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Intrinsic cerebrospinal fluid (CSF) dynamics in the brain have been extensively studied, particularly the egress sites of tagged intrinsic CSF in the meninges. Although spinal CSF recirculates within the central nervous system (CNS), we hypothesized that CSF outflows from the lumbar spinal canal. We aimed to visualize and semi-quantify the outflow using non-contrast MRI techniques. We utilized a 3 Tesla clinical MRI with a 16-channel spine coil, employing time-spatial labeling inversion (Time-SLIP) with tag-on and tag-off acquisitions, T2-weighted coronal 2D fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal 3D centric ky-kz single-shot FSE (cSSFSE). Images were acquired using time-spatial labeling inversion pulse (Time-SLIP) with tag-on and tag-off acquisitions with varying TI periods. Ten healthy volunteers with no known spinal diseases participated. Variations in tagged CSF outflow were observed across different thoracolumbar nerve root segments in all participants. We quantified CSF outflow at all lumbar levels and the psoas region. There was no significant difference among the ROIs for signal intensity. The tagged CSF outflow from the spinal canal is small but demonstrates egress to surrounding tissues. This finding may pave the way for exploring intrathecal drug delivery, understanding of CSF-related pathologies and its potential as a biomarker for peripheral neuropathy and radiculopathy.

• Diffusion in subarachnoid space was more isotropic with aging in young adults. • Other brain regions did not show an age-related decline of diffusion anisotropy. • Diffusion anisotropy in subarachnoid space was highest in the temporal lobe. • Reduced anisotropy may be relevant to reduced glymphatic transport with aging. The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. For instance, the SAS around the middle cerebral artery is known to be highly involved in glymphatic influx. While diffusion tensor imaging has been used for studying the glymphatic system, there has been limited exploration of age-related changes in diffusion anisotropy within SAS and their regional variations. Given the narrow and heterogeneous morphology of SAS, the fractional anisotropy (FA) in diverse brain regions may be more relevant to glymphatic transport than mean diffusivity (MD). The goal of this study was to investigate FA in SAS to observe age-related changes across different brain regions and to interpret the results based on the glymphatic transport. We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport. [ABSTRACT FROM AUTHOR]

The article in Brain Pathology discusses spinal intradural pseudocyst formation in patients with superficial siderosis of the central nervous system (SSCNS). The study examines three cases of SSCNS patients with spinal dural defects and intraspinal fluid collections. The findings suggest that the intradural pseudocyst observed in SSCNS patients is formed by the dissection of the spinal dura mater, leading to hemosiderin deposition and neurological symptoms. Surgical repair of the dural defect resulted in the improvement of symptoms and reduction of intraspinal fluid collection. [Extracted from the article]

Accumulation of immune cells and proteins in the subarachnoid space (SAS) is found during multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis (EAE). Whether the flow of cerebrospinal fluid (CSF) along the SAS of the spinal cord is impacted is yet unknown. Combining intravital near-infrared (NIR) imaging with histopathological analyses, we observed a significantly impaired bulk flow of CSF tracers within the SAS of the spinal cord prior to EAE onset, which persisted until peak stage and was only partially recovered during chronic disease. The impairment of spinal CSF flow coincided with the appearance of fibrin aggregates in the SAS, however, it preceded immune cell infiltration and breakdown of the glia limitans superficialis. Conversely, cranial CSF efflux to cervical lymph nodes was not altered during the disease course. Our study highlights an early and persistent impairment of spinal CSF flow and suggests it as a sensitive imaging biomarker for pathological changes within the leptomeninges. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The objective of this study was to analyze failed posterior fossa decompression (PFD) in patients with basilar invagination and atlantoaxial dislocation (BI‐AAD). Revision surgery in these patients is challenging and has been rarely reported. In addition, the anatomical variations of the vertebral artery increase the risk of revision surgery. Here, we introduce the implementation of a new type of one‐stage posterior revision surgery, whose difficulties and effects are summarized.A total of 21 patients with BI‐AAD who underwent PFD were retrospectively analyzed in our center from November 2017 to April 2021. The revision surgery in all patients was performed through the posterior approach. The Japanese Orthopaedic Association (JOA) score and the Short Term 12 (SF‐12) score were employed to evaluate the clinical symptoms and health status. The distance from the tip of the odontoid to Chamberlain's line (DCL), the atlantodental interval (ADI), the clivus‐canal angle (CCA), the diameter of the subarachnoid space (DSS), and the craniovertebral junction triangular area (CTA) were assessed radiographically. The pre‐ and postoperative results were compared by paired t test.The data of 21 consecutive patients were reviewed, with an average follow‐up period of 28 ± 14 months. Postoperative imaging showed effectively reduced compression of BI‐AAD. No implant failure or neurovascular injury occurred. Eleven patients had vertebral artery abnormalities, but none had vertebral artery injury. All patients had evidence of bone fusion on the CT scan images within a 12‐month follow‐up period. The JOA and SF‐12 scores were significantly improved 1 year postoperatively (p < 0.001).Posterior surgery using the technique of interarticular distraction, fusion with cage grafting, and fixation is a safe and effective revision surgery to treat patients with basilar invagination and atlantoaxial dislocation who failed PFD, which will result in good outcome. [ABSTRACT FROM AUTHOR]

