seizures and convulsiones en niños

8/18/2019 Seizures and convulsiones en niños

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Seizures and epilepsy in children: Initial treatment and monitoringAuthor

Angus Wilfong, MDSection Editor Douglas R Nordli, Jr, MDDeputy Editor

April F Eichler, MD, MPHDisclosures: Angus Wilfong, MD Grant/Research/linical !rial "upport# No$artis %epileps& 'E$eroli(us)*+ - %epileps& '-i$araceta()*+ Pfi.er %epileps&

'Pregaalin)*+ psher0"(ith %epileps& 'intranasal Mida.ola()*+ G0W Phar(a %epileps& 'cannaidiol)*+ 1undec2 %epileps& 'cloa.a()*+ Acorda

%epileps&*3Douglas R Nordli, r, MD Grant/Research/linical !rial "upport# N4H %ferile status, "DEP*3 onsultant/Ad$isor& -oards# Eisai %AED

'.onisa(ide, pera(panel)*3 April ! Eichler, MD, M"# E5uit& 67nership/"toc2 6ptions# Johnson 8 Johnson %De(entia 'galanta(ine), Epileps&

'topira(ate)*3

ontriutor disclosures are re$ie7ed for conflicts of interest & the editorial group3 When found, these are addressed & $etting through a (ulti0le$el

re$ie7 process, and through re5uire(ents for references to e pro$ided to support the content3 Appropriatel& referenced content is re5uired of all authors

and (ust confor( to p!oDate standards of e$idence3

$onflict of interest policy

All topics are updated as ne7 e$idence eco(es a$ailale and our peer re$ie7 process is co(plete3%iterature re&ie' current through: Fe 9:;, 9:;


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A practice para(eter for the treat(ent of a child 7ith a first unpro$o2ed sei.ure pulished & the ualit& "tandards

"uco((ittee of the A(erican Acade(& of Neurolog& and the Practice o((ittee of the hild Neurolog& "ociet& pro$ides

the follo7ing reco((endations %;*#

C!reat(ent 7ith antisei.ure drugs is not indicated for the pre$ention of the de$elop(ent of epileps&3

C!reat(ent 7ith antisei.ure drugs (a& e considered 7hen the enefits of reducing the ris2 of a second sei.ure are

greater than the ris2s of phar(acologic and ps&chosocial side effects3

!his is consistent 7ith the current practice of (ost neurologists to refrain fro( treating a child 7ith a first unpro$o2ed sei.ure3

A consensus state(ent fro( the 4nternational 1eague Against Epileps& '41AE) si(ilarl& states that in an other7ise 7ell infant,

a polic& of 7ait and see 7ith close follo7 up (onitoring is reasonale after a first aferile sei.ure %9*3 E$en if the child has a

static encephalopath&, treat(ent can e 7ithheld until a recurrence pattern is estalished3 !he ris2 of sei.ure recurrence is

higher in children 7ith a potential re(ote s&(pto(atic etiolog&, particularl& if the sei.ure 7as focal and the EEG anor(al+ in

such cases, the enefits of i((ediate antisei.ure drug therap& (a& out7eigh the ris2s3

Ris/ of seizure recurrence ? !he child 7ho is neurologicall& nor(al, has no histor& of a prior neurologic illness, and has

an unpro$o2ed sei.ure 7ith no e$ident acute cause, has a 9 percent ris2 of ha$ing another sei.ure in the neBt &ear and a

I percent ris2 o$er the neBt ; &ears %,*3

linical factors associated 7ith an increased ris2 of recurrent sei.ures include#

CPrior neurologic insult 'ie, re(ote s&(pto(atic sei.ure)

C"ignificant (agnetic resonance i(aging 'MR4) findingsCAnor(al electroencephalogra( 'EEG)

!he (agnitude of ris2 associated 7ith each one of these factors $aries, and the additi$e effects of (ultiple ris2 factors ha$e

not een clearl& estalished3 "e$eral studies illustrate the ris2 spectru(#

C4n a large prospecti$e stud& of 9> children 7ith a first0ti(e unpro$o2ed sei.ure, neurologicall& nor(al children 7ith

no histor& of prior neurologic illness had a 9 percent ris2 of ha$ing a sei.ure in the neBt &ear %,*3 !he one0&ear

recurrence ris2 increased to K percent in children 7ith a prior neurologic insult 're(ote s&(pto(atic), such as cereral

pals&, and increased to K: percent in patients 7ho had t7o sei.ures separated & at least 9 hours3 Most ut not all of

the children in this stud& 7ere not treated 7ith an antisei.ure drug3

C4n the sa(e stud&, the one0&ear recurrence ris2 7as ; percent if the EEG 7as anor(al 'epileptifor( acti$it&, focal or

generali.ed slo7ing) co(pared 7ith ;I percent in children 7ith a nor(al EEG %*3

C4n another stud&, significant (agnetic resonance i(aging 'MR4) findings, present in ;< percent of children, 7ere (ore

