytime sleepiness)

Pathway involved in speaking a heard word

ear CN VIII --> medial geniculate nucleus of thalamus--> primary auditory area (superior/transverse gyrus of L temporal lobe) = site of sound reception, brain recognizes there has been a sound but doesn't know what it is --> from there relays to Wernicke's area (where the word/sound is comprehended); to say word back to examiner, we have to travel through arcuate fasciculus (white matter, part of superior longitudinal fasciculus) to Broca's area (posterior to anterior) = where word(s) are prepared for speech output (language output center, whether by foreign language, sign language, etc.) --> then to motor strip to areas having to do with mouth, lips Wernicke's area (Broadmann's area 22) to Broca's area (Broadmann's area 44) via arcuate fasiculus

Who benefits the most from carotid endarterectomy/stenting at carotid bifurcation?

Those who have 70-99% narrowing of internal carotid artery on same side as stroke

Diseases associated with myasthenia gravis

Thymoma (malignant mediastinal tumor) Thyroid disease Widespread immune-complex disease (rheumatoid arthritis, SLE)

GABA reuptake inhibitor

Tiagabine

Typical vs. atypical absence seizure

Typical absence: brief (<30 sec), hyperventilation to induce, 3 Hz spike-wave discharges Atypical absence: longer (<60 sec), gradual onset and termination, slower 1-2 Hz spike and waver pattern, more motor signs

Spasticity

Unidirectional increase in muscular tone Involves increased tone in "anti-gravity" muscles (i.e. in UE, resistance to stretching out biceps but not triceps; in LE, resistance to stretching out quadriceps but not hamstrings Don't rely on "clasped-knife" pattern

Fasiculations of the ipsilateral resting tongue suggest

Unilateral CN XII neuropathy

Decreased retraction of the ipsilateral corner of the mouth suggests

Unilateral facial nerve lesion

Sleep deprivation: what goes... Up Down

Up: Sleepiness (homeostatic sleep drive increased -- i.e. adenosine) Sympathetic activity Hormones (cortisol, ghrelin) Insulin resistance Metabolic rate Down: Vigilance Cognition Resistance to infection Growth hormone and leptin activity

Forehead wrinkling: upper motor neuron vs. lower motor neuron

Upper motor neuron lesion: both sides of forehead wrinkle well (because each facial nerve nucleus receives both crossed and uncrossed info) Lower motor neuron lesion: flattening on side of palsy

Characteristics of upper motor neuron weakness vs. lower motor neuron weakness

Upper motor neuron: Clumsiness in greater proportion than loss of power Babinski sign present (immediate) Spasticity = increased tone (delayed, may take 1-2 weeks) Increased tendon reflexes (delayed) Little if any atrophy Lower motor neuron: Loss of power in greater proportion than clumsiness Hypotonia Muscle atrophy Muscle fascinations

Second gas effect

Uptake of large volumes of gas from alveoli increases the rate of alveolar concentration of a second gas given at the same time

Intention to treat analysis

Use every participant who was randomized according to randomized treatment assignment Ignore nonadherence, protocol deviations, withdrawal and anything that happens after randomization (i.e. include in data analysis)

Paraphasias is a measure of _______________

Use of nonexistent or inappropriate words Measure of fluency (language function)

Valgus vs. varus

Valgus: foot turned out Varus: foot turned in

AEDs associated with neural tube defects

Valproic acid and carbamazepine

Cocaine produces (vasodilation/vasoconstriction)

Vasoconstriction

How do diagnose dementia d/t vitamin B12 deficiency

Vitamin B12 blood level followed up with methylmalonic acid level if B12 level is low or borderline Can treat with B12 injection while awaiting test results (intramuscular, not absorbed through GI tract) Methylmalonic acid is ELEVATED when vitamin B12 is LOW

Affect of vitamin D on MS

Vitamin D may have protective effect and lower risk of developing MS For people who already have MS, vitamin D may lessen the frequency and severity of their symptoms A connection between vitamin D and MS could be tied to the positive effects vitamin D has on the immune system In studies of a group of nurses, the risk of developing MS was substantially less for women taking 400 international units (IUs) or more of vitamin D a day

Fascinations of characteristic of ________________________

motor neuron disease

Pathway involved in speaking a written word

optic nerve --> optic chiasm --> optic tract --> optic radiations --> primary visual receiving area (area 17), some of which is on medial aspect of occipital lobe = first cerebral (gray matter, cortex) area where info arrives (all we are seeing is white and black, don't know yet what it means) --> angular gyrus --> Wernicke's area (language comprehension area = recognition); before it got to Wernicke's area, it wasn't appreciated as written language; then the same pathway as before (i.e. from Wernicke's to Broca's via the AF)

Rate of onset of local anesthetics is determined by ___________________

% unionized (pKa)

Drugs that act primarily on K+ channels (MOA and examples)

*Cause membrane hyperpolarization and reduce excitability of neurons in brain Retigabine: opens K+ channel by acting as agonist Oxcarbazepine Valproate

Treatment of myasthenia gravis

1. Acetylcholinesterase inhibitors (pyridostigmine) 2. Thymectomy (removed even if no tumor is present) 3. Corticosteroids 4. Plasma exchange 5. Other immunosuppressants

4 steps of memory formation and storage

1. Encoding: the processes by which newly learned information is attended to and processed when first encountered 2. Consolidation: processes that alter the newly stored and still labile information to make it more stable for long-term storage; may involve expression of genes and synthesis of new protein, structural changes and LTP (hippocampus) 3. Storage: mechanism and sites by which memory is retained over time (cortex) 4. Retrieval: process hat permits recall and use of stored info; involves temporal lobe

Diagnosis of Myasthenia Gravis

1. History: distribution of weakness, fatigue 2. Exam: proximal weakness, fatigue 3. "Tensilon test" = 2-10 mg edrophonium (acetylcholinesterase inhibitor) 4. Repetitive electrical stimulation: 10% decrement in 5th muscle action potential at 3 Hz rate (electrical equivalent of fatiguing muscle) 5. Acetylcholine receptor antibodies: present in majority of cases, about half of patients without these antibodies instead have antibodies to muscle-specific kinase (MuSK)

Two main causes of ptosis (decreased size of palpebral fissures, drooping)

1. Horner's syndrome 2. Unilateral CN III palsy

Describe the two anatomically separate neural systems involved in facial expression and facial recognition

1. Located in inferotemporal cortex (temporal lobe): involved in explicit memory of facial identify 2. Located in amygdala: involved with implicit memory of appropriate cues that signal emotions expressed by faces (i.e. feeling fearful when you see a scary face)

Order of sensory function block (modality and fiber)

1. Pain (C) 2. Cold (A-delta) 3. Warmth (A-gamma) 4. Touch (A-beta) 5. Deep pressure (A-beta) 6. Motor (A-alpha)

IV anesthetics

1. Sedative-hypnotics (barbiturates, benzodiazepines, propofol, etomidate) 2. Dissociatve anesthetics (ketamine = antagonist of NMDA receptor) 3. Opioids 4. Neuromuscular blocking agents

Stages of anesthesia

1. Stage of analgesia: analgesia without amnesia, impaired judgement, vertigo/ataxia, increased respiration, BP and HR (normal reflex) 2. Stage of excitement: loss of consciousness but most difficult to manage due to irregular respirations, struggling, coughing and vomiting 3. Stage of surgical anesthesia: recurrence of regular respiration, loss of cornea, swallowing reflexes, skeletal muscle relaxation 4. Stage of medullary depression (TO BE AVOIDED): begins at cessation of spontaneous respiration --> severe depression of vasomotor and respiratory centers, without support --> death

Treatment of vascular cognitive impairment (multi-infarct dementia)

1. Treat atherosclerotic risk factors (HTN, T2DB, lipids, smoking) 2. Address other etiologies: cardiac, coagulopathy 3. Use anti-thrombotic, anti-platelet drugs (ASA) vs. anti-coagulant drugs (warfarin) depending on etiology 4. Cholinesterase inhibitors (e.g. donepezil): doesn't repair lost tissue but gives you more bang for your bck

Alpha-synuclein

140 amino acid protein Expressed in pre-synaptic terminals Regulates dopamine transporter activities Prone to aggregate under oxidative stress: then aggregate inhibits 26S proteosome from clearing misfolding proteins Dysfunction of proteosome contributes to cell death Forms Lewy Body in Parkinson's Disease

G alpha-q/11 pathway

Activates phospholipase C (PLC) which converts PIP2 to IP3 and DAG; IP3 leads to release of Ca2+ from intracellular stores whereas DAG activates PKC

Neonatal seizure

2/1000 live births, higher risk with LBW and premature gestation Most occur in first week of life (fifth-day fits) Causes: intracranial hemorrhage or infection, metabolic derangements, hypoglycemia, hypo- or hyper-natremia, hypoxic event Unique because of multifocality, asymmetry of clonic movement, lack of generalization Good outcomes, usually disappear by 2-6 months of age

What % of brain insults causing CP occur prenatally?

70-80%

About _______ % of all strokes are ischemic (not hemorrhagic)

87% ischemic > hemorrhagic

Testing similarities

A similarity can be tested by asking the patient, "How are a boat and a train alike?" Naming the category that includes both, e.g. vehicles or forms of transportation, is an abstract interpretation. Naming a common trait, such as, "They both carry people" or "They both have engines" is a concrete interpretation. "They're not alike" or "I don't know" are incorrect interpretations.

The following are all characteristics of upper motoneuron weakness EXCEPT: A. fasciculations B. spasticity C. Babinski sign present D. clumsiness E. hyper-reflexia

A. fasciculations

These items are all components of the International Headache Society diagnostic criteria for migraine without aura, EXCEPT: A. family history B. unilaterality C. pulsatility D. phonophobia E. duration of attacks

A. Family history

Acute stroke management

ABCs (airway, breathing, circulation) Oxygen-carrying capacity (Hgb/Hct) Blood sugar Body temperature (concurrent infection) = fever causes larger stroke Blood pressure issues Fluid management (saline better than glucose) Monitoring (VS's, telemetry, neuro-checks) Concurrent heart attack? (EKG, enzymes)

AEDs that decrease oral contraceptive serum levels Alternatives? AED whose concentration is reduced by oral contraceptives?

AEDs that decrease oral contraceptive serum levels: carbamazepine, phenytoin, phenobarbital, primidone, topiramate, oxcarbazepine No interaction with levetiracetam or valproate Oral contraceptives reduce lamotrigine concentrations, which then go up during week of inactive tablets

Duchenne vs. Facioscapulohumeral vs. Limb Girdle vs. Myotonic Dystrophy Age of onset Sex Pseudohypertrophy Initial distribution Involvement of face Rate of progression Contractures and deformity Inheritance

AGE OF ONSET Duchenne: childhood FSH: adolescence LG: early or late SEX Duchenne: male FSH: either LG: either MD: either PSEDUOHYPERTROPHY Duchenne: common FSH: rare LG: uncommon MD: uncommon INITIAL DISTRIBUTION Duchenne: pelvic girdle (proximal to distal) FSH: shoulder girdle (proximal to distal) LG: either (proximal to distal) MD: broad temples, frontal alopecia, skinny hand muscles (distal to proximal) INVOLVEMENT OF FACE Duchenne: rare FSH: always LG: never MD: aways (frontal alopecia, myopathic facies, triangular face, sagging jaw) RATE OF PROGRESSION Duchenne: relatively rapid FSH: slow (abortive) LG: intermediate CONTRACTURES AND DEFORMITIES Duchenne: common FSH: rare LG: occasional INHERITANCE Duchenne: X-linked recessive FSH: dominant LG: either MD: autosomal dominant, CTG repeats that lengthen in successive generations

Huntington's Chorea

Abnormal involuntary movements are both proximal and distal (affects all four limbs, trunk and neck) Involuntary movements appear to be "fragments" of what would otherwise be considered a normal, voluntary movement Many patients with this seek to cover up movement disorder by completing a normal incorporated movement into what started out as an abnormal, involuntary movement In milder or earlier forms of this condition, movement disorder tends to be more distal than proximal and not nearly as frequent or continuous in appearance

Clues that patient has psychogenic cause of movement symptoms

Abrupt onset Inconsistent movements Incongruous movements and postures Additional abnormal movements Spontaneous remission Distraction Paroxysmal Onset as a fixed posture Side-to-side mouth movements

Werdnig-Hoffman SMA reflexes?

