Is there any concern of insulin resistance and metabolic dysfunctions with antiseizure medications? A prospective comparative study of valproate vs. levetiracetam.

PURPOSE: To evaluate the incidence of insulin resistance and its association with change in serum anti-seizure medication (ASM) level and their pharmacokinetic, body composition and metabolic hormones after six months of levetiracetam (LEV) exposure in persons with epilepsy (PWE) in comparison to valproate (VPA). METHODS: This prospective-longitudinal study included clinically diagnosed PWE on VPA or LEV monotherapy (for<3 months). At enrolment, body weight/composition, BMI were measured and blood samples were collected for assessing metabolic dysfunctions by estimation of serum insulin, insulin resistance [in terms of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], leptin, adiponectin, lipid profile along with ASMs level. Subjects were followed up for six months and all the above parameters were reassessed. RESULTS: A total of 150 PWE were screened based on inclusion and exclusion criteria, and 105 number of subjects were enrolled (n = 35 in VPA and n = 70 in LEV group). Out of them, 92 subjects (n = 32 in VPA; n = 60 in LEV) completed six months follow-up. After six months, serum insulin level increased significantly in VPA group compared to baseline p < 0.001). Insulin resistance (HOMA-IR>2.5) was observed in 14.28 % of PWE in VPA group. Significantly higher percentage-change in body-weight (p = 0.003), leptin and decreased adiponectin were found in VPA-group compared to baseline ((p = 0.003, 0.02, 0.001, <0.001, respectively). These changes were independent of serum level or pharmacokinetic of VPA. On the other hand, no such changes were observed in LEV-group despite increased serum LEV level and altered pharmacokinetic parameters after six months. CONCLUSION: Six months treatment with VPA resulted in insulin resistance and metabolic dysfunctions in PWE. These alterations were not correlated with change in VPA serum level. These changes were not observed in LEV therapy suggesting its better safety profile. This may be considered while prescribing the ASM like VPA and LEV in adult patients with obesity or insulin resistance and diabetes.

Robotic-guided radiofrequency ablative disconnection of hypothalamic hamartoma.

Hypothalamic hamartomas (HHs) are benign masses, often associated with drug-refractory epilepsy (DRE). Open surgery as well as the endoscopic disconnection techniques are fraught with a high risk of morbidity and failure rates. The authors have been performing robotic-guided radiofrequency (RF) ablation for all types of HH presenting with DRE as a standard procedure at their institution. The authors have operated on 25 patients with HH using this technique over the last 8 years. This is a safe, effective, and minimally invasive technique. In this video article, the authors intend to demonstrate their technique of RF ablative disconnection under robotic guidance.

SISCOS in focal cortical dysplasia: localization and comparative analysis with MRI.

PURPOSE: This study evaluates the efficacy of SISCOS (Subtraction ictal-interictal SPECT coregistered to SPECT) in localizing the epileptogenic zone (EZ) in focal cortical dysplasia (FCD), comparing its predictive performance with MRI and post-surgical outcomes based on ILAE classification. METHODS: 84 patients with drug refractory epilepsy (DRE) who were operated and had histopathology consistent with FCD, were included in the study. All patients had undergone a complete work-up including SISCOS and MRI for EZ localization, followed by discussion in the multidisciplinary epilepsy surgery meeting prior to surgery. Ictal & interictal perfusion SPECT studies were performed with Tc-99 m Ethylene Cysteinate Dimer (Tc-99 m ECD) followed by SISCOS analysis using SPM2 and Bioimage Suite 2.6. Concordance for localization was determined by comparing with the surgical resection site and post-surgical outcomes were assessed using the ILAE classification. RESULTS: The concordance for EZ localization demonstrated by SISCOS was 73.8% and MRI was 82.1%. 52 patients (61.9%) had good surgical outcome and 31(59%) of these were FCD type 2. In patients with discordant MRI findings, SISCOS was able to provide localisation in 86% (13/15), with 69.2% showing good surgical outcomes. Sensitivity of SISCOS and MRI was 73% (95% CI = 59-84.8%) and 78% (95% CI = 67.5-90.3%) respectively with no significant difference between the two. In FCD type I, both SISCOS and MRI revealed a similar a sensitivity of 76.4% (95%CI = 50.1-93.2%). Concordant cases exhibited higher seizure-free odds ratios for both modalities. CONCLUSION: SISCOS is effective in localizing the EZ in FCD patients, comparable to MRI. Integrating SISCOS and MRI enhances lesion detection, especially in MRI discordant cases. A comprehensive diagnostic approach utilizing SISCOS and MRI can optimize the non-invasive pre-surgical assessment in DRE thereby guiding surgical decision-making in a resource-limited setting.

