LGS Medscape

8/19/2019 LGS Medscape

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Practice Essentials

Lennox-Gastaut syndrome (LGS), or childhood epileptic encephalopathy, is a pediatric epilepsy syndromecharacterized by multiple seizure types; mental retardation or regression; and abnormal indings onelectroencephalography (EEG)! See the image belo"!

Slo" spi#e "a$e pattern in a %&-year-old a"a#emale "ith Lennox-Gastaut syndrome! 'he slo" posterior bac#ground rhythm has reuent periods o %- to %!-*zdischarges, maximal in the birontocentral areas, occurring in trains as long as + seconds "ithout any clinicalaccompaniment!

Signs and symptoms

not present beore symptom onset, neurologic and neuropsychologic deicits ine$itably appear during thee$olution o LGS! actors associated "ith more common or more se$ere mental retardation include theollo"ing.

• /n identiiable etiology (ie, symptomatic as opposed to cryptogenic LGS)

• / history o 0est syndrome ( inantile spasm)

• 1nset o symptoms beore age 2%-%& months

• 3ore reuent seizures

/$erage intelligence uotient (4) score is signiicantly lo"er in patients "ith symptomatic LGS than in those"ith cryptogenic LGS! Earlier age o seizure onset is correlated "ith higher ris# o cogniti$e impairment!

ctal clinical maniestations include the ollo"ing.

• 'onic seizures (reuency, 25-67) - 8an occur during "a#eulness or sleep but are more reuent

during non9rapid eye mo$ement (:E3) sleep; may be axial, axiorhizomelic, or global; may be asymmetric

•

/typical absence seizures (reuency, 25-27) 9 8an ha$e gradual onset, "ith incomplete loss oconsciousness; associated eyelid myoclonias may be noted

• /tonic, massi$e myoclonic, and myoclonic-atonic seizures (reuency, 2-27?, complex partial >7?, absence status

epilepticus, tonic status epilepticus, noncon$ulsi$e status epilepticus)indings on general physical examination are normal in many cases! @o physical indings are pathognomonicor LGS! @e$ertheless, the general physical examination can help identiy speciic etiologies that ha$e bothsystemic and neurologic maniestations!

http://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overview


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@o neurologic examination indings are pathognomonic or LGS! *o"e$er, neurologic examination o an LGSpatient may demonstrate the ollo"ing.

• /bnormalities in mental status unction (speciically, deicits in higher cogniti$e unction consistent "ith

intellectual disability)

• /bnormalities in le$el o consciousness, cranial ner$e unction, motorAsensoryArelex examination,

cerebellar testing, or gait (nonspeciic indings that are more a relection o the underlying brain in=ury or the

eect o anticon$ulsant medications)See Presentation or more detail!

Diagnosis

@o laboratory in$estigations are #no"n to aid in the diagnosis o LGS!

EEG ("a#ing and sleep) is an essential part o the "or#up! nterictal EEG may demonstrate the ollo"ingcharacteristics.

• / slo" bac#ground that can be constant or transient

• /"a#e 9 Biuse slo" spi#e "a$e

• @on-:E3 sleep 9 Bischarges that are more generalized and more reuent, consisting o polyspi#es

and slo" "a$es

•:E3 sleep 9 Becreased spi#e "a$es

ctal EEG may demonstrate the ollo"ing characteristics.

• 'onic seizure 9 Biuse, rapid, lo"-amplitude acti$ity pattern that progressi$ely decreases in reuency

and increases in amplitude; may be preceded by a brie generalized discharge o slo" spi#e "a$es orlattening o the recording or ollo"ed by diuse slo" "a$es and slo" spi#e "a$es; no postictal lattening

• /typical absence seizure 9 Biuse, slo", and irregular spi#e "a$es; occasionally, discharges o rapid

rhythms preceded by lattening o the record or 2-% seconds, ollo"ed by progressi$e de$elopment oirregular ast rhythm in anterior and central regions and ending "ith brie spi#e "a$es

• /tonic, massi$e myoclonic, or myoclonic-atonic seizure 9 Slo" spi#e "a$es, polyspi#e "a$es, or rapid

diuse rhythms

• /bsence status epilepticus 9 8ontinuous spi#e "a$e discharges, usually at a lo"er reuency than at

baseline, and rapid rhythms during tonic status epilepticus@euroimaging is an important part o the search or an underlying etiology! 3odalities include the ollo"ing.

