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Pediatric Epilepsy: An Pediatric Epilepsy: An Overview and Update on Overview and Update on

Treatment OptionsTreatment OptionsMitzi Payne, MDMitzi Payne, MD

Pediatric NeurologyPediatric NeurologyMarshall University Marshall University

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Approach to a patient with “spells”Approach to a patient with “spells”

Paroxysmal eventsParoxysmal events

Obtain thorough history:Obtain thorough history:– Before event Before event – Description of event Description of event – After the eventAfter the event

Do descriptions vary event to event?Do descriptions vary event to event?

Are the events epileptic?Are the events epileptic?

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If the “spells” appear to be If the “spells” appear to be epileptic… epileptic…

What type of epileptic seizures?What type of epileptic seizures?

What is the cause of the seizure?What is the cause of the seizure?

Is there a syndrome associated with the Is there a syndrome associated with the seizure type?seizure type?

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““Fits, faints, and funny turns”Fits, faints, and funny turns”11

• Differential Diagnosis of “spells”Differential Diagnosis of “spells”

SyncopeSyncope

MigraineMigraine

Sleep disordersSleep disorders

Pseudoseizures (nonepileptic seizures)Pseudoseizures (nonepileptic seizures)

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Helpful tools for diagnosisHelpful tools for diagnosis

Accurate history and description of eventsAccurate history and description of events

Ask family member to “act out” eventAsk family member to “act out” event

Ask family to videotape eventAsk family to videotape event

Provoking factorsProvoking factors

ElectroencephalogramElectroencephalogram

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Some important pointsSome important pointsClassification(s)Classification(s)– seizure type seizure type an ictal event believed to represent an ictal event believed to represent

a unique pathophysiological mechanism and a unique pathophysiological mechanism and anatomic substrateanatomic substrate

– epilepsy syndrome epilepsy syndrome a complex of signs and a complex of signs and symptoms that define a unique epilepsy symptoms that define a unique epilepsy conditioncondition

Etiological categories of syndromesEtiological categories of syndromes– idiopathic idiopathic no underlying structural brain disease, no underlying structural brain disease,

presumed geneticpresumed genetic– symptomatic symptomatic seizures are the result of lesional or seizures are the result of lesional or

metabolic disease of the brainmetabolic disease of the brain– probably symptomatic (cryptogenic) probably symptomatic (cryptogenic) believed believed

symptomatic but no etiology establishedsymptomatic but no etiology established

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Seizures: focal vs. generalized Seizures: focal vs. generalized

Generalized seizureGeneralized seizure– a seizure whose initial semiology indicates, or is a seizure whose initial semiology indicates, or is

consistent with, more than minimal involvement of consistent with, more than minimal involvement of both hemispheresboth hemispheres

Focal seizure (partial, localization-related)Focal seizure (partial, localization-related)– a seizure whose initial semiology indicates, or is a seizure whose initial semiology indicates, or is

consistent with, initial activation of only part of one consistent with, initial activation of only part of one cerebral hemispherecerebral hemisphere

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Generalized seizure typesGeneralized seizure types

MyoclonicMyoclonic Sudden, <100 ms involuntary contraction of muscle(s) Sudden, <100 ms involuntary contraction of muscle(s) or muscle groupsor muscle groups

ClonicClonic Repetitive, rhythmic myoclonus at 2-3 HzRepetitive, rhythmic myoclonus at 2-3 Hz

TonicTonic Sustained muscle contraction for seconds to minutesSustained muscle contraction for seconds to minutes

Generalized Generalized tonic-clonictonic-clonic

Bilateral symmetrical tonic contraction, then bilateral Bilateral symmetrical tonic contraction, then bilateral clonic contractionsclonic contractions

AtonicAtonic Sudden, brief, 1–2 s decrease in tone without Sudden, brief, 1–2 s decrease in tone without preceding myoclonic or tonic eventpreceding myoclonic or tonic event

AstaticAstatic Loss of posture (=drop) due to atonic, myoclonic, or Loss of posture (=drop) due to atonic, myoclonic, or tonic eventtonic event

SpasmSpasm Axial contraction, may be asymmetricAxial contraction, may be asymmetric

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Generalized epilepsies Generalized epilepsies

