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Neurological System.

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Presentation on theme: "Neurological System."— Presentation transcript:

1 Neurological System

2 Symptom Overview Headache Dizziness and vertigo Confusion
Memory/mental status changes Paresthesia Tremors

3 Common Symptoms Headache Dizziness and vertigo
Inflammation/Constriction Dizziness and vertigo Irritation Confusion/memory/mental status changes Executive Function Paresthesia Nerve Inhibition Tremors Nerve Excitation

4 Basis of Neurological Problems
Autoimmune/Degenerative Pathologic excitation/inhibition nerve fibers Degeneration/Destructions nerve fibers Circulatory Ischemia/hypoxemia Decreased blood flow/decreased oxygen levels Genetic Mutations causing abnormal biochemistry Infection/Trauma Abnormal pathology through injury

5 Degenerative Conditions
Parkinson’s disease Multiple sclerosis Brain tumors

6 Circulatory TIA/CVA Aneursym AV Malformation Headaches
Migraine Tension Cluster Peripheral neuropathy

7 Infection/Trauma Meningitis and encephalitis Viral meningitis
Seizure disorders/ epilepsy Bell’s palsy Trigeminal neuralgia

8 Nerve Fibers An axon or nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma. Axons are in effect the primary transmission lines of the nervous system, and as bundles they help make up nerves. Individual axons are microscopic in diameter - typically about one micrometre across (1μm) - but may extend to macroscopic (>1mm) lengths. The longest axons in the human body, for example, are those of the sciatic nerve, which run from the base of the spine to the big toe of each foot. These single-cell fibers of the sciatic nerve may extend a meter or even longer. In vertebrates, the axons of many neurons are sheathed in myelin, which is formed by either of two types of glial cells: Schwann cells ensheathing peripheral neurons and oligodendrocytes insulating those of the central nervous system. Along myelinated nerve fibers, gaps in the sheath known as nodes of Ranvier occur at evenly-spaced intervals, enabling an especially rapid mode of electrical impulse propagation called saltation. The demyelination of axons is what causes the multitude of neurological symptoms found in the disease Multiple Sclerosis. The axons of some neurons branch to form axon collaterals, along which the bifurcated impulse travels simultaneously to signal more than one other cell.

9 Pressure/Ischemia = Neuropathy
Peripheral (extremity) Radiculopathy (“root”) Myelopathy (muscle/nerve)

10 Neuropathies involving these are called small fiber neuropathies
Small myelinated axons are responsible for light touch, pain temperature. Small unmyelinated axons are also sensory and subserve pain and temperature. Neuropathies involving these are called small fiber neuropathies Small myelinated axons are responsible for light touch, pain temperature. Small unmyelinated axons are also sensory and subserve pain and temperature. Neuropathies involving these are called small fiber neuropathies

11 Nerves have a limited number of ways to respond to injury
Damage can occur at the level of the axon—this generally results in degeneration of both the axon and the myelin sheath Damage at the motor neuron or dorsal root ganglion is often incomplete Damage at the level of the myelin sheath are often inflammatory or hereditary—these can yield a rapid recovery or a progressive diffuse course of illness

12 Severed = Paralysis

13

14 Results of Neuropathy Pain Parathesia Hyperasthesia Paralysis Burning
Numbness Hyperasthesia Sensitivity Paralysis Loss of movement

15 Various Neuropathy Conditions
Back pain Radiculopathy Sciatica Myelopathy Neuralgia/Parathesia Trigeminal Palsy (Bell’s, Ulnar) Migraine (?) Degenerative Multiple Sclerosis Amyotrophic Lateral Sclerosis Myelopathy is a term that means that there is something wrong with the spinal cord itself. This disease is very different from the radiculopathy that is caused by isolated points of pressure on individual nerve roots. This process does not commonly occur with low back pain because the spinal cord itself ends at about the level of the first and second lumbar vertebral body. From this point on, only nerve roots occupy the spinal canal. However, in certain situations where there is extensive arthritis and stenosis in the upper parts of the lumbar spine, or elsewhere in the cervical and thoracic spine, a patient may develop myelopathy as a result of compression of the spinal cord. This disease is often first detected as difficulty walking due to generalized weakness or problems with balance and coordination. Myelopathy is most commonly caused by spinal stenosis, which is a progressive narrowing of the spinal canal. In the later stages of spinal degeneration, bone spurs and arthritic changes make the space available for the spinal cord within the spinal canal much smaller. The bone spurs may begin to press on the spinal cord and the nerve roots, and that pressure starts to interfere with how the nerves function normally.

16 Radiculopathy/Myelopathy

17 Radiculopathy/Myelopathy
Burning pain along nerve Loss of muscle strength Atrophy Injury

18 Trigeminal Neuralgia Cranial Nerve V Tic douloureux 5TH Decade (V!)
Young age ? MS Multiple Cause Paroxysmal Unilateral Trigger Trigeminal neuralgia (TN), also called tic douloureux, is a chronic pain condition that causes extreme, sporadic, sudden burning or shock-like face pain that lasts anywhere from a few seconds to as long as 2 minutes per episode.  The intensity of pain can be physically and mentally incapacitating. TN pain is typically felt on one side of the jaw or cheek. Episodes can last for days, weeks, or months at a time and then disappear for months or years.  In the days before an episode begins, some patients may experience a tingling or numbing sensation or a somewhat constant and aching pain.  The attacks often worsen over time, with fewer and shorter pain-free periods before they recur.  The intense flashes of pain can be triggered by vibration or contact with the cheek (such as when shaving, washing the face, or applying makeup), brushing teeth, eating, drinking, talking, or being exposed to the wind.  TN occurs most often in people over age 50, but it can occur at any age, and is more common in women than in men.  There is some evidence that the disorder runs in families, perhaps because of an inherited pattern of blood vessel formation. Although sometimes debilitating, the disorder is not life-threatening. The presumed cause of TN is a blood vessel pressing on the trigeminal nerve in the head as it exits the brainstem. TN may be part of the normal aging process but in some cases it is the associated with another disorder, such as multiple sclerosis or other disorders characterized by damage to the myelin sheath that covers certain nerves. Treatment options include medicines such as anticonvulsants and tricyclic antidepressants, surgery, and complementary approaches. Typical analgesics and opioids are not usually helpful in treating the sharp, recurring pain caused by TN.  If medication fails to relieve pain or produces intolerable side effects such as excess fatigue, surgical treatment may be recommended. Several neurosurgical procedures are available. Some are done on an outpatient basis, while others are more complex and require hospitalization. Some patients choose to manage TN using complementary techniques, usually in combination with drug treatment.  These techniques include acupuncture, biofeedback, vitamin therapy, nutritional therapy, and electrical stimulation of the nerves.

