Presentation on theme: "Pediatric Epilepsy Overview of seizures and epilepsy and medications"— Presentation transcript:
1Pediatric Epilepsy Overview of seizures and epilepsy and medications Management of specific issuesThe first unprovoked seizureThe patient with known epilepsyFebrile SeizuresNeonatal seizures
2Does the patient have epilepsy? Seizures vs. 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 seizuresSeizure:a transient occurrence of signs and symptoms due to abnormal or excessive or synchronous neuronal activity in the brain
3Was it a seizure? Syncope- vasovagal, cardiogenic Sandifer syndrome Breath holding spellMigraineTicsPsychogenicSleep myoclonusParoxysmal dystonia
4Classification of seizures Generalizedloss of consciousnesswhole brain at onsetPartialno loss of consciousnessfocal onsetConvulsivetonic clonictonicclonicNonconvulsiveabsenceatypical absencemyoclonicatonicComplex Partialchange in level of consciousnessSimple Partialno change in consciousnessPartial Seizure evolving to secondary generalization
5Epilepsy SyndromesTriad of seizure type or types, age and EEG findingsDifferent medications for different syndromes!!Very different prognoses for different syndromesAn epileptic syndrome is characterized by a constellation of specific signs, symptoms, seizure types, prognoses, and EEG findings. Determination of the epileptic syndrome provides information on prognosis and informs management decisions.
7Benign Rolandic Epilepsy of Childhood Age: 5-16 years oldSeizure type: nocturnal, partial (anarthria), may generalizeEEG: bilateral independent central temporal spikesPrognosis: ExcellentMeds: Tegretol, any medication for partial seizures
9Absence epilepsyAge:Childhood absence epilepsy begins 5-10 years oldJuvenile absence begins around pubertySeizure type: absence, may also have generalized convulsionsEEG: 3 HZ spike wave dischargesPrognosis: excellent (particularly for childhood onset)Medication:Ethosuccimide, valproic acid, lamotrigineExacerbated by Tegretol
11Juvenile Myoclonic Epilepsy Age: begins years oldSeizure type: myoclonic jerks (usually in morning), staring spells, convulsionsEEG: 3-4 Hz generalized discharge with spike and polyspike wavesPrognosis: good (easily controlled usually,but doesn’t usually grow out of it)Medications:Valproic acid, lamotrigineExacerbated by tegretol and phenytoin
16First Generation Anticonvulsants PhenobarbitalBroad spectrum, most seizure typesExcellent safety profileSedation, hyperactivity, decreased IQUsed primarily for young infantsPhenytoinPartial, generalized seizuresWorsens absence and myoclonusGum hyperplasia, hirsutism, facial coarsening with long term useFospenytoin for statusCarbamazepineValproic acidGeneralized (convulsive and nonconvulsive)Highest risk of hepatotoxicityMost teratogenicEthosuximideAbsence only
17Phenobarbital Excellent for GTC, partial seizures Especially used in neonatesExcellent safety profileGood absorptionIV/IM/PO(liquid form)Long half lifeqD-bid dosingSide effects of sedation (acutely), hyperactivity and decrease IQ (chronic use) limits its long term useMonitor drug level and LFTsMany drug interactionsinduces cyt p450OCPs, TCAs, VPA, tegretol, dilantinUsual dosing: 3-6mg/kg/d div qD-BID
18Phenytoin (Dilantin) Useful for GTC and partial seizures Worsens absence and myoclonusPharmacokinetics: 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 coarseningIdiosyncratic effects: Stevens-Johnson, bone marrow depression, SLE, hepatitisDrug interaction: (induces cyt p450) erythro, dilantin, VPA, INH, OCP, etc.Avg.Daily Maint: 4-7mg/kg/d div qD-BIDForms: tabs, chewable, sust release, susp., IVTherap. Lvl (mcg/ml):10-20Monitoring: follow drug level, CBC, LFTs
19Carbamazepine (Tegretol) Useful for GTC and partial seizuresWorsens absence and myoclonusNo IV formPharmacokinetics: Autoinduction of metabolismSide effects:Ataxia,nystagmus,vertigo,dizziness,sedation, SIADHIdiosyncratic effects:bone marrow depression,Stevens-Johnson, hepatotoxicityDrug interactions: (induces cyt p450) erythro, dilantin, VPA, phenobarb, INH, OCPs, grapefruit juiceAvg.Daily Maint: 15-30mg/kg/d div. TIDForms: tabs, chewable, liquid,Tegretol XR,CarbatrolMonitoring: drug level,CBC, CMP, level
22Limitation of First Generation ACDS Only work 70% of the timeMany drug interactionsHepatic metabolismNeed monitoring with blood testsConcerns over safety profile
23The New Anticonvulsants Felbamate (Felbatol)Oxcarbazepine (Trileptal)Gabepentin(Neurontin)Levitaracetam(Keppra)Lamotrigine(Lamictal)Topiramate(Topamax)FosphenytoinZonisamide (Zonegran)TiagibineVigabatrimThese drugs are being used increasingly in the pediatric population both as second line add on therapy and, increasingly, first line. Vigabatrin is used widely in Europe, but it is not currently approved for use in the United States. Lamotrigine has a similar anticonvulsant spectrum as valproic acid and is being used increasingly as first line therapy
24The New Anticonvulsants UpsideDifferent mechanisms of actionMost BID or qDDon’t need blood testingFewer side effectsFewer drug interactionsDownsidesLong term side effects not knownLack of teratogenicity is not establishedCan’t monitor levels (and therefore can’t monitor compliance)Expensive!