Idiopathic Idiopathic generalized generalized epilepsiesepilepsies

Benign myoclonic epilepsy in infancyBenign myoclonic epilepsy in infancyEpilepsy with myoclonic-astatic seizuresEpilepsy with myoclonic-astatic seizuresEpilepsy with myoclonic absence seizuresEpilepsy with myoclonic absence seizuresChildhood absence epilepsyChildhood absence epilepsyIGE with variable phenotypesIGE with variable phenotypes

Juvenile absence, JME, epilepsy with GTC onlyJuvenile absence, JME, epilepsy with GTC onlyGeneralized epilepsies with febrile seizures Generalized epilepsies with febrile seizures

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Epileptic Epileptic encephalopathiesencephalopathies

Syndromes of infancySyndromes of infancyEarly myoclonic encephalopathy; Ohtahara, Early myoclonic encephalopathy; Ohtahara, Dravet, West syndromesDravet, West syndromes

Lennox-Gastaut syndromeLennox-Gastaut syndromeLandau-Kleffner syndromeLandau-Kleffner syndromeEpilepsy with continuous spike waves in SW sleepEpilepsy with continuous spike waves in SW sleep

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Focal seizure typesFocal seizure types

Focal Focal sensorysensory

with elementary sensory symptomswith elementary sensory symptomswith experiential sensory symptomswith experiential sensory symptoms

Focal Focal motormotor

with elementary clonic motor signswith elementary clonic motor signswith symmetric tonic motor signswith symmetric tonic motor signswith automatismswith automatisms

Secondarily generalized seizuresSecondarily generalized seizures

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EEG Activating Procedures:EEG Activating Procedures:HyperventilationHyperventilation

Deep and regular respirations at a rate of Deep and regular respirations at a rate of 20 / minute for 2 to 4 minutes20 / minute for 2 to 4 minutes

Drop in plasma CO2 by 4-7 ml%Drop in plasma CO2 by 4-7 ml%

Normal response (and best seen in Normal response (and best seen in children) is high amplitude slow activitychildren) is high amplitude slow activity

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EEG Activating Procedures:EEG Activating Procedures:HyperventilationHyperventilation

Hyperventilation may induce diffuse sharp Hyperventilation may induce diffuse sharp waves or spike-wave complexeswaves or spike-wave complexesPatients with generalized epilepsies are most Patients with generalized epilepsies are most likely to have these findingslikely to have these findingsActual seizures can be induced by Actual seizures can be induced by hyperventilationhyperventilation– Absence (petit mal)Absence (petit mal)– Absence (petit mal)Absence (petit mal)– Absence (petit mal)Absence (petit mal)– Temporal lobe seizuresTemporal lobe seizures

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EEG Activating Procedures:EEG Activating Procedures:Intermittent Photic StimulationIntermittent Photic Stimulation

Strobe light flashes (1-30 Hz)Strobe light flashes (1-30 Hz)Photic drivingPhotic driving

Rhythmic activity over the posterior head regionsRhythmic activity over the posterior head regions

Photomyoclonic responsePhotomyoclonic responseRepetitive muscle spikes over the anterior regions of the Repetitive muscle spikes over the anterior regions of the headhead

Photoconvulsive (-paroxysmal) responsePhotoconvulsive (-paroxysmal) responseGeneralized spike and wave complexes Generalized spike and wave complexes

15-20 Hz15-20 Hz

May have jerking or impairment of consciousnessMay have jerking or impairment of consciousness

Photosensitive epilepsiesPhotosensitive epilepsies

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EEG Activating ProceduresEEG Activating Procedures

Somatosensory stimulationSomatosensory stimulationElectrical stimulation of peripheral nervesElectrical stimulation of peripheral nerves

Epileptiform discharges in contralateral Epileptiform discharges in contralateral hemispherehemisphere

Reenactment of a triggerReenactment of a triggerVisual stimulation of geometric patternsVisual stimulation of geometric patterns

Auditory stimulationAuditory stimulation

ReadingReading

HypoglycemiaHypoglycemia

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Common Childhood Epilepsy Common Childhood Epilepsy SyndromesSyndromes

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Infantile spasmsInfantile spasmsWest syndromeWest syndrome

Onset ages 3-12 monthsOnset ages 3-12 months

Brief axial contractions Brief axial contractions – usually bilateral, may be asymmetricalusually bilateral, may be asymmetrical

