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Pediatric Epilepsy

Pediatric Epilepsy. Overview of seizures and epilepsy and medications Management of specific issues The first unprovoked seizure The patient with known epilepsy Febrile Seizures Neonatal seizures. Does the patient have epilepsy? Seizures vs. Epilepsy. Epilepsy :

hanae-zamora
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Pediatric Epilepsy

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  1. Pediatric Epilepsy • Overview of seizures and epilepsy and medications • Management of specific issues • The first unprovoked seizure • The patient with known epilepsy • Febrile Seizures • Neonatal seizures

  2. Does the patient have epilepsy?Seizures vs. Epilepsy • Epilepsy: • Most recent ILAE definition: “a disorder of the brain characterized by an enduring predispostion to generate epileptic seizures and by the neurobiological cognitive psychological and social consequences of this condition” • occurrence of two or more unprovoked seizures • Seizure: • a transient occurrence of signs and symptoms due to abnormal or excessive or synchronous neuronal activity in the brain

  3. Was it a seizure? • Syncope- vasovagal, cardiogenic • Sandifer syndrome • Breath holding spell • Migraine • Tics • Psychogenic • Sleep myoclonus • Paroxysmal dystonia

  4. Classification of seizures

  5. Epilepsy Syndromes • Triad of seizure type or types, age and EEG findings • Different medications for different syndromes!! • Very different prognoses for different syndromes

  6. Epilepsy Syndromes • Benign Rolandic Epilepsy of Childhood • Absence Epilepsy • Juvenile Myoclonic Epilepsy • Benign Occipial Epilepsy • Lennox-Gastaut Syndrome • Infantile Spasms

  7. Benign Rolandic Epilepsy of Childhood • Age: 5-16 years old • Seizure type: nocturnal, partial (anarthria), may generalize • EEG: bilateral independent central temporal spikes • Prognosis: Excellent • Meds: Tegretol, any medication for partial seizures

  8. Benign Rolandic Epilepsy

  9. Absence epilepsy • Age: • Childhood absence epilepsy begins 5-10 years old • Juvenile absence begins around puberty • Seizure type: absence, may also have generalized convulsions • EEG: 3 HZ spike wave discharges • Prognosis: excellent (particularly for childhood onset) • Medication: • Ethosuccimide, valproic acid, lamotrigine • Exacerbated by Tegretol

  10. Absence epilepsy

  11. Juvenile Myoclonic Epilepsy • Age: begins 10-15 years old • Seizure type: myoclonic jerks (usually in morning), staring spells, convulsions • EEG: 3-4 Hz generalized discharge with spike and polyspike waves • Prognosis: good (easily controlled usually,but doesn’t usually grow out of it) • Medications: • Valproic acid, lamotrigine • Exacerbated by tegretol and phenytoin

  12. Juvenile Myoclonic Epilepsy

  13. Lennox Gastaut Syndrome • Age: 2-5 years • Seizure types: generalized, atonic, myoclonic, absence, partial • EEG: “slow” spike and wave • Prognosis: poor • Medication: will usually need polypharmacy; valproic acid, topamax, lamotrigine

  14. Anticonvulsants

  15. First Generation Anticonvulsants • Phenobarbital • Phenytoin • Carbamazepine • Valproic acid • Ethosuximide

  16. First Generation Anticonvulsants • Phenobarbital • Broad spectrum, most seizure types • Excellent safety profile • Sedation, hyperactivity, decreased IQ • Used primarily for young infants • Phenytoin • Partial, generalized seizures • Worsens absence and myoclonus • Gum hyperplasia, hirsutism, facial coarsening with long term use • Fospenytoin for status • Carbamazepine • Partial, generalized seizures • Worsens absence and myoclonus • Valproic acid • Generalized (convulsive and nonconvulsive) • Highest risk of hepatotoxicity • Most teratogenic • Ethosuximide • Absence only

