Kyoung Heo

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Diffusion tensor MRI visualizes decreased subcortical fiber connectivity in focal cortical dysplasia

Diffusion tensor imaging (DTI) was applied to 12 patients with focal cortical dysplasia (FCD) in frontal or occipital cortex. Fiber tractography was obtained from seeding points in superior longitudinal fasciculus or posterior corona radiata. Mean fractional anisotropy of fiber bundles around the affected cortex was decreased in comparison to the contralateral hemisphere with statistical significance (paired t test, P = 0.0274). On visual analysis, tractography depicted decreased volume of fiber bundles connected to the dysplastic cortex invariably even in those with a normal T2 signal intensity of underlying white matter adjacent to FCD. DTI has high potential to be applied to localize the FCD and to provide a better understanding of the pathological changes in the white matter.

Antiepileptic Drug Withdrawal after Successful Surgery for Intractable Temporal Lobe Epilepsy

Summary:  Purpose: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy.

Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice

Although minocycline has been generally thought to have neuroprotective properties, the neuroprotective role of minocycline has not been investigated in the animal model of epilepsy. In this study, we investigated whether minocycline is neuroprotective against kainic acid (KA)-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Adult male ICR mice were subjected to seizures by intrahippocampal KA injection with vehicle or with minocycline. For cell death analysis, TdT-mediated dUTP-biotin nick end labeling and cresyl-violet staining were performed. Western blot analysis and immunofluorescent staining for cytochrome c and apoptosis-inducing factor (AIF) were performed. Cell death was reduced in minocycline-treated mice. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were diminished by minocycline treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also reduced in minocycline-treated mice. Thus, this study suggests that minocycline inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage after KA treatment.

A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy.

Objectives Multidrug resistance protein 2 (MRP2, ABCC2) is involved in the transport of antiepileptic drugs and is upregulated in the brain tissues of patients with epilepsy. Therefore, genetic variations in the MRP2 gene may affect individual drug responses to the antiepileptic agent carbamazepine. Methods Associations between MRP2 polymorphisms and the adverse drug reactions (ADRs) of carbamazepine were analyzed using an integrated population genetics and molecular functional approach. In the initial case–control study, five tag single nucleotide polymorphisms in the MRP2 gene were analyzed in 146 patients with epilepsy. Patients were divided into two groups: those who experienced ADRs of the central nervous system and those who did not. An independent replication study was performed using DNA samples from 279 patients. Results A nonsynonymous polymorphism, c.1249G>A (p.V417I, rs2273697), showed a strong association with the neurological ADR caused by carbamazepine (P=0.005). Logistic regression analysis with multiple clinical variables indicated that the presence of A allele at the MRP2 c.1249G>A locus was an independent determinant of central nervous system ADR caused by carbamazepine. Moreover, the positive association of c.1249A was reproduced in the replication study (P=0.042, joint P value of the replication=0.001). The functional study using ATPase assay and FACScan flow cytometer indicated that carbamazepine was a substrate of MRP2 and that the 417I variation selectively reduced carbamazepine transport across the cell membrane. Conclusion These results strongly suggest that the A-allele of the MRP2 single nucleotide polymorphism c.1247G>A is associated with adverse neurological drug reactions to carbamazepine.

The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy.

Purpose:  To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy.

Post-transfusion posterior leukoencephalopathy with cytotoxic and vasogenic edema precipitated by vasospasm.

Introduction The syndrome of posterior leukoencephalopathy (PLE) is characterized clinically by headache, vomiting, confusion, seizures, visual abnormalities, and motor signs in association with mainly posterior lesions, which suggest edema on neuroimages [1]. PLE has often been associated with various, usually systemic disorders, such as hypertensive encephalopathy, eclampsia, and the use of immunosuppressive drugs. Ito et al. [2] reported upon a patient with transfusion-related reversible PLE and angiographic evidence of vasoconstriction. It is not certain whether the mechanism of edema formation in PLE is disruption of the blood-brain barrier and fluid extravasation, or an ischemic process induced by vasospasm. Diffusion-weighted magnetic resonance imaging (DWI) can discriminate between cytotoxic and vasogenic edema and provides a clue to the mechanism of PLE [3–6]. We describe a patient with post-transfusion PLE who showed vasospasm and features suggesting cytotoxic and vasogenic edema on DWI.

Relationship between bilateral temporal hypometabolism and EEG findings for mesial temporal lobe epilepsy : Analysis of 18F-FDG PET using SPM

PURPOSE To investigate the clinical significance of bilateral temporal hypometabolism (BTH) for patients with mesial temporal lobe epilepsy (MTLE) by using statistical parametric mapping (SPM). METHODS Interictal 18F-FDG PET scans were performed for 29 patients with surgically treated MTLE. Clinical data, interictal epileptiform discharges (IEDs), ictal scalp EEG and intracarotid amobarbital test (IAT) were analyzed. To assess an 18F-FDG PET image, an SPM analysis as well as visual interpretation were applied. RESULTS In 9 of 29 patients, the 18F-FDG PET scan revealed BTH by the SPM analysis, while only 3 patients showed BTH by the visual assessment. When the patients were classified into the unilateral temporal hypometabolism (UTH) and BTH groups based on the SPM results, bitemporal IEDs occurred significantly more frequently in the BTH group than in the UTH group (66.7% versus 22.2%). Bilateral independent seizure onset seen on the scalp EEG and bitemporal epilepsy were present only in the BTH group. Lateralized ictal onset was present less frequently in the BTH group than in the UTH group (44.4% versus 83.3%). There was no statistically significant difference in age at onset, duration of epilepsy, generalized seizure, history of febrile convulsion and CNS infection, lateralization throughout the whole tracing, lateralization on the IAT test, and surgical outcome between the UTH and BTH groups. CONCLUSION Bilaterality of the EEG findings correlated with BTH on 18F-FDG PET by the SPM method. Our results suggest that analysis of 18F-FDG PET by using SPM may have a role in predicting those patients with bitemporal excitability or bitemporal independent epileptogenicity, and these patients should be monitored carefully.

Pregabalin add-on therapy using a flexible, optimized dose schedule in refractory partial epilepsies: a double-blind, randomized, placebo-controlled, multicenter trial.

Purpose:  To evaluate the efficacy and safety of pregabalin (PGB) as adjunctive therapy, using a flexible‐dosing schedule in Korean patients with refractory partial‐onset seizures.

Patient awareness of complex partial seizures

Summary:  Purpose: To assess self‐awareness of complex partial seizures (CPSs) in unselected epilepsy patients through a thorough interview.