Week 7

Non-Pharmacological Management Strategy Which of the following is NOT considered a non-pharmacological management strategy for restless leg syndrome? Behavioral modification strategies. Exercise. Avoid caffeine, alcohol or nicotine. Discontinuation of an SSRI if one is being taken.

Behavioral mod

Dementia The effect of dementia on the brain results in cerebral cortex swelling. True False

Dementia results in brain shrinkage.

Stage 5 of AD

Early Dementia to early AD: Disorientation of time and place. Difficulty remembering address and phone number. Increased need for super vison, may last for 1.5 years.

Amantadine in treament of PD

The next strategy is to use amantadine (Gocovri)This is an antiviral medication that increases endogenous dopamine production although, the mechanism is not fully understood.

Vascular Dementia

Blood supply to the brain impairs normal function of neurons Symptoms may appear suddenly after a stroke (post-stroke dementia) or gradually due to vascular wear and tear that occurs with aging or any conditions that damage or narrow blood vessels over time (high blood pressure, hyperlipidemia, and diabetes) Incidence of vascular dementia increases with age and cardiovascular risk factors.

Neuromuscular junction disorders

Periodic Limb Movement Disorder: Involves involuntary forceful dorsiflexion of the foot that occurs every 20-40 seconds during sleep. Restless Leg Syndrome: occurs when going to sleep and progresses over time.

Postural instability in PD

Postural instability: This is a late feature of PD. It causes problems with balance and can lead to falls.

bradykinesia in PD

This is slow movement. Hypokinesia is a lessened movement and akinesia is no movement. All three result from difficulty initiating movement. Examples include having the legs freeze up when attempting to walk and walking with a shuffling gate or small steps.

Lhermitte's Sign Lhermitte's sign is an electric shock that runs down the back and radiates in the limbs when bending the neck forward. True False

This statement is true. Lhermitte's sign is an electric shock that runs down the back and radiates in the limbs when bending the neck forward.

Restless Leg Syndrome Restless leg syndrome is thought to be due to impaired iron regulation and homeostasis in the body. True False

This statement is true. Restless leg syndrome is thought to be due to impaired iron regulation and homeostasis in the body.

Carpal Tunnel Syndrome The most common compressive neuropathy in the upper extremity is carpal tunnel syndrome. True False

True

PD is derived from the death of dopamine-producing (dopaminergic) neurons in the substantia nigra. True or False

True

Multi-focal nueropathy

A multi-focus neuropathy is purely a motor neuropathy that is characterized by motor deficits in the distribution of single nerve without associated sensory loss caused by vasculitis or diabetes. This type is relatively uncommon and there is always asymmetric involvement typically in the upper limbs. Weakness begins in the distal upper limbs that causes difficulty in wrist and finger extension or reduced hand grip.

Stages of Alzheimer's Disease

Because of the varied progressive nature of Alzheimer's disease, it is difficult to describe distinct stages. The stages also overlap. Keeping this in mind, the stages are described below. Note that before we review the stages of Alzheimer's disease below, it is important to recognize that to actually diagnose it, other potential causes of dementia should be ruled out including the effects of medication, trauma, vascular issues such as stroke and ischemia first. Once ruled out, it can be a presumptive diagnosis based on MRI results that demonstrate atrophy in the hippocampus.

secondary types of dementia

Dementias may also develop from metabolic and endocrine processes such as thyroid disorders and vitamin deficiencies (B1, B6, B12) or infections like Lyme disease and neurosyphilis. For these types of dementias, symptoms can be reversed.

Diabetic Neuropathies

Distal symmetric diabetic neuropathy consists of two sub-types: Large-fiber (A-type): This involves deep-seated pain (A-type); signs and symptoms include wasting and weakness; numbness, pins and needles, tingling, ataxia, impaired vibration perception; loss of position sense; loss of reflexes; impaired nerve conduction velocity; it interferes with normal life and there is a risk of falls and fractures. Small-fiber: Involves superficial pain (C-fiber type); will feel electric shock, burning, allodynia Autonomic dysfunction, thermal imperceptions; normal strength and reflexes; quantitative sensory testing and skin biopsies produces symptoms and leads to morbidity and mortality.