  17. Phenobarbital • Excellent for GTC, partial seizures • Especially used in neonates • Excellent safety profile • Good absorption • IV/IM/PO(liquid form) • Long half life • qD-bid dosing • Side effects of sedation (acutely), hyperactivity and decrease IQ (chronic use) limits its long term use • Monitor drug level and LFTs • Many drug interactions • induces cyt p450 • OCPs, TCAs, VPA, tegretol, dilantin • Usual dosing: 3-6mg/kg/d div qD-BID

  18. Phenytoin (Dilantin) • Useful for GTC and partial seizures • Worsens absence and myoclonus • Pharmacokinetics:Non linear pharamakonietics (small change in dosage can lead to large change in level) • Side effects: Short term: Ataxia, nystagmus vertigo, sedation, dizziness. Long term: hirsutism, gum hyperplasia, facial coarsening • Idiosyncratic effects: Stevens-Johnson, bone marrow depression, SLE, hepatitis • Drug interaction: (induces cyt p450) erythro, dilantin, VPA, INH, OCP, etc. • Avg.Daily Maint: 4-7mg/kg/d div qD-BID • Forms: tabs, chewable, sust release, susp., IV • Therap. Lvl (mcg/ml):10-20 • Monitoring: followdrug level, CBC, LFTs

  19. Carbamazepine (Tegretol) • Useful for GTC and partial seizures • Worsens absence and myoclonus • No IV form • Pharmacokinetics: Autoinduction of metabolism • Side effects:Ataxia,nystagmus,vertigo,dizziness,sedation, SIADH • Idiosyncratic effects:bone marrow depression,Stevens-Johnson, hepatotoxicity • Drug interactions: (induces cyt p450)erythro, dilantin, VPA, phenobarb, INH, OCPs, grapefruit juice • Avg.Daily Maint: 15-30mg/kg/d div. TID • Forms: tabs, chewable, liquid,Tegretol XR,Carbatrol • Monitoring: drug level,CBC, CMP, level

  20. Valproic Acid(Depakene/Depakote) • Seizure Type:Absence, myoclonic, atonic, GTC • Side effects: Thrombocytopenia, weight gain, tremor, platelet dysfunction, sedation, polycystic kidneys, alopecia, teratogenic • Idiosyncratic effects:Hepatotoxicity, pancreatitis, aplastic anemia, StevensJohnson • Drug interactions:TCAs, lithium, OCPs, ASA, dilantin, tegr, phenobarbAvg.Daily Maint: 15-60 mg/kg/d div TID • Forms: tabs, sprinkles, liquid, ER, IV • Monitoring: CBC, LFTs, drug level

  21. Ethosuximide(Zarontin) • Seizure Type: Absence • Side effects: Nausea, GI distress, nightmares • Idiosyncratic effects: blood dyscrasias • Drug interact: (induce cyt p450) dilantin, tegr, phenobarb, OCPs • Avg.Daily Maint: 20-40mg/kg/d qD • Forms: cap, liquid • Monitoring:CBC, LFT, U/A, level

  22. Limitation of First Generation ACDS • Only work 70% of the time • Many drug interactions • Hepatic metabolism • Need monitoring with blood tests • Concerns over safety profile

  23. The New Anticonvulsants • Felbamate (Felbatol) • Oxcarbazepine (Trileptal) • Gabepentin(Neurontin) • Levitaracetam(Keppra) • Lamotrigine(Lamictal) • Topiramate(Topamax) • Fosphenytoin • Zonisamide (Zonegran) • Tiagibine • Vigabatrim

  24. The New Anticonvulsants • Upside • Different mechanisms of action • Most BID or qD • Don’t need blood testing • Fewer side effects • Fewer drug interactions • Downsides • Long term side effects not known • Lack of teratogenicity is not established • Can’t monitor levels (and therefore can’t monitor compliance) • Expensive!

