Use of topiramate in childhood generalized seizure disorders

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children.     

Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study

We studied the antiepileptic potency of vigabatrin (gamma-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.     

Zonisamide in the management of epilepsy--Japanese experience

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51-57% responded to zonisamide treatment (achieving >or=50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22-66% of adults and children experiencing tonic-clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.     

Total or partial withdrawal of antiepileptic drugs

Total withdrawal of antiepileptic drugs leads to a mean relapse rate of approximately 50 p. 100 in adults and 25 p. 100 in children. The relapse rates are lowest in patients with benign epilepsies of childhood and epilepsies with absence seizures only and those with a short duration of epilepsy. Relapse rates are higher in patients with complex partial seizures, absences with generalized tonic-clonic seizures, juvenile myoclonic epilepsy, patients with several types of seizures, high seizure frequency prior to control, in patients with neurological, psychiatric or social handicaps and in those with emotional ambivalence towards the reduction. Guidelines for slow and safe withdrawal are given. Reduction should be actively encouraged only in patients with absence seizures or benign focal epilepsy and those with epilepsy of short duration. Slow partial withdrawal is recommended in uncontrolled epilepsy because in 80 p. 100 of the patients it results in a decrease in seizure frequency and side effects or both.     

Selective mutism and obsessive compulsive disorders associated with zonisamide.

We treated 27 children with idiopathic epilepsy with zonisamide monotherapy over a period of 2 years and observed behaviour disturbances in a prospective study. In all cases, seizure control was excellent; however, two cases (7.4%) had behaviour disturbances. The first (Case 1) was a 14-year-old girl with partial epilepsy which began at age 4 years. Zonisamide was administered at age 6 years, which was effective against her seizures, but selective mutism, violent behaviour, and lack of concentration developed at age 10 years. The second (Case 2) was a 15-year-old girl with generalized tonic-clonic seizures which began at age 10 years. Zonisamide was also effective against her seizures, but obsessive compulsive disorders (OCD) developed at age 13 years. The patients have had no other physical or mental problems and decreasing the dosage of zonisamide reduced the problems. There are few reports of behaviour disturbances provoked by zonisamide monotherapy in epileptic children who are neither physically nor mentally disturbed. While problems can develop several years later, in the present study, decreasing the zonisamide dosage maintained adequate prevention of seizures and eliminated the behaviour disturbances. Zonisamide is still a useful anticonvulsant for epileptic seizures, but physicians should be wary of its adverse behavioural side effects, which may arise several years later.     

Efficacy and safety of zonisamide monotherapy in a cohort of children with epilepsy

The aim of this study was to evaluate the efficacy and safety of zonisamide monotherapy in a cohort of children and adolescents with various types of epilepsy. Retrospective review of charts of our institution from 2001 through 2004 identified 69 children (19 males and 50 females, mean age 13.2 years) with epilepsy on zonisamide monotherapy. Seizure count and side effect profile were maintained during therapy. Sixty-one percent had idiopathic generalized epilepsy, 4% symptomatic generalized epilepsy, and 35% partial-onset epilepsy. Zonisamide was the first-line and second-line monotherapy for 32% and 68% of patients, respectively. The mean duration of follow-up on treatment was 22 months (range 3-48 months). The overall efficacy of zonisamide was 75.4% (> or = 50% seizure frequency reduction: good responders). Sixty-seven percent of good responders became seizure-free. Seventy-nine percent of patients with partial epilepsy and 71% with generalized epilepsy were good responders, of whom 79% and 63% were free of seizure, respectively. Eighteen (26%) patients developed side effects: weight loss (9), cognitive impairment (3), sleepiness (3), dizziness (2), and decreased appetite (1). In seven patients (10%), zonisamide had to be discontinued: four due to side effects and three because of poor seizure control. Zonisamide was demonstrated to be effective as monotherapy in children with epilepsy.     

