Evaluation of the First Seizure and New Onset Epilepsy Douglas R. Nordli, Jr., MD Children’s Memorial Epilepsy Center
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Hauser1990: US Incidence Estimate 100,000 80,000 60,000 # per year
40,000 20,000 0 Febrile
Epilepsy
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Acute S.
Seizures
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Hauser, 1990
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Importance of Epilepsy Etiology • Prognosis • Treatment
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Etiology 80 70 60
Idiopathic Congenital Trauma Vascular Neoplasm
50 40 30 20 10 0 Children
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Adult
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Childhood Idiopathic Epilepsies EPILEPSY GENE
FUNCTION
BFNC
Voltage- K channel
GEFS+ ADNFLE
KCNQ2 and KCNQ3 SCN1B, SCN1A, and SCN2A CHRNA4 or CHRNB
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Voltage- Na channel Acetylcholine
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First Seizure • Provoked- may require emergent evaluation • Unprovoked- usually there is time for reflection
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Non-epileptic Events • • • • • •
Breath holding Cardiac- syncope Movement Disorders Stimulatory Behaviors Migraine Psychogenic
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AAN/CNS Consensus Statement • Laboratory studies – only if clinically indicated (consider toxicology) • LP – only if indicated clinically • Imaging – MRI is preferred. Acute imaging only if indicated. • EEG: – INDICATED (Standard)
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Evaluation of the first unprovoked seizure • • • •
History Targeted physical examination EEG Sometimes brain imaging
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Impact of First Seizure Guidelines • • • •
Study at Children’s Memorial 60 patients before guidelines instituted 120 patients after guidelines Marked reduction in admissions and drug administration • Marked reduction in testing and costs
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Evaluation of the First Seizure • Physical Examination – Acute symptomatic causes • Focal findings, alteration of mentation, clues from history – Underlying predispositions • Phakomatoses
• Laboratory- only if indicated – CBC, electrolytes, GLUCOSE, Ca++, Mg++, toxic.
• LP, if evidence of CNS infection
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EEG is Useful • • • •
Risk of recurrence Seizure type Epilepsy syndrome predisposition Screen for focal abnormalities
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Imaging • MRI • CT for trauma, other acute provoked seizures
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Historical Tips • History – Setting – Sequence – Show-me • Development • Family History
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Prognosis after the first unprovoked seizure S. Shinnar et al. The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up. Pediatrics 1996;98:216-225. • Prospective, 402 children • Mean follow up was 6.3 YRS.
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Shinnar et al • Recurrence risk: 42% • Mean time to recurrence : 11.3 MOS.
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Shinnar et al • Risk Factors for Recurrence: – Remote symptomatic etiology – Abnormal EEG – Nocturnal seizure – Previous febrile seizure – Todd’s paresis
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Classic Treatment Works The First Seizure: Treatment Issues
Musicco M, Behi E, Solari A, Viani F. Neurology 1997
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British Pediatric AED Study AEDs: comparative efficacy • Lancet 1996;347:709-13 • M de Silva et al. • Ages 3-16 years, 2 GTCs or P± GTCs • 167 children randomised to PB, PHY, CBZ, or VPA • Starting doses (mg/kg/d)= 3,5,8,15 • Increments of 2,2,4,5
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Classic Drugs are Equally Effective M de Silva et al, 1996 % Seizure Free 40 35 30 25
PB PHT CBZ VPA
20 15 10 5 0
12
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36
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Classic Drugs Have Same Outcome Time to One Year Remission 1.4 1.2 1
PB PHT CBZ VPA
0.8 0.6 0.4 0.2 0
Time
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Data for Adults-VA Cooperative
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% Seizure Free
Data for Children
CBZ PHT
Pellock et al. 1991
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Time
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New Medications • Broad spectrum – Levetiracetam (Keppra) – Topiramate (Topamax) – Zonisamide (Zonegran) – Felbamate (Felbatal)
• Narrow spectrum – Oxcarbazepine (Trileptal) – Gabapentin (Neurontin) – Tiagabine (Gabatril) Copyright © 2005 Children's Memorial Hospital. All rights reserved.
