A novel epigenetic marker, Ten-eleven translocation family member 2 (TET2), is identified in the intractable epileptic brain and regulates ATP binding cassette subfamily B member 1 (ABCB1) in the blood-brain barrier.

Drug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Here, we quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain hemorrhage controls (n = 10) by immunochemical staining. TET2 and ATP binding cassette subfamily B member 1 (ABCB1) expression patterns were determined in the isolated brain capillaries of DRE patients. TET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed no differences in expression. We also found that a particularly strong expression of TET2 in the vascular tissue of DRE patients. ABCB1 and TET2 have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In blood-brain barrier (BBB) model, TET2 depletion can cause attenuated expression and function of ABCB1. Data from a cohort study and experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE.

Association of xenobiotic receptor polymorphisms with carbamazepine response in epilepsy patients.

PURPOSE: Drug-resistant epilepsy is a problem worldwide. Xenobiotic receptors may play a significant role in the establishment of resistance to antiepileptic agents. Previous studies have confirmed that the metabolism and efficacy of carbamazepine (CBZ) can be influenced by xenobiotic receptors, especially pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AHR). Therefore, this study intends to elucidate the pharmacogenomic associations of polymorphisms of these xenobiotic receptors with the CBZ response in epilepsy patients, and these genetic data may be useful for the treatment of clinical prophylaxis and individualized treatment of intractable epilepsy. METHODS: Adult patients with epilepsy who were on CBZ-based monotherapy and combination therapy (n = 257) were genotyped, and the patients were divided into drug-responsive and drug-resistant groups according to the International League Against Epilepsy criteria. We sought to tag single-nucleotide polymorphisms (SNPs) of PXR, CAR and AHR that principally represent alleles associated with drug resistance risk; in addition, a gene interaction analysis reference panel was constructed for SNP-based imputation. RESULTS: No significant effects of PXR or AHR polymorphisms were observed. However, an interaction between the CAR rs2502815 variant and CBZ response was observed: in CBZ-based monotherapy and combination therapy patients, the GG genotype of the CAR rs2502815 variant (vs. wild-type homozygous) was independently associated with CBZ response after adjusting for variables [odds ratio (OR) = 0.389, 95% confidence interval (CI) 0.203-0.743, p = 0.004]. The results of the haplotype and gene interaction case-control analyses of the CBZ response were negative. Our results provide clinical data regarding the genetic possibilities of drug responses related to CAR variation in epilepsy patients. CONCLUSION: This study is the first to indicate a potentially relevant interaction between the CAR rs2502815 polymorphism and the CBZ response in epilepsy patients.

Diagnosis and surgical treatment of non-lesional temporal lobe epilepsy with unilateral amygdala enlargement.

OBJECTIVE: Exploring the role of amygdala enlargement (AE) in temporal lobe epilepsy (TLE) without ipsilateral mesial temporal sclerosis (MTS) using comprehensive presurgical workup tools including traditional tools, automatically volumetric analysis, high-density EEG (HD-EEG) source imaging (HD-ESI), and stereoelectroencephalography (SEEG). METHODS: Nine patients diagnosed with TLE-AE who underwent resective surgeries encompassing the amygdala were retrospectively studied. HD-ESI was obtained using 256-channel HD-EEG on the individualized head model. For automatic volumetric analysis, 48 matched controls were enrolled. Diagnosis and surgical strategies were based on a comprehensive workup following the anatomo-electro-clinical principle. RESULTS: At post-operative follow-up (average 30.9 months), eight patients had achieved Engel class I and one Engel class II recovery. HD-ESI yielded unifocal source estimates in anterior mesial temporal region in 85.7% of cases. Automatic volumetric analysis showed the AE sides were consistent with the values determined through other preoperative workup tools. Furthermore, the amygdala volume of the affected sides in AE was significantly greater than that of the larger sides in controls (p < 0.001). Meanwhile, the amygdala volume lateral index (LI) of AE was significantly higher than in controls (p < 0.001). SEEG analysis showed that ictal onsets arose from the enlarged amygdala (and hippocampus) in all cases. CONCLUSION: In addition to traditional workup tools, automatic volumetric analysis, HD-ESI on individualized head model, and invasive SEEG can provide evidence of epileptogenicity in TLE-AE. Resective surgical strategies encompassing the amygdala result in better prognosis. In suspected TLE cases, more attention should be focused on detecting enlargement of amygdala which sometimes is "hidden" in "MR-negative" non-MTS cases.