Unraveling the genetic basis of epilepsy: Recent advances and implications for diagnosis and treatment.

Epilepsy, affecting approximately 1% of the global population, manifests as recurring seizures and is heavily influenced by genetic factors. Recent advancements in genetic technologies have revolutionized our understanding of epilepsy's genetic landscape. Key studies, such as the discovery of mutations in ion channels (e.g., SCN1A and SCN2A), neurotransmitter receptors (e.g., GABRA1), and synaptic proteins (e.g., SYNGAP1, KCNQ2), have illuminated critical pathways underlying epilepsy susceptibility and pathogenesis. Genome-wide association studies (GWAS) have identified specific genetic variations linked to epilepsy risk, such as variants near SCN1A and PCDH7, enhancing diagnostic accuracy and enabling personalized treatment strategies. Moreover, epigenetic mechanisms, including DNA methylation (e.g., MBD5), histone modifications (e.g., HDACs), and non-coding RNAs (e.g., miR-134), play pivotal roles in altering gene expression and synaptic plasticity, contributing to epileptogenesis. These discoveries offer promising avenues for therapeutic interventions aimed at improving outcomes for epilepsy patients. Genetic testing has become essential in clinical practice, facilitating precise diagnosis and tailored management approaches based on individual genetic profiles. Furthermore, insights into epigenetic regulation suggest novel therapeutic targets for developing more effective epilepsy treatments. In summary, this review highlights significant progress in understanding the genetic and epigenetic foundations of epilepsy. By integrating findings from key studies and specifying genes involved in epigenetic modifications, we underscore the potential for advanced therapeutic strategies in this complex neurological disorder, emphasizing the importance of personalized medicine approaches in epilepsy management.

Modified Atkins Diet in Adolescents and Adults with Drug Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy is one of the common neurological diseases which affects 65-70 million people worldwide. Modified Atkins diet (MAD) as a therapy is used as one of the treatments to reduce the seizures occurrence in epileptic patients. The purpose of this purpose is to review all evidence regarding the efficacy of the MAD from randomized controlled trials (RCTs) in adolescents and adults with drug resistant epilepsy (DRE). The total of three databases were searched (PubMed, Embase, and Cochrane Library) till 31 January 2023. Only RCTs with MAD as a one of the treatment arms were included in meta-analysis. The proportion of reduction of seizures in patients with epilepsy and relative risk to identify the relationship between MAD (as risk) to decrease the epileptic seizure was used as outcomes. The Jadad score with three domains was used to estimate the quality of RCTs included for meta-analysis. Only three RCTs were included following the stringent inclusion criteria in current meta-analysis. The pooled proportion from 142 patients going through MAD therapy shows the reduction in epileptic seizure ≥50%, by the random effect model was 0.23 (95% confidence interval [CI], 0.10 to 0.37). Our meta-analysis underlines a significant efficacy of MAD compared to the control group in seizure reduction ≥50%, The pooled relative risk was 6.47 (95% CI, 1.60 to 26.14; p-value <0.05). MAD therapy was efficacious and had better compliance for seizure reduction in subjects with DRE.

Physical fitness in Indian women with epilepsy on anti-seizure medications and its association with reproductive status, quality of life and stigma: A cross-sectional study.

