Journal of the Neurological Sciences

IntroductionDespite the broad spectrum of neurological symptomatic manifestation in COVID19 patients, the brain tissue susceptibility and permissiveness to SARS-Cov2 infection is yet uncertain. This critical appraisal aims at bridging the gap by consolidating the body of evidence for meticulous evaluation of molecular neuropathological pathways and CSF diagnostic signatures of SARS-Cov2 infection in the central nervous system (CNS) that will underpin further strategic approach for neuroprotection and treatment of neurological COVID19 Methods and AnalysisWe have developed the protocol of this review according to the provisions of Joanna Briggs Institute Reviewers Manual for Evidence Synthesis, 2015 and Arksey and O Malleys Methodological Framewotk, 2005. The articles for this review will be sourced from several electronic databases including EMBASE, PubMed, Scopus, Web of Science (WOS), Cochrane, Crossref Metadata and Semantic scholar. Herein we generated the search strategy using the medical subject headings [ MeSH Terms], term in all field bibliography at all permutations in conjunctions with boolean operators Ethical Clearance and Dissemination planHerein the review will not involve the human participants henceforth the ethical clearance approval is not applicable. We will disseminate the final findings of this review to scientific conferences at local and international level. The manuscript for final findings will be published on reputable journal of neuroscience.

Post-COVID Syndrome (PCS), also known as Long COVID, is characterized by persistent and often debilitating neurological sequelae, including fatigue, cognitive dysfunction, motor deficits, and autonomic dysregulation (Dani et al., 2021). This study investigates structural and functional alterations in the brainstem and cerebellar peduncles of individuals with PCS using diffusion tensor imaging (DTI) and volumetric analysis. Forty-four PCS patients (15 bedridden) and 14 healthy controls underwent neuroimaging. Volumetric analysis focused on 22 brainstem regions, including the superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP), periaqueductal gray (PAG), and midbrain reticular formation (mRt). Significant volume reductions were observed in the SCP (p < .001, Hedges g = 3.31) and MCP (p < .001, Hedges g = 1.77), alongside decreased fractional anisotropy (FA) in the MCP, indicative of impaired white matter integrity. FA_Avg fractional anisotropy average tested by FreeSurfer Tracula, is an index of white matter integrity, reflecting axonal fiber density, axonal diameter and myelination. These neuroimaging findings correlated with clinical manifestations of motor incoordination, proprioceptive deficits, and autonomic instability. Furthermore, volume loss in the dorsal raphe (DR) and midbrain reticular formation suggests disruption of pain modulation and sleep-wake cycles, consistent with patient-reported symptoms. Post-mortem studies provide supporting evidence for brainstem involvement in COVID-19. Radtke et al. (2024) reported activation of intracellular signaling pathways and release of immune mediators in brainstem regions of deceased COVID-19 patients, suggesting an attempt to inhibit viral spread. While viral genetic material was detectable, infected neurons were not observed. Matschke et al. (2020) found that microglial activation and cytotoxic T lymphocyte infiltration were predominantly localized to the brainstem and cerebellum, with limited involvement of the frontal lobe. This aligns with clinical observations implicating the brainstem in PCS pathophysiology. Cell-specific expression analysis of genes contributing to viral entry (ACE2, TMPRSS2, TPCN2, TMPRSS4, NRP1, CTSL) in the cerebral cortex showed their presence in neurons, glial cells, and endothelial cells, indicating the potential for SARS-CoV-2 infection of these cell types. Associations with autoimmune diseases with specific autoantibodies, including beta-2 and M-2 against G-protein coupled alpha-1, beta-1, beta-2 adrenoceptors against angiotensin II type 1 receptor or M1,2,3-mAChR, among others, voltage-gated calcium channels (VGCC) are known (Blitshteyn et al. 2015 and Wallukat and Schminke et al. 2014). These findings support the "Broken Bridge Syndrome" hypothesis, positing that structural disconnections between the brainstem and cerebellum contribute to PCS symptomatology. Furthermore, we propose that chronic activation of the Extended Autonomic System (EAS), encompassing the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, may perpetuate these symptoms (Goldstein, 2020). Perturbations in this system may relate to the elevation of toxic autoantibodies AABs (Beta-2 and M-2), specific epitopes of the COVID viruss SPIKE protein and Cytokine storm of IL-1, IL-6, and IL-8 in their increased numbers (1,000->10,000) Further research is warranted to elucidate the underlying neuroinflammatory mechanisms, EAS dysregulation, and potential therapeutic interventions for PCS.

