Neurological SystemNeurological System

Symptom OverviewSymptom Overview

• HeadacheHeadache• Dizziness and vertigoDizziness and vertigo• ConfusionConfusion• Memory/mental status changesMemory/mental status changes• ParesthesiaParesthesia• TremorsTremors

Common SymptomsCommon Symptoms

• HeadacheHeadache– Inflammation/Constriction Inflammation/Constriction

• Dizziness and vertigoDizziness and vertigo– IrritationIrritation

• Confusion/memory/mental status Confusion/memory/mental status changeschanges

– Executive FunctionExecutive Function

• ParesthesiaParesthesia– Nerve InhibitionNerve Inhibition

• TremorsTremors– Nerve ExcitationNerve Excitation

Basis of Neurological Basis of Neurological ProblemsProblems• Autoimmune/DegenerativeAutoimmune/Degenerative

– Pathologic excitation/inhibition nerve Pathologic excitation/inhibition nerve fibersfibers

– Degeneration/Destructions nerve fibersDegeneration/Destructions nerve fibers

• CirculatoryCirculatory– Ischemia/hypoxemiaIschemia/hypoxemia

• Decreased blood flow/decreased oxygen levelsDecreased blood flow/decreased oxygen levels

• GeneticGenetic– Mutations causing abnormal biochemistryMutations causing abnormal biochemistry

• Infection/TraumaInfection/Trauma– Abnormal pathology through injuryAbnormal pathology through injury

Degenerative ConditionsDegenerative Conditions

• Parkinson’s diseaseParkinson’s disease• Multiple sclerosisMultiple sclerosis• Brain tumorsBrain tumors

CirculatoryCirculatory

• TIA/CVATIA/CVA• AneursymAneursym• AV MalformationAV Malformation• Headaches Headaches

– MigraineMigraine– TensionTension– ClusterCluster

• Peripheral neuropathyPeripheral neuropathy

Infection/TraumaInfection/Trauma

• Meningitis and encephalitisMeningitis and encephalitis• Viral meningitisViral meningitis• Seizure disorders/ epilepsySeizure disorders/ epilepsy• Bell’s palsyBell’s palsy• Trigeminal neuralgiaTrigeminal neuralgia

Nerve FibersNerve Fibers

Pressure/Ischemia = Pressure/Ischemia = NeuropathyNeuropathy• Peripheral (extremity)Peripheral (extremity)• Radiculopathy (“root”)Radiculopathy (“root”)• Myelopathy (muscle/nerve)Myelopathy (muscle/nerve)

• Small myelinated axons are Small myelinated axons are responsible for light touch, pain responsible for light touch, pain temperature.temperature.

• Small unmyelinated axons are Small unmyelinated axons are also sensory and subserve pain also sensory and subserve pain and temperature.and temperature.

• Neuropathies involving these are Neuropathies involving these are called small fiber neuropathiescalled small fiber neuropathies

• Nerves have a limited number of ways to Nerves have a limited number of ways to respond to injuryrespond to injury

• Damage can occur at the level of the axon—Damage can occur at the level of the axon—this generally results in degeneration of both this generally results in degeneration of both the axon and the myelin sheaththe axon and the myelin sheath

• Damage at the motor neuron or dorsal root Damage at the motor neuron or dorsal root ganglion is often incompleteganglion is often incomplete

• Damage at the level of the myelin sheath are Damage at the level of the myelin sheath are often inflammatory or hereditary—these can often inflammatory or hereditary—these can yield a rapid recovery or a progressive yield a rapid recovery or a progressive diffuse course of illnessdiffuse course of illness

Severed = ParalysisSevered = Paralysis

Results of NeuropathyResults of Neuropathy

• PainPain– BurningBurning

• ParathesiaParathesia– NumbnessNumbness

• HyperasthesiaHyperasthesia– SensitivitySensitivity

• ParalysisParalysis– Loss of Loss of

movementmovement

Various Neuropathy Various Neuropathy ConditionsConditions• Back painBack pain

– RadiculopathyRadiculopathy– SciaticaSciatica– MyelopathyMyelopathy

• Neuralgia/ParathesiaNeuralgia/Parathesia– TrigeminalTrigeminal– Palsy (Bell’s, Ulnar)Palsy (Bell’s, Ulnar)– Migraine (?)Migraine (?)

• DegenerativeDegenerative– Multiple SclerosisMultiple Sclerosis– Amyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis

Radiculopathy/MyelopathyRadiculopathy/Myelopathy

Radiculopathy/MyelopathyRadiculopathy/Myelopathy

• Burning pain along nerveBurning pain along nerve• Loss of muscle strengthLoss of muscle strength

– AtrophyAtrophy– InjuryInjury

Trigeminal NeuralgiaTrigeminal Neuralgia

• Cranial Nerve VCranial Nerve V• Tic douloureuxTic douloureux• 55THTH Decade (V!) Decade (V!)• Young age ? MSYoung age ? MS• Multiple CauseMultiple Cause• ParoxysmalParoxysmal• UnilateralUnilateral• TriggerTrigger

Bell’s Palsy/Nerve PalsyBell’s Palsy/Nerve Palsy

• Nerve paralysisNerve paralysis• Facial Nerve (VII)Facial Nerve (VII)• Motor not Motor not

