Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: Systematic review and meta-analysis.

Epilepsia. 2012 Jan 13;

Authors: Beyenburg S, Stavem K, Schmidt D

Abstract
Purpose:? Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme-inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme-inducing AEDs. This is currently unclear. Methods:? Therefore, we performed a meta-analysis of the evidence to determine the placebo-corrected efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs versus modern enzyme-inducing AEDs that are on the market for refractory focal epilepsy. Key Findings:? Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled-risk ratio (RR) in favor of enzyme-inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77-3.18, p?<?0.001) for at least 50% seizure reduction and 4.45 (2.26-8.76, p?<?0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme-inducing AEDs over placebo was 2.28 (95% CI 2.03-2.57, p?<?0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23-4.67, p?<?0.001) for seizure freedom. In a meta-regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme-inducing AEDs (eight studies) versus nonenzyme-inducing AEDs (29 studies) was 1.01 (95% CI 0.77-1.34, p?=?0.92)). Similarly, the ratio of RRs for a seizure-free outcome for enzyme-inducing AEDs (six studies) versus nonenzyme-inducing AEDs (19 studies) was 1.38 (95% CI 0.60-3.16, p?=?0.43). Significance:? Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs is similar to that of enzyme-inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme-inducing AEDs may be useful alternatives to enzyme-inducing AEDs for treatment of refractory focal epilepsy.

PMID: 22242805 [PubMed - as supplied by publisher]

Attention-deficit/hyperactivity disorder in childhood epilepsy: A neuropsychological and functional imaging study.

Epilepsia. 2012 Feb;53(2):325-333

Authors: Bechtel N, Kobel M, Penner IK, Specht K, Klarhöfer M, Scheffler K, Opwis K, Schmitt-Mechelke T, Capone A, Weber P

Abstract
Purpose:? Children with epilepsy have a significant risk for attention-deficit/hyperactivity disorder (ADHD), which is often accompanied by deficits in working memory performance. However, it is not yet clear whether there are specific differences in the underlying mechanisms of working memory capability between children with epilepsy-related ADHD and those with developmental ADHD. There is evidence that methylphenidate can improve the behavioral difficulties in children with developmental ADHD. Whether this medication has the same effect on ADHD symptoms in patients with epilepsy is not yet well understood. The aim of the present study is, therefore, to evaluate whether boys with epilepsy-related ADHD and developmental ADHD share a common behavioral, pharmacoresponsive, and neurofunctional pathophysiology. Methods:? Seventeen boys with diagnosed combined epilepsy/ADHD, 15 boys with developmental ADHD, and 15 healthy controls (aged 8-14?years) performed on working memory tasks (N-back) while brain activation was recorded using functional magnetic resonance imaging. Each patient was tested twice: once after the intake of methylphenidate and once without in a counterbalanced order. Key Findings:? On a behavioral level, we show that boys with epilepsy-related ADHD as well as those with developmental ADHD performed similarly poorly on tasks with high cognitive load when compared to healthy controls, and that intake of methylphenidate improved performance almost to normal levels in both ADHD groups. On the functional level, both patient groups showed similar reductions of activation in all relevant parts of the functional network of working memory when compared to controls. Of interest, intake of methylphenidate did not significantly alter this activity pattern. Significance:? Our data show strong similarities between epilepsy-related and developmental ADHD on the behavioral, pharmacoresponsive, and neural level, favoring the view that ADHD with and without epilepsy shares a common underlying neurobehavioral pathophysiology.

PMID: 22242637 [PubMed - as supplied by publisher]

Mitochondrial function and pathology in status epilepticus.

Epilepsia. 2011 Oct;52 Suppl 8:6-7

Authors: Bindoff LA

Abstract
The mitochondrial respiratory chain is the final common pathway for energy production. Defects affecting this pathway can give rise to disease that presents at any age and affects any tissue. However, irrespective of genetic defect, epilepsy is common and there is a significant risk of status epilepticus. We have studied two types of mitochondrial disease: one arising from a defect in mitochondrial DNA (mtDNA) (MELAS) and one due to a nuclear gene mutation (POLG). These two disorders show similarities in their clinicopathologic evolution and in findings in postmortem samples. Our findings based on antemortem magnetic resonance imaging (MRI) and postmortem studies suggest that the status epilepticus that is seen in both appears to be the result of cortical damage resulting from a common mechanism, namely energy failure.

PMID: 21967349 [PubMed - in process]

Comparison of Three Methods for Localizing Interictal Epileptiform Discharges With Magnetoencephalography.

J Clin Neurophysiol. 2011 Oct;28(5):431-440

Authors: Shiraishi H, Ahlfors SP, Stufflebeam SM, Knake S, Larsson PG, Hämäläinen MS, Takano K, Okajima M, Hatanaka K, Saitoh S, Dale AM, Halgren E

Abstract
PURPOSE: To compare three methods of localizing the source of epileptiform activity recorded with magnetoencephalography: equivalent current dipole, minimum current estimate, and dynamic statistical parametric mapping (dSPM), and to evaluate the solutions by comparison with clinical symptoms and other electrophysiological and neuroradiological findings. METHODS: Fourteen children of 3 to 15 years were studied. Magnetoencephalography was collected with a whole-head 204-channel helmet-shaped sensor array. We calculated equivalent current dipoles and made minimum current estimate and dSPM movies to estimate the cortical distribution of interictal epileptiform discharges in these patients. RESULTS: The results for four patients with localization-related epilepsy and one patient with Landau-Kleffner Syndrome were consistent among all the three analysis methods. In the rest of the patients, minimum current estimate and dSPM suggested multifocal or widespread activity; in these patients, the equivalent current dipole results were so scattered that interpretation of the results was not possible. For 9 patients with localization-related epilepsy and generalized epilepsy, the epileptiform discharges were wide spread or only slow waves, but dSPM suggested a possible propagation path of the interictal epileptiform discharges. CONCLUSION: Minimum current estimate and dSPM could identify the propagation of epileptiform activity with high temporal resolution. The results of dSPM were more stable because the solutions were less sensitive to background brain activity.

PMID: 21946369 [PubMed - as supplied by publisher]