Journal of the Neurological Sciences

BACKGROUNDSubarachnoid hemorrhage (SAH) patients mortality rate has been decreasing, but improving survivors prognosis outcome, which impacts patients quality of life, is still limited. An Early Brain Injury (EBI), which is a period of first 72 hours after SAH, is critical phase when resident and infiltrating innate immune cells induce neuroinflammation, deciding the prognosis outcome. While the roles of microglia have been studied, little is known about the role of infiltrating immune cells, especially that of monocytes. We investigated how the absence of monocyte infiltration during EBI may affect SAH outcomes. METHODSUsing Middle cerebral artery (MCA) perforation method, we established Wild type (WT) and C-C Chemokine Receptor type 2 (CCR2) knockout transgenic mice (CCR2-/-) SAH model. Using flow cytometry, we determined differences in immune cell infiltration population. Also, through Cytometric bead array (CBA), we measured inflammatory cytokine level. We performed different behavioral experiments to assess neurological and behavioral recovery and prognosis of SAH. Furthermore, to confirm neuronal cell death severity, immunohistochemistry was performed. We also tested CCR2 antagonists in the early EBI period to see if it impacted WT mices neurological outcome. RESULTSSAH model showed increased infiltration of CD45hi immune cells, mainly Ly6C+ monocyte at 24 hours after SAH, which were nearly abolished in CCR2-/- SAH mice. Increased IL-6 and TNF- cytokine levels in cerebrospinal fluid was significantly reduced as well. Also, better neurological and motor recovery was observed from CCR2-/- SAH mice. Overall neuronal cell death by late EBI period was significantly decreased. Finally, WT SAH mice treated with CCR2 antagonists showed improved neurological outcomes 24 hours after SAH, while showing reduced total infiltrating immune cells and monocytes. CONCLUSIONClassical monocyte infiltration, which occurs via CCR2 signaling, is detrimental for neuroinflammation during EBI of SAH that leads to poor prognosis. CCR2 inhibition could be a potential target for interventional therapeutic strategy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=66 SRC="FIGDIR/small/644055v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@66726eorg.highwire.dtl.DTLVardef@1e2d390org.highwire.dtl.DTLVardef@afa86borg.highwire.dtl.DTLVardef@5a3f85_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

Chiari malformation type I(CMI) is a common condition. It is a subject of controversy from diagnosis to the management (16). Classically the diagnosis is made on clinical basis and radiological measurement of cerebellar tonsils herniation of 5mm or more below the opisthion-basion line in mid-sagittal plane(Mc Rae line.) The aim of our study was to determine the relationship between clinical presentation of CMI and cerebellar tonsil herniation measured in three dimensions, cerebellar tonsils volume and the volume ratio (cerebellar tonsils volume/Foramen magnum volume) within foramen magnum. Can the volume of cerebellar tonsils herniation and the volume ratio(cerebellar tonsils volume/volume foramen magnum) reflect better the severity of patients with CMI? the study is the first in current literature eliciting the relationship between myelopathy severity and headache severity in CMI patients; cerebellar tonsils volume and T/F volume ratio (cerebellar tonsils volume /Foramen magnum volume) MethodsWe conducted an observational cross sectional analytical study. Patients with clinical and radiological confirmation of CMI evaluated on cranial cervical MRI were enrolled. Three dimension morphometric measures of cerebellar tonsils was made, the volume of cerebellar tonsils was calculated using ellipsoid volume formula. The transverse diameter of foramen magnum was measured and the volume of foramen magnum was calculated using sphere formula. We computed various non-parametric statistical tests and hypothesis testing to analyze variation of cerebellar tonsils uniplanar measurements, cerebellar tonsils volume, and T/F volume ratio (Cerebellar tonsils volume/foramen magnum volume), and to analyze correlation between these measurements with the severity of myelopathy using modified Japanese orthopedics association score(mJOA) and headache severity using pain numeric rating scale. We did all the calculations in python 3 using scipy. stats, Wilcoxon, Pearson, seaborn, and matplotlib.pyplot packages and pandas library ResultsChiari malformation type I was more common in female with 61.5% and male patients with CMI was 38.5%. The majority of patients with CMI were in fourth and fifth decade. Occipital headache was the most presenting symptom followed by limb paraesthesia, vertigo, difficulty walking and bulbar symptoms. Scoliosis associated with CMI was found in 5% while syringomyelia associated with CMI was found in 8%. According to numeric pain scale; patients with CMI mostly presented with severe headache and moderate headache with 58.3% and 41.7 % respectively. There is difference between right and left sagittal tonsils measurement; the left median sagittal measurement is 7.8 mm while the right median sagittal measurement is 8.8 mm with P-value <0.001 The coronal and sagittal cerebellar tonsils measurements are statistically different. The median difference and interquartile range(IQR) between coronal and sagittal measurements were 0.6(-0.4 1.8) and p-value <0.001 respectively The finding showed a correlation between myelopathy severity and the volume of herniated cerebellar tonsils as well as correlation between myelopathy severity and T/F volume ratio (Cerebellar tonsils volume/Foramen magnum volume). There was no correlation between headache severity and sagittal measurement as we failed to reject hypothesis p=0.661 Spearmans correlation coefficient: -0.045 In contrast there was a correlation between headache severity and cerebellar tonsils volume as well as T/F volume ratio with P-value 0.03 in our study. ConclusionTwo dimensions radiological measurements in assessment of CMI is not reflecting the clinical severity of patients with CMI. Consideration of both clinical presentation and radiological measurement in assessment of severity of CMI is of great importance rather than only considering the cut off 5 mm descent of cerebellar tonsils herniation in midsaggital plan. Cerebellar tonsils volume and T/F volume ratio(cerebellar tonsils volume /foramen magnum volume) are the indicators of severity of myelopathy and headache severity as shown in our study.

