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Aims: We understand little of the pathogenesis of developmental cortical lesions, because we understand little of the diversity of the cell types that contribute to the diseases or how those cells interact. We tested the hypothesis that cellular diversity and cell-cell interactions play an important role in these disorders by investigating the signalling molecules in the commonest cortical malformations that lead to childhood epilepsy, focal cortical dysplasia (FCD) and tuberous sclerosis (TS)., Methods: Transcriptional profiling clustered cases into molecularly distinct groups. Using gene expression data, we identified the secretory signalling molecules in FCD/TS and characterised the cell types expressing these molecules. We developed a functional model using organotypic cultures., Results: We identified 113 up-regulated secretory molecules in FCDIIB/TS. The top 12 differentially expressed genes (DEGs) were validated by immunohistochemistry. This highlighted two molecules, Chitinase 3-like protein 1 (CHI3L1) and C-C motif chemokine ligand 2 (CCL2) (MCP1) that were expressed in a unique population of small cells in close proximity to balloon cells (BC). We then characterised these cells and developed a functional model in organotypic slice cultures. We found that the number of CHI3L1 and CCL2 expressing cells decreased following inhibition of mTOR, the main aberrant signalling pathway in TS and FCD., Conclusions: Our findings highlight previously uncharacterised small cell populations in FCD and TS which express specific signalling molecules. These findings indicate a new level of diversity and cellular interactions in cortical malformations and provide a generalisable approach to understanding cell-cell interactions and cellular heterogeneity in developmental neuropathology., (© 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC)., (© 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Purpose: Subdural hematoma (SDH) is quickly becoming the most common neurosurgical pathology due to the aging population. Middle meningeal artery embolization (MMAE) has recently emerged as an effective adjunct to surgical SDH evacuation by decreasing recurrence risk. MMAE has also shown promise as a standalone SDH intervention, but clinical and radiographic predictors of successful MMAE remain ill-defined., Methods: Retrospective chart review from 2020 to 2023 at a single center identified all MMAE cases performed as primary SDH treatment. Cases were classified by hematoma internal architecture as homogeneous, separated, laminar, or trabecular. SDH maximal thickness was assessed on all follow-up imaging and any recurrences or expansions requiring surgery were denoted as treatment failures., Results: 164 standalone MMAE cases were reviewed. Most cases were in male patients (75.0%) with a mean age of 73.2 years. The overall MMAE treatment failure rate was 6.7% with a 4.9% periprocedural complication rate. The cases with trabecular and laminar collections were slightly larger than those with homogeneous and separated collections (16.2 mm vs. 14.2 mm, p = 0.008*), but other baseline characteristics were similar. The MMAE failure rate was significantly lower in the laminar and trabecular subgroup (1.2%) compared to the homogeneous and separated subgroup (12.4%) (p = 0.005*). Homogeneous and separated internal hematoma architecture was the only predictor of MMAE failure in multivariate analysis (OR 10.5, p = 0.027*) and was also associated with delayed SDH resorption (ANOVA: F = 4.8, p = 0.0025*)., Conclusions: Standalone MMAE is an effective, safe, and durable treatment for non-acute SDHs, and is especially effective for SDHs with more membranous internal architecture., Competing Interests: Declarations. Ethical approval: This study was approved by the Northwell Feinstein Institute Human Research Protection Program Institutional Review Board: #24–0246 and adheres to the Declaration of Helsinki. Informed consent: As documented in the study protocol approved by our institutional review board and referenced above, informed consent was waived due to the retrospective, non-interventional nature of this study. Competing interests: The authors declare that this research was conducted in the absence of any commercial, financial, or other non-financial relationships that could be construed as a competing interest or a conflict of interest. The authors therefore have no relevant conflicts of interest or competing interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic subdural hematoma (SDH) is a particularly challenging pathology due to high recurrence rates (2%-37%) and complex medical comorbidities that