Epileptogenesis in Sturge-Weber syndrome

Sturge-Weber syndrome(SWS)is a sporadic congenital neurocutaneous disorder characterized by facial port-wine stain,glaucoma and leptomeningeal angioma.It is hypothesized that somatic mutation in GNAQ(p.R183Q),which is associated with the disruption of vascular development,may be a possible mechanism of SWS.The neurological course of this disease may be progressive,and its major morbidity includes epilepsy,stroke-like episodes and intellectual retardation.The earlier the time point of the mutation,the severer the disease presents itself later in life.However,the relationship between SWS and epileptogenesis is still unknown.

Bipolar electrocoagulation on functional cortex(BCFC)for intractable epilepsy involving eloquent cortex:a review

Twenty percent to forty percent of patients with epilepsy are medically refractory.For these patients,epilepsy surgeries such as resecting the epileptogenic focus may provide an alternative option.However,when the epileptogenic focus is located in the eloquent cortex,the resection of epileptogenic focus may lead to unacceptable functional deficits.Bipolar electrocoagulation on functional cortex(BCFC)is a surgical technique that holds the same principles with multiple subpial transections(MST)and aims to benefit patients with epilepsy whose epileptogenic zone is located in the eloquent cortex.It uses thermal injury to interrupt the horizontal fibers in the cortex while mechanical injury is used in MST.Here,we reviewed the rationale,surgical procedure,laboratory research,and clinical application of BCFC.We also discussed the ongoing challenges of BCFC.

Predictors of perioperative complications after surgical intervention of Sturge-Weber syndrome

Objective:lobectomy is an effective therapy for patients with Sturge-Weber syndrome(SWS).Perioperative complications often play a critical role for SWS patients’rehabilitation.This study aimed to explore and the factors of perioperative complications in SWS patients.Methods:we reviewed retrospectively the clinical profile of totally 60 SWS patients who received surgically treatments in Sanbo Brain Hospital,Capital Medical University,from March 2009 to April 2018.Univariate analyses were used to identify the potential predictors of perioperative complications.Results:the average hospitalization time of 60 patients was(35.57±10.79)d.After surgery,54(90.00%)patients reached Engle I level.The most common postoperative complications were fever(83.33%),motor function damage(38.33%)and hyponatremia(55.00%).Univariate analyses revealed that mental retardation,seizure types and surgery types could be the predictive factors for postoperative complications.Conclusion:postoperative complications are common in SWS patients.Prediction of the severity can help doctors know what kind of special care SWS patients need to help them for further rehabilitation.

Local field potentials,spiking activity,and receptive fields in human visual cortex

The concept of receptive field(RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals,while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials(LFPs) and spiking activity in human visual cortex(V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from lowfrequency activity(LFA, 0.5–30 Hz) were larger than those estimated from low-gamma activity(LGA, 30–60 Hz) and high-gamma activity(HGA, 60–150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.

Consensus on pediatric epilepsy Che up surgery for young children:an investigation by the China Association Against Epilepsy task force on epilepsy surgery

Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors,particularly in the population of young children.To standardize the protocols of preoperative evaluation and sur-gery of young children for epilepsy surgery,the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients.It adopted the modifed Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists,epileptologists,pediatric epilepsy surgeons,and functional neurosurgeons.The survey contents contained:(1)the participants,comprising children aged≤6 years;(2)adopted DRE definition proposed by the International League Against Epilepsy in 2010;and(3)investigated epilepsy surgery,principally referring to curative epilepsy surgeries.The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries.According to the Delphi process,a con-sensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment,sur-gical strategies and techniques,and perioperative and long-term postoperative management,despite controversial opinions on certain items.We hope the results of this consensus will improve the level of surgical treatment and man-agement of intractable epilepsy in young children.

Expression of human cytomegalovirus components in the brain tissues of patients with Rasmussen＇s encephalitis

Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger for RE. However, no viral antigens have been detected in the brains of patients with RE; thus, a possible clinical linkage between viral infections and RE has not been firmly established. In this study, we evaluated the expression of HCMV pp65 antigen in brain sections from 26 patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associations between HCMV infection and clinical parameters.Elevated expression of HCMV pp65 protein and DNA was observed in 88.5%(23/26) and 69.2%(18/26) of RE cases, respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity of HCMV pp65 staining was correlated with a shorter duration of the prodromal stage, younger age of seizure onset, and more severe unilateral cortical atrophy. Elevated expression of HCMV pp65 was observed in RE brain tissue and was correlated with the clinical features of RE disease. In summary, our results suggested that HCMV infection may be involved in the occurrence and progression of RE disease. Thus, further studies are needed to determine whether early treatment with anti-HCMV antibodies could modulate the course of RE.

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen's Encephalitis

Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis,intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8?T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8?T cells are involved in the pathogenesis of RE.

Laminar Distribution of Neurochemically-Identified Interneurons and Cellular Co-expression of Molecular Markers in Epileptic Human Cortex

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy,schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity,interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the coexpression of molecular markers in epileptic human cortex.We found that parvalbumin(PV) and somatostatin(SST)neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase(TH) and neuropeptide Y(NPY) were abundant in the deep layers and white matter.Cholecystokinin(CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted*7.2%(PV), 2.6%(SST), 0.5%(TH), 0.5%(NPY), and4.4%(CCK) of the gray-matter neuron population. Doubleand triple-labeling revealed that NPY neurons were also SST-immunoreactive(97.7%), and TH neurons were more likely to express SST(34.2%) than PV(14.6%). A subpopulation of CCK neurons(28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.

Elevated expression of EBV and TLRs in the brain is associated with Rasmussen's encephalitis

Rasmussen's encephalitis(RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus(EBV) antigens as well as of Toll-like receptor 3(TLR3), TLR9, and downstream adapter TIRdomain-containing adapter-inducing interferon-β(TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry(IHC). In the RE group, EBV antigens were detected in 53% of individuals at various expression levels. In contrast, there was no detectable EBV antigen expression in control brain tissues. Moreover, we found marked increases in the expression of TLR3, TLR9, and TRIF in the brain tissues of RE patients compared with levels in the control group. Furthermore, among RE cases, EBV expression and high TLR3 expression were associated with more severe brain atrophy. Our results suggest that the elevated expression of EBV and TLRs may be involved in RE occurrence through the activation of downstream molecules.