predicti$e of short0ter( sei.ure recurrence than EEG findings %I*3

"tatus epilepticus as the presenting sei.ure (a& e another ris2 factor for recurrent sei.ures, although the a$ailale data are

less consistent %,*3 Ho7e$er,

at one and t7o &ears, the nu(er of patients 7ho re(ained sei.ure0free in the earl& treat(ent and dela&ed treat(ent

groups 7ere si(ilar '> to >K percent at one &ear,


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Second unpro&o/ed seizure ? Most children 7ho present 7ith a second unpro$o2ed sei.ure are started on antisei.ure

drug therap&, since sei.ure recurrence indicates that the patient has a sustantiall& increased ris2 for additional sei.ures 'ie,

epileps&)3

!here are so(e eBceptions, ho7e$er3 Man& parents elect no antisei.ure drugs if the sei.ures are infre5uent and/or (ild3 !he

definitions of @infre5uent@ and @(ild@ (a& $ar& fro( parent to parent3 4n contrast, children 7ith asence sei.ures, atonic

sei.ures or drop attac2s, and infantile spas(s are $irtuall& al7a&s treated, since the& usuall& present to the clinician 7ith an

alread& estalished pattern of fre5uent sei.ures3

Acute symptomatic seizure ? hildren 7ho ha$e a sei.ure in the setting of an acute illness 'eg, acute infection, acute

head inur&) ha$e a lo7 ris2 of sei.ure recurrence co(pared 7ith other children 7ith a first sei.ure %;:*3 When a sei.ure is

associated 7ith a specific underl&ing acute etiolog&, sei.ure recurrence is li2el& onl& if the underl&ing etiolog& recurs3

EBa(ples include sei.ures associated 7ith ferile illnesses, (etaolic derange(ents such as h&ponatre(ia, and

concussion3 Manage(ent of these sei.ures should e focused on correction of the acute pro$o2ing illness or ano(al& and

pre$enting its recurrence3

!e0rile seizure ? hildren presenting 7ith a first0ti(e ferile sei.ure ha$e an approBi(atel& : to I percent chance of

ha$ing another ferile sei.ure during earl& childhood3 Although antisei.ure drugs ha$e een sho7n to lo7er the ris2 of

recurrent ferile sei.ures, gi$en the enign nature of ferile sei.ures, the ris2s of side effects fro( antisei.ure drugs

generall& out7eigh the enefits for (ost patients3 !his is discussed in (ore detail separatel&3 '"ee @!reat(ent and prognosis

of ferile sei.ures@, section on Role of pre$enti$e therap&3)

Neonatal seizure ? Neonatal sei.ures (a& e the first, and so(eti(es the onl&, clinical sign of a central ner$ous s&ste(disorder in the ne7orn infant3 "ei.ures (a& indicate the presence of a potential treatale etiolog& and should pro(pt an

i((ediate e$aluation to deter(ine the cause and institute etiologic0specific therap&3 '"ee @linical features, e$aluation, and

diagnosis of neonatal sei.ures@, section on Etiologic e$aluation3)

!he decision 7hether or not to institute antisei.ure drug therap& depends on (ultiple factors, including sei.ure duration and

se$erit& as 7ell as sei.ure etiolog&3 !he (anage(ent of neonatal sei.ures is discussed in (ore detail separatel&3

'"ee @!reat(ent of neonatal sei.ures@3)

SE%E$(I)N )! AN AN(ISEI+*RE DR* ? "ingle0drug therap& is the goal of epileps& treat(ent3 Monotherap& is

associated 7ith etter co(pliance, fe7er ad$erse effects, less potential for teratogenicit&, and lo7er cost than is pol&therap&3

Drug interactions are a$oided and phar(aco2inetics are si(plified3

!here is an e$er0gro7ing list of antisei.ure drugs and nonphar(acologic therapies a$ailale to (anage childhood epileps&3

!raditionall&, the (edications ha$e een separated into @older@ and @ne7er@ groups ased upon their historic regulator&

appro$al and a$ailailit&3 !&picall&, 7hen a (edication is first appro$ed for epileps&, it recei$es an @on0lael indication@ foradd0on 'aduncti$e) therap& for partial0onset sei.ures in adults3 !hen, as eBperience gro7s and other studies are done, the

use of the drug (a& eBpand to other sei.ure t&pes and &ounger age groups3

Seizure.related considerations ? !he antisei.ure drug chosen for initial therap& should e one that is highl& effecti$e for a

particular sei.ure t&pe or s&ndro(e %;;,;9*3 !he initial 7or20up should include an atte(pt to deter(ine the specific t&pe of

sei.ure the child eBperienced and, if possile, the epileps& s&ndro(e3 !he opti(al choice of antisei.ure drug depends on the

t&pe of sei.ure and the epileps& s&ndro(e3 '"ee @"ei.ures and epileps& in children# lassification, etiolog&, and clinical

features@ and @Epileps& s&ndro(es in children@3)