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Matching the AED to the Child • • • • •
Co-existent Conditions Compliance Concurrent Medications Cosmetic Concerns Prior Drug Reactions
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Summary of AAN evidence-based guidelines level A or B recommendations AED
Newly Diagnosed Monotherapy Partial/mixed
Newly Diagnosed Absence
Gabapentin
Yes*
No
Lamotrigine
Yes*
Yes*
Topiramate
Yes*
No
Tiagabine
No
No
*Not FDA approved for this indication
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Summary of AAN evidence-based guidelines level A or B recommendations AED
Newly Diagnosed Monotherapy Partial/mixed
Newly Diagnosed Absence
Oxcarbazepine
Yes
No
Levetiracetam
No
No
Zonisamide
No
No
*Not FDA approved for this indication
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All Drugs Have AE 80 70 60 50 40 30 20 10 0
%
CBZ
PHT
PB
PRM
VPA
Herrenz et al.
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Cognitive side effects of antiepileptic drugs in children • Loring DW, Meador KJ. Neurology 2004;62:872-877. • Authoritative review of literature
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Phenobarbital • Decreases in IQ: Farwell JR, Lee YJ, Hirtz DG, et al. Phenobarbital for febrile seizures-effects on intelligence and on seizure recurrence. N Enlg J Med 1990;322:364-9. • Lingering effects on academic achievement 3- 5 years later • Sulzbacher S, Farwell JR, Temkin N, et al. Late cognitive effects of early treatment with phenobarbital . Clin Pediatrics 1999;38:387-94.
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Phenobarbital • Effects on attention • Camfield CS, Chaplin S, Doyle AB, et al. Side effects of phenobarbital in toddlers: behavioral and cognitive aspects. J Pediatrics 1979;95:361-5. • Reduced processing efficiency • Riva D, Devoti M. Discontinuation of phenobarbital in children: effects on neurocognitive behavior. Pediatr Neruol 1996;14:36-40. Copyright © 2005 Children's Memorial Hospital. All rights reserved.
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Carbamazepine • No effect on global IQ • Modest effect on memory • Seidel WT, Mitchell WG. Cognitive and behavioral effects of carbamazpine in children: data from benign rolandic epilepsy. J Child Neurol 1999;91:101-105.
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Phenytoin • • •
Smaller effect on IQ compared with PB Similar effects upon memory c/w CBZ Forsythe I, Butler R, Berg, I McGuire R. Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin, and sodium valproate. Dev Med Child Neurol 1991;33:524-34.
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Valproate • Small study, valproate had fewer negative effects upon memory than CBZ or PHT. • Less pronounced effect than PB upon IQ, memory and academic achievement. • Vining EP, Mellitis ED, Dorsen MM et al. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobaribtal and valproic acid. Pediatrics 1987;80:165-74. Copyright © 2005 Children's Memorial Hospital. All rights reserved.
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New Drugs • • • • •
No formal neuropsychological investigations All report some drowsiness GBP- aggressive behavior Wolf et al, Tallian et al. LTG- some improvements LVT- behavioral effects in 15 of 39 patients (aggression in 6, sedation in 6, hyperactivity in 4 and other behaviroal events in 9) Wheless JW and Ng YT. Levetircetam in refractoy pediatric epilepsy. J Child Neurol 2002;17:413-5.
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New Drugs • TGB- asthenia (19%), nervousness (10%) and somnolence (17%) Uldall Et al, 2000. • TPM- emotional lability 12%, fatige 15%, difficulty with attenion and concentration 12% forgetfulness/impaired memory 7%. Study of 86 children, Elterman et al, 1999. • VGB- antisocial behavior, irritability and excitability. Zamponi et al. • ZNS- psychosis, obsessive-compulsive symptoms
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Remission Rates, Sillanpaa et al, 1998; 30 year follow-up 100 90 80 70 60 50 40 30 20 10 0
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All Pts Incident Idiopathic Cryptogen Symptom
%
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Sillanpaa et al, 1998 • • • •
Completed only six years of school 2.13 Unemployed 3.76 Not married 3.5 No children 3.0
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What does this mean? • Epilepsy is more than just 2 seizures
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School Problems • • • • •
A- attention B- behavior C- cognition D- disability, depression, drugs (AEDs) E- expectations
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What is out there? • Newer Treatments – “Neuroprotective”
• Newer Studies – other outcome measures including development; collaborative designs
• Comprehensive treatment plans
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