SensorySensory• Sir Charles BellSir Charles Bell• IdiopathicIdiopathic• Altered TasteAltered Taste• Hyper Hyper

LacrimationLacrimation

Nerve PalsiesNerve Palsies

• NeuropathyNeuropathy• ““Saturday Night Saturday Night

Palsy”Palsy”• Nerve pressure Nerve pressure

causing paralysiscausing paralysis• Sleeping Sleeping

standing upstanding up• Hours to MonthsHours to Months

EPSEPS

Testing NeuropathiesTesting Neuropathies

• Electromyography (EMG)Electromyography (EMG)– Needles into the muscleNeedles into the muscle– Measures muscle action potentialsMeasures muscle action potentials– A surface EMG (SEMG) is not accurateA surface EMG (SEMG) is not accurate

• Nerve Conduction Velocity (NCV)Nerve Conduction Velocity (NCV)– Usually done at the same time as Usually done at the same time as

EMGEMG

• Evoked potentialEvoked potential– Basis for EMG, can be auditory, visualBasis for EMG, can be auditory, visual

EMG

Treatment for NeuropathiesTreatment for Neuropathies

• First treat the underlying cause First treat the underlying cause thenthen symptom managementsymptom management– TCAsTCAs– Muscle relaxantsMuscle relaxants– SSRIsSSRIs– Antiseizure medsAntiseizure meds– Vitamin B12Vitamin B12– Lidocaine patchLidocaine patch– AnalgesicsAnalgesics– TENS unit, acupuncture, BiofeedbackTENS unit, acupuncture, Biofeedback

HeadacheHeadache

HeadachesHeadaches

• MigrainesMigraines• Cluster Cluster

HeadachesHeadaches– ““Cluster cycle”Cluster cycle”

• Tension Tension HeadachesHeadaches– ““Stress”, muscle Stress”, muscle

tension, neck tension, neck painpain

MigrainesMigraines

Migraine HeadachesMigraine Headaches

• TypesTypes

– Simple or Simple or ClassicClassic

– Complex Complex

• HemiplegicHemiplegic

• Possible Aggravating Possible Aggravating factors (“triggers”)factors (“triggers”)

– Stress / EmotionStress / Emotion– GlareGlare– AlcoholAlcohol– ExerciseExercise– Stimulants: Excess Stimulants: Excess

Caffeine, cocaine, Caffeine, cocaine, amphetaminesamphetamines

– FoodsFoods– Analgesic reboundAnalgesic rebound– Estrogen Estrogen

MigrainesMigraines

• Trigeminal Nerve Trigeminal Nerve SymptomsSymptoms

• Several CriteriaSeveral Criteria– PhotophobiaPhotophobia– Nausea/VomitingNausea/Vomiting– AuraAura

• RecurrentRecurrent

MRI of a Migraine

Diagnostic Requirements of Diagnostic Requirements of MigraineMigraine• At least two of the following features:At least two of the following features:

– Unilateral locationUnilateral location– Throbbing characterThrobbing character– Worsening pain with routine activityWorsening pain with routine activity– Moderate to severe intensityModerate to severe intensity

• At least one of the following features:At least one of the following features:– Nausea and/or vomitingNausea and/or vomiting– Photophobia Photophobia andand phonophobia phonophobia International Headache Society International Headache Society

Classification of HeadacheClassification of Headache

Acute Migraine TreatmentAcute Migraine Treatment• ErgotamineErgotamine

– - Unknown- Unknown

– ““Abortive” or “rescue” txAbortive” or “rescue” tx

– Dosage forms – oral, sublingual, Dosage forms – oral, sublingual, rectal, parenteralrectal, parenteral

– ContraindicationsContraindications

• Cardiac diseaseCardiac disease

• Peripheral vascular diseasePeripheral vascular disease

• Cerebrovascular diseaseCerebrovascular disease

• SepsisSepsis

• Advanced Liver and Kidney Advanced Liver and Kidney diseasedisease

• Pregnancy, Breast FeedingPregnancy, Breast Feeding

• CaffeineCaffeine

– Increases intestinal Increases intestinal absorption of absorption of ergotamineergotamine

– Potentiates Potentiates vasoconstriction and vasoconstriction and pain relief when pain relief when combined with combined with ergotamine and ergotamine and analgesicsanalgesics

– Adverse effectsAdverse effects

• GI disturbancesGI disturbances

• NauseaNausea

• VomitingVomiting

• AnorexiaAnorexia

Acute Migraine Treatment- Acute Migraine Treatment- TriptansTriptans• Sumatriptan Sumatriptan

– Dosage FormsDosage Forms

• Subcutaneous injectionSubcutaneous injection

• Oral tabletOral tablet

• Nasal SprayNasal Spray

– Adverse effectsAdverse effects

• Oral - nausea and vomiting, Oral - nausea and vomiting, malaise, dizzinessmalaise, dizziness

• Intranasal – bitter, unpleasant Intranasal – bitter, unpleasant tastetaste

• Subcutaneous Injection - mild Subcutaneous Injection - mild pain, redness, rebound HApain, redness, rebound HA