For so(e epileps& s&ndro(es, a$ailale data support choosing certain antisei.ure drugs o$er others as first0line therap&3

EBa(ples include#

Corticotropin 'A!H) for infantile spas(s 'see @Manage(ent and prognosis of infantile spas(s@, section on

Hor(onal therap&)

CEthosuBi(ide or $alproate for childhood asence epileps& 'see @hildhood asence epileps&@, section on !reat(ent)

Calproate for u$enile (&oclonic epileps& 'see @Ju$enile (&oclonic epileps&@, section on alproate)

For others, such as focal epileps& due to a re(ote s&(pto(atic cause or (esial te(poral sclerosis, there are no clear

differences in efficac& a(ong $arious antisei.ure drugs, and clinicians generall& chose first0line therap& ased on other drug0

related factors such as side effects, cost, and dosing inter$als3 '"ee Drug0related considerations elo73)

4n so(e cases, particularl& for generali.ed epileps& s&ndro(es, sei.ures (a& e aggra$ated & the ad(inistration of a

narro70spectru( antisei.ure drug, 7hen a road0spectru( antisei.ure drug is (ore appropriate 'tale ;)3 As

eBa(ples, cara(a.epine andphen&toin ha$e een reported to 7orsen asence and (&oclonic sei.ures in indi$iduals 7ith

http://www.uptodate.com/contents/seizures-and-epilepsy-in-children-initial-treatment-and-monitoring/abstract/10http://www.uptodate.com/contents/treatment-and-prognosis-of-febrile-seizures?source=see_link&sectionName=Role+of+preventive+therapy&anchor=H762181856#H762181856http://www.uptodate.com/contents/treatment-and-prognosis-of-febrile-seizures?source=see_link&sectionName=Role+of+preventive+therapy&anchor=H762181856#H762181856http://www.uptodate.com/contents/treatment-and-prognosis-of-febrile-seizures?source=see_link&sectionName=Role+of+preventive+therapy&anchor=H762181856#H762181856http://www.uptodate.com/contents/treatment-and-prognosis-of-febrile-seizures?source=see_link&sectionName=Role+of+preventive+therapy&anchor=H762181856#H762181856http://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-neonatal-seizures?source=see_link&sectionName=ETIOLOGIC+EVALUATION&anchor=H530063767#H530063767http://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-neonatal-seizures?source=see_link&sectionName=ETIOLOGIC+EVALUATION&anchor=H530063767#H530063767http://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-neonatal-seizures?source=see_link&sectionName=ETIOLOGIC+EVALUATION&anchor=H530063767#H530063767http://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-neonatal-seizures?source=see_link&sectionName=ETIOLOGIC+EVALUATION&anchor=H530063767#H530063767http://www.uptodate.com/contents/treatment-of-neonatal-seizures?source=see_linkhttp://www.uptodate.com/contents/treatment-of-neonatal-seizures?source=see_linkhttp://www.uptodate.com/contents/seizures-and-epilepsy-in-children-initial-treatment-and-monitoring/abstract/11,12http://www.uptodate.com/contents/seizures-and-epilepsy-in-children-initial-treatment-and-monitoring/abstract/11,12http://www.uptodate.com/contents/seizures-and-epilepsy-in-children-classification-etiology-and-clinical-features?source=see_linkhttp://www.uptodate.com/contents/seizures-and-epilepsy-in-children-classification-etiology-and-clinical-features?source=see_linkhttp://www.uptodate.com/contents/seizures-and-epilepsy-in-children-classification-etiology-and-clinical-features?source=see_linkhttp://www.uptodate.com/contents/epilepsy-syndromes-in-children?source=see_linkhttp://www.uptodate.com/contents/epilepsy-syndromes-in-children?source=see_linkhttp://www.uptodate.com/contents/management-and-prognosis-of-infantile-spasms?source=see_link&sectionName=HORMONAL+THERAPY&anchor=H4#H4http://www.uptodate.com/contents/management-and-prognosis-of-infantile-spasms?source=see_link&sectionName=HORMONAL+THERAPY&anchor=H4#H4http://www.uptodate.com/contents/management-and-prognosis-of-infantile-spasms?source=see_link&sectionName=HORMONAL+THERAPY&anchor=H4#H4http://www.uptodate.com/contents/ethosuximide-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/valproate-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/valproate-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/childhood-absence-epilepsy?source=see_link&sectionName=TREATMENT&anchor=H383785509#H383785509http://www.uptodate.com/contents/valproate-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/juvenile-myoclonic-epilepsy?source=see_link&sectionName=Valproate&anchor=H1409477#H1409477http://www.uptodate.com/contents/juvenile-myoclonic-epilepsy?source=see_link&sectionName=Valproate&anchor=H1409477#H1409477http://www.uptodate.com/contents/juvenile-myoclonic-epilepsy?source=see_link&sectionName=Valproate&anchor=H1409477#H1409477http://www.uptodate.com/contents/seizures-and-epilepsy-in-children-initial-treatment-and-monitoring?source=search_result&search=convulsiones+en+los+ni%C3%B1os&selectedTitle=2~150#H1539284308http://www.uptodate.com/contents/seizures-and-epilepsy-in-children-initial-treatment-and-monitoring?source=search_result&search=convulsiones+en+los+ni%C3%B1os&selectedTitle=2~150#H1539284308http://www.uptodate.com/contents/image?imageKey=NEURO%2F78021&topicKey=PEDS%2F6203&rank=2~150&source=see_link&search=convulsiones+en+los+ni%C3%B1oshttp://www.uptodate.com/contents/carbamazepine-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/carbamazepine-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/phenytoin-pediatric-drug-information?source=see_linkhttp://www.uptodate.com/contents/seizures-and-epilepsy-in-children-initial-treatment-and-monitoring/abstract/10http://www.uptodate.com/contents/treatment-and-prognosis-of-febrile-seizures?source=see_link&sectionName=Role+of+preventive+therapy&anchor=H762181856#H762181856http://www.uptodate.com/contents/treatment-and-prognosis-of-febrile-seizures?source=see_link&sectionName=Role+of+preventive+therapy&anchor=H762181856#H762181856http://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-neonatal-seizures?source=see_link&sectionName=ETIOLOGIC+EVALUATION&anchor=H5300637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idiopathic generali.ed epileps& %;0;