BackgroundDiagnostic errors in gliomas, a major group of brain tumors originating from glial cells, can have severe consequences for patients and healthcare systems. Despite the serious implications of a glioma diagnosis, there is a lack systematic evidence on the frequency of diagnostic errors. This study aimed to assess the prevalence of misdiagnosis and underdiagnosis of gliomas and their potential impact. MethodsWe conducted a systematic review of English-language original studies, including those with more than 10 participants, reporting diagnostic errors in gliomas. A search of Medline and Embase was performed from inception until October 28, 2024. We evaluated the proportions of diagnostic errors and their potential consequences, and assessed the risk of bias using a modified Newcastle-Ottawa Scale. ResultsOf 1,860 studies screened, 22 met the inclusion criteria. Our analysis indicates that gliomas are frequently underdiagnosed (i.e., the correct diagnosis is missed) and, though less extensively reported, also misdiagnosed (i.e., assigned incorrect diagnoses). Overall, diagnostic errors ranged from 1.9 to 11.6% with a median of 5% (mis-/underdiagnosis: 5%, range 1.9-20%, misgrading: 11.6% range: 0.6-47%). While diagnosing gliomas is complex, evidence suggests that clinical tools such as MRI and pathological methods, including neuroendoscopic biopsy and specific cytology techniques, can achieve high diagnostic accuracy. Diagnostic errors were linked to relevant patient consequences, with both overtreatment and undertreatment commonly reported. ConclusionDiagnostic errors in gliomas are common and can have serious implications for patients. More rigorous data are needed to better understand the causes of these errors, which is key for reducing misdiagnosis and underdiagnosis in the future.

Purpose DICER1-mutant primary intracranial sarcoma (PIS-DICER1) is a rare, recently defined high-grade intracranial tumor. This systematic review and meta-analysis aimed to comprehensively investigate its imaging characteristics to improve preoperative diagnostic accuracy and facilitate differential diagnosis. Methods A systematic literature search was conducted in PubMed and Web of Science for studies published up to December 31, 2025. Original studies with pathologically and molecularly confirmed PIS-DICER1 and detailed imaging data were included. Imaging features, including tumor location, margin definition, meningeal contact, intratumoral hemorrhage, enhancement pattern, cystic components, peritumoral edema, and advanced imaging findings (SWI, DWI, MRS, PWI), were extracted and analyzed. Pooled proportions with 95% confidence intervals (CIs) were calculated using a random-effects model. Results Twenty-four studies comprising 110 patients with detailed imaging data were included. The pooled mean age was 18.6 years (95% CI: 15.2-22.0), with a slight female predominance (53.3%, 96/180). Tumors were predominantly supratentorial (87%, 95% CI: 80%-93%). Substantial heterogeneity was observed across studies for location (I2 = 78%). Intratumoral hemorrhage was observed in 85% (95% CI: 78%-91%). Contrast-enhanced MRI demonstrated heterogeneous enhancement in all cases (100%, 95% CI: 96%-100%). Due to sparse data, advanced MRI features could not be quantitatively synthesized, underscoring a critical knowledge gap. Conclusion PIS-DICER1 exhibits imaging features including supratentorial location, intratumoral hemorrhage, heterogeneous enhancement, well-defined margins, and meningeal involvement. These features, particularly in children and young adults with hemorrhagic supratentorial masses, should prompt differential diagnosis. Definitive diagnosis requires molecular confirmation, but recognition of these characteristics facilitates diagnosis and preoperative planning.

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.