• Drug InteractionsDrug Interactions

– Ergot alkaloidsErgot alkaloids

– LithiumLithium

– Serotonin-specific Serotonin-specific reuptake inhibitorsreuptake inhibitors

– Other triptansOther triptans

– Monoamine Oxidase Monoamine Oxidase Inhibitors - use with Inhibitors - use with these products may these products may precipitate serotonin precipitate serotonin syndromesyndrome

Acute Migraine TreatmentAcute Migraine Treatment• Second Generation Second Generation

triptanstriptans

• Eli-, zolma-, nara-, frova-Eli-, zolma-, nara-, frova-

• Acute treatment of Acute treatment of migrainesmigraines

• Comparison to Comparison to sumatriptansumatriptan

– Similar pharmacologic Similar pharmacologic featuresfeatures

– Improved oral Improved oral bioavailabilitybioavailability

– Able to cross blood brain Able to cross blood brain barrierbarrier

• Possible reasons for Possible reasons for treatment failurestreatment failures

– Medication Medication administration too lateadministration too late

– Swallowing Sublingual Swallowing Sublingual productsproducts

– Vomiting tablet prior to Vomiting tablet prior to absorptionabsorption

– Rebound headache due Rebound headache due to overuseto overuse

– Dehydration/ Dehydration/ ketosis/acidosisketosis/acidosis

– Analgesic reboundAnalgesic rebound

– Diagnosis?Diagnosis?

Intractable migrainesIntractable migraines

• Sumatriptan subcutaneous injectionSumatriptan subcutaneous injection

• Parenteral form of ergot derivativesParenteral form of ergot derivatives

• IV antiemeticIV antiemetic

• Corticosteroid - oral or parenteralCorticosteroid - oral or parenteral

• Hydration! Hydration!

• Parenteral Narcotic analgesicsParenteral Narcotic analgesics

Migraine Adjunctive therapyMigraine Adjunctive therapy

• AntiemeticsAntiemetics– Systemic relief of nausea and Systemic relief of nausea and

vomitingvomiting

– Increased absorption of other Increased absorption of other medications, prokineticmedications, prokinetic

• NSAIDSNSAIDS– Not approved by FDA for migraine Not approved by FDA for migraine

headache indicationheadache indication

– Selected NSAIDS effective as abortive Selected NSAIDS effective as abortive therapytherapy

Migraine Prophylactic Migraine Prophylactic therapytherapy• GoalsGoals

– Reduces frequencyReduces frequency

– Reduces severityReduces severity

• CriteriaCriteria

– Headaches that occur twice monthly or more Headaches that occur twice monthly or more oftenoften

– Disabling headache that occurs less frequently Disabling headache that occurs less frequently but are unresponsive to usual abortive therapybut are unresponsive to usual abortive therapy

– Abortive agents contraindicatedAbortive agents contraindicated

– Headaches that occur in unpredictable patternsHeadaches that occur in unpredictable patterns

Migraine Prophylactic Migraine Prophylactic therapy- cont’d.therapy- cont’d.• TopomaxTopomax

Use in low dose of 25 to 50 Use in low dose of 25 to 50 mg at hs to prevent mg at hs to prevent migranemigrane

• Valproic AcidValproic Acid

– 1000mg po q HS prophylaxis1000mg po q HS prophylaxis

Cluster HeadachesCluster Headaches

• Gender - males>femalesGender - males>females

• Onset - second and fourth decade of Onset - second and fourth decade of lifelife

• Intensity of Headache PainIntensity of Headache Pain

• Same side of head, tearing, flushSame side of head, tearing, flush

• Severe throbbing/stabbingSevere throbbing/stabbing

• Not preceded by auraNot preceded by aura

• Last 45-60 minutesLast 45-60 minutes

Cluster Headache Abortive Cluster Headache Abortive TherapyTherapy• Oxygen inhalationOxygen inhalation

• ErgotamineErgotamine

Tension Type HeadachesTension Type Headaches

• Gender - women 88%, males 69%Gender - women 88%, males 69%

• Intensity of headache painIntensity of headache pain

• No auraNo aura

• No nausea, vomitingNo nausea, vomiting

• No photophobiaNo photophobia

Tension Headache TherapyTension Headache Therapy

• Abortive-Abortive-

– NSAID’sNSAID’s

– Muscle relaxantsMuscle relaxants

– AnxiolyticsAnxiolytics

– Analgesics Analgesics

• ProphylacticProphylactic

– Antidepressants Antidepressants

• Non-drug Non-drug techniquestechniques

– MassageMassage

– Hot bathHot bath

– AcupunctureAcupuncture

– Biofeedback Biofeedback

SeizuresSeizures

• VFib of the brainVFib of the brain• Various ReasonsVarious Reasons

– ElectricalElectrical– IschemicIschemic– ChemicalChemical

Seizure Disorders- Seizure Disorders- Pharmacologic TreatmentPharmacologic Treatment• Optimization of drug therapyOptimization of drug therapy

• Choice of appropriate AEDChoice of appropriate AED

• Individualization of dosingIndividualization of dosing

• ComplianceCompliance

Therapeutic endpoints: Therapeutic endpoints: Patient responsePatient response• Seizure frequency and severitySeizure frequency and severity

• Presence and severity of Presence and severity of symptoms of dose related symptoms of dose related toxicitytoxicity

