Xin-Tong Wu

Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502 allele in Chinese Han population

BACKGROUND Recent study demonstrated that HLA-B*1502 was a common risk allele in aromatic antiepileptic drugs (AEDs) induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. However, the association of AEDs-induced mild maculopapular eruption (MPE) with HLA-B*1502 remains unclear until recently. In the present study, we conducted a pilot study to detect a possible association of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han population. METHODS We enrolled 90 subjects involving 9 patients with OXC-induced MPE and two groups of controls, 9 OXC-tolerant and 72 normal controls. High-resolution HLA genotyping was performed by specific kit. The results of HLA genotyping are expressed as positive or negative for HLA-B*1502 allele. Differences in genotype frequencies between groups were assessed by the Fishers exact test. RESULTS Four cases were detected as positive for HLA-B*1502 amongst 9 patients. However, only 1 subject was positive amongst 9 tolerant controls, and 6 subjects were positive amongst 72 normal controls. The difference in HLA-B*1502 allele frequencies between the MPE group and normal controls was statistically significant (OR: 8.8; 95% CI: 1.853-41.790; P=0.011). In addition, we also observed an increased frequency of HLA-B*1502 allele in patients (44.44%) compared with tolerant controls (11.11%), although it failed to reach statistical significance (P=0.294). CONCLUSIONS Our findings indicate that HLA-B*1502 allele may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han population. In order to safer AEDs use, we recommend that HLA-B*1502 allele should be tested for patients with OXC-induced MPE before changing to other AEDs, and AEDs with similar chemical structure should be avoided in individuals who test positive for HLA-B*1502 allele. It should be pointed out that, however, our results may well be just by chance owing to the small sample size and should be further confirmed in future studies.

Economic burden of epilepsy in a developing country: a retrospective cost analysis in China.

Purpose:  To study the cost of epilepsy in China, and, therefore, provide essential information on the burden of the disease to individuals and society.

Resting-state fMRI study of treatment-naïve temporal lobe epilepsy patients with depressive symptoms.

BACKGROUND Patients with temporal lobe epilepsy are at high risk for comorbid depression, and it is hypothesized that these two diseases are share common pathogenic pathways. We aimed to characterize regional brain activation in treatment-naïve temporal lobe epilepsy patients with depressive symptoms and compare the results to epilepsy patients without depressive symptoms and to healthy controls. SUBJECTS AND METHODS We recruited 23 treatment-naïve patients (including anti-epilepsy drugs (AEDs) and antidepressants) and 17 matched healthy controls for this study. The patients were further divided into two groups: patients with depressive symptoms and patients without; the patients then used a self-rating depression scale (SDS) to assess their depression. All participants underwent resting functional magnetic resonance imaging (fMRI) scans using the Trio Tim magnetic resonance (MR) image system (3.0 T). The data were processed and analyzed using REST and SPSS11.5 software. RESULTS The patients with depressive symptoms showed significantly higher activity in the bilateral thalamus, insula and caudate and right anterior cingulate compared with the two other groups (p<0.05, corrected). Brain network connectivity analysis revealed that connectivity decreased in the prefrontal-limbic system and increased within the limbic system and angular gyrus in patients with depressive symptoms (p<0.05, corrected). CONCLUSION The epilepsy patients with depressive symptoms showed regional brain activity alterations and disruption of the mood regulation network at the onset of seizures. The present study offers further insight into the underlying neuropathophysiology of epilepsy with depressive symptoms.

Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese

The aims of this study were to clarify the possible associations of carbamazepine (CBZ)- and lamotrigine (LTG)-induced maculopapular exanthema (MPE) with the human leukocyte antigen (HLA) alleles in Chinese patients. A total of 249 subjects, including 40 patients with CBZ-induced MPE (CBZ-MPE), 43 patients with LTG-induced MPE (LTG-MPE), 52 CBZ-tolerant controls, 42 LTG-tolerant controls and 72 healthy controls, were included in this study. High-resolution HLA genotyping was performed by a specific kit. Differences in the allele frequencies among the groups were assessed. The allele frequencies of HLA-A*0201 and HLA-DRB1*1405 were significantly higher (P=0.033 and P=0.003, respectively), but those of HLA-B*5801 and HLA-DRB1*0301 (P=0.037 and P=0.024, respectively) were lower in the CBZ-MPE patients when compared with the CBZ-tolerant group. We also observed two significantly increased alleles of HLA-A*3001 and HLA-B*1302 (P=0.013 and P=0.013, respectively) and a decreased allele of HLA-A*3303 (P=0.048) in the LTG-MPE patients when compared with those in the LTG-tolerant group. Our results support the hypothesis that these HLA alleles contribute to the genetic susceptibility to CBZ/LTG-MPE and may be valuable as potential biomarkers for CBZ/LTG-MPE in Han Chinese.