• The FROUNT inhibitor, Disulfiram, suppressed inflammatory cell infiltration. • Disulfiram suppressed microglia activation after subarachnoid hemorrhage in animals. • Disulfiram suppressed the death after experimental subarachnoid hemorrhage. • Disulfiram prevented the neuronal death after experimental subarachnoid hemorrhage. • Disulfiram prevented the vasospasm after experimental subarachnoid haemorrhage. Subarachnoid hemorrhage due to rupture of intracranial aneurysms has a poor outcome, making this disease being the social problem. Inflammation evoked by the increase in intracranial pressure and the clot in the subarachnoid space after the onset of SAH exacerbates neuronal death and vasospasm, resulting in the poor outcome and severe aftereffects. Here, FROUNT mediates CCR2 and CCR5 signaling as an intracellular molecule binding to these chemoattractant receptors which facilitate the migration of inflammatory cells, such as macrophages, in situ to trigger inflammation there. Animal model of subarachnoid hemorrhage was established in rats through intrathecal injection of autologous blood. The effect of the FROUNT inhibitor, disulfiram, on survival rate, neuronal death in hippocampus or vasospasm was then examined. The intrathecal administration of disulfiram significantly suppressed the infiltration of CD68-positive macrophages and myeloperoxidase-positive neutrophils toward the clot in the cistern in situ. In this condition, disulfiram ameliorated the death of animals after the onset of subarachnoid hemorrhage in rats. In addition, disulfiram suppressed both the two major events after subarachnoid hemorrhage, the neuronal death in hippocampus and vasospasm. The pharmacological inhibition of CCR2 and CCR5 signaling by disulfiram could thus be the therapeutic strategy to improve the outcome of subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the histological and biochemical neuroprotective effects of secukinumab (SEC) on brain damage induced by subarachnoid hemorrhage (SAH) in male Wistar Albino rats. Forty male Wistar Albino rats were randomly divided into 4 groups of equal size: control, SEC, SAH, and SAH + SEC. SAH was induced the SAH and SAH + SEC groups by injecting autologous blood collected from the hearts of the rats into the subarachnoid space via the foramen magnum. SEC was administered intraperitoneally once a week to the SEC and SAH + SEC groups after the surgical procedure. On the 14th day of surgery, the rats were sacrificed and their cerebral tissues were collected for biochemical analysis and histopathological examination. SAH led to changes in oxidative stress parameters by increasing malondialdehyde levels and decreasing superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. Histopathologically, cerebral tissues in the SAH groups showed alterations such as congestion and cell infiltration. Treatment with SEC significantly reduced malondialdehyde levels and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. SEC also decreased histopathological alterations in brain tissues. This study revealed that SEC (3 mg/kg) therapeutically influenced oxidative and histopathological changes in blood parameters and brain tissues caused by experimental SAH. SEC helps reduce brain damage in rats with SAH and possesses antioxidant and neuroprotective properties. Further advanced studies are needed to prove its potential benefits for humans. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) circulates throughout the ventricles, cranial and spinal subarachnoid spaces, and central spinal cord canal. CSF protects the central nervous system through mechanical cushioning, regulation of intracranial pressure, regulation of metabolic homeostasis, and provision of nutrients. Recently, investigators have characterized the glial-lymphatic (glymphatic) system, the analog of the lymphatic system in the central nervous system, and described a fourth meningeal layer; the subarachnoid lymphatic-like membrane (SLYM)relevant to the CSF. A narrative review was conducted. In this review, we summarize these advances. We describe the development of the original model, controversies, a revised model, and a new conceptual framework. We characterize the biological functions, influence of sleep-wake cycles, and effect of aging with relevance to the glymphatic system. We highlight the role of the glymphatic system in Alzheimer's disease, idiopathic normal pressure hydrocephalus, ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Next, we characterize the structure and role of the SLYM. Finally, we explore the relevance of the glymphatic system and SLYM to neurosurgery. This manuscript will inform clinicians and scientists regarding preclinical and translational advances in the understanding of the structure, dynamics, and function of the CSF. [ABSTRACT FROM AUTHOR]

Bronchial-subarachnoid fistulas are rare occurrences, which are not well defined in the literature. This uncommon clinical phenomenon may result in symptomatic pneumorrhachis and presents unique clinical challenges. This report details a case of a 53-year-old female whose treatment for recurrent chondrosarcoma of the thoracic spine included multiple surgeries and radiotherapy. Two weeks after her most recent debulking surgery, she experienced a rapid onset of unusual symptoms, including headache, back and neck spasms, bladder incontinence, and confusion. The source of her symptoms was found to be secondary to pneumorrhachis from a pre-existing bronchial-pleural fistula that had fistulized to the subarachnoid space discovered on computed tomography (CT) and confirmed intraoperatively. The patient was treated successfully with high-flow oxygen therapy and bed rest, followed by surgical correction of both a pleural air leak and a dural defect with muscular flaps. The patient was discharged home in stable condition and remained clinically free of recurrent bronchial-subarachnoid fistula six months after surgical repair. This case contributes to the existing literature by providing detailed clinical insights into the diagnosis and successful management of a bronchial-subarachnoid fistula leading to pneumorrhachis, thereby highlighting the importance of early recognition and intervention and underscoring the need for further research in this area. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (Csf) leak is the leakage of CSF from subarachnoid space into the nasal cavity.Csf rhinorrhoea is classified as traumatic and non traumatic causes (Ommaya et al. J Neurol Neurosurg Psychiatry 31(3):214, 1968). Spontaneous csf leaks occur due to increased intracranial pressure. Early diagnosis of spontaneous csf leaks may prevent complications like meningitis. This was a cross sectional prospective study done in a tertiary care hospital. Group A—spontaneous csf leak patients and Group B- Non csf leak matched controls. The anterior skull base thickness from fovea ethmoidalis, cribriform plate and lateral lamella were compared between the groups using high resolution computed tomography of paranasal sinus with 2 mm cuts. The anterior skull base thickness was measured by a senior radiologist in our tertiary centre. In this study, total of forty six patients were included, twentythree in each group. The Mean age in Group A and Group B was 48.95 and 48.78 respectively. Body mass index (BMI) was compared between the two groupsand spontaneous csf leak patients had higher value than non csf leak controls. The mean anterior skull base thickness of Group A (cribriform plate-0.56 mm, lateral lamella-0.66 mm, Fovea ethmoidalis-0.91 mm) was lower than Group B (cribriform plate-0.86 mm, lateral lamella-0.84 mm, Fovea ethmoidalis-0.97 mm) which was statistically significant (p value-< 0.05). [ABSTRACT FROM AUTHOR]

There is an urgent unmet need for a reliable noninvasive tool to detect elevations in intracranial pressure (ICP) above guideline-recommended thresholds for treatment. Gold standard invasive ICP monitoring is unavailable in many settings, including resource-limited environments, and in situations such as liver failure in which coagulopathy increases the risk of invasive monitoring. Although a large number of noninvasive techniques have been evaluated, this article reviews the potential clinical role, if any, of the techniques that have undergone the most extensive evaluation and are already in clinical use. Elevations in ICP transmitted through the subarachnoid space result in distension of the optic nerve sheath. The optic nerve sheath diameter (ONSD) can be measured with ultrasound, and an ONSD threshold can be used to detect elevated ICP. Although many studies suggest this technique accurately detects elevated ICP, there is concern for risk of bias and variations in ONSD thresholds across studies that preclude routine use of this technique in clinical practice. Multiple transcranial Doppler techniques have been used to assess ICP, but the best studied are the pulsatility index and the Czosnyka method to estimate cerebral perfusion pressure and ICP. Although there is inconsistency in the literature, recent prospective studies, including an international multicenter study, suggest the estimated ICP technique has a high negative predictive value (> 95%) but a poor positive predictive value (≤ 30%). Quantitative pupillometry is a sensitive and objective method to assess pupillary size and reactivity. Proprietary indices have been developed to quantify the pupillary light response. Limited data suggest these quantitative measurements may be useful for the early detection of ICP elevation. No current noninvasive technology can replace invasive ICP monitoring. Where ICP monitoring is unavailable, multimodal noninvasive assessment may be useful. Further innovation and research are required to develop a reliable, continuous technique of noninvasive ICP assessment. [ABSTRACT FROM AUTHOR]

