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Arch Dis Child 1999;81:351–355 351 Arch Dis Child: first published as 10.1136/adc.81.4.351 on 1 October 1999. Downloaded from CURRENT TOPIC

Typical absence and their treatment

C P Panayiotopoulos

Typical absences (previously known as petit there are inappropriate generalisations regard- mal) are generalised seizures that are distinc- ing their use in the treatment of other tively diVerent from any other type of epileptic . fit.1 They are pharmacologically unique2–5 and demand special attention in their treatment.6 The prevalence of typical absences among Typical absence seizures children with epilepsies is about 10%, probably Typical absence seizures are defined according with a female preponderance.6 Typical ab- to clinical and electroencephalogram (EEG) 16 sences are easy to diagnose and treat. There- ictal and interictal expression. Clinically, the fore, it is alarming that 40% of children with hallmark of the absence is abrupt and brief typical absences were inappropriately treated impairment of consciousness, with interrup- with contraindicated drugs, such as car- tion of the ongoing activity, and usually unresponsiveness. The lasts for a few to Department of Clinical bamazepine and , according to a 7 20 seconds and ends suddenly with resumption Neurophysiology and recent report from London, UK. Epilepsies, St Thomas’ The purpose of this paper is to oVer some of the pre-absence activity, as if had not been Hospital, London guidance to paediatricians regarding diagnosis interrupted. Although some absence seizures SE1 7EH, UK and management of typical absence seizures. can manifest with impairment of consciousness C P Panayiotopoulos This is also important because of the introduc- only, this is often combined with the following: tion of new antiepileptic drugs. These are + mild clonic jerks of the eyelids, corner of the Correspondence to: mouth, or other muscles Dr Panayiotopoulos. mainly tested in partial (focal) epilepsies and + atonic components leading to drooping of Girl born 1978 Video EEG 1992 Overbreathing with breath counting the head, slumping of the trunk, dropping of the arms, and relaxation of the grip Fp2-F4 + tonic muscular contraction causing head http://adc.bmj.com/ F4-C4 retropulsion or arching of the trunk C4-P4 + automatisms that are common and range from lip licking and swallowing to fumbling P4-O2 with clothes or aimless walking + autonomic components, such as , and Fp1-F3 less frequently flushing, sweating, dilatation of pupils, and incontinence of urine.1 F3-C3 EEG is pathognomonic. In more than 90% C3-P3 of these children, absence seizures are docu- on September 23, 2021 by guest. Protected copyright. P3-O2 mented mainly during . Nor- 31 32Opens eyes–Unresponsive–Eyes to the right I am OK mal EEG results from a child suspected for absence seizures makes this diagnosis unlikely. 100 µV 1 sec The ictal EEG is characteristic, and usually has Girl born 1989 Video EEG 1998 Overbreathing regular and symmetrical generalised discharges of 3–4 Hz “spike and slow” wave complexes, Fp2-F4 and may also have multiple spike and slow wave complexes (fig 1).1 The background F4-C4 interictal EEG is usually normal. However, it C4-P4 should be stressed that asymmetries of the ictal P4-O2 discharge and focal abnormalities of mainly functional spikes are common.689 These Fp1-F3 should not be interpreted as evidence of focal F3-C3 with secondary generalisation, which 7 C3-P3 could cause errors in treatment. P3-O2

Opens eyes–Stops OB–Unresponsive–Fumbling 200 µV 1 sec Epileptic syndromes manifested with typical absence seizures Figure 1 Top:part of a video EEG recording of patient 1 at age 14 years before adding The term typical absences does not refer to a small doses of to adequate doses of sodium . Numbers annotate breath stereotype symptom but to a cluster of clinico- counting, which stopped after the onset of the discharge. Bottom: part of a video EEG recording of patient 2 at age 8 years before changing from syrup to tablets of sodium EEG manifestations, which might be syndrome valproate. related.610 352 Panayiotopoulos