MS triad

Dysarthria: Difficulty or unclear speech that is due to plaques in the brain stem. Nystagmus: This is involuntary rapid eye movement due to plaques on the nerves that cause eye movements. Intention tremor: This can be caused by plaques along the motor pathways of the spinal cord which can affect outbound signals and skeletal muscle control.

Stage 6 of AD

Moderately severe AD: unable to remember family and friends names, but able to recognize faces. Patient will need help with basic ADL's

Charcot's triad

Multiple sclerosis (nystagmus, intention tremor, scanning speech), cholangitis (jaundice, RUQ pain, fever)

Clinical Manifestations of Parkinson's Disease

Tremor, Rigidity, Bradykinesia, Postural instability

Stages of Alzheimer's Disease 1

early to mild stage of AD, Can last between 2-7 years

Treatment of Parkinsons disease.

Dopamine itself cannot cross the blood-brain barrier. But its precursor Levodopa can. Once in the brain, levodopa is converted to dopamine by dopa decarboxylate in the remaining nigrostriatal neurons.

Pharmacological treatment of RLS

Dopaminergic agents Ropinirole Pramipexole Carbidopa/levodopa Requip Mirapex Sinemet Alpha-2 agonists Gabapentin Pregabalin Neurontin Lyrica Benzodiazepines Clonazepam Temazepam Klonopin Restoril Opioid agents Codeine Tramadol Oxycodone Hydrocodone Methadone Tylenol ( #3/#4) Ultram Roxycodone Vicodin

Does PD produce weakness?

No, Despite these multiple effects in movement, PD does not produce weakness. This helps to differentiate it from diseases that affect the motor cortex or corticospinal pathway diseases.

Types of MS

Relapsing Remitting MS (RRMS): Remyelination takes place for a period of time. There is no disability between episodes. Secondary Progressive MS (SPMS): The immune attack becomes constant over time which causes a steady progression of disability. Primary progressive MS (PPMS): There is one constant attack on the myelin. Progressive Relapsing MS (PRMS): This also involves one constant attack where the disability happens very fast.

focal neuropathy

A focal neuropathy is a chronic condition with sensory, motor, or mixed involvement. It involves microvascular compression that results in neural ischemia, paresthesia, intraneural edema that leads to more microvascular compression. Demyelination occurs that results in fibrosis and loss of axon. The first sensations lost include light touch, pressure and vibration followed by later loss of pain and temperature sensation. The most common compressive neuropathy in the upper extremity is carpal tunnel syndrome. The diagram below shows compression of the median nerve at the wrist that results in pain and numbness.

Restless Leg Syndrome Select all items below that are part of the DSM-5 criteria for diagnosing restless leg syndrome: Is equally worse during the day and night. Cannot be due to another cause such as intoxication or medication. Symptoms improve with movement. Worsens with activity. Is worse at night and associated with inactivity. Experiences urge to move the legs usually followed by discomfort if movement not performed. Dorsiflexion of the feet worsens the pain.

DSM-5 criteria for diagnosing restless leg syndrome includes: Experiences urge to move the legs usually followed by discomfort if movement not performed. Is worse at night and associated with inactivity. Symptoms improve with movement. Cannot be due to another cause such as intoxication or medication.

Diagnosis of neuropathies

Diagnosis The practitioner must collect a thorough health history specifically determining if the neuropathy can be associated with a systemic disease (diabetes, hypothyroidism). Medication history should be collected to determine if there are neuropathic side effects. A social history should be collected to identify drug and alcohol use. All patients should be assessed for HIV risk factors, foreign travel (leprosy), diet, vitamin use (vitamin B-12) and any history of tick bite (Lyme disease). Family history should be obtained to identify any hereditary factors that may contribute to neuropathy. A complete review of systems will help to determine any organ involvement and any malignancy.

Multiple Sclerosis Diagnostic Tests Review the diagnostic tests below and check the ones used to diagnose Multiple Sclerosis: Electroencephalography. Visual evoked potential. An MRI that shows multiple CNS lesions called white matter plaque. Cerebrospinal fluid analysis. Electrocardiogram.

