epilepsy overview for 3rd year medical students

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Epilepsy Overview for 3rd year medical students. SAID S. DAHBOUR,MD Associate professor of Medicine and Neurology Faculty of Medicine – Jordan University Amman - Jordan. Outline. General Aspects New AED Epilepsy Surgery Drugs used for Status Epilepticus Conclusions. - PowerPoint PPT Presentation

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  • Epilepsy Overview for 3rd year medical studentsSAID S. DAHBOUR,MDAssociate professor of Medicine and NeurologyFaculty of Medicine Jordan UniversityAmman - Jordan

  • OutlineGeneral Aspects New AED Epilepsy Surgery Drugs used for Status Epilepticus Conclusions

  • Seizures and EpilepsySeizure: abnormal hypersynchronous electrical discharge form cerebral cortical neurons.Clinical seizure: the clinical manifestation of the electric seizure that depends on the site of onste and path of propagationEpilepsy =Recurrent Unprovoked Seizures

  • International classification of epileptic seizures NEJM 2002:344(15)1145-51Partial (focal, local) seizures simple complex evolving to generalized seizuresGeneralized seizures absence : typicalatypical tonic clonic (grand mal) myoclonic clonic tonic atonic Unclassified neonatal infantile spasm febrile seizures

  • Modified ILAE classification of epilepsy syndromes Idiopathic : no cause identified; presumed genetic- inherited

    Localization relatedGeneralizedBECTSBenign occipital epilepsyAD nocturnal frontal lobe epilepsyBenign familial neonatal epilepsyBenign myoclonic epilepsy of infancyChildhood absenceJuvenile absenceJMEEpilepsy with GTC upon awakening

  • Modified ILAE classification of epilepsy syndromes Symptomatic: of underlying structural disease

    Localization- related generalizedTemporal lobeFrontal lobeParietal lobeOccipital lobeEarly myoclonic encephalopahtyEarly infantile epileptic ncephalopathy with suppression- burstCortical malformationMetabolic abnormalitiesWest syndrome ( with pathology)LGS (with pathology)

  • Modified ILAE classification of epilepsy syndromes

    Cryptogenic: presumed underlying structural disease

    Localization-relatedGeneralizedAny occurrence of partial seizures without obvious pathology (eg, MRI negative)Epilepsy with myoclonic astatic seizuresEpilepsy with myoclonic absenceWest syndrome (unidentified pathology)LGS (unidentified pathology)

  • Modified ILAE classification of epilepsy syndromes

    Special syndromes or undetermined epilepsiesFebrile convulsionsIsolated unprovoked seizures or isolated status epilepticusNeonatal seizures of any etiologyEpilepsy with continuous spike-wave during slow wave sleep (electric status epilepticus of sleep)Acquired epileptic aphasia (Landau-Kliffner syndrome)

  • a Rochester Minnesota Epilepsy Study (1935-1974)

  • Epilepsy: DiagnosisHistoryPhysical examinationEEGMRISpecial testing

  • RIGHT ANTERIOR TEMPORAL SHARPS.

  • INTERICTAL GENERALIZED 3 HTZ SPIKE-WAVE DISCHARGE

  • GENERALIZED SEIZURE

  • Differential diagnosis of seizures in adultsVasovagal syncopeCardiogenic syncopeMigraineTIAPsychogenic pseudosizuresPanic attacksRage attacks

  • Differential diagnosis of seizures in childrenTicsInfantile syncopeBreath holding spellsNight terrorsGastroesophegeal refluxShudder attacksBenign sleep myoclonus

  • DIFFERENCES BETWEEN SYNCOPE AND SEIZURES

    FEATURE

    SYNCOPE

    SEIZURUE

    POSTURE

    UPRIGHT

    ANY POSTURE

    PALLOR AND SWEATING

    INVARIABLE

    UNCOMMON

    ONSET

    GRADUAL

    SUDDEN/ AURA

    INJURY

    RARE

    NOT UNCOMMON

    CONVULSIVE JERKS

    RARE

    COMMON

    INCONTENENCE

    RARE

    COMMON

    UNCONSIOUSNESS

    SECONDS

    MINUTES

    RECORY

    RAPID

    OFTEN SLOW

    POST ICTAL CONFUSION

    RARE

    COMMON

    FREQUENCY

    INFREQUENT

    MAY BE FREQUENT

    PRECIPITATING FACTORS

    CROWDED PLACES, LACK OF FOOD, UNPLEASENT CONDITIONS

    RARE

  • DIFFERENCES BETWEEN SEIZURES AND PSEUDOSEIZRUES

    FEATURE

    EPILEPTIC SZ

    PSEUDO SZ

    ONSET

    SUDDEN

    MAY BE GRADUAL

    RETAINED CONSCIOUSNESS

    IN PROLONGE SEIZURES.