Absent

What is one of the highest levels of cognitive performance?

Abstraction (involves frontal lobes and other association areas) Evaluator can rate proverbs, similarities and idioms for abstract vs. concrete vs. incorrect interpretations. Example: "People who live in glass houses shouldn't throw stones." "Don't accuse someone of an act you might be guilty of yourself," is an abstract interpretation. "You'll break the glass," is a concrete interpretation. "You might start a fire," or "I don't know," are incorrect or non-interpretations Proverbs > similarities > idioms

Main REM sleep neurotransmitter

Acetylcholine

Function of major sleep and wake neurotransmitters Acetylcholine Adenosine GABA Glutamate Glycine Hypocretin

Acetylcholine: main REM sleep neurotransmitter Adenosine: responsible for homeostatic sleep drive (caffeine is antagonist) GABA: main NREM neurotransmitter, main CNS inhibitory neurotransmitter Glutamate: main CNS excitatory neurotransmitter Glycine: main spinal cord inhibitory neurotransmitter, responsible for REM muscle atonia/hypotonia Hypocretin: dysfunction associated with narcolepsy-cataplexy

Dementia

Acquired, persisting confusional state

Difference b/w action potential and graded potential (EPSP/IPSP)

Action potential: all or nothing, must reach threshold EPSP/IPSP: does not have to reach threshold, size of potential driven by intensity of stimulus

Advantages of crossover trial

All of the advantages of RCT but equitable Participants serve as own controls (error variance reduced, eliminates within-patient confounding, smaller sample size needed -- i.e. powerful and efficient) All participants receive treatment Use statistical tests assuming randomization Blinding can be maintained Opportunity for head-to-head trials

G stimulatory protein coupled receptor pathway

Alpha binds to adenylyl cyclase, causing increased production of cyclic AMP (cAMP) which activates protein kinase A (PKA)

Alpha motor neurons vs. gamma motor neurons

Alpha motor neurons: project to extrafusal skeletal muscles to cause contraction Gamma motor neurons: project to intrafusal fibers to regulate muscle tone (constantly sending action potentials)

Basic EEG wave frequencies Alpha Beta Delta Theta K complex Sleep spindle

Alpha: 8-13; drowsiness with eyes closed Beta: >13; alert wakefulness Delta: <4; N3 sleep Theta: 4-7; N1, N2 and REM K complex: N2 Sleep spindle: run of wave 12-14, duration >0.5 seconds; N2

Diseases in which hippocampus is clinically implicated

Alzheimer's Disease Epilepsy Depression and stress, biopolar Schizophrenia

Learned emotional responses are processed in the _____________

Amygdala

What is the major output of the limbic system?

Amygdala (well-connected with hypothalamus via striate terminales)

Describe the function of the amygdala's projections to the: Parabrachial nucleus Lateral hypothalamus Cingulate gyrus and locus coeruleus Periaqueductal grey

Amygdala --> parabrachial nucleus: increased respiratory rate Amygdala --> lateral hypothalamus: sympathetic discharge Amygdala --> cingulate gyrus & locus coeruleus: NE release, increased HR, BP and fear (i.e. fight or flight) Amygdala --> periaqueductal grey: defensive behavior, freezing, jumping and running

A β protein accumulates in the brain of patients with Alzheimer's disease in what form?

Amyloid

How are senile plaques formed?

Amyloid/senile plaques are dense, insoluble deposits of amyloid-beta proteins, which are fragments of amyloid precursor proteins (APP), a transmembrane neuronal protein As these proteins are enzymatically broken down, they clump together, forming dense structures identifiable as amyloid plaques (accumulate in association cortices and hippocmapus)

ALS

Amyotrophic Lateral Sclerosis/Lou Gehrig's Disease Upper motor neuron and lower motor signs; no Babinski sign but hyperreflexia present Typically starts in arms or legs

Dystonic writer's cramp

An action focal dystonia that results in sustained twisting movement (i.e. progressive flexion of fingers, wrist) of one hand that occurs only during handwriting

Testing idioms

An idiom can be tested by asking the patient, "What does it mean when you say someone has 'a warm heart?'" "They're kind," is an abstract interpretation. "Their heat is still beating," is a concrete interpretation. "It means they also have kidneys," or "I don't know," are incorrect interpretations.

Where do 85% of congenital cerebral aneurysms?

Anterior circulation

The _________ connects the two amygdala

Anterior commissure

Consequence's of H.M.'s surgery (removal of hippocampus)

Anterograde amneisa (can't make new memories) and failure to form explicit (declarative) memories (implicit/non-declarative memory intact)

Anterograde vs. retrograde amnesia

Anterograde: can't make new memories Retrograde: can't recall past memories

Anti-thrombotic drugs in secondary stroke prevention

Anti-platelet drugs are superior for prevention of non-cardiac embolic strokes - Plavix (clopidogrel) provides optical balance b/w efficacy and bleeding complications - For those who can't take Plavix, ASA by itself and Aggrenox (ASA + dipyridamole) are also effective - Plavix + ASA = greater stroke prevention but increased risk of bleeding

Monoameinegic receptor hypothesis Why isn't this the full story?

Antidepressants work by regulating serotonin autoreceptors Autreceptors inhibit the serotonergic neruron from making and releasing 5-HT Prolonged exposure to 5-HT densensitizes these autoreceptors and reduces the number of 5-HT1A receptors (coupled to Gi/o = inhibit AC, reduced cAMP, activate K+ channel, inhibit Ca2+ channel) = neurons continue releasing neurotransmitter, even at higher levels At a certain point, neurons will go back to lower level of serotonin release (even without 5HT-1 receptor inhibiting them) Eventually reset

Increase in CREB activity has overall (depressive/antidepressive) effect

Antidepressive

Use of acetylcholinesterase inhibitors for Alzheimer's disease

Approved for "MILD" dementia symptoms (i.e. b/w 29-20 on Folstein Mini-Mental Exam) Donepezil (Aricept) Galantamine (Razadyne) Rivastigmine (Exelon)

"Association" areas of neocortex are so called because they:

Are not directly connected to sensory relay nuclei of the thalamus

Anterior spinal artery syndrome

Artery compressed by bone or cartilage spicules; affects ventral and lateral spinal cord (posteromedial section spared) Motor function and pain sensation lost bilaterally below injured segment; position sense preserved

Febrile seizures

Associated with fever (not about degree but about how quickly you came up or down) No evidence of intracranial infection More common in males Simple: 80%, generalized, <15 minutes, no more than 1 event in 24 hours Complex: multiple seizures within 24 hours, prolonged in duration, focal

Highest risk factors for stroke

Atrial fibrillation Hypertension Smoking Alcohol *In that order, cumulative

Main source of cardioembolic stroke

Atrial fibrillation (45%) = irregularly irregular heartbeat causing dead zones and non-laminar flow

Evidence supports benefit in preventing migraines by all these drugs, EXCEPT: A. Divalproex sodium B. Lorazepam C. Topiramate D. Propranolol E. Amitriptyline

B. Lorazepam (B) is correct because no benzodiazepine drug has shown efficacy against migraine in rigorous studies. Divalproex sodium, topiramate and propranolol are all first-line drugs for migraine prevention, while amitriptyline is a second-line drug for migraine prevention

Which of the following is a representative of the branchiomotor (musculature derived from pharyngeal arch neural crest--SVE) column in the pons? A. abducens nucleus B. facial nucleus C. principal trigeminal nucleus D. dorsal motor nucleus of the vagus E. lateral lemniscus

B. facial nucleus

A class of drugs which enhances the binding of GABA to its receptor is:

Barbiturates such as phenobarbital

Amantadine in PD treatment

Benefit for PD found by accident in 1978 MOA unclear May have effects on dopamine neurons Weak NMDA (glutamate receptor) antagonist

Most common type of partial epilepsy (peds)

Benign Rolandic Epilepsy: Onset b/w 5-10 years Simple seizure Centrotemporal spikes Unilateral facial sensory-motor, drooling, unable to speak Child is awake Usually have remission of seizure by 17 y/o

Pharmacotherapy for insomnia

Benzodiazepine receptor agonists: benzodiazepines, non-benzodiazepine BZRAs Selective melatonin receptor agonists Doxepin Several classes of medication are used "off label" such as trazodone May enhance sleep (total sleep time) but often do not improve daytime performance Minimal long-term beneficial effect on sleep following drug discontinuation (CBT better0 Side effects common

Rigidity

Bi-directional increase in tone to passive range of motion Seen in Parkinson's disease and other extrapyramidal disorders Resistance to passive range of motion is relatively independent of degree of force or rate)

Spinal segment and peripheral nerve involved in the following reflexes: Biceps Triceps Finger flexion Knee Ankle

Biceps: C6, musculocutaneous n. Triceps: C7, radial n. Finger flexion: C8, median and ulnar nn. Knee: L3, femoral n. Ankle: S1, sciatic n.

Paratonia

Bidirectional resistance to passive range of motion that increases with force and rate of movement, as if voluntary Also known as gegenhalten (to hold against) Commonly seen in dementia (but not diagnostic)

Kluver-Bucy Syndrome

Bilateral ablation of the amygdala causing 1) fearlessness 2) extreme curiosity 3) rapid forgetfulness 4) hyperorality 5) hypersexuality

Mental status abnormalities that demonstrate multiple domains of impairment but without a preponderance of abnormalities favoring one hemisphere over another suggest...

Bilateral diseases: metabolic encephalopathy, dementia

Polyneuropathy

Bilaterally symmetric (distinct from mononeuropathy and multiple mononeuropathies) "Stocking and glove" pattern of sensory loss (areas do not match up with known territories of individual nerve bundles) Muscles that are most distal get weakest first (longest axons) Disrupts DRTs more than other forms of lower motor neuron weakness Distal-greater-than-proximal weakness Distal-greater-than-proximal numbness Length-dependent neuropathy (longer axons affected first)

MOA of local anesthetics

Bind directly to intracellular voltage-dependent sodium channels (block primarily open and inactive sodium channels at specific sites)

Most common MS symptoms

Bladder Fatigue Spasticity Sexual dysfunction Pain Cognitive dysfunction Bowel dysfunction Depression

SSRI MOA

Blocks SERT (5-HTT) to prolong actions of 5-HT

Ethosuximide

Blocks T-type Ca2+ channels (which, when activated, induce a brief repetitive firing of action potentials) *Highly effective for treating absence seizures

Lamotrigine

Blocks voltage-dependent sodium channels at high firing frequencies Inhibits Ca2+ channels Inhibits glutamate release

2 main dopaminergic pathways in brain

Both originate in midbrain very close to one other 1) Ventral tegmental area: project to limbic (mesolimbic projection) and cortical (mesocrotical projection) areas 2) Substantia nigra: project to striatum

What happens when an eye affected by unilateral optic nerve impairment is illuminated during the swinging flashlight test (Marcus-Gunn) maneuver?

Both pupils constrict less than when the good eye is illuminated

Absence vs. partial complex seizure Brain involvement Age of patient Duration Symptoms recalled by patient Movements or behaviors After-effects EEG pattern Underlying cause Effective treatment

Brain involvement: generalized vs. focal Age of patient: childhood/early adult vs. any age Duration: less than 30 sec vs 2-3 min Symptoms recalled by patient none/missing time vs. complex (i.e. odors, deja vu, emotions) Movements or behaviors: no more than flutter of eyelids or brief shiver vs. complex automatisms (chewing, picking, peering) After-effects: none vs. confusion and tiredness EEG patterns: generalized, 3 Hz spike and slow wave discharges vs. temporal or peri-temporal focal spikes Underlying cause: often familial vs. not familial, something wrong with focal brain tissue Effective treatment: ethosuximide vs. not ethosuximide

BDNF

Brain-derived neurotropic factor: CREB controlled gene, expression is increased with chronic antidepressant use (all antidepressants) BDNF binding to TrkB activates several signaling pathways which control cell survival, neuronal growth and synpatic plasticity BDNF levels in hippocampus are decreased in depression When BDNF is increased in hippocampus, anti-depressant like behavior affects are achieved as well as elevated Ras-MAPK and PI3K-Akt pathways

What ion is responsible for synaptic transmission?