• 3agnetic resonance imaging (3:) 9 Generally preerred

• 8omputed tomography (8') 9 Preerred in selected situations

• :outine positron emission tomography (PE') and single-photon emission 8' (SPE8') 9 Lac#ing

current indications or LGS but may be useul in potential candidates or epilepsy surgerySee 0or#up or more detail!

Management

3edical treatment options may be di$ided into the ollo"ing C ma=or groups.

• irst-line treatments based on clinical experience or con$entional "isdom 9 Dalproic acid,

benzodiazepines (speciically, clonazepam, nitrazepam, and clobazam)

• 'reatments suspected to be eecti$e on the basis o open-label uncontrolled studies 9 Digabatrin,

zonisamide• 'reatments pro$en eecti$e by double-blind placebo-controlled studies 9 Lamotrigine, topiramate,

elbamate, ruinamideSurgical options include the ollo"ing.

• 8orpus callosotomy 9 Eecti$e in reducing drop attac#s but not typically helpul or other seizure types;

considered palliati$e rather than curati$e

• Dagus ner$e stimulation 9 B/-appro$ed as ad=uncti$e treatment or reractory partial-onset seizures

in adults and adolescents older than 2% years

http://emedicine.medscape.com/article/1176735-clinicalhttp://emedicine.medscape.com/article/1176735-clinicalhttp://emedicine.medscape.com/article/1176735-workuphttp://emedicine.medscape.com/article/1176735-workuphttp://emedicine.medscape.com/article/1176735-clinicalhttp://emedicine.medscape.com/article/1176735-workup


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• ocal cortical resection 9 3ay impro$e seizure control in rare cases

'he #etogenic dietin$ol$ing a high ratio o ats (#etogenic oods) to proteins and carbohydrates (anti#etogenicoods)may be useul in patients "ith LGS reractory to medical treatment!

See 'reatment and 3edication or more detail!

Fac#ground

8hildhood epileptic encephalopathy, or Lennox-Gastaut syndrome (LGS), is a de$astating pediatric epilepsysyndrome constituting 2-&7 o childhood epilepsies! >2?'he syndrome is characterized by multiple seizure types;mental retardation or regression; and abnormal indings on electroencephalogram (EEG), "ith paroxysms oast acti$ity and generalized slo" spi#e-and-"a$e discharges (2!-% *z)!

'he most common seizure types are tonic-axial, atonic, and absence seizures, but myoclonic, generalizedtonic-clonic, and partial seizures can be obser$ed (see 8linical Presentation)! /n EEG is an essential part othe "or#up or LGS! @euroimaging is an important part o the search or an underlying etiology (see 0or#up)!

/ $ariety o therapeutic approaches are used in LGS, ranging rom con$entional antiepileptic agents to diet andsurgery (see 'reatment and 3anagement)! nortunately, much o the e$idence supporting these approachesis not robust, and treatment is oten ineecti$e!

See the ollo"ing articles or more inormation.

• irst Pediatric Seizure

• @eonatal Seizures

• Pediatric Status Epilepticus

• Fenign 8hildhood Epilepsy

• Fenign @eonatal 8on$ulsions

• Hu$enile 3yoclonic Epilepsy

• 3yoclonic Epilepsy Feginning in nancy or Early 8hildhood

Pathophysiology

'he pathophysiology o LGS is not #no"n! @o animal models exist!

/ $ariety o possible pathophysiologies ha$e been proposed! 1ne hypothesis states that excessi$epermeability in the excitatory interhemispheric path"ays in the rontal areas is present "hen the anterior partso the brain mature!

n$ol$ement o immunogenetic mechanisms in triggering or maintaining some cases o LGS is hypothesized! /lthough one study ound a strong association bet"een LGS and the human lymphocyte antigen class antigen F5, a second study did not! @o clear-cut or homogeneous metabolic pattern "as noted in % separatereports o positron emission tomography (PE') studies in children "ith LGS!