BackgroundInfusing young mouse blood into old mice makes the old mice biologically younger. When an old mouse and a young mouse share a circulatory system, the old mouses muscle function is improved, and the production of olfactory neurons is increased. GDF11 seems to be a crucial element of the young blood in both instances. MethodsBecause of GDF11s potential neuroprotective actions, we used The Cancer Genome Atlas (TCGA) to assess the effect of GDF11 expression in malignant gliomas. We analyzed the GDC TCGA lower grade glioma data set. To access TCGA data we used the Xena platform and cBioportal. Statistical analysis was done with SPSS v26. Resultsincreased GDF11 expression in IDH1 mutant subjects was significant. There was significantly increased survival (p = 0.00065, log rank test) with high GDF11 expression in grade 3 gliomas. The survival effect was less prominent in grade 2 gliomas. GDF11 gene expression was highest in anaplastic oligodendrogliomas and mixed gliomas with 1p 19q co-deletions and few or no TP53 or ATRX mutations. GDF11 gene expression was lowest in anaplastic astrocytomas with no 1p 19q co-deletions and many TP53 and ATRX mutations. ConclusionGDF11 or an analogue might be therapeutic in grade 3 glioma. GDF11 does not cross the blood brain barrier but affects the brain by acting on brain endothelial cells. GDF11 might be delivered to a brain tumor intranasally.

BackgroundChronic subdural hematoma (CSDH) is characterized by the collection of blood beneath the dura mater. Traditional treatments involve surgical drainage of the hematoma, but recurrence rates can be high. A highly vascularized neo-membrane irrigated by the middle meningeal artery (MMA) may be involved in CSDH re-accumulation. ObjectiveWe conducted a systematic review and meta-analysis of studies that compared the efficacy and safety of MMA embolization to conventional treatment alone for CSDH. Material and MethodsA systematic search of PubMed, Embase Ovid, and ClinicalTrials.gov identified observational and randomized clinical studies comparing MMA embolization to conventional treatment for chronic subdural hematoma. The efficacy outcomes were hematoma recurrence and good functional outcome (as defined by a modified Rankin Scale score (mRS) of 0-2). Safety outcomes were the rate of major complication and mortality. Heterogeneity among studies were evaluated using the I2 statistic. Analyses were conducted using Cochrane Review Manager software, with risk ratios (RR) and 95% confidence intervals (95% CI) presented for key outcomes. Absolute risk reduction (ARR, 95% CI) 1000 patients were also calculated using GRADEpro software. ResultsThe analysis included data from 13 studies (4 RCTs and 9 observational studies) with a total number of 2960 patients (35.3% in the MMA group and 64.7% in the conventional treatment group). Compared to conventional treatment, MMA embolization decreased risk of hematoma recurrence by 60% (13 studies, RR=0.40, 95% CI 0.25-0.63; I2=50%), for an absolute effect of 119 fewer events/1000 patients (95% CI 70-149), with similar risk of major complications (9 studies, RR=0.82, 95% CI=0.54-1.25) and mortality risk (13 studies, RR=0.90, 95% CI=0.54-1.51). In subgroup analyses by study type, pooled results from RCTs showed similar direction effects as those from observational studies for both efficacy and safety outcomes. ConclusionMMA embolization in CSDH management is a safe and effective approach for CSDH.