Serum drug concentrationsSerum drug concentrations• Indications for useIndications for use

– Uncontrolled seizures Uncontrolled seizures despite greater than despite greater than average dosesaverage doses

– Seizure recurrence in a Seizure recurrence in a previously controlled previously controlled patientpatient

– Documentation of Documentation of intoxicationintoxication

– Assessment of complianceAssessment of compliance

– Dose changeDose change

– Assessment of therapyAssessment of therapy in in patients with infrequent patients with infrequent seizuresseizures

• When dosage changes are When dosage changes are mademade

– Interpretation of serum Interpretation of serum concentrationsconcentrations

– Laboratory variabilityLaboratory variability

– Interindividual variabilityInterindividual variability

– Active metabolites of AED’s Active metabolites of AED’s may not be measuredmay not be measured

– Binding of serum proteinsBinding of serum proteins

• Therapeutic blood levels Therapeutic blood levels useful for:useful for:

– PhenytoinPhenytoin

– ValproateValproate

– CarbamazepineCarbamazepine

– PhenobarbitalPhenobarbital

Idiopathic Grand Mal Idiopathic Grand Mal EpilepsyEpilepsy• DrugsDrugs

– Phenytoin (hydantoins) (Dilantin)Phenytoin (hydantoins) (Dilantin)

– Valproic Acid=DepakoteValproic Acid=Depakote

– Carbamazepine (Tegretol)Carbamazepine (Tegretol)

– Phenobarbital (barbiturates)Phenobarbital (barbiturates)

– Topiramate (Topomax)Topiramate (Topomax)

• Duration of therapyDuration of therapy

– Seizure free for 2-5 years or may be lifetimeSeizure free for 2-5 years or may be lifetime

• Withdrawal of AED’sWithdrawal of AED’s

– Two to three months withdrawal scheduleTwo to three months withdrawal schedule

– Multiple therapy - each drug tapered separatelyMultiple therapy - each drug tapered separately

Complex Partial Seizures Complex Partial Seizures with secondary with secondary generalizationgeneralization

• Carbamazepine (Tegretol)Carbamazepine (Tegretol)

• Lamotrigine (Lamictal)Lamotrigine (Lamictal)

• Gabapentin (Neurontin)Gabapentin (Neurontin)

• Tiagabine=GabitrilTiagabine=Gabitril

• Levatiracetam=KeppraLevatiracetam=Keppra

• Oxcarbazepine=TrileptalOxcarbazepine=Trileptal

• Pregabalin=LyricaPregabalin=Lyrica

Absence SeizuresAbsence Seizures

• Valproate when secondary Valproate when secondary tonic/clonic alsotonic/clonic also

• ClonazepamClonazepam

Febrile SeizuresFebrile Seizures

• Fever controlFever control

• Anticipatory management in the Anticipatory management in the future future

Testing SeizuresTesting Seizures

• EEGEEG

EEG

Circulation ProblemsCirculation Problems

Think VascularThink Vascular

CVA/TIACVA/TIA

• Vascular insultVascular insult• DyslipidemiaDyslipidemia• Clotting/emboliClotting/emboli• Risk FactorsRisk Factors

– AgeAge– Family historyFamily history– SmokingSmoking– DyslipidemiaDyslipidemia– DiabetesDiabetes

Two kinds of CVATwo kinds of CVA

Hemorrhagic Embolic

HemorrhageHemorrhage

EmbolicEmbolic

• Multiple causesMultiple causes– FatFat– AirAir– BloodBlood

• ‘‘Brain attack’Brain attack’• Destroys nervesDestroys nerves• ‘‘Cuts the wires’Cuts the wires’

Testing for Vascular Testing for Vascular ProblemsProblems• MRAMRA• AngiographyAngiography• UltrasoundUltrasound

Consequences of wrong testConsequences of wrong test

Medications for embolic CVAMedications for embolic CVA

• IV tissue plasminogen activator tPA IV tissue plasminogen activator tPA 0.9mg/kg in highly selected cases 0.9mg/kg in highly selected cases within 3 hours of ischemic strokewithin 3 hours of ischemic stroke

• ECASAECASA• Dipyridamole-aspirin (Aggrenox) Dipyridamole-aspirin (Aggrenox)

extended release, 200mg/25mg extended release, 200mg/25mg capsule PO BIDcapsule PO BID

• Clopidogrel (Plavix) 75mg/dayClopidogrel (Plavix) 75mg/day• Warfarin INR adjusted doseWarfarin INR adjusted dose

Surgical MeasuresSurgical Measures

• Carotid endartectomy (CEA) is Carotid endartectomy (CEA) is indicated for stenosis of 70-99%indicated for stenosis of 70-99%

• CEA is of modest benefit for CEA is of modest benefit for carotid stenosis of 50-69% and carotid stenosis of 50-69% and depends on risk factorsdepends on risk factors

• No benefit <50%No benefit <50%

Risk Factor ManagementRisk Factor Management

• Blood PressureBlood Pressure– 130/80130/80– JNC 7JNC 7– Starting antihypertensive drug Starting antihypertensive drug

therapy after TIA/Stroketherapy after TIA/Stroke– ACE InhibitorsACE Inhibitors

Risk Factor ManagementRisk Factor Management

• SMOKINGSMOKING““the risk of stroke in persons of either sex the risk of stroke in persons of either sex

and all ages was 50 percent higher in and all ages was 50 percent higher in smokers than in nonsmokers”smokers than in nonsmokers”