Diagnostic tests used to diagnose Multiple Sclerosis include: An MRI that shows multiple CNS lesions called white matter plaque. Cerebrospinal fluid analysis. Visual evoked potential.

Treatment of Multiple Sclerosis Select all drugs that are used in the treatment of Multiple Sclerosis: Methotrexate (Otrexup) Cephalosporin (Cefuroxime) Cyclophosphamide (Cytoxan) Methylprednisolone (Solumedrol) Intravenous immunoglobulin (Flebogamma) Clonidine (Catapres)

Drugs that are used in the treatment of Multiple Sclerosis include: Methylprednisolone (Solumedrol). Cyclophosphamide (Cytoxan). Intravenous immunoglobulin (Flebogamma).

Drugs used to treat restless leg syndrome.

Drugs used to treat restless leg syndrome include: Dopamine drugs. Benzodiazepines. Opioids. Anticonvulsants. Alpha-2 agonists. Iron.

Types of neuropathy

Focal: Chronic condition with sensory, motor, or mixed involvement that involves microvascular compression. Multi-focal: Is purely a motor neuropathy that is characterized by motor deficits in the distribution of single nerve without associated sensory loss caused by vasculitis or diabetes. Symmetric: Can be proximal or distal with primarily motor involvement.

Frontotemporal Dementia

It is characterized by neuronal cell death in the frontal and temporal lobes of the brain. The areas associated with this relates to behaviors and language. Common signs and symptoms include changes in behaviors (social inappropriateness, impulsivity, apathy, emotional indifference) and language deficits This type has a strong genetic component and tends to occur earlier between the ages of 40-50 years.

Parkinson's Disease Which of the following is considered the main treatment strategy for Parkinson's disease to increase dopamine signaling in the brain? Administer amantadine Administer levodopa Administer bromocriptine Administer pramipexole

Levodopa is the main treatment strategy although the other drugs may be given during the disease process of PD.

Stages of AD 2

Mild Cognitive decline: issues with remembering recent events, subtle misplacing of items.

MMSE

Motor and sensory function should be tested along with deep tendon reflexes. Neuropsychological tests to objectively measure the patient's current memory and mental abilities can be performed: Mini-mental state examination (MMSE): this helps in diagnosing dementia because it looks at orientation, memory and attention. The patient is asked to follow verbal or written commands or write a sentence spontaneously or copy a complex shape. Depending on the score, a certain level of dementia might be suggested. The rating scale is below:20-24: Mild dementia13-20: Moderate dementia< 13: Severe dementiaPatients with Alzheimer's disease tend to drop 2-4 points on average/year. Mini-Cog:Name 3 objects and repeat them back to the practitioner. Next draw a clock and designate a specific time.Then the patient is asked to repeat the original 3 objects. If the patient fails one or all the tasks, it is suggestive of dementia where further evaluation is recommended.

Toxic neuropathies

One of the most common causes of toxic neuropathy is from complications of cancer treatment following the administration of chemotherapy. Chemotherapeutic drugs commonly associated with toxic neuropathy include platinum-derived, taxane, and vinca alkaloid compounds. High levels of these drugs are found in the dorsal root ganglia and peripheral nerves. Reversibility of the signs and symptoms following discontinuation of the drugs vary:

Parkinson's Disease

Parkinson's disease (PD) is a movement disorder where the dopamine-producing neurons and substantia nigra of the brain undergo neuron degeneration. It is one of the most common neurological disorders. It is progressive with its onset during adulthood. Therefore, it is more common with age. Most of the time, there is no known cause. In some cases, however, there may be a genetic cause. In this case, there are mutations in the PINK1, Parkin, or Alpha synuclein genes. In rare cases, Parkinsonian symptoms may be caused by MPTP, a toxic impurity that is found in the recreational drug MPPP (synthetic opioid).

The substantia nigra can be split into two subregions:

Pars reticulata: It receives signals from another part of the basal ganglia called the striatum. It relays messages to the thalamus via by the neurotransmitter Gamma amino butyric acid (GABA). Pars compacta: This is the part of the substantia nigra that is affected in PD. It sends messages to the striatum via neurotransmitter dopamine via the nigrostriatal pathway which helps to stimulate the cerebral cortex to initiate movement. Therefore, when substantia nigra pars compacta neurons die, the individual might be in a hypokinetic, low movement state which is commonly seen in PD. In addition to simply initiating movements, the substantia nigra helps to calibrate and fine-tune the way that movements happen. This leads to the clinical features of PD.

