Felbamate monotherapy: controlled trial in patients with partial onset seizures.

Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single-center, randomized, double-blind, parallel-group trial. During the 56-day baseline period, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one-third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria. Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in highest 2-day seizure frequency, single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria (p less than 0.001, chi-square test). When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile.     

Topiramate Monotherapy for Partial Onset Seizures

Summary: Purpose: Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.
Methods: A total of 48 patients were evaluated in a doubleblind, parallel-group trial. During a 56-day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs). After 1–2 weeks of open-label treatment with TPM 100 mg/day, patients were randomly assigned, in equal proportions, to receive double-blind therapy with TPM 100 or 1,000 mg/day in a 5-week conversion and an 11-week monotherapy period. The study endpoint was completion of 112 study days (success) or fulfillment of one or more exit criteria: doubling of average 28- day or highest 2-day baseline seizure rate, a generalized tonic-clonic seizure (GTCS) if none had occurred at baseline, or significant prolongation of generalized seizure duration.
Results: Time until exit was longer (p = 0.002) and success frequency was higher (p = 0.005) with TPM 1,000 as compared with 100 mg/day. Seizure-rate reductions of 50, 75, or 100% were achieved by 46, 25, and 13% of the 1,000-mg/day group, respectively, as compared with 13, 8, and 0% of the 100-mg/day group, respectively. Most adverse events (AE) were mild or moderate in severity.
Conclusions: Monotherapy with TPM 1,000 mg/day for partial onset seizures with or without secondarily generalized seizures was effective, with a favorable safety profile.     

Treatment of Severe Myoclonic Epilepsy in Infants with Bromide and Its Borderline Variant

Summary: We studied the efficacy of bromides (BR) as add-on therapy in 11 patients with severe myoclonic epilepsy in infants (SME) and in another 11 with the borderline variant of SME (BVSME). Study subjects were aged 8.5–183 months (mean 64.4 months). Longest duration of BR treatment was 37 months (range 4–37 months; mean 19.7 months). Eight of 22 (36%) of patients with generalized tonic-clonic seizures (GTCS) had an excellent effect (>75% reduction in total seizure frequency or duration) and 9 (41%) had a moderate effect (50–75% reduction) 3 months after introduction of BR. Twelve months after initiation of BR, 5 of the patients with significant improvement were no longer responsive; ultimately, therefore, 6 had an excellent effect and 2 had a moderate effect. Of those with partial seizures (n=5) and myoclonic/absence seizures (n = 5), only 1 patient in each group showed a moderate effect at the 12-month time-point. Dosages and serum concentrations of BR ranged from 30 to 100 mg/kg (mean 58 mg/kg) and from 64 to 159 mg/dl (mean 101 mg/dl), respectively. Of the 12 patients experiencing side effects, including drowsiness, appetite loss, and skin rash, 1 required a reduction in BR dosage because of an extensive acneiform rash on the face. The results show that BR treatment holds promise for patients with SME and BVSME and should therefore be investigated further.     

Valproate Monotherapy in 30 Patients with Partial Seizures

This retrospective pilot study describes 30 patients diagnosed and treated for complex partial seizures (CPS) and simple partial seizures (SPS) with and without generalization who received valproate (VPA) monotherapy after lack of response or allergic reaction for carbamazepine (CBZ), phenytoin (PHT), or phenobarbital (PB). Seizures were tabulated daily on seizure calendars by the patients. Three time periods were examined for seizure frequency, 90 days before VPA treatment and 90 and 180 days after VPA treatment. Twenty-two were "controlled" or "improved" (reduction of seizure activity by greater than or equal to 51%) 6 months following the initiation of VPA. VPA was particularly effective in 17 patients who had secondarily generalized tonic-clonic seizures (GTCS) as a subtype of partial seizures. Failure of response to VPA in eight patients appears to be related to their type of partial seizure (SPS or CPS alone, without GTCS) and duration of uncontrolled recurrent seizures. Etiology and compliance were not related to treatment failure. This study supports the need for a double-blind controlled trial with VPA in patients with partial seizures.     

The long-term use of felbamate in children with severe refractory epilepsy.