– Smoking cessationSmoking cessation

Risk Factor ManagementRisk Factor Management

• Blood lipid levelsBlood lipid levels– StatinStatin

• Diabetes mellitusDiabetes mellitus– Increases the overall risk by 25 to 50%Increases the overall risk by 25 to 50%

• Antiplatelet therapyAntiplatelet therapy– clopidogrel (Plavix), ticlopidine clopidogrel (Plavix), ticlopidine

(Ticlid), and aspirin-dipyridamole (Ticlid), and aspirin-dipyridamole (Aggrenox)(Aggrenox)

• AspirinAspirin• 50-325mg/day50-325mg/day

Degenerative DiseaseDegenerative Disease

Think progressiveThink progressive

ParkinsonsParkinsons

• Reduction of Reduction of Dopamine Dopamine productionproduction

• Causes resting Causes resting tremorstremors

Dopamine/AcetylcholineDopamine/Acetylcholine

Testing for Parkinson’sTesting for Parkinson’s

Parkinson’s SymptomsParkinson’s Symptoms

• Symptom spectrumSymptom spectrum– Bradykinesia/ akinesiaBradykinesia/ akinesia– Rest tremorRest tremor– Mask faciesMask facies– Progressive dementiaProgressive dementia– Depression (functional?)Depression (functional?)

Parkinson’s Disease Parkinson’s Disease Non-pharmacologic Non-pharmacologic InterventionsInterventions

• ExerciseExercise

• Physical activityPhysical activity

• NutritionNutrition

• Psychologic supportPsychologic support

Parkinson’s Pharmacologic Parkinson’s Pharmacologic

Interventions: Dopamine AgonistsInterventions: Dopamine Agonists • AmantadineAmantadine

– Mechanism of Mechanism of action ?action ?

– ↑ ↑ dopamine dopamine release from release from presynaptic nerve presynaptic nerve terminalsterminals

• Initiation of Initiation of therapytherapy

– Twice daily, Twice daily, Morning and lunchMorning and lunch

• Adverse effectsAdverse effects

– Anticholinergic Anticholinergic

• GastrointestinalGastrointestinal

• CardiovascularCardiovascular

• CNSCNS

– Mild elevations of BUN Mild elevations of BUN and alkaline and alkaline phosphatasephosphatase

• Monitoring Monitoring ParametersParameters

– GI and CNS complaintsGI and CNS complaints

– BUN, Cr every 3 monthsBUN, Cr every 3 months

Parkinson’s- cont’d.Parkinson’s- cont’d.• Dopamine agonists- besides Dopamine agonists- besides

amantidineamantidine– Pramipexole (Mirapex)Pramipexole (Mirapex)

– Bromocriptine (Parlodel)Bromocriptine (Parlodel)

– Pergolide (Permax)Pergolide (Permax)

– Ropinirole (Requip)Ropinirole (Requip)

• Monoamine Oxidase-B Inhibitors: Monoamine Oxidase-B Inhibitors: Selegiline (Eldepryl))Selegiline (Eldepryl))

• Antioxidant Therapy- Antioxidant Therapy- questionable efficacyquestionable efficacy

Serotonin SyndromeSerotonin SyndromeSymptoms Associated with Serotonin SyndromeSymptoms Associated with Serotonin Syndrome

Mental status changesMental status changesConfusion (51%)Confusion (51%)Agitation (34%)Agitation (34%)Hypomania (21%)Hypomania (21%)Anxiety (15%)Anxiety (15%)Coma (29%)Coma (29%)

CardiovascularCardiovascularSinus tachycardia (36%)Sinus tachycardia (36%)Hypertension (35%)Hypertension (35%)Hypotension (15%)Hypotension (15%)

GastrointestinalGastrointestinalNausea (23%)Nausea (23%)Diarrhea (8%)Diarrhea (8%)Abdominal pain (4%)Abdominal pain (4%)Salivation (2%)Salivation (2%)

References 2, 4References 2, 4

Motor AbnormalitiesMotor AbnormalitiesMyoclonus (58%)Myoclonus (58%)Hyperreflexia (52%)Hyperreflexia (52%)Muscle rigidity (51%)Muscle rigidity (51%)Restlessness (48%)Restlessness (48%)Tremor (43%)Tremor (43%)Ataxia/incoordination (40%)Ataxia/incoordination (40%)Shivering (26%)Shivering (26%)Nystagmus (15%)Nystagmus (15%)Seizures (12%)Seizures (12%)

OtherOtherDiaphoresis (45%)Diaphoresis (45%)Unreactive pupils (20%)Unreactive pupils (20%)Tachypnea (26%)Tachypnea (26%)Hyperpyrexia (45%)Hyperpyrexia (45%)

(Nolan, 2005)

AnticholinergicsAnticholinergics• Mechanism of action Mechanism of action

– Blocks excitatory Blocks excitatory neurotransmitter Ach neurotransmitter Ach in substantia nigrain substantia nigra