Outpatient sleep recording during antiepileptic drug monotherapy

The effects of sleep and sleep deprivation on epilepsy are well known, but the effects of seizures and antiepileptic drugs (AEDs) on sleep have been less well studied. We recorded nocturnal sleep in 17 patients receiving antiepileptic monotherapy with ambulatory cassette EEG devices. Twelve patients had complex partial seizures and five had tonic-clonic convulsions. Two patients' seizures were largely nocturnal, and no seizures occurred during sleep recording. Five patients each were taking phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), and two were taking clonazepam (CZP), all with therapeutic serum levels and no toxic symptoms. Total sleep time was reduced, wakefulness increased, and sleep latency prolonged in partial seizures as compared with generalized epilepsy. REM sleep was reduced and its latency decreased in partial seizure patients. Both groups had decreased slow wave sleep; that of partial seizure patients was decreased more markedly. PHT increased sleep latency and decreased sleep time, and CBZ increased awakening and diminished slow wave and REM sleep. Patients taking VPA had slight reduction in slow wave sleep; those taking CPZ had decreased sleep and REM latencies. Epilepsy may affect nocturnal sleep, and the effects of partial and generalized seizure disorders may be different. AEDs may also have differential effects on nighttime sleep. These may prove important in the long-term management of epileptic patients.     

Refractory grand mal seizures with onset during infancy including severe myoclonic epilepsy in infancy.

In 1978, Dravet proposed a clinical entity called severe myoclonic epilepsy in infancy (SMEI). In the same year, a patient group, which was later called high voltage slow wave-grand mal syndrome (HVSW-GM), is reported in Japan. Both syndromes are very similar, except for seizure manifestation: generalized tonic-clonic convulsions (GTC) with myoclonic and other polymorphic seizures in SMEI vs. GTC only in HVSW-GM. To study the pathophysiology of these refractory epilepsies, the author formulated new clinical diagnostic criteria common to both syndromes as follows: GTC with onset before the age of 1 year as the principal seizure type; an epilepsy entity unclassifiable either as partial or generalized by all the clinical data including EEG findings; mental and motor dysfunction absent prior to seizure onset but appearing later; absence of epileptiform activities on EEG in the initial stage; stubborn refractoriness to conventional antiepileptic medication. Twenty-two patients meeting all of five clinical criteria above mentioned were recruited in the study. Detailed analysis of clinico-electrical features and long-term follow-up of these patients led the author to the conclusion that GTC in combination with seizures of other types will contribute to an unfavorable pathophysiological or prognostic conditions, and, especially when GTC exists in combination with myoclonic seizures, the severity of epilepsy will increase. The author claimed that the three clinical entities, SMEI, HVSW-GM, and their variant form, share certain characteristics in common and may constitute a unique epilepsy syndrome for which a new name of infantile refractory grand mal syndrome (IRGMS) was offered. This is a more basic concept with broader spectrum than SMEI, encompassing not only SMEI but also related borderlands like HVSW-GM. More recently, the author observed that early zonisamide medication within 1 year after seizure onset may improve seizure prognosis in IRGMS, by preventing the development of myoclonic seizures.     

Rapid Arrest of Seizures with an Inhalation Aerosol Containing Diazepam

Summary: Diazepam (DZP) and a mixture of Chinese herbs customarily used to treat epilepsy were prepared as an aerosol under the trade name Aerosolum Diaiepami Compositae or Flvalscop (FVS). FVS was studied in a single-blind trial in 101 patients with seizures preceded by an aura and in 19 without an aura to whom was administered by another person. FVS or a control preparation was administered. In 16–22 s, (average 18.5 s), the aura was interrupted and no seizure ensued in 90% of the cases treated with FVS and in 26% of cases treated with the control preparation. Of the 120 patients, 8 had elementary partial seizures with Jacksonian march, 18 had complex partial seizures (CPS), 7 had simple partial seizures with autonomic symptoms, and 87 had secondarily generalized tonic-clonic seizures. Eleven patients have now received FVS for 2 years (400 ml each). Forty patients for 1 year (150–200 ml each); none of these patients have shown any side effects or abnormal laboratory findings. An aerosol-administered drug may be a valuable adjunct to the antiepileptic drug (AED) arsenal and merits more extensive evaluation.     