IntroductionMoyamoya disease (MMD) is a rare and chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the blood vessels within the terminal intracranial aspect of the internal carotid artery and the circle of Willis, leading to the compensatory development of a fragile collateral vessel network at the base of the brain. These vascular features are responsible for the recurrent ischemic and/or hemorrhagic strokes seen in affected patients. Numerous studies have attempted to clarify the clinical features of Moyamoya, including its etiopathology and interventions. In recent years, the development of neuroimaging and surgical techniques has enhanced the understanding of MMD in patients. The purpose of this review is to discuss the hypothesized etiopathogenesis, clinical manifestations, and the current possible treatment options available for Moyamoya disease. MethodsThe PRISMA protocol was utilized to perform an extensive literature search on Google Scholar, Scopus, Web of Science, and PubMed for articles about etiopathogenesis and clinical presentation of Moyamoya disease and the treatment protocols followed in different parts of the world. A comprehensive analysis was also conducted for original articles to better understand the possible clinical presentation and diagnostic criteria used. ResultsBased on the literature review, the RNF213 mutation, mitochondrial dysfunction, and misregulation of growth factors in endothelial cells are the most acceptable etiopathogenesis of MMD via their involvement in neurovascular inflammation. ConclusionThe diagnostic test of choice is magnetic resonance angiography while direct & indirect revascularization surgeries are both effective and established treatments for managing symptoms of Moyamoya disease.

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.

BackgroundThe COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people and can result in both immediate and prolonged neurological effects, including severe complications. While numerous studies have explored the occurrence and consequences of neurological issues in COVID-19, they have often involved limited sample sizes. PurposeThis paper aims to determine the overall occurrence of neurological complications in COVID-19, examine their links with patient demographics, and assess their impact on patient outcomes. Additionally, it seeks to provide an overview of the current understanding of the underlying mechanisms. MethodologyTwo systematic reviews were conducted to investigate acute and chronic neurological complications associated with COVID-19. A comprehensive search of medical databases was performed, and relevant studies were evaluated following PRISMA guidelines. Meta-analysis was carried out using the Mantel-Haenszel method, with subgroup analysis and meta-regression used to assess heterogeneity. ResultsThe analysis of acute complications included 20,011 patients with an average age of 58.1 years and a slight male predominance (55.2%). Common neurological symptoms included loss of taste and smell, headaches, acute encephalopathy, and stroke. For the analysis of long-term complications, 2,094 patients were included. Survivors of COVID-19 experienced ongoing neurological issues ranging from sensory impairments to fatigue, headaches, strokes, and even cognitive and psychiatric problems. ConclusionBy examining various neurological symptoms, this study found a significant association between these manifestations and worse overall outcomes, especially in patients over 60 years old. Identifying high-risk individuals and maintaining a high level of suspicion are crucial for enhancing our understanding of the underlying mechanisms, validating biomarkers, and improving the management of these neurological issues.

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.

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 ObjectivesFocal cerebral arteriopathy (FCA) is a recognized cause of pediatric stroke, but its presentation in adults is poorly defined, with limited cohorts and scarce advanced imaging data. We aimed to describe the clinical spectrum, radiological features, treatment strategies, and outcomes of adult FCA in the largest single-center cohort to date. MethodsWe retrospectively reviewed consecutive adults (>18 years) with ischemic stroke admitted between 2017 and 2024. FCA was defined as unilateral focal stenosis/irregularity of anterior circulation arteries (terminal ICA, M1, M2, A1) after excluding mimics such as vasculitis, dissection, embolic occlusion, and intracranial atherosclerosis. All underwent MRI with contrast-enhanced vessel wall imaging and confirmation on a second modality. Clinical, radiological, and outcome data were collected. Severity was scored using the FCA Severity Score (FCASS). ResultsOf 2,237 stroke admissions, 47 patients (2.1%) met criteria for FCA. Median age was 30 years, with near-equal sex distribution. Hemiparesis with or without aphasia predominated, and strokes were generally mild (median NIHSS 3, mRS 1.2). Preceding clustered TIAs occurred in one-third, and 32% reported new unilateral headache. Infarcts often involved lenticulostriate and MCA watershed territories. Median FCASS was 4. Vessel wall imaging showed concentric enhancement in 74.5%. All patients received antiplatelets; 49% received additional immunosuppression, most often IV methylprednisolone. Over a median 6-month follow-up (mean 12.4), no stroke recurrences occurred, though 5 patients showed radiological progression and 2 developed contralateral stenosis. Functional outcomes were favorable, with 87% achieving mRS 0-2. DiscussionAdult FCA is uncommon but clinically distinct, marked by mild strokes, clustered TIAs, and concentric vessel wall enhancement. The course was largely monophasic, with favorable functional outcomes and no recurrent strokes, regardless of immunosuppressive therapy. Radiological progression was rare but included contralateral involvement, raising the possibility of overlap with unilateral moyamoya disease. Vessel wall imaging is valuable for diagnosis, and longer follow-up is needed to clarify pathogenesis and treatment strategies.