tend to afflict the patient population. Recently, there have been several case series published describing the use of middle meningeal artery (MMA) embolization as an alternative to surgery for treatment of new or recurrent chronic SDH., Objective: To describe our first 60 cases of MMA embolization for chronic SDH., Methods: MMA embolization was performed using angiography, selective microcatheterization of the MMA, and infusion of polyvinyl alcohol particles. Outcomes were assessed clinically and with interval imaging studies at 1 d, 2 wk, and 6 wk postprocedure, and additional intervals as indicated., Results: MMA embolization was performed successfully on 60 total SDHs in 49 patients. This includes upfront treatment for new (not previously treated) SDH in 42, for recurrence in 8, and prophylaxis (soon after surgical evacuation) in 10. There were 3 mortalities (unrelated to the procedure), and no procedural complications. Of the 50 nonprophylactic cases, there were 4 (8.9%) cases of recurrence requiring surgical evacuation, and 31 (68.9%) that had resolution or reduction in size >50% of SDH at longest follow-up. Overall, 41 (91.1%) were stable or decreased in size and able to avoid surgery., Conclusion: MMA embolization may represent a minimally-invasive alternative to surgery for new or recurrent chronic SDH, or as prophylaxis to reduce the risk of recurrence after surgery. Given our encouraging results with a 91% long-term success rate, a large scale clinical trial is warranted., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background: Embolization of the middle meningeal artery (MMA) has recently been proposed as an alternative to surgery for treatment of chronic subdural hematoma (SDH). There is increasing evidence that fragile neovasculature arising from distal branches of the MMA found within the membrane that forms around a chronic SDH is responsible for high recurrence rates due to chronic, repeated rebleeding. Embolization of the MMA could thus potentially eliminate the blood supply to this membrane and prevent further rebleeding., Methods: The cases of 6 patients with 7 recurrent SDHs treated with MMA embolization with polyvinyl alcohol particles were retrospectively reviewed., Results: MMA embolization was performed successfully in all 6 patients with no complications. Of the 7 SDHs treated, 1 required surgical reevacuation due to recurrence. The other 6 were able to avoid surgery, with reduction in size from 12 mm to 11 mm over 3 weeks, 14 mm to 9 mm over 9 weeks, 21 mm to 5 mm over 31 weeks, 17 mm to 9 mm over 12 weeks, 18 mm to 3 mm over 8 weeks, and 25 mm to 6 mm over 24 weeks. All patients had resolution of symptoms at longest follow-up., Conclusions: In this case series of 6 patients harboring 7 recurrent, chronic SDHs, 6 of the 7 were successfully treated with MMA embolization and able to avoid surgery for reevacuation, suggesting that this minimally invasive technique may represent an effective alternative to surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and purpose Embolization of the middle meningeal artery (MMA) has recently been proposed as an alternative to surgery for treatment of chronic subdural hematoma (SDH), and several case reports have been published supporting its efficacy. It has been suggested that the primary pathologic process in chronic SDH is repeated microhemorrhaging into the subdural collection from fragile neovasculature within the SDH membrane that arises from distal branches of the MMA. Embolization could thus provide a means of eliminating this chronic rebleeding. Materials and methods Images were selected from MMA embolization procedures performed at our institution in order to illustrate the technique and theory behind its efficacy for treatment of chronic SDH. Results Images from MMA angiograms demonstrate the variability of MMA anatomy and help illustrate the importance of avoiding potential ophthalmic collaterals and branches supplying cranial nerves. The findings of irregular wispiness of the distal MMA vasculature, contrast outlining of the SDH membrane on angiography, and homogenous increased density within the SDH on postembolization head computed tomography are described. Conclusion MMA embolization may provide a safe alternative for treatment of chronic SDH, but careful angiographic assessment of MMA anatomy should be performed to avoid potential complications. The findings illustrated here lend support to the theory that the pathologic process of chronic SDH is repeated leakage of blood products from an inflamed, abnormal arterial neovasculature within the SDH membrane that arises from the MMA, and thus selective embolization could provide an effective treatment.

