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Diagnosis & Treatment of Pediatric Epilepsy. Joseph E. Sullivan, M.D. Assistant Professor of Clinical Neurology & Pediatrics Director, UCSF Pediatric Epilepsy Center. Outline. Proper seizure/epilepsy classification Why treat? When to treat? Treatment options Outcomes.
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Diagnosis & Treatment of Pediatric Epilepsy • Joseph E. Sullivan, M.D. • Assistant Professor of Clinical Neurology & Pediatrics • Director, UCSF Pediatric Epilepsy Center
Outline • Proper seizure/epilepsy classification • Why treat? • When to treat? • Treatment options • Outcomes
Epilepsy Classification • History, history, history • Tests are ancillary and rarely confirmatory • Describe what the observer saw FIRST! • Behavior arrest • Staring • Eye deviation • Myoclonic jerk
“New-onset” seizure clinic • History, history, history from the WITNESS • 74% were diagnosed epileptic (94/127) • 36% had previous ambiguous event • 41% had abnormal EEG • 64% were imaged and 18% were abnormal Hamiwaka, LD, et.al. Epilepsia, 48(6):1062-66, 2007
Focal Seizures • Focal sensory • Focal motor • Clonic • Asymmetric tonic posturing • With automatisms • Gelastic • Secondarily generalized seizures
EEG • Evaluate background • Screen for inter-ictal discharges or focal slowing • Rarely capture an event/seizure • Video EEG
EEG • 2-5% of normal children may have abnormal EEG • 50% of children with epilepsy may have normal single EEG • 3 EEG’s including sleep 90% abnormal • Treat patients NOT EEG abnormalities
Classification • 59% of newly diagnosed children have focal epilepsy • 20% may have specific epilepsy syndrome diagnosis • 12% unable to be classified at diagnosis
Reasons to order urgent neuroimaging (usually in ED)? • Diagnose an underlying condition that requires immediate intervention. • Hemorrhage • Stroke • Cerebral Abscess • Tumor with resultant hydrocephalus
Abnormal Imaging Scenarios • Must know prior to d/c from ED • New bleed, abscess • Good to know within 2-4 weeks • Tumor • Whenever • Malformation of cortical development, remote encephalomalacia
Evidence based? • 500 children with a first non-febrile seizure • 475 imaged in the ER • 8% with “clinically significant” abnormalities • 3/475 had findings needed immediate intervention • 1 shunt failure • 1 increased intra-cranial pressure after head trauma • 1 with new-onset infantile spasms and a neoplasm Sharma et al. Pediatrics 2003;111:1-5
High risk groups • High-risk groups to image in the ER • Known bleeding or clotting disorders • Known hx of malignancy • HIV infection • Closed head injury • Less than 33 months with a focal seizure Sharma et al. Pediatrics 2003;111:1-5
Who was missed Sharma et al. Pediatrics 2003;111:1-5
But what about a brain tumor! • 200 consecutive children with new diagnosis of brain tumor • 30/200 (9%) presented with a seizure • 19/30 had focal seizures • 11/30 had generalized seizures Wilne et al. AJDC 2006;91:502-506
Of the 30 patients presenting with seizures • 17 had no other symptoms and a normal exam • 14/17 focal seizures • 3/17 generalized seizures • 2/3 had focal slowing on EEG • 1/3 atypical absence seizures Wilne et al. AJDC 2006;91:502-506
AAN Practice Parameter Recommendation“Evaluating a first nonfebrile seizure in children” • If a neuroimaging study is obtained, MRI is the preferred modality. • Emergent neuroimaging should be performed if there is a post-ictal focal deficit not quickly resolving, or who has not returned to baseline within several hours after the seizure. Hirtz, D Neurology 2000;55:616-623
Who to admit • Children less than 1 year old • Prolonged seizure (>15 minutes) • Not back to baseline after 4 hours
What to tell parents • Back to some key components in the history • Child neurologically normal? • Did the seizure occur while awake or asleep? • Simple questions but very important
Overall Recurrence Risk • 42% recurrence • Mean time to recurrence 11.3 months • 36% in first month • 53% in 6 months • 88% in 2 years
Normal Child vs Abnormal Child • Cryptogenic (ie otherwise normal)=37% • Remote symptomatic (ie neonatal HIE, history of stroke, autism, etc)=68%