19 Bell’s Palsy/Nerve Palsy
Nerve paralysis Facial Nerve (VII) Motor not Sensory Sir Charles Bell Idiopathic Altered Taste Hyper Lacrimation Ideopathic: From an unknown cause. Bell's palsy is a form of temporary facial paralysis resulting from damage or trauma to one of the two facial nerves.  It is the most common cause of facial paralysis. Generally, Bell's palsy affects only one of the paired facial nerves and one side of the face, however, in rare cases, it can affect both sides.  Symptoms of Bell's palsy usually begin suddenly and reach their peak within 48 hours.  Symptoms range in severity from mild weakness to total paralysis and may include twitching, weakness, or paralysis, drooping eyelid or corner of the mouth, drooling, dry eye or mouth, impairment of taste, and excessive tearing in the eye. Bell’s palsy often causes significant facial distortion. Most scientists believe that a viral infection such as viral meningitis or the common cold sore virus -- herpes simplex-- causes the disorder when the facial nerve swells and becomes inflamed in reaction to the infection. There is no cure or standard course of treatment for Bell's palsy. The most important factor in treatment is to eliminate the source of the nerve damage. Some cases are mild and do not require treatment since the symptoms usually subside on their own within 2 weeks. For others, treatment may include medications such as acyclovir -- used to fight viral infections -- combined with an anti-inflammatory drug such as the steroid prednisone -- used to reduce inflammation and swelling. Analgesics such as aspirin, acetaminophen, or ibuprofen may relieve pain, but because of possible drug interactions, patients should always talk to their doctors before taking any over-the-counter medicines. In general, decompression surgery for Bell's palsy -- to relieve pressure on the nerve -- is controversial and is seldom recommended

20 Nerve Palsies Neuropathy “Saturday Night Palsy”
Nerve pressure causing paralysis Sleeping standing up Hours to Months Saturday night palsy, is a colloquial term for radial neuropathy, a type of mononeuropathy. The condition results from acute trauma to the radial nerve that runs the length of the arm. Symptoms vary depending on the severity and location of the trauma; however, common symptoms include wrist drop (the inability to flex the wrist upward when the hand is palm down); numbness of the back of the hand and wrist; and inability to voluntarily straighten the fingers. There are many ways to acquire radial neuropathy. The term Saturday Night Palsy refers to nerve damage that can occur if a drunk person falls asleep with the back of their arms compressed by a bar edge, bench back, or like object. Radial neuropathy is also called honeymooners palsy, since it can be acquired by sitting with an arm draped arm over the back of a neighboring chair (or movie-theater seat) for a long time. Both Saturday night palsy and honeymooners palsy refer to the fact that the nerve damage is generally forewarned by arm pain to a degree that only excessive love or liquor would drive a person to keep their arm in such an uncomfortable position. Breaking the humerus and deep puncture wounds can also cause the condition. Radial neuropathy is not necessarily permanent. However, since nerves regenerate slowly, the effects of the trauma can last for months or years. Transient Paresthesia is yet another term for the condition.

21 EPS EPs=Evoked potentials

22 Testing Neuropathies Electromyography (EMG)
Needles into the muscle Measures muscle action potentials A surface EMG (SEMG) is not accurate Nerve Conduction Velocity (NCV) Usually done at the same time as EMG Evoked potential Basis for EMG, can be auditory, visual In neurophysiology, an evoked potential (or "evoked response") is an electrical potential recorded from a human or animal following presentation of a stimulus, as distinct from spontaneous potentials such as electroencephalograms or electromyograms. Evoked potential amplitudes tend to be low, ranging from less than a microvolt to several microvolts, compared to tens of microvolts for EEG, millivolts for EMG, and often close to a volt for EKG. To resolve these low-amplitude potentials against the background of ongoing EEG, EKG, EMG and other biological signals and ambient noise, signal averaging is usually required. The signal is time-locked to the stimulus and most of the noise occurs randomly, allowing the noise to be averaged out with averaging of repeated responses. Signals can be recorded from cerebral cortex, brainstem, spinal cord and peripheral nerves. Usually the term "evoked potential" is reserved for responses involving either recording from, or stimulation of, central nervous system structures. Thus evoked CMAP (compound motor action potentials) or SNAP (sensory nerve action potentials) as used in NCV (nerve conduction studies) are generally not thought of as evoked potentials, though they do meet the above definition.