The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pathomechanisms of neurodegenerative disease. Here we show that continued 26S proteasome dysfunction in mouse brain cortical neurons causes paranuclear accumulation of fragmented dysfunctional mitochondria, associated with earlier recruitment of Parkin and lysine 48-linked ubiquitination of mitochondrial outer membrane (MOM) proteins, including Mitofusin-2. Early events also include phosphorylation of p62/SQSTM1 (p62) and increased optineurin, as well as autophagosomal LC3B and removal of some mitochondria, supporting the induction of selective autophagy. Inhibition of the degradation of ubiquitinated MOM proteins with continued 26S proteasome dysfunction at later stages may impede efficient mitophagy. However, continued 26S proteasome dysfunction also decreases the levels of essential autophagy proteins ATG9 and LC3B, which is characterised by decreases in their gene expression, ultimately leading to impaired autophagy. Intriguingly, serine 351 phosphorylation of p62 did not enhance its binding to Keap1 or stabilise the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor in this neuronal context. Nrf2 protein levels were markedly decreased despite transcriptional activation of the Nrf2 gene. Our study reveals novel insights into the interplay between the UPS and autophagy in neurons and is imperative to understanding neurodegenerative disease where long-term proteasome inhibition has been implicated.

Aims: Published reports of brain weight in sudden infant death syndrome (SIDS) are contradictory, although several have concluded that brain weight is increased in SIDS compared with controls or reference data. This is important as, if brain weight is significantly different, it may be of diagnostic use or provide insights into the aetiology of SIDS. The aim of this study was to use a large series of well-characterized sudden unexpected infant deaths from a single centre to provide definitive data regarding this issue., Methods: A retrospective review identified 1100 infants who had died suddenly and undergone a comprehensive autopsy at Great Ormond Street Hospital between 1996 and 2011. They were split into two groups: those in whom death could be explained and those whose deaths remained unexplained despite full investigation (SIDS/unexplained sudden unexpected death in infancy)., Results: There were 1100 cases of whom 573 (52%) were unexplained and 527 (48%) explained. Multiple regression analysis, which adjusted for sex, age and post-mortem interval, showed no difference in the ratio of brain weight : body weight between those infants dying of explained causes and those in whom no cause could be found. This finding remained true when restricting analysis to those with macroscopically normal brains., Conclusions: In this large series of infants dying of both explained and unexplained causes, brain weight, once corrected for body weight, did not vary consistently with the cause of death. Brain weight cannot be used as a diagnostic indicator of the cause of death or to inform hypothetical models of the pathogenesis of SIDS., (© 2015 British Neuropathological Society.)

Background: An 18-month-old boy developed encephalopathy, for which extensive investigation failed to identify an etiology, 6 weeks after stem cell transplant. To exclude a potential infectious cause, we performed high-throughput RNA sequencing on brain biopsy., Methods: RNA-Seq was performed on an Illumina Miseq, generating 20 million paired-end reads. Nonhost data were checked for similarity to known organisms using BLASTx. The full viral genome was sequenced by primer walking., Results: We identified an astrovirus, HAstV-VA1/HMO-C-UK1(a), which was highly divergent from human astrovirus (HAstV 1-8) genotypes, but closely related to VA1/HMO-C astroviruses, including one recovered from a case of fatal encephalitis in an immunosuppressed child. The virus was detected in stool and serum, with highest levels in brain and cerebrospinal fluid (CSF). Immunohistochemistry of the brain biopsy showed positive neuronal staining. A survey of 680 stool and 349 CSF samples identified a related virus in the stool of another immunosuppressed child., Conclusions: The discovery of HAstV-VA1/HMO-C-UK1(a) as the cause of encephalitis in this case provides further evidence that VA1/HMO-C viruses, unlike HAstV 1-8, are neuropathic, particularly in immunocompromised patients, and should be considered in the differential diagnosis of encephalopathy. With a turnaround from sample receipt to result of <1 week, we confirm that RNA-Seq presents a valuable diagnostic tool in unexplained encephalitis., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet. Here, we performed methylation-based DNA profiling and transcriptome RNA sequencing analysis of 80 ST-EPN ZFTA-RELA investigating the clinical significance of various molecular patterns. The principal types of ZFTA-RELA fusions, based on breakpoint location, demonstrated no significant correlations with clinical outcomes. Multigene analysis disclosed 1892 survival-associated genes, and a metagene set of 100 genes subdivided ST-EPN ZFTA-RELA into favorable and unfavorable transcriptome subtypes composed of different cell subpopulations as detected by deconvolution analysis. BGN (biglycan) was identified as the top-ranked survival-associated gene and high BGN expression levels were associated with poor survival (Hazard Ratio 17.85 for PFS and 45.48 for OS; log-rank; p-value < 0.01). Furthermore, BGN immunopositivity was identified as a strong prognostic indicator of poor survival in ST-EPN, and this finding was confirmed in an independent validation set of 56 samples. Our results indicate that integrating BGN expression (at mRNA and/or protein level) into risk stratification models may improve ST-EPN ZFTA-RELA outcome prediction. Therefore, gene and/or protein expression analyses for this molecular marker could be adopted for ST-EPN ZFTA-RELA prognostication and may help assign patients to optimal therapies in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Aims: Abnormalities of the hippocampus are associated with a range of diseases in children, including epilepsy and sudden death. A population of rod cells in part of the hippocampus, the polymorphic layer of the dentate gyrus, has long been recognized in infants. Previous work suggested that these cells were microglia and that their presence was associated with chronic illness and sudden infant death syndrome. Prompted by the observations that a sensitive immunohistochemical marker of microglia used in diagnostic practice does not typically stain these cells and that the hippocampus is a site of postnatal neurogenesis, we hypothesized that this transient population of cells were not microglia but neural progenitors., Methods: Using archived post mortem tissue, we applied a broad panel of antibodies to establish the immunophenotype of these cells in 40 infants dying suddenly of causes that were either explained or remained unexplained, following post mortem investigation., Results: The rod cells were consistently negative for the microglial markers CD45, CD68 and HLA-DR. The cells were positive, in varying proportions, for the neural progenitor marker, doublecortin, the neural stem cell marker, nestin and the neural marker, TUJ1., Conclusions: These data support our hypothesis that the rod cells of the polymorphic layer of the dentate gyrus in the infant hippocampus are not microglia but a population of neural progenitors. These findings advance our understanding of postnatal neurogenesis in the human hippocampus in health and disease and are of diagnostic importance, allowing reactive microglia to be distinguished from the normal population of neural progenitors., (© 2013 British Neuropathological Society.)