The aim of the study was to assess the efficacy and safety of felbamate (FBM) as add-on therapy in pediatric patients with severe uncontrolled seizures during a 3-year follow-up. Thirty-six patients were enrolled between February 1994 and February 1997. Patients suffered from partial epilepsy (n=13), Lennox-Gastaut syndrome (LGS) (n=9), infantile spasms (IS) n=8 or other forms of generalized epilepsy (n=6). FBM was titrated weekly from 15 up to 45 mg/kg. By February 1995, all patients had hematological and biochemical monitoring prior to FBM therapy and every 15 days during the study. The results achieved at different treatment durations were analyzed. Overall efficacy measured as > or =50% reduction in seizure frequency varied during follow-up: 69% at 3 months, progressively decreasing to 66% at 6 months, to 47% at 1 year and 41% of the initial cohort at the end of the study. Most frequent side effects were anorexia, weight loss, urinary retention, somnolence, nervousness and insomnia. FBM controlled a broad spectrum of otherwise refractory seizures. Best results were obtained against simple partial seizures with or without secondary generalization, tonic and atonic seizures. A substantial improvement in seizure control was maintained in one-third of the patients for at least 3 years.     

Felbamate: A Clinical Trial for Complex Partial Seizures

We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM.     

Felbamate in the Treatment of Lennox-Gastaut Syndrome: Results of a 12-Month Open-Label Study Following a Randomized Clinical Trial

Summary: Felbamate (FBM) is a new antiepileptic drug (AED) that has been evaluated in partial seizures and in the Lennox-Gastaut syndrome (LGS). When tested against placebo in an add-on, randomized, double-blind trial in 73 children with LGS, FBM significantly reduced the frequencies of astatic (atonic) seizures and generalized tonic-clonic seizures plus total seizure counts. In addition, FBM-treated subjects improved significantly on a parent-rated global evaluation and had fewer injuries. Overall, ˜50% of subjects experienced a 50% or greater reduction in total seizure frequency and a dose-response relationship was apparent. The improvement that occurred in the double-blind study has been sustained for at least 12 months in subsequent open-label follow-up studies. In the first month of FBM treatment, 62% of the subjects who had previously received placebo had a reduction in total seizure frequency of >50%. By the 12-month follow-up point, approximately half of the patients had a 50% reduction in total seizure count. Astatic seizures responded even better, with two-thirds of patients having a reduction of >50% in astatic seizure frequency after 12 months of treatment. Based on adverse experience reports thus far, FBM appears to be well tolerated. FBM is the first drug to be shown effective in the LGS in randomized controlled trials. Although few subjects with LGS became seizure free, the frequency of the most severe seizure types decreased and the patients' global functioning improved.     

Felbamate in refractory partial epilepsy

This open-label study was performed to evaluate efficacy and safety of Felbamate (FBM) add-on therapy in drug-refractory partial epilepsy. We evaluated 36 patients (12 males) aged 11-68 years (mean 29.8) in which FBM was titrated gradually from 300 mg/day to a mean total maintenance daily dose of 1936 mg. Patients were monitored according to clinical practice and performed regularly laboratory tests. Mean follow-up of FBM therapy was 10 months (range 2-27). In this study, 5% of patients resulted to be seizure-free, 11% showed a seizure reduction more than 75%, 23% decreased their seizure frequency between 50% and 75% (P = 0.0001). The adverse events which were reported more frequently were: nausea, vomiting, anorexia and weight loss. Even if the patients sample is small FBM proves its efficacy in partial epilepsy, showing a relatively well tolerated profile.     

Clinical experience with zonisamide monotherapy and adjunctive therapy in children with epilepsy at a tertiary care referral center