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infor(ed of the ris2s associated 7ith $alproate use during pregnanc& 'see @Ris2s associated 7ith epileps& and

pregnanc&@, section on alproate) as 7ell as the relati$e ris2s and enefits of alternati$e treat(ent options3 6ptions for

effecti$e contraception in the setting of antisei.ure drug therap& should also e re$ie7ed3 '"ee Additional

considerations in adolescent girls elo73)

CWhen $alproate is used in girls and 7o(en of childearing potential, it should e prescried at the lo7est effecti$e

dose and 7hen possile, at doses not eBceeding I:: to


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!he antisei.ure drug dose should e increased until sei.ures stop, unre(itting ad$erse effects occur, or seru( le$els reach

a high or supratherapeutic range 7ithout a significant i(pact upon sei.ure fre5uenc&3 !he reco((ended upper therapeutic

seru( le$els of (ost of the antisei.ure drugs can e eBceeded if side effects are asent3 !his should e done 7ith particular

caution 7ith phen&toin ecause of its nonlinear phar(aco2inetics and 7ith $alproate ecause of dose0related

thro(oc&topenia 'tale 9A0-)3

4f side effects appear 7ith up7ard titration ut are tolerale, the dose should re(ain stale for se$eral 7ee2s to deter(ine if

the s&(pto(s re(it3 Dose increases can continue at a slo7er rate if side effects re(it and sei.ures continue3

"o(e patients (a& re5uire greater than standard doses of an antisei.ure drug to reach therapeutic le$els3 1o7 le$els at high

doses often are caused & poor co(pliance ut also (a& e secondar& to h&per(etaolis( of the antisei.ure drug 'ie,

higher than nor(al clearance ecause of increased hepatic (etaolis()3 4f le$els are not increasing as anticipated and

nonco(pliance is unli2el&, the child should e gi$en a loading dose under (edical oser$ation and le$els should e

(easured o$er the neBt ;9 to 9 hours3 A geneticall& regulated h&per(etaolis( proal& eBists if le$els re(ain lo7, and

higher dail& doses are indicated3

6ccasionall&, children (anifest slo7 drug clearance, often caused & inherited $ariations in the degradation en.&(es3 !hese

indi$iduals re5uire lo7er (aintenance doses3

4deall&, dail& antisei.ure drug doses should e gi$en at inter$als shorter than the half0life in order to a$oid 7ide eBcursions in

seru( le$els3 !he longer the half0life, the less fre5uent the dosing3 o(pliance is i(pro$ed 7hen (edications are ta2en on

schedule and pro(pted & an association 7ith a routine dail& acti$it&, such as (ealti(e or rushing teeth3 A $ariation of an

hour or so in scheduled dosing is usuall& not significant3 hildren should not e a7a2ened at night to ta2e antisei.ure drugs3

As a child gro7s, the antisei.ure drug dose (a& need to e increased to 2eep up 7ith his or her od& (ass3 Ho7e$er, the

clearance of so(e antisei.ure drugs decreases and approaches adult rates in adolescence3 "eru( le$els (a& re(ain stale

as the declining per 2ilogra( dose is alanced & the declining clearance3

Additional considerations in adolescent girls ? A nu(er of issues are i(portant to consider in preadolescent and

adolescent girls 7hen initiating antisei.ure drug therap&3 As discussed ao$e, the potential teratogenicit& of $arious

antisei.ure drugs should e discussed and 7eighed 7hen choosing a specific antisei.ure drug in girls, since in (an& cases

initial therap& 7ill e continued long0ter(, into the childearing &ears3 '"ee !eratogenicit& ao$e and @Ris2s associated 7ith

epileps& and pregnanc&@, section on Effect of antisei.ure drugs on the fetus3)

