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).
We studied 94 consecutive patients (age 15 or over) to investigate which aspects of the history and clinical findings help to distinguish seizures from syncope and related conditions. Clonic movements or automatism observed by an eyewitness classified an event as a seizure. The seizure group consisted of 41 patients and the syncope group of 53 patients. The likelihood ratio was used to calculate the predictive power of single findings and logistic regression to analyse combinations of findings. The best discriminatory finding was orientation immediately after the event according to the eyewitness and the age of the patient in the absence of an eyewitness report (P less than 0.001). We found a seizure five times more likely than syncope if the patient was disoriented after the event and three times more likely if the patient was less than 45 years of age. Nausea or sweating before the event were useful to exclude a seizure. Incontinence and trauma were not discriminative findings.
Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photosensitivity after lamotrigine administration. Five subjects with frequent interictal spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half-life (t1/2) of lamotrigine in subjects taking sodium valproate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co-medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.
Cognitive impairment is regarded as the link between epileptic conditions and the inability to learn in school. The neuropsychological approach to learning disabilities in epilepsy, therefore, first concentrates on analyzing the differential effects of epileptic factors on cognitive function. The impact of seizure activity, localization of epileptogenic foci, and antiepileptic treatment on cognitive functioning can be evaluated based upon the results of continuous assessment with a computerized neuropsychological test system. Second, learning disabilities may be evaluated on observations made during classroom performance. Three issues seem to predominate in learning studies among disabled children with epilepsy: test-retest variability, deterioration, and the supposed specificity of the learning disabilities.
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