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Carolinas Pediatric Neurology Care Jamie Parrott, MD. Seizures in Children. First Seizure. Metabolic Derangement Infectious Disorder Trauma/Brain Injury Nonrecurrent Epilepsy Search for reversible acute cause. Prognosis. Idiopathic: 25% recurrence one year, 45% over 14 years
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Carolinas Pediatric Neurology Care Jamie Parrott, MD Seizures in Children
First Seizure • Metabolic Derangement • Infectious Disorder • Trauma/Brain Injury • Nonrecurrent • Epilepsy • Search for reversible acute cause
Prognosis • Idiopathic: 25% recurrence one year, 45% over 14 years • Remote Symptomatic: 37% one year risk of recurrence • Two seizures separated by >24 hours, 70% one year recurrence risk • TBI/acute illness: Low risk
Treatment • Long term prognosis not influenced by acute initiation of treatment • Any short term benefit of acute prophylactic treatment lost at 3 years • No effect on long term risk of relapse • No effect on long term risk of mortality
Predictors of Recurrence • Abnormal EEG (41% one year recurrence) • Increased risk with abnormal MRI brain (15%) • Status Epilepticus not associated with increased risk of recurrence • Increased risk of recurrent Status Epilepticus if child is later diagnosed with epilepsy (5 fold)
Long-term Remission • 75% two year remission (24% will relapse) • 70% long term remission • 20% not achieving remission are medically intractable • Age of onset<9yo, idiopathic etiology positive predictors • Symptomatic origin and low IQ predictors of intractable epilepsy
Recommendations • Treatment with antiepileptic drugs (AEDs) is not indicated for the prevention of development of epilepsy • Treatment with AEDs should be based on risk and benefit basis • Quality of Life • Treatment of atonic/tonic (drop attacks) seizures, infantile spasms, absence seizures are exceptions
Antiepileptic Drug Therapy • Older Drugs: Broader indications for initial therapy • Newer Drugs: Adjunctive indication typically expanded with experience, further studies • Chosen for seizure type: i.e., phenytoin and carbamazepine may worsen absence and myoclonic seizures
AEDs • Half life: smooth serum levels, less frequent dosing, improved compliance • Cost effectiveness • Suspensions, chewable tablets • IV formulations • Nonlinear Kinetics: Phenytoin, Valproate, Carbamazepine
AED Dosing • Titration reduces side effects (tolerance) and improves compliance • Increase no more frequently than five half lives • Titrate to lowest effective dose • Continue titration for break-through seizures • Titrate to seizure freedom, intolerance, or maximum effective dose
AED Dosing • Dosing interval less than one half-life • Adjust effective dose to body mass • Clearance may decrease with age • With poor response consider genetic factors, compliance, drug interactions
Serum Levels • Used only as a guide to therapy • Baseline level when seizure control achieved • Breakthrough seizures (i.e. ER evaluation) • Compliance concerns • Generic formulation switch
Compliance • Up to 60% nonadherence in first 6 months • Side effects • Complexity of drug regimen • Low socioeconomic status
Adding a Second AED • 20-40% failure of first AED • Lack of efficacy and side effects equally culpable • Titration/taper of AEDs is an art, based on efficacy, tolerability, compliance concerns
Monotherapy vs Polytherapy • Monotherapy is the goal • Improved compliance, lower cost, fewer side effects, lower teratogenicity • Polytherapy considered in patients unresponsive to monotherapy trials • Consider nonpharmacologic adjunctive therapies • Synergistic polytherapy (i.e. Absence Epilepsy)
Laboratory Monitoring • Routine lab screening for hepatic and hematologic function is not necessary or cost effective (exception Felbamate) • Suicidal risk increased for all AEDs • Baseline CBC, CMP • Metabolic studies when neurometabolic disorder suspected • Monitoring based on suspicion of adverse effects
Transmucosal Rescue AEDs • Rectal Valium safe and effective (home) • Respiratory depression rare (absorption rate) • Buccal midazolam equal to or superior to rectal Valium (EMT/ER) • Intranasal midazolam or lorazepam • All Oral suspensions may be considered rectally for short periods • IV: Benzodiazepines, levetiracetam, lacosamide, valproate sodium, phenytoin, phenobarbitol
Stopping AED Therapy • Two years seizure free recurrence rate 30 to 40%; minimal gain over longer periods • Recurrent intractable seizures rare • Symptomatic epilepsy, abnormal EEG at time of withdrawal associated with higher risk of recurrence, 47 to 54% • Younger age and certain seizure types positive predictors of success • Tapering reduces risk of acute seizures
Ketogenic Diet • High fat, low carbohydrate diet with additional protein, water, and calorie restrictions • Effective: 50% with 50% seizure reduction • 10 to 15 % seizure free • Reduced medication load common • Hypercholesterolemia, kidney stones, acidosis, bone health, constipation • Modified Atkins and Low Glycemic Index Diets
Vagal Nerve Stimulator • Programable pulsed vagal nerve stimulation • Can be triggered by magnet acutely • 1/3 of patients with 50% reduction in seizures • Hoarseness, throat discomfort • Antidepressant properties • Possibility of reduced AED load
Epilepsy Surgery • Consider in children with intractable epilepsy interfering with normal development • Lesionectomy and Hemispherectomy • Temporal Lobectomy: most common surgery, 80% cure; transient language dysfunction, 2% permanent memory dysfunction, personality change, reading dysfunction
Extratemporal Lesionectomy • Similar outcome to temporal lobectomy if discreet lesion is present on neuroimaging • Post operative deficits less predictable • Nonlesional/MRI negative success rates less than 40%, but improving with improved preoperative assessment tools (SPECT, PET, intracranial EEG monitoring)
Hemispherectomy • Hemimegalencephaly, Sturge-Weber syndrome, Rasmussen's disease, infarction, cortical dysplasia • Shorter seizure duration, higher developmental progress positive predictors • >50% seizure free at 5 year follow-up • Hemiplegia typically improved/no change • Developmental gains modest
Corpus Callosotomy • Partial (anterior 2/3's), and Complete • Atonic/tonic seizures primarily • Studies suggest improvement in generalized and other seizure types • Improvements include IQ, quality of life, behavior
Long Term Prognosis • Remission more common in children, 50% • Early seizure control, younger age at onset, idiopathic epilepsy associated with good outcome • Status epilepticus more common in children • Effects of AEDs in developing brain • Mortality increased threefold from general population in children with epilepsy • 30% sudden unexplained death
Prognosis • Patients with epilepsy may have psychological, behavioral, cognitive, neurologic, academic, and social problems caused by their seizures, medications, chronic neurologic condition, independent of seizures • Multidisiplinary approach may be needed