2 Symptom Overview Headache Dizziness and vertigo Confusion Memory/mental status changesParesthesiaTremors
3 Common Symptoms Headache Dizziness and vertigo Inflammation/ConstrictionDizziness and vertigoIrritationConfusion/memory/mental status changesExecutive FunctionParesthesiaNerve InhibitionTremorsNerve Excitation
8 Nerve FibersAn 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.
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 neuropathiesSmall 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 sheathDamage at the motor neuron or dorsal root ganglion is often incompleteDamage 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
14 Results of Neuropathy Pain Parathesia Hyperasthesia Paralysis Burning NumbnessHyperasthesiaSensitivityParalysisLoss of movement
15 Various Neuropathy Conditions Back painRadiculopathySciaticaMyelopathyNeuralgia/ParathesiaTrigeminalPalsy (Bell’s, Ulnar)Migraine (?)DegenerativeMultiple SclerosisAmyotrophic Lateral SclerosisMyelopathy 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.
17 Radiculopathy/Myelopathy Burning pain along nerveLoss of muscle strengthAtrophyInjury
18 Trigeminal Neuralgia Cranial Nerve V Tic douloureux 5TH Decade (V!) Young age ? MSMultiple CauseParoxysmalUnilateralTriggerTrigeminal 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 paralysisFacial Nerve (VII)Motor not SensorySir Charles BellIdiopathicAltered TasteHyper LacrimationIdeopathic: 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 paralysisSleeping standing upHours to MonthsSaturday 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.
22 Testing Neuropathies Electromyography (EMG) Needles into the muscleMeasures muscle action potentialsA surface EMG (SEMG) is not accurateNerve Conduction Velocity (NCV)Usually done at the same time as EMGEvoked potentialBasis for EMG, can be auditory, visualIn 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.
28 Migraine Headaches Types Simple or Classic Complex HemiplegicPossible Aggravating factors (“triggers”)Stress / EmotionGlareAlcoholExerciseStimulants: Excess Caffeine, cocaine, amphetaminesFoodsAnalgesic reboundEstrogenTwo 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 ClassicThrobbing unilateral painAssociated with N/V, photophobia, and phonophobiaHemiplegicUnilateral 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 PhotophobiaNausea/VomitingAuraRecurrentMRI of a Migraine
30 Diagnostic Requirements of Migraine At least two of the following features:Unilateral locationThrobbing characterWorsening pain with routine activityModerate to severe intensityAt least one of the following features:Nausea and/or vomitingPhotophobia and phonophobiaInternational Headache Society Classification of Headache
31 Acute Migraine Treatment Ergotamine- Unknown“Abortive” or “rescue” txDosage forms – oral, sublingual, rectal, parenteralContraindicationsCardiac diseasePeripheral vascular diseaseCerebrovascular diseaseSepsisAdvanced Liver and Kidney diseasePregnancy, Breast FeedingCaffeineIncreases intestinal absorption of ergotaminePotentiates vasoconstriction and pain relief when combined with ergotamine and analgesicsAdverse effectsGI disturbancesNauseaVomitingAnorexiaCan’t mix ergotamine & TriptansTriptans-essentially no significant difference between them-all take 2 hours
32 Acute Migraine Treatment- Triptans SumatriptanDosage FormsSubcutaneous injectionOral tabletNasal SprayAdverse effectsOral - nausea and vomiting, malaise, dizzinessIntranasal – bitter, unpleasant tasteSubcutaneous Injection - mild pain, redness, rebound HADrug InteractionsErgot alkaloidsLithiumSerotonin-specific reuptake inhibitorsOther triptansMonoamine Oxidase Inhibitors - use with these products may precipitate serotonin syndrome
33 Acute Migraine Treatment Second Generation triptansEli-, zolma-, nara-, frova-Acute treatment of migrainesComparison to sumatriptanSimilar pharmacologic featuresImproved oral bioavailabilityAble to cross blood brain barrierPossible reasons for treatment failuresMedication administration too lateSwallowing Sublingual productsVomiting tablet prior to absorptionRebound headache due to overuseDehydration/ ketosis/acidosisAnalgesic reboundDiagnosis?