Lamotrigine therapy of epilepsy in tuberous sclerosis

PURPOSE: Lamotrigine (LTG), a newer antiepileptic drug (AED), has activity against both partial-onset and generalized seizures. Its reported benefits for behavior, and its effectiveness in Lennox-Gastaut syndrome and other forms of refractory epilepsy, make it a logical choice for treatment of epilepsy in tuberous sclerosis complex (TSC). We present our experience with LTG therapy of epilepsy in 57 patients with TSC. METHODS: Patients fulfilled the diagnostic criteria for clinically definite TSC. LTG was initiated and increased until improvement in seizure frequency was noted, intolerable side effects occurred, or maximal doses were reached. Seizure frequency and behavioral changes were recorded during LTG therapy and compared with those prior to the introduction of LTG. RESULTS: Twenty-four (42%) were seizure free, and 21 (37%) had a >50% reduction in seizure frequency. Eighteen (32%) had subjectively improved behavior and/or alertness with daily activities. Thirty-eight (67%) had no change in this regard, whereas one (2%) became worse. Responders were more likely to not have a history of infantile spasms, and to have experienced only partial seizures (p < 0.05). Otherwise no phenotypic correlations with response were apparent. CONCLUSIONS: Among patients with TSC and epilepsy, LTG was effective and well tolerated, including as initial monotherapy. Improved alertness and behavior were apparent in many patients. The incidence of side effects is similar to that reported for other pediatric populations with symptomatic partial epilepsy. The usefulness of LTG in TSC may relate to an underlying defect of glutamatergic neurotransmission in partial epilepsy.     

Mah-Jong-induced epilepsy: a special reflex epilepsy in Chinese society.

We present five patients of epilepsy in which seizures were triggered by playing or watching the traditional Chinese gambling game "Mah-Jong." One patient also experienced seizures while playing a computer version of the Mah-Jong game. This condition appeared to have a predominance of males (80%) and middle-aged onset (39.4 years). Four patients had generalized tonic-clonic seizures and one patient had partial seizures with secondary generalization. No spontaneous seizure occurred in these patients. Three patients had been receiving antiepileptic drug therapy, but without effective control over their seizures. Mah-Jong-induced epilepsy is a very peculiar form of complex reflex epilepsy that involves the higher mental activities. This phenomenon may consist of distinct pathophysiologic mechanisms from other reflex epilepsy induced by thinking and spatial tasks in idiopathic generalized epilepsies. This unusual reflex epilepsy is relatively benign in nature and antiepileptic drug therapy has uncertain benefits. It may be necessary to avoid playing the Mah-Jong game in order to prevent seizures.     

原发性癫痫合并阻塞性睡眠呼吸暂停低通气综合征的临床特点

目的探讨原发性癫痫合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者的临床特点。方法回顾性分析2007-06-2014-06在我院确诊的16例原发性癫痫合并OSAHS患者的临床资料(包括病史、多导睡眠脑电图及治疗随访)。结果癫痫形式表现为全面强直阵挛发作13例,部分性发作3例,其中夜间发作11例,白天发作5例;多导睡眠脑电图(polysomnography,PSG)显示均为阻塞性睡眠呼吸暂停低通气综合征(OSAHS),其中重度9例,中度4例,轻度3例。所有患者经抗癫痫药物治疗及OSAHS的指导性治疗。其中4例癫痫伴重度OSAHS经单纯药物治疗仍反复发作,联合丙戊酸钠和经鼻持续气道正压通气(CPAP)治疗,随访0.5~3a,发作频率减少3例,发作停止1例。结论原发性癫痫合并OSAHS一般以中老年男性多见,癫痫类型以夜间全面强直阵挛性发作为主,对于单纯抗癫痫药物治疗不佳者,药物联合CPAP治疗可取得明显效果。     

Selection of drugs for the treatment of epilepsy

Antiepileptic drug selection is based on efficacy for specific seizure types and epileptic syndromes. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the drug of choice is valproate. Secondary generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single drug or combination of drugs. The drugs of choice for absence seizures are ethosuximide and valproate. For control of tonic-clonic seizures, any of the other major antiepileptic drugs can be effective. If valproate cannot be used, carbamazepine, phenobarbital, phenytoin, or primidone is effective, but ethosuximide or a benzodiazepine needs to be added to control associated absence or myoclonic seizures. The drugs of first choice for partial epilepsies with partial and secondarily tonic-clonic seizures are carbamazepine and phenytoin. Increasing evidence suggests that valproate may be a third alternative. Phenobarbital and primidone are second choice selections because of side effects. A combination of two of these five major antiepileptic drugs may be necessary for inadequately controlled patients. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, and alcoholic epilepsy require specific drug treatment. For all these seizure types and epilepsy syndromes, treatment ultimately must be selected to provide maximal efficacy and minimal adverse effect for each individual patient.     