IntroductionGlioblastoma is a devastating brain tumor with poor prognosis despite current treatment modalities. Chimeric antigen receptor T-cell (CAR T-cell) therapy has shown promise in other cancers but has yielded mixed results in glioblastoma. This augmented meta-analysis aims to address the limitations of previous studies and evaluate the safety and efficacy of CAR T-cell therapy for recurrent glioblastoma. MethodsWe followed PRISMA guidelines, including specific inclusion and exclusion criteria, for our literature review. Eight studies with 108 patients were included. We used standard and augmented meta-analyses to assess outcomes, complications, and publication bias. ResultsIt was found that the mean overall survival for glioblastoma patients who underwent CAR T-cell therapy was 6.49 months, demonstrating no significant deviation from the median survival observed in those following the standard protocol. CAR T-cell therapy did not lead to a statistically significant improvement in achieving complete responses, with only 80% of patients exhibiting this outcome. Conversely, 44% of patients experienced stable disease, while 58% faced disease progression after CAR T-cell therapy. Adverse events were notable, with CAR T cell therapy-related encephalopathy affecting 37% of treated patients, while cytokine release syndrome was a rare event, observed in only 3% of cases. ConclusionsTo our knowledge, this is the first study that utilizes this novel statistical technique to predict the outcomes of CAR T-cell therapy for recurrent glioblastoma. The results of this study are predictive rather than confirmatory. CAR T-cell therapy for glioblastoma was not predicted to significantly improve survival or achieve substantial complete responses. Stable disease rates are modest, while disease progression is notable. Adverse events, especially CAR T-cell therapy-related encephalopathy, raise safety concerns. Further trials and refinements are needed to enhance CAR T-cell therapys effectiveness and safety in glioblastoma treatment, Manuscript Click here to view linked References potentially through optimizing administration routes and target antigens or combining it with other therapies. This challenging disease necessitates continued research to improve patient outcomes.

Neuromyelitis optica is rare, autoimmune-mediated inflammation and demyelination of the central nervous system with a prevalence of 1-2 persons per 100,000 populations. We aim to generate a head-to-head comparison of these drugs with appropriate evidence to guide future trials and treatment guidelines in a patient with recurrent attacks of NMO. We searched the databases like PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase for studies published prior to April 2021 using the keywords. Over all 929 patients from 11 different publications were included in the study. Five studies were included for quantitative synthesis. Pooling of studies showed significant mean reduction of ARR in the monoclonal antibody group (-0.26 [-0.35, -0.17], P <0.00001, I2=0%) and the mean difference in EDSS score from baseline in monoclonal antibodies was - 0.23(95% CI [-0.43, -0.03], P=0.02, I2=0%). There was no significant difference in frequency of total reported adverse events between monoclonal antibody and the comparator arm (RR: 1.01 [0.95, 1.07], P=0.74, I2=14%). Our findings, particularly seen from the context of a few RCTs, support the pursuit of larger, multi-center RCTs that evaluate the effectiveness of each of the currently available monoclonal antibodies and better describe their adverse risk profile.

IntroductionDespite the new SARS-CoV-2 (COVID-19) be the seventh of the coronavirus family viruses known to cause human disease, little is known about potential symptoms and syndromes secondary to the compromise of the central and peripheral nervous systems. We reviewed neurological manifestations due to the new coronavirus, thus far published in the literature, as well as guidelines issued by sub-specialties in Neurology, to tackle the disease. Methodswe searched medical databases, such as PubMed, PubMed Central, LILACS and Google scholar for papers (case reports, short letters, case series, etc) describing neurological symptoms in patients with confirmed or suspect COVID-19 diagnosis and also searched webpages of associations and organizations that deal with neurological disorders. Resultswe describe briefly each article considered for this review. Forty-one papers were found associating neurological conditions and COVID-19. Cases are divided by disease groups and, within each disease group, results are listed in chronological order or publication date. We also discuss briefly recommendations for neurological patients, according to disease group. ConclusionAlthough there is evidence of neurological manifestations with previous coronaviruses, COVID-19 is assuring a volume of published papers not seen before for other coronavirus infections. Most neurological cases are not life-threatening, but 10 to 20% of cases will require hospitalization and are in risk for sequelae and death. Although a lot of data coming from these papers is amassing, researchers must bear in mind that many papers currently published are not yet peer-reviewed, and thus are prone to further corrections.