– typically flexor, may be extensortypically flexor, may be extensor

– usually in clusters, less likely randomusually in clusters, less likely random

– typically on awakening, or when drowsytypically on awakening, or when drowsy

EEG shows hypsarrhythmia EEG shows hypsarrhythmia – multifocal spikesmultifocal spikes

– high voltage, chaotic backgroundhigh voltage, chaotic background

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Flexor spasmFlexor spasm

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2020

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Infantile spasmsInfantile spasms• ““Symptomatic” casesSymptomatic” cases

– congenital infectionscongenital infections– CNS malformationsCNS malformations– metabolic disordersmetabolic disorders– genetic syndromesgenetic syndromes– tuberous sclerosistuberous sclerosis– perinatal asphyxiaperinatal asphyxia– postnatal trauma postnatal trauma – acquired infectionsacquired infections– immunizationsimmunizations

OftenOften “cryptogenic” “cryptogenic”• no definite cause no definite cause

established but child is established but child is delayeddelayed

RarelyRarely “idiopathic” “idiopathic”• no cause established and no cause established and

child is normalchild is normal

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Infantile spasmsInfantile spasms

Short term treatment to stop spasms, improve Short term treatment to stop spasms, improve EEGEEG– ACTH effective, dose not establishedACTH effective, dose not established

oral steroids not proven effectiveoral steroids not proven effective

– Vigabatrin, especially in tuberous sclerosis Vigabatrin, especially in tuberous sclerosis not available in US, not available in US,

potential retinal toxicitypotential retinal toxicity

Data insufficient to show early treatment or Data insufficient to show early treatment or any treatment changes long term outcome any treatment changes long term outcome

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West SyndromeWest Syndrome

Infantile SpasmsInfantile Spasms

Hypsarrhythmia on EEGHypsarrhythmia on EEG

Developmental regression that begins Developmental regression that begins concurrently with the onset of spasmsconcurrently with the onset of spasms

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Prognosis of West SyndromePrognosis of West Syndrome22

Series of 150 patients with West Series of 150 patients with West Syndrome between 1954 and 1970Syndrome between 1954 and 1970– Idiopathic (n = 44)Idiopathic (n = 44)– Symptomatic (n = 106)Symptomatic (n = 106)

Outcomes measured by school type or Outcomes measured by school type or residence (home or hospital)residence (home or hospital)

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OutcomeOutcome

Idiopathic cases: Idiopathic cases: – Normal school 37%Normal school 37%– Death 6%Death 6%– Other seizure types 43%Other seizure types 43%– Neurologic abnormality 31%Neurologic abnormality 31%

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OutcomeOutcome

Symptomatic cases:Symptomatic cases:– Normal school - noneNormal school - none– Death 37%Death 37%– Other seizure types 59%Other seizure types 59%– Neurological abnormality 65%Neurological abnormality 65%

– Large number progress to develop Lennox Large number progress to develop Lennox Gastaut SyndromeGastaut Syndrome

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Rolandic epilepsyRolandic epilepsyOnset ages 2-12 yrs, peak 5-10 yrsOnset ages 2-12 yrs, peak 5-10 yrs

Characteristic seizuresCharacteristic seizures

Infrequent simple partial seizuresInfrequent simple partial seizures– tingling in mouth, on face, speech arrest tingling in mouth, on face, speech arrest – rare GTCS in sleeprare GTCS in sleep

Resolve by pubertyResolve by puberty

Characteristic EEGCharacteristic EEG– high voltage centrotemporal spikes high voltage centrotemporal spikes – usually bilateralusually bilateral

Imaging normalImaging normal

Considered an idiopathic focal epilepsy Considered an idiopathic focal epilepsy – some evidence for genetic basissome evidence for genetic basis

Treatment Treatment – may not be necessarymay not be necessary– may respond to many drugsmay respond to many drugs

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Centrotemporal spikes in Benign Centrotemporal spikes in Benign Rolandic EpilepsyRolandic Epilepsy

Presentation of “staring spells”

• Complex partial seizures• Absence seizures• Behavior staring

Complex Partial Seizures

• Commonly temporal lobe focus• Begins in one area, then spreads enough

to impair consciousness, but not to evoke a generalized tonic-clonic seizure

• Staring is often part of the initial spread• Also can see automatisms…

Automatisms

• Coordinated involuntary movements• Consciousness impaired• Patient does not recall activity• Simple