Pathophysiology of RLS

Pathophysiology of RLS There is a strong genetic and family history component for RLS. It is thought to be due to impaired iron regulation and homeostasis in the body. Either the iron is not working effectively, or the iron is not being utilized by the body. There may also be an impaired dopamine pathway. It can also be secondary to a folate or magnesium deficiency, amyloidosis, diabetes, Lyme disease or even pregnancy. Once secondary issues are resolved, the symptoms go away.

What is the reason for levodopa to be added to carbidopa in treatment of PD?

Peripheral dopa decarboxylase also exists which can metabolize levodopa before it gets to the blood-brain barrier and via additional enzymes, metabolize it into other catecholamines like epinephrine. This is the reason that levodopa is administered with carbidopa a dopa decarboxylase inhibitor that is not able to cross the blood-brain barrier.

Rigidity in PD

Rigidity: This is stiffness that can appear as a cogwheel rigidity. This is a series of catches or stalls in movement as the extremity is passively moved by someone else. Rigidity is also responsible for stooped posture and almost expressionless face.

Diagnosis of Restless Leg Syndrome

The DSM-5 criteria may be used to diagnose RLS as there is a psychological component to the disease. It is important to note that it is a patient-reported disease. Therefore, there is no specific lab that diagnoses it. From a diagnosis standpoint, the individual must: Have an urge to move the legs usually followed by discomfort if the person does not move the legs. It is worse at night and when the individual is inactive. The symptoms improve with movement. It gets better with movement Can't be due to another cause such as intoxication or medication.

Tremor in PD

Tremor: This is involuntary shakiness most noted in the hands (pill-rolling movement). This is called a resting tremor indicating that it is present at rest. It diminishes with intentional movement.

Multiple Sclerosis

Type for Hypersensitivity reaction

Restless Leg Syndrome Which of the following is considered a non-pharmacological management strategy for restless leg syndrome? Exercise. Discontinuation of an SSRI if one is being taken. Avoid caffeine, alcohol or nicotine. All of the above.

All are non-pharmacological measures for RLS.

Alzheimer's Disease There are some very well-known causes of Alzheimer's disease. True False

Although there are theories on what causes it, the cause of Alzheimer's disease is unknown.

glutamate excitotoxicity

Another theory on what causes Alzheimer's disease involves glutamate excitotoxicity. Glutamate is another excitatory neurotransmitter of the CNS. It works on the neuron. If we have a neuron and we want that neuron to fire off an action potential, starting at the cell body and send it to the neurotransmitters, we need to excite it. Glutamate can be given. Glutamate comes down to the cell body to bind with glutamate receptors. Once this occurs, the action potential is sent. Remember that neurons are negative on the inside of the cells. Positive ions located on the outside rush into the cell in a domino effect. Glutamate stimulates this by binding to receptors to open the calcium channels that allows calcium to rush inside the cell. When the positive ion Calcium enters the cell, it will lead to depolarization and production of an action potential. In Alzheimer's disease, the patient may have too much glutamate being released which results in a toxic effect. If too much glutamate binds with the neuron, then too much calcium is going into the cell. Too much calcium entering a cell usually results in cell death. This is one thought on how cells begin to die off in Alzheimer's disease. The diagram below depicts the result of too much calcium ion entering the cell with the increase in free radical, degradation of the cell membrane and proteins.