!he i(portance of an effecti$e (ethod of contraception should also e re$ie7ed 7ith girls 7ho are seBuall& acti$e or (a&

eco(e seBuall& acti$e 7hile ta2ing antisei.ure drugs3 ertain antisei.ure drugs ha$e the potential to lo7er the efficac& of

hor(onal contraception through hepatic en.&(e induction 'tale


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)ther la0oratory monitoring ? Although routine laorator& screening of he(atologic and hepatic function is co((onl&

done in children recei$ing antisei.ure drugs, e$idence is con$incing that this routine laorator& testing is not cost effecti$e or

necessar& %9,9*3

With the eBception of fela(ate, 7hich is associated 7ith a relati$el& high ris2 of aplastic ane(ia and re5uires close

laorator& (onitoring, the ris2 of serious side effects 7ith (ost of the antisei.ure drugs is eBtre(el& s(all and, in (ost

instances, appears in the first fe7 (onths after the antisei.ure drug is initiated3 Man& idios&ncratic reactions related to

antisei.ure drugs, including "te$ens0Johnson s&ndro(e, toBic epider(al necrol&sis, seru( sic2ness reactions, andpancreatitis, are not predicted & pres&(pto(atic lood test anor(alities '7ith the eBception of cara(a.epine0induced

h&persensiti$it& reactions related to certain H1A t&pes)3 '"ee Role of pretreat(ent H1A testing ao$e3)

6nce a child has een on a stale antisei.ure drug regi(en for se$eral (onths, there is little indication for routine (onitoring

of laorator& studies 'tale 9A0-)3 !he clinician should e clinicall& $igilant and ha$e a lo7 indeB of suspicion for ad$erse

e$ents in an& child recei$ing chronic antisei.ure drugs3 A see(ingl& enign illness that lasts for (ore than a fe7 da&s should

pro(pt a - and/or li$er function studies3 o(iting 'the (ost co((on earl& s&(pto( of hepatotoBicit& or pancreatitis),

prolonged uneBplained fe$er, eas& ruising, eBtre(e fatigue or letharg&, flu0li2e s&(pto(s, uneBplained 7orsening of

sei.ures, change in (ental status, and ado(inal pain should lead to further in$estigations %9I*3

A fa(il& histor& can e helpful in (a2ing decisions aout laorator& testing3 Ad$erse reactions to (edications, particularl&

those that are he(atologic or cutaneous, or a strong fa(il& histor& of autoi((une disorders, should heighten the concern for

idios&ncratic reactions and he(atological co(plications3 A fa(il& as 7ell as personal histor& of renal stones should e

sought 7hen topira(ate or .onisa(ide is considered %9:: to

;:::, the (edication should e stopped3

C!opira(ate and .onisa(ide !hese antisei.ure drugs are partial caronic anh&drase inhiitors and (a& cause a (ild

to (oderate chronic (etaolic acidosis in up to t7o0thirds of children and can also cause nephrolithiasis %9


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disease or concurrent use of a 2etogenic diet %9,* 'see @!he 2etogenic diet@ and @"ei.ures and epileps& in children#

Refractor& sei.ures and prognosis@, section on !he 2etogenic diet)3 Potential co(plications of chronic (etaolic

acidosis in children include i(paired gro7th, ric2ets, or osteo(alacia %,I*3

For these reasons, the seru( icaronate should e (easured at aseline and (onitored periodicall& thereafter in

children treated 7ith topira(ate or .onisa(ide3 Dose reduction or drug discontinuation should e considered in patients

7ith persistent or se$ere (etaolic acidosis3 4f the drug is continued, al2ali therap& (a& e 7arranted as in t&pe 9

'proBi(al) renal tuular acidosis3 '"ee @!reat(ent of distal 't&pe ;) and proBi(al 't&pe 9) renal tuular acidosis@3)

C6Bcara.epine H&ponatre(ia has een reported 7ith the use of oBcara.epine, ut this is $er& rare in children3 !he

t7o predo(inant ris2 factors appear to e conco(itant use of other @sodiu(0depleting@ (edications 'eg, tric&clic

antidepressants, thia.ide diuretics, at&pical antips&chotics) and eBcessi$e free 7ater consu(ption3 !he effect is dose0

related and usuall& occurs 7ithin the first three (onths of therap& or follo7ing the addition of another sodiu(0depleting

(edication3 4t is not usuall& necessar& to reduce or stop oBcara.epine due to h&ponatre(ia+ the seru( sodiu( le$el

usuall& graduall& returns to nor(al or re(ains at a (ildl& reduced le$el and is nearl& al7a&s as&(pto(atic3 For sodiu(

le$els less than ;9: (e5/1 or s&(pto(s of h&ponatre(ia, a dose reduction of oBcara.epine or (ild fluid restriction is

usuall& successful3 '"ee @Antisei.ure drugs# Mechanis( of action, phar(acolog&, and ad$erse effects@, section on