Background and aimsRecent reports reveal incidences of spinal cord involvement in form of para-infectious or post-infectious myelitis raising potential concerns about the possibilities of SARS-CoV-2 behind the pathogenesis of spinal cord demyelination. In this study, we intend to summarise so far available pieces of evidence documenting SARS-CoV-2 mediated spinal demyelination in terms of clinical, laboratory parameters and imaging characteristics. MethodologyThis review was carried out based on the existing PRISMA (Preferred Report for Systemic Review and Meta-analyses) consensus statement. Data was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers up till 10th September, 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2", "COVID-19", "demyelination" etc. ResultsA total of 21 cases were included from 21 case reports after screening from various databases and preprint servers. Biochemical analysis reveals that the majority of cases showed elevated CSF protein as well as lymphocytic pleocytosis. Interestingly, a majority of cases were found to be associated with long extensive transverse myelitis (LETM), and remaining cases were found to be associated with isolated patchy involvement or isolated short segment involvement or combined LETM and patchy involvement. Few cases were also found with significant co-involvement of the brain and spine based on the imaging data. ConclusionIt can be interpreted that SARS-CoV-2 may play a potential role in spinal demyelinating disorders in both para-infectious and post-infectious forms. HighlightsO_LIImaging data reveals LETM, short and patchy involvements C_LIO_LIPara infectious myelitis precedes post-infectious manifestation C_LIO_LIAltered CSF parameters and myelitis-like symptoms at the onset of COVID-19 C_LIO_LISimilar spinal cord involvements in related HCoVs infections C_LI

Background and ObjectivesStacked proportional bar graphs (nicknamed "Grotta bars") are commonly used to visualize functional outcome scales in stroke research and are also used in other domains of neurological research. In observational studies that present adjusted effect estimates, Grotta bars can mislead readers if they show unadjusted, confounded comparisons. In a sample of recent observational neurology studies with confounding-adjusted effect estimates, we aimed to determine the frequency with which Grotta bars were used to visualize functional outcomes and how often unadjusted Grotta bars were presented without an accompanying adjusted version. We also assessed the methods used to generate adjusted Grotta bars. MethodsIn this meta-research study, we systematically examined all observational studies published in the top 15 Clinical Neurology journals between 2020-2021 with an ordinal functional outcome and confounding-adjusted effect estimate. We determined whether at least one comparison using Grotta bars was present, whether the visualized comparisons were adjusted, and which adjustment strategies were applied to generate these graphs. Results250 studies met all inclusion criteria. Of these, 93 (37.2%) used Grotta bars to depict functional outcome scale distributions, with 73 (81.7%) presenting only Grotta bars without model-based adjustment. Amongst the 17 studies that presented Grotta bars adjusted using a model, the adjustment strategies included propensity score matching (n=10; 58.8%), regression (n=6; 35.3%), and inverse probability weighting (n=1; 5.9%). Most studies with Grotta bars (n=87; 87.9%) were stroke studies. DiscussionGrotta bars were most often used in stroke research within our sample. Papers that present adjusted associations for functional outcomes commonly showed only unadjusted Grotta bars, which alone may be misleading for causal questions. In observational research, Grotta bars are most informative if an adjusted version, aligning with adjusted effect estimates, is presented directly alongside the unadjusted version. Based on our findings, we offer recommendations to help authors generate informative Grotta bars and facilitate correct interpretation for readers.

BackgroundChronic subdural haematoma (CSDH) is a common neurosurgical condition. Occurring predominantly in the elderly, its incidence is on the rise. A clinical practice guideline has been formed to offer best practice care recommendations and expose the key knowledge gaps for future research. This article presents the prioritised knowledge gaps. MethodForty-one clinical questions, across 11 themes were identified by a multidisciplinary guideline development groups. A comprehensive systematic literature search was performed on 1st May 2022. 6,024 articles were screened. Themes and questions for which no relevant studies were identified are presented in this study, alongside the prioritisation of knowledge gaps a multi-disciplinary guideline group, including patients. ResultsIn total, 19 of the 41 questions (46%) were identified as having no published literature applicable for review. The questions lay within seven themes - antithrombotic, communication, decision-making, transfer and pathway, palliative care, postop and recovery, and natural history. Within both the transfer and pathway, and the palliative care theme, 100% of the questioned posed had no applicable literature. The stakeholder group identified the top three priorities as Management of antithrombotics, Benefits of Protocolised Multi-disciplinary care, and Natural history of epidemiology of non-operative CSDH with a cross-cutting need for a research database supported throughout. ConclusionsDespite the high incidence of CSDH, almost half of the high priority research questions identified by the ICENI had studies in the published literature that could inform evidence-based recommendations. In particular, there is a paucity of literature surrounding conservatively managed cases, palliative care, and transfer pathways in CSDH.