Autonomic neuropathy

Autonomic neuropathy involves damage to the nerves that regulate body functions that is out of the individual's control. It includes regulation of heart rate, blood pressure, perspiration and digestion. One of the best examples to illustrate autonomic neuropathy is reviewing the signs of autonomic diabetic neuropathy summarized in the diagram below. It shows the extent of body systems involved along with associated responses and treatments: Cardiovascular:Resting tachycardia, reduced exercise tolerance, orthostatic hypotension, asymptomatic myocardial ischemia Symptomatic treatment including ACE-inhibitors, beta-blockers, clonidine, graded exercise programs, lifestyle advice, managing cardiovascular comorbidity GastrointestinalEsophageal dysmobility, gastroparesis, diarrhea, bacterial overgrowthProkinetic agents, anti-diarrheals (e.g. loperamide), antiemetics GenitourinaryErectile dysfunction, cystopathy, female sexual dysfunctionPDE5 inhibitors (e.g. sildenafil), psychological counseling, prostacyclin lubricants, intermittent catherization Metabolic Hypoglycemic awareness, autonomic failureOptimal glycemic control SudomotorAnhidrosis, heat intolerance, gustatory sweating, dry skinEmollients, vasodilatiors, glycopyrrolate, botulinum toxin

Treatment of Alzheimer's Disease

Cholinesterase Inhibitors Under normal conditions, cholinergic neurons in the brain synthesize acetylcholine from acetyl coenzyme A (acetyl CoA) and choline, in a reaction catalyzed by an enzyme choline acetyltransferase. Upon arrival of neuronal impulses, ACH enters the synaptic cleft where it interacts with ACH receptors located on the post-synaptic neuron. Shortly afterwards, an enzyme, acetyl cholinergic esterase ACHL and butyryl cholinesterase (BuChE), break down acetylcholine into acetate and choline that terminate stimulating signals. Since Alzheimer's disease has been linked to a deficiency of ACH in the brain, cholinesterase inhibitors are introduced to alleviate the symptoms. They work by inhibiting cholinesterase enzyme from breaking down ACH by increasing both the level and duration of the action of ACH. The three commonly prescribed cholinesterase inhibitors are: Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Reminyl) It is important to note that out of the three medications, rivastigmine (Exelon) is the only one that shows significant inhibition of both acetylcholine esterase and butyryl cholinesterase.

Small fiber neuropathy

Damage occurs in the small fibers of the peripheral nervous system. Several diseases may lead to small-fiber neuropathy and include: Metabolic syndrome and impaired glucose tolerance. Vitamin B-12 deficiency. Thyroid dysfunction. Neurotoxic medications. Sarcoidosis. HIV. Paraneoplastic syndromes. Celiac disease. Paraproteinemia.

Small Fiber Neuropathies Identify the types of causes of small fiber neuropathies: Hypertension. Peptic ulcer disease. Vitamin B-12 deficiency. Thyroid dysfunction. Migraine. Metabolic syndrome.

Types of causes of small fiber neuropathies include: Metabolic syndrome. Vitamin B-12 deficiency. Thyroid dysfunction.

Tau Hypothesis

In the healthy brain, the Tau protein helps to lengthen and support the microtubule structure. Microtubules play a crucial role in the transport of nutrients and information molecules throughout the neuron. When Tau dissociates, the microtubule assembly becomes compromised thereby disrupting the neuron's transport system leading to malfunctions in biochemical communication between neurons. Neurofibrillary tangles are involved in this process. Remember that healthy brain neurons will send signals from the cell body down the axons to the synapse so that it can release neurotransmitters. In addition to sending action potentials, neurons also send proteins, nutrients and other important molecules. The microtubules are responsible for carrying these. In Alzheimer's disease, the microtubules become misfolded and tangled which alters their function. These are called neurofibrillary tangles.

Symmetric neuropathy

In a symmetric neuropathy, it is important to determine if it is proximal or distal. Motor neuropathies are predominantly proximal (Guillain-Barre syndrome). Proximal sensory neuropathies are rare (porphyria). In distal symmetric neuropathy, this is seen with most metabolic, toxic and nutritional issues. It is predominantly in the axon and is length dependent. Symptoms begin in the feet and progress with the characteristic stocking glove pattern. Dysfunction first occurs in the distal portions of the longest axons, thus in the most distal portions of the extremities. Small diameter axons are most susceptible to metabolic injury due to their small size. Initial symptoms include autonomic dysfunction and small fiber sensory modalities, including loss of pain and temperature. Patients will present with numbness, paresthesia, burning discomfort, with loss of sensation in the distal lower extremity. Later there will be loss of an Achilles tendon reflex and weakness of the intrinsic foot muscles.