Four epileptic syndromes with typical ab- Absence seizures may also manifest with Arch Dis Child: first published as 10.1136/adc.81.4.351 on 1 October 1999. Downloaded from sences have been recognised by the Inter- subtle clinical manifestations during the typical national League Against Epilepsy, namely10: 3 Hz spike wave discharges. These are incon- childhood absence epilepsy, juvenile absence spicuous to the patient and imperceptible to epilepsy, juvenile , and myo- the observer (phantom absences). In these clonic absence epilepsy. The first three are cases, medical consultation is sought only after genetically determined idiopathic generalised a generalised tonic clonic seizure, probably epilepsies; that is, they occur in patients with long after the onset of absences.11 normal physical and mental states. Myoclonic Symptomatic typical absences mainly as a absence epilepsy is categorised among the result of frontal lesions are well established but cryptogenic/symptomatic generalised epilep- these are extremely rare.12 sies. Idiopathic refers to syndromes without an underlying cause other than a possible heredi- Biological basis tary predisposition.10 Symptomatic epilepsies Absences are provoked by an abnormal are the consequence of a known or suspected thalamo–cortical circuitry that activates abnor- disorder of the nervous system.10 Cryptogenic mal oscillatory rhythms, generating the gener- epilepsies are presumed symptomatic epileptic alised 3 Hz spike and wave discharges of typical 2–5 syndromes of an unknown, hidden, or occult absence seizures. The basic cellular mecha- aetiology.10 nisms involve low current T calcium channels; Childhood absence epilepsy (pyknolepsy) is exerts its anti-absence eVect by the archetypical epileptic syndrome of typical blocking these channels. GABA is the neurotransmitter that appears absence seizures with onset usually before the B to play the most prominent role. GABA age of 10 years and a peak at 5–6 years. B Absences are frequent (tens or hundreds each agonists, such as baclofen, aggravate and GABA antagonists suppress absences.2–5 day) manifesting with sudden, severe, and brief B Vigabatrin13 and tiagabine14 are GABA-ergic impairment of consciousness. As a rule, drugs, which interferes with degradation or absences are the only type of seizure. They re-uptake of GABA, and thus induces absences usually respond well to ethosuximide or and absence . sodium valproate and remit within 2–5 years from onset.610 DiVerential diagnosis Similarly, absences in juvenile absence epi- The diVerential diagnosis of typical absence lepsy are severe, frequent, and the main seizure seizures with severe impairment of conscious- type. However, onset is often later, after the age ness in children is relatively easy, although such of 10 years, and regularly generalised tonic seizures can be missed if they are mild, or in clonic seizures and random myoclonic jerks 610 babies, if they are not associated with myo- occur. Treatment may be life long. clonic components.6 Their brief duration with Conversely, in juvenile myoclonic epilepsy, abrupt onset and termination, their daily

absences occur in only one third of the patients frequency, as well as their nearly invariable http://adc.bmj.com/ and they are usually mild without concurrent provocation with hyperventilation makes them 610 myoclonic jerks or automatisms. Juvenile one of the easiest types of seizures to diagnose. myoclonic epilepsy is a common idiopathic Automatisms, such as lip smacking or licking, generalised epilepsy characterised mainly by swallowing, fumbling with clothes, or aimless myoclonic jerks after awakening and general- walking, are common and should not be taken ised tonic clonic seizures. Myoclonic jerks start as evidence of complex partial (focal) seizures, in mid-teens but these may be predated by which require entirely diVerent management. absences. Juvenile myoclonic epilepsy is often In practical terms, a child suspected of having on September 23, 2021 by guest. Protected copyright. mild and responds well to treatment. However, typical absences should be asked to over- appropriate medication, usually with sodium breathe for three minutes while standing, valproate may be needed, even many decades counting his/her breaths, and with hands after cessation of seizures. extended in front of him/her. This will provoke Myoclonic absence epilepsy occurs mainly in an absence in as many as 90% of aVected indi- children with learning diYculties or other viduals. neurological deficits. Absences are associated Typical absence seizures of idiopathic gener- with rhythmic myoclonic jerks of the facial alised epilepsies are also easy to diVerentiate muscles, head, and limbs. The prognosis is from atypical absences that occur only in the poor.610 context of mainly severe symptomatic or cryp- Other epileptic syndromes can be associated togenic epilepsies of children with learning dif- with typical absences, such as eyelid myoclonia ficulties, who also suVer from frequent other with absences (Jeavons syndrome), perioral types of seizures such as atonic, tonic, and myoclonia with absences, stimulus sensitive myoclonic seizures.110 absence epilepsies, and others awaiting further The EEG should confirm the diagnosis of studies and confirmation.6 Of these syndromes, typical absence seizures in more than 90% of eyelid myoclonia with absences consists of pro- aVected children, with ictal recordings mainly nounced eyelid myoclonia followed by brief during hyperventilation.1610 Focal spike ab- and mild absence. Main seizure precipitants normalities and asymmetrical onset of the ictal are eye closure and photosensitivity. Onset is in 3–4 Hz spike wave discharges are common,68 childhood and seizures usually persist into and may be a cause of misdiagnosis, particu- adult life, often with infrequent generalised larly in resistant cases.7 Ideally, all children with .6 absence seizures should have video EEG Typical absence seizures and their treatment 353