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal infant death in the developed world. The cause of SIDS is unknown but several hypotheses have been proposed, including the 'triple risk hypothesis', which predicts that foetal development of infants who subsequently succumb to SIDS is abnormal, leaving them unable to respond appropriately to stressors. Consistent with this hypothesis, a large number of studies have reported changes in the brain in SIDS. However, on nearly every subject, the reported findings vary widely between studies. Inconsistencies in the definitions of SIDS used and in control group selection are likely to underlie much of this variability. Therefore, in our analysis, we have included only those studies that met simple criteria for both the definition of SIDS and the control group. Of the 153 studies retrieved by our review of the literature, 42 (27%) met these criteria. Foremost among the findings reported by these studies are abnormalities of the brain stem, in particular brain stem gliosis and defects of neurotransmission in the medulla. However, these studies have not identified what could be considered in diagnostic terms a causative structural or biochemical abnormality for use in routine clinical practice. An assessment of changes in the architecture and composition of brain regions and changes in neurotransmission in multiple systems in a single, large cohort of well- and consistently characterized infants dying suddenly of a range of causes is needed before the inter-relation of these different features can be appreciated., (© 2013 British Neuropathological Society.)

Background: The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size., Methods: Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports., Results: Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size., Conclusions: Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size.

Focal cortical dysplasia (FCD) is a localized malformation of cortical development and is the commonest cause of severe childhood epilepsy in surgical practice. Children with FCD are severely disabled by their epilepsy, presenting with frequent seizures early in life. The commonest form of FCD in children is characterized by the presence of an abnormal population of cells, known as balloon cells. Similar pathological changes are seen in the cortical malformations that characterize patients with tuberous sclerosis complex (TSC). However, the cellular and molecular mechanisms that underlie the malformations of FCD and TSC are not well understood. We provide evidence for a defect in autophagy in FCD and TSC. We have found that balloon cells contain vacuoles that include components of the autophagy pathway. Specifically, we show that balloon cells contain prominent lysosomes by electron microscopy, immunohistochemistry for LAMP1 and LAMP2, LysoTracker labelling and enzyme histochemistry for acid phosphatase. Furthermore, we found that balloon cells contain components of the ATG pathway and that there is cytoplasmic accumulation of the regulator of autophagy, DOR. Most importantly we found that there is abnormal accumulation of the autophagy cargo protein, p62. We show that this defect in autophagy can be, in part, reversed in vitro by inhibition of the mammalian target of rapamycin (mTOR) suggesting that abnormal activation of mTOR may contribute directly to a defect in autophagy in FCD and TSC.

Infantile-onset X-linked spinal muscular atrophy (SMAX2) is a rare lethal disorder linked to mutations in the UBA1 (previously UBE1) gene, encoding ubiquitin-activating enzyme 1 that has an important role in the ubiquitin-proteasome pathway. Published pathological reports are scarce. Here we report a male infant who presented from birth with predominantly truncal hypotonia following an antenatal history of reduced fetal movements. He had a myopathic face, profound weakness, multiple contractures and areflexia. Creatine kinase was moderately raised. Brain MRI showed non-specific symmetrical periventricular white matter changes. Neurophysiology revealed evidence of motor and sensory involvement and muscle biopsy showed marked inflammatory changes with subtle features suggestive of acute denervation. UBA1 sequencing revealed a novel hemizygous missense mutation (c.1670A>T; p.Glu557Val). He died from progressive respiratory failure at 4 months. On post mortem assessment, in addition to severe ventral motor neuron pathology, there was widespread involvement of the sensory system, as well as developmental and degenerative cerebellar abnormalities. In contrast to typical SMN1-associated SMA, the thalamus was unaffected. These findings indicate that SMAX2 is more accurately classified as a motor sensory neuronopathy rather than a pure anterior horn cell disorder. Ubiquitin-proteasome pathway defects may not only cause neurodegeneration but also affect normal neuronal development., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. α-synuclein is the main component of LB, but the pathological mechanisms that lead to neurodegeneration associated with LB formation remain unclear. Three pivotal elements have emerged in the development of PD: α-synuclein, mitochondria and protein degradation systems. We previously reported a unique model, created by conditional genetic depletion of 26S proteasomes in the SNpc of mice, which mechanistically links these three elements with the neuropathology of PD: progressive neurodegeneration and intraneuronal inclusion formation. Using this model, we tested the hypothesis that α-synuclein was essential for the formation of inclusions and neurodegeneration caused by 26S proteasomal depletion. We found that both of these processes were independent of α-synuclein. This provides an important insight into the relationship between the proteasome, α-synuclein, inclusion formation and neurodegeneration. We also show that the autophagy-lysosomal pathway is not activated in 26S proteasome-depleted neurones. This leads us to suggest that the paranuclear accumulation of mitochondria in inclusions in our model may reflect a role for the ubiquitin proteasome system in mitochondrial homeostasis and that neurodegeneration may be mediated through mitochondrial factors linked to inclusion biogenesis.