23 EMG

24 Treatment for Neuropathies
First treat the underlying cause then symptom management TCAs Muscle relaxants SSRIs Antiseizure meds Vitamin B12 Lidocaine patch Analgesics TENS unit, acupuncture, Biofeedback

25 Headache

26 Headaches Migraines Cluster Headaches Tension Headaches
“Cluster cycle” Tension Headaches “Stress”, muscle tension, neck pain

27 Migraines

28 Migraine Headaches Types Simple or Classic Complex
Hemiplegic Possible Aggravating factors (“triggers”) Stress / Emotion Glare Alcohol Exercise Stimulants: Excess Caffeine, cocaine, amphetamines Foods Analgesic rebound Estrogen Two different categories for headaches: primary and secondary. Primary headache is an actual clinical condition and not a symptom of or caused by another disorder. Primary headaches include migraine, tension-type headache, and cluster headache. Secondary headaches are caused by other medical conditions, such as sinus disease, allergies, dental disorders, head injury, or brain tumors. Simple or Classic Throbbing unilateral pain Associated with N/V, photophobia, and phonophobia Hemiplegic Unilateral sensory and motor deficits (dysarthria, aphasia, ataxia, tinnitus, vertigo, transient global amnesia, confusion, fever) *Neuro events may outlast headache by days/weeks

29 Migraines Trigeminal Nerve Symptoms Several Criteria Recurrent
Photophobia Nausea/Vomiting Aura Recurrent MRI of a Migraine

30 Diagnostic Requirements of Migraine
At least two of the following features: Unilateral location Throbbing character Worsening pain with routine activity Moderate to severe intensity At least one of the following features: Nausea and/or vomiting Photophobia and phonophobia International Headache Society Classification of Headache

31 Acute Migraine Treatment
Ergotamine - Unknown “Abortive” or “rescue” tx Dosage forms – oral, sublingual, rectal, parenteral Contraindications Cardiac disease Peripheral vascular disease Cerebrovascular disease Sepsis Advanced Liver and Kidney disease Pregnancy, Breast Feeding Caffeine Increases intestinal absorption of ergotamine Potentiates vasoconstriction and pain relief when combined with ergotamine and analgesics Adverse effects GI disturbances Nausea Vomiting Anorexia Can’t mix ergotamine & Triptans Triptans-essentially no significant difference between them-all take 2 hours

32 Acute Migraine Treatment- Triptans
Sumatriptan Dosage Forms Subcutaneous injection Oral tablet Nasal Spray Adverse effects Oral - nausea and vomiting, malaise, dizziness Intranasal – bitter, unpleasant taste Subcutaneous Injection - mild pain, redness, rebound HA Drug Interactions Ergot alkaloids Lithium Serotonin-specific reuptake inhibitors Other triptans Monoamine Oxidase Inhibitors - use with these products may precipitate serotonin syndrome

33 Acute Migraine Treatment
Second Generation triptans Eli-, zolma-, nara-, frova- Acute treatment of migraines Comparison to sumatriptan Similar pharmacologic features Improved oral bioavailability Able to cross blood brain barrier Possible reasons for treatment failures Medication administration too late Swallowing Sublingual products Vomiting tablet prior to absorption Rebound headache due to overuse Dehydration/ ketosis/acidosis Analgesic rebound Diagnosis?

34 Intractable migraines
Sumatriptan subcutaneous injection Parenteral form of ergot derivatives IV antiemetic Corticosteroid - oral or parenteral Hydration! Parenteral Narcotic analgesics

35 Migraine Adjunctive therapy
Antiemetics Systemic relief of nausea and vomiting Increased absorption of other medications, prokinetic NSAIDS Not approved by FDA for migraine headache indication Selected NSAIDS effective as abortive therapy Prevention Depakote/Neurontin Beta-blockers/Calcium Channel Blockers Tricyclic antidepressants/SSRIs Abortive Therapy NSAIDs/Ultram Midrin/Butalbital Ergotamine/DHE (Migranol) Triptans (Zomig, Imitrex, Maxalt, Amerge, Exert, Frova, Relpax) *Add Reglan or Compazine for nausea

36 Migraine Prophylactic therapy
Goals Reduces frequency Reduces severity Criteria Headaches that occur twice monthly or more often Disabling headache that occurs less frequently but are unresponsive to usual abortive therapy Abortive agents contraindicated Headaches that occur in unpredictable patterns Prevention Depakote/Neurontin Beta-blockers/Calcium Channel Blockers Tricyclic antidepressants/SSRIs Abortive Therapy NSAIDs/Ultram Midrin/Butalbital Ergotamine/DHE (Migranol) Triptans (Zomig, Imitrex, Maxalt, Amerge, Exert, Frova, Relpax) *Add Reglan or Compazine for nausea

37 Migraine Prophylactic therapy- cont’d.
Topomax Use in low dose of 25 to 50 mg at hs to prevent migrane Valproic Acid 1000mg po q HS prophylaxis Patients with hepatic function impairment may have increased Topiramate plasma concentrations and a dosage adjustments may be needed. Avoid alcohol while taking this drug. Use extra caution if you have any liver or kidney impairment. ( The metabolic breakdown of Topomax will be reduced increasing the duration and intensity of its effects ). Topomax may increase the frequency of kidney stones.

38 Cluster Headaches Gender - males>females
Onset - second and fourth decade of life Intensity of Headache Pain Same side of head, tearing, flush Severe throbbing/stabbing Not preceded by aura Last minutes Recur daily or almost daily for a period of usually 4 to 8 weeks. Increases in intensity within 10 to 15 minutes and lasts for minutes. Attacks may occur one or more times per day and frequently awake the sufferer from sleep. Almost always one sided, and the most common sites of pain are around the eye, temple, and side of the head. Cluster periods typically recur every 1 to 2 years. Rarely is it chronic with no periods of remission.

39 Cluster Headache Abortive Therapy
Oxygen inhalation Ergotamine Fifty-two randomly selected patients diagnosed as having either active episodic or chronic cluster headaches were evaluated for symptomatic response to oxygen inhalation. At the onset of attacks, 100% oxygen was administered through a facial mask at a rate of 7 liters per minute, for 15 minutes. Each patient self-treated ten attacks, and timed the rated reduction of pain. A successful treatment result required complete or almost complete reduction of pain in seven of ten attacks, within 15 minutes.In a second (crossover) trial involving an additional 50 patients, sublingual ergotamine tartrate (ErgomarÒ) was compared to oxygen inhalation for symptomatic relief of cluster attacks. Each patient treated ten attacks with either preparation in accordance with the crossover design. Oxygen was administered as described above. Sublingual ergotamine was used every five minutes, to a maximum of three tablets, if necessary.