Neurological manifestations of SARS-CoV-2 infection described in isolated case reports and single institutions do not accurately reflect the clinical spectrum of disease across all geographies in a global pandemic. Data collected during peak of the Covid-19 pandemic from stroke centers in five states reveal few similarities to what has recently been published. Given the diversity in phenotype, we caution policymakers and health care providers when considering cerebrovascular complications from SARS-CoV-2 infection.

PurposeCerebral vasospasm following aneurysmal subarachnoid haemorrhage (aSAH) is a significant complication associated with poor neurological outcomes. We present a novel, semi-automated pipeline in ITK-SNAP to segment subarachnoid blood volume from initial CT head (CTH) scans and use this to predict future radiological vasospasm. Methods42 patients were admitted between February 2020 and December 2021 to our tertiary neurosciences centre, and whose initial referral CTH scan was used for this retrospective cohort study. Blood load was segmented using a semi-automated random forest classifier and active contour evolution implemented in the open-source medical imaging analysis software ITK-SNAP. Clinical data were extracted from electronic healthcare records in order to fit models aimed at predicting radiological vasospasm risk. ResultsSemi-automated segmentations demonstrated excellent agreement with manual, expert-derived volumes (mean Dice coefficient=0.92). Total normalised blood volume, extracted from CTH images at first presentation, was significantly associated with greater odds of later radiological vasospasm, increasing by approximately 7% for each additional cm3 of blood (OR=1.069, 95% CI: 1.021-1.120; p<.005). Greater blood volume was also significantly associated with vasospasm of a higher Lindegaard ratio, of longer duration, and a greater number of discrete episodes. Total blood volume predicted radiological vasospasm with a greater accuracy as compared to the modified Fisher scale (AUC= 0.86 vs 0.70), and was of independent predictive value. ConclusionSemi-automated methods provide a plausible pipeline for the segmentation of blood from CT head images in aSAH, and total blood volume is a robust, extendable predictor of radiological vasospasm, outperforming the modified Fisher scale. Greater subarachnoid blood volume significantly increases the odds of subsequent vasospasm, its time course and its severity.

BackgroundThe inflammatory response within the central nervous system is a key driver of secondary brain injury after hemorrhagic stroke, both in patients with intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to characterize inflammatory molecules in the blood and cerebrospinal fluid (CSF) of patients within 72 hours of hemorrhage to understand how such molecules vary across disease types and disease severity. MethodsBiological samples were collected from patients admitted to a single-center Neurosciences Intensive Care Unit with a diagnosis of ICH or aSAH between 2014 and 2022. Control CSF samples were collected from patients undergoing CSF diversion for normal pressure hydrocephalus. A panel of immune molecules in the plasma and CSF samples was analyzed using Cytometric Bead Array assays. Clinical variables, including demographics, disease severity, and intensive care unit length of stay were collected. ResultsPlasma and/or CSF samples were collected from 260 patients (188 ICH patients, 54 aSAH patients, 18 controls). C-C motif chemokine ligand-2 (CCL2), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF), were detectable in the CSF within the first 3 days after hemorrhage, and all were elevated compared to plasma. Compared with controls, CCL2, IL-6, IL-8, G-CSF, and VEGF were elevated in the CSF of both ICH and aSAH patients (p<0.01 for all comparisons). VEGF was increased in ICH patients compared to aSAH patients (p<0.01). CCL2, G-CSF, and VEGF in the CSF were associated with more severe disease in aSAH patients only. ConclusionsWithin 3 days of hemorrhagic stroke, proinflammatory molecules can be detected in the CSF at higher concentrations than in the plasma. Early concentrations of some pro-inflammatory molecules may be associated with markers of disease severity.

Background and purposeIn 2010, a multidisciplinary research group proposed a consensus term and definition for the complication of delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (SAH). We assessed the use of this term and its definition as an endpoint in observational studies and clinical trials. MethodsFirstly, we performed a MEDLINE abstract search from Jan 2008 to Dec 2017 for observational cohort studies and clinical trials to investigate the used terminology over the years. Next, we studied trends in citations of the original paper citing the consensus definitions since publication in 2010. ResultsThe number of publications citing the 2010 consensus definitions has steadily increased from 18 in 2011 to 54 in 2017. Between 2010 and 2017, 527 papers were published with delayed cerebral ischemia, or another term to describe the same complication, as an endpoint. However, the term delayed cerebral ischemia was used only in 131/527 (25%) of papers and only 14/81 (17%) of clinical trials/cohort studies published in 2017 cited the consensus definitions when outlining study endpoints. ConclusionsDespite publication of consensus terminology and definitions for DCI in 2010, the majority of cohort studies and clinical trials in patients with SAH are not using these. Researchers and editors should be reminded of the importance of using these consensus terminology and definitions in future studies, which will promote the comparability of results between studies, understand the true impact of an intervention, aggregate results in meta-analyses, and construct guidelines with a high level of evidence.