  25. Oxcarbazepine(Trileptal) • Similar profile to carbamazepine, but with fewer side effects, bid dosing, no blood monitoring needed • Converts to 10-hydroxy-carbazepine • Side Effects: hyponatremia, headache, somnolence, dizziness • Drug interactions: OCPs, pheytoin, lamotrigine, VPA • Avg.Daily Maint: 20-40 mg/kg/d div BID (can switch over from tegretol by increasing dose by 1.5x overnight) • Forms: tabs, liquid • Monitoring: not routinely needed; consider monitor sodium

  26. Lamotrigine(Lamictal) • Broad spectrum- useful for convulsive and nonconvulsive seizures • Side effects: dizzy, somnolence, tremor, weight gain • Idiosyncratic effects:rash, Stevens-Johnson • Drug interactions: VPA, dilantin, tegretol • Avg.Daily Maint: 5-15 mg/kg/d div BID (1-5 mg/k/d if on VPA) • Forms: tabs, chewable dispersible

  27. Levitaracetam(Keppra) • Broad spectrum. Approved for JME, GTC • Indic: adjunctive for GTC> 6yo, myoclonic seizures >12 yo with juvenile myoclonic epilepsy, partial onset >4 yo. • Side effects: somnolence, agitation, behavior change • Drug interactions: none • Avg.Daily Maint: 20-40mg/kg/d div BID • Form: tabs (can be chewed), liquid, parenteral

  28. Topiramate(Topamax) • Indic: adjunct. for partial,GTC>2,Lennox-Gastaut >2; monotherapy >10 partial, GTC • Mech. Of Action: potentiate GABA effect; carbonic anhydrase inhibitor • Side effects/Idiosync. Effects: word finding difficulty, psychmotor slowing, weight loss, kidney stones, myopia, glaucoma, oligohydrosis • Drug interactions: (induce cyt p450)dilantin, tegret, VPA, acetazolamide • Avg.Daily Maint: 5-9 mg/kg/d div BID • Form: tabs, sprinkle caps • Therap. Lvl (mcg/ml): not routinely sent • Monitoring: no routine blood testing

  29. Initiating Drug Treatment of Epilepsy • In general, long term anticonvulsants rarely started after a first seizure • Obtain baseline bloods (depending on which ACD used) • Start low and build up to low end of maintenance over two to four weeks (increase weekly) • When at steady dose for approximately one week, check trough level and blood parameters (depends on ACD) • Continue to (slowly) push ACD until either seizure free or drug toxicity • For “first line” medications, I monitor CBC, CMP and drug level every 3 months in first year and every 6 months after that

  30. First Unprovoked Seizure in Childhood • Was it a seizure? • Look for etiology of seizure (acute symptomatic seizures) • Treat any underlying causes of seizure

  31. Was it a seizure? • Syncope- vasovagal, cardiogenic • Sandifer syndrome • Breath holding spell • Migraine • Tics • Psychogenic • Sleep myoclonus • Paroxysmal dystonia

  32. Acute Symptomatic Seizures • Fever • Infectious • Meningitis • Abscess • Encephalitis • Neurovascular • Ischemic stroke • Hemorrhagic stroke (AVM, aneurysm, etc) • Trauma • Tumor • Metabolic • Hypoglycemia • Hypocalcemia • Hyponatremia

  33. Managing a First Unprovoked Seizure in ChildhoodHistory Describe seizure very carefully Length of seizure- do not take parents estimate of time lapsed at face value! What was child doing when the seizure occurred? What did seizure look like at its onset? During the seizure? What happened after the seizure? What does the child remember? Possible precipitants of seizure Head trauma? Possible ingestion? New medication or supplement?Fever? Dehydration? Rash? Change in mental status? Recent travel? Ask about other seizure types! Absence: does your child ever stop an stare and not respond Myoclonus Review of systems Headaches, double vision, weakness, numbness, vomiting, etc General ROS PMH Developmental History