BackgroundThe most frequent primary intracranial tumor is a meningiomas; however, atypical (WHO grade II) and an plastic (WHO grade III) variants are more aggressive and have increased rates of recurrence and being lethal. The current Histopathological grading is not specific in making predictions. New molecular and genetic profiling has identified key biomarkers potentially used as prognostic refinements, or targets in the personalized medicine strategy. ObjectivesTo describe the molecular and genetic repertoire of atypical and an plastic meningiomas and evaluate their prognostic impact, to inform targeted therapy options. Study designA Retrospective Study. Place and duration of studyDepartment of Neurosurgery MMC Hospital Mardan from jan 2024 to Jan 2025 KPK PAKISTAN MethodsPatient-derived tumor samples were classified as having atypical and an plastic meningiomas and underwent whole exam sequencing, RNA sequencing, and DNA methylation profiling. Key markers (Ki-67, p53, PR) were tested by immunohistochemistry. Molecular alterations were statistically associated with clinical data, such as recurrence and survival. In the bioinformatics analysis, there was one common mutation and signaling pathways. T-tests, Kaplan-Meier survival analysis, and Cox regression modeling statistics were applied to determine statistical significance. ResultsFifty patients (25 atypical and 25 an plastic). Patients were diagnosed at a mean age of 58.4 years (SD +/- 11.6). The ratio between males and females was 1:1.3. There was a major disparity between the two groups in terms of overall survival (p = 0.038), and plastic meningiomas were related to a reduced survival rate. The most common mutations were NF2 (47%), deletions of CDKN2A/B (29%) and TERT promoter mutations (18%). Tumor clustering into specific subgroups based on methylation profiling was found to correlate with prognosis. ConclusionAtypical and an plastic meningiomas differ, with molecular and genetic profiles indicating various changes linked to prognosis. The application of these findings into clinical care can positively affect the risk stratification and the development of targeted therapies. It is reasonable to develop this direction further and analyze the validity of these biomarkers and be able to gauge their usefulness in predicting therapeutic response and survival.

BackgroundSpontaneous intracerebral haemorrhage (ICH) has high rates of death and disability, and no proven haemostatic treatment. Tranexamic acid might limit haematoma expansion and improve outcomes. We conducted the first individual patient data meta-analysis to evaluate the effect of tranexamic acid on functional outcomes in spontaneous ICH. MethodsThis systematic review and individual patient data meta-analysis included randomised controlled trials comparing intravenous tranexamic acid to placebo in adults with spontaneous ICH treated within 12 hours of onset. MEDLINE, EMBASE, CENTRAL, Web of Science, and WHO ICTRP were searched to November 2024. The primary outcome was functional status at 90 days after randomisation, measured by the modified Rankin Scale. Adverse events (seizures, thromboembolic events) were also summarised. Analyses used generalised linear mixed models with random intercepts for trial. Risk of bias was assessed using the Cochrane RoB 2 tool. The study was registered with PROSPERO (CRD42022345775). ResultsWe identified 1,131 records; nine trials (3,194 participants) were eligible for inclusion and five trials (2860 participants; 90% of those available) provided individual patient data for the primary analysis. Risk of bias was low across all included trials. At 90 days, 757/1423 (53.2%) patients assigned to tranexamic acid had a worse functional outcome compared with 759/1415 (53.6%) assigned to placebo, the difference was not statistically significant (adjusted common odds ratio 0.93 (95% CI 0.81 to 1.07; p = 0.30). Serious adverse events were similar between the groups, with no significant differences observed. There was no evidence of between-trial heterogeneity based on model fit (likelihood ratio test). DiscussionCompleted clinical trials provide no evidence that tranexamic acid improves functional outcome after spontaneous ICH. However, given the reduction in hematoma expansion and early mortality it remains to be seen if this translates to improved functional outcome in larger ongoing clinical trials. Even a small beneficial effect could have potential for global impact given the burden of ICH. FundingNo funding source.

BackgroundThe potential of Glibenclamide to improve functional outcomes in patients with acute ischemic stroke remains controversial. This study aims to evaluate the benefit of Glibenclamide for patients with acute ischemic stroke and at risk of malignant brain edema. MethodsA comprehensive search was undertaken in January 2025 across several electronic databases, including PubMed, Scopus, Cochrane Library, Web of Science, and Embase. RCTs and observational studies were both considered eligible. Data extraction and analysis were done using Review Manager (RevMan) version 5.4. ResultsSix studies (four RCTs and two cohort studies) involving 1,244 patients were included; five were eligible for meta-analysis. Glibenclamide significantly reduced MMP-9 levels (MD = - 20.35; 95% CI: -23.65 to -17.04; P < 0.00001; I{superscript 2} = 0%) and midline shift (MD = -2.37 mm; 95% CI: -4.00 to -0.73; P = 0.005; I{superscript 2} = 83%). However, it did not significantly improve modified Rankin Scale scores or reduce the need for decompressive craniotomy. Glibenclamide was associated with a higher risk of hypoglycemia (RR = 3.30; 95% CI: 1.26-8.66; P = 0.02; I{superscript 2} = 0%) and serious adverse events (RR = 1.12; 95% CI: 1.01-1.24; P = 0.04; I{superscript 2} = 0%). No significant differences were observed in other adverse effects. ConclusionGlibenclamide may reduce inflammation and cerebral edema, but it increases the risk of hypoglycemia and serious adverse events. Given limitations in sample size and study variability, larger high-quality RCTs are needed to confirm efficacy and safety.

