Controlling Seizures Staying Health Orrin Devinsky, M.D. Department of Neurology NYU Langone School of Medicine

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  • Controlling Seizures Staying HealthOrrin Devinsky, M.D.Department of NeurologyNYU Langone School of Medicine

  • What is Epilepsy?Occasional, sudden, excessive, rapid, and local discharge of grey matter (Jackson, 1890)We focus on what we see, not what is missingSudden there are continuous disorders of neural functioningExcessive there is often deficient inhibition of neuronal activityRapid changes may be fast at the human sensory level but slow at the cellular level

  • Diagnostic ChallengesDefine epilepsy syndromeVideo-EEG monitoring Understand the cause of epilepsyHigh resolution MRIGenetic studies (GEFS+, Chromosomal microarrays)Define factors that provoke seizuresFAILUREIdentify long-term effects of epilepsy &s its treatment

  • Therapeutic ChallengesNo seizures, no side effects If patients had their choice: No doctors, No MedicinesIn general, would rather see doctor than take medication

  • Therapeutic ChallengesOngoing assessment: consequences of seizures and therapyHow aggressive to pursue seizure control?Do we treat interictal EEG?? Benign rolandic epilepsyHow to assess effects of long-term therapies?

  • Fooled by Experience: Toms Seizure9 am Saturday morning Tonic-clonic seizure, witnessed by his childrenMy first question: any provocative factor? Missed meds, sleep deprivation, alcohol?Nothing reallyMissed meds, but cant be that I do it all the time

  • Risks, Rewards, Perfect StormsKnown provocative factorsMissed medicationsSleep deprivation/time zone sExcess alcohol (> 2 drinks)Physical or emotional stressFactors are not additive but synergisticLinear or non-linearMany factors unknown

  • Seeing patterns, Finding MeaningWWII V2 rockets in London Germans precisely targeted areas &avoided spiesCancer clusters in CA 5000 census areas, 2,750 with statistically significant but random elevations of some cancerYour idea: find evidence it is wrong, not only right

  • Missing PatternsOur mind sees stabilityIt fills in holes from your visual blindspot to the sentences you hearOn chronic AED therapy and this may only be months one may start to forget how they felt or their relative behaved before the medicineThis is especially problematic when medicine dose is increased slowly and other factors (eg, seizures, stress) are present

  • Mistakes Ive Made

    Relying on prior diagnosisBecoming invested in a course of actionNot listening to the informationNot challenging ones own conclusionFinding information that supportsExplaining information that doesnt fit

  • Physician Selection of AEDs AED relative efficacy:toxicityKnowledgePublished studiesRandomized v. open-labelDose range, methodologyStatistical v. clinical significanceInformation from colleaguesPersonal experienceBelief, Bias, & Comfort Zone

  • A Case Study29 y.o. woman monthly CPS, rare GTCsRoutine 6 mo. Checkup: complains of some tiredness, blurred vision, nauseaExam - mild nystagmus, tremorLabs - slightly elevated LFTsMDs perspective - doing greatWomans perspective - doing poorly; not driving, underemployed, fearful of seizures, troubled by AEs

  • What is Seizure Control?Relative termAre there things to encourage the resolution of epilepsy?Epileptogenesis the process by which epilepsy develops, for example, after a head injuryAnti-epileptogenesis preventing the process by which epilepsy developsReverse epileptogenesis reversing the process by which epilepsy develops

  • Why is Seizure Control Important?Quality of lifePrevention of injury, accident, SUDEPPrevention of progressionThe longer you are seizure free, the longer you stay seizure freeThe longer you are seizure free, the greater the chances of staying seizure free off medication

  • Progression of EpilepsyFor some, epilepsy is a progressive disorderMRI progressive hippocampal atrophy with continued seizures41 years old 44 years old75 Partial Seizures & 5 GTCS in 3 yearsFuerst et al, Ann Neurol 2003

  • Mental Status and Seizures in TSCGomez M 1979;18-19.

    Mental StatusNo EpilepsyWith Epilepsy TotalNormal194059MR 08989Total19129148

  • Mental Status and Seizures in TSCGomez M 1979;18-19.