We evaluated our clinical experience with zonisamide, a broad-spectrum antiepileptic drug, in a group of children with predominantly medically refractory epilepsy. A retrospective chart review was conducted on patients at our tertiary referral center following Institutional Review Board approval. Observers documented reports of seizure frequency, and seizure types were identified either clinically or by prior video-electroencephalography monitoring. We identified 68 patients (age range 1.9-18.1 years [median 6.9 years]; male to female ratio 1.3:1) treated with zonisamide for 0.7 to 28.9 months; at the last visit, 22% and 78% were on monotherapy and adjunctive therapy, respectively. The median duration of treatment and maintenance dose at the end of the follow-up were 11.2 months and 8.0 mg/kg/day, respectively. Seizure types included generalized (primary generalized tonic-clonic, myoclonic, tonic, atonic, absence) and partial (simple, complex, and secondarily generalized tonic-clonic seizures); 10 (15%) patients had both partial and generalized seizures. Sixteen (25.8%) patients were seizure free, although five of them were already in remission prior to starting zonisamide. Thirteen (21.0%) patients had a > 50% seizure reduction, 10 (16.1%) patients had a < 50% seizure reduction, 14 (22.6%) had no improvement in baseline seizures, and 9 (14.5%) reported having increased seizures. The latter were mostly associated with dosage alterations in concomitant antiepileptic drugs. Common side effects were central nervous system related, including behavioral or psychiatric (23.5%), cognitive dysfunction (12.0%), and sedation (10.3%). Eleven (16.2%) patients ultimately discontinued zonisamide, but only five were strictly due to side effects. Zonisamide is clinically effective against multiple seizure types in a significant proportion of children with epilepsy across a broad age range. Drug discontinuation as a result of side effects is uncommon.     

Felbamate in the Treatment of Partial-Onset Seizures

Summary: Felbamate (FBM, Felbatol/Taloxa) has been the object of several trials that are innovative and unique. First, FBM is the first antiepileptic drug (AED) to have been submitted to a controlled efficacy study in patients with the Len-nox-Gastaut syndrome (LGS) before being submitted for regulatory approval. Second, FBM was tested in patients discontinued from other AEDs for presurgical monitoring. Third, FBM was the first experimental AED to have been tested in controlled monotherapy trials. Overall, these studies succeeded in demonstrating that FBM is relatively safe and effective against both partial-onset seizures and the generalized seizures occurring in the LGS. The results of some of these studies could not always be expressed by using the more familiar concept of percent seizure reduction because, for ethical reasons, the efficacy variable had to be defined in terms of time to the n^lh seizure or in terms of escape criteria. This may make it more difficult to evaluate just how effective FBM is in comparison with other AEDs. Another reason why the efficacy of FBM cannot yet be fully assessed is that in all the studies the FBM dosage was limited to a maximum of 3,600 mg/day or 45 mg/kg/day. At this dosage, FBM produced no toxicity in the majority of patients, and its full therapeutic effect may have to be re-evaluated in the future at higher dosages.     

左乙拉西坦单药或添加治疗癫痫的临床观察

目的观察左乙拉西坦单药和添加治疗癫痫的临床疗效和不良反应。方法对91例门诊癫痫患者进行左乙拉西坦开放性治疗;其中少儿组54例,成人组37例;简单部分性发作(SPS)19例,复杂部分性发作(CPS)20例,全面性强直阵挛性发作(GTCS)32例,继发性全面性强直阵挛性发作(sGTCS)20例;采用单药治疗66例,添加治疗25例。左乙拉西坦起始剂量即为治疗剂量,儿童为10 mg/(kg.d),成人为0.5～3.0 g/d;治疗6个月时根据发作频率自身对照评价疗效,观察不良反应。结果治疗6个月时本组癫痫控制率为52.7%(48例),总有效率为75.8%;少儿组控制率和总有效率分别为64.8%及90.7%,明显高于成人组(35.1%,54.1%;均P<0.01);单药治疗组分别为62.1%及81.8%,明显高于添加治疗组(28.0%,60.0%;均P<0.01);SPS、CPS和GTCS的控制率分别为68.4%和55.0%及53.1%,明显高于sGTCS(35.0%,均P<0.01);SPS控制率明显高于GTCS(P<0.05)。本组不良反应发生率为16.5%,多较轻微,2例因明显脱发而换药。结论左乙拉西坦对多种类型的癫痫发作具有较好的疗效,对儿童及单药治疗的患者疗效更好;儿童及成人患者均有较好的耐受性。     

Zonisamide as adjunctive therapy for refractory partial seizures

Zonisamide (Zonegran) has been used extensively worldwide (>2 million patient-years experience) for the effective treatment of a broad range of epilepsy indications. Four randomised, placebo-controlled trials (duration or=300 mg/day to be efficacious in treating refractory partial seizures in adults. In a pivotal European study, zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency. Pooled data from all four placebo-controlled trials demonstrate an excellent tolerability and safety profile; adverse events are generally of mild-moderate severity with few leading to discontinuation, and incidence of serious adverse events is comparable to placebo. These data support the use of zonisamide in combination with commonly used antiepileptic drugs to provide efficacious and well-tolerated treatment for patients with refractory partial seizures.     