PurposeThe NeuroDiscovery AI database is a comprehensive real-world data (RWD) repository containing de-identified electronic health record (EHR) data from U.S.-based neurology outpatient clinics. The structured data encompasses sociodemographic details, clinical examinations, social, medical, and lifestyle histories, International Classification of Diseases (ICD-9/ICD-10) diagnoses, and prescribed medications. Additionally, the database integrates neuroimaging data and laboratory results, providing a robust resource for clinical research. This paper describes a subset of the NeuroDiscovery AI dataset and outlines the processes involved in its development. ParticipantsAs of October 15, 2024, the dataset includes EHR data from 355,791 patients, of whom 40.72% are male. Over 40.06% of the patients are aged 60 or older, spanning across 14,797 distinct diagnosis codes. The data represents more than 15 years of longitudinal patient information, with 26.87% of patients classified as active (defined as having had clinical encounters within the last 18 months). The median follow-up duration for active patients is 19.54 months. LimitationThe large sample size, rigorous data processing, and robust data security of the NeuroDiscovery AI dataset are key strengths, enabling comprehensive studies on disease progression, treatment responses, and long-term outcomes in neurology. The dataset aligns closely with published demographic trends for various neurological conditions, including a female predominance in migraines, multiple sclerosis, and vertigo, with slight variations in age and gender distribution for conditions such as ALS. However, challenges remain, including missing data and data heterogeneity. Ongoing efforts to expand and diversify the dataset aim to improve its applicability and representativeness. Future planThe NeuroDiscovery AI dataset will expand by incorporating data from more providers and improving diversity, aiming to become one of the largest neurology-focused datasets. The platform will continue to evolve into a comprehensive analytical tool, integrating cohort building and data interrogation functionalities to streamline clinical workflows. These enhancements will enable faster, more accurate decision-making, and future efforts will focus on identifying key trends in neurological conditions and patient outcomes.

BackgroundGlioblastoma (GBM) remains one of the most aggressive primary brain tumors, with limited survival despite maximal safe resection and chemoradiotherapy. Neoadjuvant bevacizumab (BEV) has been proposed to reduce peritumoral edema, improve functional status, and potentially enhance progression-free survival (PFS). However, its survival benefit in newly diagnosed, surgically resectable GBM remains unclear. ObjectiveTo systematically review and quantitatively synthesize the evidence on neoadjuvant BEV in adult patients with newly diagnosed, resectable GBM, focusing on survival and functional outcomes. MethodsFollowing PROSPERO registration (CRD420251078761), we searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library up to July 20, 2025, without language restrictions. Eligible randomized trials, non-randomized trials, and cohort studies compared neoadjuvant BEV (alone or with other therapies) to standard care without BEV. Primary outcomes were overall survival (OS) and PFS; secondary outcomes included Karnofsky Performance Status (KPS), steroid use, radiological response, and biomarkers. Data were pooled using a random-effects model. ResultsThirteen studies (2 RCTs, 7 non-randomized trials, 4 cohorts) met the inclusion criteria; four (n=751) were eligible for meta-analysis. Pooled HR for OS was 0.72 (95% CI: 0.42-1.25, p=0.246) and for PFS was 0.72 (95% CI: 0.42-1.22, p=0.220), both with low heterogeneity (I2=0%). Functional outcomes suggested improved KPS and reduced steroid dependence, but certainty was low. Biomarker and radiological findings were inconsistent. ConclusionsNeoadjuvant BEV in resectable GBM does not significantly improve OS or PFS but may offer symptomatic and functional benefits. Current evidence is limited by small sample sizes, heterogeneous protocols, and low methodological quality. Well-designed multicenter RCTs are warranted.