H&ponatre(ia3)

Cigaatrin igaatrin is associated 7ith ris2s of per(anent retinal d&sfunction and concentric $isual field constriction

that ha$e een noted as earl& as nine (onths after initiation of treat(ent %


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sut&pe of ADHD, rather than the h&peracti$e0i(pulsi$e sut&pe %;,*3 '"ee @Attention deficit h&peracti$it& disorder in

children and adolescents# linical features and e$aluation@, section on ADHD3)

Recognition of ADHD in children 7ith epileps& is i(portant ecause effecti$e treat(ents eBist, and ADHD has een

associated 7ith decreased health0related 5ualit& of life in children 7ith epileps& %;*3 "ti(ulants ha$e not een 7ell studied in

patients 7ith epileps& ecause of concern that the& (a& lo7er the sei.ure threshold, and patients 7ith epileps& 7ere

eBcluded fro( clinical trials estalishing the safet& and efficac& of sti(ulant (edications3 Although one dose0escalation stud&

of sustained0release (eth&lphenidate in children 7ith epileps& found a slight increase in sei.ure fre5uenc& at high doses%*, other data, pri(aril& in the for( of retrospecti$e case series and s(all prospecti$e studies, suggest that lo7 to (ediu(

doses of (eth&lphenidate are safe and effecti$e, e$en in children 7ith acti$e sei.ures %I0I9*3

4n our eBperience, ADHD is $er& pre$alent in children 7ith epileps&3 We reco((end that all children 7ith epileps& undergo

standardi.ed ps&choeducational testing through their school or in our clinic3 6nce a diagnosis of ADHD is (ade, eha$ioral

therapies are offered as first0line inter$ention3 4f acade(ic prole(s persist, then therap& 7ith sti(ulant (edication is offered

to all ut the (ost unstale patients3 aregi$ers and classroo( teachers are ad$ised to (onitor the childs sei.ure urden

carefull& 7hen the sti(ulant (edication is first introduced3 4n our eBperience, it is rare to see a significant deterioration in

sei.ure control3

!he treat(ent of children and adolescents 7ith ADHD is discussed in detail separatel&3 '"ee @Attention deficit h&peracti$it&

disorder in children and adolescents# 6$er$ie7 of treat(ent and prognosis@3)

Adherence to antiseizure drugs ? Rates of nonadherence to prescried antisei.ure drug therap& are difficult to (easure,

ut are proal& higher than is generall& appreciated and can contriute to inade5uate sei.ure control3

6ne prospecti$e oser$ational stud& in ;9 children '9 to ;9 &ears old) 7ith ne7l& diagnosed epileps& found that I> percent

de(onstrated nonadherence during the first siB (onths of treat(ent %I*3 A pattern of nonadherence 7as often estalished

7ithin the first (onth3 4n a follo7 up stud& of the sa(e cohort, nonadherence during the first siB (onths 7as associated 7ith

7orse sei.ure control at four &ears %I*3

!he co(pleBit& of drug regi(ens and the occurrence of side effects are elie$ed to contriute to nonadherence3 1o7

socioecono(ic status has also een identified as a ris2 factor %I*3

"(all studies ha$e eBplored 7a&s to i(pro$e upon adherence in patients 7ith epileps&3 A s&ste(atic re$ie7 of rando(i.ed

trials testing the effecti$eness of adherence inter$entions in adults 'I trials) and children '; trial) 7ith epileps& found that

eha$ioral inter$entions 'eg, use of intensi$e re(inders) 7ere associated 7ith so(e7hat etter results than education and

counselling %II*3

RE!RA$()R- SEI+*RES ? Most children 7ith epileps& achie$e reasonal& good sei.ure control 7ith antisei.ure drug

therap&, ut so(e are refractor& despite nu(erous (edications3 Medical treat(ent failure is often apparent earl& in the

course of treat(ent3 4n these cases, referral to a co(prehensi$e epileps& center is appropriate to eBplore addition

therapeutic options, including epileps& surger&, $agus ner$e sti(ulation, and the 2etogenic diet3 '"ee @"ei.ures and epileps&

in children# Refractor& sei.ures and prognosis@3)

S()""IN AN(ISEI+*RE DR* (#ERA"- ? Withdra7al of antisei.ure drug therap& should e considered in (ost

children after t7o &ears 7ithout sei.ures regardless of the etiolog& of the sei.ures3 !he li2elihood of recurrence after a t7o0

&ear period 7ithout sei.ures is approBi(atel& : to : percent %I*3 1onger sei.ure0free periods are associated 7ith onl& a slightl& lo7er incidence of recurrence, and therefore longer

oser$ation periods 'ie, T9 &ears) are not 7arranted3

!he ris2 of recurrent intractale sei.ures after discontinuing antisei.ure drugs in sei.ure0free children is $er& lo73 4n a cohortstud& of 9