– Lip smacking, chewing, uttering sounds, picking, tapping, walking straight or in circles

• Complex (behavior involved)– Undressing, chewing inedible objects,

wandering, aggression

Complex Partial Seizure

Complex Partial Seizure

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Complex Partial Seizure

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Treatment of complex partial seizures

• Use medications for focal onset seizures– Levetiracetam (Keppra)– Oxcarbamazepine (Trileptal)– Carbamazepine (Tegretol/ Carbatrol)– Lamotrigine (Lamictal)– Topiramate (Topamax)– Zonisimide (Zonegran)– Phenobarbital– Valproic Acid (Depakote)– Lacosamide (Vimpat)

Absence epilepsy

Childhood absence (petit mal) epilepsy

• Peak onset age 4-6 years • Many seizures daily• Seizures last seconds• 70+% have associated automatisms

– eyelid flutter– simple vocalizations– picking movements

• Typical EEG with 3 Hz spike wave• Majority resolve by adolescence

slightly irregular 3 per second spike wave ▼

Absence Seizure

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Absence Seizure

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Absence Seizure

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Pathophysiology of Absence Seizures

• Generalized discharges occur from abnormal oscillatory rhythm in thalamocortical circuits

• High density of T-type calcium channels in thalamus, thought to be involved

Treating absence seizures

• Ethosuximide (Zarontin)• Valproic Acid (Depakote)• Lamotrigine (Lamictal)• Levetiracetam (Keppra)

Absence v. Complex Partial Sz

• Absence• < 30 sec• Non-convulsive status

epilepticus• Frequent (100’s a day)• Sudden onset, sudden

termination• No post-ictal state• Hyperventilation a trigger• EEG: 3-4 Hz spike and

wave• Rare interictal

abnormalities

Complex Partial• > 1 minute• Rare non-convulsive

epilepticus• Occur ≤ daily• Frequent simple, complex

automatisms• Evolve to other sz

manifestations• Post-ictal state• EEG: Interictal focal

abnormalities

Behavioral Staring

• Most commonly seen in children with ADD, PDD, MR

• Occurs when “bored” or over-stimulated• Does not typically make the patient fall or

stop an activity abruptly• Can be stopped with close contact /

stimulation• Also can be seen in children with epilepsy!

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Evaluation of a Evaluation of a 11stst unprovoked seizure unprovoked seizure

Good evidence recommends EEG Good evidence recommends EEG – EEG can help diagnose the eventEEG can help diagnose the event

– EEG can identify a specific syndromeEEG can identify a specific syndrome

– EEG can help with prognosisEEG can help with prognosis

– timing of EEG not determinedtiming of EEG not determined

immediate EEG may show abnormality or post immediate EEG may show abnormality or post ictal slowingictal slowing

– abnormal EEG best predictor of recurrence in abnormal EEG best predictor of recurrence in neurologically normal childrenneurologically normal children

– abnormal neuro exam also strong predictor of abnormal neuro exam also strong predictor of recurrencerecurrence

Generalized burst

Benign focal spike

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Evaluation of a Evaluation of a 11stst unprovoked seizure unprovoked seizure

• Insufficient evidence for routine labs, LP, imagingInsufficient evidence for routine labs, LP, imaging– consider emergent imagingconsider emergent imaging

if postictal focal deficit, or not at baseline in several hoursif postictal focal deficit, or not at baseline in several hours

– consider nonurgent MRIconsider nonurgent MRIwith significant neuro abnormalities of unknown etiologywith significant neuro abnormalities of unknown etiology

a seizure of focal onset a seizure of focal onset

in children under 1 year of agein children under 1 year of age

– consider LPconsider LPin the very young child (<6 months)in the very young child (<6 months)

in the patient who fails to return to baselinein the patient who fails to return to baseline

in any patient with meningeal signsin any patient with meningeal signs

if increased ICP suspected, image before LPif increased ICP suspected, image before LP

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How likely is How likely is a 2a 2nd nd seizure?seizure?