For centuries, the meninges have been described as three membranes: the inner pia, middle arachnoid and outer dura. It was therefore sensational when in early 2023 Science magazine published a report of a previously unrecognized — 4th — meningeal membrane located between the pia and arachnoid. Multiple features were claimed for this new membrane: a single cell layer marked by the transcription factor Prox1 that formed a barrier to low molecular weight substances and separated the subarachnoid space (SAS) into two fluid-filled compartments, not one as previously described. These features were further claimed to facilitate unidirectional glymphatic cerebrospinal fluid transport. These claims were immediately questioned by several researchers as misinterpretations of the authors' own data. The critics argued that (i) the 4th meningeal membrane as claimed did not exist as a separate structure but was part of the arachnoid, (ii) the "outer SAS" compartment was likely an artifactual subdural space created by the experimental procedures, and (iii) the 4th membrane barrier property was confused with the arachnoid barrier. Subsequent publications in late 2023 indeed showed that Prox1 + cells are embedded within the arachnoid and located immediately inside of and firmly attached to the arachnoid barrier cells by adherens junctions and gap junctions. In a follow-up study, published in this journal, the lead authors of the Science paper Kjeld Møllgård and Maiken Nedergaard reported additional observations they claim support the existence of a 4th meningeal membrane and the compartmentalization of the SAS into two non-communicating spaces. Their minor modification to the original paper was the 4th meningeal membrane was better observable at the ventral side of the brain than at the dorsal side where it was originally reported. The authors also claimed support for the existence of a 4th meningeal membrane in classical literature. Here, we outline multiple concerns over the new data and interpretation and argue against the claim there is prior support in the literature for a 4th meningeal membrane. [ABSTRACT FROM AUTHOR]

Histological studies have for decades documented that each of the classical meningeal membranes contains multiple fibroblast layers with distinct cellular morphology. Particularly, the sublayers of the arachnoid membranes have received attention due to their anatomical complexity. Early studies found that tracers injected into the cerebrospinal fluid (CSF) do not distribute freely but are restricted by the innermost sublayer of the arachnoid membrane. The existence of restrictions on CSF movement and the subdivision of the subarachnoid space into several distinct compartments have recently been confirmed by in vivo 2-photon studies of rodents, as well as macroscopic imaging of pigs and magnetic resonance imaging of human brain. Based on in vivo imaging and immunophenotyping characterization, we identified the structural basis for this compartmentalization of the subarachnoid space, which we term 'Subarachnoid lymphatic-like membrane', SLYM. The SLYM layer engages the subarachnoid vasculature as it approaches the brain parenchyma, demarcating a roof over pial perivascular spaces. Functionally, the separation of pial periarterial and perivenous spaces in the larger subarachnoid space is critical for the maintenance of unidirectional glymphatic clearance. In light of its close apposition to the pial surface and to the brain perivascular fluid exit points, the SLYM also provides a primary locus for immune surveillance of the brain. Yet, the introduction of SLYM, in terms of its anatomic distinction and hence functional specialization, has met resistance. Its critics assert that SLYM has been described in the literature by other terms, including the inner arachnoid membrane, the interlaminate membrane, the outer pial layer, the intermediate lamella, the pial membrane, the reticular layer of the arachnoid membrane or, more recently, BFB2-3. We argue that our conception of SLYM as an anatomically and functionally distinct construct is both necessary and warranted since its functional roles are wholly distinct from those of the overlying arachnoid barrier layer. Our terminology also lends clarity to a complex anatomy that has hitherto been ill-described. In that regard, we also note the lack of specificity of DPP4, which has recently been introduced as a 'selected defining marker' of the arachnoid barrier layer. We note that DPP4 labels fibroblasts in all meningeal membranes as well as in the trabecula arachnoides and the vascular adventitial layers, thus obviating its utility in meningeal characterization. Instead, we report a set of glymphatic-associated proteins that serve to accurately specify SLYM and distinguish it from its adjacent yet functionally distinct membranes. [ABSTRACT FROM AUTHOR]

Background: Encephalocele refers to protrusion of the meninges and brain tissue through a skull bone defect. It results from congenital, traumatic, neoplastic, or spontaneous reasons. Traumatic encephalocele occurs because of the posttraumatic fracture of the skull bone or iatrogenic causes. The manifestations vary a lot, such as rhinorrhea, seizures, headaches, and focal neurological deficits. Case presentation: A 20-year-old Syrian male presented to our department with the complaint of clear cerebrospinal fluid drainage from his right nostril, which started 6 years ago after a head trauma, moderate headache, and episodes of tonic–clonic seizures without any response to medical treatment. Then, 2 months ago, the patient had meningoencephalitis, so he was admitted to the intensive care unit and treated for a month until he was cured. The patient underwent radiological investigations, which showed that he had a base fracture with an encephalocele in the nasal cavity. The brain tissues with the meninges herniated through the skull base fracture with a significant expansion of the subarachnoid spaces in the right hemisphere. He was advised to undergo surgical repair at that time, but he refused the surgery. During this visit, surgery was indicated. The surgery was done by a specialist who returned the herniated brain tissues to their normal location, repaired the meninges, and reconstructed the skull base with bone cement and bio-glue. The patient's recovery after the surgery was uneventful. Conclusion: Traumatic encephalocele is a rare and unexpected complication of trauma, but we should keep it in mind when the patient comes with head trauma because of its life-threatening consequences. This complication can happen after years of trauma if the patient refuses treatment, therefore, we must educate patients about the dangerous results of neglecting cerebrospinal fluid leakage and skull fractures. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic Normal pressure hydrocephalus (iNPH) is an under-diagnosed in elderly patients but none of the diagnostic tests are currently sufficiently sensitive or specific. The objective of this study was to analyze the dynamics of neurofluids by PC-MRI in relation to clinical evolution as measured using the iNPH grading scale after tap-test. Method: We prospectively included patients with suspected iNPH. All these patients underwent PCMRI to assess craniospinal hemohydrodynamics with analysis of the stroke volume of the cephalospinal fluid (CSF) within the Sylvius' aqueduct, within the high cervical subarachnoid spaces and the arteriovenous stroke volume. By this means, we calculated a compliance index. Morphological analysis was carried out using the DESH score. The infusion test was measuring the resistance to CSF flow. We analysed all these parameters according to the clinical improvement of the patients. Results: 23 patients were included. Compliance index assessed by PC-MRI was significantly higher in the group of patients with improvement > 10% (p = 0.015). Conclusions: Our study highlights the importance of investigating arteriovenous and CSF interactions in iNPH. This involves understanding the physiological and pathophysiological mechanisms related to the circulation of neurofluids. The analysis of the interactions of these neurofluids allows for a comprehensive understanding of the system. [ABSTRACT FROM AUTHOR]

