Felbamate in the Treatment of Lennox-Gastaut Syndrome

Summary: Felbamate (FBM, Felbatol/Taloxa), a new an-tiepileptic drug (AED), was tested in a placebo-controlled add-on design in 73 patients with therapy refractory Lennox-Gastaut syndrome. Results of the efficacy analysis showed that FBM was statistically significantly more effective (p < 0.05) than placebo for four of five predefined efficacy variables. The total number of seizures, for example, decreased by 26% during treatment with FBM compared with an increase of 5% during placebo (p < 0.001). Retrospective analysis of percentage of patients with specific response rates confirmed results of the predefined efficacy variables. Approximately 50% of patients randomized to FBM obtained at least a 50% reduction in seizure frequency compared with about 15% receiving placebo. In addition, 12-month follow-up data in patients who completed the controlled part of the study confirmed the long-term efficacy of FBM. In general, FBM was well tolerated, with only gastrointestinal symptoms and somnolence seen more often with FBM compared with placebo. FBM is the first compound shown to be effective in a controlled study in patients with Lennox-Gastaut syndrome.     

Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: A randomized placebo-controlled trial

Purpose:   To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged ≥16 years with refractory partial seizures.
Methods:   This double-blind, placebo-controlled, randomized, parallel-group, multicenter trial included an 8-week baseline phase and a 13-week double-blind phase. Treatment was initiated with rufinamide 400 mg twice daily or placebo; rufinamide was titrated to 1600 mg twice daily. Percentage change in partial seizure frequency was the primary outcome measure. Secondary outcome measures included total partial seizure frequency and the percentage of subjects experiencing a ≥50% reduction in partial seizure frequency.
Results:   Three hundred thirteen subjects were randomized; 156 subjects received rufinamide and 157 received placebo. Rufinamide-treated subjects experienced a 20.4% median reduction in partial seizure frequency relative to baseline, while placebo-treated subjects had an increase of 1.6% (p = 0.02). Exclusion of subjects taking carbamazepine in a post hoc analysis resulted in a reduction of 29.2% versus 0.7% in the placebo group (p = 0.05), whereas the treatment difference in subjects taking carbamazepine was not significant. Of rufinamide-treated subjects, 28.2% experienced a ≥50% decrease in partial seizure frequency versus 18.6% of placebo-treated subjects (p = 0.04). The most common adverse events associated with rufinamide treatment were dizziness, nausea, diplopia, and ataxia; they occurred primarily during the titration phase.
Discussion:   Adjunctive therapy with rufinamide 3200 mg/day compared with matching placebo demonstrated efficacy and was generally well tolerated in adults with partial seizures. Further study of this agent in adults with partial seizures taking a range of baseline AEDs is warranted.     

Felbamate Monotherapy: Implications for Antiepileptic Drug Development

Summary: We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 ± 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 had an episode of panic. There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy.     

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 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.     

Adjunctive lamotrigine XR for primary generalized tonic-clonic seizures in a randomized, placebo-controlled study

Efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for primary generalized tonic-clonic (PGTC) seizures in epilepsy were evaluated. Patients (n = 153) ≥ 13 years old diagnosed with epilepsy with PGTC seizures were randomized to once-daily adjunctive lamotrigine XR or placebo in a double-blind, parallel-group trial comprising a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase. Lamotrigine XR was more effective than placebo with respect to median percentage reduction from baseline in weekly PGTC seizure frequency (primary endpoint-19-week treatment phase: 75.4% vs 32.1%, P<0.0001; escalation phase: 61.9% vs 30.6%, P = 0.0016; maintenance phase: 89.7% vs 33.3%, P<0.0001). Lamotrigine XR was more effective than placebo with respect to the percentage of patients with ≥50% reduction in PGTC seizure frequency. Significant separation from placebo for ≥50% reduction in PGTC seizures was observed beginning on treatment day 8. The most common adverse event was headache (lamotrigine XR 14%, placebo 16%).     

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.     

Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures.

BACKGROUND: Zonisamide is a sulfonamide antiepilepsy drug with sodium and calcium channel-blocking actions. Experience in Japan and a previous European double-blind study have demonstrated its efficacy against partial-onset seizures. METHODS: A randomized, double-blind, placebo-controlled trial enrolling 203 patients was conducted at 20 United States sites to assess zonisamide efficacy and dose response as adjunctive therapy for refractory partial-onset seizures. Zonisamide dosages were elevated by 100 mg/d each week. The study design allowed parallel comparisons with placebo for three dosages and a final crossover to 400 mg/d of zonisamide for all patients. The primary efficacy comparison was change in seizure frequency from a 4-week placebo baseline to weeks 8 through 12 on blinded therapy. RESULTS: At 400 mg/d, zonisamide reduced the median frequency of all seizures by 40.5% from baseline, compared with a 9% reduction (p = 0.0009) with placebo treatment, and produced a > or =50% seizure reduction (responder rate) in 42% of patients. A dosage of 100 mg/d produced a 20.5% reduction in median seizure frequency (p = 0.038 compared with placebo) and a dosage of 200 mg/d produced a 24.7% reduction in median seizure frequency (p = 0.004 compared with placebo). Dropouts from adverse events (10%) did not differ from placebo (8.2%, NS). The only adverse event differing significantly from placebo was weight loss, though somnolence, anorexia, and ataxia were slightly more common with zonisamide treatment. Serum zonisamide concentrations rose with increasing dose. CONCLUSION: Zonisamide is effective and well tolerated as an adjunctive agent for refractory partial-onset seizures. The minimal effective dosage was 100 mg/d, but 400 mg/d was the most effective dosage.     

