Sleep deprivation increases the risk of recurrent seizures in epileptic patients. We identified 10 patients with recurrent seizures and sleep disruption related to obstructive sleep apnoea. Two patients were treated with positional therapy and the remaining eight patients were treated with continuous positive airway pressure. Three of the patients became seizure free and a fourth patient had a greater than 95% reduction in seizure frequency following only the initiation of therapy for the sleep apnoea. Three of these four patients responding to therapy, had a state-dependent seizure pattern. Two of the four responders did not exhibit the typical body habitus for obstructive sleep apnoea. Three additional patients improved in seizure frequency with change in anticonvulsant medication and treatment of the obstructive sleep apnoea. The remaining three patients had less than 50% reduction in seizure frequency with treatment of the obstructive sleep apnoea. These results indicate sleep disruption caused by sleep apnoea may increase the seizure frequency in some epileptic patients. Regardless of body habitus, epilepsy patients should be questioned carefully for a history of sleep disturbance and state dependence to their seizures. Treatment of sleep disorders in this population may lower the frequency of recurrent seizures.
ObjectiveTo evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy.MethodsThis historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16–70 years on stable doses of 1–2 antiepileptic drugs (AEDs) and experiencing 2–40 partial-onset seizures per 28 days during the 8-week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment was the Kaplan-Meier–predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%).ResultsFour hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥1 exit criterion; the Kaplan-Meier–predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6–35.5%) was lower than the historical control. When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8–37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity. Seventy-two patients (16.9%) discontinued due to TEAEs. Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.SignificanceLacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy.
This systematic review supports the extrapolation of efficacy results in adults to predict a similar adjunctive treatment response in 2- to 18-year-old children with POS.
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