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