Calcium

Dantrolene

Calcium release blocker used to reverse malignant hyperthermia

Risk factors that heighten suspicious of brain injury (CP)

Breech deliveries (lower extremities or buttocks first) Vascular or respiratory problems in the infant during birth. Physical birth defects such as faulty spinal bone formation, groin hernias, or an abnormally small jaw bone. A low Apgar score 10-20 minutes after delivery. A low birth weight and premature delivery. Being a twin or part of a multiple birth. A congenital nervous system malformation, such as an abnormally small head (microcephaly). Seizures shortly after birth.

Myoclonic seizure

Brief contractions of a muscle or muscle group EEG: 2-8 Hz generalized spike, spike and wave, or polyspike and wave discharges with frontal predominance

Which of the following contributes to the rapidity of induction of general anesthesia by various inhaled gaseous agents? A. greater solubility in plasma (blood:gas partition coefficient) B. greater cardiac output C. greater ventilation rate D. lesser minimum alveolar concentration (MAC) E. increasing molecular weight

C. greater ventilation rate Greater solubility slows induction because more anesthetic needs to dissolve in order to bring the partial pressure up to levels required for anesthesia. Greater cardiac output also slows induction because the blood is less likely to have time to equilibrate with alveolar anesthetic gas as it goes through the lung. Equilibration may require more passes of blood through the lung. Greater ventilation increases the alveolar concentration of inhaled anesthetic to cause more rapid uptake. MAC is related to potency, but not to rate of induction. Molecular weight is not related to rate of induction.

Dermatomes C5 C6 C7 C8 T1 T4 T6 T10 T12 L2 L3 L4 L5 S1 S2 S3-5

C5: anterolateral shoulder C6: thumb C7: middle finger C8: little finger T1: medial arm T4: nipple line T6: xiphoid process T10: navel T12: pubis L2: medial thigh L3: medial knee L4: medial ankle, great toe L5: dorsum of foot S1: lateral foot S2: posteromedial thigh S3-5: perianal area

Even when spanned over several segments, muscles often behave clinically as if they are associated with one segment C5 C6 C7 C8/T1 L3 L5 S1

C5: deltoid (abduction of shoulder) C6: biceps brachii (flexion of elbow) C7: triceps brachii (extension of elbow) C8/T1: intrinsic hand muscles (body of muscle is distal to wrist) L3: adductors, quadriceps L5: tibialis anterior (dorsiflexion and eversion of ankle) S1: gastrocnemius/soleus (plantar flexion and inversion of ankle)

Bell's Palsy vs. Ramsay Hunt Syndrome (Herpes Zoster Oticus) Cause Anatomic target Ear pain Rash Other neural deficits Diagnosis Course Complete recovery Treatment

CAUSE BP: probably viral RHS: herpes zoster reactivation (shingles) ANATOMIC TARGET BP: peripheral facial nerve RHS: geniculate ganglion of facial nerve EAR PAIN BP: common RHS: common (typically deep and severe) RASH BP: none RHS: redness and vesicles of ear, lip, palate or tongue OTHER NEURAL DEFICITS BP: other branches of facial nerve (e.g. taste) RHS: CNs VIII > IX > V > VI (decreasing likelihood) DIAGNOSIS BP: clinical RHS: clinical but may include other (Tzanck smear of vesicle for multi-nucleated giant cells) COURSE BP: maximal weakness in 1st week, improves slowly RHS: maximal weakness in 1st week, improves slowly COMPLETE RECOVERY BP: in up to 80-90% of cases RHS: in less than 50% of cases TREATMENT BP: corticosteroids, protect cornea from dryness and abrasions RHS: corticosteroids, acyclovir, protect cornea from dryness and abrasions

Ancillary testing for suspected seizures

CBC (keep in mind that there is a transient increase in WBC immediately after major motor seizure that does not indicate infection) Chemistries: glucose, sodium, calcium, renal and hepatic function tests Brain imaging to look for macroscopic focal disease such as tumor, stroke, AVM or developmental anomaly *IDEAL: MRI INCLUDING CORONAL SECTIONS THROUGH MEDIAL TEMPORAL LOBES EEG, preferably sleep-deprived to increase sensitivity

The pupillary light reflex (i.e., a predictable pupillary constriction in response to increased ambient light) is best characterized by which of the following statements concerning reflex arcs?

CN II to CN III reflex arc in the rostral midbrain

Asymmetry b/w pupil sizes

CN III lesion

What protein marker is contained within amyloid and thus may be predictive for AD?

CSF A-beta42

What biomarkers/imaging tests may be useful in Alzheimer's detection and staging?

CSF A-beta42 Amyloid imaging CSF tau FDG-PET MRI-hippocampus Cognitive function based on report and mental status exam Function in real world (driving, losing things, etc.)

List 4 principle neuronal 2nd messenger systems

Ca2+ cAMP cGMP DAG and IP3

Types of seizures that AEDs exacerbate Carbamazepine Oxcarbazepine Phenytoin Phenobarbital Tiagabine Vigabatrin Gabapentin Lamotrigine

Carbamazepine: absence, atonic, myoclonic Oxcarbazepine: absence, atonic, myoclonic Phenytoin: absence, atonic, myoclonic Phenobarbital: absence, atonic Tiagabine: absence, myoclonic Vigabatrin: absence, myoclonic Gabapentin: myoclonic Lamotrigine: myoclonic

Entacapone

Catechol-O-methyl-transferase (COMT) inhibitor: increases bioavailability of levodopa by inhibiting COMT enzyme peripherally, thus slowing down breakdown of levodopa Used as adjunctive therapy to levodopa to reduce some of adverse effects related to long-term levodopa treatment (results in smoother levodopa plasma levels, decrease in motor functions in patients)

Diffusion hypoxia

Caused by discontinuation of nitrous oxide: massive amounts of NO exit the bloodstream and displace O2 in alveoli (second gas effect)

Lacunar infarcts

Caused by occlusion of smaller, penetrating arteries (i.e. striates) Secondary to hypertension, vessel lumen almost completely obstructed by thickened media and enlarged to about 3x normal size; pink staining fibrinoid materials within walls

A mass or cyst of the central canal that expands outward will first affect __________

Central commissure = crossing over of pain and temp

Ataxia indicates a __________ lesion

Cerebellar

The _________ is the major long-term repository for many aspects of declarative memory

Cerebral cortex

Chorea vs. athetosis vs. ballism

Chorea: involuntary, continuous, abrupt, rapid, brief, un-sustained and irregular movement that flow randomly from body parts Athetosis: slow form of chorea consisting of writhing movements Ballism: forceful, flinging, high-amplitude coarse form of chorea

What is the hypothesis of signaling adaptation?

Chronic antidepressants induce adaptive changes in post-receptor signaling cascades and in gene expression (i.e. activation of G-proteins alters neuronal gene transcription) Phosphorylation of CREB (cAMP response element binding protein): many different phosphorylation sites, determines which genes are transcribed Increased amount of 5HT or NE --> increased expression of genes BDNF (brain-derived neurotropic factor): CREB controlled gene, expression is increased with chronic antidepressant use BDNF binds to TrkB and activates several different signaling pathways controlling cell survival, neuronal growth, synaptic plasticity

Neuroplasticity and SSRIs (in rats) Clinical significance?

Chronic fluoxetine reactivates a critical period-like plasticity in adult rat Combine fluoxetine treatment with stimulus: can restore vision Explains why antidepressants on their own are not enough to experience recovery: usually combine with cognitive processes, therapy to induce change in synaptic plasticity, reestablishing connections within hippocampus and prefrontal cortex

How does stress affect neuroplasticity?

Chronic stress leads to atrophy of neuronal processes and decreased number of synapses, dendritic spines in hippocampus and prefrontal cortex

Genetics and immunology of multiple sclerosis

Chronic, immune-mediated disease precipitated by unknown environmental factors in genetically susceptible individuals Occurs more frequently in individuals with HLA-DR2 Humoral immune effects: B cells make anti-oligodendrocytic glycoprotein antibody and anti-myelin basic protein antibody Cellular immune effects: Th1 lymphocytes are primary mediator of demyelination

MS

Chronic, immune-mediated disease precipitated by unknown environmental factors in genetically susceptible individuals Pathological hallmark is inflammatory demyelinating plaques in CNS, especially in white matter (but also affecting gray matter)

Limbic system pathway

Cignulate gyrus --> cingulum --> parahippocampal gyrus --> hippocampus --> amygdala --> hippocampus --> fimbrae continue to become crus of fornix, then fornix body and then fornix --> mammillary bodies --> nuclei of thalamus --> through corona radiata to cingulate gyrus

The limbic system connects with anterior or pre-frontal association cortex via the _______

Cingulate gyrus

Cerebral palsy classifications

Classified according to main type of motor disorder involved Spastic CP: most common type of CP (80%), muscle tone is increased as result of damage to corticospinal pathways (pyramidal tract findings = clumsiness, hyperreflexia, upgoing toes on Babinski); slight hip flexion and adduction, knee flexion and plantar-flexion throughout gait = inefficient gait with high energy expenditure (tend to hit with toe instead of heel), narrow base of support Dyskinetic CP: includes athetoid (sustained twisting movement), choreo-athetoid (brief flicking movements) and dystonic so movements can be slow and writhing or rapid and jerky; when it involves upper and lower extremities, it can interfere with sitting and walking; when it involves face and tongue, can interfere with sucking, swallowing and talking; damage to basal ganglia is implicated = EXTRA-PYRAMIDAL SYMPTOMS Ataxic CP: problems with balance and coordination (DAMAGE TO CEREBELLUM IS IMPLICATED); unsteady when they walk, widen stance to compensate; have a hard time with quick movements or those that require a lot of control, such as writing; may have difficulty controlling their hands or arms when they reach for something (equivalent of intention tremor) Mixed CP (most common is spastic-dyskinetic)

Huntington's Disease (clinical presentation, genetics, treatment)

Clinical presentation of chorea preceded or accompanied by mental symptoms; causes atrophy of caudate nucleus (lateral ventricles appear expanded) Autosomal dominant with high penetrance, abnormal gene on chromosome 4 No cure available, genetic counseling can be useful Dopamine blockers partially suppress chorea (i.e. haloperidol post-synaptically or tetrabenazine pre-synaptically)

Creutzfeldt-Jakob Disease: clinical presentation, etiology, diagnosis, treatment

Clinical presentation: rapidly progressive, fatal dementia involving prominent motor symptoms such as rigidity, clumsiness and myoclonic jerks; akinetic mutism Etiology: transmissible "spongiform" encephalopathy involving abnormal proteins called prions 3 categories: sporadic (85%) with no known risk factors, hereditary (5-10%), acquired (1%) involving transmission by exposure to brain or nervous system tissue (as in transplant) Diagnosed with certainty only by brain biopsy; MRI (increased basal ganglia signals on T2-weighted images and increased cortical, ribbon-like signals on diffusion-weighted images), EEG (periodic tri-phasic/triangular waves) and CSF testing (positive 14-3-3; can have false positive from herpes simplex encephalitis) can be helpful; can do prion stain No cure

Wernicke's Encephalopathy

Clinical triad of confusion, extra-ocular dysmotility and gait disorder Associated with SUBACUTE thiamine deficiency (poor diet or impaired absorption) Pathology shows infarcts or hemorrhages in mammillary bodies of hypothalamus and other midline structures Treatable with IV or IM thiamine (not by mouth) Chronic form is Korsakoff's: confabulation (need to fill in information, details whether true or not)

Normal pressure hydrocephalus

Clinical triad: magnetic gait disturbance, urinary incontinence, cognitive disturbance Imaging: ALL FOUR VENTRICLES ENLARGED Impaired reabsorption of CSF at arachnoid granulations; can be predisposed by meningitis or subarachnoid hemorrhage

Dementia with Lewy Bodies

Clinically resembles a blend b/w Alzheimer's and Parkinson's diseases Usual fluctuations in cognitive functioning Visual hallucinations common Pathologically, intracellular Lewy bodies appear diffusely in cerebral cortex (not confined to cerebral cortex)

Respiration without intercostal involvement

Clue to cord damage at high thoracic level

Cardiovascular complications of cocaine vs. other local anesthetics

Cocaine: Blocks uptake of catecholamine (epinephrine or norepinephrine) increasing their concentrations Increases heart rate and blood pressure Other local anesthetics: Decrease myocardial excitability, conduction rate and force of contraction Decrease HR Decrease BP

What are some non-motor features of Parkinson's disease?