Background: Current guidelines for the investigation of sudden unexpected death in infancy (SUDI) include full neuropathological examination with recommendations for brain fixation for 1-2 weeks. Little evidence is available regarding the yield of such examination in determining cause of death in clinical practice. This study examines the frequency of neuropathological findings determining cause of death at postmortem examination in SUDI in relation to clinical and macroscopic features., Methods: All postmortem examinations performed for the indication of SUDI at a single specialist centre over a 14-year period were reviewed, including clinical history, macroscopic and neuropathological findings., Results: 6% of postmortem examinations performed for cases of SUDI demonstrated a neuropathological cause of death; in almost all (>90%) the clinical history and/or macroscopic examination suggested the cause of death. In 2% of all cases the cause of death was determined by histological neuropathological examination, but there were no cases in which histological neuropathological examination of a macroscopically normal brain revealed the cause of death in the absence of a 'neurological history'. Macroscopic brain abnormalities and the presence of a 'neurological history' were significantly more likely to yield histological brain abnormalities (11-fold and fourfold, respectively)., Conclusions: Histological neuropathological examination rarely determines the cause of death in SUDI in the absence of macroscopic abnormalities or neurological clinical history. A macroscopically abnormal brain and the presence of a clinical history of possible neurological disease or of inflicted injury are significantly more likely to be associated with significant histological brain abnormalities.

Objective: To report the clinical and radiologic features in a patient with myelofibrosis who developed atypical progressive multifocal leukoencephalopathy., Design: Case report., Setting: Tertiary referral center. Patient A 72-year-old man with myelofibrosis and mild leukopenia experienced progressive limb weakness and dysarthria., Results: Imaging revealed almost complete sparing of the white matter with isolated involvement of the brainstem and deep gray matter. Postmortem examination led to definitive diagnosis of progressive multifocal leukoencephalopathy and demonstrated an unusual miliary pattern of disease rather than the typical confluent involvement. Genetic analysis revealed a mutation in the transcription control region of the JC polyomavirus, prompting speculation about the pathogenesis of progressive multifocal leukoencephalopathy., Conclusions: Leukopenia may render patients effectively immunosuppressed. The differential diagnosis should include progressive multifocal leukoencephalopathy even in patients with atypical clinical and radiologic features.

This report introduces a novel surgical technique for middle meningeal artery embolization (MMAE) during a mini-craniotomy for subdural hematoma (SDH) evacuation. A patient with multiple health issues presented with a 14 mm right subacute SDH. During surgery, the MMA was retrogradely catheterized and embolized using Onyx 18. This approach, combining MMAE with hematoma evacuation, resulted in successful resolution of the SDH without complications. The procedure offers a more efficient workflow by integrating 2 interventions into 1, potentially reducing recurrence rates of SDH. [ABSTRACT FROM AUTHOR]

Objective: Chronic subdural hematoma (CSDH) is a common neurologic disorder with increasing incidence, which can be preceded by head trauma or occur in the absence of trauma. In order to deeply understand the clinical characteristics of this disease, we conducted this retrospective study to explore the clinical differences between traumatic and not otherwise specified (NOS) CSDH. Methods: According to the inclusion and exclusion criteria, 168 traumatic CSDH patients and 133 NOS CSDH patients were recruited from January 2015 to October 2023 in our cohort. The collected data and compared parameters including baseline clinical features and radiological outcomes of hematoma within 24 h of hospital admission, as well as the treatment method and clinical outcome of traumatic and NOS CSDH patients. Results: Compared to NOS CSDH patients, the average age was younger, epilepsy was more frequent, asymptomatic cases were more common, and the taking of anticoagulants and antiplatelet drugs were rarer in traumatic CSDH patients (all P < 0.05). However, no differences were found in the radiological presentations of hematoma at admission, the treatment methods and clinical outcomes of traumatic and NOS CSDH patients (all P > 0.05). Conclusion: Traumatic CSDH patients were more likely to be asymptomatic or have seizures, while NOS CSDH were more common in elder people and in individuals with the history of taking anticoagulants and antiplatelet drugs. The treatment methods and clinical outcomes were similar in traumatic and NOS CSDH patients. [ABSTRACT FROM AUTHOR]

