Clinical Epilepsy: Syndromes, Causes, and EffectsSeizures vs EpilepsyPartial (focal) SeizuresLocalization of Partial Seizure FocusTemporal Lobe Complex Partial SeizurePrimarily Generalized SeizuresAbsence SeizureSeizure vs EpilepsyEpidemiology of Seizures and EpilepsySeizure PrecipitantsEEG AbnormalitiesSlide 12Slide 13Slide 14Slide 15Rational Use of AEDs: All Prescriptions Market Dynamics for All Indications and EpilepsySlide 17Summary of Serious and Non-serious Adverse Events of the Newer AEDsSlide 19Treatment/Evaluation Sequence for Pharmacoresistent EpilepsyOther Treatments of EpilepsyEvaluation for Surgery- NeuroimagingEpilepsy Surgery- NeuroimagingEvaluation for Surgery- Subdural Grid ElectrodesLeft Anterior Temporal LoectomyFactors Affecting Adaptation in EpilepsyFactors Affecting Cognitive Function in EpilepsyWhat Seizure Related Factors May Affect Cognition in Epilepsy?Seizure-Related Variables That May Affect Cognition and BehaviorEpileptic SyndromeIdiopathic SyndromesAdverse SyndromesLocalization Related SyndromesSlide 34Adults with Childhood Seizure OnsetTotal and Segmented Volumes (7.8 years vs. 23.3 years)Total Lobar White MatterCause or Effect?Age of Onset and Neuropsychological OutcomeChildhood TLE OnsetSlide 41EtiologySlide 43Seizure BurdenCumulative Seizure Effects? (is epilepsy progressive?)Progressive Hippocampal SclerosisNeuropsychological Effects of Poorly Controlled SeizuresNeuropsychological Effects of SeizuresCross-sectional TLE Neuropsychological OutcomeEducational Attainment and Seizure DurationEpilepsy and Quality of LifeSlide 52Comparison of Average Monthly Seizure Rate to HRQOLSlide 54Psychiatric ComorbiditiesSlide 56Clinical Epilepsy: Syndromes, Causes, and EffectsRussell M. Bauer, Ph.D.Department of Clinical & Health Psychology2Seizures vs EpilepsyDefinition: the clinical manifestation of an abnormal and excessive excitation of a population of cortical neuronsIncidence: approximately 80/100,000 per yearLifetime prevalence: 9% (1/3 benign febrile convulsions)Definition: a tendency toward recurrent seizures unprovoked by systemic or neurologic insultsIncidence: approximately 45/100,000 per year Approximately 181,000 people will experience seizures or develop epilepsy each yearPoint prevalence: 0.5-1% (2.5 million)14 years or younger 13% 15 to 64 years 63%65 years and older 24% Cumulative risk of epilepsy through 74 years old: 1.3% - 3.1%Seizures Epilepsy3Partial (focal) Seizures•Simple Partial Seizure–no loss of awareness•Complex Partial Seizure–Impaired consciousness/ level of awareness (staring)–Clinical manifestations vary with origin & degree of spread–Presence and nature of aura•Temporal lobe: smell, epigastric sensation, deja vu–Automatisms (manual, oral)–Other motor activityFrontal: bicycling and fencing posture–Duration (typically 30 seconds to 3 minutes)–Amnesia for event•Partial Seizure with Secondary GeneralizationLocalization of Partial Seizure Focus70%70%10%10%20%20%Temporal Lobe Complex Partial SeizureRhythmic 5-7 Hz theta from the mesial temporal lobeRhythmic 5-7 Hz theta from the mesial temporal lobe6Primarily Generalized Seizures•Absence–Typical (3 Hz spike and wave)–Atypical (2.5 to 4.5 Hz spike and wave, polyspike)–Brief staring (<30sec); automatisms rare; not post-ictal confusion•Myoclonic–Brief, shock-like muscle contractions- Head- Upper extremities–Usually bilaterally symmetrical–Consciousness preserved–Precipitated by awakening or falling asleep–May progress into clonic or tonic-clonic seizure–May be associated with a progressive neurolgic deterioration–Juvenile Myoclonic Epilepsy (JME)•Polyspike wave•Onset late adolescence•Chromosome 6p–Progressive Myoclonic Epilepsies•Atonic/ Tonic/ Tonic-ClonicAbsence Seizure3 Hz spike and waveSeizure vs EpilepsySeizuresCardiovascularDrug relatedSyncopeMetabolic (glucose, Na, Ca, Mg)Toxic (drugs, poisons)PoisonInfectiousFebrile convulsionsNonepileptic seizuresAlcohol/drug withdrawalSubstance abusePsychiatric disordersSleep disorders (parasomnias, cataplexy)Nonepileptic Epilepsy(recurrent seizures)Idiopathic(primary)Symptomatic(secondary)9Epidemiology of Seizures and Epilepsy01020304050607080900 10 20 30 40 50 60 70 80AgeIncidence per 100,000PartialGeneralized tonic-clonicPrimary GeneralizedEpilepsy: Incidence Rates by Seizure TypeEpilepsy: Incidence Rates by Seizure TypeData from Rochester, Minn (1935-1979). Adapted with permission from Annegers JF. In: The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997:165-172.Hauser et al, 1992 Ramsay RE, et al. Neurology. 2004;62(5 suppl 2):S24-S29Hemorrhage2%Head Trauma7%Other*19%Atherosclerosis15%Cerebral Infarct33%Unknown24%CHI5%Con4%Id85%D1%N4%V1%Inf0%.* Includes known etiologies such as arteriovenous malformation and venous angioma.Seizure PrecipitantsLow (less often high) blood glucoseLow sodiumLow calciumLow magnesiumStimulant or other proconvulsant toxicity (i.e., cocaine)Sedative (i.e., valium or alcohol) withdrawalSevere sleep deprivationEEG Abnormalities•Background abnormalities-Significant asymmetries and/or degree of slowing inappropriate for clinical state•Transient abnormalities associated with seizures-Spikes (< 70 m sec)-Sharp waves (~70 – 200 msec)-Spike-wave complexes•May be focal, lateralized or generalizedEEG AbnormalitiesTreatment of New Onset EpilepsyKwan P, Brodie MJ. N Engl J Med 2000; 342: 314-9.S z -fre e w/ 1st AED47%Sz -fre e w/ 3rd AED/Polyth e rapy4%S z -fre e w/ 2n d AED13%Re fractory/Ph arm acore si stan t36%S z-free w/ 1st AEDS z-free w/ 2nd AEDS z-free w/ 3rd AED/PolytherapyRefractory/PharmacoresistantKwan and Brodie. NEJM 2000; 342: 314-319.Mohanraj and Brodie. Epil Behav 2005; 6: 382-387Kwan and Brodie. NEJM 2000; 342: 314-319.Mohanraj and Brodie. Epil Behav 2005; 6: 382-387Rational Use of AEDs: All PrescriptionsMarket Dynamics for All Indications and EpilepsyTOPAMAX14.8%TRILEPTAL8.0%LAMICTAL8.1%GABITRIL1.8%ZONEGRAN2.1%KEPPRA4.7%NEURONTIN60.6%050000000100000000150000000200000000250000000300000000350000000400000000450000000 Second Gen. AEDs First Gen. AEDs27%44%9%5%15%EpilepsyPsychiatric d/ o'sPain disordersHeadache/ migraineOther01020304050Carbamaz epine Depakote DRDepakote ER Depakote sprinklesKeppra LamictalNeurontin PhenytoinTopomax TrileptalAED Prescription Volume (%)AED Prescription Volume (%)Age Group (years)PharMetrics. April 2002 to June 2003.