Multiple Sclerosis Multiple sclerosis is classified as a: Type I hypersensitivity reaction. Type II hypersensitivity reaction. Type III hypersensitivity reaction. Type IV hypersensitivity reaction.

MS is a type IV hypersensitivity reaction.

Stages of AD 4

Mild AD: Lasts for approx 2 years. Issues with math, finances. Issues with driving and cooking. Patients can still identify family and friends.

Stage of AD 3

Mild cognitive impairment where there are signs of early confusion

Myelopathies

Myelopathies occur at the level of the myelin sheath due to heredity or inflammation. In hereditary demyelinating neuropathies the axons are spared. Therefore, complete recovery can occur in a few weeks to months. This type of neuropathy is characterized by patchy, segmental injuries. Neuropathies can be examined based on their pattern of involvement: focal, multifocal, or symmetric.

Treatment of AD

NMDA Receptor Antagonists NMDA receptors belong to a family of ionotropic glutamate receptors that mediate most of the excitatory synapse transmission in the brain. They are thought to play an important role in learning and remembering information. Beta amyloid proteins accumulate in the brain of Alzheimer's patients and may cause an abnormal rise in extra synaptic glutamate levels by inhibiting glutamate uptake or triggering glutamate release from the glial cells. The binding of glutamate to the NMDA receptor results in the influx of extracellular calcium which controls membrane excitability and synaptic transmission. When glutamate levels become abnormally elevated, overstimulation of NMDA receptors can result, leading to excessive influx of calcium ultimately causing cell rupture and death. Memantine is an NMDA receptor antagonist that works by blocking NMDA receptors which limits the influx of calcium into the neuron. Common side effects are diarrhea, headache and insomnia.

Neuropathies

Neuropathies Peripheral neuropathy has multiple etiologies but there are only a few ways, however, that nerves can respond to an injury. The damage can occur at: Level of the axon (axonopathy). Distal to the site of injury (Wallerian degeneration). Distal portion of the axon (degeneration of axon and myelin sheath).

Substantia nigra

Under a microscope, Lewy bodies which are eosinophilic, round occlusions made up of alpha-synuclein protein are present in the affected substantia nigra neurons before they die. The function of alpha-synuclein is unknown as well as the significance of Lewy bodies. They are also both found in other diseases like Lewy body dementia and multiple-system atrophy.

Clinical Manifestations of Neuropathy

The clinical manifestations and overall course of the neuropathy depends on its etiology. If the neuropathy is caused by trauma or ischemia, it will have an acute onset and will demonstrate the most severe symptoms at that time. Neuropathies with a metabolic or inflammatory etiology will have a subacute course that may last from days to weeks. Characteristically, toxic and metabolic neuropathies are chronic, lasting from weeks to months. Inherited neuropathies are chronic and slowly progressing. Finally, some neuropathies have a relapsing and remitting course as in the case of Guillain-Barre syndrome. The practitioner can examine the symptoms closely to determine the type of axons involved: Ischemic neuropathies: Pain is the most prominent feature. Small fiber neuropathies present with burning, lightening, or aching pain or paresthesia; may be intolerant to sensations. e.g. when a sheet touches their feet (allodynia); may also described band-like sensation around ankles or wrists. Sensory symptoms: Tingling, paresthesia, hypesthesia, numbness. Distal symmetric axonal neuropathies initially involve the tips of toes and progress progressively in a stocking-glove distribution. Multifocal neuropathies: Mononeuritis multiplex that is caused by polyarteritis nodosa. Can present as restless leg syndrome. Proximal involvement: May involve difficulty climbing stairs, getting out of a chair, lifting and swallowing.

Pharmacological treatment of RLS

The treatment for RLS and PLMD is similar. However, for PLMD, the decision to initiate treatment is controversial. For both RLS and PLMD, the treatment must be individualized based on the severity of the symptoms and its impact on the patient's quality of life. The medication recommendations below are based on the American Academy of Neurology 2016 and the American Academy of Sleep Medicine 2012 guidelines. Note that the mechanism of action of these drugs are not completely understood in symptom relief of RLS or PLMD but are thought to act on the dopaminergic projects descending from the A11 region of the hypothalamus to the spinal neuronal systems. It is dysfunction here that causes the symptoms. On the somatic side of the spinal cord there are sites for the effects of dopamine, adenosine A1, adenosine A2 and opioid receptor in the dorsal horn that help to alleviate the symptoms. On the autonomic side, actions of dopamine and adenosine receptors have been identified on sympathetic preganglionics with evidence of opioid action here as well. Alpha-2 agonists modifies the excitability of the target tissues by directly binding to calcium channels.