Efficacy of zonisamide: our experience

The current overview of zonisamide use and effectiveness is based on both a long-term prospective postmarketing survey and current zonisamide use at the Saitama Medical College, Department of Neuropsychiatry. Survey data, which were collected from individual physicians and 23 survey groups throughout Japan, assessed the effectiveness of zonisamide in 1631 patients. Zonisamide was highly effective for treating partial seizures, with 70% of patients reporting improvement. More than half of patients with generalized seizures (58%) and half of patients with myoclonic and atypical absence seizures showed improvement with zonisamide treatment. Among the different epileptic syndromes, zonisamide was highly effective in treating generalized idiopathic epilepsy (≥78% improvement) and partial epilepsy (≥58% improvement). However, only 28% of patients with West syndrome or Lennox-Gastaut syndrome showed improvement. Among 60 outpatients treated with zonisamide at our facility as of October 1998, most had partial seizures or generalized seizures subsequent to partial seizures. The majority of patients received zonisamide in combination with other antiepilepsy drugs. Patients receiving zonisamide monotherapy showed greater improvement than did patients receiving polytherapy. We conclude that zonisamide is highly effective for partial seizures and generalized seizures, and that there appears to be no decrease in efficacy with long-term use.     

Absence seizures with evolution into generalized tonic-clonic activity: clinical and EEG features

PURPOSE: To report the clinical and electrographic features of absence seizures evolving into generalized tonic-clonic (GTC) activity in six patients with idiopathic generalized epilepsy. METHODS: All patients were referred for evaluation of refractory seizures and underwent video-EEG monitoring after discontinuation of their antiepileptic drugs (AEDs). We analyzed the video-EEG recordings for seizure semiology as well as ictal and interictal activity. We also reviewed the initial clinical data in all patients. RESULTS: All patients were women, with a mean age of 27 years (range, 14-43 years). The mean age at seizure onset was 12 years (range, 5-15 years). Family history was positive for epilepsy in four patients. All patients had recorded seizures with an onset that was characteristic of generalized absence clinically and electrographically, with evolution into GTC activity. The EEG onset was with generalized 2.5-to 5-Hz spike-and-wave discharges, with evolution into faster rhythmic activity. Interictal EEG recordings showed generalized 2-to 5-Hz spike-and-wave discharges. All had normal background activity. All patients were treated with divalproex monotherapy. Five patients have been seizure free, and one had a single breakthrough GTC seizure during a follow-up period of 12-36 months. CONCLUSIONS: GTC activity may evolve from typical absence seizures. This seizure type should be included in the International Classification of Seizures. Its recognition and distinction from complex partial seizures with secondary generalization are important for appropriate therapy.     

Amantadine hydrochloride for refractory generalized epilepsy in adults

Amantadine hydrochloride has been shown in several open studies to benefit children with refractory generalized epilepsy. We used amantadine as adjunctive therapy in 10 adolescents and adults with generalized tonic-clonic, myoclonic, or absence seizures refractory to therapeutic levels of valproate, carbamazepine, phenytoin, and benzodiazepines. Seven patients were men and 3 were women aged 18-29 years, and 8 of 10 patients were mentally retarded. All patients had generalized epileptiform paroxysms on EEG, with generalized or absence seizure recorded in 9. Five patients had both absence and tonic-clonic seizures, and 2 had all three seizure types. Amantadine was added to the existing regimens in weekly increments to 400 mg/day. Two patients had greater than 90 per cent seizure reduction, both with vomiting and somnolence. Two patients had seizure reduction between 50 and 90 per cent, 1 with anorexia and sleepiness. Three patients had no change in seizures, and 3 had worse tonic-clonic seizures. Amantadine may have some antiepileptic efficacy of unknown mechanism, but it may worsen generalized tonic-clonic seizures and is likely to be of limited value in adults.     

Broad-spectrum efficacy of zonisamide at 12 months in children with intractable epilepsy

In a retrospective study of 35 children (ages 8 months to 22 years; mean age 9 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of zonisamide therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications, and the number of previous anticonvulsant drugs. Good to excellent seizure control (50-100% reduction) was attained in seven (54%) patients with generalized seizures, two (40%) patients with focal seizures, five (35%) patients with mixed seizures, and one (33%) patient with infantile spasms. In this group of children, the efficacy of zonisamide was comparable for focal, generalized, and mixed seizures. The efficacy of zonisamide was independent of cognitive status.Adverse effects were not associated with a higher mean dose. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of zonisamide and levetiracetam had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of mechanisms of action of zonisamide and levetiracetam and/or their pharmacodynamic interactions.     