25Oxcarbazepine(Trileptal) Similar profile to carbamazepine, but with fewer side effects, bid dosing, no blood monitoring neededConverts to 10-hydroxy-carbazepineSide Effects: hyponatremia, headache, somnolence, dizzinessDrug interactions: OCPs, pheytoin, lamotrigine, VPAAvg.Daily Maint: mg/kg/d div BID (can switch over from tegretol by increasing dose by 1.5x overnight)Forms: tabs, liquidMonitoring: not routinely needed; consider monitor sodium
26Lamotrigine(Lamictal) Broad spectrum- useful for convulsive and nonconvulsive seizuresSide effects: dizzy, somnolence, tremor, weight gainIdiosyncratic effects: rash, Stevens-JohnsonDrug interactions: VPA, dilantin, tegretolAvg.Daily Maint: 5-15 mg/kg/d div BID (1-5 mg/k/d if on VPA)Forms: tabs, chewable dispersible
27Levitaracetam(Keppra) Broad spectrum. Approved for JME, GTCIndic: adjunctive for GTC> 6yo, myoclonic seizures >12 yo with juvenile myoclonic epilepsy, partial onset >4 yo.Side effects: somnolence, agitation, behavior changeDrug interactions: noneAvg.Daily Maint: 20-40mg/kg/d div BIDForm: tabs (can be chewed), liquid, parenteral
28Topiramate(Topamax)Indic: adjunct. for partial,GTC>2,Lennox-Gastaut >2; monotherapy >10 partial, GTCMech. Of Action: potentiate GABA effect; carbonic anhydrase inhibitorSide effects/Idiosync. Effects: word finding difficulty, psychmotor slowing, weight loss, kidney stones, myopia, glaucoma, oligohydrosisDrug interactions: (induce cyt p450) dilantin, tegret, VPA, acetazolamideAvg.Daily Maint: 5-9 mg/kg/d div BIDForm: tabs, sprinkle capsTherap. Lvl (mcg/ml): not routinely sentMonitoring: no routine blood testingadjunctive therapy for adults and pediatric patients ages 2-16 years with partial onset seizures or primary generalized tonic-clonic seizures and in patients 2 years of age and older with seizures associated with Lennox-Gastaut Syndrome.
29Initiating Drug Treatment of Epilepsy In general, long term anticonvulsants rarely started after a first seizureObtain 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 toxicityFor “first line” medications, I monitor CBC, CMP and drug level every 3 months in first year and every 6 months after that
30First Unprovoked Seizure in Childhood Was it a seizure?Look for etiology of seizure (acute symptomatic seizures)Treat any underlying causes of seizure
31Was it a seizure? Syncope- vasovagal, cardiogenic Sandifer syndrome Breath holding spellMigraineTicsPsychogenicSleep myoclonusParoxysmal dystonia
33Managing a First Unprovoked Seizure in Childhood History Describe seizure very carefullyLength 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 seizureHead 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 respondMyoclonusReview of systemsHeadaches, double vision, weakness, numbness, vomiting, etcGeneral ROSPMHDevelopmental History
34Managing a First Unprovoked Seizure in Childhood Physical General examIncluding: vital signs, signs of head trauma, signs of meningitis and sepsis, rash, etcDirected general examHead circumferenceDysmorphic featuresNeurocutaneous stigmataExtremity abnormalityOrganomegalyNeurologic ExamMental status, including assessment of developmental levelCranial NervesM otorReflexesToneGaitCerebellar
35Managing a First Unprovoked Seizure in Childhood Laboratory Evaluation “The decision to perform other studies, including LP, laboratory tests, and neuroimaging, for the purpose of determining the cause of the seizure and detecting potentially treatable abnormalities, will depend on the age of the patient and the specific clinical circumstances. Children of different ages may require different management strategies” Hertz D et al: Practice Parameter: Evaluating a first nonfebrile seizure in children. Neurology 2000; 55:616.