Cognitive function: confusion, decreased attention Emotional function: depression, anxiety Sleep: insomnia, restless legs, dreaming Autonomic function: bladder disturbance, sweating, orthostatic hypotension, sexual function GI function: dysphagia, constipation, incontinence Sensory function: pain, paresthesias Other fatigue, blurred vision, weight changes

Meningioma tissue of origin and classification in spinal cord neoplasms

Comes from arachnoid matter Extramedullary (inside dura but outside the cord)

Crossed extensor reflex

Complex reflex that consists of an ipsilateral withdrawal reflex and a contralateral extensor reflex, which allows the body to compensate on one side for a stimulus on the other This keeps you from falling over, for example if you step on something painful. When you pull your foot back, the other leg responds to hold you up Activates alpha motor neuron that innervates flexor muscles (hamstrings) muscle contraction --> withdrawal At same time, sensory input also activates interneuron, crosses midline and activates alpha motor neuron projecting to extensor muscles --> causes that leg to stand and prepare to bear weight = helps us maintain proper posture when we encounter harmful stimulus

Which of the following is not part of the Patient Protection and Affordable Care Act's reform of Medicare? A. Expansion of preventative care services B. Closing of the Medicare Part D "donut hole" by 2020 C.New incentives for care coordination between primary care physicians, long-term care professionals, and specialists such as neurologists D. The ability to buy drugs from countries such as Canada, where drug prices are more highly regulated than in the United States

D

Cause of unilateral intention tremor

Damage to ipsilateral cerebellum

G protein alpha-o

Decrease in Ca2+

Genetic defect in Limb-Girdle Muscular Dystrophy

Defects in multiple genes can produce the same clinical picture; diseases are divided into autosomal dominant and recessive forms, which will probably be consistent within 1 family

Effect of a spinal cord segment lesion at T2 or T3 Deficit Independence Aids required

Deficit: impaired respiration, reflex bladder, paraplegia Independence: complete Aids: Wheelchair, leg braces

Effect of a spinal cord segment lesion at C8 or T1 Deficit Independence Aids required

Deficit: impaired respiration, reflex bladder, paraplegia, hand weakness Independence: personal care, drives car Aids required: wheelchair, special braces

Effect of a spinal cord segment lesion at S2 or S3 Deficit Independence Aids required

Deficit: nonreflex bladder Independence: complete Aids: catheter

Effect of a spinal cord segment lesion at L4 or L5 Deficit Independence Aids required

Deficit: paraplegia, reflex bladder Independence: complete Aids required: foot braces

Effect of a spinal cord segment lesion at T12, L1 Deficit Independence Aids required

Deficit: paraplegia, reflex bladder Independence: complete Aids required: leg braces, foot braces

Effect of a spinal cord segment lesion at C6 or C7 Deficit Independence Aids required

Deficit: quadriplegia Independence: minimal Aids required: wheelchair, hand splints

Effect of a spinal cord segment lesion at C4 or C5 Deficit Independence Aids required

Deficit: quadriplegia, impaired respiration, reflex bladder Independence: none Aids required: wheelchair, constant care

Syringomyelia

Degenerative, cystic lesion Primary cause of anterior commissural syndrome (band loss of pain and temperature) Always close to central canal Most typically occurs in cervical spinal cord

Which dementia conditions get worse with antipsychotics?

Dementia with Lewy Bodies and Parkinson's Dementia (d/t dopamine blockade)

What affect does MS have on axons?

Demyelination = saltatory conduction is disrupted

Diseases in which the amygdala is implicated

Depression and stress Emotional dysregulation Autism (volume may be reduced) Alzheimer's Disease Epilepsy Schizophrenia

What is the monoaminergic hypothesis and why is it not the whole story?

Depression is caused by a decreased availability of monoaminergic neurotransmitters Antidepressants increase amount of serotonin within synapse within hours but takes minimum of 2-8 weeks for SSRIs to be clinically effective Can also deplete a healthy person of tryptophan (precursor of 5-HT) and depression-like symptoms are not induced Lead to monoaminergic receptor hypothesis

Blood:gas partition coefficient

Describes an anesthetic's relative affinity for blood compared to are More soluble compounds (higher blood:gas ratios) have slow induction *The higher the solubility, the slower the onset Desflurane: 0.45 NO: 0.47 Halothane: 2.5

Causes of polyneuropathy

Diabetes mellitus (most common cause) Alcohol Genetic (Charcot-Marie-Tooth) Lead poisoning (pure motor) Arsenic poisoning (pure sensory) Guillain Barre syndrome (rapidly progressive) Cisplastin, vincristine, isoniazid

Restless Leg Syndrome (Willis-Ekbom Disease): Diagnosis Pathophysiology Treatment

Diagnosis: 1. Urge to move leg, unpleasant or discomfort sensation relieved with movement, worsening in night 2. Symptoms not accounted for by another medical or behavioral condition 3. Sleep disturbance, function concerns or impairment Pathophysiology: Central nervous system dopamine regulation Brain iron deficiency Genetic association: BTBD9, MEIS1, MAP2K5/LBXCOR, PTPRD Treatment: Dopaminergic agents (Ropinirole, Pramipexol = 1st line treatment, FDA approved) Anti-epileptic medications (Gabapentin, Lyrica = 2nd line) Opioids (methadone = most effective but reserved for worst cases) Behavioral treatments: leg exercise, heating pads, sleep hygiene

Rest tremor

Distal, rotational tremor maximal when hands are in repose, 4-6 Hz = highly correlated with Parkinsonism as well as Parkinson's disease Often oscillates about pronator-supinator axis instead of flexor-extensor; fingers can give appearance of pill-rolling Decreases (but doesn't necessarily disappear) when hands are help up or are put to use = the most visible but least disabling feature of Parkinsonism

In Parkinson's there is a macroscopic loss of ____________

Dopamine (i.e. dark staining) in substantia nigra, pars compacta

Drugs for Parkinson's Disease

Dopamine agonists and promoters Acetylcholine antagonists Amantadine

What is contained within the lumbar cistern?

Dorsal rootlets of spinal nerves (enlargement of subarachnoid space)

During sleep what goes... Down Up

Down: Sympathetic activity Respiratory system (PaO2 and SatO2, tidal volume and minute ventilation, activity of accessory muscles of respiration) Cardiovascular system (HR, CO, BP) Gastrointestinal system (swallowing rate and salivary production, esophageal and intestinal motility) Renal system (glomerular filtration) Endocrine system (cortisol levels decrease during N3 sleep, insulin secretion) Cord body temp Muscle tone (completely lost during REM) Up: Parasympathetic activity Respiratory system (PaCO2) Renal system (renal water reabsorption) Endocrine system (growth hormone, prolactin, parathyroid, renin, ADH, testosterone)

Plantar reflex

Draw a blunt object downward along lateral aspect of plantar surface (sole of foot) from heel to toe Normal: downward flexion (curling) of toes Abnormal (Babinski's): great toe dorsiflexes (points up) and the smaller toes fan laterally Tests spinal cord from L4 to S2 Indirectly determines if corticospinal tracts of brain are working (normal in infants up to one year old because their nervous system is not completely myelinated)

Atonic seizure

Drop attacks, head drop EEG: polyspike and wave or sudden suppression

Genetic defect in Duchenne Muscular Dystrophy

Dystrophin gene on short arm of X chromosome (encodes for dystrophin = cytoskeletal structural protein)

Enzyme inducer vs. enzyme inhibitor AEDs vs. AEDs that have no effect on metabolism of other AEDs

Enzyme inducers (accelerate metabolism of other AEDs): phenytoin, phenobarbital, primidone, carbamazepine, topiramate, oxcarbazepine Enzyme inhibitors (decelerate metabolism of other AEDs): valproic acid, felbamate No effect: ethosuximide, gabapentin, lamotrigine, tiagabine, levetiracetam, zonisamide, benzodiazepines

Which of the following is true of a muscle spindle reflex? A. It is disynaptic to the homonymous muscle (the muscle from which the reflex was triggered) and its agonists. B. It is monosynaptic to antagonists. C. It is designed to signal a change in muscle tension. D. It is made less sensitive by excitation of gamma efferents. E. It is triggered by muscle stretch.

E. It is triggered by muscle stretch. A. There is a monosynaptic excitatory connection with the homonymous muscle and its synergists. B. There is an inhibitory disynaptic connection with antagonists. C. It signals a change in muscle length. D. Excitation of gamma efferents keeps the spindle taut and so maximally sensitive to muscle stretch. E. Correct; it is triggered by the change in muscle length that accompanies a muscle stretch.

Long-term changes in levodopa response

Early PD: 6-8 hours Moderate PD: 3-5 hours Advanced PD: 0.5-2 hours Early in PD, patients will notice big difference on meds As disease becomes more advanced, it's quicker in and quicker out Have to take more to get into target zone, overshoot where you get adverse symptoms (called dyskinesias = wiggly things that look like chorea) and then drops done like a rock With advanced PD, even shorter duration of effective action, more tendency to stay down in zone where it doesn't do you any good or in zone where it does you bad

MS early vs. late plaques

Early plaques: demyelination and inflammation Late plaques: gliosis and variable re-myelination

What are carryover effects and how can you eliminate them?

Effects of the treatment administered during the first period persist into the second period Sufficient washout period b/w treatments can eliminate carryover effects (allow sufficient time for symptoms to return to baseline levels before second treatment)

Vigabatrin

Elevates GABA levels by irreversibly inhibiting its main catabolic enzyme, GABA-transaminase

Superficial reflexes

Elicited by gentle cutaneous stimulation Important because they involve upper motor neuron pathways (brain) in addition to spinal cord neurons

Embolus vs. thrombosis

Embolus: clot fragment (composed of cellular material, white cells, cholesterol crystals, etc.) carried from heart or more proximal artery, causes wedge-shaped infarct Thrombosis: occlusion occurs directly where pathology is (i.e. atherosclerosis), larger area of infarct

Causes of stroke in young people

Endocarditis (subacute bacterial endocarditis, SLE endocarditis) Hypercoagulable states (hormone-induced, pregnancy-associated) Vascular spasm: complicated migraine Vascular malformation: AVM, aneurysm Hemoglobinopathy: sickle cell disease

Aneurysm management

Endovascular coiling and surgical clipping

What structure carries all memory information out of the hippocampus?