40 Tension Type Headaches
Gender - women 88%, males 69% Intensity of headache pain No aura No nausea, vomiting No photophobia

41 Tension Headache Therapy
Abortive- NSAID’s Muscle relaxants Anxiolytics Analgesics Prophylactic Antidepressants Non-drug techniques Massage Hot bath Acupuncture Biofeedback

42 Seizures VFib of the brain Various Reasons Electrical Ischemic
Chemical

43 Seizure Disorders- Pharmacologic Treatment
Optimization of drug therapy Choice of appropriate AED Individualization of dosing Compliance Absence - start in childhood 4-14 lasting 2-20 seconds Tonic-clonic-tonic phase followed by clonic ( sec) with bil jerking cyanosis, hypersalivation, tongue biting, incontinence usually urina post-ictal state, confusion, fatigue atonic - sudden loss of postural tone causing fall

44 Therapeutic endpoints: Patient response
Seizure frequency and severity Presence and severity of symptoms of dose related toxicity

45 Serum drug concentrations
Indications for use Uncontrolled seizures despite greater than average doses Seizure recurrence in a previously controlled patient Documentation of intoxication Assessment of compliance Dose change Assessment of therapy in patients with infrequent seizures When dosage changes are made Interpretation of serum concentrations Laboratory variability Interindividual variability Active metabolites of AED’s may not be measured Binding of serum proteins Therapeutic blood levels useful for: Phenytoin Valproate Carbamazepine Phenobarbital

46 Idiopathic Grand Mal Epilepsy
Drugs Phenytoin (hydantoins) (Dilantin) Valproic Acid=Depakote Carbamazepine (Tegretol) Phenobarbital (barbiturates) Topiramate (Topomax) Duration of therapy Seizure free for 2-5 years or may be lifetime Withdrawal of AED’s Two to three months withdrawal schedule Multiple therapy - each drug tapered separately

47 Complex Partial Seizures with secondary generalization
Carbamazepine (Tegretol) Lamotrigine (Lamictal) Gabapentin (Neurontin) Tiagabine=Gabitril Levatiracetam=Keppra Oxcarbazepine=Trileptal Pregabalin=Lyrica

48 Absence Seizures Valproate when secondary tonic/clonic also Clonazepam

49 Febrile Seizures Fever control Anticipatory management in the future

50 Testing Seizures EEG EEG

51 Circulation Problems Think Vascular

52 CVA/TIA Vascular insult Dyslipidemia Clotting/emboli Risk Factors Age
Family history Smoking Diabetes

53 Two kinds of CVA Hemorrhagic Embolic

54 Hemorrhage

55 Embolic Multiple causes ‘Brain attack’ Destroys nerves
Fat Air Blood ‘Brain attack’ Destroys nerves ‘Cuts the wires’

56 Testing for Vascular Problems
MRA Angiography Ultrasound Magnetic resonance imaging (MRI) is a method of producing extremely detailed pictures of body tissues and organs without the need for x-rays. The electromagnetic energy that is released when exposing a patient to radiofrequency waves in a strong magnetic field is measured and analyzed by a computer, which forms two- or three-dimensional images that may be viewed on a TV monitor. MR angiography (MRA) is an MRI study of the blood vessels. It utilizes MRI technology to detect, diagnose and aid the treatment of heart disorders, stroke, and blood vessel diseases. MRA provides detailed images of blood vessels without using any contrast material, although a special form of contrast material is often given to make the MRI images even clearer. The procedure is painless, and the magnetic field is not known to cause tissue damage of any kind.

57 Consequences of wrong test

58 Medications for embolic CVA
IV tissue plasminogen activator tPA 0.9mg/kg in highly selected cases within 3 hours of ischemic stroke ECASA Dipyridamole-aspirin (Aggrenox) extended release, 200mg/25mg capsule PO BID Clopidogrel (Plavix) 75mg/day Warfarin INR adjusted dose IV tissue plasminogen activator tPA 0.9mg/kg in highly selected cases within 3 hours of ischemic stroke ECASA mg/day Dipyridamole-aspirin (Aggrenox) extended release, 200mg/25mg capsule PO BID Clopidogrel (Plavix) 75mg/day Warfarin INR adjusted dose. For patients with atrial fib and cardioembolic stroke Currently available antiplatelet agents for stroke prophylaxis include aspirin, clopidogrel (Plavix), ticlopidine (Ticlid), - 2.4% develop neutropenia and aspirin-dipyridamole (Aggrenox). Except in patients with special conditions such as atrial fibrillation, anticoagulation has no advantages over antiplatelet therapy and is associated with an increased risk of bleeding Contraindicated in pressence of hematopoietic disorders or hemostatic disorder or conditions associated with active bleeding or severe liver disfunction Unless contraindicated, anticoagulation therapy is appropriate in patients with high-risk cardioembolic conditions.3 These conditions include atrial fibrillation, a known cardioembolic source (confirmed thrombus), or a suspected cardioembolic source (recent large myocardial infarction, mechanical valve, dilated cardiomyopathy, rheumatic mitral valve stenosis). Warfarin can interact with ASA NSAIDS Antibiotics and tranquilizers The rate of stroke recurrence after acute stroke in patients with atrial fibrillation currently is under debate. Reported recurrence rates for the initial weeks vary widely (2.5 to 20 percent).