Gain of chromosome 1q locus is a common cytogenetic feature associated with intracranial ependymomas; however, candidate non-coding RNAs on this locus have not been identified. Recent studies have reported somatic copy number alterations for long non coding RNA (lncRNA) FAL1/FALEC residing on chromosome 1q to stabilize BMI1, an epigenetic repressor and PRC1 component, leading with to downregulation of p21/CDKN1A tumor suppressor gene. We aimed to study the role of FAL1 in ependymomas, its association with 1q gain, BMI1/p21 regulatory axis and clinicopathological parameters. Using SNP array analysis (GSE32101), 31% (discovery cohort) and 63.8% (in-house cohort) showed amplification/gain of FAL1 locus with higher prevalence in intracranial tumors. Copy number gain of FAL1 locus was significantly associated with increased FAL1 (p=0.003) and BMI1 (p=0.007) levels, and reduced p21 (p=0.001) expressions. Interestingly, gain of FAL1 locus and FAL1 transcripts did not show any association with 1q gain or RELA fusions. Subcellular localization reported FAL1 to be expressed in nuclear compartment in ependymomas. Chromatin immunoprecipitation-qPCR demonstrated in-vivo binding of BMI1 at p21 promoter locus with BMI1 target genes to be enriched in cell architecture related pathways. A 3-tier survival analysis between FAL1 gain and increased expression levels of FAL1 and BMI1 correlated with poor outcome in our cohort. Ours is the first study demonstrating gain of FAL1 locus and its interplay with the BMI1/p21 axis in intracranial ependymomas. Further studies into this epigenetic regulatory mechanism will unravel novel driver mutations in intracranial ependymomas HighlightsSomatic variations in enhancer long non-coding RNA has been recently attributed for various clinical malignancies including cancers. Gain of 1q locus is a common cytogenetic variation observed in intracranial ependymomas. Our study has demonstrated, focal amplification of enhancer lncRNA mapping to Chromosome 1q, FAL1/FALEC, to be involved in oncogenicity/ progression of ependymomas. Moreover, our data suggests a positive association with BMI1 (a PRC1 component) with FAL1 levels, indicating downregulation of BMI1 target gene involved in cell cycle, p21. Furthermore, a 3-tier prognosis analysis (between FAL1 gain, FAL1 and BMI1 expressions) suggests a negative survival outcome. Our study highlights the importance of somatic variation in non-coding genome with ependymoma survival.

Multiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been made and plagued with clinical failures. Most studies for ICH detection have insufficient data or weak annotations. We sought to determine whether a deep-learning algorithm for ICH detection trained on a strongly annotated dataset outperforms that trained on a weakly annotated dataset, and whether a weighted ensemble model that integrates separate models trained using datasets with different ICH subtypes is more accurate. We used publicly available brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training datasets. For external testing, 600 CT scans (327 with ICH) from Dongguk University Medical Center and 386 CT scans (160 with ICH) from Qure.ai were used. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and compared. We then developed a weighted ensemble model combining separate models trained on all ICH, subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), and small-lesion ICH cases. The final weighted ensemble model was compared to four well-known deep-learning models. Six neurologists reviewed difficult ICH cases after external testing. InceptionResNetV2, MobileNetV2, and VGG19 models outperformed when trained on strongly annotated datasets. A weighted ensemble model combining models trained on SDH, SAH, and small-lesion ICH had a higher AUC than a model only trained on all ICH cases. This model outperformed four well-known deep-learning models in terms of sensitivity, specificity, and AUC. Strongly annotated data are superior to weakly annotated data for training deep-learning algorithms. Since no model can capture all aspects of a complex task well, we developed a weighted ensemble model for ICH detection after training with large-scale strongly annotated CT scans. We also showed that a better understanding and management of cases challenging for AI and human is required to facilitate clinical use of ICH detection algorithms. Key PointsQuestion Can a weighted ensemble method and strongly annotated training datasets develop a deep-learning model with high accuracy to detect intracranial hemorrhage? Findings A deep-learning algorithm for detecting ICH trained with a strongly annotated dataset outperformed models trained with a weakly annotated dataset. After ensembling separate models that were trained with only SDH, SAH, and small-lesion ICH, a weighted ensemble model had a higher AUC. Meaning This study suggests that to enhance the performance of deep-learning models, researchers should consider the distinct imaging characteristics of each hemorrhage subtype and use strongly annotated training datasets.

BackgroundMultiple sclerosis is a chronic disease of the central nervous system characterized by autoimmune demyelination. Various immunomodulatory medications are available for its treatment, among which anti-CD20 monoclonal antibodies have demonstrated superior efficacy compared to other disease-modifying therapies. However, there is a lack of direct comparison between the four available anti-CD20 monoclonal antibodies. Therefore, this study aims to systematically assess the relative efficacy and safety of anti-CD20 monoclonal antibodies for treating relapsing multiple sclerosis. Materials and MethodsWe will conduct a systematic review of phase IIb and phase III clinical trials of anti-CD20 monoclonal antibodies for the treatment of relapsing multiple sclerosis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive review of the Cochrane Central Register of Controlled Trials; MEDLINE; Embase; ClinicalTrials; International Clinical Trials Registry Platform; OpenGray; and MedRxiv will be performed. Two independent reviewers will select titles, abstracts, and eligible full texts to execute the data extraction. The risk of bias will be assessed with the Cochrane RoB 2 tool. Data on pre-specified outcomes will be analyzed for the selected articles using a random-effects network meta-analysis with a frequentist framework. Summary statistics, along with 95% confidence intervals will be presented, and the effectiveness and safety of each intervention will be ranked using the surface under the cumulative ranking curve. A missing data and a sensitivity analysis will be conducted. We will use the GRADE approach to assess the certainty of the direct, indirect, and network estimate for all outcomes. Results and ConclusionThe results will provide evidence of the relative efficacy and safety of anti-CD20 monoclonal antibodies for the treatment of relapsing multiple sclerosis. Systematic review registrationPROSPERO registration number CRD42023437996