Etiology

LGS can be classiied according to its suspected etiology as either idiopathic or symptomatic! Patients may beconsidered to ha$e idiopathic LGS i normal psychomotor de$elopment occurred prior to the onset osymptoms, no underlying disorders or deinite presumpti$e causes are present, and no neurologic orneuroradiologic abnormalities are ound! n contrast, symptomatic LGS is diagnosed i a li#ely cause can beidentiied as being responsible or the syndrome!

Population-based studies ha$e ound that 5-5+7 o patients "ith LGS ha$e symptomatic LGS! nderlyingpathologies in these cases include the ollo"ing.

• Encephalitis andAor meningitis

• 'uberous sclerosis

• Frain malormations (eg, cortical dysplasias)

• Firth in=ury

• *ypoxia-ischemia in=ury

• rontal lobe lesions

http://emedicine.medscape.com/article/1176735-treatmenthttp://emedicine.medscape.com/article/1176735-treatmenthttp://emedicine.medscape.com/article/1176735-treatmenthttp://emedicine.medscape.com/article/1176735-medicationhttp://emedicine.medscape.com/article/1179097-overviewhttp://emedicine.medscape.com/article/1177069-overviewhttp://emedicine.medscape.com/article/908394-overviewhttp://emedicine.medscape.com/article/1181649-overviewhttp://emedicine.medscape.com/article/1175719-overviewhttp://emedicine.medscape.com/article/1185061-overviewhttp://emedicine.medscape.com/article/1176055-overviewhttp://emedicine.medscape.com/article/1176735-treatmenthttp://emedicine.medscape.com/article/1176735-medicationhttp://emedicine.medscape.com/article/1179097-overviewhttp://emedicine.medscape.com/article/1177069-overviewhttp://emedicine.medscape.com/article/908394-overviewhttp://emedicine.medscape.com/article/1181649-overviewhttp://emedicine.medscape.com/article/1175719-overviewhttp://emedicine.medscape.com/article/1185061-overviewhttp://emedicine.medscape.com/article/1176055-overview


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• 'rauma

nantile spasms precede the de$elopment o LGS in 6-C67 o patients!

n addition to idiopathic and symptomatic LGS, some in$estigators add IcryptogenicJ as a third etiologiccategory!>%? 'his category encompasses cases in "hich the epilepsy appears to be symptomatic but a causecannot be identiied! n an epidemiologic study in /tlanta, Georgia, &&7 o patients "ith LGS "ere in thecryptogenic group! n a series o %C patients "ith cryptogenic LGS, %!-&5!+7 had a amily history o epilepsy

and ebrile seizures!

n %2, the nternational League /gainst Epilepsy (L/E) 'as# orce on 8lassiication and 'erminologyproposed to include LGS among the epileptic encephalopathies! 'hese are conditions in "hich not only theepileptic acti$ity but also the epileptiorm EEG abnormalities themsel$es are belie$ed to contribute to theprogressi$e disturbance in cerebral unction! >C?

Epidemiology

1$erall, LGS accounts or 2-&7 o patients "ith childhood epilepsy but 27 o patients "ith onset o epilepsy"hen younger than years! 'he pre$alence o LGS in /tlanta, Georgia, "as reported as !%< per 2 li$ebirths!

LGS is more common in boys than in girls! 'he pre$alence is !2 per 2 population or boys, $ersus !% per 2 population or girls (relati$e ris#, !C2)!

'he mean age at epilepsy onset is %

3ortality rate is reported at C7 (mean ollo"-up period o +! y) to 57 (mean ollo"-up period o 6!5 y)! Beathoten is related to accidents! / high rate o in=uries is associated "ith atonic andAor tonic seizures!

'he se$erity o the seizures, reuent in=uries, de$elopmental delays, and beha$ior problems ta#e a large tollon e$en the strongest parents and amily structures! Pay attention to the psychosocial needs o the amily(especially siblings)! 'he proper educational setting also is important to help the patient "ith LGS reach his orher maximal potential!

http://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overviewhttp://emedicine.medscape.com/article/1176431-overview


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Patient Education

Patients and their amilies need to be inormed o the ris# or the ollo"ing se$ere idiosyncratic reactions rom Ccommonly used antiepileptic medications or LGS.