PURPOSE: To determine the status of physical fitness, reproductive abnormalities, QOL and epilepsy associated stigma in women with epilepsy (WWE) and their association with ASM therapy and seizure frequency. METHODS: This cross-sectional study included WWE of reproductive age (18-50 years) on antiseizure medications (ASMs) for at least three months before enrolment. Physical fitness was assessed using International Physical Activity Questionnaires (IPAQ) and Body composition analysis. Subjects were interviewed for menstrual abnormalities [menstrual disturbance or Polycystic Ovary Syndrome (PCOS)/hirsutism]. Validated questionnaires were used for assessment of, QOL (QOLIE-10) and Stigma in epilepsy (Epilepsy Stigma Scale). Sub-group analysis was done to compare the above parameters on the basis of a) type of therapy (mono or polytherapy), b) type of ASMs treatment (conventional, newer, or conventional + newer ASMs), and c) seizure type and (d) seizure frequency. Correlation and regression analysis were done to find out the association among different variables with physical fitness. RESULTS: The overall prevalence of poor physical fitness, reproductive abnormalities, worsened QOL and stigma in the enrolled WWE (n = 203) were 21.18 %, 20.19 %, 52.7 %, and 21.67 %, respectively. Sub-group analysis revealed that WWE on monotherapy (n = 99) had higher median IPAQ score (p = 0.002), comparatively less reproductive abnormalities (24.03 %, p = 0.008), and higher stigma (24.03 %, p = 0.04) than polytherapy group. WWE on conventional ASMs had significantly higher IPAQ scores compared to newer and conventional + newer ASMs groups (p = 0.02). The prevalence of poor physical fitness and stigma was significantly higher in WWE with higher number of seizures (p = 0.007, <0.001, respectively). No significant difference in QOL was observed on the basis of ASM type and therapy; however, WWE with generalized onset seizures had worsened QOL compared to those with focal onset seizures (p = 0.04). A significant negative correlation was found among seizure frequency and IPAQ score in WWE (p = 0.04). CONCLUSION: WWE on polytherapy were physically less active, higher occurrence of reproductive abnormalities, and stigma compared to the monotherapy group. WWE with higher seizure frequency had poor physical fitness, and higher stigma compared to those with lesser number of seizures. These findings may aid value in optimization of ASM treatment in WWE of reproductive age.

Role of non-receptor tyrosine kinases in epilepsy: significance and potential as therapeutic targets.

INTRODUCTION: Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatment options, which include >20 antiseizure medications. It is therefore imperative that new medications with novel targets and mechanisms of action are developed. AREAS COVERED: Clinical studies and preclinical research increasingly implicate Non-receptor tyrosine kinases (nRTKs) in the pathogenesis of epilepsy. To date, several nRTK members have been linked to processes relevant to the development of epilepsy. Therefore, in this review, we provide insight into the molecular mechanisms by which the various nRTK subfamilies can contribute to the pathogenesis of epilepsy. We further highlight the prospective use of specific nRTK inhibitors in the treatment of epilepsy deriving evidence from existing literature providing a rationale for their use as therapeutic targets. EXPERT OPINION: Specific small-molecule inhibitors of NRTKs can be employed for the targeted therapy as already seen in other diseases by examining the precise molecular pathways regulated by them contributing to the development of epilepsy. However, the evidence supporting NRTKs as therapeutic targets are limiting in nature thus, necessitating more research to fully comprehend their function in the development and propagation of seizures.

The multifaceted role of Wnt canonical signalling in neurogenesis, neuroinflammation, and hyperexcitability in mesial temporal lobe epilepsy.

Epilepsy is a neurological disorder characterised by unprovoked, repetitive seizures caused by abnormal neuronal firing. The Wnt/ß-Catenin signalling pathway is involved in seizure-induced neurogenesis, aberrant neurogenesis, neuroinflammation, and hyperexcitability associated with epileptic disorder. Wnt/ß-Catenin signalling is crucial for early brain development processes including neuronal patterning, synapse formation, and N-methyl-d-aspartate receptor (NMDAR) regulation. Disruption of molecular networks such as Wnt/ß-catenin signalling in epilepsy could offer encouraging anti-epileptogenic targets. So, with a better understanding of the canonical Wnt/-Catenin pathway, we highlight in this review the important elements of Wnt/-Catenin signalling specifically in Mesial Temporal Lobe Epilepsy (MTLE) for potential therapeutic targets.

Integrated Proteomics and Protein Co-expression Network Analysis Identifies Novel Epileptogenic Mechanism in Mesial Temporal Lobe Epilepsy.