34 Intractable migraines Sumatriptan subcutaneous injectionParenteral form of ergot derivativesIV antiemeticCorticosteroid - oral or parenteralHydration!Parenteral Narcotic analgesics
35 Migraine Adjunctive therapy AntiemeticsSystemic relief of nausea and vomitingIncreased absorption of other medications, prokineticNSAIDSNot approved by FDA for migraine headache indicationSelected NSAIDS effective as abortive therapyPreventionDepakote/NeurontinBeta-blockers/Calcium Channel BlockersTricyclic antidepressants/SSRIsAbortive TherapyNSAIDs/UltramMidrin/ButalbitalErgotamine/DHE (Migranol)Triptans (Zomig, Imitrex, Maxalt, Amerge, Exert, Frova, Relpax)*Add Reglan or Compazine for nausea
36 Migraine Prophylactic therapy GoalsReduces frequencyReduces severityCriteriaHeadaches that occur twice monthly or more oftenDisabling headache that occurs less frequently but are unresponsive to usual abortive therapyAbortive agents contraindicatedHeadaches that occur in unpredictable patternsPreventionDepakote/NeurontinBeta-blockers/Calcium Channel BlockersTricyclic antidepressants/SSRIsAbortive TherapyNSAIDs/UltramMidrin/ButalbitalErgotamine/DHE (Migranol)Triptans (Zomig, Imitrex, Maxalt, Amerge, Exert, Frova, Relpax)*Add Reglan or Compazine for nausea
37 Migraine Prophylactic therapy- cont’d. TopomaxUse in low dose of 25 to 50 mg at hs to prevent migraneValproic Acid1000mg po q HS prophylaxisPatients 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 lifeIntensity of Headache PainSame side of head, tearing, flushSevere throbbing/stabbingNot preceded by auraLast minutesRecur 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 inhalationErgotamineFifty-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 painNo auraNo nausea, vomitingNo photophobia
42 Seizures VFib of the brain Various Reasons Electrical Ischemic Chemical
43 Seizure Disorders- Pharmacologic Treatment Optimization of drug therapyChoice of appropriate AEDIndividualization of dosingComplianceAbsence - start in childhood 4-14 lasting 2-20 secondsTonic-clonic-tonic phase followed by clonic ( sec) with bil jerkingcyanosis, hypersalivation, tongue biting, incontinence usually urinapost-ictal state, confusion, fatigueatonic - sudden loss of postural tone causing fall
44 Therapeutic endpoints: Patient response Seizure frequency and severityPresence and severity of symptoms of dose related toxicity
45 Serum drug concentrations Indications for useUncontrolled seizures despite greater than average dosesSeizure recurrence in a previously controlled patientDocumentation of intoxicationAssessment of complianceDose changeAssessment of therapy in patients with infrequent seizuresWhen dosage changes are madeInterpretation of serum concentrationsLaboratory variabilityInterindividual variabilityActive metabolites of AED’s may not be measuredBinding of serum proteinsTherapeutic blood levels useful for:PhenytoinValproateCarbamazepinePhenobarbital
46 Idiopathic Grand Mal Epilepsy DrugsPhenytoin (hydantoins) (Dilantin)Valproic Acid=DepakoteCarbamazepine (Tegretol)Phenobarbital (barbiturates)Topiramate (Topomax)Duration of therapySeizure free for 2-5 years or may be lifetimeWithdrawal of AED’sTwo to three months withdrawal scheduleMultiple therapy - each drug tapered separately