Fimbrae --> fornix Projects to mammillary bodies, anterior nucleus of the thalamus, subcallosal cortex and to association area of neocortex

Epidural hematoma

Epidural hematomas are accumulations of blood between the skull and the dura, and typically occur after significant blunt head trauma. Fractures of the temporal bone can disrupt the middle meningeal artery, leading to high-pressure bleeding within the cranial vault. Acute bleeding is bright white on CT. The shape of the blood collection is characteristically biconvex or lens shaped in an epidural hematoma

___________ is usually included in local anesthetic solutions to prolong action

Epinephrine

Postural tremor compared to rest tremor

Essential tremor which is more symmetric and rapid (6-12 Hz) than a rest tremor as seen in Parkinsonism (4-6 Hz); typically oscillates in flexor-extensor axis and is maximal on posture-holding or when hands are put to use, decreasing when hands are at rest (opposite for rest tremor)

Essential tremor vs. Parkinson's disease tremor

Essential tremor: Action tremor More rapid frequency Not associated with slow movements, muscle rigidity and postural changes Bilateral Often familial Parkinson's tremor: Resting tremor Slower frequency Associated with slowing, shuffling, rigidity, stooped posture, imbalance Usually worse on one side Rarely familial

Esters vs. Amides

Esters: cleared in blood Ester hydrolysis via psedocholinesterase (can have deficiency) Shorter duration of action Cocaine is exception (metabolized in liver) One "i" in generic name Amides: metabolized by liver Aromatic hydroxylation and amide hydrolysis (can be affected by liver diseases) Two "i"s in generic name

Malignant Hyperthermia (MH)

Excessive heat and CO2 production caused by combination of inhaled gas anesthetics and muscle relaxers (causes altered calcium regulation) *Reverse with DANTROLENE (calcium release blocker)

What is the hypothesis of neuroplasticity?

Experience in dependent activity in neuronal network strengthens and maintains or eliminates connections (heightened during critical periods of development) Chronic antidepressant use changes neuroplasticity, cellular resilience and synaptic plasticity

Explicit (declarative) vs. implicit (non-declarative) memory

Explicit (declarative): memory for everyday facts and events involving conscious recollection -- i.e. can be concisely expressed in declarative statements *Medial temporal lobe (hippocampus) *Factual, autobiographical information Implicit (non-declarative): memory for motor skills or procedures recalled without conscious awareness *Tied to sensory and motor systems *Repetition memory, recall is automatic *Can be studied in simple organisms

Brain imaging in suspected stroke

FIRST TEST = CT: bad for seeing infarct but you need to r/o hemorrhage Then: Carotid duplex imaging Magnetic resonance angiography (MRA) Computed tomographic angiography (CTA) Angiography (catheter-based) Non-invasive or minimally invasive imaging: CTA or MRA (good for detecting pathology in large vessels) but not as good as detecting pathology in small vessels (use catheter-based angiography for this)

Muscle fatigue during a sustained maximum voluntary contraction in myasthenia gravis results primarily from:

Failure of transmitter released at the neuromuscular junction to elicit suprathreshold excitatory post-synaptic potentials

T/F: In the acute aftermath of a stroke, you should be aggressive about bringing down BP

False: In people who have had chronic HTN, they still have zone of autoregulation but shifted to the R In ischemic zone, autoregulation disappears and you have straight, linear relationship = how much blood is flowing through a tissue bed is intimately connected to changes in blood pressure (MAP) As blood pressure decreases = decreased perfusion (via medications, orthostatic hypotension) Do not want people up in walking in first 48 hours of stroke = orthostasis = can cause blood pressure drop that decreases cerebral perfusion, can extend stroke

T/F: For prevention of non-cardiac embolic strokes, anti-coagulants (i.e. warfarin) are superior

False: For prevention of non-cardiac-embolic strokes "anti-platelet" drugs are superior (examples: plavix/clopidogrel, ASA)

T/F: After stroke, you should not consider putting your patient on statins if they do not have high cholesterol

False: if you've had a previous stroke and you take a statin even if you don't have high cholesterol, you are less likely to have another stroke

Which spinal cord structure would be most susceptible to ischemia if there were a blockage in the posterior spinal artery?

Fasciculi cuneata and gracilis (the portion of the arterial vasocorona (AVC) that delivers blood to the fasciculus cuneatus, as well as the fasciculus gracilis, is supplied almost entirely by the posterior spinal artery)

Common symptoms/treatments in MS

Fatigue: Amantadine, modafinil, CBT, aerobic exercise Pain: anti-epileptic drugs, tricyclic antidepressants, cannabinoids Spasticity: baclofen, diazepam, stretches, PT, botulinum toxin Depression: SSRIs, CBT, exercise Bladder dysfunction: anticholinergics, pelvic floor muscle training, self-catheterization Sexual dysfunction: eliminate drug effects, use lubricants, slidenafil Gait impairment: 4-aminopyridine, visuo-spatial feedback, Tai Chi

Cranial Dystonia/Meige Syndrome

Form of focal dystonia characterized by blepharospasm (sustained, bilateral eye blinking) + lower facial/neck movement (prolonged and sustained) Contraction of face and neck muscles occurs independently of eye blinking Distract with other neurological tests: sustained blinking continues

If mass is impinging spinal cord from outside-in, what area of the body would lose function first? What if mass was impinging spinal cord from inside-out?

From outside-in: sacrum From inside-out:cervical

What make up the basal ganglia?

Functionally defined: putamen, caudate, globus pallidus, subthalamic nuclei and substantia nigra

Amygdala functions, inputs and outputs

Functions: emotion (emotional learning/memory, fear and reward, feeding) and facial expression/recognition (via connections to facial and trigeminal nerves) Receives signals from olfactory system and neocortices; anterior commissure connects the two amygdala Projects to: Hypothalamus via stria terminales (can affect HR, RR, BP) Cingulate gyrus (limbic system, also some CV function) Mammillary bodies (emotional flavor) Nuclei in brainstem (facial, trigeminal = responsible for facial expression/recognition) Ventral striatum of basal ganglia Hippocampus

Main NREM neurotransmitter, main CNS inhibitory neurotransmitter

GABA

Location of sleep-promoting NTs GABA Adenosine Glycine Acetylcholine

GABA (gamma-aminobutyric acid): ventrolateral preoptic nucleus (VLPA), hypothalamus and basal forebrain Adenosine: basal forebrain Glycine: spinal cord Acetylcholine: PPT/LDT (pons) and basal forebrain

Tiagabine

GABA-reuptake inhibitor *Interferes with GABA re-uptake by blocking GABA transporter 1 (GAT-1)

CSF protein electrophoresis in MS

Gamma globulin (antibodies, immunoglobulin) stripes = oligoclonal bands (d/t small number of over-producing B cells making antibodies)

______________ regulate the sensitivity of the a stretch reflex or sensitivity of a muscle spindle

Gamma motor neurons

Location of each wakefulness neurotransmitter Glutamate Dopamine Hypocretin Norepinephrine Serotonin Histamine Acetylcholine

Glutamate: ascending reticular formation Dopamine: substantia nigra Hypocretin: hypothalamus (perifornical) Norepinephrine: (locus ceruleus) Serotonin: Raphe nucleus Histamine: tuberomammillary nucleus Acetylcholine: basal forebrain

The transmitter released from long, projection neurons, and whose effects within the central nervous system are mostly, if not exclusively, excitatory is:

Glutamic acid

Responsible for REM muscle atonia/hypotonia, main spinal cord inhibitory neurotransmitter

Glycine

Use of DMDs in MS

Goal: slow down disease, whether in frequency of attacks, accumulation of disabling symptoms or (as a secondary measure) in decreasing the accumulation of new MRI lesions For initial RR-MS: interferon drug, glatiramer acetate, dimethyl fumarate, fingolimod, teriflunomide, ocrelizumab For refractory agressive RR-MS: natalizumab, alemtuzunab For PP-MS: mitoxantrone, ocrelizumab *MS category helps you pick you DMD

Duchenne's clinical presentation

Gower's sign, indicating weakness of pelvic girdle (proximal lower extremity) muscles

Babinski sign

Great toe dorsiflexes (points up) and the smaller toes fan laterally Indicates damage to primary motor cortex or corticospinal tract (normal in infants up to one year old because their nervous system is not completely myelinated)

The ________ is responsible for explicit/declarative memories

HIppocampus (medial temporal lobe)

Intraparenchymal hemorrhage causes

HTN AVMs

Damage to the trigeminal nerve before it enters the brainstem will result if loss of perception of somatosensory information from what areas?

Head/face/meninges on the same side of the midline as the damaged nerve. Interrupting the trigeminal nerve before it enters the brainstem will always result in loss in perception of sensory modalities on the same side of the body as the nerve damage, as the incoming (afferent) information has not crossed the midline yet

Vitamin B12 deficiency

Hematologic disease from vitamin B12 deficiency = pernicious anemia (form of megaloblastic anemia) Neurological consequences as well = subacute combined degeneration Dorsal roots, posterior columns, dorsal spinocerebellar tracts and lateral corticospinal tracts damaged = combination of upper motor neuron weakness (due to damage to corticospinal tracts) and trouble detecting vibration and position sense (due to damage to posterior columns) Need to treat ASAP to reverse

Hemi vs. para/di vs. quad/tetra

Hemi: one half of the body as defined by sagittal section (for example, R UE and R LE) Para/di: one half of body defined by transverse/horizontal section (for example, R and L LEs) Quad/tetra: both UEs and LEs affected

Lesion to subthalmic nuclus (i.e. stroke)

Hemiballismus

Halothane metabolism

Hepatic -- i.e. can cause liver toxicity

What brain structure is often visualized to be atrophied on coronal MRI in AD?

Hippocampus

Major components and functions of limbic system

Hippocampus (memory, learning) Amygdala (emotions, fear and reward) Cortical areas (cingulate and parahippocampal gyri) Additional structures functioning in emotion and memory: Mammillary bodies Anterior nucleus of thalamus Olfactory bulb and olfactory cortex Hypothalamus Ventral striatum Nucleus accumbens

Metabolic etiologies of dementia

Hypo- (episodic) or hyper-glycemia Hypo or hypernatremia Hypercalcemia (hypocalcemia does not cause cognitive impairment) Renal failure Hepatic failure Hypothyroidism Hypoxemia Hypercarbia

Hypokinesia vs. hyperkinesia (examples)

Hypokinesia: Parkinsonism Drop attacks (cataplexy) Catatonia Rigidity, stiff muscles Hypothyroid slowness Hyperkinesia: Chorea Ballisms Dystonias Myoclonus Tremor Tics, RLS

WHO criteria for diagnosis of sporadic CJD

I. Rapidly progressive dementia II. A. Myoclonus B. Visual or cerebellar signs C. Pyramidal or extrapryramidal features D. Akinetic mutism (don't move or talk much) III. A. EEG showing period tri-phasic wave complexes B. Positive 14-3-3 analysis of CSF

Parkinson's tremor unilateral or bilateral initially?

In Parkinson's disease (one subtype of Parkinsonism), tremor usually starts on one side Even if it eventually involves both sides, it will typically be worse on one side > the other

Motor and cognitive symptoms in Alzheimer's, Parkinson's and Lewy Body Dementia

In Parkinson's, motor is way early, can eventually lead to cognitive impairment In Alzheimer's, cognitive precedes motor In LBD, both occur at the same time and progress in equal measure (hand-in-hand)

In depression, _____________ levels are decreased in the ____________

In depression, BDNF levels are decreased in the hippocampus (leading to reduced activity of TrkB, Ras-MAPK and PI3K-Akt pathway) causing decrease cell survival, neuronal growth and synaptic plasticity

In most myopathies, which muscles are weaker -- proximal or distal? What is the exception?

In most myopathies, proximal muscles are weaker than distal (exception is myotonic dystrophy)

Which mechanism is most important for the repolarization phase of the nerve action potential?

Inactivation of voltage-gated sodium channels

Which of the following is the most prominent result of a partial blockade of voltage-gated K+ channels on the action potential?