59 Surgical Measures Carotid endartectomy (CEA) is indicated for stenosis of 70-99% CEA is of modest benefit for carotid stenosis of 50-69% and depends on risk factors No benefit <50% In medically fit patients with non-disabling stroke, carotid endartectomy (CEA) is indicated for stenosis of 70-99% CEA is of modest benefit for carotid stenosis of 50-69% and depends on risk factors. No benefit <50%

60 Risk Factor Management
Blood Pressure 130/80 JNC 7 Starting antihypertensive drug therapy after TIA/Stroke ACE Inhibitors Elevated blood pressure (above 140/90 mm Hg) is the most important treatable risk factor for TIA and stroke Important new guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) require lifestyle modifications (weight reduction, sodium restriction, regular aerobic activity, limited alcohol intake) to prevent cardiovascular disease in prehypertensive patients with a systolic blood pressure of 120 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg Starting Antihypertensive Drug Therapy After a TIA or Stroke. Typically, blood pressure lowers without treatment in the first two weeks after a stroke. Therefore, it is rational to wait two weeks before continuing or beginning antihypertensive drug therapy. Angiotensin-Converting Enzyme (ACE) Inhibitors. Increased attention is being directed at ACE inhibitors because of the results of the recent Heart Outcomes Prevention Evaluation (HOPE) study. Over four years, the relative reduction in the risk of stroke was 32% in persons given an ACE inhibitor. (Debate currently centers on whether the HOPE study findings were unique to ACE inhibitors as a class or occurred because of a more general blood pressure-lowering effect that also could be obtained with other antihypertensive drug classes )

61 Risk Factor Management
SMOKING “the risk of stroke in persons of either sex and all ages was 50 percent higher in smokers than in nonsmokers” Smoking cessation

62 Risk Factor Management
Blood lipid levels Statin Diabetes mellitus Increases the overall risk by 25 to 50% Antiplatelet therapy clopidogrel (Plavix), ticlopidine (Ticlid), and aspirin-dipyridamole (Aggrenox) Aspirin 50-325mg/day Recent data indicate that in patients with CHD, treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) results in a 30 to 32 percent reduction of the stroke risk increases the overall risk of stroke by approximately 25 to 50 percent There is no conclusive evidence that "tight" glucose control results in a reduction of ischemic stroke or other macrovascular events. Currently available antiplatelet agents for stroke prophylaxis include aspirin, clopidogrel (Plavix), ticlopidine (Ticlid), - 2.4% develop neutropenia and aspirin-dipyridamole (Aggrenox). Except in patients with special conditions such as atrial fibrillation, anticoagulation has no advantages over antiplatelet therapy and is associated with an increased risk of bleeding Contraindicated in pressence of hematopoietic disorders or hemostatic disorder or conditions associated with active bleeding or severe liver disfunction Aspirin is the most widely used and most economical antiplatelet agent. Aspirin therapy after a stroke or TIA reduces the long-term relative risk of stroke and increases the chance of a full recovery.26 The optimal aspirin dosage for use in the prevention of stroke or TIA remains controversial, but a range of 50 to 325 mg per day has been recommended. ECASA for peptic ulcer disease, hypersensitivity, or bronchospastic reaction. May potentiate sulfonylurea, hypoglcemic agents In patients who are taking an antiplatelet agent (most often, aspirin), the annual rate of recurrent stroke is estimated to be about 8 percent (range: 4 to 14 percent).30

63 Degenerative Disease Think progressive

64 Parkinsons Reduction of Dopamine production Causes resting tremors DA

65 Dopamine/Acetylcholine
The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. It is a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans. Acetylcholine is the neurotransmitter in all autonomic ganglia. Acetylcholine is an ester of acetic acid and choline with chemical formula CH3COOCH2CH2N+(CH3)3. This structure is reflected in the systematic name, 2-(acetyloxy)-N,N,N-trimethylethanaminium. Acetylcholine (ACh) was first identified in 1914 by Henry Hallett Dale for its actions on heart tissue. It was confirmed as a neurotransmitter by Otto Loewi who initially gave it the name vagusstoff because it was released from the vagus nerve. Both received the 1936 Nobel Prize in Physiology or Medicine for their work. Later work showed that when acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens voltage gated sodium channels in the membrane. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine, while inducing contraction of skeletal muscles, instead induces decreased contraction in cardiac muscle fibers. This distinction is attributed to differences in receptor structure between skeletal and cardiac fibers. Acetylcholine is also used in the brain, where it tends to cause excitatory actions. The glands that receive impulses from the parasympathetic part of the autonomic nervous system are also stimulated in the same way.

66 Testing for Parkinson’s
There are not lab tests to definitively diagnose Parkinson's disease. A systematic neurological exam will include testing reflexes and observing things like muscle strength throughout the body, coordination, balance, and other details of movement. Blood tests, urine tests, CT scans, or MRI scans may also be done. Although none of these tests actually diagnose Parkinson's disease, they may reveal the presence of some other conditions that could be responsible for the symptoms. MRI may reveal structural changes in the substantia nigra.

67 Parkinson’s Symptoms Symptom spectrum Bradykinesia/ akinesia
Rest tremor Mask facies Progressive dementia Depression (functional?) Parkinson's disease is a chronic neurological condition named after Dr. James Parkinson, who first identified and described the syndrome in The disease progresses slowly, affecting a small area of cells in the mid-brain known as the substantia nigra. Degeneration of these cells causes a reduction in the chemical called dopamine, and this reduction results in the signs and symptoms of Parkinson's disease. Resting tremor- “pill rolling” Involves pronation-supination of forearm or flexion-extension at elbow Dampens when hands are in motion & during sleep Worse with stress What causes Parkinson's disease? It is caused by the progressive loss of brain cells (neurones) in a part of the brain called the substantia nigra, which produces the chemical dopamine. As the cells die, less dopamine is produced and transported to the striatum, the area of the brain that co-ordinates movement. Symptoms develop as neurones die off and dopamine levels drop. Research suggests Parkinson's sufferers may also lack other brain chemicals including serotonin (linked to mood), noradrenaline (linked to blood pressure control) and acetylcholine (linked to mental state).