recordings in an untreated state because these lamotrigine was increased, despite the initial Arch Dis Child: first published as 10.1136/adc.81.4.351 on 1 October 1999. Downloaded from might reveal features favouring a specific good response when it was first introduced epileptic syndrome and, therefore, determine in small doses. It should be of concern that long term prognosis and management.6 If this no benefit was achieved in some by reducing is not possible, I suggest that it is mandatory lamotrigine again. This is probably the that the clinical manifestations of the seizures result of a pharmacodynamic interaction of are documented with camcorders by the small doses of lamotrigine with adequate parents or the treating physicians. I advise them doses of sodium valproate.16 17 Lamotrigine to videotape the absences while the child is is either ineVective,518 or has a weak overbreathing for three minutes, holding his/ anti-absence eVect19 in animal models. her hands in front, and counting his/her Based on our experience, our approach for breaths. This might be particularly useful if the management of cases resistant to sodium absences are resistant to treatment, other valproate is to escalate lamotrigine according seizures develop, or for future genetic advise. to clinical response and not to recommended “therapeutic” doses. We ask the patient to add Treatment 25 mg lamotrigine (10 mg for a child 5–10 Ethosuximide and sodium valproate are years old) to the existing regimen with sodium equally eVective as monotherapy in controlling valproate. If seizures stop, we discourage any the absences of more than 80% of children and other modification. If in two weeks no signifi- there appears to be no clear benefit in measur- cant change occurs or seizures improve, we add ing plasma concentrations.15 Many clinicians another similar dose of lamotrigine and give prefer sodium valproate because this drug, as the same advice as above. According to their opposed to ethosuximide, also controls myo- response, similar increments at the same inter- clonic jerks and generalised tonic clonic vals may be advised for a higher total dose of seizures, but this might not be of concern in the lamotrigine, or until unwanted adverse eVects pure form of childhood absence epilepsy, occur. which is not complicated by other types of Acetazolamide20 and benzodiazepines20 seizures.61015 Monotherapy should not be might also be tried in the few remaining cases abandoned before making sure that the maxi- of failure with the above three drugs. Clon- mum tolerated dose has been achieved if azepam, sometimes in small doses, might be smaller doses have failed. There is also an particularly eVective as “add on” in the anecdotal report,2 which I have confirmed (fig treatment of absence seizures with myoclonic 1), whereby children might not respond to components, such as eyelid myoclonia with syrup of sodium valproate, despite adequate absences or myoclonic absence epilepsy.6 Fel- concentrations, but seizures stop if this is bamate was probably a good drug for absences replaced by tablets of sodium valproate. It is but it has been withdrawn because of serious also anecdotal experience that when seizure adverse reactions. cessation has been achieved, sodium valproate

can safely be reduced to more moderate doses CONTRAINDICATED DRUGS http://adc.bmj.com/ without relapses. ,7 vigabatrin,13 and tiagabine14 If monotherapy fails or unacceptable adverse are contraindicated in the treatment of absence reactions appear with sodium valproate or seizures, irrespective of cause and severity. This ethosuximide, replacement of one by the other is based on clinical and experimental is the alternative. More than half of the cases evidence.71314In particular, vigabatrin and tia- resistant to monotherapy do well when these gabine, which are GABA agonists, can be used two drugs are combined.15 to induce (not treat) absence seizures and A new extraordinary development in the absence status epilepticus. The error of pre- on September 23, 2021 by guest. Protected copyright. management of typical absence seizures came scribing these drugs in the treatment of from our open studies documenting the absence seizures would be of the same magni- dramatic beneficial eVect of extremely low tude as prescribing a gluten rich diet in the doses of lamotrigine, added to adequate doses treatment of coeliac disease. Similarly, pheny- of sodium valproate (fig 1).16 17 Although this toin, phenobarbitone, and should has important practical and theoretical impli- not be used in the treatment of absence cations it is often not cited and may lead to seizures because they are ineVective.5 failures and unacceptable side eVects if not well understood. ILLUSTRATIVE “RESISTANT” CASES WHO 16 17 We found that: RESPONDED WELL TO MILD MODIFICATIONS OF + absences stopped in nearly half of the THEIR DRUG TREATMENT patients immediately after small doses (25– Figure 1 shows EEG ictal samples of typical 50 mg) of lamotrigine were added to absence seizures in two girls with intractable adequate doses of sodium valproate (fig 1) typical absences, who became free from + patients would relapse if sodium valproate seizures after adding small doses of lamotrigine was reduced, despite increasing doses of to sodium valproate (patient 1) and changing lamotrigine from syrup to tablets of sodium valproate + patients who did not respond to small doses (patient 2). did not benefit by increasing lamotrigine. This beneficial eVect of lamotrigine was Patient 1 maintained in 4–5 years of follow up. It is This normal woman had onset of typical also our experience that some other patients absence seizures at age 7 years. These lasted for we saw after these reports relapsed when 10–20 seconds each and occurred in tens or 354 Panayiotopoulos

