Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil‐ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer‐blinded, parallel‐group clinical trial with VPA or TPM given as first‐line add‐on therapy to steady‐state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25‐mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline‐to‐end point comparisons, one test measuring short‐term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline‐to‐titration comparisons also show one statistically significant difference, again for a test measuring short‐term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).

Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.

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Summary:Purpose: Univerricht-Lundborg disease (ULD), with its major symptom of action myoclonus, is supposed to be very rare in the Netherlands and western Europe. We hypothesized that the syndrome may be underdiagnosed in patients with myoclonus epilepsy.Methods: Mutation analysis of the cystatin B gene was performed in 21 cases with uncontrolled myoclonus.Results: Seven of the 21 evaluated cases carried mutations in the cystatin B gene. Diagnosis of ULD was made with a mean delay of 20 years from symptom onset.Conclusions: This study from a country without previous reports of ULD suggests that underdiagnosis of the syndrome is likely. These findings also indicate that persons with juvenile-onset myoclonus epilepsy with action myoclonus should be analyzed for ULD.

Background and purpose: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial. Methods: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events. Results: After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04-3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88-2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed. Discussion: In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life.