Rasmussen's encephalitis: advances in management and patient outcomes.

PURPOSE: Rasmussen's encephalitis (RE) is a hemispheric inflammatory disorder resulting in progressive epilepsy, hemiparesis, and cognitive decline. Controversy surrounds the most effective timing of surgery with respect to language dominance, functional status, and seizure outcome. We describe our experience with RE to inform treatment decisions. METHODS: A retrospective chart review was performed in children diagnosed with RE from 1983 to 2012. RESULTS: Thirteen consecutive cases were identified: six males and seven females with a mean age of 10.6 years (range 5-18). Nine patients received immunotherapy, with transient benefit in three, treatment-associated complications in two, and no difference in their mean time to treatment (5.38 vs 6.37 years p = 0.74) or long-term outcome. Mean follow-up was 5.6 years (range 0.58-12.25). There was no difference in outcome based on pre-operative duration of seizures. At last follow-up, 63 % of surgically treated patients achieved seizure freedom, 100 % had improved seizure control, 90 % had improved cognitive function, 36 % stopped medication, and 63 % tapered medication. Language improved in 83 % of patients with dominant disease. These findings were not associated with age at treatment. All surgical patients were ambulatory at last follow-up. CONCLUSIONS: Hemispherotomy achieves good seizure control with cognitive improvement and ambulatory status post-operatively. Time to surgery and dominant disease were not associated with outcome, suggesting that hemispherotomy can be offered early or late, with expectations of good seizure control and functional outcome, even with dominant disease.

Benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is a common disorder in childhood. After a brief overview of BECTS, a review of the data in favor of treatment with anticonvulsant medications is followed by the data indicating that treatment is not indicated. Some children appear to have cognitive consequences from BECTS. The parents and children with BECTS require a full discussion of the pros and cons of treatment, but based on data available at this time, it is concluded that treatment is generally not indicated for most patients. Future research may lead to changes in the recommendations.

A Role for Diminished GABA Transporter Activity in the Cortical Discharge Phenotype of MeCP2-Deficient Mice.

Cortical network hyper-excitability is a common phenotype in mouse models lacking the transcriptional regulator methyl-CPG-binding protein 2 (MeCP2). Here, we implicate enhanced GABAB receptor activity stemming from diminished cortical expression of the GABA transporter GAT-1 in the genesis of this network hyper-excitability. We found that administering the activity-dependent GABAB receptor allosteric modulator GS-39783 to female Mecp2(+/-) mice at doses producing no effect in wild-type mice strongly potentiated their basal rates of spontaneous cortical discharge activity. Consistently, administering the GABAB receptor antagonist CGP-35348 significantly decreased basal discharge activity in these mice. Expression analysis revealed that while GABAB or extra-synaptic GABAA receptor prevalence is preserved in the MeCP2-deficient cortex, the expression of GAT-1 is significantly reduced from wild-type levels. This decrease in GAT-1 expression is consequential, as low doses of the GAT-1 inhibitor NO-711 that had no effects in wild-type mice strongly exacerbated cortical discharge activity in female Mecp2(+/-) mice. Taken together, these data indicate that the absence of MeCP2 leads to decreased cortical levels of the GAT-1 GABA transporter, which facilitates cortical network hyper-excitability in MeCP2-deficient mice by increasing the activity of cortical GABAB receptors.

Evidence that clozapine directly interacts on the GABAB receptor.

Neurophysiological studies suggest that clozapine may facilitate γ-aminobutyric acid (GABAergic) neurotransmission. Therefore, we studied the interaction between clozapine and the GABAB receptor (GABABR). We showed that clozapine, and not N-desmethylclozapine, which is a metabolite of clozapine, increased the binding of the GABABR antagonist, [³H]-CGP54626A, at GABABRs. Linear regression analysis showed that the correlation between the dose of clozapine and the increase of [³H]-CGP54626A binding was significant. The curve of specific [³H]-CGP54626A binding in competition with different concentrations of GABA was left shifted in the presence of clozapine. With HEK293 cells overexpressing GABABR, we showed that clozapine had a significant increase of [³H]-CGP54626A binding at GABABR1 subunit, which provided a clue of the potential therapeutic target of clozapine.