    VERY RARE

    COMMON

    FLAILIN, THRASHING, ASYNCHRONUS LIMB MOVEMENTS

    RARE

    COMMON

    PELVIC THRUSTING

    RARE

    COMMON

    ROLLING MOVEMETNS

    RARE

    COMMON

    MOVEMENTS WAXING & WAINING

    RARE

    COMMON

    CYANOSIS

    COMMON

    UNUSUAL

    TOUNGE BITING AND OTHER INJURY

    COMMON

    LESS COMMON

  • DIFFERENCES BETWEEN SEIZURES AND PSEUDOSEIZRUES

    FEATURE

    EPILEPTIC SZ

    PSEUDO SZ

    STEREOTYPICAL ATTACKS

    USUAL

    UNCOMMON

    DURATION

    SECONDS ,MINUTES

    OFTEN PROLONGED

    RESISTANCE TO PASSIVE LIMB MOVEMENT OR EYE OPENING

    UNUSUAL

    COMMON

    PREVNTION OF HAND FALLIN ON FACE

    UNUSUAL

    COMMON

    INDUCED BY SUGGESTION

    RARELY

    OFTEN

    POSTICTAL DROWSINESS OR CONFUSION

    USUAL

    OFTEN ABSENT

    ICTAL EEG ABNORMALITY

    ALMOST ALWAYS

    ALMOST NEVER

    POST ICTAL EEG ABNORMALITY

    USUALLY

    RARE

  • ADVERSE PROGNOSTIC FACTORS IN EPILEPSYSYMPTOMATIC ETIOLOGY.PARTIAL ONSET SEIZURES.ATONIC SEIZURES.LATE ONSET OR FIRST YEAR EPILEPSYADDITIONAL MENTAL OR MOTOR HANDICAP.LONG DURATION PRIOR TO THERAPY.POOR INITIAL RESPONSE TO THERAPY.

  • Intractable EpilepsyImpairment of quality of life due to Seizures &/ or Drugs20-30% of epileptics are intractablePatients failing 2 drugs are likely to be intractable30-40% newly diagnosed partial epilepsy will not attain a seizure remission with pharmacotherapy.

  • Intractable EpilepsyTreatment options New AED surgery Vagus nerve stimulation special diets in children

  • New Anti Epileptic Drugs

  • There is scarcely a substance in the world ,capable of passing through the gullet of man , that has not at one time or the other enjoyed a reputation of being an anti-epileptic Sieveking 1858

  • Potential benefits of AED related seizure controlReduced social stigmaReduced negative cognitive effects from frequent seizures.Reduced risk of status epilepticus ( if compliant)Reduced risk of physical injuryImprove employment likelihoodHelps maintain driving privileges

  • Risks of AED related adverse effectsBehavioral problems Cognitive impairmentIdiosyncratic reactionsSystemic toxicityTeratogenicityExpense

  • Ideal Antiepileptic DrugAntiepileptogenic

    Complete Seizure Suppression

    Minimal Side Effects

  • FACTS:50 % of patients fail to achieve the goal of treatment. (1985) NEJM 1/3 of patients treated 1984-1997 failed to become seizure free in the first year of treatment. (2000) NEJM

  • Possible Advantages of New AEDMore effectiveBetter toleratedSaferBetter for womenLess interactionBroader spectrum

  • New AED Label Indications

    FelbamateMonotherapy and add-on partial and generalized SZGabapentinAdd-on for partial SZLamotrigineMonotherapy and add-on partial and generalized SZOxacarbazineMonotherapy and add-on partial SZTiagabineAdd-on partial SZTopiramateAdd-on and monotherapy partial and generalized SZLevetiracetamAdd-on partial SZZonisamideAdd-on partial SZ

  • New AED: common concernHigh cost Dose related toxicity Pharmacodynamic interactions Drug levels of limited use

  • New AED : how they compareSimilar in : Responder rate 40% Seizure free rate < 10%Differ in : Adverse effects Pharmacokinetic profile Efficacy for seizure type(s)

  • AED: Future DevelopmentActions at NMDA receptorsActions at AMPA receptorsGABA B receptors and absence seizuresGABA and Glutamate transportersMetabotropic glutamate receptorsSeretoninNeurosteroidsGenetic studies and the nicotinic acetylcholenergic system

  • Epilepsy Surgery

  • Surgical CandidatesMedically refractory seizuresPhysically, socially disabledLocalization-related epilepsyLow risk of morbidityPotential for rehabilitation

  • Response to AED in newly diagnosed epileptics. Kwan et al NEJM, 2000

  • Epilepsy Surgery: TypesMedial temporal lobe epilepsy: MTS Most common Most successful Lesionectomy: Tumor Vascular anomaly Cortical malformationHemispherectomy: Rausmusens encephalitisCorpus callosotomy: LGSVagal nerve stimulation: intractable, not surgical candidatesMultiple subpial transection: elequent areas

  • CONTRAINDICATIONS TO EPILEPSY SURGERYAbsolute: Primary generalized epilepsy Minor seizures that do not impair quality of life Relative: Progressive medical or neurological disorders Behavioral problems that impair post op rehabilitation Serious medical disorder that may increase surgical mortality Poor memory function in the opposite hemisphere Active psychosis not related to peri-ictal period

  • Pre surgical evaluationRoutine EEG Brain MRI (seizure protocol)Long term video EEG monitoringVisual perimetryNeuropsychometrySodium amobarbital test

  • Epilepsy surgery : RisksVisual field loss < 10% (temporal lobectomy)Any surgical complication < 5%Death or serious complication
  • Temporal lobectomy efficacySperling et al, JAMA 1996: 276:470-75%Long term (5 yr) operative outcome of 89 patients

  • Vagus nerve stimulationIndicated for patients with intractable epilepsy who are not surgical candidates

  • Status EpilepticusContinuous or recurrent seizures without recovery of consciousness for 30 minutes or more ( tendency now to use shorter time definition like 5 minutes and more.

  • AED in Status Epilepticus

    DrugLoading doseMaintenance doseAdverse effectDiazepam 10-20 mgNone Respiratory depressionHypotension Sialorrhea Lorazepam4 mgNone As abovePhenytoin 20mg/kg5mg/kg/dayCardiac depressionHypotension Phosphenytoin30mg/kgNone HypotensionParasthesia

  • AED in Status Epilepticus

    DrugLoading doseMaintenance doseAdverse effectPhenobarbital 20mg/kg1-4 mg/kg/hrRespiratory suppression Pentobarbital 2-8mg/kg0.5-5 mg/kg/hrRespiratory suppression Hypotension Midazolam 0

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