hundreds each day, frequently with inconti- discharges of 1–4 Hz spikes or polyspikes and Arch Dis Child: first published as 10.1136/adc.81.4.351 on 1 October 1999. Downloaded from nence of urine. On video EEG at age 14 years, slow waves. The background interictal EEG five clinical absences lasting from nine to 17 might be normal in idiopathic cases or seconds were recorded. Clinically, there was abnormal in symptomatic cases. Like absence severe impairment of consciousness, with con- seizures, absence status epilepticus is catego- sistent eyebrow rhythmic , automa- rised as typical of mainly idiopathic generalised tisms, and vocalisations. Ictal EEG consisted of epilepsies or atypical of symptomatic and cryp- high amplitude generalised spike/multiple togenic generalised epilepsies. Furthermore, spike and slow waves at 3 Hz (fig 1). Interic- absence status epilepticus can be caused by the tally, there were brief generalised bursts of introduction or withdrawal of certain drugs spikes and multiple spikes as well as focal sharp (mainly diazepines), intoxication, or electrolyte waves occurring independently on both sides of disturbances. It may also be caused by severe the anterior brain regions. brain anoxia or other brain damage as reported Ethosuximide at age 7 was partially benefi- in adult populations.22 cial but was discontinued because of adverse Typical absence status epilepticus occurs in eVects. On referral, aged 14, she had three to 10–30% of idiopathic generalised epilepsies 20 absences each day despite 1000 mg val- with absences,21 22 and it might be incompatible proate daily. Increasing valproate to 1500 mg with the pure form of childhood absence had partial benefit. The addition of 125 mg epilepsy.22 ethosuximide three times daily could not be tolerated. However, all absences stopped after TREATMENT OF ABSENCE STATUS EPILEPTICUS the first dose of 50 mg lamotrigine every other The traditional treatment is intravenous di- day added to 1500 mg valproate. Absences azepam or sodium valproate but this may be reappeared when she stopped valproate, de- available only in hospitalised patients. Self spite doubling the dose of lamotrigine. She has administration of rectal preparations of di- remained free from seizures in the past six years azepine as soon as the first symptoms appear of follow up on 1000 mg valproate and 50 mg may stop absence status, but this advice is often lamotrigine. Only twice, aged 15, she had a not followed. Some patients could avoid a gen- generalised tonic clonic seizure preceded by eralised tonic clonic seizure by taking a clusters of absences, after missing her medi- substantial amount (usually double their daily cation. dose) of sodium valproate at the onset of absence status. A new important development Patient 2 is that buccal application of midazolam may This normal girl aged 8 years had uncontrolla- stop absence status and prevent the develop- ble typical absences from the age of 5 years. ment of generalised tonic clonic seizures.23 24 Absences were severe, of 8–15 seconds dura- Five to 10 mg (1–2 ml) of midazolam dissolved tion, and as frequent as tens or hundreds each in 5 ml of peppermint (otherwise it smells and day. Despite adequate doses of syrup of sodium tastes awful) is swirled in the mouth for five