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.

BackgroundPerihematomal edema (PHE) expansion exacerbates neurological outcomes in hypertensive intracerebral hemorrhage (HICH). This study investigates the role of fibrinogen in PHE progression. MethodsWe analyzed 94 HICH patients stratified by fibrinogen quartiles (Q1-Q4). Primary outcome was PHE volume on follow-up imaging. Generalized additive models (GAM) and mixed-effects models evaluated associations between fibrinogen, clinical variables, and edema dynamics. ResultsFibrinogen levels differed significantly across quartiles (P<0.001). The highest quartile (Q4: 29.15{+/-}24.38 mL) exhibited larger edema volumes versus Q1-Q3 (23.70{+/-}14.19 mL). Adjusted models revealed fibrinogen ({beta}=1.32, 95%CI 0.87-1.77), hemoglobin ({beta}=-0.45), aspartate aminotransferase ({beta}=0.21), and apolipoprotein B ({beta}=2.15) as independent predictors (all P<0.05), with model R2=0.41-0.42. Coagulation markers (PTA, D-dimer) and imaging features (blend sign) showed secondary associations. ConclusionElevated fibrinogen independently predicts PHE expansion in HICH, suggesting potential therapeutic targeting of hyperfibrinogenemia.

ObjectiveTo report three patients infected with COVID-19 with severe respiratory syndrome requiring intubation, who developed acute demyelinating encephalomyelitis (ADEM). MethodPatient data were obtained from medical records from the North Memorial Health Hospital, Robbinsdale, MN, USA ResultsThree patients (two men and one woman, aged 38 - 63) presented with fatigue, cough and fever leading to development of acute respiratory distress syndrome secondary to COVID-19 infection requiring intubation and ventilatory support. Two patients were unresponsive, one with strong eye deviation to the left and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. All three of the patients received Convalescent plasma therapy for COVID-19. All patients were treated with intravenous corticosteroids and improved, although two responded minimally. Two patients treated with IVIG showed no further improvement. ConclusionNeurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune mediated complication of COVID-19 infection, which may be responsive to corticosteroid treatment. Early recognition of this complication and treatment is important to avoid long term complications.

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.

With ischemic strokes being one of the most pervasive medical issues globally, identifying methods for their accurate diagnosis is becoming increasingly crucial. Two common ischemic stroke subtypes are acute ischemic stroke (AIS) and transient ischemic attack (TIA). Although these two subtypes exhibit similar symptoms, AIS is far more severe than TIA. If AIS is misdiagnosed for TIA, this can lead to inadequate treatment and worse long-term outcomes for patients. Currently, stroke diagnosis relies heavily on patient medical history and imaging techniques, causing high rates of misdiagnosis. However, identifying protein biomarker concentrations associated with AIS and TIA is a promising new method for stroke diagnosis. In this meta-analysis, ten protein biomarkers were analyzed to determine whether or not they would serve as effective diagnostic tools for AIS and TIA. After collecting the mean concentration of each biomarker from 18,160 AIS patients and 3,410 TIA patients, means were compared between AIS and TIA patient groups, determining which biomarkers had a statistically significant difference in concentration between the two stroke subtypes. Biomarkers that yielded statistically significant results were S100B, sNfl, copeptin, IL-6, and MMP-9. MMP-9 yielded the highest difference in concentration between AIS and TIA patients (536.41 {+/-} 134.24 ng/mL in AIS patients vs. 0.11 {+/-} 0.03 ng/mL in TIA patients). A limitation to this study was the smaller sample size of TIA patients included. While this study establishes a baseline for promising protein biomarkers that can be utilized to differentiate AIS and TIA, future studies may want to further investigate each individual biomarker, establishing clear biomarker concentration ranges for AIS and TIA.