Real-time effects of centrotemporal spikes on cognition in rolandic epilepsy: An EEG-fMRI study

Objective: To identify the real-time effects of interictal rolandic spikes (or centrotemporal spikes [CTS]) on language, behavior, and cognitive function in patients with rolandic epilepsy (RE). Methods: We studied 22 medication-naive patients with RE using EEG-fMRI with a 3T MRI scanner. We used simultaneous EEG to define the pre-CTS, CTS, and post-CTS periods. We analyzed the dynamic functional connectivity maps of the rolandic network during the 3 interictal CTS periods. Results: The analysis of dynamic changes revealed positive correlations between the bilateral rolandic areas and the left inferior frontal gyrus (IFG; Broca area), the left inferior parietal lobe and the supramarginal gyrus (areas responsible for receptive language function), and the right IFG and left caudate. Anti-correlations were found in the default mode network (bilateral superior frontal gyrus, left middle frontal gyrus, left middle temporal gyrus, and right precuneus). Conclusions: Interictal CTS directly disrupts the functional brain networks responsible for language, behavior, and cognition in children with typical RE. It is important to suppress discharges to reduce the risk of neuropsychological impairments in children with RE.

Interictal magnetoencephalography used in magnetic resonance imaging-negative patients with epilepsy.

This study aims to investigate the contributions of magnetoencephalography (MEG) in magnetic resonance imaging (MRI)‐negative patients.

MEG in frontal lobe epilepsies: Localization and postoperative outcome

Purpose:  This study aimed to analyze magnetoencephalography (MEG) localizations of epileptic clusters in different cortical regions of the frontal lobe and relate these findings to postoperative outcomes associated with frontal lobe epilepsy (FLE).

Phenytoin-induced Stevens–Johnson syndrome with negative HLA-B*1502 allele in mainland China: Two cases

Antiepileptic drugs-induced Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction. Recent studies in Thailand and Taiwan showed a significant association between phenytoin (PHT)-induced SJS and human leucocyte antigen HLA-B*1502 allele. Although the US FDA had issued an alert to clinicians, insufficient information is available to recommend testing for HLA-B*1502 in Asian patients in line for PHT treatment. Therefore, extended studies are necessary to further evaluate the potential association between PHT-induced SJS and HLA-B*1502 allele in various populations. To date, no similar data exist in mainland China. Here, we describe two Chinese Han cases of PHT-induced SJS with negative HLA-B*1502 allele, in which HLA high-resolution genotyping showed two heterozygous HLA-B*4601/B*5102 and HLA-B*3701/B*4601 allele, respectively. Our findings provide evidence to support that other genetic markers or nongenetic factors could contribute to the susceptibility of PHT-induced SJS, except for HLA-B*1502 allele. Further studies are encouraged to investigate the genetic link with PHT-induced serious skin reactions in future.

Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task

OBJECTIVE Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). METHODS Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. RESULT The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. CONCLUSION Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function.

Complementary use of video-electroencephalography and magnetoencephalography in frontal lobe epilepsy

PURPOSE The aim of this study was to compare magnetoencephalography (MEG) and video-electroencephalography (VEEG) source localization in frontal lobe epilepsy (FLE) and determine if these methods can be complementary to each other in clinical practice. METHOD Thirty patients with pharmaco-resistant FLE who underwent epilepsy surgery were retrospectively enrolled. Video EEG was recorded using an IT-med system using 10/20 system. Regional localization of spikes in VEEG was defined as spikes discharged from adjacent electrodes and no further propagation to a large and/or contralateral area. Magnetoencephalography was recorded for the purpose of focus assessment. Magnetoencephalography spikes were detected for dipole localization of the epileptogenic cortex and the epileptogenic area was classified as mono- or multi-focal. RESULTS Regional spike discharges were identified in the interictal VEEG of 20 patients and in the ictal VEEG of 17 patients. Thirteen patients had regional spikes in both interictal and ictal VEEG. Mono-focal localization was identified in the MEG of 20 patients. Fourteen of these patients had regional spike discharges in VEEG. In the remaining six patients, sources localization was only identified by MEG and there were no regional spike discharges either interictal or ictal VEEG. CONCLUSION In clinical practice, VEEG is the routine procedure in the presurgical evaluation of FLE. However, we found six cases in which VEEG failed to locate the epileptogenic area that was identified by MEG. We therefore propose that combining VEEG and MEG will optimize the noninvasive presurgical evaluation of epileptiform activities in FLE.