Hydrocephalus can affect brain function and motor ability. Current treatments mostly involve invasive surgeries, with a high risk of postoperative infections and failure. A successful animal model plays a significant role in developing new treatments for hydrocephalus. Hydrocephalus was induced in Sprague–Dawley rats by injecting 25% kaolin into the subarachnoid space at the cerebral convexities with different volumes of 30, 60 and 90 μL. Magnetic resonance imaging (MRI) was performed 1 month and 4 months after kaolin injection. The behavioral performance was assessed weekly, lasting for 7 weeks. The histopathological analyses were conducted to the lateral ventricles by hematoxylin–eosin (HE) staining. Transcriptomic analysis was used between Normal Pressure Hydrocephalus (NPH) patients and hydrocephalus rats. MRI showed a progressive enlargement of ventricles in hydrocephalus group. Kaolin‐60 μL and kaolin‐90 μL groups showed larger ventricular size, higher anxiety level, bigger decline in body weight, motor ability and cognitive competence. These symptoms may be due to higher‐grade inflammatory infiltrate and the damage of the structure of ependymal layer of the ventricles, indicated by HE staining. The overlap upregulated genes and pathways mainly involve immunity and inflammation. Transcriptomic revealed shared pathogenic genes CD40, CD44, CXCL10, and ICAM1 playing a dominance role. 60 μL injection might be recommended for the establishment of hydrocephalus animal model, with a high successful rate and high stability. The hydrocephalus model was able to resemble the inflammatory mechanism and behavioral performance observed in human NPH patients, providing insights for identifying therapeutic targets for hydrocephalus. [ABSTRACT FROM AUTHOR]

A subarachnoid hemorrhage (SAH) is life-threatening bleeding into the subarachnoid space that causes brain damage. Growing evidence has suggested that melatonin provides neuroprotection following SAH. Exploring the mechanisms underlying melatonin-mediated neuroprotection contributes to its clinical application in SAH. The plasma and cerebrospinal fluid (CSF) were collected from SAH patients, and SAH mice were established via pre-chiasmatic injection. Circodz3 expression, levels of IL-1β and TNF-α, brain water content, neurological and beam-waling scores were determined. Ferroptosis was evaluated by analyzing levels of iron, lipid ROS, MDA, and GSH. The colocalization of circodz3 and Iba-1 was analyzed by immunofluorescence staining. Interaction of circodz3 and HuR was determined with RNA pull-down and RNA immunoprecipitation assays. Herein, we found that circodz3 was highly abundant in SAH patients and mice. Colocalization of circodz3 and Iba-1 in the left hemisphere of SAH mice suggested the implication of circodz3 in regulating microglia activation following SAH. Melatonin alleviated brain edema, neurological impairment, and microglia activation and inhibited circodz3 expression in SAH mice. Moreover, melatonin inhibited M1 polarization, oxidative stress and ferroptosis and restrained circodz3 expression in primary microglia following SAH. These effects were abrogated by circodz3 overexpression. Circodz3 knockdown inhibited ferroptosis and M1 polarization of BV2 microglia after SAH. Circodz3 interacted with HuR to facilitate β-Trcp1-mediated ubiquitination and degradation, thus restraining the expression of SLC7A11 and GPX4. Collectively, melatonin exerted neuroprotection following SAH via inhibiting ferroptosis and M1 polarization through the circodz3/HuR axis. Our study suggests potential application of melatonin in the treatment of SAH. Highlights: CircODZ3 is highly abundant in the plasma and cerebrospinal fluid from SAH patients. Melatonin protects against SAH by inhibiting circodz3 expression. Silencing of circodz3 inhibits ferroptosis and M1 polarization of BV2 microglia. Circodz3 interacts with HuR to promote its ubiquitination and degradation. Circodz3 degrades HuR to reduce SLC7A11 and GPX4 expression. [ABSTRACT FROM AUTHOR]

Purpose: The traditional imaging findings reported in Sturge–Weber syndrome (SWS) include endpoints of cortical injury—cortical atrophy and cortical calcifications—but also what has been termed a "leptomeningeal angiomatosis," the latter recognized and reported as a leptomeningeal enhancement on magnetic resonance imaging (MRI). The objective of this study is to demonstrate through neuropathological correlation that the "leptomeningeal angiomatosis" in patients with Sturge–Weber syndrome (SWS), represents a re-opened primitive venous network in the subarachnoid space that likely acts as an alternative venous drainage pathway, seen separately to abnormal pial enhancement. Materials and methods: Retrospective review of MR imaging and surgical pathology of patients that underwent surgery for epilepsy at a tertiary, children's hospital. A pediatric radiologist with more than 20 years of experience reviewed the MR imaging. Surgically resected brain specimens that had been sectioned and fixed in 10% paraformaldehyde for histologic processing, following processing and paraffin embedding, were cut into 5-µm unstained slides which were subsequently stained with hematoxylin and eosin (H&E). Slides were re-examined by a board-certified pediatric neuropathologist, and histologic features specifically relating to cerebral surface and vascularity were documented for correlation with MR imaging of the resected region performed prior to resection. Results: Five patients were reviewed (3 boys and 2 girls; the median age at the onset of seizures was 12 months (IQR, 7 to 45 months); the median age at surgery was 33 months (IQR, 23.5 to 56.5 months)). Surgical procedures included the following: 4, hemispherotomy (right: 2, left: 2) and 1, hemispherectomy (right). A subarachnoid space varicose network was present on both MRI and histology in 4 patients. Calcifications were seen on both MRI and histology in 3 patients. Abnormal leptomeningeal enhancement was present in 5 patients and seen separately from the subarachnoid vascular network in 4 patients. Conclusion: Histopathology confirmed the MRI findings of a subarachnoid space varicose network seen separately from leptomeningeal enhancement and presumed to represent an alternative venous drainage pathway to compensate for maldevelopment of cortical veins, the primary abnormality in SWS. No pial-based angioma was identified. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH), known as nontraumatic cerebrovascular rupture and hemorrhage, often occurs in the deep basal brain segment. It is known for its high morbidity and mortality rates. Subarachnoid hemorrhage (SAH) is a clinical syndrome caused by the rupture of blood vessels at the base or surface of the brain that allows blood to flow directly into the subarachnoid space. It progresses quickly and typically manifests at younger ages compared with ICH. ICH and SAH are both devastating events in the category of hemorrhagic strokes and are attracting increasing attention from researchers. Flavonoids, being important natural molecules, have remarkable anti-inflammatory and antioxidant effects. Flavonoids have extensive biological activities in inflammation and oxidative stress (OS), and have protective effects in vascular function associated with cerebrovascular diseases. They have an impact on the onset of ICH and SAH by targeting various pathways, including the suppression of inflammation and OS. Recently, the role of flavonoid compounds in ICH and SAH has also received increasing interest. Thus, to serve as a resource for the prevention and treatment of ICH and SAH, the present review provided an overview of the research on flavonoid compounds in the prevention of brain damage after these two conditions have occurred. [ABSTRACT FROM AUTHOR]

Summary: This case report describes the successful conservative management of a comminuted fracture of the atlas and occiput involving the atlanto‐occipital joint. To the authors' knowledge, treatment of fractures involving the atlanto‐occipital joint in the horse and intrathecal subarachnoid space corticosteroid injection in the standing sedated patient has not been previously reported. Clinical signs following atlanto‐occipital (AO) fracture included acute onset ataxia, proprioceptive deficits and neck stiffness; which developed immediately post‐trauma during head and tail rope‐assisted recovery from general anaesthesia. Radiographic examination was not diagnostic immediately post‐trauma and computed tomography (CT) imaging subsequently identified articular fractures of the atlas and occiput. Treatment included ultrasound‐guided intrathecal medication of the subarachnoid space and intra‐articular medication of the left AO joint under standing sedation. Medication resulted in a marked improvement in clinical signs (grade 4 ataxia to grade 1 ataxia) and a return to ridden exercise 12 months post‐injury. [ABSTRACT FROM AUTHOR]