Increase in duration

Antidepressant goals, types and MOAs

Increase noradrenergic or serotonergic transmission SSRIs, SNRIs, TCAs: block reuptake of NE and/or 5-HT by pre-synaptic transporters MAOIs: reduce catabolism of neurotransmitter

CSF analysis in CJD

Increased levels of CSF protein 14-3-3 95% sensitive in sporadic form of CJD False positives exist: herpes simplex encephalitis Protein serves modulating function for protein kinases (i.e. not purely pathological)

Benzodiazepines (MOA and examples)

Increases frequency of GABA-mediated chloride channel openings to enhance potency of GABA Diazapam Clonazapam

Consequence of altering concentrations of neurotransmitters in brain with antidepressants

Increases signaling through GPCRs, alters gene transcription and ultimately promotes neuronal plasticity, survival and growth

Aging: what... Increases Decreases

Increases: Nocturnal sleep disturbance Excessive daytime sleepiness Napping Tolerance to sleep deprivation Prevalence of sleep disorders such as insomnia, OSA, CSA, RLS, PLMD, RBD and ASPS Decreases: N3 sleep Melatonin secretion Amplitude of circadian sleep-wake rhythms Homeostatic sleep drive Arousal threshold GH secretion during sleep

Axon regeneration in the CNS is less successful than in the PNS because of:

Inefficient phagocytosis by microglia

Climbing fibers synapsing on Purkinje cells in the cerebellum originate in the:

Inferior olive

Carbidopa

Inhibitor fo dopa-decarboxylase Dopa-decarboxylase turns levodopa into dopamine (good for inside brain neuron but we want to keep levodopa in peripheral circulation as such so that it can be taken across BBB) If you block DDC, less levodopa will be wasted in circulation by being converted into nausea-causing dopamine

Descending influences are mainly (excitatory/inhibitory). Clinical significance?

Inhibitory - but they take a while to develop In infants the descending motor tracts are not fully developed, so the spinal withdrawal reflex (big toe extension) is present - the positive Babinski reflex In adults, stroking of the plantar surface results in plantar flexion, mediated by long loop reflexes via the descending motor tracts, which inhibit and override the spinal withdrawal reflex Loss of descending influence in adults from spinal cord injury can produce a positive Babinski

GABA-A receptor agonists

Inotropic Cl- channels CNS depressants Barbituates, benzodiazepines, profolol, volatile/inhaled anaesthetics, alcohol

Which GABA channels are inotropic vs. metabotropic?

Inotropic: GABA-A and GABA-C Metabotropic: GABA-B

Amygdala input and output

Input: parahippocampal gyrus, hippocampus, olfactory bulb/cortex Output: mammillary bodies (emotion and flavor), brainstem (ventral tegmental area = contains many dopaminergic neurons functioning in emotion, addition and impulsive behavior), and striatum of basal ganglia

Cingulate gyrus: inputs and projections, function, clinical implications

Inputs: from anterior nucleus of thalamus and neocortex, somatosensory areas Projects to: parahippocampal gyrus or enterohinal cortex via cingulum, insula Function: emotion formation and learning, memory; affective and emotional response to pain Clinical implications: Pain Bipolar disorders and depression Schizophrenia Alcohol dependence ADHD

Extramedullary

Inside dura but outside the cord

Two main systems for expanding thoracic cavity. Which is more powerful?

Intercostal system (thoracic spinal nerves) and diaphragmatic system (C3-C5) Intercostal system is more powerful and ordinarily moves more air

Internal vs. external validity

Internal validity: extent to which a study's results can be interpreted accurately (affected by loss to follow up/attrition, lack of randomization) *In other words, could there be an alternative cause(s) that explains my observations and results? External validity: extent to which a study's results can be generalized (affected by loss to follow-up, response rate, narrow inclusion criteria)

Lewy Body

Intracellular inclusion of aggregated alpha-synuclein, hallmark of PD

Examples of inotropic CNS receptors

Ionotropic = ligand-gated ion channels Acetylcholine: nicotinic Glutamte: AMPA (Na+, K+), NMDA (Na+, K+, Ca2+) and kainite (Na+, K+) GABA: GABA-A and GABA-C (Cl-) Glycine: Cl- Serotonin: 5-HT3 Metabotropic = G-protein coupled receptors, activation of 2nd messenger systems to effect voltage gated ion channels Acetylcholine: muscarinic Dopamine: D1 and D2 Glutamate: mGlu GABA: GABA-B Serotonin: 5-HT subfamilies 1, 2A, 4, 5A, 6, 7 Norephinephrine: alpha and beta-adrenergic Histamine Neuropeptides

Clonic seizure

Jerking EEG: fast activity (10 Hz)

Anticholinergic drugs used for PD (examples, MOA, side effects, contraindications)

MOA: probably help by working on interneurons in cuadate-putamen (striatum) Trihexyphenidyl Benztropine Diphenhydramine All have prominent side effects: dry mouth, sedation, mood changes, "mental slowness", blurred vision, increased intraocular pressure Contraindicated in patient with prostatic enlargement, narrow-angle glaucoma, obstructive GI

Stretch reflex

MONOSYNAPTIC REFLEX 1. Stretching of a muscle activates a muscle spindle receptor 2. An impulse is transmitted by afferent fibers to the spinal cord 3. Motor neurons in the spinal cord cause the stretched muscle to contract to resist stretching *Same input also activates inhibitory interneuron -- i.e. inhibits alpha motor neuron that projects to antagonist muscles Ipsilateral Monosynaptic Shortest latency (quickest) Increases alpha motor neuron activity Influenced by CNS via gamma motor neurons (inhibitory or facilitatory) Integration area in spinal cord = polysynaptic reflex arc to antagonist muscle causing it to relax (reciprocal innervation) Provides automatic regulation of skeletal muscle length

MS plaques are most distinct in which type of imaging?

MRI FLAIR

What autoantigen(s) is(are) the principal target of autoimmune responses in multiple sclerosis?

MS involves inflammatory demyelination in central nervous system white matter. The major specific antigens are believed to be myelin basic protein and myelin oligodendrocyte glycoprotein (myelin structural proteins)

What part of the limbic system is implicated in thiamine deficiency d/t alcohol intoxication?

Mammillary bodies (atrophy)

Gabapentin

May facilitate GABA biosynthesis and interfere with re-uptake

Motor neurons supplying muscles of the trunk are located in the:

Medial part of the ventral horn

Which tumor tends to occur in children, is solid, midline, rapidly growing and has a poor prognosis if not treated with radiation therapy?

Medulloblastoma

Neural crest cells that migrate dorsally between the ectoderm and the somites will become:

Melanocytes of the epidermis The only type of trunk neural crest cells that migrate dorsally are those that become melanocytes. The dorsal root ganglion neurons arise from neural crest cells that either migrate through the somite or remain in place next to the neural tube. The other choices (chromaffin cells, parasympathetic neurons, Schwann cells) all migrate ventrally between the somites and the neural tube

What causes CP?

Most cases come from pre-natal (i.e. in utero) injury to brain (70-80%); 85-95% of cases involve injury up to and including birth (the rest are within 1 year) Hypoxic injury at birth can cause but not cause of majority of cases Common denominator: injury to developing brain (not necessarily traumatic) Causes: infections (rubella, cytomegalovirus), genetic abnormalities, physical trauma (mom in car accident), jaundice, periventricular leukomalacia (germinal plate in cerebrum from which tissue grows, more likely to bleed in pre-mature delivery), asphyxia, bleeding and placental defects; IN MANY CASES YOU DO NOT FIND A SPECIFIC CAUSE

Clinical features of chorea

Movements can be partially or temporarily suppressed Motor impersistence: inability to maintain voluntary contraction (milkmade grip, tongue protrusion) May be manifestation of neurodegenerative disorder (Huntington's) or as a complication of systemic, toxic disorder

Fatiguing weakness

Myasthenia gravis

Neuromuscular conditions or movement disorders that cause hand on chin

Myasthenia gravis Torticollis

Myelopathy

Myelo = spinal cord Pathy = disease

A newborn baby has a sac-like structure covered by skin over the lumbar spine that contains fluid, meninges and portions of spinal cord and lumbar nerve roots. The diagnosis is:

Myelomeningocele

CPK will be markedly increased in _____________

Myopathies

Where are you likely to find MS plaques in the brain?

Near the lateral ventricles

2 microscopic hallmarks of Alzheimer Disease brain on silver stain

Neurofibrilary tangles: intracellular, neurofibrillary tangles have taken up too much silver (tau protein clumps and disintegrating microtubules) Senile/amyloid plaques: extracellular trash piles (made of amyloid)

Tardive dyskinesia vs. akathesia

Neuroleptic medications: caffeine, valproic acid, stimulants, lithium, antidepressants, alcohol withdrawal, etc. Tardive dyskinesia: involuntary movements of tongue, lips, jaw/lower face (puckering) Akathesia: syndrome of restless appearing limb movements (lacks the typical oral, buccal or lingual dyskinesia seen in tardive dyskinesia)

How do you distinguish b/w movement disorder symptoms caused by neurological and malingering conditions?

Neurologic movement disorders get better when you call attention to them while psychogenic movement disorders get better when you distract from them

Pathological activation of NMDA receptors implicated in AD

No recycling back to closed state so pore stays open all the time = excessive calcium entry into brain cells

Paroxysms of hemiballismus and testing

Non-rhythmic, non-stereotypic unilateral movements with prominent involvement of proximal muscle groups When testing affected limb, no weakness or numbness detected Placing arms in winged position accentuates proximal components of a movement disorder Give mental tasks to distract them from voluntarily suppressing movements

Commissural syndrome

Normal pain and temperature everywhere else because they have already crossed over and avoided lesion as they passed up anterolateral tracts

General anesthesia MOA

Not clear but there is known to be an increased threshold for neuronal firing, resultant decrease in neuronal activity Evidence for several mechanisms: *FACILITATION OF GABA-A RECEPTOR-MEDIATED CL- CHANNELS) Activate K+ channels (hyperpolarization) Inhibit NMDA (glutamate) receptors Inhibit synaptic proteins (decrease NT release) Block nicotinic receptor subtypes Enhance glycine effect Interaction with membrane lipid matrix (Meyer-Overton principle)

Is decrease in BDNF responsible for depression?

Not necessarily -- but BDNF is necessary for antidepressants to work the way that they do (i.e. in order to see long term effects, benefits of antidepressants)

What is preservation? What part of the mental status exam does it fit within?

Observational item in which patient, by words or behavior, shows an inability to shift appropriately from one mental task to another Component of attention

Thromosis

Occlusion occurs at location of pathology, not downstream (embolus)

Charcot-Bouchard microaneurysms

Occur on penetrating arteries most often as a result of HTN and are different from sacular (Berry) aneurysms, which occur near circle of Willis Lenticulostriate vessels most commonly affected (affects basal ganglia, internal capsule and other deep, penetrating structures)

Cranial nerves that innervate extraocular muscles

Oculomotor nerve (CN III): medial rectus, superior rectus, inferior rectus, inferior oblique and levator palpebrae Trochlear nerve (CN IV): superior oblique Abducens nerve (CN VI): lateral rectus

Partial seizure affecting medial temporal lobe:

Olfactory hallucinations, automatism, psychic symptoms

MS features antibodies directed against which two elements

Oligodendrocytic glycoprotein Myelin basic protein

Meds for CP

One of the few that we have that is helpful for motor impairment with CP (spasticity only): botox Ongoing process, injections wear off Oral meds may be helpful for widespread spasticity: baclofen, dantrolene, diazepam (valium), tizanidine = anti-spasticity drugs For wide-spread spasticity, can pump baclofen into CSF (intrathetically)

Brown-Sequard's Syndrome

One side of cord affected (hemisection) Loss of motor function and position sense on same side and of pain sense on opposite side

Infantile Spasms (West Syndrome)

Onset usually b/w 4-8 months Brief, symmetric contractions of neck, trunk and extremities Tend to develop with onset of sleeping or when arousing EEG shows chaotic pattern of high voltage (hypsarrhythmia) Look for tuberous sclerosis (single most common cause of infantile spasms) 60% sill develop other seizure types/syndromes

What does palpebral fissure refer to?