56 Testing for Vascular Problems MRAAngiographyUltrasoundMagnetic 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.
58 Medications for embolic CVA IV tissue plasminogen activator tPA 0.9mg/kg in highly selected cases within 3 hours of ischemic strokeECASADipyridamole-aspirin (Aggrenox) extended release, 200mg/25mg capsule PO BIDClopidogrel (Plavix) 75mg/dayWarfarin INR adjusted doseIV tissue plasminogen activator tPA 0.9mg/kg in highly selected cases within 3 hours of ischemic strokeECASA mg/dayDipyridamole-aspirin (Aggrenox) extended release, 200mg/25mg capsule PO BIDClopidogrel (Plavix) 75mg/dayWarfarin INR adjusted dose. For patients with atrial fib and cardioembolic strokeCurrently 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 bleedingContraindicated in pressence of hematopoietic disorders or hemostatic disorder or conditions associated with active bleeding or severe liver disfunctionUnless 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 tranquilizersThe 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 MeasuresCarotid endartectomy (CEA) is indicated for stenosis of 70-99%CEA is of modest benefit for carotid stenosis of 50-69% and depends on risk factorsNo 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 Pressure130/80JNC 7Starting antihypertensive drug therapy after TIA/StrokeACE InhibitorsElevated blood pressure (above 140/90 mm Hg) is the most important treatable risk factor for TIA and strokeImportant 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 HgStarting 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 levelsStatinDiabetes mellitusIncreases the overall risk by 25 to 50%Antiplatelet therapyclopidogrel (Plavix), ticlopidine (Ticlid), and aspirin-dipyridamole (Aggrenox)Aspirin50-325mg/dayRecent 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 riskincreases the overall risk of stroke by approximately 25 to 50 percentThere 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 bleedingContraindicated in pressence of hematopoietic disorders or hemostatic disorder or conditions associated with active bleeding or severe liver disfunctionAspirin 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 agentsIn 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
64 ParkinsonsReduction of Dopamine productionCauses resting tremorsDA
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 tremorMask faciesProgressive dementiaDepression (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 elbowDampens when hands are in motion & during sleepWorse with stressWhat 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 ExercisePhysical activityNutritionPsychologic support
69 Parkinson’s Pharmacologic Interventions: Dopamine Agonists AmantadineMechanism of action ?↑ dopamine release from presynaptic nerve terminalsInitiation of therapyTwice daily, Morning and lunchAdverse effectsAnticholinergicGastrointestinalCardiovascularCNSMild elevations of BUN and alkaline phosphataseMonitoring ParametersGI and CNS complaintsBUN, Cr every 3 monthsAmantadine (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 completelyMay 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 neededOther 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 eczemaEpilepsy or other seizure disorder (history of)—Amantadine may increase the frequency of convulsions (seizures) in patients with a seizure disorderHeart disease or other circulation problems orSwelling of feet and ankles—Amantadine may increase the chance of swelling of the feet and ankles, and may worsen heart disease or circulation problemsKidney disease—Amantadine is removed from the body by the kidneys; patients with kidney disease will need to receive a lower dose of amantadineMental or emotional illness—Higher doses of amantadine may cause confusion, hallucinations, and nightmaresSubstance 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 efficacyLevodopa 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.
72 Anticholinergics Mechanism of action Aids treatment of tremor Drugs Blocks excitatory neurotransmitter Ach in substantia nigraAids treatment of tremorless effective than levodopa/carbidopa or dopamine agonistsDrugstrihexyphenidyl (Artane)benztropine (Cogentin)Adverse effectsIncreased intraocular pressureConfusionImpairment of recent memoryHallucinationsDelusionsDry mouthBlurred visionConstipationUrinary retentionACH = acetylcholineAnticholinergics 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 therapyE.g. sinemet 10/100 t.i.d., increase q 2-3 days as tolAdverse effectsDyskinesiasMental changesLevodopa Drug interactionsNeuroleptic drugs – (Phenothiazine, Prochlorperazine, Fluphenazine, Chlorpromazine)Butyrophenones: HaloperidolAntihypertensives – (Reserpine and Methyldopa)MAOi’s- serotonin syndromeOther: Metoclopramide, Pyridoxine, Ferrous sulfate, Phenytoin, BenzodiazepinesHow 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 blockersClozapineSurgeryDeep brain stimulationPotential dietary/nutritional interactionsTryptophan, tyramine, melatoninBeta-adrenergic blockers block the release of epinephrine in the bodyClozapine: 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