Evidence from multiple Class III studiesEvidence from multiple Class III studies

Recurrence ranged from 14%-65%Recurrence ranged from 14%-65%

Most recurrences early (in 1Most recurrences early (in 1stst year) year)

Factors increasing recurrence riskFactors increasing recurrence risk– abnormal EEGabnormal EEG– etiologyetiology

remote symptomatic seizure recurrence >50%remote symptomatic seizure recurrence >50%

idiopathic seizure recurrence 30-50%idiopathic seizure recurrence 30-50%

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Summary of evidence:Summary of evidence:

Treatment of 1Treatment of 1st st unprovoked seizureunprovoked seizure

Most children with a 1Most children with a 1stst seizure have few or no seizure have few or no recurrencesrecurrences

10% will have many seizures regardless of initial Rx10% will have many seizures regardless of initial Rx

Rx after 1Rx after 1stst vs. 2 vs. 2ndnd seizure does not affect long term seizure does not affect long term prognosisprognosis

Rx in adults and children leads to decreased recurrencesRx in adults and children leads to decreased recurrences

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Recommendations:Recommendations:

Treatment of a 1Treatment of a 1stst Seizure Seizure

Anticonvulsant treatment after a 1Anticonvulsant treatment after a 1stst seizure must be seizure must be individualizedindividualized– treatment is not indicated for prevention of epilepsy treatment is not indicated for prevention of epilepsy – treatment may be considered if risks of recurrent seizure out treatment may be considered if risks of recurrent seizure out

weigh risks of Rx weigh risks of Rx

Treatment must take into account patient and family Treatment must take into account patient and family preferencespreferences

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Febrile seizuresFebrile seizuresThe most common seizures in childhoodThe most common seizures in childhood

In US affect 2-4% of children < age 5 yrsIn US affect 2-4% of children < age 5 yrs8% Japan, 14% Guam8% Japan, 14% Guam

1/3 have at least 1 recurrence1/3 have at least 1 recurrence

Risk factors for recurrence Risk factors for recurrence first febrile seizure < 1 year of agefirst febrile seizure < 1 year of age

low degree of fever at first febrile seizurelow degree of fever at first febrile seizure

family history of febrile seizuresfamily history of febrile seizures

brief duration between fever onset and febrile seizurebrief duration between fever onset and febrile seizure

4 risk factors = 70% recurrence 4 risk factors = 70% recurrence

No risk factors = 20% recurrence No risk factors = 20% recurrence

•

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Febrile seizuresFebrile seizures

SimpleSimple– generalized generalized – andand <15 minutes duration <15 minutes duration

ComplexComplex– focalfocal– oror >15 minutes >15 minutes– oror recurrent within 24 hours recurrent within 24 hours

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Evaluation of the child Evaluation of the child with simple febrile seizureswith simple febrile seizures

Lumbar punctureLumbar puncture– if meningeal signsif meningeal signs

– in infants < 12 monthsin infants < 12 months

– with prior antibiotic Rxwith prior antibiotic Rx

Blood studies not needed routinelyBlood studies not needed routinely

Imaging not necessaryImaging not necessary

EEG not necessary in simple febrile seizuresEEG not necessary in simple febrile seizures

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Treatment of the child Treatment of the child with simple febrile seizureswith simple febrile seizures

Effective in reducing recurrences but Effective in reducing recurrences but with potential toxicitieswith potential toxicities– continuous phenobarbital or valproic acidcontinuous phenobarbital or valproic acid– intermittent diazepamintermittent diazepam

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Treatment options for Treatment options for pharmacoresistant epilepsypharmacoresistant epilepsy

Ketogenic dietKetogenic diet

Vagus nerve stimulationVagus nerve stimulation

SurgerySurgery

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Ketogenic dietKetogenic diet Very high fat, very low CHO, Very high fat, very low CHO, minimum RDA proteinminimum RDA protein

Vitamins, mineral supplements Vitamins, mineral supplements necessarynecessary

Rigid compliance essentialRigid compliance essential

Effective in 1/3-1/2 casesEffective in 1/3-1/2 cases– all seizure typesall seizure types– all ages, but easiest to maintain in all ages, but easiest to maintain in

childrenchildren

breakfast

lunch

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Ketogenic diet formulationsKetogenic diet formulationsFormulated in fat:CHO ratiosFormulated in fat:CHO ratios– generally between 4:1 and 3:1generally between 4:1 and 3:1– Atkins diet is about 2.2:1Atkins diet is about 2.2:1

Traditional dietTraditional diet – uses 40% cream, fatty foodsuses 40% cream, fatty foods