Epilepsietherapie mit Antiepileptika der dritten Wahl

BACKGROUND: We retrospectively analysed the anticonvulsant efficacy of add-on treatment with felbamate (FBM), tiagabine (TGB), or sulthiame (STM) in patients with intractable focal and/or secondarily generalised seizures. RESULTS: Forty-one patients (25 men, 16 women, mean age 29 years, mean duration of epilepsy 25 years) were treated with FBM. In nine patients (21.9%) seizure frequency was reduced by more than 50% (mean FBM dosage 3211 mg), and 13 patients (31.7%) reported side effects. Fifty-three patients (26 men, 27 women, mean age 38 years, mean duration of epilepsy 24 years) were treated with TGB. In seven patients (13.2%) seizure frequency was reduced by more than 50% (mean TGB dosage 32.9 mg), and 28 patients (52.8%) reported side effects. Twenty-eight patients (14 men, 14 women, mean age 32.6 years, mean duration of epilepsy 24.9 years) were treated with STM. In five patients (17.8%) seizure frequency was reduced by more than 50% (mean STM dosage 275 mg), and four patients (14.2%) reported side effects. CONCLUSION: Third-line antiepileptic drugs, especially FBM and STM, are fairly well tolerated and contribute to seizure control.     

Treatment of partial seizures with gabapentin: double-blind, placebo-controlled, parallel-group study

This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.     

Levetiracetam monotherapy for elderly patients with epilepsy.

We retrospectively identified 14 elderly patients with a history of partial seizures who received levetiracetam (LEV) monotherapy. Patients began LEV either as first line therapy (n=5) or were converted to LEV monotherapy (n=9) after failing prior antiepileptic medications (AEDs). Thirteen patients continued on LEV monotherapy for at least 6 months. One patient was lost to follow-up. Eight patients (61.5%) became seizure free. Four patients who began LEV as a first line therapy became seizure free, whereas the remaining four patients who converted to LEV after they failed their previous AEDs became seizure free. Four patients (30.7%) had more than a 50% seizure reduction of seizures. Only one patient had no significant change in seizure frequency after started on LEV. The total dosages used to control seizures were 500-3000 mg/day, (mean 1839.2 mg/day). LEV monotherapy can be effective and well tolerated in this group of patients. A prospective, larger, double blind monotherapy study is needed to confirm this finding.     

Early clinical experience with lacosamide as adjunctive therapy in patients with refractory focal epilepsy and nocturnal seizures

This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13-24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p>0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures.     

A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome)

OBJECTIVE: Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure-induced EEG paroxysms, and photosensitivity. We conducted an open-label trial of levetiracetam in EMA. PATIENTS AND METHODS: Patients were recruited in different Italian Epilepsy Centres. Levetiracetam was administrated at starting dose of 10 mg/kg/day up to 50-60 mg/kg/day in two doses. Treatment period included a 5-6 week up-titration phase and a 12-week evaluation phase. The number of days with EM (i.e., days with seizures, DwS) and number of generalized tonic-clonic seizures (GTCS) were evaluated. Analysis of intent-to-treat population was performed using Fisher's and Wilcoxon tests. RESULTS: Thirty-five patients (23 F) with a mean age of 19 +/- 6 years were recruited. Twenty-seven had previously undergone one to five adequate trials of antiepileptic drugs. The median number of DwS/month was 12 +/- 8.2. Twenty-one patients experienced GTCS (median number/month: 1 +/- 0.2). Thirty-four subjects completed the trial. Levetiracetam was well tolerated (mean dose: 1985 mg/day). Responders were 28/35 (80%) patients, nine taking levetiracetam as monotherapy. Six patients were seizure-free, 15 had > or =75% and seven >50% seizure reduction. GTCS remitted in 14 out of 21 (66.6%) patients. The number/month of DwS (median: 12 vs 5; p = 0.0001) and of GTCS (median: 1 vs 0; p = 0.0001) decreased compared to baseline period. Disappearance or clear reduction in paroxysmal abnormalities at eye closure occurred in 20 of the responders and photoparoxysmal response in 19. Mean follow-up was 23.9 +/- 18.5 months. CONCLUSION: Levetiracetam is effective and well tolerated in EMA. Placebo-controlled studies should confirm these findings.     