68 Parkinson’s Disease Non-pharmacologic Interventions
Exercise Physical activity Nutrition Psychologic support

69 Parkinson’s Pharmacologic Interventions: Dopamine Agonists
Amantadine Mechanism of action ? ↑ dopamine release from presynaptic nerve terminals Initiation of therapy Twice daily, Morning and lunch Adverse effects Anticholinergic Gastrointestinal Cardiovascular CNS Mild elevations of BUN and alkaline phosphatase Monitoring Parameters GI and CNS complaints BUN, Cr every 3 months Amantadine (a-MAN-ta-deen) is an antiviral. It is used to prevent or treat certain influenza (flu) infections (type A). Amantadine also is an antidyskinetic. It is used to treat Parkinson's disease, sometimes called paralysis agitans or shaking palsy. It may be given alone or with other medicines for Parkinson's disease. By improving muscle control and reducing stiffness, this medicine allows more normal movements of the body as the disease symptoms are reduced. Amantadine is also used to treat stiffness and shaking caused by certain medicines used to treat nervous, mental, and emotional conditions. Do not suddenly stop taking this medicine without first checking with your doctor since your Parkinson's disease may get worse very quickly. Your doctor may want you to reduce your dose gradually before stopping the medicine completely May also potentiate the anticholinergic s/e of dry mouth, etc. For the treatment of Parkinson's disease or movement problems: Older adults—100 milligrams once a day to start. The dose may be increased slowly over time, if needed. Adults—100 milligrams one or two times a day. Your doctor may increase this dose, if needed Other medical problems—The presence of other medical problems may affect the use of amantadine. Make sure you tell your doctor if you have any other medical problems, especially: Eczema (recurring)—Amantadine may cause or worsen eczema Epilepsy or other seizure disorder (history of)—Amantadine may increase the frequency of convulsions (seizures) in patients with a seizure disorder Heart disease or other circulation problems or Swelling of feet and ankles—Amantadine may increase the chance of swelling of the feet and ankles, and may worsen heart disease or circulation problems Kidney disease—Amantadine is removed from the body by the kidneys; patients with kidney disease will need to receive a lower dose of amantadine Mental or emotional illness—Higher doses of amantadine may cause confusion, hallucinations, and nightmares Substance abuse (drug or alcohol abuse), history of—The chance of side effects from this medicine may be increased

70 Parkinson’s- cont’d. Dopamine agonists- besides amantidine
Pramipexole (Mirapex) Bromocriptine (Parlodel) Pergolide (Permax) Ropinirole (Requip) Monoamine Oxidase-B Inhibitors: Selegiline (Eldepryl)) Antioxidant Therapy- questionable efficacy Levodopa combined with a peripheral dopa-decarboxylase inhibitor (DCI) has been considered the therapy of choice for Parkinson's disease (PD). Levodopa is nearly always effective, but has a high incidence of adverse effects with long term use, including response fluctuations (on/off phenomena) and dyskinesias. Dopaminergic agonists, acting directly at the receptor level, would be able to decrease the incidence of these motor complications.In progressive neurodegenerative diseases, such as PD, modification of the rate of disease progression (often referred to as neuroprotection) is currently a highly debated topic. Increased oxidative stress is thought to be involved in nigral cell death, that is characteristic of PD. This oxidative stress may be further exacerbated by levodopa therapy. These mechanisms have been proven in vitro and animal models, but it's relevance in humans remains speculative.Based on the considerations above, the emerging therapeutic strategies for PD advocate early use of dopamine agonists in the treatment of PD. A number of recent well-controlled studies have proven the efficacy of dopamine agonists used as monotherapy. Moreover, as predicted by animal studies, on the long term, dopaminergic agonists induce significantly less motor complications than levodopa.In the last 2years, three new dopamine agonists have been launched, including ropinirole, pramipexole and cabergoline. These new agonists have been added, as therapeutical options to well-established drugs, like pergolide, bromocriptine or talipexole. The recently launched compounds have proven efficacy in monotherapy and as adjunctive therapy to levodopa. Pergolide has proven to be a superior drug to bromocriptine as adjunctive therapy to levodopa in a significant number of studies and is considered the gold standard dopamine agonist.

71 Symptoms Associated with Serotonin Syndrome
Mental status changes Confusion (51%) Agitation (34%) Hypomania (21%) Anxiety (15%) Coma (29%) Cardiovascular Sinus tachycardia (36%) Hypertension (35%) Hypotension (15%) Gastrointestinal Nausea (23%) Diarrhea (8%) Abdominal pain (4%) Salivation (2%) References 2, 4 Motor Abnormalities Myoclonus (58%) Hyperreflexia (52%) Muscle rigidity (51%) Restlessness (48%) Tremor (43%) Ataxia/incoordination (40%) Shivering (26%) Nystagmus (15%) Seizures (12%) Other Diaphoresis (45%) Unreactive pupils (20%) Tachypnea (26%) Hyperpyrexia (45%) (Nolan, 2005)

72 Anticholinergics Mechanism of action Aids treatment of tremor Drugs
Blocks excitatory neurotransmitter Ach in substantia nigra Aids treatment of tremor less effective than levodopa/carbidopa or dopamine agonists Drugs trihexyphenidyl (Artane) benztropine (Cogentin) Adverse effects Increased intraocular pressure Confusion Impairment of recent memory Hallucinations Delusions Dry mouth Blurred vision Constipation Urinary retention ACH = acetylcholine Anticholinergics were the first drugs available for the symptomatic treatment of Parkinson's disease and they are still widely used today, both as monotherapy and as part of combination regimes. They are commonly believed to be associated with a less favourable side effect profile than other antiparkinsonian drugs, in particular with respect to neuropsychiatric and cognitive adverse events. They have been claimed to exert a better effect on tremor than on other parkinsonian features.

