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Neurological System Symptom Overview • • • • • • Headache Dizziness and vertigo Confusion Memory/mental status changes Paresthesia Tremors Common Symptoms • • • • • – – – – – Headache Inflammation/Constriction Dizziness and vertigo Irritation Confusion/memory/mental status changes Executive Function Paresthesia Nerve Inhibition Tremors Nerve Excitation 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 Degenerative Conditions • Parkinson’s disease • Multiple sclerosis • Brain tumors Circulatory • • • • TIA/CVA Aneursym AV Malformation Headaches – Migraine – Tension – Cluster • Peripheral neuropathy Infection/Trauma • • • • • Meningitis and encephalitis Viral meningitis Seizure disorders/ epilepsy Bell’s palsy Trigeminal neuralgia Nerve Fibers Pressure/Ischemia = Neuropathy • Peripheral (extremity) • Radiculopathy (“root”) • Myelopathy (muscle/nerve) • 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 • 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 Severed = Paralysis Results of Neuropathy • Pain – Burning • Parathesia – Numbness • Hyperasthesia – Sensitivity • Paralysis – Loss of movement Various Neuropathy Conditions • Back pain – Radiculopathy – Sciatica – Myelopathy • Neuralgia/Parathesia – Trigeminal – Palsy (Bell’s, Ulnar) – Migraine (?) • Degenerative – Multiple Sclerosis – Amyotrophic Lateral Sclerosis Radiculopathy/Myelopathy Radiculopathy/Myelopathy • Burning pain along nerve • Loss of muscle strength – Atrophy – Injury Trigeminal Neuralgia • • • • • • • • Cranial Nerve V Tic douloureux 5TH Decade (V!) Young age ? MS Multiple Cause Paroxysmal Unilateral Trigger Bell’s Palsy/Nerve Palsy • • • • • • • Nerve paralysis Facial Nerve (VII) Motor not Sensory Sir Charles Bell Idiopathic Altered Taste Hyper Lacrimation Nerve Palsies • Neuropathy • “Saturday Night Palsy” • Nerve pressure causing paralysis • Sleeping standing up • Hours to Months EPS 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 EMG 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 Headache Headaches • Migraines • Cluster Headaches – “Cluster cycle” • Tension Headaches – “Stress”, muscle tension, neck pain Migraines 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 Migraines • Trigeminal Nerve Symptoms • Several Criteria – Photophobia – Nausea/Vomiting – Aura • Recurrent MRI of a Migraine 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 Acute Migraine Treatment • Ergotamine • Caffeine – - Unknown – “Abortive” or “rescue” tx – Dosage forms – oral, sublingual, rectal, parenteral – Increases intestinal absorption of ergotamine • Peripheral vascular disease – Potentiates vasoconstriction and pain relief when combined with ergotamine and analgesics • Cerebrovascular disease – Adverse effects – Contraindications • Cardiac disease • Sepsis • GI disturbances • Advanced Liver and Kidney disease • Nausea • Pregnancy, Breast Feeding • Vomiting • Anorexia Acute Migraine TreatmentTriptans • Sumatriptan – Dosage Forms • Drug Interactions – Ergot alkaloids • Subcutaneous injection – Lithium • Oral tablet – Serotonin-specific reuptake inhibitors • Nasal Spray – Adverse effects • Oral - nausea and vomiting, malaise, dizziness • Intranasal – bitter, unpleasant taste • Subcutaneous Injection - mild pain, redness, rebound HA – Other triptans – Monoamine Oxidase Inhibitors - use with these products may precipitate serotonin syndrome 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? Intractable migraines • Sumatriptan subcutaneous injection • Parenteral form of ergot derivatives • IV antiemetic • Corticosteroid - oral or parenteral • Hydration! • Parenteral Narcotic analgesics 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 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 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 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 45-60 minutes Cluster Headache Abortive Therapy • Oxygen inhalation • Ergotamine Tension Type Headaches • Gender - women 88%, males 69% • Intensity of headache pain • No aura • No nausea, vomiting • No photophobia Tension Headache Therapy • Abortive– NSAID’s • Non-drug techniques – Muscle relaxants – Massage – Anxiolytics – Hot bath – Analgesics – Acupuncture • Prophylactic – Antidepressants – Biofeedback Seizures • VFib of the brain • Various Reasons – Electrical – Ischemic – Chemical Seizure DisordersPharmacologic Treatment • Optimization of drug therapy • Choice of appropriate AED • Individualization of dosing • Compliance Therapeutic endpoints: Patient response • Seizure frequency and severity • Presence and severity of symptoms of dose related toxicity 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 • 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: – Dose change – Phenytoin – Assessment of therapy in patients with infrequent seizures – Valproate – Carbamazepine – Phenobarbital 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 Complex Partial Seizures with secondary generalization • Carbamazepine (Tegretol) • Lamotrigine (Lamictal) • Gabapentin (Neurontin) • Tiagabine=Gabitril • Levatiracetam=Keppra • Oxcarbazepine=Trileptal • Pregabalin=Lyrica Absence Seizures • Valproate when secondary tonic/clonic also • Clonazepam Febrile Seizures • Fever control • Anticipatory management in the future Testing Seizures • EEG EEG Circulation Problems Think Vascular CVA/TIA • • • • Vascular insult Dyslipidemia Clotting/emboli Risk Factors – – – – – Age Family history Smoking Dyslipidemia Diabetes Two kinds of CVA Hemorrhagic Embolic Hemorrhage Embolic • Multiple causes – Fat – Air – Blood • ‘Brain attack’ • Destroys nerves • ‘Cuts the wires’ Testing for Vascular Problems • MRA • Angiography • Ultrasound Consequences of wrong test 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 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% Risk Factor Management • Blood Pressure – 130/80 – JNC 7 – Starting antihypertensive drug therapy after TIA/Stroke – ACE Inhibitors 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 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 Degenerative Disease Think progressive Parkinsons • Reduction of Dopamine production • Causes resting tremors Dopamine/Acetylcholine Testing for Parkinson’s Parkinson’s Symptoms • Symptom spectrum – – – – – Bradykinesia/ akinesia Rest tremor Mask facies Progressive dementia Depression (functional?) Parkinson’s Disease Non-pharmacologic Interventions • Exercise • Physical activity • Nutrition • Psychologic support 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 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 Serotonin Syndrome 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) Anticholinergics • Mechanism of action – 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 Parkinson’s Tremor • Symptoms may be • Levodopa Drug interactions controllable with Benadryl – Neuroleptic drugs – (Phenothiazine, • Dopamine Precursors Prochlorperazine, (Levodopa - Sinemet – Fluphenazine, Stalevo) Chlorpromazine) – Initiation of therapy – Butyrophenones: Haloperidol • E.g. sinemet 10/100 t.i.d., increase q 2-3 days as tol – Antihypertensives – (Reserpine and Methyldopa) – Adverse effects – MAOi’s- serotonin syndrome • Dyskinesias – Other: Metoclopramide, Pyridoxine, Ferrous sulfate, Phenytoin, Benzodiazepines • Mental changes Adjunctive Treatment of Parkinsonian Tremor • B-adrenergic blockers • Clozapine • Surgery • Deep brain stimulation • Potential dietary/nutritional interactions – Tryptophan, tyramine, melatonin Multiple Sclerosis • Demyelination – Energy Diffusion – Reduced conduction – Nerve degeneration Types of MS • Relapsing-remitting (80%) – 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 MS Testing • MRI Brain and spinal cord – Remember MS is CNS – White matter “Demyelination” • Lumbar Puncture – WBCs, Antibodies • EMG Studies 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. • 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. • 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. • 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 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 Prevention of Relapses • recombinant interferon-ß's – Betaseron – Avonex • Copaxone • Rebif Treatment Options Symptomatic Therapy • • • • • • • • • Fatigue Vertigo Spasticity and Muscle Spasms Psychological Problems Urinary Dysfunction Sexual Problems Tremor and Incoordination Pain Cognitive Dysfunction 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 Compare… 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 Dementia Think Multi-causal degeneration 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 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 Diagnostic Criteria for Dementia • Impaired social or occupational function • Impaired memory + 1 or more changes in: – – – – Abstract/problem solving Judgment Language Personality Depression vs. Dementia • Depression – Fast onset – Depressed before demented – Patient complains more than family • Dementia – very slow onset – Demented then depressed – Patient denies Depression vs. Dementia • Depression – 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 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 “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 PET Scan NORMAL ALZHEIMERS DISEASE MMSE - The Clock (1:45) Risk Factors for Alzheimer's • • • • • Family History of Alzheimer's disease APO Genotype Aging and estrogen deficiency Head injury Low education Brain Iron Distribution Dementia Normal 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. Behavior problems • Personality change: – apathetic or more impulsive • Anxiety: – apprehension over upcoming events • Aggression: – physical or verbal • Wandering • Screaming • Sleep disruption & “Sundowning”: very common 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 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 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 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 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 Infections Think bug! 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 Strep Pneumo Meningitis Testing for Meningitis • Lumbar Puncture • Clinical Exam • Labs/Blood cultures