Although typically associated with onset in young adults, multiple sclerosis (MS) also attacks aged people, which is termed late-onset MS. The disease can be recapitulated and studied in the aged mouse model of experimental autoimmune encephalomyelitis (EAE). The onset of induced EAE is delayed in aged mice, but the disease severity is increased relative to standard EAE in young mice. Given that CD4+FoxP3+ regulatory T (Treg) cells play an ameliorative role in MS/EAE severity and the aged immune system accumulates Treg cells, failure of these cells to prevent or ameliorate EAE disease is enigmatic. When analyzing the distribution of Treg cells in EAE mice, the aged mice exhibited a higher proportion of polyclonal(pan) Treg cells and a lower proportion of antigen-specific-Treg cells in their periphery, but lower proportions of pan- and antigen-specific-Treg cells in the central nervous system (CNS). Furthermore, in the aged CNS, Treg cells exhibited a higher plasticity and T effector (Teff) cells exhibited a greater clonal expansion, which disrupted the Treg/Teff balance. Transiently inhibiting FoxP3 expression in peripheral Treg cells partially ameliorated the disease and corrected Treg distribution in the aged mice. These results provide evidence that accumulated aged Treg cells play a detrimental role in neuronal inflammation of aged MS. HighlightsO_ST_ABSQuestionC_ST_ABSCD4+ regulatory T (Treg) cells typically play an ameliorative role in multiple sclerosis (MS) onset and severity. However, why aged immune system has accumulated peripheral Treg cells, but the elderly has more severe MS symptoms? FindingsAged Treg cells cannot easily distribute to the CNS of aged EAE mice, and those aged Treg cells that did enter the CNS exhibited increased plastic features. However, transient inhibition of peripherally accumulated Treg cells corrected Treg distribution and partially ameliorated the disease in the aged mice. Conclusion and mechanistic insightsAccumulated aged Treg cells within an "inflammaging" condition do not play an ameliorative role but are potentially detrimental for inflamed CNS repair processes in aged EAE mice due to impeding the trafficking of immune cells into the inflamed CNS. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

BackgroundGlioblastoma is most commonly reported in the second (pediatric form) and seventh (adult form) decade of life. Pathogenic germline variants (PGVs) and its association to late onset glioblastoma remains unclear. This study aimed to investigate the genetic predisposition to adult glioblastoma. MethodsWe performed an in-depth analysis of whole genome sequencing (WGS) data of tumor-normal tissue pairs of 98 glioma WHO grade 4 patients for potential presence of PGVs, in a comprehensive set of 170 genes associated with cancer predisposition. All candidate pathogenic events were also assessed for second-hit somatic events. ResultsIn 11 patients (11%), PGVs were observed that were considered relevant by clinical experts in the context of glioblastoma. In these patients, 13 PGVs were found in genes known for a strong association with familial glioblastoma (MSH6 (3x), PMS2 (5x), MSH2, TP53, NF1 and BRCA1) or with medulloblastoma (SUFU). In eight of these patients (73%) causality was supported by a second (somatic) event and/or a matching genome-wide mutational signature. ConclusionsGermline predisposition does also play a role in the development of adult glioblastoma, with mismatch repair deficiency being the main mechanism. Our results do illustrate benefits of tumor-normal WGS for glioblastoma patients and their relatives beyond the identification of potentially actionable mutations for therapy guidance. Key pointsO_LIPathogenic germline variants occur in more than 10% of adult glioblastoma C_LIO_LIMismatch repair deficiency is the main predisposition mechanism C_LIO_LIPathogenic germline variants could be used for (targeted) treatment selection C_LI Importance of the StudyThe hereditary of adult glioblastoma is still largely unexplored. With the option of broad molecular testing, it is crucial that clinicians are aware of the a priori probability of finding germline predisposition in a glioblastoma patient. Here, we studied the genetic predisposition to adult glioblastoma in an unselected, average cohort. We observed that pathogenic germline variants occurred in about 1 out of 10 patients, with mismatch repair deficiency being the main predisposition mechanism. This information should be kept in mind when broad molecular testing, like WGS, is discussed with the patient. Clinicians and patients should discuss the probability of finding evidence of heredity of the tumor and potential consequences for relatives.