The study evaluates chronic subdural hematoma (cSDH) middle meningeal artery (MMA) embolization efficacy and safety. A prospective interventional study was conducted in Viet Duc Hospital from November 2021 to April 2024. All consecutive cSDH MMA embolization patients were included. Clinical and imaging data were collected before and one month after treatment. The study included 31 42-cSDH patients. Of these, 25.8% had hematoma evacuation, 83.9% were treated with surgery and embolization, and 16.1% with embolization alone. 92.9% of procedures used polyvinyl alcohol particles. The success rate was 92.9% and complications 7.1%. Asymptomatic external carotid artery vasospasm and MMA rupture occurred. Functional improvement occurred in 91.7% of patients one month after treatment. Significantly lower mean modified Rankin Scale (mRS) score (0.2±0.7 vs. 1.7±0.9; P=0.000) and higher proportion of patients with =2 mRS score (95.8% vs. 74.1%) were observed after treatment. Hematoma thickness decreased significantly (P=0.00) from 21.5±7.9 mm to 8.3±4.1 mm. The midline shift decreased significantly from 7.4±5.0 mm to 0.7±1.2 mm (P=0.00). Just one patient (4.2%) needed surgery. MMA embolization alone or with surgery appears to treat cSDH safely and effectively. [ABSTRACT FROM AUTHOR]

Purpose: To identify prognostic factors with emphasis on chronic subdural hematoma (CSDH) architecture that determines short-term outcome of middle meningeal artery embolization (MMAE)., Methods: Consecutive CSDH patients treated by MMAE (November 2019 and March 2022) were retrospectively analyzed. Four architectures were analyzed: homogeneous, laminar, separated, and trabecular types. Predictor variables from baseline CT were correlated with radiological endpoint (≥ 50% of hematoma volume reduction), time to reach the endpoint, and rate of volume reduction., Results: Study included 50 patients with 56 CSDHs (median age [first quartile, Q1; third quartile, Q3] 70.5 [60, 78.3] years; 36 were men). Separated type reached the endpoint at a lower rate on both bivariate (p = 0.02) and multivariate Cox model (0.034). Kaplan-Meier curves demonstrated that the median [Q1, Q3] time for 50% of the hematomas to reach the endpoint was 5 [4, 8], 4 [3, 5], 15 [15, 15], and 11 [4, 19] weeks for homogeneous, laminar, separated, and trabecular types, respectively. Linear mixed-effect model demonstrated a significant variation in the slope of hematoma volume reduction that was - 4.16 (95% confidence interval [CI] - 5.4, - 2.9), - 6.7 (95% CI - 8.35, - 5.1), - 2.03 (95% CI - 4.14, 0.08), and - 5.06 (95% CI - 6.8, - 3.32) ml per week for homogeneous, laminar, separated, and trabecular subtypes, respectively., Conclusion: Separated CSDH is a poor prognostic type in achieving radiological endpoint and a slower rate of volume reduction. While, homogeneous and laminar types reached the endpoint faster than separated and trabecular types on short-term follow-up., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The results from studies that compare middle meningeal artery (MMA) embolization vs conventional management for patients with chronic subdural hematoma are varied., Objective: To conduct a systematic review and meta-analysis on studies that compared MMA embolization vs conventional management., Methods: Medline, PubMed, and Embase databases were searched. Primary outcomes were treatment failure and surgical rescue; secondary outcomes were complications, follow-up modified Rankin scale > 2, mortality, complete hematoma resolution, and length of hospital stay (day). The certainty of the evidence was determined using the GRADE approach., Results: Nine studies yielding 1523 patients were enrolled, of which 337 (22.2%) and 1186 (77.8%) patients received MMA embolization and conventional management, respectively. MMA embolization was superior to conventional management for treatment failure (relative risk [RR] = 0.34 [0.14-0.82], P = .02), surgical rescue (RR = 0.33 [0.14-0.77], P = .01), and complete hematoma resolution (RR = 2.01 [1.10-3.68], P = .02). There was no difference between the 2 groups for complications (RR = 0.93 [0.63-1.37], P = .72), follow-up modified Rankin scale >2 (RR = 0.78 [0.449-1.25], P = .31), mortality (RR = 1.05 [0.51-2.14], P = .89), and length of hospital stay (mean difference = -0.57 [-2.55, 1.41], P = .57). For MMA embolization, the number needed to treat for treatment failure, surgical rescue, and complete hematoma resolution was 7, 9, and 3, respectively. The certainty of the evidence was moderate to high for primary outcomes and low to moderate for secondary outcomes., Conclusion: MMA embolization decreases treatment failure and the need for surgical rescue without furthering the risk of morbidity and mortality. The authors recommend considering MMA embolization in the chronic subdural hematoma management., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Middle meningeal artery (MMA) embolization has recently emerged as a treatment option for chronic subdural hematoma (cSDH). It is considered a simple and potentially safe endovascular procedure., Objective: To compare between 2 different embolic agents; onyx (ethylene vinyl alcohol) and emboparticles (polyvinyl alcohol particles-PVA) for endovascular treatment of cSDH., Methods: A retrospective analysis of all patients who underwent MMA embolization for cSDH treatment in 2 comprehensive centers between August 2018 and December 2021. Primary outcomes were failure of embolization and need for rescue surgical evacuation., Results: Among 97 MMA embolizations, 49 (50.5%) received onyx and 48 (49.5%) received PVA. The presence of acute or subacute on cSDH was higher in the PVA group 11/49 (22.5%) vs 30/48 (62.5%), respectively, P < .001. There were no significant differences between both groups regarding failure of embolization 6/49 (12.2%) vs 12/48 (25.0%), respectively, P = .112, and need of unplanned rescue surgical evacuation 5/49 (10.2%) vs 8/48 (16.7%), respectively, P = .354. Hematoma thickness at late follow-up was significantly smaller in the PVA group 7.8 mm vs 4.6 mm, respectively; P = .017., Conclusion: Both onyx and PVA as embolic agents for cSDH can be used safely and have comparable clinical and surgical outcomes., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Middle meningeal artery embolization (MMAE) for chronic subdural hematomas (cSDHs) has evolved as a potential treatment alternative for these lesions. The indications for using this treatment modality and the pathophysiology of cSDHs are an area of considerable interest. A retrospective review was performed including all major papers addressing this topic. Although considered a relatively new treatment option, MMAE for cSDHs is gaining widespread popularity. There are many questions that need to be addressed regarding its indications, some of which are the subject of ongoing clinical trials. The efficacy of this treatment modality in carefully selected patients has also provided new insights into the potential pathophysiology of cSDHs. This concise review will focus on the current evidence supporting the use of embolization in the treatment of this disease and highlight unanswered relevant clinical questions regarding MMAE indications and technique., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