73 Parkinson’s Tremor Symptoms may be controllable with Benadryl
Dopamine Precursors (Levodopa - Sinemet – Stalevo) Initiation of therapy E.g. sinemet 10/100 t.i.d., increase q 2-3 days as tol Adverse effects Dyskinesias Mental changes Levodopa Drug interactions Neuroleptic drugs – (Phenothiazine, Prochlorperazine, Fluphenazine, Chlorpromazine) Butyrophenones: Haloperidol Antihypertensives – (Reserpine and Methyldopa) MAOi’s- serotonin syndrome Other: Metoclopramide, Pyridoxine, Ferrous sulfate, Phenytoin, Benzodiazepines How does it work? This medicine contains the active ingredients levodopa and carbidopa, sometimes known in combination as co-careldopa. It is used in Parkinson’s disease to increase the levels of dopamine in the brain. Dopamine is a substance known as a neurotransmitter. Neurotransmitters are present in the brain and nervous system and are involved in transmitting messages between nerves. These messages allow the normal functioning of the body. The neurotransmitter dopamine is known to be reduced or absent in the brains of people with Parkinson's disease, and this is thought to be the cause of the disease symptoms. When you take levodopa, it is converted into dopamine in the brain. This replaces the lost dopamine and therefore reduces some of the symptoms of the disease. Unfortunately, levodopa is also converted into dopamine in the rest of the body, which can cause unwanted side effects such as nausea and palpitations. Carbidopa is used in combination with the levodopa to prevent this happening. It blocks the conversion of levodopa to dopamine in the body and so prevents these side effects. (Carbidopa cannot pass into the brain and so does not affect the conversion of levodopa to dopamine in the brain.)

74 Adjunctive Treatment of Parkinsonian Tremor
B-adrenergic blockers Clozapine Surgery Deep brain stimulation Potential dietary/nutritional interactions Tryptophan, tyramine, melatonin Beta-adrenergic blockers block the release of epinephrine in the body Clozapine: an atypical antipsychotic drug that blocks some of the dopamine receptors, allowing for more balance. Used for both tremor and parkinson’s psychosis. Pallidotomy-the lesioning of a portion of the globus pallidus. * Can influence nigrostriatal degeneration

75 Multiple Sclerosis Demyelination Energy Diffusion Reduced conduction
Nerve degeneration

76

77 Types of MS Relapsing-remitting (80%) Secondary progressive
Periods of relapse, when symptoms flare up Periods of remission, when symptoms improve Secondary progressive Develops from Relapsing/Remitting shorter periods of remission and worse symptoms during relapses. 50% to the secondary progressive stage in first 10 years Primary progressive (3 in 20) no periods of remission This causes increasing disability, and can reduce life expectancy

78 MS Testing MRI Brain and spinal cord Lumbar Puncture EMG Studies
Remember MS is CNS White matter “Demyelination” Lumbar Puncture WBCs, Antibodies EMG Studies

79 MS Treatment Options - General Considerations
Exercise Appropriate exercise program is beneficial Simple exercises such as normal walking, swimming, using exercise bike strongly advise against overheating (saunas, hot tubs, sunbathing, etc.) to prevent declines in neurologic function. Exercising in a cool, well aerated environment is strongly encouraged.

80 MS Treatment Cont. Physical Therapy
PT/OT including ankle braces and devices that provide assistance with walking, personalized exercise program and counseling on work and daily activities.

81 Nutrition MS Society recommends low fat, low cholesterol diet Obese patients appear to lose any reserve muscle strength they may have left because of their weight. Some patients with medullary lesions and difficulty swallowing may require feeding tubes to prevent aspiration and resulting pneumonia.

82 Treatment of Infections and Elevated Body Temperatures
Increased body temperature may lead to transient increase in neurologic symptoms or even precipitate exacerbation. If a fever is due to an infection, infection needs to be identified and treated, and antipyretics need to be administered. UTI’s are common

83 Treatment of Relapses Solu-Medrol (Methylprednisone) is often used for treatment of severe exacerbations. Typical doses range from 500 to 1000 mg/day for 3 to 5 days

84 Prevention of Relapses
recombinant interferon-ß's Betaseron Avonex Copaxone Rebif

85 Treatment Options - Symptomatic Therapy
Fatigue Vertigo Spasticity and Muscle Spasms Psychological Problems Urinary Dysfunction Sexual Problems Tremor and Incoordination Pain Cognitive Dysfunction

86 Huntington’s Disease Degenerative Disease of the Brain
Tremors Progressive dementia Genetic Inheritance 5 in 100,000 cases Diagnosed at symptom onset Usually after 30 Usually after children are born

87 Compare…

88 Testing Huntington’s Disease
CT/MRI (Specific finding) loss of a normally convex bulge of the caudate nucleus into the lateral ventricles Enlarged lateral ventricles Labs Genetic testing

89 Think Multi-causal degeneration
Dementia Think Multi-causal degeneration

90 DR SEUSS ON AGING I cannot see    I cannot pee    I cannot chew    I cannot screw    Oh, my God, what can I do?    My memory shrinks    My hearing stinks    No sense of smell    I look like hell    My mood is bad -- can you tell?    My body's drooping    Have trouble pooping    The Golden Years have come at last    The Golden Years can kiss my ass

91 Overview of Dementia Population is aging Dementia increases with age
Amnesia Isolated memory loss may be the first sign of dementia Delirium is a deficit of attention

92 Diagnostic Criteria for Dementia
Impaired social or occupational function Impaired memory + 1 or more changes in: Abstract/problem solving Judgment Language Personality

93 Depression vs. Dementia
Fast onset Depressed before demented Patient complains more than family Dementia very slow onset Demented then depressed Patient denies

94 Depression vs. Dementia
Appears depressed Response of "I don't know" Inconsistent Cognitive impairment antidepressant works Dementia May not appear depressed Tries to answer Consistent Cognitive impairment Antidepressant may not work