  34. Managing a First Unprovoked Seizure in ChildhoodPhysical • General exam • Including: vital signs, signs of head trauma, signs of meningitis and sepsis, rash, etc • Directed general exam • Head circumference • Dysmorphic features • Neurocutaneous stigmata • Extremity abnormality • Organomegaly • Neurologic Exam • Mental status, including assessment of developmental level • Cranial Nerves • M otor • Reflexes • Tone • Gait • Cerebellar

  35. Managing a First Unprovoked Seizure in ChildhoodLaboratory Evaluation “The decision to perform other studies, including LP,laboratory tests, and neuroimaging, for the purpose of determiningthe cause of the seizure and detecting potentially treatableabnormalities, will depend on the age of the patient and thespecific clinical circumstances. Children of different agesmay require different management strategies” Hertz D et al: Practice Parameter: Evaluating a first nonfebrile seizure in children. Neurology 2000; 55:616.

  36. Managing a First Unprovoked Seizure in ChildhoodLaboratory Evaluation • Blood: CBC, CMP • Urine: Utox; urinalysis • Neuroimaging • CT • If focal onset seizure, Todd’s paralysis, focal exam, possibility of trauma • If onset of seizure not witnessed • If follow up not assured • MRI • May be done as outpatient if felt to be warranted • EEG: outpatient

  37. Recurrence Risk for Unprovoked Seizure • Children with a first unprovoked seizure have a one-third rate of recurrence • Children with a second unprovoked seizure have a 75% rate of recurrence; children with a third unprovoked seizure have a 90% rate of recurrence • Most recurrences occur within the first year; 90% occur within 2 years. • Risk factors for recurrence: • Family history of epilepsy • Abnormal EEG • Abnormal neuroimaging • First seizure in sleep • Todds paralysis • Remote symptomatic seizures • Developmental delay ornneurologic abnormality

  38. General consensus is not to treat patients after a first unprovoked seizure. do not forget to find out whether or not this is indeed the first seizure!!! Ask about prior seizures, history of staring spells, history of myoclonic jerks

  39. First unprovoked seizureDischarge planning • General consensus is not to treat patients with anticonvulsants after a first unprovoked seizure (do not forget to find out whether or not this is indeed the first seizure!!!) • Counseling • Seizure precautions: anything in which loss of consiouness can be extremely dangerous (eg., water, bicycling in street) • Basic first aid: Don’t place anything in mouth, turn head to side if vomiting, tilt chin up if trouble breathing • Consider Diastat prescription (for the patient who presented with status epilepticus or cluster of seizures) • Follow up • Schedule outpatient EEG • Pediatric neurology follow up

  40. Diastat • Dosage: 0.5 mg/kg, round up • DIASTAT AcuDial • 10mg delivery system with a 4.4 cm tip(delivers doses of 5, 7.5 and 10 mg) • 20 mg delivery system with a 6.0 cm tip(delivers doses of 10, 12.5 and 20 mg) • Twin Pack of 2 pre-filled configurations (pharmacist locks in proper dosage)

  41. Management of the known epilepsy patient with a breakthrough seizure • Take the time to get accurate history • Medication • Dosage in mg/kg/d. • That means I need a weight! • Do not get dosage from the bottle; ask mother what she is giving • Has the patient missed pills or started any new medication?,been sick, hurt self, etc • When was the dosage last changed? • Epilepsy History: • What epilepsy syndrome, if known? • What is the baseline seizure frequency? • What medications has the patient been on previously? • Acute History • Any fever, trauma, rash, possibility of ingestion • Any new mediations, supplements

  42. Management of the known epilepsy patient with a breakthrough seizure • Blood tests • Check level if patient is on VPA, phenytoin, carbamazepine, phenobarbital or ethosuximide • Check cbc, cmp if patient on above medications • Do not jump to CT scan!! • Get CT scan if patient is not waking up to baseline (can give 4-6 hours for this) • Consider CT there hs been a clear change in seizure type or frequency

  43. Adjust medications as neccessary • What is the dosage; what is the dosage in mg/kg/d. • That means I need a weight! • Do not get dosage from the bottle; ask mother what she is giving • What is preparation? • Can’t adjust medications unless know what they are taking • Has the patient missed pills, started a new medication,been sick, hurt self, etc • What is the baseline seizure frequency? • When was the dosage last changed? • What medications has the patient been on previously?