• Aids treatment of Aids treatment of tremortremor– less effective than less effective than

levodopa/carbidopa or levodopa/carbidopa or dopamine agonists dopamine agonists

• DrugsDrugs– trihexyphenidyl trihexyphenidyl

(Artane)(Artane)

– benztropine benztropine (Cogentin)(Cogentin)

• Adverse effectsAdverse effects– Increased intraocular Increased intraocular

pressurepressure

– ConfusionConfusion

– Impairment of recent Impairment of recent memorymemory

– HallucinationsHallucinations

– DelusionsDelusions

– Dry mouthDry mouth

– Blurred visionBlurred vision

– ConstipationConstipation

– Urinary retentionUrinary retention

Parkinson’s Tremor Parkinson’s Tremor • Symptoms may be Symptoms may be

controllable with controllable with BenadrylBenadryl

• Dopamine Precursors Dopamine Precursors (Levodopa - Sinemet – (Levodopa - Sinemet – Stalevo)Stalevo)

– Initiation of therapyInitiation of therapy• E.g. sinemet 10/100 E.g. sinemet 10/100

t.i.d., increase q 2-3 t.i.d., increase q 2-3 days as toldays as tol

– Adverse effectsAdverse effects

• DyskinesiasDyskinesias

• Mental changesMental changes

• Levodopa Drug interactionsLevodopa Drug interactions

– Neuroleptic drugs – Neuroleptic drugs – (Phenothiazine, (Phenothiazine, Prochlorperazine, Prochlorperazine, Fluphenazine, Fluphenazine, Chlorpromazine)Chlorpromazine)

– Butyrophenones: Butyrophenones: HaloperidolHaloperidol

– Antihypertensives – Antihypertensives – (Reserpine and (Reserpine and Methyldopa)Methyldopa)

– MAOi’s- serotonin MAOi’s- serotonin syndromesyndrome

– Other: Metoclopramide, Other: Metoclopramide, Pyridoxine, Ferrous Pyridoxine, Ferrous sulfate, Phenytoin, sulfate, Phenytoin, BenzodiazepinesBenzodiazepines

Adjunctive Treatment of Adjunctive Treatment of Parkinsonian TremorParkinsonian Tremor• B-adrenergic blockersB-adrenergic blockers

• ClozapineClozapine

• SurgerySurgery

• Deep brain stimulationDeep brain stimulation

• Potential dietary/nutritional Potential dietary/nutritional interactionsinteractions

– Tryptophan, tyramine, melatoninTryptophan, tyramine, melatonin

Multiple SclerosisMultiple Sclerosis

• DemyelinationDemyelination– Energy DiffusionEnergy Diffusion– Reduced Reduced

conductionconduction– Nerve Nerve

degenerationdegeneration

Types of MSTypes of MS

• Relapsing-remitting (80%)Relapsing-remitting (80%)– Periods of relapse, when symptoms flare up Periods of relapse, when symptoms flare up – Periods of remission, when symptoms improvePeriods of remission, when symptoms improve

• Secondary progressive Secondary progressive – Develops from Relapsing/Remitting Develops from Relapsing/Remitting – shorter periods of remission and worse symptoms shorter periods of remission and worse symptoms

during relapses. during relapses. – 50% to the secondary progressive stage in first 10 50% to the secondary progressive stage in first 10

yearsyears

• Primary progressive (3 in 20)Primary progressive (3 in 20)– no periods of remissionno periods of remission– This causes increasing disability, and can reduce This causes increasing disability, and can reduce

life expectancylife expectancy

MS TestingMS Testing

• MRI Brain and spinal cordMRI Brain and spinal cord– Remember MS is CNSRemember MS is CNS– White matter “Demyelination”White matter “Demyelination”

• Lumbar PunctureLumbar Puncture– WBCs, AntibodiesWBCs, Antibodies

• EMG StudiesEMG Studies

MS Treatment Options - MS Treatment Options - General ConsiderationsGeneral Considerations• ExerciseExercise• Appropriate exercise program is beneficialAppropriate exercise program is beneficial• Simple exercises such as normal walking, Simple exercises such as normal walking,

swimming, using exercise bike swimming, using exercise bike • strongly advise against overheating (saunas, strongly advise against overheating (saunas,

hot tubs, sunbathing, etc.) to prevent hot tubs, sunbathing, etc.) to prevent declines in neurologic function. Exercising in declines in neurologic function. Exercising in a cool, well aerated environment is strongly a cool, well aerated environment is strongly encouraged. encouraged.

•

MS Treatment Cont.MS Treatment Cont.

• Physical TherapyPhysical Therapy

• PT/OT including ankle braces and PT/OT including ankle braces and devices that provide assistance with devices that provide assistance with walking, personalized exercise program walking, personalized exercise program and counseling on work and daily and counseling on work and daily activities.activities.

• NutritionNutrition• MS Society recommends low fat, low MS Society recommends low fat, low

cholesterol diet cholesterol diet • Obese patients appear to lose any reserve Obese patients appear to lose any reserve

muscle strength they may have left because muscle strength they may have left because of their weight. of their weight.