95 Causes of Dementia Alzheimer's disease
Most common cause in the elderly Incidence: 123.3 new cases/100,000 population/ year Prevalence: 10% over age 65, 47% over age 84

96 “Probable” Alzheimer's Dementia
Abnormal clinical exam Abnormal Mini Mental status Exam Deficits in 2 or more areas of cognition Progressive decline No disturbance of consciousness Absence of other cause

97 PET Scan NORMAL ALZHEIMERS DISEASE

98 MMSE - The Clock (1:45)

99 Risk Factors for Alzheimer's
Family History of Alzheimer's disease APO Genotype Aging and estrogen deficiency Head injury Low education Apo E genotype is a blood test that looks for a particular form of the apolipoprotein E (apo E) gene. Researchers have linked this gene to late-onset Alzheimer's disease. The apo E gene has several different forms, most commonly e2, e3 and e4. Studies indicate that the presence of apo E e4 may increase the risk of Alzheimer's. About 35 percent to 50 percent of all people with late-onset Alzheimer's have this gene. Most Alzheimer's specialists don't recommend routine apo E testing because the test has limited predictive value. In other words, if you have this gene, you're at increased risk of Alzheimer's but still may not develop the disease. Likewise, if you don't have this gene, you may still develop Alzheimer's. Apo E isn't a diagnostic or screening test for Alzheimer's. It's a risk factor — and currently used only to help confirm a diagnosis of Alzheimer's in adults with other symptoms. At this time, Alzheimer's isn't preventable. If preventive treatment becomes available, the usefulness of this test may become more clear.

100 Brain Iron Distribution
Dementia Normal

101 Psychotic & Affective disturbance
Delusions: (false beliefs) 30-70% of patients (Usually simple delusions Hallucinations Not common. If present usually visual. Depression very common, difficult to diagnose. Suicide is rare. Severe depression more in vascular dementia.

102 Behavior problems Personality change: Anxiety: Aggression: Wandering
apathetic or more impulsive Anxiety: apprehension over upcoming events Aggression: physical or verbal Wandering Screaming Sleep disruption & “Sundowning”: very common

103 Multi-infarct Dementia
Abrupt onset with stepwise deterioration Fluctuating course: improvement between strokes Relative preservation of personality  Nocturnal confusion    Depression and Somatic complaints Emotional incontinence Cardiovascular Hx/Signs History of hypertension Evidence of atherosclerosis (PVD, MI) Focal Neurological symptoms (TIA) Focal neurological sign

104 Normal Pressure Hydrocephalus
3 main symptoms: Dementia, Gait Apraxia, Incontinence Language functions preserved Most common cause of gait abnormality plus Dementia is multiinfarct dementia Progressive (months-years) with plateau MRI shows large ventricles LP may result in temporary improvement Treatment is VP or LP shunt

105 HIV dementia Younger patient Memory loss
Frontal lobe dysfunction, personality change, social withdraw Progresses over months Sometimes initial symptoms of AIDS May have other brain infection/tumor

106 Other causes of Dementia
Toxic/Metabolic/Nutritional: Alcohol or drugs Vitamin deficiencies Hormonal disturbances Primary progressive Aphasia: progressive aphasia without true dementia Jacob Creutzfeld Disease: progressive dementia with seizures, myoclonus, ataxia, visual disturbance, motor neuron dysfunction

107 Other Dementias Chronic infections, vasculitis:
Cryptococcal, fungal. Progressive multifocal leukoencephalopathy Bilateral Subdural hematoma Brain tumor: especially frontal glioma Neurodegenerative Disorders Parkinson's disease Lewy body dementia Progressive supranuclear palsy Frontotemporal dementias (e.g., Pick's disease, primary progressive aphasias) Cortical-basal degeneration Hippocampal sclerosis Dementia with Lewy bodies (DLB) is one of the most common types of progressive dementia. The central feature of DLB is progressive cognitive decline, combined with three additional defining features:  (1) pronounced “fluctuations” in alertness and attention, such as frequent drowsiness, lethargy, lengthy periods of time spent staring into space, or disorganized speech; (2) recurrent visual hallucinations,  and (3) parkinsonian motor symptoms, such as rigidity and the loss of spontaneous movement.   People may also suffer from depression.  The symptoms of DLB are caused by the build-up of Lewy bodies – accumulated bits of alpha-synuclein protein -- inside the nuclei of neurons in areas of the brain that control particular aspects of memory and motor control.  Researchers don’t know exactly why alpha-synuclein accumulates into Lewy bodies or how Lewy bodies cause the symptoms of DLB, but they do know that alpha-synuclein accumulation is also linked to Parkinson's disease, multiple system atrophy, and several other disorders, which are referred to as the "synucleinopathies." The similarity of symptoms between DLB and Parkinson’s disease, and between DLB and Alzheimer’s disease, can often make it difficult for a doctor to make a definitive diagnosis. In addition, Lewy bodies are often also found in the brains of people with Parkinson's and Alzheimer’s diseases.  These findings suggest that either DLB is related to these other causes of dementia or that an individual can have both diseases at the same time.  DLB usually occurs sporadically, in people with no known family history of the disease. However, rare familial cases have occasionally been reported. Pick's Disease causes a slow shrinking of brain cells due to excess protein build-up. Patients initially exhibit marked personality and behavioral changes, and a decline in the ability to speak coherently

108 Infections Think bug!

109 Meningitis/Encephalitis
Inflammatory process Driven by foreign invaders (usually) Fungal, Bacterial, Viral, or Parasitic Symptoms Caused by increased pressure/edema Pressure on nerve fibers Temperature changes

110 Strep Pneumo Meningitis

111 Testing for Meningitis
Lumbar Puncture Clinical Exam Labs/Blood cultures


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