• Dalproate - *epatotoxicity, pancreatitis

• Lamotrigine - Ste$ens-Hohnson syndrome, toxic epidermal necrolysis

• elbamate - /plastic anemia, hepatotoxicity*istory

/lthough approximately %-C7 o children "ith Lennox-Gastaut syndrome (LGS) are ree rom neurologic andneuropsychologic deicits prior to onset o symptoms (ie, idiopathic LGS), these problems ine$itably appearduring the e$olution o LGS! actors associated "ith more common or more se$ere mental retardation includethe ollo"ing.

• /n identiiable etiology (ie, symptomatic LGS)

• / history o 0est syndrome ( inantile spasm)

• 1nset o symptoms beore age 2%-%& months

• 3ore reuent seizures

/$erage intelligence uotient (4) score is signiicantly lo"er in patients "ith symptomatic LGS than in those"ith cryptogenic LGS (ie, patients or "hom no cause o LGS can be identiied but a cause is suspected)! n

one study, 4 testing sho"ed $ariable degrees o mental retardation in


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myoclonias or progressi$e lexion o the head secondary to a loss o tone! /utomatisms may be obser$ed!Seizures may end gradually in some patients and abruptly in others!

/tonic seizures, massi$e myoclonic seizures, and myoclonic-atonic seizures ha$e a reuency o 2-


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Go to EEG in 8ommon Epilepsy Syndromes, Epileptiorm @ormal Dariants on EEG, andGeneralized Epilepsies

on EEG or more inormation on these topics!

nterictal electroencephalography

nterictal EEG is characterized by a slo" bac#ground that can be constant or transient! Permanent slo"ing o

the bac#ground is associated "ith poor cogniti$e prognosis!

'he hallmar# o the a"a#e interictal EEG in patients "ith LGS is the diuse slo" spi#e "a$e (see the image

belo")! 'his pattern consists o bursts o irregular and generalized spi#es or sharp "a$es ollo"ed by a

sinusoidal C-&-millisecond slo" "a$e "ith an amplitude o %-+ micro$olts, "hich can be symmetric or

asymmetric!

'he amplitude oten is higher in the anterior region or in the rontal or rontocentral areas, but in some patients

the acti$ity may dominate in the posterior head regions! 'he reuency o the slo" spi#e "a$e acti$ity

commonly is ound at 2!-%! *z!

Slo" spi#e "a$e pattern in a %&-year-old a"a#e

male "ith Lennox-Gastaut syndrome! 'he slo" posterior bac#ground rhythm has reuent periods o %- to %!-*z

discharges, maximal in the birontocentral areas, occurring in trains as long as + seconds "ithout any clinical

accompaniment!

Slo" spi#e "a$es usually are not acti$ated by photic stimulation! *yper$entilation rarely induces slo" spi#e

"a$es, although mental retardation pre$ents adeuate cooperation in many patients! Buring non9rapid eye

mo$ement (:E3) sleep, discharges are more generalized, more reuent, and consist o polyspi#es and slo"

"a$es! n :E3 sleep, spi#e "a$es decrease! Buring periods o reuent seizures, the total duration o :E3

sleep is reduced!

ctal electroencephalography

http://emedicine.medscape.com/article/1138154-overviewhttp://emedicine.medscape.com/article/1138154-overviewhttp://emedicine.medscape.com/article/1140563-overviewhttp://emedicine.medscape.com/article/1140724-overviewhttp://emedicine.medscape.com/article/1140724-overviewhttp://emedicine.medscape.com/article/1140724-overviewhttp://emedicine.medscape.com/article/1138154-overviewhttp://emedicine.medscape.com/article/1140563-overviewhttp://emedicine.medscape.com/article/1140724-overviewhttp://emedicine.medscape.com/article/1140724-overview


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Buring a tonic seizure, the EEG is characterized by a diuse, rapid (2-2C *z), lo"-amplitude acti$ity pattern,

mainly in the anterior and $ertex areas (Nrecruiting rhythmN) that progressi$ely decreases in reuency and

increases in amplitude!

/ brie generalized discharge o slo" spi#e "a$es or lattening o the recording may precede this pattern!

Biuse slo" "a$es and slo" spi#e "a$es may ollo" it!