MCT dietMCT diet– adds oils to “normal foods”adds oils to “normal foods”

Tube feeding dietTube feeding diet – CHO-free formula + microlipids or CHO-free formula + microlipids or

cooking oilcooking oil

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Surgical treatment of epilepsySurgical treatment of epilepsyLobectomyLobectomy– anterior temporal lobectomy most frequent procedureanterior temporal lobectomy most frequent procedure– 70% of selected patients become seizure-free70% of selected patients become seizure-free

Extratemporal resectionExtratemporal resection– nature and extent of pathology determine resultsnature and extent of pathology determine results

Hemispherectomy, multilobar resectionsHemispherectomy, multilobar resections– done in cases with extensive pathologydone in cases with extensive pathology

Corpus callosotomyCorpus callosotomy– rarely performed as sole procedurerarely performed as sole procedure

Multiple subpial transectionsMultiple subpial transections– Palliative, done when focus is in “eloquent cortex”Palliative, done when focus is in “eloquent cortex”

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Epilepsy surgery evaluation Epilepsy surgery evaluation (for example)(for example)

Record seizures Record seizures

MRI, MRA, SPECT, PETMRI, MRA, SPECT, PET

Speech and memory testsSpeech and memory tests– Wada testWada test– neuropsych testingneuropsych testing– fMRIfMRI

Electrocorticography, Electrocorticography, intracranial monitoring intracranial monitoring

Brain mappingBrain mapping

SPECT

VideoEEG

Intracranial grid

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Vagus nerve stimulation (VNS)Vagus nerve stimulation (VNS)

FDA approved 1997FDA approved 1997– adjunctive treatment adjunctive treatment

pharmacoresistant partial-pharmacoresistant partial-onset epilepsyonset epilepsy

– ages 12 and olderages 12 and older

Over 25,000 implantedOver 25,000 implanted– 5,000 in children <125,000 in children <12

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Vagus nerve stimulationVagus nerve stimulation

Mild electrical Mild electrical pulses sent to pulses sent to L vagusL vagus

Automatic, Automatic, intermittent stimulationintermittent stimulation

On-demand stimulation with On-demand stimulation with magnetmagnet

In-office programmingIn-office programming

Compliance assuredCompliance assured

Programming

Magnet activation

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VNS pulse generator and leadVNS pulse generator and lead>25,000 patients worldwide>25,000 patients worldwide

Model 102 (June 2002) Model 102 (June 2002) – single pin leadsingle pin lead– 6.9 mm thick6.9 mm thick– weight 25 gramsweight 25 grams– 6-11 year battery life6-11 year battery life

Outpatient implantationOutpatient implantation– 1 hour surgery1 hour surgery– device test in OR, activated device test in OR, activated

laterlater

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Seizure-response dogsSeizure-response dogs

How do they do it?How do they do it?

Trained by several Trained by several organizationsorganizations

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Diastat Diastat

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Rectal diazepam Rectal diazepam

- - Given for seizures lasting longer than 5 minutesGiven for seizures lasting longer than 5 minutes

- Diastat is a safe way to give rescue seizure medication in - Diastat is a safe way to give rescue seizure medication in the home or school environmentthe home or school environment- Dose varies by age and weight- Dose varies by age and weight- If seizure continues 5 minutes after Diastat given, then - If seizure continues 5 minutes after Diastat given, then EMS should be contactedEMS should be contacted- Some children have seizures that consistently are - Some children have seizures that consistently are prolonged; in the case Diastat may be prescribed to be prolonged; in the case Diastat may be prescribed to be given at onset of seizure, instead of waiting 5 minutes.given at onset of seizure, instead of waiting 5 minutes.- Not FDA approved in children less than 2 years of age- Not FDA approved in children less than 2 years of age

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Other Rescue Medication OptionsOther Rescue Medication Options- - Nasal midazolam - children refractory to DiastatNasal midazolam - children refractory to Diastat- Oral lorazepam - seizure clusters- Oral lorazepam - seizure clusters- Routine seizure medications are NOT given as rescue - Routine seizure medications are NOT given as rescue medications medications - If a child routinely requires rescue medications on a - If a child routinely requires rescue medications on a consistent basis, then routine scheduled seizure consistent basis, then routine scheduled seizure medications need to be changedmedications need to be changed

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Thank you! Thank you!

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