There are some neuropathies that present with an uncommon pattern:

There are some neuropathies that present with an uncommon pattern: Neuropathies that involve the cranial nerves as in the case with Guillain-Barre syndrome that can involve the facial nerves. Greater involvement of the arms than the legs. This is the case with leprosy that tends to involve cutaneous nerves in the cooler areas of the body (tip of the nose).

Diagnosis of Alzheimer's Disease

There is no one test that will show if someone has dementia or Alzheimer's disease since the typical symptoms like memory loss, confusion, and others can have many possible causes. It is not completely diagnosed until a complete medication assessment is performed and other causes of dementia ruled (medication, trauma, vascular issues). Once those are ruled out, MRI may reveal hippocampus atrophy that can point to Alzheimer's type dementia.

Cholinergic Hypothesis

This hypothesis involves reduced levels of acetylcholine (ACH). ACH, is a cholinergic, excitatory neurotransmitter in the central nervous system. It is important in forming new neuronal function and synapses that involve memory. It is unclear why ACH is reduced in Alzheimer's disease. But it provides us an opportunity manage the signs and symptoms pharmacologically. If there is reduced ACH, it needs to be increased. One of the ways to increase ACH is by reducing the amount of enzyme that breaks down ACH. The enzyme is called acetylcholine esterase (ACH esterase). If a patient can receive an ACH esterase inhibitor, it will stop the enzyme from destroying ACH and improve ACH levels in the system. Note that there is no cure for Alzheimer's disease and the neurodegenerative process cannot be stopped, but if ACH can be increased for as long as possible, then some symptoms can be controlled.

amyloid hypothesis

This hypothesis involves the formation of senile plaques (amyloid plaques). Beta-amyloid is a metabolic waste disorder found in the fluid between the brain cells. It induces neuroinflammation and disrupts communication between the neurons. On the plasma membrane, there are numerous proteins. Some proteins ensure appropriate neurotransmitter function at the synapse. Other proteins, like the neurofibrillary tangles also misfold, malfunction and then get released into the extracellular fluid and come together to form an even larger misfolded protein (Beta-amyloid clump). This is a senile plaque. The diagram to the right depicts neurofibrillary tangles.

Autonomic Neuropathy Autonomic neuropathy involves damage to the nerves that regulate body functions that is out of the individual's control. True False

This statement is true. Autonomic neuropathy involves damage to the nerves that regulate body functions that is out of the individual's control.

Conduction nerve studies can help determine if the neuropathy is axonal, demyelinating or both. True False

This statement is true. Conduction nerve studies can help determine if the neuropathy is axonal, demyelinating or both.

Alzheimer's Disease In Alzheimer's disease, the microtubules become misfolded and tangled which alters their function. True False

This statement is true. In Alzheimer's disease, the microtubules become misfolded and tangled which alters their function.

Neuropathies can also be grouped according to the fiber type that is mostly involved:

Toxic and metabolic neuropathies are sensory initially, but later involve the motor fibers. Total sensory neuropathies may result from drug toxicity (cisplatin), nutritional deficiencies, and paraneoplastic syndromes. Total motor neuropathies include Guillain-Barre syndrome. Painful neuropathies include alcoholism and diabetes due to small-fiber involvement. It is also important to determine if the neuropathy is axonal, demyelinating or both. The best method for determining this is through nerve conduction studies (NCS) and electromyography (EMG).

Essential tremor vs PD tremor

the resting tremor of PD helps to differentiate it from cerebellar diseases which may result in an action or intention tremor. This is the opposite of a resting tremor where the tremor actually worsens with movement.

Stage 7 AD

very severe decline-unable to communicate, control movement or respond to surroundings, difficulty swallowing, help with all ADLs