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.     

Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy)

Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults. Rufinamide is well absorbed after oral administration, demonstrates low protein binding, and is metabolized by enzymatic hydrolysis without involvement of cytochrome P450 enzymes, conferring a low drug interaction potential. In a randomized, double-blind trial involving 138 adult and pediatric patients with LGS, compared with placebo, rufinamide 45 mg/kg/day resulted in significantly superior reductions in drop attacks (median change −42.5% vs +1.4% with placebo) and total seizures (−32.1% vs −11.7% with placebo), accompanied by significantly higher responder rates. These results are comparable with findings reported for other AEDs in randomized, controlled clinical trials in patients with LGS. Rufinamide produced statistically significant seizure reduction which was maintained during long-term therapy and accompanied by good tolerability. The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%). Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.     

Clinical efficacy of zonisamide in Lennox-Gastaut syndrome: Korean multicentric experience

PURPOSE: To evaluate the efficacy and safety of zonisamide (ZNS) as long-term adjunctive therapy in children with Lennox-Gastaut syndrome (LGS). METHOD: We evaluated the seizure frequency, cognitive outcomes, and side effects of 62 LGS patients maintained on ZNS for at least 12 months in three tertiary centers. RESULTS: Of the 62 LGS patients maintained on ZNS, 3 (4.8%) had 100% seizure control; 14 (22.6%) had >75% to <100% reduction in seizure frequency; 15 (24.2%) had >50% to <75% reduction in seizure frequency; 6 (9.7%) had >0% to <50% reduction in seizure frequency, and 24 (38.7%) had no seizure reduction. Seizure outcomes were not related to seizure types or etiologies. Adverse events included somnolence and anorexia, but all were transient and successfully managed by careful follow-up. CONCLUSION: Our results indicate that adjunctive treatment with ZNS is safe and effective in pediatric LGS patients.     

Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial

OBJECTIVE: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial. METHODS: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study. RESULTS: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p /=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. CONCLUSION: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.     

Efficacy and safety of Losigamone in partial seizures: a randomized double-blind study

The objective of the study was to investigate the efficacy and safety of two different dosages of Losigamone (LSG) in add-on treatment of partial seizures. In a multi-center, double-blind, randomized clinical trial, patients received one of three 12-week treatments: placebo, LSG 1200 mg/day, or 1500 mg/day, in addition to up to three standard anticonvulsants after a prospective period of 12 weeks to assess baseline seizure frequency. The primary efficacy measure was the relative reduction of seizure frequency per 4 weeks in the double-blind phase as compared to baseline. In the intention-to-treat population of 264 patients, the relative median reduction of partial seizure frequency was 3.3% for placebo, 19.7% for LSG 1200 mg/day, and 25.3% for LSG 1500 mg/day. The differences of both LSG groups versus placebo were significant (P<0.01, two-tailed). In the responder analysis, 11.8% of the patients in the placebo group, 17.2% in the LSG 1200 mg/day group, and 29.3% in the LSG 1500 mg/day group showed a seizure reduction versus baseline of at least 50%. A positive association between dosage and response was observed (P=0.003). Adverse events during treatment were reported by 58.8% of the patients for placebo, by 62.1% for LSG 1200 mg/day and by 76.1% for LSG 1500 mg/day. Most events in the LSG groups occurred during the first 4 weeks of double-blind (during or immediately after up-titration) and subsided quickly. Over the last 4 weeks of treatment, the incidence of adverse events in the LSG groups was close to the placebo level. Based on the study's results, LSG is an effective and safe add-on drug for refractory partial epilepsy in adults.     

Felbamate in the Treatment of Refractory Partial-Onset Seizures

Summary: Felbamate (FBM) is a new antiepileptic drug (AED) that has been tested in open and controlled studies in patients with therapy-refractory partial-onset seizures. Proof of efficacy is based on results of five controlled studies (three with polytherapy and two with monotherapy). In two of the three polytherapy studies, a classic placebo crossover design was used. The third study used a novel design evaluating the efficacy of FBM in a placebo-controlled parallel design in patients completing an evaluation for epilepsy surgery. The primary efficacy variable in this study was the number of patients who experienced a fourth seizure before the end of the study. Forty-six percent of patients randomized to FBM stopped treatment prematurely because of the occurrence of a fourth seizure compared with 88% randomized to placebo. Two studies investigating the efficacy in monotherapy were performed. Both studies used an identical trial design comparing FBM with a low dosage of valproate (VPA). The efficacy of FBM was found to be superior to the low-dosage VPA for both studies. Open long-term follow-up studies have confirmed the long-term efficacy of FBM for up to 12 months. Overall, FBM was well tolerated in both poly- and monotherapy.     