Clinical and genetic aspects of juvenile absence epilepsy

Fifteen patients aged 11–25 years (mean 15.37, SD 3.89) suffering from juvenile absence epilepsy are presented. Only 3 (20%) had absences (AS) as the only seizure type, 12 (80%) had associated generalized tonic-clinic seizures (GTCS) and in the remaining 3 with absences and GTCS there was also sporadic myoclonus. We found a higher frequency of AS in our patients by clinical history and video-EEG than has been previously reported. In our patients the mean age of onset in years was 11.4, SD 1.24 for AS, 13.12, SD 2.31 for GTCS and 12.5, SD 2.18 for myoclonus. The correct diagnosis was not made on referrals for any of the patients. It took an average of 3–5.5 years from the onset of the AS (range: 6–120 months) and 2 years from the occurrence of GTCS (average: 1–72 months) to make the correct diagnosis and institute proper treatment, which was valproic acid (VPA). The GTCS were controlled in all patients whereas AS continued in 6 (40%), but to a significantly lesser degree. The frequency and the duration of the GTCS before the start of VPA treatment seemed to have an adverse effect on AS control. We documented no circadian rhythm in either AS or the GTCS, except in 2 patients who had AS and GTCS mainly when they awoke in the morning. The sample size was too small to perform a proper genetic study, though a positive history of epilepsies of mixed types was obtained in 35.7% of the parents and the siblings of the probands.     

Limited efficacy of gabapentin in severe therapy-resistant epilepsies of learning-disabled patients

Knowledge on the effects of gabapentin (GBP) in learning disabled patients is limited. The objective of this study was to assess antiepileptic efficacy and tolerability of GBP in routine therapy. A retrospective open observational study design was applied. Twenty-nine consecutive residential patients with simple and/or complex partial seizures with or without secondary generalization and with different degrees of learning disability were included. All patients had severe therapy-resistant epilepsy. GBP was administered as add-on therapy. Dosages were progressively increased up to 1600-2400 mg/day (in a number of cases up to 4800 mg/day), in accordance with clinical requirements. The seizure frequency was recorded and compared between a baseline and a treatment period (after 3 months of titration) of 3 months duration each.Only three patients (10.3%) had a reduction of their seizure frequency by 50% or more. No patient became seizure-free. Unwanted side effects, mostly mild and dose-dependent, occurred in 37.9% of all patients. Somnolence and ataxia were the most frequently observed unwanted effects. In two cases hyperphagia/weight increase, and in two other cases edema occurred.We conclude the efficacy of GBP in learning disabled patients with highly therapy-resistant partial seizures is limited.     

Efficacy and tolerability of adjunctive therapy with zonisamide in childhood intractable epilepsy

Purpose: This study investigated the efficacy and safety of zonisamide (ZNS) adjunctive therapy in children with intractable epilepsy to existing antiepileptic drugs (AEDs). Methods: A clinical retrospective study was performed from 2003 to 2005 at two tertiary epilepsy centers. We reviewed the data from 163 children (107 boys and 56 girls) who experienced more than four seizures per month, whose seizures were intractable to an initial 2 or more AEDs, and could be followed up for at least 6 months after ZNS adjunctive therapy initiation. Efficacy was estimated by seizure reduction rate according to seizure types including infantile spasms, and adverse events were also measured. Results: Seventy-nine patients (48.5%) out of 163 patients experienced a reduction in seizure frequency of more than 50%, and 25 patients (15.3%) became seizure-free. The rate of seizure reduction greater than 50% in children with partial seizures was 40.5% (17/42) and in children with generalized seizures was 51.2% (62/121). Of 36 patients who manifested mainly myoclonic seizures, 20 patients (55.6%) showed a seizure reduction of more than 50% and 9 patients (25.0%) were seizure-free. Mean maintenance dosage of drug was 8.2 mg/kg/day (range 5.0-16.0 mg/kg/day). Adverse events were documented in 15 children (9.2%), including somnolence (8 patients), fatigue, and anorexia, but all were transient and successfully managed. One patient discontinued ZNS therapy due to acute pancreatitis. Conclusion: ZNS adjunctive therapy is an effective and safe treatment in various childhood intractable epilepsy.