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Diagnosis & Treatment of Pediatric Epilepsy

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

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  1. Diagnosis & Treatment of Pediatric Epilepsy • Joseph E. Sullivan, M.D. • Assistant Professor of Clinical Neurology & Pediatrics • Director, UCSF Pediatric Epilepsy Center

  2. Outline • Proper seizure/epilepsy classification • Why treat? • When to treat? • Treatment options • Outcomes

  3. Epilepsy Classification • History, history, history • Tests are ancillary and rarely confirmatory • Describe what the observer saw FIRST! • Behavior arrest • Staring • Eye deviation • Myoclonic jerk

  4. “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

  5. Infantile Spasm

  6. Head drop/atonic

  7. Atonic-myoclonic

  8. Eyelid Myoclonia

  9. Focal Seizures • Focal sensory • Focal motor • Clonic • Asymmetric tonic posturing • With automatisms • Gelastic • Secondarily generalized seizures

  10. Focal clonic

  11. Frontal

  12. Supplementary Motor

  13. EEG • Evaluate background • Screen for inter-ictal discharges or focal slowing • Rarely capture an event/seizure • Video EEG

  14. 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

  15. Classification • 59% of newly diagnosed children have focal epilepsy • 20% may have specific epilepsy syndrome diagnosis • 12% unable to be classified at diagnosis

  16. Neuroimaging

  17. Reasons to order urgent neuroimaging (usually in ED)? • Diagnose an underlying condition that requires immediate intervention. • Hemorrhage • Stroke • Cerebral Abscess • Tumor with resultant hydrocephalus

  18. 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

  19. 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

  20. 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

  21. Who was missed Sharma et al. Pediatrics 2003;111:1-5

  22. 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

  23. 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

  24. 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

  25. Who to admit • Children less than 1 year old • Prolonged seizure (>15 minutes) • Not back to baseline after 4 hours

  26. 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

  27. Overall Recurrence Risk • 42% recurrence • Mean time to recurrence 11.3 months • 36% in first month • 53% in 6 months • 88% in 2 years

  28. Normal Child vs Abnormal Child • Cryptogenic (ie otherwise normal)=37% • Remote symptomatic (ie neonatal HIE, history of stroke, autism, etc)=68%

  29. 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

  30. 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

  31. 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

  32. When to treat? • Depends on the patient/family and seizure frequency • Daily, weekly, monthly seizures • Every 6 months • Yearly • Prolonged seizures/convulsions

  33. 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

  34. Treatment options • Daily anti-epileptic drugs (AED’s) • Abortive medications • Specialized diets • Surgery • Resective • Devices, ie Vagal nerve stimulator

  35. No seizures and No side effects!

  36. Medications • 16 anti-epileptic drugs (AED’s) available in U.S. • Many used “off-label” • Very few studies in children

  37. 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

  38. Special siutation AED’s • Vigabatrin (Sabril)-infantile spasms, seizures in setting of tuberous sclerosis • ACTH/steroids-infantile spasms • Felbatol-medically resistant atonic/drop seizures

  39. 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

  40. 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)

  41. Common Co-morbidities • Weight gain-ox-carbazepine, valproate, gabapentin, pregabalin • Weight loss-topiramate, zonisamide • Altered blood counts- carbamazepine, valproate • Headaches-topiramate, carbamazepine, valproate, levetiracetam

  42. 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

  43. Pediatric formulations ** 3-4 times per day

  44. 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

  45. 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

  46. 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

  47. When to wean? • Seizure free for 2 years • Single seizure type • Normal EEG on AED’s • Normal IQ • Normal neurologic examination

  48. Less “favorable” factors • Age greater than 12 years • Family history of epilepsy • Frequency of seizures at onset (>21) • Slowing on EEG • Remote etiology

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