'hese ast discharges are common during non-:E3 sleep! nli#e tonic-clonic seizures, no postictal lattening

occurs "ith these seizures! 8linical maniestations appear !-2 second ater the onset o EEG maniestations

and last se$eral seconds longer than the discharge!

Buring an atypical absence seizure, the EEG is characterized by diuse, slo" (%-%! *z), and irregular spi#e

"a$es, "hich may be diicult to dierentiate rom interictal bursts! 1ccasionally, discharges o rapid rhythms

may be obser$ed preceded by lattening o the record or 2-% seconds, ollo"ed by progressi$e de$elopment o

irregular ast rhythm in the anterior and central regions, and ending "ith brie spi#e "a$es!

Buring atonic, massi$e myoclonic, and myoclonic-atonic seizures, the EEG is characterized by slo" spi#e

"a$es, polyspi#e "a$es, or rapid diuse rhythms! Simultaneous $ideoAEEG recording can help dierentiate

these seizure types! n most patients, these C types o seizures coexist!

'he EEG during absence status epilepticus re$eals continuous spi#e "a$e discharges, usually at a lo"er

reuency than at baseline, and rapid rhythms during tonic status epilepticus!

@euroimaging Studies

n general, a magnetic resonance imaging (3:) scan is the preerred neuroimaging study or a patient "ith

LGS, rather than a 8' scan! 8' scans may be preerred in selected situations (eg, e$aluation o suspected

intracranial in=ury andAor hematoma in a patient "ith head trauma resulting rom a seizure)!

/bnormalities re$ealed by neuroimaging associated "ith LGS include tuberous sclerosis, brain malormations(eg, cortical dysplasias), hypoxia-ischemia in=ury, or rontal lobe lesions!

@o current indication exists or routine positron emission tomography (PE') or single-photon emission

computed tomography (SPE8') scanning in patients "ith LGS! *o"e$er, PE' or SPE8' scans may be useul

in patients undergoing e$aluation as candidates or epilepsy surgery!

/pproach 8onsiderations

'he goals o treatment or patients "ith Lennox-Gastaut syndrome (LGS) are the same as or all patients "ithepilepsy. the best uality o lie "ith the e"est seizures (ideally, none), the e"est ad$erse treatment eects,and the least number o medications!

/ $ariety o therapeutic approaches are used in LGS, ranging rom con$entional antiepileptic agents to diet andsurgery! nortunately, much o the e$idence supporting these approaches is not robust, and treatment is otenineecti$e!>+, 6?

'he medical treatment options or patients "ith LGS can be di$ided into the ollo"ing C ma=or groups.

• irst-line treatments based on clinical experience or con$entional "isdom (eg, $alproic acid,

benzodiazepines >speciically clonazepam, nitrazepam, clobazam >2, 22, 2%? ?)

• 'reatments suspected to be eecti$e on the basis o open-label uncontrolled studies (eg,

$igabatrin, >2C? zonisamide >2&? )


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• 'reatments pro$en eecti$e by double-blind placebo-controlled studies (eg,

lamotrigine, >2? topiramate, >226? , ruinamide >%, %2, %%? )'he #etogenic diet may be useul in patients "ith LGS reractory to medical treatment! Surgical options or LGSinclude corpus callostomy, $agus ner$e stimulation, and ocal cortical resection! >%C?

/ntiepileptic 'herapy

/ntiepileptic drugs (/EBs) are the mainstay o therapy or patients "ith LGS! nortunately, no one /EB gi$essatisactory relie or all or e$en most patients "ith LGS! / combination o agents reuently is reuired!Patients "ith LGS experience reuent exacerbations o their seizures that may reuire inpatient ad=ustment o /EBs!

Patients "ith LGS ha$e a recognized high ris# or status epilepticus! Fecause o the conseuent ris# o in=ury or death, a medication or emergency inter$ention (eg, rectal diazepam) should be prescribed!

Valproate

Dalproate (Bepa#ote, Bepa#ene, Bepacon) has been considered the irst-line treatment option or children "ithLGS or the past % decades! t is reported to be more eecti$e in patients "ith cryptogenic LGS than in those"ith symptomatic LGS!