Over 50 million people worldwide are affected by epilepsy, a common neurological disorder that has a high rate of drug resistance and diverse comorbidities such as progressive cognitive and behavioural disorders, and increased mortality from direct or indirect effects of seizures and therapies. Despite extensive research with animal models and human studies, limited insights have been gained into the mechanisms underlying seizures and epileptogenesis, which has not translated into significant reductions in drug resistance, morbidities, or mortality. To better understand the molecular signaling networks associated with seizures in MTLE patients, we analyzed the proteome of brain samples from MTLE and control cases using an integrated approach that combines mass spectrometry-based quantitative proteomics, differential expression analysis, and co-expression network analysis. Our analyses of 20 human brain tissues from MTLE patients and 20 controls showed the organization of the brain proteome into a network of 9 biologically meaningful modules of co-expressed proteins. Of these, 6 modules are positively or negatively correlated to MTLE phenotypes with hub proteins that are altered in MTLE patients. Our study is the first to employ an integrated approach of proteomics and protein co-expression network analysis to study patients with MTLE. Our findings reveal a molecular blueprint of altered protein networks in MTLE brain and highlight dysregulated pathways and processes including altered cargo transport, neurotransmitter release from synaptic vesicles, synaptic plasticity, proteostasis, RNA homeostasis, ion transport and transmembrane transport, cytoskeleton disorganization, metabolic and mitochondrial dysfunction, blood micro-particle function, extracellular matrix organization, immune response, neuroinflammation, and cell signaling. These insights into MTLE pathogenesis suggest potential new candidates for future diagnostic and therapeutic development.

Comparative Analysis of Hemispherotomy in Adults versus Children- A Prospective Observational Series.

BACKGROUND: Hemispherotomy (HS) is an effective treatment for unilateral hemispheric onset epilepsy. There are few publications for HS in adults, and there is no series comparing adults and pediatric patients of HS. OBJECTIVE: To compare the hemispherotomies done in adult patients with pediatric ones in terms of efficacy and safety. METHODS: Data was prospectively collected for HS patients (up to 18 years and more) from Aug 2014 to Aug 2018. Comparison between the groups was made for seizure onset, duration of epilepsy, frequency of seizures, number of drugs, intraoperative blood loss, postoperative seizure control, postoperative stay, postoperative motor functions, and preoperative and postoperative intelligence quotient. Follow-up was one year. RESULTS: A total of 61 pediatric and 11 adults underwent HS. The seizure onset was earlier in children, and the duration of epilepsy was longer in adults. The frequency of seizures per day was more in children being 14.62 ± 26.34 in children, and 7.71 ± 5.21 per day in adults (P - 0.49). The mean number of drugs was similar in the preoperative and postoperative periods in both. Class I seizure outcome was similar in both the groups being 85.24% in children and 90.9% in adults (P - 0.56). Blood loss, postoperative stay, was similar in both the groups. No patient had a new permanent motor deficit. Power worsened transiently in 1 pediatric patient and in 4 adult patients. The visual word reading and object naming improved in both the groups (no intergroup difference), and IQ remained the same in both groups. One adult patient had meningitis, and another had hydrocephalus requiring shunt placement. CONCLUSION: Hemispherotomy is a safe and effective procedure in adults as in children in appropriately selected patients.

Quantification of Neuronal Dendritic Spine Density and Lengths of Apical and Basal Dendrites in Temporal Lobe Structures Using Golgi-Cox Staining.

The objective of this chapter is to provide an overview of the methods used to investigate the connectivity and structure of the nervous system. These methods allow neuronal cells to be categorized according to their location, shape, and connections to other cells. The Golgi-Cox staining gives a thorough picture of all significant neuronal structures found in the brain that may be distinguished from one another. The most significant characteristic is its three-dimensional integrity since all neuronal structures may be followed continuously from one part to the next. Successions of sections of the brain's neurons are seen with the Golgi stain. The Golgi method is used to serially segment chosen brain parts, and the resulting neurons are produced from those sections.

Quantification of Neuroinflammatory Markers in Blood, Cerebrospinal Fluid, and Resected Brain Samples Obtained from Patients.

Cytokines have the potential to be the ideal biomarkers to track the onset and progression of immune-mediated diseases, study the development of novel therapeutic strategies, and they can serve as outcome parameters due to their crucial role in the regulation of immune and inflammatory responses. It is vital to keep track of the entire cytokine spectrum due to the complex interactions, pleiotropic effects, and redundancy in the cytokine network. The multiplex immunoassay (MIA) is, therefore, the best method for achieving that goal. This chapter addresses the key methodological processes of this technique, such as sample preparation, antibody coupling to beads, and assay procedure.

Emerging insights into cephalic neural crest disorders: A single center experience.