The effect of seizure type and medication on cognitive and behavioral functioning in children with idiopathic epilepsy

Antiepileptic drugs have been reported to have a variety of adverse effects on behavior and performance in children with epilepsy. Previous studies investigating these side effects, however, have not controlled for the baseline status of the child (e.g. underlying neurological condition, seizure type, socioeconomic status, family variables), making it difficult to determine whether changes in function are attributable to the use of medication. We investigated the cognitive and behavioral profiles of 43 children, aged from 4 to 16 years, with new onset, idiopathic seizures. Twenty-six of these children participated in a 6-month follow-up study, and 12 in a 12-month follow-up study, investigating the effects of antiepileptic medications on psychological functioning. The children were of average intelligence (mean 1Q108) and had not previously been treated with antiepileptic medication. Children were classified as having either generalized convulsive, generalized non-convulsive (absence), simple partial, or complex partial seizures. Prior to the initiation of treatment, children with partial seizures were found to perform better than children with generalized seizures on measures of cognitive functioning. Children with convulsive seizures obtained significantly higher cognitive scores than those with non-convulsive seizures. Children with generalized non-convulsive seizures had lower cognitive scores than subjects with other types of seizure. No differences were found between groups at baseline prior to the initiation of antiepileptic medications. Analysis of subjects' performance after 6 and 12 months of antiepileptic therapy showed no significant deterioration attributable to medication. The differences in cognitive performance of the four seizure groups at baseline were not apparent at the time of follow-up. These results indicate that intrinsic and environmental variables may play a more significant role in predisposing certain children to cognitive and learning problems than do antiepileptic medications.     

Zonisamide – a review of experience and use in partial seizures

Zonisamide is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. Preclinical studies have reported a range of potential mechanisms of action for zonisamide, such as blocking voltage-gated sodium channels, reduction of T-type calcium channel currents, and enhancement of gamma-aminobutyric acid (GABA)-mediated inhibition, which are indicative of its broad antiseizure effects. Zonisamide has a favorable linear pharmacokinetic profile, a long half-life, and a low incidence of protein-binding interactions with other AEDs. Hepatically metabolized through the cytochrome P450 pathway, zonisamide does not induce its own metabolism or liver enzymes. For more than 2 decades, zonisamide has been extensively used as monotherapy and adjunctive therapy for the treatment of partial and generalized seizures in pediatric and adult patients in Japan. Zonisamide was approved in the USA in 2000 as adjunctive therapy for partial seizures in adults. With over 2 million patient-years of exposure internationally, zonisamide has demonstrated safety and efficacy against a multitude of epilepsy and seizure types, including both partial and generalized seizures. This review focuses on the experience and use of zonisamide in partial seizures, as well as possible new uses for zonisamide.     

Lamotrigine therapy of epilepsy with Angelman's syndrome

PURPOSE: Angelman syndrome (AS) is a neurogenetic disorder characterized by developmental delay and a frequently refractory epileptic condition. Valproate, clonazepam and/or phenytoin are said to be the most effective antiepileptic drugs (AEDs) against the seizures in AS. Experience with the newer AEDs is very limited despite their better safety profile and tolerability. Considering its favorable side effect profile and its effectiveness against both partial and generalized seizures, we hypothesized that lamotrigine (LTG) might be more efficacious and better tolerated. METHODS: Potential patients for this retrospective study were identified from the epilepsy clinics at Notre-Dame, Sainte-Justine, and Yale New Haven hospitals. Patients were included in the study if they had AS along with refractory seizures. The medical record of each patient was reviewed with interest on seizure types, previous AEDs and response to LTG. RESULTS: Five patients (2M, 3F) were included in this study. Age at LTG ranged from 10 to 33 years old. All had >or=2 seizure types, mainly generalized tonic-clonic, myoclonic seizures, and atypical absences. Previously tried AEDs included valproic acid (5), benzodiazepines (5), phenytoin (4), carbamazepine (3), and topiramate (1). One patient had pancreatitis on phenytoin, one had worsened seizures on carbamazepine, and one developed hepatic encephalopathy on valproic acid. Three patients became seizure-free with LTG (9, 20, and 36 months FU), one was seizure-free for 1 year with subsequent loss of efficacy, and one showed >50% reduction in myoclonic seizures (20 months FU). No side effects were reported. CONCLUSION: LTG can be efficacious and well tolerated in patients with AS.