Lamotrigine

'he eicacy o lamotrigine (Lamictal) as ad=uncti$e therapy against seizures associated "ith LGS "asdemonstrated in % controlled trials and multiple open-label studies! 'his agent is $aluable or patients "ith LGS,despite its ris# o idiosyncratic dermatologic reactions, and its use should be considered as soon as diagnosiso LGS is made! Proper attention to concomitant medications, lo" starting dose, and $ery slo" titration canminimize the ris# o dermatologic reactions!

Topiramate

n a multicenter, double-blind, placebo-controlled trial, topiramate ('opamax) "as ound to be sae and eecti$eas ad=uncti$e therapy or patients "ith LGS!>2+? 'he target dose "as < mgA#gAd! n a long-term open-labelextension portion o this trial (mean dosage 2 mgA#gAd), drop attac#s "ere reduced by greater than hal in 7o patients, and 27 o patients "ere ree o drop attac#s or o$er < mo at the last $isit! >25?

Felbamate

elbamate (elbatol) "as ound to be sae and eecti$e in patients "ith LGS in a randomized, double-blind,placebo-controlled ad=uncti$e therapy trial, and 2%-month ollo"-up in patients "ho completed controlled part o study conirmed long-term eicacy!>26? Bespite the eicacy o elbamate, the signiicant ris# o idiosyncraticreactions associated "ith its use ma#e it a third-line or ourth-line drug or LGS!

Zonisamide

'he eecti$eness o zonisamide (Oonegran) in LGS has been in$estigated in C small open-label studies, "ithpromising results! / multicenter study o zonisamide or long-term ad=uncti$e therapy in


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indi$iduals aged &-C years!>%? / %6 open-label European study also demonstrated decreased seizurereuency amongst those "ith LGS!>%2?

n a multicenter clinical trial o 6 patients "ith LGS, ruinamide "as ound to decrease the reuency o tonic-atonic seizures by %&!%7, $ersus C!C7 "ith placebo, and total seizures by C%!67, $ersus C!C7 "ith placebo! /d$erse e$ents in the ruinamide group included decreased appetite (25!%7), somnolence (25!%7), and$omiting (2C!+7)!>%?

n ebruary %2, ruinamide "as appro$ed in pediatric patients aged 2 to & years based on a pharmaco#ineticbridging study o a Phase clinical trial "hich demonstrated the pharmaco#inetic and saety proiles areconsistent "ith those seen in ages Q & years!>C&?

#en$odia$epines

8lonazepam (Rlonopin) is considered an eecti$e irst-line /EB therapy or seizures associated "ith LGS!*o"e$er, the ad$erse eects and de$elopment o tolerance limit its useulness o$er time! Bosing on an e$ery-other-day schedule or alternating % benzodiazepines daily may slo" de$elopment o tolerance! 'hebenzodiazepine clobazam, "hich is "idely used as an anticon$ulsant in other countries, "as appro$ed by theB/ in 1ctober %22!>2%? 'he combination o $alproic acid and a benzodiazepine may be better than either drugalone!

n the 81@'/@ study o patients "ith LGS gi$en clobazam, more than 7 o patients had a 7 or greater

decrease in "ee#ly drop- and total-seizure reuency! 'he percentage o patients achie$ing 27 reduction indrop seizures "as CC7 or clobazam-treated patients ($s! 57 or placebo) in 4uartile 2 (least se$ere LGS), and7 o clobazam-treated patients in 4uartile & (most se$ere LGS) achie$ed 27 reduction in drop seizures,$ersus 7 or placebo!>%


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beneits o the diet or people "ith epilepsy include e"er seizures, less dro"siness, better beha$ior, and needor e"er concomitant /EBs!

Fased on multiple open-label and, most recently, randomized controlled studies, the #etogenic diet appears tobe a useul therapy or patients "ith LGS! Eicacy appears greatest or atonic, myoclonic, and atypical absenceseizures, but other seizure types (tonic-clonic, secondarily generalized tonic-clonic) may also respond!

n a %+ randomized controlled trial o the #etogenic diet in children "ith daily seizures "ho had a poorresponse to at least % /EBs, C+7 o the children in the diet arm had a greater than 7 reduction in seizures!1 the 2& children randomized to the #etogenic diet or control, only 2& had LGS! >C2?