    Age (yr) Sz OnsetNormal IntelligenceMentally Retarded0-17722-41395-96310-1421=>15112Total3987

  • Histological Studies of TLEDendritic spine density remote from seizure focus reduced with increased epilepsy durationMultani et al, Epilepsia 1994;35:728-36Hippocampal neuron density declines with chronic habitual seizuresMathern et al, Brain 1995 Epilepsy Res 1996

  • PET Temporal HypometabolismResults from neuronal loss and functional factors. Can occur without atrophy. Extends beyond seizure focus.Associated with epilepsy duration

  • Extratemporal Volume Loss & Hypometabolism in TLEWhole brain volumes reduced In TLE, thalamic volumes & metabolism are reduced Thalamic reduction ipsilateral to focus epilepsy duration cerebellar metabol

  • Normalization of PET Abnormalities after Successful TLE SurgeryMetabolism normalizes in contralateral mesial temporal lobe and in ipsilateral frontal cortex and thalamus after temporal lobectomy!

  • Normalization of MRS Abnormalities after Temporal LobectomyNAA/Cr increased to normal range on side of surgery in seizure free patientsNAA/Cr (Ipsilateral & Contralateral) increased 50% by 6mos and 95% by 25 mos in seizure-free patients Contralateral hippocampus NAA improves

  • Cross Sectional Neuropsychological Studies in Epilepsy PatientsRelationship of Epilepsy Duration & Mental DeteriorationSTRONGMODERATELennox & Lennox (1960)Dikman & Matthews (1977)Dodrill & Troupin (1976)Jokeit & Ebner (1999)Gomez (1979)Jokeit et al (2000)Dodrill (1986)Hermann et al (2002) Oyegbile et al (2004)

    MILDNONE BUT + AGE ONSETTrimble (1988)Strauss et al (1995)Jokeit et al (1999)Helmstaedter & Elger (1999)

  • The Value of ExerciseExercise is good for your brain, whether you are a mouse or personSalk studies mice given access to running wheels produce more brain cells in a vital memory area of the brainWomen age 70-80 with mild cognitive impairment, brisk walking or weight training prevents memory decline and in some cases, improvements (compared with toning)

  • Exercise & EpilepsyAnimal studies aerobic exercise increases the threshold to evoke epilepsy in several animal models (Airda)Swedish military recruits individuals who entered military and had low cardiovascular fitness had a 79% increase of developing epilepsy after controlling for education, heredity, and other factors (Ben-Menachem)

  • The Value of SleepMentalImproved mood, memory, attention, judgment and reasoningCardiovascular lower risk of diseaseImmune suppressionGrowth suppressionObesityAdult onset diabetes

  • Sleep & EpilepsySleep deprivation reliable method to evoke seizuresCircadian shifts can lower seizure threshold without sleep deprivationSudden shifts need a plane

  • Diet & EpilepsyKetogenicModified AtkinsLow glycemic

  • Dietary Supplements & Epilepsy? Less restrictive carbohydrate dietsNo evidence that any supplement reduces seizure frequency outside rare genetic/nutritional disordersPyridoxine & Vitamin E deficiencies


  • Alternative Therapies for EpilepsyWhat to do: medicine fails, problems persist?Limits of proving any efficacyDoctors get it wrongInternal mammary artery bypassPatients get it wrongAutism and vaccineNeed really good data otherwise, impossible to know

  • EVIDENCE: HEIGHT OF ABSURDITYParachute to prevent death & trauma related to gravitational challenge: systematic review of randomized controlled trials1No RCTs of parachute use Basis for parachute use is purely observational; apparent efficacy could be explained by a healthy cohort effectIndividuals who insist that all interventions need to be validated by a RCT need to come down to earth with a bump 1Smith, GCS, Pell, JP BMJ 2003

  • Stopping Prolonged Seizures &Seizure ClustersHow much water to put out a fire?Prolonged febrile seizuresLessons from Dravet if you know there is a tendency to have prolonged seizures, hit them early, and hard if neededOptionsDiastat (rectal diazepam)Buccal midozalamIntranasal midazolam

  • Double-Blind, Placebo-Controlled Randomized Trial Doctors and patients are biasedInternal mammary artery bypassBeta blockers vs. ACE inhibitors for hypertensionMotivated reasoningConfirmational biasIf you support the Death Penalty, can you objectively evaluate new data? The Myth of Associationism-CausationVaccines and seizuresMercury and autism

  • Concluding ThoughtsThink healthy - we largely are who we decide we will beAct health work hard to be physically active, eat healthy, limit alcohol, sleep well, avoid stressorsTake your own pulse as patient, as caregiverSearch hard to understand, be humble

    TOP: Missense (circles), inframe deletions (triangles) BOTTON: Truncation (stars)TOP: Missense (circles), inframe deletions (triangles) BOTTON: Truncation (stars)TOP: Missense (circles), inframe deletions (triangles) BOTTON: Truncation (stars)*