Oxidative stress is associated with several infectious diseases, as well as the severity of inflammatory reactions. The control of inflammation during parasite destruction is a target of neurocysticercosis treatment, as inflammation is strongly related to symptom severity. In this study, we investigated the presence of malondialdehyde and protein carbonyl, two by-products of reactive oxygen species (ROS), in an experimental model of extraparenchymal neurocysticercosis. Twenty male and twenty female rats were inoculated with 50 cysts of Taenia crassiceps in the subarachnoid space of the cisterna magna. Ten animals (five males and five females) were used as controls. Three months after inoculation, their brains were harvested for oxidative stress and histological assessments. Infected animals had higher scores for inflammatory cell infiltrates, malondialdehyde, and protein carbonyl. These results encourage future efforts to monitor oxidative stress status in neurocysticercosis, particularly in the context of controlling inflammation. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) plays a critical role in metabolic waste clearance from the brain, requiring its circulation throughout various brain pathways, including the ventricular system, subarachnoid spaces, para‐arterial spaces, interstitial spaces, and para‐venous spaces. The complexity of CSF circulation has posed a challenge in obtaining noninvasive measurements of CSF dynamics. The assessment of CSF dynamics throughout its various circulatory pathways is possible using diffusion magnetic resonance imaging (MRI) with optimized sensitivity to incoherent water movement across the brain. This review presents an overview of both established and emerging diffusion MRI techniques designed to measure CSF dynamics and their potential clinical applications. The discussion offers insights into the optimization of diffusion MRI acquisition parameters to enhance the sensitivity and specificity of diffusion metrics on underlying CSF dynamics. Lastly, we emphasize the importance of cautious interpretations of diffusion‐based imaging, especially when differentiating between tissue‐ and fluid‐related changes or elucidating structural versus functional alterations. [ABSTRACT FROM AUTHOR]

Abstract Accumulation of immune cells and proteins in the subarachnoid space (SAS) is found during multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis (EAE). Whether the flow of cerebrospinal fluid (CSF) along the SAS of the spinal cord is impacted is yet unknown. Combining intravital near-infrared (NIR) imaging with histopathological analyses, we observed a significantly impaired bulk flow of CSF tracers within the SAS of the spinal cord prior to EAE onset, which persisted until peak stage and was only partially recovered during chronic disease. The impairment of spinal CSF flow coincided with the appearance of fibrin aggregates in the SAS, however, it preceded immune cell infiltration and breakdown of the glia limitans superficialis. Conversely, cranial CSF efflux to cervical lymph nodes was not altered during the disease course. Our study highlights an early and persistent impairment of spinal CSF flow and suggests it as a sensitive imaging biomarker for pathological changes within the leptomeninges.

Abstract Hydrocephalus can affect brain function and motor ability. Current treatments mostly involve invasive surgeries, with a high risk of postoperative infections and failure. A successful animal model plays a significant role in developing new treatments for hydrocephalus. Hydrocephalus was induced in Sprague–Dawley rats by injecting 25% kaolin into the subarachnoid space at the cerebral convexities with different volumes of 30, 60 and 90 μL. Magnetic resonance imaging (MRI) was performed 1 month and 4 months after kaolin injection. The behavioral performance was assessed weekly, lasting for 7 weeks. The histopathological analyses were conducted to the lateral ventricles by hematoxylin–eosin (HE) staining. Transcriptomic analysis was used between Normal Pressure Hydrocephalus (NPH) patients and hydrocephalus rats. MRI showed a progressive enlargement of ventricles in hydrocephalus group. Kaolin‐60 μL and kaolin‐90 μL groups showed larger ventricular size, higher anxiety level, bigger decline in body weight, motor ability and cognitive competence. These symptoms may be due to higher‐grade inflammatory infiltrate and the damage of the structure of ependymal layer of the ventricles, indicated by HE staining. The overlap upregulated genes and pathways mainly involve immunity and inflammation. Transcriptomic revealed shared pathogenic genes CD40, CD44, CXCL10, and ICAM1 playing a dominance role. 60 μL injection might be recommended for the establishment of hydrocephalus animal model, with a high successful rate and high stability. The hydrocephalus model was able to resemble the inflammatory mechanism and behavioral performance observed in human NPH patients, providing insights for identifying therapeutic targets for hydrocephalus.

BACKGROUND: Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and is typically diagnosed through visualization of the cysts in the cerebral parenchyma by neuro-imaging. However, neuro-imaging may not detect extraparenchymal neurocysticercosis (EPNCC), which is a rare manifestation of the disease involving the subarachnoid, meningeal, and intraventricular spaces. We report 2 cases of extraparenchymal neurocysticercosis, and discuss the diagnostic challenges and management of this entity. METHODS: Two cases were identified through clinical records. RESULTS: Both patients had an insidious onset with slow progression of disease, and presented with papilledema and cerebrospinal fluid (CSF) eosinophilia. One case was diagnosed with spinal cord biopsy. The other was diagnosed with CSF serology and next-generation sequencing-based pathogen analysis. Both patients were treated with ventriculoperitoneal shunt, systemic antiparasitic agents, and immunosuppression. CONCLUSIONS: EPNCC is less common than parenchymal NCC. A high level of clinical suspicion is required given its rarity, long incubation period, and slow progression. Diagnosis and treatment can be challenging and requires a multidisciplinary approach.