A novel histomolecular tumor of the central nervous system (CNS), the "diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC)," has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis. [ABSTRACT FROM AUTHOR]

Balloon cells (BCs) are specific pathological marker of cortical malformations during brain development, often associated with epilepsy and development delay. Although a large number of studies have investigated the role of BCs in these diseases, the specific function of BCs as either epileptogenic or antiepileptic remains controversial. Therefore, we reviewed literatures on BCs, delved into the molecular mechanisms and signaling pathways, and updated their profile in several aspects. Firstly, BCs are heterogeneous and some of them show progenitor/stem cell characteristics. Secondly, BCs are relatively silent in electrophysiology but not completely isolated from their surroundings. Notably, abnormal mTOR signaling and aberrant immunogenic process have been observed within BCs-containing malformations of cortical development (MCDs). The question whether BCs function as the evildoer or the defender in BCs-containing MCDs is further discussed. Importantly, this review provides perspectives on future investigations of the potential role of BCs in epilepsy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic subdural hematoma (CSDH) has significant patient morbidity and recurrence that drives the management towards less invasive procedures. We describe the different indications of middle meningeal artery embolization (MME) in management of CSDH. OBJECTIVE: We aimed to report and evaluate our institutional experience using MME in management of CSDH. PATIENTS AND METHODS: Retrospective analysis was conducted between 2020 and 2023, we reviewed the different indications of MME using different embolization material. Clinical and radiological outcomes were described 6 months and 1 year postoperatively. RESULTS: Twenty one CSDHs were treated in 16 patients (5 patients had bilateral CSDH). In patients with bilateral CSDH each hematoma was considered separately. Of the 21 hematomas, 7 (33.3%) were treated upfront without prior surgical treatment, 4 (19.1%) were treated for recurrence after prior surgical evacuation, and 10 (47.6%) were treated prophylactically following surgical evacuation. Post embolization, one hematoma needed to be evacuated due to failure of hematoma volume reduction. By the end of one year follow up, 50% reduction in hematoma size was achieved in 13 hematomas (62%), while total disappearance was evident in 7 hematomas (33.3%). Recurrence was noted in one patient on renal dialysis which was managed conservatively. The modified Rankin scale (mRS) improved after 6 months in comparison to the admission time from 3 ± 1.2 to 1.6 ± 0.63 with p value of 0.003. CONCLUSION: The MME is a safe and effective technique that should be considered in management of CSDH in patients with multiple morbidities and patients who have high risk of recurrence. [ABSTRACT FROM AUTHOR]