Gabapentin as Add-On Therapy in Children with Refractory Partial Seizures: A 12-Week, Multicentre, Double-Blind, Placebo-Controlled Study

PURPOSE: To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add-on therapy for refractory partial seizures in paediatric patients aged 3-12 years. METHODS: After a 6-week baseline period, 247 patients (54 centres) entered a 12-week double-blind phase and were randomized to receive either GBP (t.i.d., titrated to 23-35 mg/kg/ day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well-being. RESULTS: RRatio for all partial seizures was significantly lower (better) for GBP-treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (-17.0%) was better than that for the placebo group (-6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (-35%) and secondarily generalized seizures (-28%) when compared with placebo (-12%, +13%, respectively). A greater percentage of GBP-treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure-frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double-blind treatment period. GBP was well tolerated. CONCLUSIONS: GBP was effective and well tolerated as an add-on therapy for partial seizures in paediatric patients with previously drug-resistant seizures.     

Double-Blind, Placebo-Controlled Trial of Topiramate (600 mg Daily) for the Treatment of Refractory Partial Epilepsy

Summary: Purpose : We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study.
Methods : Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks.
Results : TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity.
Conclusions : The results of the present trial indicate that TPM 600 mgiday is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.     

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.     

多中心、随机、双盲、安慰剂对照评价唑尼沙胺添加治疗癫(癎)部分性发作的疗效和安全性

目的 评价唑尼沙胺作为添加治疗癫(癎)部分性发作的疗效和安全性.方法 确诊为有癫(癎)部分性发作的217例癫(癎)患者,随机分配入唑尼沙胺治疗组(n=111)与安慰剂组(n=106)进行随机、双盲、安慰剂对照、多中心平行设计添加治疗.在3个月回顾性基线期后,给予患者初始剂量唑尼沙胺(100 mg/片)或安慰剂每次1片,每日1次口服,4周内递增至每次2片,每日2次.分别在治疗0、2、4、8、12和16周时进行随访.主要疗效指标为治疗结束后与基线期比较发作次数减少的中位百分比;次要疗效指标为发作次数减少大于50%的比例.同时观察研究药物的安全性与不良反应情况.结果 总发作次数减少率中位数在唑尼沙胺组为33.33%,安慰剂组为0;唑尼沙胺组总发作次数减少>50%者38例(34.23%),安慰剂组21例(19.81%),差异有统计学意义(χ3=5.7159,P=0.0168).唑尼沙胺组治疗后无发作13例(11.71%),有效25例(22.52%),临床有效率为34.23%;安慰剂组无发作5例(4.72%),有效16例(15.09%),临床有效率为19.81%,2组间比较差异有统计学意义(U=2.4701,P=0.0135).唑尼沙胺组与安慰剂组比较,其不良反应发生率差异无统计学意义,唑尼沙胺组较常见的不良反应有思睡、乏力、食欲下降、胃肠道不适、失眠和便秘.结论 唑尼沙胺作为部分性癫(癎)发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.     

The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome

We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between them. 6-h video-electroencephalography was recorded following each observation period. In addition to examining the effects of the drugs with parental reports and video-EEG, we compared video-EEG data with families' seizure reports. Based on parental counts for the 7-week observation periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test) and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7% when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a significant effect on drop attack frequency, although not total number of seizures. FBM's therapeutic effect on drop attacks is due in part to increased VPA levels, although the combination may be synergistic for the effect on total seizure number.     

Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox-Gastaut syndrome

PURPOSE: To compare the efficacy of corpus callosotomy and vagus nerve stimulation (VNS) for long-term adjunctive therapy in children with Lennox-Gastaut syndrome (LGS). METHOD: Fourteen patients underwent a total corpus callosotomy and 10 patients received VNS implantation. The patients were monitored for more than 12 months after treatment, and seizure rates and complications were retrospectively evaluated. RESULTS: Seizure types among the 24 patients included atonic or tonic seizures with head-drops in 17 patients, generalized tonic seizures in two patients, atypical absence seizures in one patient, generalized tonic-clonic seizures in one patient, and myoclonic seizures in three patients. Of the 14 patients who underwent a corpus callosotomy, nine (64.3%) had a greater than 50% reduction in seizure frequency and five (35.7%) had a greater than 75% reduction. Of the 10 patients who underwent VNS implantation, seven (70.0%) had a greater than 50% reduction in seizure frequency and two (20.0%) had a greater than 75% reduction. There was no significant difference between the two procedures in terms of final efficacy. Complications of corpus callosotomy included aphasia in one patient, ataxia in another, and paresis in a third. Among patients receiving VNS, one patient experienced dyspnea while sleeping and one patient suffered from drooling. These complications were transient and tolerable, and were controlled by simple adjustments of VNS treatment parameters. CONCLUSION: The efficacy and safety of corpus callosotomy and VNS were comparable in children with LGS.