Introduction: Toward further cerebro-spinal flow quantification in clinical practice, this study aims at assessing the variations in the cerebro spinal fluid flow pattern associated with change in the morphology of the subarachnoid space of the cervical canal of healthy humans by developing a computational fluid dynamics model. Methods: 3D T2-space MRI sequence images of the cervical spine were used to segment 11 cervical subarachnoid space. Model validation (time-step, mesh size, size and number of boundary layers, influences of parted inflow and inflow continuous velocity) was performed a 40-year-old patient-specific model. Simulations were performed using computational fluid dynamics approach simulating transient flow (Sparlart-Almaras turbulence model) with a mesh size of 0.6, 6 boundary layers of 0.05 mm, a time step of 20 ms simulated on 15 cycles. Distributions of components velocity and WSS were respectively analyzed within the subarachnoid space (intervertebral et intravertebral levels) and on dura and pia maters. Results: Mean values cerebro spinal fluid velocity in specific local slices of the canal range between 0.07 and 0.17 m.s-1 and 0.1 and 0.3 m.s-1 for maximum values. Maximum wall shear stress values vary between 0.1 and 0.5 Pa with higher value at the middle of the cervical spine on pia mater and at the lower part of the cervical spine on dura mater. Intra and inter-individual variations of the wall shear stress were highlighted significant correlation gwith compression ratio (r = 0.76), occupation ratio and cross section area of the spinal cord. Conclusion: The inter-individual variability in term of subarachnoid canal morphology and spinal cord position influence the cerebro-spinal flow pattern, highlighting the significance of canal morphology investigation before surgery. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is caused by abnormal blood vessel dilation and subsequent rupture, resulting in blood pooling in the subarachnoid space. This neurological insult results in the activation of the inflammasome, a multiprotein complex that processes pro-inflammatory interleukin (IL)-1 cytokines leading to morbidity and mortality. Moreover, increases in inflammasome proteins are associated with clinical deterioration in many neurological diseases. Limited studies have investigated inflammasome protein expression following aSAH. Reliable markers of the inflammatory response associated with aSAH may allow for earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. Here, we investigated whether inflammasome signaling proteins may serve as potential biomarkers of the inflammatory response in aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls and hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of inflammasome signaling proteins and downstream pro-inflammatory cytokines. Protein measurements were carried out using Simple Plex and Single-Molecule Array (Simoa) technology. The area under the curve (AUC) was calculated using receiver operating characteristics (ROCs) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, a Spearman r correlation matrix was performed to determine the correlation between inflammasome protein levels and clinical outcome measures. aSAH subjects demonstrated elevated caspase-1, apoptosis-associated speck-like protein with a caspase recruiting domain (ASC), IL-18 and IL-1β levels in serum, and CSF when compared to controls. Each of these proteins was found to be a promising biomarker of inflammation in aSAH in the CSF. In addition, ASC, caspase-1, and IL-1β were found to be promising biomarkers of inflammation in aSAH in serum. Furthermore, we found that elevated levels of inflammasome proteins in serum are useful to predict worse functional outcomes following aSAH. Thus, the determination of inflammasome protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes. [ABSTRACT FROM AUTHOR]

Superficial siderosis (SS) of the central nervous system is a rare disease characterized by deposition of hemosiderin along the leptomeninges due to chronic or recurrent bleeding into the subarachnoid space. The association of unruptured intracranial aneurysm (IA) and cortical SS is quite rare. A systematic literature review to assess possible commonalities and/or differences of previous reported cases was undertaken. We report an additional case from our institution. A 40-year-old woman presented with a history of generalized seizures over the past year. There was no clinical history suggestive of aneurysm rupture. Magnetic resonance imaging revealed 2 aneurysms of the right middle cerebral artery (MCA) bifurcation associated with hemosiderin deposition along the right sylvian fissure and a third aneurysm of the left MCA bifurcation. Magnetic resonance imaging showed wall enhancing thickening of the larger right MCA aneurysm. The patient underwent surgical clipping of all 3 MCA aneurysms in a staged procedure. Histological examination revealed hemosiderin deposits within the aneurysm wall and surrounding gliosis. Our literature review found 24 reported cases of unruptured IA associated with cortical SS. The possible source for leakages could be neovessels visible in IA walls. The case reported illustrates an uncommon presentation of recurrent bleeding from an IA as a source of SS. The presence of an apparently unruptured IA surrounded by cortical SS on imaging studies is of high relevance as this should be considered a sign of aneurysm wall instability and should indicate prompt treatment. [ABSTRACT FROM AUTHOR]

The nervous system is divided topographically into two parts: the central nervous system and the peripheral nervous system. From a functional perspective, however, the two systems are intimately connected and function in an integrated and coordinated manner. The central nervous system comprises the brain and spinal cord, while the peripheral nervous system is made up of the cranial and peripheral nerves and associated neurological structures. This article presents a broad and general overview of the structure and organization of the nervous system emphasizing several important functional features. [ABSTRACT FROM AUTHOR]

Introduction: Equine trigeminal-mediated headshaking is a painful neuropathic disorder comparable to trigeminal neuralgia in humans. The selective destruction of pain fibers within the trigeminal ganglion, called rhizotomy, is the surgical treatment of choice for idiopathic trigeminal neuralgia refractory to medical treatment in humans. The human trigeminal ganglion is enclosed by a dural recess called the Meckel's or trigeminal cave, in which the ganglion is surrounded by a cerebrospinal fluid (CSF)-filled subarachnoid space. During glycerol rhizotomy, glycerol is percutaneously injected in this CSF-filled space. Until now, information about the anatomy of the dural recess and the subarachnoid space surrounding the trigeminal ganglion is lacking in horses. The aim of this study was to explore if a CSF-filled subarachnoid space around the trigeminal ganglion exists in horses. Materials and methods: Six equine cadaver heads were investigated for CSF accumulation around the ganglion with a 3 Tesla MRI. After anatomical dissection to expose the trigeminal root, a polymer-based radiopaque contrast agent was injected through the porus trigeminus into the subarachnoid space (cisternography). The exact delineation and the volume of the contrast agent accumulation were determined on subsequent micro-computed tomographic scans and segmentation. Finally, the distribution of the contrast agent within the subarachnoid space was examined histologically in three specimens. Results: In all 12 specimens included in this study, the trigeminal ganglion was surrounded by a subarachnoid space forming a trigeminal cistern. The mean volume of the trigeminal cave in this study was 0.31 mL (±SD: 0.11 mL). Distribution of the contrast agent along the peripheral nerves (i.e., ophthalmic, maxillary and/or mandibular nerve) was observed in 7 out of 12 specimens. Discussion/conclusion: A subarachnoid space surrounding the trigeminal ganglion exists in the horse and could be targeted for glycerol rhizotomy in horses suffering from trigeminal-mediated headshaking. However, the clinical relevance of contrast agent distribution along the peripheral nerves remains to be assessed. [ABSTRACT FROM AUTHOR]