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical condition with a high risk of recurrence after treatment., Objective: To assess and compare the risk of recurrence, morbidity, and mortality across various treatments for CSDH., Methods: A systematic review and meta-analysis was performed. PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched from January 01, 2000, to July 07, 2021. The primary outcome was recurrence, and secondary outcomes were morbidity and mortality. Component network meta-analyses (CNMAs) were performed for surgical and medical treatments, assessing recurrence and morbidity. Incremental risk ratios (iRRs) with 95% CIs were estimated for each component., Results: In total, 12 526 citations were identified, and 455 studies with 103 645 cases were included. Recurrence occurred in 11 491/93 525 (10.8%, 95% CI 10.2-11.5, 418 studies) cases after surgery. The use of a postoperative drain (iRR 0.53, 95% CI 0.44-0.63) and middle meningeal artery embolization (iRR 0.19, 95% CI 0.05-0.83) reduced recurrence in the surgical CNMA. In the pharmacological CNMA, corticosteroids (iRR 0.47, 95% CI 0.36-0.61) and surgical intervention (iRR 0.11, 95% CI 0.07-0.15) were associated with lower risk. Corticosteroids were associated with increased morbidity (iRR 1.34, 95% CI 1.05-1.70). The risk of morbidity was equivalent across surgical treatments., Conclusion: Recurrence after evacuation occurs in approximately 10% of cSDHs, and the various surgical interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Neurodegenerative disorders are typically featured by the occurrence of neuronal inclusions. In the case of Parkinson's disease (PD) these correspond to Lewy bodies (LBs), which are routinely defined as proteinaceous inclusions composed of alpha-synuclein (alpha-syn). In turn, alpha-syn is considered to be the key protein in producing PD and fostering its progression. Recent studies challenged such a concept and emphasized the occurrence of other proteins such as p62 and poly-ubiquitin (Poly-ub) in the composition of LBs, which are also composed of large amounts of tubulo-vesicular structures. All these components, which accumulate within the cytosol of affected neurons in PD, may be the consequence of a dysfunction of major clearing pathways. In fact, autophagy-related systems are constantly impaired in inherited PD and genetic models of PD. The present study was designed to validate whether a pharmacological inhibition of autophagy within catecholamine cells produces cell damage and accumulation of specific proteins and tubulo-vesicular structures. The stoichiometry counts of single proteins, which accumulate within catecholamine neurons was carried out along with the area of tubulo-vesicular structures. In these experimental conditions p62 and Poly-ub accumulation exceeded at large the amounts of alpha-syn. In those areas where Poly-ub and p62 were highly expressed, tubulo-vesicular structures were highly represented compared with surrounding cytosol. The present study confirms new vistas about LBs composition and lends substance to the scenario that autophagy inhibition rather than a single protein dysfunction as key determinant of PD., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article., (© 2024. The Author(s).)

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Objective: Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. Methods: The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. Results: The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. Conclusion: Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review and meta-analysis evaluating the efficacy of middle meningeal artery embolization in terms of both clinical and radiographic outcomes, when performed with different embolic agents. Methods: A systematic literature review and meta-analysis was performed to evaluate the impact of embolic agents on outcomes for middle meningeal artery (MMA) embolization. The use of polyvinyl alcohol (PVA) with or without (±) coils, N-butyl cyanoacrylate (n-BCA) ± coils, and Onyx alone were separately evaluated. Primary outcome measures were recurrence, the need for surgical rescue and in-hospital periprocedural complications. Results: Thirty-one studies were identified with a total of 1,134 patients, with 786 receiving PVA, 167 receiving n-BCA, and 181 patients receiving Onyx. There was no difference in the recurrence rate (5.5% for PVA, 4.5% for n-BCA, and 6.5% for Onyx, with P=0.71) or need for surgical rescue (5.0% for PVA, 4.0% for n-BCA, and 6.9% for Onyx, with P=0.89) based on the embolic agent. Procedural complications also did not differ between embolic agents (1.8% for PVA, 3.6% for n-BCA, and 1.6% for Onyx, with P=0.48). Conclusions: Rates of recurrence, need for surgical rescue, and periprocedural complication following MMA embolization are not impacted by the type of embolic agent utilized. Ongoing clinical trials may be used to further investigate these findings. [ABSTRACT FROM AUTHOR]