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C"hort treat(ent period '< to ;9 (onths) prior to discontinuation %


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V!reat(ent 7ith an antisei.ure drug reduces the ris2 of recurrent sei.ures, ho7e$er, 7ithholding treat(ent until

after the second sei.ure does not alter the long0ter( prognosis of epileps&3 '"ee Effects of earl& $ersus deferred

therap& ao$e3)

CMost neurologists refrain fro( starting antisei.ure drug therap& in a child 7ith a first unpro$o2ed sei.ure, esti(ating

that the ris2s of side effects out7eigh the (odest enefit of antisei.ure drug therap& in pre$enting a recurrent sei.ure3

E$en if the child has a static encephalopath&, treat(ent can e 7ithheld until a recurrence pattern is estalished3 !he

ris2 of sei.ure recurrence is higher in children 7ith a potential re(ote s&(pto(atic etiolog&, particularl& if the sei.ure

7as focal and the EEG anor(al+ in such cases, the enefits of i((ediate antisei.ure drug therap& (a& out7eigh the

ris2s3 '"ee First0ti(e unpro$o2ed sei.ure ao$e3)

CWe reco((end initiating antisei.ure drug therap& in children 7ith recurrent, unpro$o2ed sei.ures 'rade 3A)3

6ccasionall&, antisei.ure drug therap& is deferred in this setting if sei.ures are rief, nondisrupti$e, and infre5uent3

'"ee "econd unpro$o2ed sei.ureao$e3)

C!he antisei.ure drug chosen for initial therap& should e one that is highl& effecti$e for a particular sei.ure t&pe or

s&ndro(e and that is safe and 7ell tolerated3 6ther considerations include dose for(ulation, does fre5uenc&, the

relati$e ris2 of certain side effects, the potential for drug0drug interactions3 '"ee 4nitiation of antisei.ure drug

therap& ao$e3)

CRoutine laorator& screening of he(atologic and hepatic function is co((onl& done in children recei$ing antisei.ure

drugs, ut the $alue of this practice and a reco((ended fre5uenc& is not defined3 '"ee Follo7 up and

(onitoring ao$e3)

VMost clinicians otain screening laorator& tests efore initiating antisei.ure drug therap& 7ith a - and platelet

count, li$er and renal function tests, glucose, electrol&tes, total protein, alu(in, and gloulin3 '"ee -aseline

laorator& e$aluation ao$e3)

VMan& idios&ncratic reactions related to antisei.ure drugs, including "te$ens0Johnson s&ndro(e, toBic epider(al

necrol&sis, seru( sic2ness reactions, and pancreatitis, are not predicted & pres&(pto(atic lood test

anor(alities, 7ith the eBception of h&persensiti$it& reactions related to cara(a.epine 'and

possil& phen&toin and oBcara.epine) in patients 7ith certain hu(an leucoc&te antigen 'H1A) t&pes3 '"ee Role

of pretreat(ent H1A testing ao$e3)

V4n children under the age of three or those 7ho (ight ha$e a neuro(etaolic disorder, one should consider

otaining seru( a((onia, p&ru$ate, lactate, and carnitine le$els and seru( a(ino acid and urine organic acid

anal&ses efore initiating $alproic acid3 alproate should e a$oided if there is clinical suspicion that the childs

illness is progressi$e 7hen no etiolog& has een deter(ined3 '"ee "pecific drugs ao$e3)

V6nce a child has een on a stale antisei.ure drug regi(en for se$eral (onths, there is little indication for

routine (onitoring of laorator& studies3 !he clinician should e clinicall& $ igilant and ha$e a lo7 indeB of

suspicion for ad$erse e$ents in an& child recei$ing chronic antisei.ure drugs3 A see(ingl& enign illness that lasts

for (ore than a fe7 da&s should pro(pt a - and/or li$er function studies3 o(iting 'the (ost co((on earl&

s&(pto( of hepatotoBicit& or pancreatitis), prolonged uneBplained fe$er, eas& ruising, eBtre(e fatigue or

letharg&, flu0li2e s&(pto(s, uneBplained 7orsening of sei.ures, change in (ental status, and ado(inal pain

should lead to further in$estigations3 '"ee 6ther laorator& (onitoring ao$e3)

V4ncreased suicidalit& has een lin2ed to se$eral antisei.ure drugs3 Patients ta2ing antisei.ure drugs should e

(onitored for e(ergence or 7orsening of suicidal ideation or depression3 '"ee Ps&chiatric and eha$ioral health

screening ao$e3)

CMost children 7ith epileps& achie$e reasonal& good sei.ure control 7ith antisei.ure drug (onotherap& or

pol&therap&, ut so(e are refractor& despite nu(erous (edications3 Medical treat(ent failure is often apparent earl& in

the course of treat(ent3 4n these cases, referral to a co(prehensi$e epileps& center is appropriate to eBplore addition

therapeutic options, including epileps& surger&, $agus ner$e sti(ulation, and the 2etogenic diet3 '"ee @"ei.ures and

epileps& in children# Refractor& sei.ures and prognosis@3)