Urinary incontinence following deep brain stimulation of the globus pallidus internus: case report.

Deep brain stimulation (DBS) is a well-established therapy for patients with advanced Parkinson's disease (PD), dystonia, and other movement disorders. In contrast to the strong positive effects that have been documented for motor symptoms, the effects of DBS on nonmotor symptoms have not been fully elucidated. Some reports suggest that stimulation of the subthalamic nucleus may improve lower urinary tract symptoms in patients with PD; however, reports of the effects of globus pallidus internus (GPi) DBS on urinary symptoms are limited. The authors present the case of a 49-year-old woman with PD who developed severe urinary incontinence after 27 months of GPi DBS. The urinary incontinence disappeared when stimulation was turned off, and reemerged after it was turned on again. After activation of a more dorsal contact in the left electrode, the patient's urinary dynamics returned to normal.

Predictors to quality of life improvements after subthalamic stimulation in Parkinson's disease.

INTRODUCTION: Subthalamic deep brain stimulation (STN DBS) has been reported to improve the quality of life (QoL) related to Parkinson's disease (PD). However, not all subjects are satisfied with the postsurgical QoL outcome. We aimed to detect the related factors and possible predictors to QoL improvement for those PD patients one year after STN DBS. MATERIALS AND METHODS: A total of 45 PD patients with bilateral STN DBS surgery were included and followed up for 1 year. The Reliable Change Index (RCI) was adapted to determine the individual postsurgical QoL outcome. The changes of QoL were correlated with baseline parameters and the changes of progression parameters using Pearson's correlation. The exploratory stepwise regressions were adopted to detect the extents of baseline variables and progression parameters. The predictors to QoL outcome were detected using the logistic regression analysis. RESULTS: A total of 51.1% of the patients reported a better QoL, 40.0% of patients reported an unchanged QoL, while 8.9% of patients reported a worsening of QoL. The subdomains of mobility, activity of daily living, cognition, and bodily discomfort improved significantly after the surgery. The presurgical factors including QoL, dopaminergic medication burden, disease stages, depression scores, and postsurgical reductions in depression and nonmotor scores were found to correlate with QoL changes. Furthermore, the greater presurgical QoL burden, lesser dopaminergic medication exposure, and earlier disease stages were predictors to QoL improvements. CONCLUSION: The clinicians should carefully evaluate the nonmotor symptoms and life quality in those patients at relatively earlier stages and with lower medicine dosage to get more successful DBS outcomes.

[Prospective comparison of functional magnetic resonance imaging and intraoperative motor evoked potential monitoring for cortical mapping of primary motor areas].

OBJECTIVE: To compare the relation between the preoperative functional magnetic resonance imaging (fMRI) with blood oxygen level dependent (BOLD) technique and intraoperative motor evoked potential (MEP) monitoring for cortical mapping of primary motor cortex in patients with tumors near the central area. And to determine whether non-invasive preoperative fMRI can provide results equivalent to those achieved with the invasive neurosurgical "gold standard". METHODS: A prospective study of 16 patients with various pathological tumors of the central area was conducted. Preoperative fMRI scans using the BOLD contrast technique in each patient were performed. An activation scan was achieved by using a motor task paradigm, which consisted of simple flexion-extension finger movements and finger-to-thumb touching in a repeating pattern. The anatomical structure was delineated by the T(1)-weighted three-dimensional fast spoiled gradient recalled sequence (3D/FSPGR) immediately afterward. The BOLD images were overlaid on the T(1)-weighted 3D/FSPGR images, and then co-registered to the neuronavigation system. The fMRI activations were documented by using a neuronavigation system in sequence, and compared to standardized intraoperative MEP monitoring, which included direct cortical electrical stimulation (DCES) or transcranial cortical electrical stimulation (TCES) or their combination. The compound muscle action potentials of forearm flexor and hand muscle responses were recorded during either TCES or DCES. Two techniques were compared to determine the accuracy for cortical mapping of primary motor areas with fMRI. RESULTS: Overall, the intraoperative MEP monitoring showed good correlation with fMRI activation in 92.3% of cases. The coincidence rate, however, was 100.0% between TCES and fMRI, and 66.7% between DCES and fMRI respectively. There was no statistically difference between two cortical mapping techniques, chi-square test of paired comparison of enumeration data, P < 0.01. CONCLUSION: BOLD fMRI was a high sensitive and reliable technique to locate the position of the primary motor areas and their spatial relation with adjacent tumor, especially for the presurgical planning in patients with central area brain tumor.