/ blinded, crosso$er study o the #etogenic diet in % children "ith LGS sho"ed a moderate reduction inparent-reported myoclonic-atonic e$ents! Retosis "as not eliminated in the placebo arm; thus, there "as nodierence obser$ed bet"een the % groups regarding reduction in EEG-identiied e$ents! 0hen patients "hoare seizure ree or extended periods o time should be "eaned rom the diet is not clear!>C%?

'he #etogenic diet is not al"ays successul! 'he ollo"ing C actors are associated "ith successulimplementation o the diet.

• Bedicated, compliant amily "illing to alter the entire amilyMs liestyle

• amily able to ollo" ("ithout "a$ering) the strict guidelines o the diet

•

'eam o proessionals (centered around a dietitian) trained and experienced in the use o the dietPotential serious ad$erse eects include dehydration, clinically signiicant metabolic acidosis "hen the diet isinitiated, renal stones, cardiac abnormalities, and abnormal lipid proile!

n=ury Pre$ention

Some patients "ith LGS "ear protecti$e helmets "ith ace guards to maximize protection o the orehead,nose, and teeth (see the image belo")! nortunately, some patients "ith LGS do not tolerate the helmet "ithace guards, and e$en i tolerated, helmets oten are uncomortable and rarely are cosmetically acceptable!

Patient "ith Lennox-Gastaut syndrome "earinga helmet "ith ace guard to protect against acial in=ury rom atonic seizures

8onsultations

Pediatric neuropsychologists can assess intellectual unction and educational needs and ad$ise onnonpharmacologic management o beha$ioral problems! Pediatric psychiatrists can ad$ise on pharmacologicmanagement o beha$ioral problems! @eurosurgeons can assist in the placement o a $agus ner$e stimulator


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and assess the patient as a candidate or corpus callosotomy or ocal resection! Bietitians can assist in theinstitution and maintenance o the #etogenic diet!

3edication Summary

'he goals o pharmacotherapy in Lennox-Gastaut syndrome (LGS) are to reduce morbidity and pre$ent

complications! Pharmacotherapeutic agents used in such patients include anticon$ulsants and

benzodiazepines!

/nticon$ulsants

8lass Summary

'hese agents pre$ent seizure recurrence and terminate clinical and electrical seizure acti$ity!

Die" ull drug inormation

Dalproate (Bepa#ote, Bepa#ene, Bepacon, Sta$zor)

Dalproate has been considered the irst-line treatment option or children "ith LGS or the past % decades! t is

reported to be more eecti$e in patients "ith cryptogenic LGS than in those "ith symptomatic LGS!


Lamotrigine (Lamictal, Lamictal 1B', Lamictal :)

Lamotrigine is $aluable or patients "ith LGS despite ris# o idiosyncratic dermatologic reactions! 8onsider it or

use as soon as the diagnosis o LGS is made! Proper attention to concomitant medications, a lo" starting

dose, and $ery slo" titration can minimize the ris# o dermatologic reactions! 'he initial dose, maintenancedose, titration inter$als, and titration increments depend on concomitant medications!


'opiramate ('opamax)

'opiramate has been ound to be sae and eecti$e as ad=uncti$e therapy (target dose < mgA#gAd) or patients

"ith LGS!


elbamate (elbatol)

elbamate has been ound to be sae and eecti$e in patients "ith LGS! *o"e$er the signiicant ris# o

idiosyncratic reactions associated "ith its use ma#e it a third-line or ourth-line drug or LGS!


http://reference.medscape.com/drug/depakote-divalproex-sodium-999832http://reference.medscape.com/drug/depakote-divalproex-sodium-999832http://reference.medscape.com/drug/lamictal-lamotrigine-343012http://reference.medscape.com/drug/lamictal-lamotrigine-343012http://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023http://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023http://reference.medscape.com/drug/felbatol-felbamate-343009http://reference.medscape.com/drug/felbatol-felbamate-343009http://reference.medscape.com/drug/zonegran-zonisamide-343025http://reference.medscape.com/drug/depakote-divalproex-sodium-999832http://reference.medscape.com/drug/depakote-divalproex-sodium-999832http://reference.medscape.com/drug/lamictal-lamotrigine-343012http://reference.medscape.com/drug/lamictal-lamotrigine-343012http://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023http://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023http://reference.medscape.com/drug/felbatol-felbamate-343009http://reference.medscape.com/drug/felbatol-felbamate-343009http://reference.medscape.com/drug/zonegran-zonisamide-343025


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Oonisamide (Oonegran)

Oonisamide is eecti$e as long-term ad=uncti$e therapy in children "ith LGS!