  44. Adjust medications as neccessary • If level low • Missed doses- give extra dose and leave maintenance the same • If no missed doses and daily dosage is within the typical range for maintenance, then give bolus (usually in the range of one extra dose) and raise daily dosage by 10% • If level high • Is this peak or trough level? • Is high level of ACD potentially a cause of seizure • Eg, tegretol

  45. 11 year old boy with epilepsy who came in with two GTCs, each 30 seconds long and spaced by 15 minutes. The patient is on carbamazepine and the level is 4 (range 8-12) • Dosage: 200mg PO BID; 12 mg /k/d • Tegretol XR 200mg tabs • Dosage last increased 1 month ago • Has seizures around once a month • No missed doses • Has follow up appointment in 2 months

  46. 11 yo boy with epilepsy with breakthrough seizure • Plan • Since had two seizures, observe for several hours in the ED • Increase carbamazepine • Continue Tegretol XR : 200mg tab in AM and 300mg tab in PM (can only do 2 different tabs if family has means to understand this) • Mom needs to make follow up appointment sooner

  47. Examples of Histories Gone Bad • 5 yo girl with epilpesy Dilantin, came in following a seizure; level sent and given 5/kg dilantin in the meantime . Level comes back 25. • Dosage was 10/k/d- double what should be given. Had not been calculated prior to dosing • 6 month girl on phenobarbital comes in with seizure. Bottle gives a dosage that is 5/k/d. • I had written new prescription with higher dose 5 days previously which mom filled However, she did not actually increase the dose. • 7 yo girl on Tegretol arrives in status. Level was 14. • Dosage was 30/k/d (high end of range). Dose had been increased (doubled by outside MD) 2 weeks prior. • I’m told the 3 year old girl is on 500mg lamictal 1 tab twice a day. • Ooops, patient is dead. And can’t get that size pill anyway.

  48. Examples of Histories Gone Bad • 8 yr old , first seizure 1 year ago, 6 mo ago had second seizure and had medication adjusted. Now on oxcarbazepine 2 tab in am and 3 tab in pm. Mom thinks pills are 200mg • Does this history make sense? Were meds really started after the first seizure?? • Oxcarbazepine does not come in 200mg tabs. • Patient comes in with third seizure, followed at Montefiore. On Depakote and Keppra. • Does this history make sense?

  49. Benign febrile seizure Definition 6 months to 6 years Fever Neurologically normal before and after seizure Generalized seizure Lasts less than fifteen minutes No other obvious cause of seizure AAP recommendations The evaluation should be directed towards the diagnosis of the cause of the fever. Lumbar Puncture Over 18 months: not necessary as long as there is no clinical suspicion of meningitis. 12 months and 18 months of age : consider Under 12 months of age: strongly consider, as signs of meningitis can be subtle in this age group. EEG, blood studies and neuroimaging are generally not required. Long term anticonvulsants generally not used Diastat for home use indicated if there is a history of prolonged febrile seizure or cluster of seizures (ie, not benign febrile seizures)

  50. Home treatments • Diastat • Dosage: 0.5 mg/kg, round up • DIASTAT AcuDial • 10mg delivery system with a 4.4 cm tip(delivers doses of 5, 7.5 and 10 mg) • 20 mg delivery system with a 6.0 cm tip(delivers doses of 10, 12.5 and 20 mg) • Twin Pack of 2 pre-filled configurations (pharmacist locks in proper dosage) • Intranasal midazolam

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