Opening b/w upper eyelid and lower eyelid

G beta-gamma protein pathway

Opens K+ channels, efflux = hyperpolarization of cell Also involved in adenylate cyclase (cAMP) increase or decrease and phospholipase C (IP3)

Causes of Parkinsonism

Parkinson's disease: associated with degeneration of substantia nigra cells and intracellular Lewy bodies Parkinson-plus syndromes: degenerative disorders, such a multiple system atrophy and progressive supranuclear palsy (difficulty with vertical gaze -- i.e. problems looking up and down, will often spill things down their fronts) Dementia with Lewy bodies: combined dementia with Parkinson-like motor changes (both start at about the same time and progressively worsen hand-in-hand) Dopamine-blockers: such as haloperidol (psych), risperidone (psych) and metoclopramide (GI med) MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine): neurotoxin that destroys dopaminergic neurons in substantia nigra; mimicked Parkinson's in young people, now an animal model

Partial vs. generalized seizures

Partial: Simple (preservation of awareness) Complex (impairment of consciousness) Generalized: Absence Myoclonic Tonic-clonic Tonic Atonic

Narcolepsy: Pathogenesis Treatment

Pathogenesis: - In dogs, autosomal recessive disorder caused by deletion in hypocretin receptor gene - In humans, specific HLA type (DQB1*0602) and a specific T-cell receptor may, in combination with a specific environmental antigen, cause destruction of hypocretin synthesizing cells Treatment of Daytime Sleepiness: Methylphenidate, amphetamine, methamphetamine and dextroamphetamine Modafinil (standard) Sodium oxybate (often not available in pharmacies) *Be aware of side effects such as arrhythmia, sudden death, psychosis and abuse Treatment of Cataplexy: Tricyclic antidepressants (protriptyline, clomipramine, imipramine) SSRIs (less effective but fewer side effects) SNRIs (venlafaxine) Sodium oxybate (standard = best treatment but not readily available in pharmacies)

What are denial and neglect syndromes? How do you test for them? What do they suggest?

Patients with heliplegia may deny any problems or, more specifically, deny the presence of left-sided weakness that is obvious to anyone else; patients may deny ownership of left-sided body parts, such as left hands Patients with neglect syndromes do not attend to the L halves of their visual worlds, including the left halves of their own bodies (i.e. not shaving the L half of the face) Tested with line bisection task *INDICATE DAMAGE TO RIGHT PARIETAL LOBE

Core body temp peak and nadir

Peak: late afternoon and early evening (6-8 P.M.) Nadir: 2 hours prior to usual wake time (4-5 A.M.)

AEDs that can be given via IV

Phenytoin (as fosphenytoin) Phenobarbital Valproic acid (Depacon) Levetiracetam Pregabalin Carbamazepine (Carnexiv)

Drugs that act primarily on Na+ channels (MOA?)

Phenytoin, Carbamazepine Block voltage-dependent Na+ channel by binding to *inactivation gate* of sodium channel Time-dependent block: takes time for bound drug to dissociate from inactivation gate Use-dependent block: blocks voltage-dependent sodium channels at high frequencies

Say what type of seizure each is used to treat: Phenytoin Valproic acid Carbamazepine Benzodiazepines Phenobarbital Oxcarbazepine Gapapentin Levetiracetam Lamotrigine Tiagabine Ethosuximide Vigabatrin

Pheyntoin: focal Valproic acid: most Carbamazepine: focal Benzodiazepines: most Phenobarbital: most Oxcarbazepine: focal Gapapentin: focal Levetiracetam: most Lamotrigine: most Tiagabine: focal Ethosuximide: absence seizures only Vigabatrin: infantile seizures

Physiological and psychological imitators of epilepsy

Physiological imitators: Syncope Cardiac arrhythmia Transient ischemic attacks Confusional migraine Hypoglycemia Sleep disorders Movement disorders Vertigo Delirium Psychological imitators: Psychogenic seizures Episodic dyscontrol Panic attacks/anxiety Malingering Night terrors Breath-holding spells

Equinas position

Plantar-flexed foot (toes hit ground first instead of heel)

Topiramate

Pleiotropic AED Blocks voltage-dependent sodium channels at high firing frequencies Blocks voltage-dependent Ca2+ channels Antagonizes glutamate action at AMPA receptor Increases frequency at which GABA opens Cl- channels (different site than benzodiazepines)

Oxcarbazepine

Pleiotropic AED Blocks voltage-gated sodium channels, inhibiting repetitive neuronal firing and propagation of synaptic impulses Enhances K+ conductance Inhibits voltage-gated calcium channels

Valproate

Pleiotropic AED Enhances GABAergic transmission by inhibiting GABA-T and GABA uptake Blocks voltage-dependent sodium channels May also augment K+ channels

Levitracetam

Pleiotropic AED Used for partial onset, myoclonic or tonic-clonic seizures Inhibits neurotransmitter release by blocking presynaptic calcium channels and synaptic vesicle glycoprotein

Acquired myopathies

Polymyositis Dermatomyositis (rash) Viral Corticosteroid administration

Polymyositis and dermatomyositis vs. myotonic dystrophy

Polymyositis and dermatomyositis are acquired, show proximal weakness > distal weakness, pain, autoimmune Myotonic dystrophy is genetic, shows distal weakness > proximal weakness

Diminished/reduced DTRs

Polyneuropathy

CSF protein will be increased in _________________

Polyneuropathy (GB syndrome)

Tonic-clonic seizure EEG

Polyspike activity = tonic phase Each slow wave is a jerk After seizure ends, waves are slower and look very different from pre-seizure waves (post-ictal state)

Information to the cerebellum from cerebral cortex involves a two neuron chain. The synapse between these two neurons is located in the:

Pontine nuclei

Decreased glucose utilization/metabolism preferentially affects what area of the brain in AD?

Posterior cerebrum > anterior cerebrum

Essential tremor characteristics

Postural and/or kinetic tremor Frequency of 4.0-12.0 Hz Anatomic distribution (hands, head, voice, leg, jaw, face, trunk, tongues) Typically bilateral Hands and forearms affected (70%) Sporadic or inherited (60%) Alcohol responsive (74%)

Dopamine agonists used in PD

Pramipexole Ropinirole Bromocriptine

Cortical loop of limbic system

Prefrontal lobe --> uncus --> parahippocampal gyrus --> cingulum --> cingulate gyrus --> prefrontal lobe

Dopamine synthesis and degradation

Presynaptic neuron makes dopamine from amino acid tyrosine --> catalyzed to L-DOPA via tyrosine hyroxylase --> L-DOPA then decarboxylated to dopamine via dopadecraboxylase and stored in vesicles, which activates second messenger systems inside the cell causing changes in excitability, metabolism and gene expression Reuptake of dopamine is by dopamine transporter; if unstored in cytosol, dopamine is oxidized by monoamine oxidase (MAO)

Primary (Ia) vs secondary (II) afferent axons

Primary (Ia): receive information from both chain fibers and bag fibers (detect both stretch/length and rate/speed of stretch) Secondary (II): innervate only nuclear bag fibers (thus only detect stretch/change in length)

Grand Mal Seizure

Primary generalized tonic-clonic seizure Sudden loss of consciousness Tonic-clonic, tonic or clonic contractions Perioral cyanosis Lose bladder control 30-60 minutes of postictal state

Descending pathways that go directly (without synapsing) to the spinal cord originate from cells in the:

Primary motor cortex

Primary vs. secondary purpose of randomization

Primary: reduces selection bias in allocation of intervention (each participant has equal chance of being in experimental or control group) Secondary: if large sample size, experimental and control groups should have similar baseline characteristics; helps to control for known and unknown factors

Pro-inflammatory vs. anti-inflammatory cytokines and sleep

Pro-inflammatory cytokines (IL-1B and TNF-alpha) increase sleepiness Anti-inflammatory cytokines (IL-4 and IL-10) decrease sleepiness

How is AD diagnosed?

Probable: deficits in two or more domains of cognition; progressive decline of memory and other cognitive functions with preserved consciousness; onset b/w 40 and 90; absence of systemic or other brain diseases that could account for symptoms Definite: tissue diagnosis by biopsy or autopsy (not generally done because no treatment available) By time diagnosis is made, disease has been present for yearas

Local anesthetic drug interactions

Procaine is hydrolyzed to p-aminobenzoic acid, which inhibits action of sulfonamide antibiotics

Myotonia

Stiff muscles, prolonged after contraction

Upper motor neuron vs. lower motor neuron? Progressive bulbar palsy Amyotrophic lateral sclerosis Spinal muscular atrophy

Progressive bulbar palsy: brainstem Amyotrophic lateral sclerosis: UMN + LMN Spinal muscular atrophy: LMN

Pick's Disease

Progressive dementia clinically similar to Alzheimer's disease (i.e. progressive, smooth, non-stepwise decline in function, behavior and cognition) Early, prominent involvement of FRONTAL and TEMPORAL lobes ("frontotemporal dementia") Pick bodies (composed of randomly arrayed strands of tau) found intracellulary Gyri in frontal and anterior temporal lobes are shriveled, leaving behind giant sulci

Barbiturates (MOA and examples)

Prolong GABA-mediated chloride channel openings; in large doses, enhances potency and efficacy of GABA with some blockade of voltage-dependent sodium channels *Lower margin of safety (reaches maximal effect quickly = can overdose easily) Phenobarbital Primidone

What effect does BDNF have on neuroplasticity?

Promotes growth of axons and dendrites, increases synapse formation, dendritic branching Increases neurotransmitter release, promotes synaptic transmission and LTP through TrkB receptors

Placing arms in winged position accentuates ____________ components of a movement disorder

Proximal

Characteristics of desirable inhaled anesthetic agents

Quick induction and recovery Low solubility (little/no metabolic degradation) Ample potency (can be given with O2) Little/no side effects Safe (not flammable, explosive) Low cost

Denial and neglect syndromes indicate damage to the ___________________

R parietal lobe

Drawing is largely a (L/R) hemisphere task mediated by the ______________

R: R parietal lobe

Clinical weakness of which muscle would be most rare in myasthenia gravis?

Rectal sphincter Extrocular muscle weakness is typically severe, causing ptosis (i.e., levator palpebrae superioris m.) and diplopia (e.g., superior rectus m.). The disease typically progresses to other muscles, including those associated with the trunk and extremities (i.e., gluteus maximus and deltoid mm.)

Reflex bladder vs. non-reflex bladder

Reflex bladder: descending inhibitory pathway is inhibited; sacral segmental reflex arc is no longer inhibited, produces bladder that is - Small - Hypertonic ("spastic") - Wants to empty and fails to fill Non-reflex bladder: sacral spinal cord is damaged, disrupting sacral segmental reflex arc; produces bladder that is - Large - Hypotonic ("boggy") - Wants to fill and fails to empty

Types of MS (4)

Relapsing-remitting (RR): most common type (85%), symptoms flare up (called relapses or exacerbations) unexpectedly and then disappear (remission) but never returns to baseline before attack (partial recovery after each but attack but not complete) Primary-progressive (PP): steady worsening of neurological function without any relapses or remissions, overall disability is continuous; this form occurs equally in men and women and age of onset is about 10 years later than in relapsing-remitting MS Secondary-progressive (SP): follows relapsing-remitting MS; the majority of people with RR-MS will eventually transition to having SP-MS; after period of relapses and remissions, disease will start to progress steadily Progressive-relapsing (PR): least common form (5%), steady disease progression and worsening neurological function (as seen in PP-MS) along with occasional relapses like people with RR-MS (individual attacks but get worse linearly)

During low intensity muscular efforts only small alpha motor units are recruited because:

Resistance is inversely dependent on fiber diameter, and thus the excitatory post synaptic potential is larger for a given synaptic current in small than large motor neurons

Rest vs. postural vs. intention tremor

Rest tremor: maximal in repose, characteristic of Parkinsonism Postural tremor: maximum on posture holding (i.e. arms outstretched), in flexor-extensor axis, typical of familial or essential tremor disorders; also seen with hyperthyroidism and certain medications such as lithium divalproex and bronchodilators (8-12 Hz = harder to fake) Intention tremor: increases with approach to target such as in finger-to-nose testing (axis is perpendicular to line of flight), typically seen with damage to cerebellum or its connections

Deep brain stimulation in PD

Reversibly inhibits or disrupts neuronal activity to relieve symptoms in patients with Parkinson's disease The electrodes typically target subthalamic nuclei or globus pallidus interna To help both sides of brain, you will need to have 2 stimulators

Language in left vs. right handed individuals

Right handed: all language function is on left side (putting all your eggs in one basket) Left handed: mostly on L side but some language function on R hemisphere (lesion to one side may not be as dramatic)

What is the most common cause of a subdural hematoma?