• Some patients with medullary lesions and Some patients with medullary lesions and difficulty swallowing may require feeding difficulty swallowing may require feeding tubes to prevent aspiration and resulting tubes to prevent aspiration and resulting pneumonia. pneumonia.

• Treatment of Infections and Elevated Body Treatment of Infections and Elevated Body TemperaturesTemperatures

• Increased body temperature may lead to Increased body temperature may lead to transient increase in neurologic symptoms or transient increase in neurologic symptoms or even precipitate exacerbation. even precipitate exacerbation.

• If a fever is due to an infection, infection If a fever is due to an infection, infection needs to be identified and treated, and needs to be identified and treated, and antipyretics need to be administered. antipyretics need to be administered.

• UTI’s are commonUTI’s are common

Treatment of RelapsesTreatment of Relapses

• Solu-Medrol (Methylprednisone) is Solu-Medrol (Methylprednisone) is often used for treatment of severe often used for treatment of severe exacerbations. exacerbations.

• Typical doses range from 500 to 1000 Typical doses range from 500 to 1000 mg/day for 3 to 5 daysmg/day for 3 to 5 days

Prevention of RelapsesPrevention of Relapses

• recombinant interferon-ß's recombinant interferon-ß's – BetaseronBetaseron– AvonexAvonex

• CopaxoneCopaxone

• RebifRebif

Treatment Options - Treatment Options - Symptomatic TherapySymptomatic Therapy• FatigueFatigue• VertigoVertigo• Spasticity and Muscle SpasmsSpasticity and Muscle Spasms• Psychological ProblemsPsychological Problems• Urinary DysfunctionUrinary Dysfunction• Sexual ProblemsSexual Problems• Tremor and IncoordinationTremor and Incoordination• PainPain• Cognitive DysfunctionCognitive Dysfunction

Huntington’s DiseaseHuntington’s Disease

• Degenerative Disease of the BrainDegenerative Disease of the Brain– TremorsTremors– Progressive dementiaProgressive dementia

• Genetic InheritanceGenetic Inheritance• 5 in 100,000 cases5 in 100,000 cases• Diagnosed at symptom onsetDiagnosed at symptom onset

– Usually after 30Usually after 30– Usually after children are bornUsually after children are born

Compare…Compare…

Testing Huntington’s Testing Huntington’s DiseaseDisease• CT/MRI (Specific finding)CT/MRI (Specific finding)

– loss of a normally convex bulge of loss of a normally convex bulge of the caudate nucleus into the lateral the caudate nucleus into the lateral ventriclesventricles

– Enlarged lateral ventriclesEnlarged lateral ventricles

• LabsLabs– Genetic testingGenetic testing

DementiaDementia

Think Multi-causal Think Multi-causal degenerationdegeneration

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 DementiaOverview of Dementia

• Population is aging Population is aging • Dementia increases with age Dementia increases with age • AmnesiaAmnesia

– Isolated memory lossIsolated memory loss– may be the first sign of dementia may be the first sign of dementia

• Delirium is a deficit of attentionDelirium is a deficit of attention

Diagnostic Criteria for Diagnostic Criteria for DementiaDementia• Impaired social or occupational Impaired social or occupational

function function • Impaired memory + 1 or more Impaired memory + 1 or more

changes in: changes in: – Abstract/problem solving Abstract/problem solving – Judgment Judgment – Language Language – PersonalityPersonality

Depression vs. Dementia Depression vs. Dementia

• DepressionDepression– Fast onset Fast onset – Depressed before Depressed before

demented demented – Patient complains Patient complains

more than family more than family

• DementiaDementia– very slow onset very slow onset – Demented then Demented then

depressed depressed – Patient deniesPatient denies

Depression vs. Dementia Depression vs. Dementia

• DepressionDepression– Appears Appears

depressed depressed – Response of "I Response of "I

don't know" don't know" – Inconsistent Inconsistent

Cognitive Cognitive impairmentimpairment

– antidepressant antidepressant worksworks

• DementiaDementia– May not appear May not appear

depressed depressed – Tries to answerTries to answer– Consistent Consistent

Cognitive Cognitive impairmentimpairment

– Antidepressant Antidepressant may not workmay not work

Causes of DementiaCauses of Dementia

• Alzheimer's diseaseAlzheimer's disease– Most common cause in the elderly Most common cause in the elderly – Incidence: Incidence:

• 123.3 new cases/100,000 population/ 123.3 new cases/100,000 population/ year year

– Prevalence: Prevalence: • 10% over age 65, 47% over age 8410% over age 65, 47% over age 84

““Probable” Alzheimer's Probable” Alzheimer's DementiaDementia• Abnormal clinical exam Abnormal clinical exam • Abnormal Mini Mental status Abnormal Mini Mental status

Exam Exam • Deficits in 2 or more areas of Deficits in 2 or more areas of

cognition cognition • Progressive decline Progressive decline • No disturbance of consciousnessNo disturbance of consciousness• Absence of other causeAbsence of other cause

PET ScanPET Scan

NORMAL ALZHEIMERS DISEASE

MMSE - The Clock (1:45)MMSE - The Clock (1:45)

Risk Factors for Alzheimer'sRisk Factors for Alzheimer's

• Family History of Alzheimer's Family History of Alzheimer's disease disease

• APO Genotype APO Genotype • Aging and estrogen deficiency Aging and estrogen deficiency • Head injury Head injury • Low educationLow education

Brain Iron DistributionBrain Iron Distribution

Dementia Normal

Psychotic & Affective Psychotic & Affective disturbancedisturbance• Delusions: (false beliefs) Delusions: (false beliefs)

– 30-70% of patients (Usually simple 30-70% of patients (Usually simple delusions delusions

• HallucinationsHallucinations– Not common. If present usually visual. Not common. If present usually visual.