Digabatrin (Sabril)

Digabatrin "as appro$ed by S ood and Brug /dministration (B/) in %6 as monotherapy or patients "ith

inantile spasms aged 2 month to % years and as ad=uncti$e therapy or adults "ith reractory complex partial

seizures!


Le$etiracetam (Reppra, Reppra :)

Le$etiracetam is appro$ed by B/ or partial seizures, but may ha$e eicacy against a range o seizure types

in LGS!


:uinamide (Fanzel)

/n antiepileptic agent that is structurally unrelated to current antiepileptics, ruinamide modulates sodium

channel acti$ity, particularly prolongation o the channelMs inacti$e state! t signiicantly slo"s sodium channel

reco$ery and limits sustained repetiti$e iring o sodium-dependent action potentials! t is indicated or

ad=uncti$e therapy in adults and children aged 2 year or older "ith seizures associated "ith LGS!

Fenzodiazepines

8lass Summary

Fy binding to speciic receptor-sites, these agents appear to potentiate the eects o gamma-aminobutyrate

(G/F/) and acilitate inhibitory G/F/ neurotransmission and other inhibitory transmitters!


8lonazepam (Rlonopin)

8lonazepam is considered an eecti$e irst-line /EB therapy or seizures associated "ith LGS! /d$erse eectsand de$elopment o tolerance limit useulness o$er time; dosing on an e$ery-other-day schedule or alternating

% benzodiazepines daily may slo" de$elopment o tolerance! 'he benzodiazepine nitrazepam (3ogadon) is not

appro$ed by B/ but is a$ailable in many countries! 'he combination o $alproic acid and a benzodiazepine

may be better than either drug alone!


http://reference.medscape.com/drug/zonegran-zonisamide-343025http://reference.medscape.com/drug/sabril-vigabatrin-343008http://reference.medscape.com/drug/sabril-vigabatrin-343008http://reference.medscape.com/drug/keppra-spritam-levetiracetam-343013http://reference.medscape.com/drug/keppra-spritam-levetiracetam-343013http://reference.medscape.com/drug/banzel-rufinamide-343010http://reference.medscape.com/drug/banzel-rufinamide-343010http://reference.medscape.com/drug/klonopin-clonazepam-342900http://reference.medscape.com/drug/klonopin-clonazepam-342900http://reference.medscape.com/drug/onfi-clobazam-999696http://reference.medscape.com/drug/zonegran-zonisamide-343025http://reference.medscape.com/drug/sabril-vigabatrin-343008http://reference.medscape.com/drug/sabril-vigabatrin-343008http://reference.medscape.com/drug/keppra-spritam-levetiracetam-343013http://reference.medscape.com/drug/keppra-spritam-levetiracetam-343013http://reference.medscape.com/drug/banzel-rufinamide-343010http://reference.medscape.com/drug/banzel-rufinamide-343010http://reference.medscape.com/drug/klonopin-clonazepam-342900http://reference.medscape.com/drug/klonopin-clonazepam-342900http://reference.medscape.com/drug/onfi-clobazam-999696


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8lobazam (1@)

2,-benzodiazepine that possesses potent anticon$ulsant properties! Exact mechanism o action is not ully

understood; thought to potentiate G/F/ergic neurotransmission resulting rom binding to G/F/-/ receptor!

'he acti$e metabolite, @-demethylclobazam, is largely responsible or its long duration o action! t is indicated

or ad=uncti$e treatment o seizures associated "ith Lennox-Gastaut syndrome (LGS) in patients older than %

years!
http://reference.medscape.com/drug/onfi-clobazam-999696http://reference.medscape.com/drug/onfi-clobazam-999696

Documents

LGS Medscape