Objectives: Neural crest cells (NCCs) are transient structures in the fetal life in vertebrates, which develop at the junctional site of the non-neural and neural ectoderm, sharing a common developmental origin for diverse diseases. After Epithelio-mesenchymal (EMT) of the NCCs within the neural tube, delamination of NCCs occurs. After delamination, the transformation of these cells into various cell lineages produces melanocytes, bones, and cartilage of the skull, cells of the enteric and peripheral nervous system. After the conversion, these cells migrate into various locations of the entire body according to the cell lineage. Abnormalities in neural crest (NC) formation and migration result in various malformations and tumors, known as neurocristopathy. Material and Methods: Herein, this case series describes a single-center experience in cephalic NC disorders over the past 3 years, including 17 cases of varying composition (i.e., vascular, dysgenetic, mixed, and neoplastic forms) involving the brain and occasionally skin, eyes, and face of the patients. Results: In our study of 17 patients with cephalic NC disease, 6 (35.3%) patients had vascular form, 5 (29.4%) had dysgenetic form, 4 (23.5%) had mixed form, and 2 (11.7%) had neoplastic form. Brain involvement in the form of vascular or parenchyma or both vascular and parenchymal was seen in all of our patients (100%), skin in 6 (35.3%) patients, eye in 2 (11.7%), and face in 1 (5.9%) patient. Treatment was planned according to the various manifestations of the disease. Conclusion: Neural crest diseases (NCDs) are a rare and under-recognized group of disorders in the literature and may have been under-reported due to a lack of awareness regarding the same. More such reporting may increase the repertoire of these rare disorders such that clinicians can have a high degree of suspicion leading to early detection and timely counseling and also improve preventive strategies and help in developing new drugs for these disorders or prevent them.

Neuropsychological Rehabilitation for Epilepsy in India: Looking Beyond the Basics.

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Translation and Adaptation of Cognistat in Hindi Language: For Computerized Evaluation of Cognitive Functioning.

OBJECTIVE: Cognitive assessment is a crucial element of the mental health screening process. However, there is a lack of culturally appropriate cognitive screening tools for the Hindi-speaking aging population in India. We aimed to translate and culturally tailor the English version of the computerized Cognistat test for the Hindi-speaking aging population. METHOD: The computer-based Cognistat Assessment System was culturally adapted for the North Indian Hindi-speaking population. Participants with mild cognitive impairment (MCI) (n = 30), depression (n = 30), and healthy control (n = 30) groups between the age range of 50 and 83 years were assessed using the translated version of the tool. The group differences were analyzed using analysis of variance, multivariate analysis of variance, Tukey's post hoc analysis for continuous variables, and Fisher's exact test for categorical variables. The correlation between the Cognistat domains was analyzed using Pearson's correlation, and test reliability was assessed using Cronbach's alpha. RESULTS: The MCI group had significantly lower scores as compared with the depression and control groups on orientation, language, repetition, and calculation domain tasks. For attention and construction tasks, the MCI group had lower scores than the control group. MCI group scores were significantly lower than the control group on naming domain. The Hindi version of the test was reliable for the Hindi-speaking aging population. CONCLUSIONS: Cognistat Hindi can be used by trained healthcare professionals with Hindi-speaking populations for culturally tailored primary evaluation of cognitive difficulties. Future research should focus on further validation and assessment of its properties.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Cold atmospheric plasma (CAP) treatment increased reactive oxygen and nitrogen species (RONS) levels in tumor samples obtained from patients with low-grade glioma.

Low-grade gliomas (LGGs) are a heterogeneous group of tumors with an average 10-year survival rate of 40%-55%. Current treatment options include chemotherapy, radiotherapy, and gross total resection (GTR) of the tumor. The extent of resection (EOR) plays an important role in improving surgical outcomes. However, the major obstacle in treating low-grade gliomas is their diffused nature and the presence of residual cancer cells at the tumor margins post resection. Cold Atmospheric Plasma (CAP) has shown to be effective in targeted killing of tumor cells in various glioma cell lines without affecting non-tumor cells through Reactive Oxygen and Nitrogen Species (RONS). However, no study on the effectiveness of CAP has been carried out in LGG tissues till date. In this study, we applied helium-based CAP on tumor tissues resected from LGG patients. Our results show that CAP is effective in promoting RONS accumulation in LGG tissues when CAP jet parameters are set at 4 kV voltage, 5 min treatment time and 3 lpm gas flow rate. We also observed that CAP jet is more effective in thinner slice preparations of tumor as compared to thick tumor samples. Our results indicate that CAP could prove to be an effective adjunct therapy in glioma surgery to target residual cancer cells to improve surgical outcome of patients with low-grade glioma.