36Managing a First Unprovoked Seizure in Childhood Laboratory Evaluation Blood: CBC, CMPUrine: Utox; urinalysisNeuroimagingCTIf focal onset seizure, Todd’s paralysis, focal exam, possibility of traumaIf onset of seizure not witnessedIf follow up not assuredMRIMay be done as outpatient if felt to be warrantedEEG: outpatient
37Recurrence Risk for Unprovoked Seizure Children with a first unprovoked seizure have a one-third rate of recurrenceChildren with a second unprovoked seizure have a 75% rate of recurrence; children with a third unprovoked seizure have a 90% rate of recurrenceMost recurrences occur within the first year; 90% occur within 2 years.Risk factors for recurrence:Family history of epilepsyAbnormal EEGAbnormal neuroimagingFirst seizure in sleepTodds paralysisRemote symptomatic seizuresDevelopmental delay ornneurologic abnormality; 75% of these will have a third seizure and 75% of these will have a fourth.[1The major risk are todds, abn eeg, abn neuroimaging,fam hx of epile, first sz in sleep. These risk factors can guide the decision as to whether to place a child on long-term anticonvulsants. Overall, the
38General 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
39First unprovoked seizure Discharge 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!!!)CounselingSeizure 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 breathingConsider Diastat prescription (for the patient who presented with status epilepticus or cluster of seizures)Follow upSchedule outpatient EEGPediatric neurology follow up
40Diastat 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)
41Management of the known epilepsy patient with a breakthrough seizure Take the time to get accurate historyMedicationDosage in mg/kg/d.That means I need a weight!Do not get dosage from the bottle; ask mother what she is givingHas the patient missed pills or started any new medication?,been sick, hurt self, etcWhen 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 HistoryAny fever, trauma, rash, possibility of ingestionAny new mediations, supplements
42Management of the known epilepsy patient with a breakthrough seizure Blood testsCheck level if patient is on VPA, phenytoin, carbamazepine, phenobarbital or ethosuximideCheck cbc, cmp if patient on above medicationsDo 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
43Adjust 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 givingWhat is preparation?Can’t adjust medications unless know what they are takingHas the patient missed pills, started a new medication,been sick, hurt self, etcWhat is the baseline seizure frequency?When was the dosage last changed?What medications has the patient been on previously?
44Adjust medications as neccessary If level lowMissed doses- give extra dose and leave maintenance the sameIf 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 highIs this peak or trough level?Is high level of ACD potentially a cause of seizureEg, tegretol
45Dosage: 200mg PO BID; 12 mg /k/d Tegretol XR 200mg tabs 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/dTegretol XR 200mg tabsDosage last increased 1 month agoHas seizures around once a monthNo missed dosesHas follow up appointment in 2 months
4611 yo boy with epilepsy with breakthrough seizure PlanSince had two seizures, observe for several hours in the EDIncrease carbamazepineContinue 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
47Examples 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 dosing6 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.
48Examples 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 200mgDoes 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?
49Benign febrile seizure Definition6 months to 6 yearsFeverNeurologically normal before and after seizureGeneralized seizureLasts less than fifteen minutesNo other obvious cause of seizureAAP recommendationsThe evaluation should be directed towards the diagnosis of the cause of the fever.Lumbar PunctureOver 18 months: not necessary as long as there is no clinical suspicion of meningitis.12 months and 18 months of age : considerUnder 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 usedDiastat for home use indicated if there is a history of prolonged febrile seizure or cluster of seizures (ie, not benign febrile seizures)
50Home treatments Diastat Intranasal midazolam Dosage: 0.5 mg/kg, round upDIASTAT AcuDial10mg 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
55Neonatal Status Epilepticus Treatment Etiology specific treatment if possibleHypoglycemiaCorrect with 10% glucose solution IV 2cc/kgMaintenance glucose infusion to max of 8 mg/kg/minHypocalcemiaTreat with 10% calcium gluconate (100 mg/kg or 1ml/kg IV over 5-10 minutes while monitoring heart rate and infusion site; or calcium chloride (20mg/kg or 0.2 ml/kg)HypomagnesemiaOften associated with hypocalcemiaTreat with 50% solution of magnesium sulfate IM, 0.25 ml/kgPyridoxine dependencyUsed empirically in infants with refractory seizuresWhile EEG monitoring, give 100 mg/kg IV
56Neonatal Status Epilepticus Treatment PhenobarbitalUsually used firstProlonged half life—100 hours after day 5-7; therefore watch for toxicity20 mg/kg IV (up to 40 mg); repeat 10/kg every minutes times twoPhenytoin/Fosphenytoin20 mg/kg (over minutes)Half-life 100 hoursNonlinear kinetics; redistribution, variable rate hepatic metabolism require individualization of maintenance dosingBenzodiazepineDiazepam0.25mg/kg IV bolus or 0.5 mg/kg PRLorazepam0.05 mg/kg IV over2-5 minutesMidazolam infusion