CWithdra7al of antisei.ure drug therap& should e considered in (ost children after t7o &ears 7ithout sei.uresregardless of the etiolog& of the sei.ures3 !he li2elihood of recurrence after a t7o0&ear period 7ithout sei.ures is

approBi(atel& : to : percent3 antisei.ure drugs should e tapered rather than halted aruptl&3 '"ee "topping

antisei.ure drug therap& ao$e3)

se of p!oDate is suect to the "uscription and 1icense Agree(ent3

RE!EREN$ES

;3 Hirt. D, -erg A, -ettis D, et al3 Practice para(eter# treat(ent of the child 7ith a first unpro$o2ed sei.ure# Report of the ualit& "tandards "uco((ittee of the A(erican Acade(& of Neurolog& and the Practice o((ittee of the hildNeurolog& "ociet&3 Neurolog& 9::+


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93 Wil(shurst JM, Gaillard WD, ina&an OP, et al3 "u((ar& of reco((endations for the (anage(ent of infantilesei.ures# !as2 Force Report for the 41AE o((ission of Pediatrics3 Epilepsia 9:;I+ II3

3 "hinnar ", -erg A!, Mosh "1, et al3 Ris2 of sei.ure recurrence follo7ing a first unpro$o2ed sei.ure in childhood# aprospecti$e stud&3 Pediatrics ;LL:+ >I#;:K:3

I3 Arthur !M, deGrau7 !J, Johnson ", et al3 "ei.ure recurrence ris2 follo7ing a first sei.ure in neurologicall&nor(al children3 Epilepsia 9::>+ L#;LI:3

#;K:I3

>3 Musicco M, -eghi E, "olari A, iani F3 !reat(ent of first tonic0clonic sei.ure does not i(pro$e the prognosis ofepileps&3 First "ei.ure !rial Group 'F4R"! Group)3 Neurolog& ;LLK+ L#LL;3

L3 Marson A, Jaco& A, Johnson A, et al3 4((ediate $ersus deferred antiepileptic drug treat(ent for earl& epileps&and single sei.ures# a rando(ised controlled trial3 1ancet 9::I+ 3

9;3 enters for Disease ontrol and Pre$ention3 Moridit& and Mortalit& Wee2l& Report 'MMWR)3 3"3 MedicalEligiilit& riteria for ontracepti$e se, 9:;:3 Adapted fro( the World Health 6rgani.ation Medical Eligiilit& riteria for

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ontracepti$e se, th edition3 Earl& release 0 Ma& 9>, 9:;:3 http#//7773cdc3go$/((7r/pre$ie7/((7rht(l/rrILe:I9>a;3ht('Accessed on Ma& 9>, 9:;:)3

993 "heinerg R, He&(an E, Dagan Z, et al3 orrelation et7een efficac& of le$etiraceta( and seru( le$els a(ongchildren 7ith refractor& epileps&3 Pediatr Neurol 9:;I+ I9#L+ ;:#;:3

93 Pelloc2 JM, Will(ore 1J3 A rational guide to routine lood (onitoring in patients recei$ing antiepileptic drugs3Neurolog& ;LL;+ ;#L3 Wall M, -aird01a(ert J, -uchanan N, Farrell G3 1i$er function tests in persons recei$ing anticon$ulsant

(edications3 "ei.ure ;LL9+ ;#;>K3

9L3 Mendis GP, Gierd F-, Hunt HA3 Plas(a acti$ities of hepatic en.&(es in patients on anticon$ulsant therap&3"ei.ure ;LL+ 9#;L3

:3 Dreifuss FE, 1anger DH3 Hepatic considerations in the use of antiepileptic drugs3 Epilepsia ;L>K+ 9> "uppl 9#"93

;3 "eethara( MN, Pelloc2 JM3 Ris20enefit assess(ent of cara(a.epine in children3 Drug "af ;LL;+ 3

93 Mu2hin NA, Oo.lo$s2aia 1, -o2o$a 4N, et al3 %!he 2e& role of tuulointerstitiu( re(odeling in progression ofchronic renal diseases*3 Ar2h Patol 9::+


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93 !ho(e0"ou.a ", Ouc.&ns2i E, Assu(p[\o F Jr, et al3 Which factors (a& pla& a pi$otal role on deter(ining thet&pe of ps&chiatric disorder in children and adolescents 7ith epileps&X Epileps& -eha$ 9::+ I#L>>3

3 Hesdorffer D, 1ud$igsson P, 6lafsson E, et al3 ADHD as a ris2 factor for incident unpro$o2ed sei.ures andepileps& in children3 Arch Gen Ps&chiatr& 9::+ 3 Gross0!sur , Manor 6, $an der Meere J, et al3 Epileps& and attention deficit h&peracti$it& disorder# is(eth&lphenidate safe and effecti$eX J Pediatr ;LLK+ ;:#


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seizures and convulsiones en niños

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