But the seizure was 1 hour long! • First time seizure as status does NOT affect recurrence risk • 12% of Shinnar cohort presented with status • Recurrence risk at 2 years is still 38% for cryptogenic kids • Of those with status 21% of those who had a recurrence had recurrence of status. • Don’t be afraid to give Diastat in these cases
Why do we treat? • Reduce recurrence risk • Prevent prolonged seizures • Minimize impact on development/academic achievement • Does NOT affect natural history • if you are going to outgrow it, you will regardless of treatment
The Normal Child • Awake, and normal EEG=19% • Asleep, normal EEG-37% • Awake, abnormal EEG=42% • Asleep, abnormal EEG=63% Shinnar, S Pediatrics 1996 ; 98:216-225
When to treat? • Depends on the patient/family and seizure frequency • Daily, weekly, monthly seizures • Every 6 months • Yearly • Prolonged seizures/convulsions
Treatment? • Every child/family is different • Treatment may reduce recurrence risk by as much as 50%. • AED’s are toxic medications! • For the most part we do not treat after a first time seizure. • The one exception- Remote symptomatic presenting in status. Shinnar, S Pediatrics 1996 ; 98:216-225
Treatment options • Daily anti-epileptic drugs (AED’s) • Abortive medications • Specialized diets • Surgery • Resective • Devices, ie Vagal nerve stimulator
Medications • 16 anti-epileptic drugs (AED’s) available in U.S. • Many used “off-label” • Very few studies in children
First generation Phenobarbital Phenytoin (Dilantin) Carbamazepine (Tegretol) Ethosuxamide (Zarontin) Valproate (Depakote,Depakene) Benzodiazepines Lorazepam (Ativan) Midazolam (Versed) Diazepam (Valium) Clonazepam (Klonipin) Chlorazepate (Tranxene) Second generation Ox-carbazepine (Trileptal) Lamotrigine (Lamictal) Gabapentin (Neurontin) Topiramate (Topamax) Levetiracetam (Keppra) Zonisamide (Zonegran) Pregabalin (Lyrica) Lacosamide (Vimpat) First vs Second generation
Special siutation AED’s • Vigabatrin (Sabril)-infantile spasms, seizures in setting of tuberous sclerosis • ACTH/steroids-infantile spasms • Felbatol-medically resistant atonic/drop seizures
What is the difference? • 2nd generation AED’s have wider therapeutic windows • No need to follow levels • Can increase based on side effects • Less interactions with other drugs • Most have similar efficacy
Just pick a drug from a hat? • Some AED’s are better for specific seizure types/syndromes • Absence-Ethosuxamide (carbamazpine is contraindicated) • Juvenile myoclonic epilepsy-valproate, lamotrigine, levetiracetam • Co-morbidities • Avoid AED’s that could worsen co-morbidities • Favor AED’s that may help co-morbidities • Formulation (liquid, sprinkle, tablet, capsule)
Common Co-morbidities • Weight gain-ox-carbazepine, valproate, gabapentin, pregabalin • Weight loss-topiramate, zonisamide • Altered blood counts- carbamazepine, valproate • Headaches-topiramate, carbamazepine, valproate, levetiracetam
Side Effects • Phenobarbital-sedation • Valproate-weight gain, liver toxicity, decreased platelets, pancreatitis • Sodium abnormalities-ox-carbazepine • Lamotrigine-Steven’s Johnson syndrome • Topiramate-weight loss, language dysfunction, kidney stones, glaucoma • Levetiracetam-irritability,agitation
Pediatric formulations ** 3-4 times per day
Treatment Goal • Single medication at a dose with NO side effects • If first medication does not work-trial of another single medication • If second medication alone is not effective, trial of polytherapy (2 or more drugs) • Rarely are 3 medications better than 2 • Side effects increase
Outcomes • Most children with epilepsy do VERY well • One study 83% required a single AED in first year of treatment • 61% of these were seizure free off meds at end of study---REMISSION • Only 4% with favorable response in first year developed intractable epilepsy • 17% with inadequate control • 42% still achieved remission • 29% develop intractable epilepsy Camfield, PR et.al., J Pediatr, 1997:131:821-24
Long Term Follow-up • 37 year f/u of 144 patients • 31% enter remission in first year of Rx • 19% are resistant from the beginning • Overall 67% achieve terminal remission • 14% on AED’s • 86% off AED’s Sillanpaa, M & Schmidt, D Brain 2006, 129, 671-624
When to wean? • Seizure free for 2 years • Single seizure type • Normal EEG on AED’s • Normal IQ • Normal neurologic examination
Less “favorable” factors • Age greater than 12 years • Family history of epilepsy • Frequency of seizures at onset (>21) • Slowing on EEG • Remote etiology