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Background: Achieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studies. Methods: A three-dimensional (3D) in vitro model of a cynomolgus monkey, based on MRI data, was developed to evaluate the impact of lumbar injection parameters on intrathecal solute dispersion. The parameters evaluated were (a) injection location, (b) bolus volume, (c) flush volume, (d) bolus rate, and (e) flush rate. To simulate the CSF flow within the subarachnoid space (SAS), an idealized CSF flow waveform with both cardiac and respiratory-induced components was input into the model. A solution of fluorescein drug surrogate tracer was administered in the lumbar region of the 3D in vitro model filled with deionized water. After injection of the tracer, the CSF system wide-solute dispersion was imaged using high-resolution cameras every thirty seconds for a duration of three hours. To ensure repeatability each injection protocol was repeated three times. For each protocol, the average spatial–temporal distribution over three hours post-injection, the area under the curve (AUC), and the percent injected dose (%ID) to extra-axial CSF (eaCSF) at three hours were determined. Results: The changes to the lumbar injection parameters led to variations in solute distribution along the neuro-axis. Specifically, injection location showed the most impact, enhancing the delivery to the eaCSF up to + 10.5%ID (p = 0.0282) at three hours post-injection. Adding a post-injection flush of 1.5 ml at 1 ml/min increased the solute delivery to the eaCSF by + 6.5%ID (p = 0.0218), while the larger bolus volume resulted in a + 2.3%ID (p = 0.1910) increase. The bolus and flush rates analyzed had minimal, statistically non-significant effects. Conclusion: These results predict the effects of lumbar injection parameters on solute distribution in the intrathecal space in NHPs. Specifically, the choice of injection location, flush, and bolus volume significantly improved solute delivery to eaCSF. The in vitro NHP CSF model and results offer a system to help predict and optimize IT delivery protocols for pre-clinical NHP studies. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions The optic nerve sheath diameter (ONSD) is a commonly used estimate of intracranial pressure (ICP). The rationale behind this is that pressure changes in the cerebrospinal fluid affect the optic nerve subarachnoid space (ONSAS) thickness. Still, possible effects on other compartments of the optic nerve sheath (ONS) have not been studied. This is the first study ever to analyze all measurable compartments of the ONS for associations with elevated ICP.We measured changes in ICP and changes in ONS compartments in 75 patients treated with invasive ICP monitoring at the Karolinska University Hospital. Associations between changes in ICP and changes in ONS compartments were estimated with generalized estimating equations. The potential to identify elevated ICP was assessed with the area under the receiver operating characteristic curve (AUROC) for ONS compartments associated with ICP changes.Both ONSAS and perioptic dura mater thickness were significantly associated with changes in ICP in multivariable modeling. ONSAS was the only compartment that independently predicted changes in ICP, with an AUROC of 0.69 for predicting ICP increase. Still, both the perioptic dura mater thickness and the optic nerve diameter added value in predicting ICP changes in multivariable modeling.The results from this study challenge the current understanding of the mechanism behind the association between ICP and ONSD. Contrary to the common opinion that ONSAS is the only affected compartment, this study shows a more complex picture. It suggests that all ONS compartments may add value in predicting changes in ICP. [ABSTRACT FROM AUTHOR]

The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined. [ABSTRACT FROM AUTHOR]

Cerebrovascular alterations in acute bacterial meningitis significantly contribute to adverse patient outcomes, with reported complication rates ranging from 10% to 29%. Focal alterations in arterial lumens, leading to vasoconstriction, are common in cerebral ischemic and inflammatory conditions, such as bacterial meningitis, presenting neurological complications, such as seizures, brain swelling, hydrocephalus, hearing loss and ischemic or hemorrhagic brain damage. The observed arterial narrowing during meningitis is attributed to diverse factors, including direct encroachment by inflammatory exudate, vascular wall edema, vasospasm, and vasculitis due to cellular infiltration and vessel remodeling. Early‐stage constriction might result from a watery exudate's encroachment, whereas persistent inflammation leads to thicker exudates, attracting inflammatory cells and inducing arteriopathic growth factor synthesis. This process promotes structural modifications in the vessel wall, progressing from subintimal infiltration to organic intimal thickening, culminating in vasculitis and the risk of cerebral ischemia. Accordingly, this review seeks to more clearly delineate the intricate relationship between subarachnoid space inflammation and acute and chronic vessel wall remodeling during bacterial meningitis. Conceivably, understanding this pathological process holds promise in unveiling potential treatment avenues to improve patient outcomes, and reduced morbidity and mortality associated with cerebrovascular complications during bacterial meningitis. [ABSTRACT FROM AUTHOR]

Introduction: Penttinen premature aging syndrome is caused by mutations in the PDGFRB gene. We describe the case of a 10-year-old girl with a de novo c.1994T>C variant in PDGFRB who developed multiple cranial, intracranial, and spinal manifestations, including macrocephaly, enlarged convexity subarachnoid spaces crossed by numerous vascularized arachnoid trabecule, hydrocephalus, spinal epidural lipomatosis, a low conus medullaris, calvarial thinning with large anterior fontanelle, and a skull fracture with bilateral epidural hematomas. Vascularized arachnoid granulations, spinal epidural lipomatosis, and low conus medullaris have not been previously described in Penttinen syndrome. Case Presentation: A female with Penttinen syndrome diagnosed at 9 years of age initially presented as an infant with cutaneous hemangiomas and macrocephaly; imaging showed enlarged convexity subarachnoid spaces. Her convexity subarachnoid spaces continued to expand, leading to subdural shunt placement. At surgery, her enlarged subarachnoid spaces were found to contain numerous abnormally thick, vascularized arachnoid trabecule. Eventually, her subdural shunt failed and her ventricles enlarged, leading to ventricular shunt placement. A large, sunken anterior fontanelle which did not diminish in size led to cranioplasty with a custom implant. She later developed chronic back pain and imaging revealed spinal epidural lipomatosis, a low conus medullaris, and mild scoliosis. At 10 years of age, a fall from a chair resulted in a depressed skull fracture and bilateral parietal epidural hematomas. Emergency left parietal craniotomy was performed for evacuation of the left hematoma, and the patient recovered without complications. Intraoperatively, it was noted that her skull was extremely thin. Conclusion: This case report highlights the clinical presentation and multifaceted neurosurgical management of a patient with Penttinen syndrome. The patient exhibited characteristic features including hypertrophic skin lesions, macrocephaly, and skeletal abnormalities. Our patient's vascularized arachnoid trabecule, spinal epidural lipomatosis, and low conus medullaris have not previously been reported in Penttinen syndrome. Her thin skull potentially contributed to the extent of her depressed skull fracture after her backwards fall and predisposed her toward developing epidural hematomas. Patients with Penttinen syndrome can have multiple cranial, intracranial, and spinal manifestations which may need the attention of a neurosurgeon. [ABSTRACT FROM AUTHOR]

Throughout history, knowledge about the meninges has evolved from the first records in the Edwin Smith papyrus to the present, where SLYM, a fourth meninge that separates the subarachnoid space into a superficial compartment and another, has been described deep, to which semipermeable barrier and immune cell niche functions are attributed for the surveillance and protection of the central nervous system. The FIPAT contains a group of terminologies that are globally accepted for the description of the structures of the human body, however, in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica, the term SLYM to represent a fourth meninge is not yet included, perhaps because be a recent discovery. The objective of this study was to suggest a new term that agrees with the FIPAT guidelines and with the Regular Anatomical Terminology (RAT) rules to replace SLYM, in addition to proposing its inclusion in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica, previously review and approval by the respective FIPAT committee. The acronym SLYM and the elements that make it up (Subarachnoid Lymphatic-like Membrane) were reviewed from an etymological approach. This analysis was accompanied by a review of the RAT rules accepted by FIPAT, which were considered to examine their compliance by the acronym SLYM. It was found that SLYM, like the terms that compose it, do not fully comply with the RAT rules. The SLYM acronym does not provide an adequate description of the structure it represents, which contradicts the RAT rules. The term suprapiamater is proposed as an alternative, for inclusion in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica, based on Latin elements that describe its location and function, improving precision and clarity in scientific communication. [ABSTRACT FROM AUTHOR]