valproate, ethosuximide, and lamotrigine, minutes and then spat out. In uncooperative http://adc.bmj.com/ alone or usually in combination, she continued patients, the lips are parted and the same solu- to have frequent daily absences. When she was tion is squirted through a syringe around the first seen at age 8 she was on 600 mg syrup buccal mucosa.23 24 Swallowing midazolam sodium valproate and 150 mg lamotrigine. On does not harm the patient. On preliminary evi- video EEG, seven clinical absences lasting from dence, I am of the opinion that this is probably eight to 15 seconds were recorded at that stage. the best practical treatment option in absence Clinically, there was severe impairment of con- status epilepticus. However, the individuals sciousness, often with automatisms associated involved should be informed that midazolam is on September 23, 2021 by guest. Protected copyright. with high amplitude 3 Hz generalised spike not yet licensed for this type of treatment. and slow wave discharges (fig 1). All absences stopped within a week of replacing the syrup Withdrawing antiepileptic medication with tablets of 800 mg sodium valproate and This is syndrome related.6 In the pure form of reducing lamotrigine. One year later she childhood absence epilepsy, drug treatment remained seizure free on tablets of 600 mg can be withdrawn gradually (within 3–6 sodium valproate and 50 mg lamotrigine. months) after 2–3 years free from seizures. In others, such as juvenile absence epilepsy, juve- Absence status epilepticus nile myoclonic epilepsy, or eyelid myoclonia Absence status epilepticus is a prolonged with absences, treatment might be life long.6 seizure lasting for more than half an hour, Finally, it is my conviction that the manage- sometimes hours or days.21 22 Clinically it is ment of epilepsies cannot be satisfactory unless characterised mainly by the continuous impair- the current theme of “how to treat epilepsy” is ment of consciousness (absence) concurrent redirected to “how to diagnose and treat with EEG generalised discharges of spikes/ epilepsies”.9 polyspikes and slow wave discharges. Impair- ment of consciousness may be mild or severe Addendum and associated with other mainly motor distur- While this report was in press, a multicentre bances, as described in the absence seizure. study was published on lamotrigine mono- The symptoms can be continuous or repetitive therapy in newly diagnosed patients with typi- without full recovery before the cessation of the cal absence seizures.25 The design was “re- status. The ictal EEG is characteristic, usually sponder enriched” with open label dose with regular and symmetrical generalised escalation followed by placebo controlled, Typical absence seizures and their treatment 355