77 Types of MS Relapsing-remitting (80%) Secondary progressive Periods of relapse, when symptoms flare upPeriods of remission, when symptoms improveSecondary progressiveDevelops from Relapsing/Remittingshorter periods of remission and worse symptoms during relapses.50% to the secondary progressive stage in first 10 yearsPrimary progressive (3 in 20)no periods of remissionThis causes increasing disability, and can reduce life expectancy
78 MS Testing MRI Brain and spinal cord Lumbar Puncture EMG Studies Remember MS is CNSWhite matter “Demyelination”Lumbar PunctureWBCs, AntibodiesEMG Studies
79 MS Treatment Options - General Considerations ExerciseAppropriate exercise program is beneficialSimple exercises such as normal walking, swimming, using exercise bikestrongly 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 NutritionMS Society recommends low fat, low cholesterol dietObese 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 RelapsesSolu-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'sBetaseronAvonexCopaxoneRebif
85 Treatment Options - Symptomatic Therapy FatigueVertigoSpasticity and Muscle SpasmsPsychological ProblemsUrinary DysfunctionSexual ProblemsTremor and IncoordinationPainCognitive Dysfunction
86 Huntington’s Disease Degenerative Disease of the Brain TremorsProgressive dementiaGenetic Inheritance5 in 100,000 casesDiagnosed at symptom onsetUsually after 30Usually after children are born
90 DR SEUSS ON AGINGI 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 AmnesiaIsolated memory lossmay be the first sign of dementiaDelirium is a deficit of attention
92 Diagnostic Criteria for Dementia Impaired social or occupational functionImpaired memory + 1 or more changes in:Abstract/problem solvingJudgmentLanguagePersonality
93 Depression vs. Dementia Fast onsetDepressed before dementedPatient complains more than familyDementiavery slow onsetDemented then depressedPatient denies
94 Depression vs. Dementia Appears depressedResponse of "I don't know"Inconsistent Cognitive impairmentantidepressant worksDementiaMay not appear depressedTries to answerConsistent Cognitive impairmentAntidepressant may not work
95 Causes of Dementia Alzheimer's disease Most common cause in the elderlyIncidence:123.3 new cases/100,000 population/ yearPrevalence:10% over age 65, 47% over age 84
96 “Probable” Alzheimer's Dementia Abnormal clinical examAbnormal Mini Mental status ExamDeficits in 2 or more areas of cognitionProgressive declineNo disturbance of consciousnessAbsence of other cause
99 Risk Factors for Alzheimer's Family History of Alzheimer's diseaseAPO GenotypeAging and estrogen deficiencyHead injuryLow educationApo 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.
101 Psychotic & Affective disturbance Delusions: (false beliefs)30-70% of patients (Usually simple delusionsHallucinationsNot common. If present usually visual.Depressionvery common, difficult to diagnose.Suicide is rare.Severe depression more in vascular dementia.
102 Behavior problems Personality change: Anxiety: Aggression: Wandering apathetic or more impulsiveAnxiety:apprehension over upcoming eventsAggression:physical or verbalWanderingScreamingSleep disruption & “Sundowning”: very common
103 Multi-infarct Dementia Abrupt onset with stepwise deteriorationFluctuating course: improvement between strokesRelative preservation of personality Nocturnal confusion Depression and Somatic complaintsEmotional incontinenceCardiovascular Hx/SignsHistory of hypertensionEvidence of atherosclerosis (PVD, MI)Focal Neurological symptoms (TIA)Focal neurological sign
104 Normal Pressure Hydrocephalus 3 main symptoms:Dementia, Gait Apraxia, IncontinenceLanguage functions preservedMost common cause of gait abnormality plus Dementia is multiinfarct dementiaProgressive (months-years) with plateauMRI shows large ventriclesLP may result in temporary improvementTreatment is VP or LP shunt
105 HIV dementia Younger patient Memory loss Frontal lobe dysfunction, personality change, social withdrawProgresses over monthsSometimes initial symptoms of AIDSMay have other brain infection/tumor
106 Other causes of Dementia Toxic/Metabolic/Nutritional:Alcohol or drugsVitamin deficienciesHormonal disturbancesPrimary progressive Aphasia:progressive aphasia without true dementiaJacob Creutzfeld Disease:progressive dementia with seizures, myoclonus, ataxia, visual disturbance, motor neuron dysfunction
107 Other Dementias Chronic infections, vasculitis: Cryptococcal, fungal.Progressive multifocal leukoencephalopathyBilateral Subdural hematomaBrain tumor:especially frontal gliomaNeurodegenerative DisordersParkinson's diseaseLewy body dementiaProgressive supranuclear palsyFrontotemporal dementias(e.g., Pick's disease, primary progressive aphasias)Cortical-basal degeneration Hippocampal sclerosisDementia 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
109 Meningitis/Encephalitis Inflammatory processDriven by foreign invaders (usually)Fungal, Bacterial, Viral, or ParasiticSymptomsCaused by increased pressure/edemaPressure on nerve fibersTemperature changes