Rupture of bridging veins Subdural hematomas are most often caused by head injury when rapidly changing velocities within the skull may stretch and tear small veins that traverse and bridge the meningeal layers

Effects of stimulating the amygdala

Same effects as those elicited by directly stimulating hypothalamus Several types of involuntary movement (because amygdala projects to basal ganglia) Emotional responses (Rage or pleasure) Sexual activities

What are the two types of explicit memory?

Semantic: memory for FACTS (objective knowledge learned in school and from books) Episodic: memory for EVENTS and PERSONAL EXPERIENCE (i.e. when we recall that we saw the first flowers of spring)

Multiple sclerosis symptoms at disease onset

Sensory symptoms in arms/legs Unilateral vision loss (optic neuritis) Polysymptomatic onset Slowly progressive motor deficit Acute motor deficit Diplopia

Irreducible minimum of MS diagnosis

Separate focal CNS lesions separated in space (different locations) and time At least one of the focal lesions needs to be clinical (and not merely by MRI scan)

An electroencephalogram in a 17-year-old girl with epilepsy shows about 3 spikes per minute emanating from the right occipital lobe. There are no associated clinical symptoms. Which of the following describes her most likely epileptic seizures?

She experiences flashes of light in her left visual fields.

An electroencephalogram in a 17-year-old girl with epilepsy shows several bursts of generalized, 3-Hz, spike-and-slow-wave discharges lasting 1-2 seconds each. There are no associated clinical symptoms. Which of the following describes her most likely epileptic seizures?

She stops and stares for 8 seconds without responding to external stimuli or losing posture. She immediately returns to normal.

An electroencephalogram in a 17-year-old girl with epilepsy shows about 3 spikes per minute emanating from the right temporal lobe. There are no associated clinical symptoms. Which of the following describes her most likely epileptic seizures?

She stops and stares for about 2 minutes without responding to external stimuli or losing posture. During this time she appears to be chewing on something and picking at the buttons of her shirt. Subsequently, she acts confused for another 2-3 minutes.

CBT for insomnia

Short-term benefits are comparable to pharmacologic therapy Long-term: CBT is more effective than pharmacotherapy (which has many side effects) Decreases sleep latency (SOL) better than pills Increases total sleep time (TST) less effectively than pills

Short- and long-term signaling pathways in neuroplasticity

Short-term function: influence the information processing function of synapses Insertion of AMPA receptors (glutamate-responsive) Modulation of CaMKII activity (to increase AMPA conductance) Long-term function: memory formation, sensory cortex development, fear conditioning and extinction, learning Activation of CREB Induction of BDNF

_________ is the single most important factor in determining the speed of induction and recovery in use of general, inhaled anesthetics

Solubility in blood

What is the most common type of CP?

Spastic CP (80%)

Spasticity vs. rigidity vs. paratonia

Spasticity: unidirectional increase in muscular tone, involves increased tone in "anti-gravity" muscles Rigidity: bi-directional increase in tone to passive range of motion that is relatively independent of degree of force or rate of speed (seen in Parkinson's) Paratonia: bi-directional increase in tone to passive range of motion that increases with force and rate of movement as if voluntary (seen in dementia)

Stages of sleep

Stage W (wakefulness): awake Stage N1 (NREM1): drowsy to light sleep Stage N2 (NREM2): light to deep sleep) Stage N3 (NREM3): deep sleep Stage R (REM): predominance of dreaming

Adult sleep stage scoring Stage W Stage N1 Stage N2 Stage N3 Stage R

Stage W: 50% of epoch contains alpha waves Stage N1: 50% of epoch contains theta waves; no K complexes, sleep spindles or rapid eye movements Stage N2:K complexes and sleep spindles Stage N3: 20% of epoch contains high amplitude delta waves Stage R: theta waves, rapid eye movements, low chin EMG tone

Stretch reflex vs. tendon reflex

Stretch reflex is caused by muscle stretch; tendon reflex is caused by muscle contraction Because of this, tendon reflex is generally to protect muscle/tendon from damage caused by extreme muscle contraction Tendon reflex is less sensitive than stretch reflex; activated when over threshold (lifting heaving things)

Stretching muscles activates the __________________ Contracting the muscle _____________

Stretching muscle activates the muscle spindle: there is an increased rate of action potentials in primary Ia afferent fibers Contracting the muscle reduces tension on the muscle spindle: there is a decreased rate of action potential in primary Ia afferent fibers Gamma motor neurons modify the sensitivity of the muscle spindle sensory afferents to stretch, involves CNS

What is the name of the connection b/w the amygdala and hypothalamus?

Striate terminales

A non-demented 70-year-old man develops new, recurrent, tonic-clonic seizures. Which underlying cause is most likely?

Stroke Strokes are most common in elderly people. Brain tumors are most common in middle adulthood. Abscesses as causes of new seizures are rare, and not particularly associated with any age group. Genetics and meningitis typically produce first seizures in childhood.

What is a typical cause of hemiballismus?

Stroke in subthalamic nucleus of Luys on side contralateral to affected limb

Mammillary bodies: structure, function and clinical implications

Structure: consist of two groups of nuclei (the medial and lateral mammillary nuclei) Function: relay impulses coming from hippocampi and amygdalae via the mammillothalamic tract to the thalamus and cortex; vital for memory affection and emotion Clinical implications: Alcohol intoxication (thiamine deficiency) Autism Amnesia

Focal disease processes causing dementia w/ or w/o focal exam findings

Subdural hematomas Epidural hematomas Vascular cognitive impairment (multi-infarct dementia) Brain tumors

What CNS structure is atrophic in idiopathic Parkinson's disease?

Substantia nigra

What is cataplexy?

Sudden loss of muscle tone with retained consciousness, usually bilaterally symmetrical Episode < 2 minutes Precipitated by strong emotions such as laugh Transient reversible loss of deep tendon reflexes In children, may present as facial hypotonia with droopy eyelids, mouth opening and protruded tongue or gait unsteadiness not clearly related to emotion

Myoclonus

Sudden, brief, shock-like involuntary movements caused by muscular contraction or inhibition, originating either in CNS or PNS

Sacral sparing

Suggests the lesion is impinging on the spinal cord from the outside-in Clinically, if you want to know whether lesion is from inside out or outside in = check pain and temp of buttocks If spared = probably inside out If lost = probably outside in

When would you use a crossover design?

Suitable for treatments used to manage symptoms or improve control of chronic conditions (e.g. pain, asthma, diabetes, etc.) Suitable for treatments with short-term effects Not suitable for treatment that cures a condition Not suitable for treatment that leads to permanent change (i.e. surgery)

Most commonly affected locations of cerebral thrombosis

Superior sagittal sinus Lateral sinuses

CSF is returned to venous circulation via the:

Superior sagittal sinus (arachnoid granulations)

Delta wave origin

Thalamus (generated by thalamocortical cells)

EEG signals are generated mostly by:

Synaptic potentials in large pyramidal neurons of cortex

Dystonia

Syndrome of sustained muscle contractions, frequently causing twisting, repetitive movements or abnormal postures The movements are a long duration and both agonist/antagonist muscles are contracting = results in twisting movement

Cerebral palsy

Syndrome, not a diagnosis: group of conditions involving motor dysfunction d/t non-progressive lesions in developing brains leading to permanent problems The most common motor disability in childhood All people with CP have problems with movement and posture; many also have problems with intellectual disability, seizures, visual changes, hearing changes, speech, spine changes (scoliosis) or joint problems (contractures) Common but not the only cause of motor delays in infants Classified based on main type of movement disorder involved: spastic, dyskinetic, ataxic, mixed (most common is spastic-dyskinetic)

Detection bias

Systematic differences b/w groups in how outcomes are determined (i.e. how you detect something) Blinding of outcome assessors may reduce the risk that knowledge of which intervention was received, rather than the intervention itself, affects outcome measurement. Blinding of outcome assessors can be especially important for assessment of subjective outcomes, such as degree of postoperative pain

Black holes

T1 (hypointense) Indicate irreversible tissue damage (d/t MS) May be predicted by prior inflammatory activity shown on Gd-enhanced scans

Progressive bulbar palsy

Tends to first manifest in things connected to lower brainstem (muscles of speech, swallowing and mastication) Arms and legs unaffected at first but eventually progresses there Similar to ALS but difference is which muscles are affected first

The primary mediator of demyelination in MS

Th1 lymphocytes

The high amplitude, low frequency activity that characterizes EEG during slow wave sleep originates largely in the:

Thalamus

Sleep spindle origin

Thalamus (generated by reticulothalamic cells)

When would a shunt be helpful in NPH?

The full clinical triad is present (r/o other reason for urinary incontinence). Magnetic gait (like you got stuck to ground) was the earliest and most prominent impairment. The ventricles are substantially enlarged. Sometimes, a trial lumbar puncture can be predictive (drain a large amount of CSF and see if cognitive symptoms, gait and urinary incontinence improve

Spinal cord blood supply

The portion of the arterial vasocorona (AVC) that delivers blood to the fasciculus cuneatus, as well as the fasciculus gracilis, is supplied almost entirely by the posterior spinal artery. The sulcal artery that delivers blood to the dorsal and ventral horn of the gray matter are supplied by the anterior spinal artery. Both the lateral corticospinal tract and spinothalamic tract (part of the ALS) receive blood from the sulcal artery, as well as the portion of AVC that is supplied by both the posterior and anterior spinal arteries

Ischemic penumbra

There is a central core of forever-lost brain cells that no treatment can revive surrounded by a larger zone of sick brain cells that may or may not recover - depending on acute management

Tourette's Syndrome

Tick disorder defined by extra, inappropriate excessive movements with motor and vocal involvement (which are multiple in type = one doesn't look exactly like another, can be some recurrence of individual movements) Distinguished from tremor b/c tick is non-rhythmic Not completely stereotypic: all movements do not look the same Vocalizations possible (i.e. throat clearing) Usual age of onset during teenage years

Pleiotropic AEDs

Topiramate Valproate Oxcarbazepine Levitracetam Lamotrigine

-Plegia

Total paralysis

A symptomatic Toxoplasma encephalitis is evidence of an advancing HIV infection. This situation is likely the result of:

Toxoplasma is usually maintained at an asymptomatic level by CD4 cells

Hippocampus function in memory

Transfers (explicit -- i.e. those that can be stated) memories from short-term to long-term storage

How do you distinguish b/w a tremor and a tick (as in Tourette's Syndrome)?

Tremor: rhythmic Tick: non-rhythmic, not completely stereotypic (one movement does not look exactly like another)

T/F: An absent armswing on one side can be the earliest manifestation of Parkinson's disease

True

Narcolepsy Type I vs. Type II

Type I: A. Daily periods of irrepressible needs to sleep or daytime lapses into sleep for at least 3 months B. At least one of 1. Cataplexy and 2. CSF Hcrt-1 <110 pg/mL or 1/3 of normal mean values Type II: A. Daily periods of irrepressible need to sleep or daytime lapses into sleep for at least 3 months Cataplexy is absent CSF Hcrt-1 not measured or >110 pg/mL

G protein alpha-t

cGMP-phosphidesterase increase (vision)

Acute anti-thrombotic interventions

t-PA (tissue plasminogen activator) given intravenously?—only if within 3 hours and fully meeting inclusion and exclusion criteria - i.e. have already had CT scan, blood tests) Fractionated or unfractionated heparins given subcutaneously?—for DVT prevention only (mini-dose to prevent blood clots in bed-ridden patients) Aspirin or other platelet-oriented drugs?—Aspirin (given orally or rectally) has a small benefit acutely