• Depression Depression – very common, difficult to diagnose.very common, difficult to diagnose.– Suicide is rare. Suicide is rare. – Severe depression more in vascular Severe depression more in vascular

dementia.dementia.

Behavior problemsBehavior problems

• Personality change: Personality change: – apathetic or more impulsive apathetic or more impulsive

• Anxiety: Anxiety: – apprehension over upcoming events apprehension over upcoming events

• Aggression: Aggression: – physical or verbalphysical or verbal

• WanderingWandering• ScreamingScreaming• Sleep disruption & “Sundowning”: Sleep disruption & “Sundowning”:

very commonvery common

Multi-infarct DementiaMulti-infarct Dementia

• Abrupt onset with stepwise deteriorationAbrupt onset with stepwise deterioration• Fluctuating course: improvement between Fluctuating course: improvement between

strokesstrokes• Relative preservation of personality  Relative preservation of personality  • Nocturnal confusion    Nocturnal confusion    • Depression and Somatic complaintsDepression and Somatic complaints• Emotional incontinenceEmotional incontinence• Cardiovascular Hx/SignsCardiovascular Hx/Signs

– History of hypertensionHistory of hypertension– Evidence of atherosclerosis (PVD, MI)Evidence of atherosclerosis (PVD, MI)– Focal Neurological symptoms (TIA)Focal Neurological symptoms (TIA)– Focal neurological sign Focal neurological sign

Normal Pressure Normal Pressure HydrocephalusHydrocephalus• 3 main symptoms: 3 main symptoms:

– Dementia, Gait Apraxia, Incontinence Dementia, Gait Apraxia, Incontinence

• Language functions preserved Language functions preserved • Most common cause of gait abnormality Most common cause of gait abnormality

plus Dementia is multiinfarct dementiaplus Dementia is multiinfarct dementia• Progressive (months-years) with plateau Progressive (months-years) with plateau • MRI shows large ventricles MRI shows large ventricles • LP may result in temporary improvement LP may result in temporary improvement • Treatment is VP or LP shuntTreatment is VP or LP shunt

HIV dementiaHIV dementia

• Younger patient Younger patient • Memory loss Memory loss • Frontal lobe dysfunction, personality Frontal lobe dysfunction, personality

change, social withdraw change, social withdraw • Progresses over months Progresses over months • Sometimes initial symptoms of AIDS Sometimes initial symptoms of AIDS • May have other brain May have other brain

infection/tumorinfection/tumor

Other causes of DementiaOther causes of Dementia

• Toxic/Metabolic/Nutritional: Toxic/Metabolic/Nutritional: – Alcohol or drugsAlcohol or drugs– Vitamin deficienciesVitamin deficiencies– Hormonal disturbancesHormonal disturbances

• Primary progressive Aphasia: Primary progressive Aphasia: – progressive aphasia without true dementiaprogressive aphasia without true dementia

• Jacob Creutzfeld Disease: Jacob Creutzfeld Disease: – progressive dementia with seizures, progressive dementia with seizures,

myoclonus, ataxia, visual disturbance, myoclonus, ataxia, visual disturbance, motor neuron dysfunctionmotor neuron dysfunction

Other DementiasOther Dementias• Chronic infections, vasculitis: Chronic infections, vasculitis:

– Cryptococcal, fungal. Cryptococcal, fungal. • Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy • Bilateral Subdural hematoma Bilateral Subdural hematoma • Brain tumor: Brain tumor:

– especially frontal gliomaespecially frontal glioma• Neurodegenerative Disorders Neurodegenerative Disorders

– Parkinson's disease Parkinson's disease – Lewy body dementia Lewy body dementia – Progressive supranuclear palsyProgressive supranuclear palsy– Frontotemporal dementias Frontotemporal dementias

• (e.g., Pick's disease, primary progressive aphasias)(e.g., Pick's disease, primary progressive aphasias)– Cortical-basal degeneration Hippocampal sclerosisCortical-basal degeneration Hippocampal sclerosis

InfectionsInfections

Think bug!Think bug!

Meningitis/EncephalitisMeningitis/Encephalitis

• Inflammatory processInflammatory process• Driven by foreign invaders (usually)Driven by foreign invaders (usually)• Fungal, Bacterial, Viral, or ParasiticFungal, Bacterial, Viral, or Parasitic• SymptomsSymptoms

– Caused by increased pressure/edemaCaused by increased pressure/edema– Pressure on nerve fibersPressure on nerve fibers– Temperature changesTemperature changes

Strep Pneumo MeningitisStrep Pneumo Meningitis

Testing for MeningitisTesting for Meningitis

• Lumbar PunctureLumbar Puncture• Clinical ExamClinical Exam• Labs/Blood culturesLabs/Blood cultures