Pharmacological evaluation of E2730, a novel selective uncompetitive GAT1 inhibitor, on epileptiform activities in resected brain tissues from human focal cortical dysplasia ex vivo.

Focal cortical dysplasia (FCD) is an important etiology of focal epilepsy in children and adults. However, only a few preclinical models sufficiently reproduce the characteristic histopathologic features of FCD. To improve the success rate of clinical trials for antiseizure medications (ASMs) in patients with FCD, more human-relevant preclinical models are needed, and epileptic foci resected from patients are a powerful tool for this purpose. Here, we conducted ex vivo studies using epileptic foci resected from patients with FCD type II to evaluate the pharmacologic effects of the ASM candidate E2730, a selective uncompetitive inhibitor of γ-aminobutyric acid transporter 1. We used the same ex vivo assay system to assess carbamazepine (CBZ), an ASM often prescribed for focal epilepsy, as a reference. At the higher dose tested (200 µM), both E2730 and CBZ suppressed spontaneous epileptiform activities almost completely. At the lower dose (100 µM), CBZ reduced the area of brain tissue showing epileptiform activity, whereas E2730 significantly decreased the number of epileptiforms. These findings suggest that E2730-both as a single agent and in combination with CBZ-merits evaluation in clinical trials involving patients with FCD.

Importance of changes in abnormal muscle responses during microvascular decompression for hemifacial spasm.

Objective: To determine if compression sites of the facial nerve correlate with immediate postoperative outcomes in patients with hemifacial spasm (HFS), and if changes in the waveform of abnormal muscle response (AMR) during microvascular decompression (MVD) for HFS can predict the postoperative course. Methods: In this retrospective review, we evaluated 50 patients with HFS who underwent AMR monitoring during MVD. The ratios of amplitude and duration of AMR waveforms were computed by comparing baseline with final examinations. Vascular compression sites were categorized into four portions of the facial nerve. Postoperatively, we classified patients into two groups based on symptom relief as those whose symptoms disappeared immediately (DI group), and those whose symptoms disappeared gradually (DG group). Results: The compression sites significantly correlated with postoperative outcomes at discharge (p < 0.001) but not with outcomes after 6 months of MVD. Lower duration ratios of AMRs from the mentalis muscle were significantly associated with an increased chance of classification into the DI group based on the results of multivariate logistic regression analysis (p = 0.017). Conclusions: Relationship between compression sites and immediate outcomes could provide useful information to surgeons for predicting if symptoms will resolve over long term. Moreover, changes in AMRs recorded from the mentalis muscle could predict the postoperative course of HFS. Significance: These findings can help surgeons evaluate the changes in AMR amplitude and duration during MVD for HFS.

Comparison of visual outcomes between medical treatment alone and Ahmed glaucoma valve implantation in Shiba dogs with primary angle closure glaucoma.

OBJECTIVE: The objective of the study was to evaluate visual outcomes between medical treatment alone (MED) and Ahmed glaucoma valve implantation (AGVI) in Shiba dogs with primary angle closure glaucoma (PACG). PROCEDURES: Records of 65 Shiba dogs (104 eyes) with PACG were retrospectively reviewed. Vision was assessed qualitatively using both the menace response and maze testing. The significance of age, sex, intraocular pressure (IOP), and duration of clinical signs (≤72 h or >72 h) at first presentation (V1) was assessed. Eyes with vision at V1 were divided into groups according to subsequent treatment method (MED versus AGVI), and vision as a survival outcome was compared between group by the Kaplan-Meier method. RESULTS: At V1, 65 eyes (62.5%) of 54 dogs had vision. There was no statistically significant difference in age or sex on the presence of vision at V1. Median IOP was higher in blind (52 mmHg) compared to sighted eyes (28 mmHg) (p < .001). Eyes presenting in ≤72 h of the onset of clinical signs were more likely to have vision (86.7%) compared to those presenting after 72 h (44.1%) (p < .001). By the Kaplan-Meier analysis, the cumulative visual retention rate was significantly higher with AGVI than with MED (69.2% vs. 7.7%; p < .01) at 12 months. The median time to visual loss was 39.9 months with AGVI vs. 1.7 months with MED. CONCLUSIONS: AGVI resulted in better visual outcomes than MED and should be considered in Shiba dogs with PACG that are visual at the time of presentation and suitable for surgery.