double blind testing of lamotrigine. A patient 2 Marescaux C, Vergnes M. Animal models of absence Arch Dis Child: first published as 10.1136/adc.81.4.351 on 1 October 1999. Downloaded from seizures and absence epilepsies. In: Duncan JS, Panayi- was considered “seizure free” only on hyper- otopoulos CP, eds. Typical absences and related epileptic syn- ventilation and EEG (HV-EEG) documenta- dromes. London: Churchill Communications Europe, 1995:8–18. tion, which may not be an absolute criterion 3 Futatsugi Y, Riviello JJ, Jr. Mechanisms of generalised (see text). Whether the patients were also absence epilepsy. Brain Dev 1998;20:75–9. 4 Danober L, Deransart C, Depaulis A, Vergnes M, seizure free in their daily life was not Marescaux C. Pathophysiological mechanisms of genetic considered and is not mentioned. absence epilepsy in the rat. Prog Neurobiol 1998;55:27–57. 5 Coulter DA. Antiepileptic drug cellular mechanisms of Forty two children and young adolescents action: where does lamotrigine fit in? J Child Neurol 1997; completed the open label lamotrigine escala- 12(suppl 1):S2–9. 6 Panayiotopoulos CP.Absence epilepsies. In: Engel JJ, Pedley tion phase. The patients had HV-EEG testing TA, eds. Epilepsy: a comprehensive textbook. Philadelphia: after each dose increment. If this failed to Lippincott-Raven Publishers, 1997:2327–46. 7 Parker AP, Agathonikou A, Robinson RO, Panayiotopoulos induce absences (a probability that is likely to CP. Inappropriate use of carbamazepine and vigabatrin in increase with serial trials over time, reducing typical absence seizures. Dev Med Child Neurol 1998;40: 517–19. number of absences or both) the patient was 8 Lombroso CT. Consistent EEG focalities detected in considered seizure free and entered the second subjects with primary generalised epilepsies monitored for two decades. Epilepsia 1997;38:797–812. double blind phase. Thirty (71.4%) patients 9 Panayiotopoulos CP. Benign childhood partial seizures and met this criterion with a median dose of 5 mg/ related epileptic syndromes. London: John Libbey and Com- pany, 1999. kg/day. The earliest this was achieved was four 10 Commission on Classification and Terminology of the weeks to probably longer than two months. International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilep- However, for more than half of the patients the sia 1989;30:389–99. upper target dose was increased to 15 mg/kg/ 11 Panayiotopoulos CP, Koutroumanidis M, Giannakodimos S, Agathonikou A. Idiopathic generalised epilepsy in adults day (or a maximum of 1000 mg/day), which is manifested by phantom absences, generalised tonic-clonic double the recommended maximum dose, also seizures, and frequent absence status. J Neurol Neurosurg Psychiatry 1997;63:622–7. demanding more HV-EEG trials. 12 Ferrie CD, Giannakodimos S, Robinson RO, Panayiotopou- The vulnerability of the “seizure free” crite- los CP. Symptomatic typical absence seizures. In: Duncan JS, Panayiotopoulos CP, eds. Typical absences and related rion is shown when these patients were tested epileptic syndromes. London: Churchill Communications for a second time in the double blind phase. Europe, 1995:241–52. 13 Panayiotopoulos CP, Agathonikou A, Sharoqi IA, Parker Five of 14 “seizure free” patients had absences AP. Vigabatrin aggravates absences and absence status. despite receiving the same dose of lamotrigine. 1997;49:1467. 14 Schapel G, Chadwick D. and non-convulsive sta- However, 11 of the 14 patients relapsed when tus epilepticus. Seizure 1996;5:153–6. lamotrigine was replaced by placebo, but three 15 Richens A. Ethosuximide and valproate. In: Duncan JS, Panayiotopoulos CP, eds. Typical absences and related epilep- remained seizure free. The diVerence was tic syndromes. London: Churchill Communications Europe, significant (p < 0.02) providing that both 1995:361–7. 16 Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO. groups had equal numbers of tests. In un- Interaction of lamotrigine with sodium valproate. Lancet treated or partially treated patients more 1993;341:445. 17 Ferrie CD, Robinson RO, Knott C, Panayiotopoulos CP. HV-EEG tests are expected to be positive than Lamotrigine as an add-on drug in typical absence seizures. negative, and the probability of having at least Acta Neurol Scand 1995;91:200–2. 18 van Rijn CM, Weyn Banningh EW, Coenen AM. EVects of one negative trial is higher with increasing lamotrigine on absence seizures in rats. Pol J Pharmacol numbers of trials. 1994;46:467–70. http://adc.bmj.com/ 19 Hosford DA, Wang Y. Utility of the lethargic (lh/lh) mouse Therefore, according to these results lamot- model of absence seizures in predicting the eVects of lamo- rigine as a single agent is eVective in probably trigine, vigabatrin, tiagabine, gabapentin, and topiramate against human absence seizures. Epilepsia 1997;38:408–14. 50% of newly diagnosed patients with typical 20 Gram L. Acetazolamide, benzodiazepines and lamotrigine. absence seizures. For valproate this is around In: Duncan JS, Panayiotopoulos CP, eds. Typical absences and related epileptic syndromes. London: Churchill Europe 80% and the eVect is within days to a few Communications, 1995:368–75. weeks because of insignificant escalation 21 Livingston J. Status epilepticus. In: Wallace S, ed. . London: Chapman and Hall Medical, 1996: problems. However, sodium valproate may 429–48 have unacceptable side eVects particularly in 22 Agathonikou A, Panayiotopoulos CP, Giannakodimos S, on September 23, 2021 by guest. Protected copyright. Koutroumanidis M. Typical absence status in adults: diag- women. Lamotrigine may be an alternative for nostic and syndromic considerations. Epilepsia 1998;39: these patients. A comparative study of lamot- 1265–76. 23 Trevathan E, Murphy CC, Yeargin-Allsopp M, et al. Preva- rigine versus sodium valproate is well overdue. lence and descriptive epidemiology of Lennox-Gastaut We also need to understand better the interac- syndrome among Atlanta children. Buccal absorption of tion between these two drugs as detailed in the midazolam: pharmacokinetics and EEG pharmacodynam- ics. Epilepsia 1998;39:290–4. text. 24 Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet 1 Commission of Classification and Terminology of the Inter- 1999;353:623–6. national League Against Epilepsy. Proposal for revised 25 Frank LM, Enlow T, Holmes GL, et al. Lamictal clinical and electroencephalographic classification of epi- (lamotrigine) monotherapy for typical absence seizures in leptic seizures. Epilepsia 1981;22:489–501. children. Epilepsia 1999;40:973−9.