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity. [Display omitted] Here are 3 highlights of our research: • A significant increase in TXNIP expression was observed in bupivacaine-induced neurotoxicity both in vitro and in vivo. • Bupivacaine exposure activates TXNIP which positively regulates oxidative stress and apoptosis in vitro and in vivo. • Knocking down TXNIP protects against bupivacaine-induced neurotoxicity by inhibiting oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Leptomeningeal metastasis (LM) is a serious late complication in patients with solid tumors, which is common in patients with lung cancer, breast cancer and melanoma. In recent years, due to the progress of diagnosis, the diagnosis rate of LM has gradually increased. The main goal of the therapy is to maintain neurological function, improve the quality of life and the overall survival rate, and prolong the progression-free survival time of patients. Intrathecal therapy is one of the main treatments for LM, which can deliver drugs directly to the subarachnoid space. The traditional intrathecal drugs are methotrexate, cytarabine and thiotepa. With the development of new research, a variety of chemotherapeutic drugs, targeted drugs and immune checkpoint inhibitors have also been used in intrathecal therapy. In addition, different ways of intrathecal administration also bring new hope to patients. This article reviewed the clinical research progress of intrathecal therapy in the treatment of LM. [ABSTRACT FROM AUTHOR]

• Supraspinal TNFR1/p38αMAPK mediates pain chronification in a sex-dependent manner. • Male supraspinal TNFR1/p38αMAPK activity mediates pain chronification in CCI. • ER β inhibition results in a "male-like" female response to sTNF/p38MAPK inhibitors. Upregulation of soluble tumor necrosis factor (sTNF) cytokine signaling through TNF receptor 1 (TNFR1) and subsequent neuronal hyperexcitability are observed in both animal models and human chronic neuropathic pain (CNP). Previously, we have shown that estrogen modulates sTNF/TNFR1 signaling in CNP, which may contribute to female prevalence of CNP. The estrogen-dependent role of TNFR1-mediated supraspinal neuronal circuitry in CNP remains unknown. In this study, we interrogated the intersect between supraspinal TNFR1 mediated neuronal signaling and sex specificity by selectively removing TNFR1 in Nex + neurons in adult mice (NexCreERT2::TNFR1f/f). We determined that mechanical hypersensitivity induced by chronic constriction injury (CCI) decreases over time in males, but not in females. Subsequently, we investigated two downstream pathways, p38MAPK and NF-κB, important in TNFR1 signaling and injury response. We detected p38MAPK and NF-κB activation in male cortical tissue; however, p38MAPK phosphorylation was reduced in NexCreERT2::TNFR1f/f males. We observed a similar recovery from acute pain in male mice following CCI when p38αMAPK was knocked out of supraspinal Nex + neurons (NexCreERT2::p38αMAPKf/f), while chronic pain developed in female mice. To explore the intersection between estrogen and inflammation in CNP we used a combination therapy of an estrogen receptor β (ER β) inhibitor with a sTNF/TNFR1 or general p38MAPK inhibitor. We determined both combination therapies lends therapeutic relief to females following CCI comparable to the response evaluated in male mice. These data suggest that TNFR1/p38αMAPK signaling in Nex + neurons in CNP is male-specific and lack of therapeutic efficacy following sTNF inhibition in females is due to ER β interference. These studies highlight sex-specific differences in pathways important to pain chronification and elucidate potential therapeutic strategies that would be effective in both sexes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to compare the effects of low-dose subarachnoid injections of 2% lidocaine (LIDO) and 0.5% bupivacaine (BUPI) in goats. ANIMALS: 6 healthy, privately owned female goats. METHODS In this randomized blind crossover clinical trial, each goat received 0.05 mL/kg-1 of LIDO, BUPI, or sterile saline solution into the lumbosacral subarachnoid space, with a seven-day washout. Cardiorespiratory variables, rectal temperature, and somatosensory (pinprick) and motor (ataxia) functions were recorded at baseline (time 0) and 2, 5, 10, 15, and 30 minutes after injection, then every 20 minutes until the goat was standing and able to walk. Time to regain somatosensory and motor functions was compared between treatments using Kaplan-Meier survival curves and the Cox proportional hazards model. Linear mixed-effects models were used to compare cardiorespiratory variables between treatments and over time. A P value ≤ .05 was considered significant. RESULTS: Somatosensory recovery was longer with BUPI, though not statistically significant. The median time to stand was 50 (50, 67) minutes after LIDO injection and 104 (101, 156) minutes after BUPI injection (P = .031). The median time to walk was 72 (54, 85) minutes after LIDO versus 225 (220, 245) minutes after BUPI injection (P = .031). Cardiovascular and respiratory variables showed no significant differences between treatments. CLINICAL RELEVANCE: Despite prolonged ataxia with BUPI, pinprick sensation recovery did not differ. At reduced doses, both LIDO and BUPI are deemed acceptable for short procedures of the flank, pelvic limb, or tail in healthy goats. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients. • No preoperative magnetic resonance imaging (MRI) finding was associated with shunt response in idiopathic normal-pressure hydrocephalus (iNPH) patients. • It is still unclear whether preoperative MRI findings can predict shunt response. • Postshunt corpus callosal hyperintensity was observed in 4.2% of iNPH patients. [ABSTRACT FROM AUTHOR]

Objectives: Prenatally diagnosed complex arachnoid cysts are very rare. While the true prenatal incidence is still unknown, they account for approximately 1% of intracranial masses in newborns. They rarely exhibit rapid growth or cause obstructive hydrocephalus, but if they increase to such a dimension during pregnancy, the ideal management is not well established. We present our detailed perinatal experience, covering prenatal diagnosis, a compassionate delivery process, and neonatal stabilization. Finally, a thorough postnatal neurosurgical intervention was performed. Initially, our focus was on the gradual reduction of cyst size as a primary effort, followed by subsequent definitive surgical treatment. Methods: This case series shows the treatment course of three fetuses with antenatally diagnosed large arachnoid cysts. We present pre- and postnatal management and imaging, as well as the surgical treatment plan and the available clinical course during follow-up. Results: Two girls and one boy were included in the current review. All three cases presented with prenatally diagnosed complex arachnoid cysts that increased in size during pregnancy. The mean gestational age at delivery was 35 weeks (range 32 to 37 weeks), and all patients were delivered by a caesarian section. Increasing head circumference and compression of brain structures were indications for delivery, as they are associated with a high risk of excess intracranial pressures and CSF diapedesis, as well as traumatic delivery and maternal complications. All cysts were supratentorial in location; one expanded into the posterior fossa, and one was a multicompartment cyst. All children underwent an initial surgical procedure within the first days of life. To relieve cyst pressure and achieve a reduction in head circumference, an ultrasound-guided or endoscopic-assisted internal shunt with drainage of the cyst to the ventricles or subdural/subarachnoid space was inserted. Definite surgical therapy consisted of cyst marsupialization and/or cysto-peritoneal shunt implantation. All children survived without severe neurodevelopmental impairments. Conclusion: With the cases presented, we demonstrate that the slow reduction of immense cyst size as an initial procedure until optimal requirements for final surgical treatment were achieved has proven to be optimal for neurological outcome. Special emphasis has to be taken on the delicate nature of premature newborn babies, and surgical steps have to be thoroughly considered within the interdisciplinary team. [ABSTRACT FROM AUTHOR]

Background: Idiopathic intracranial hypertension (IIH) is a rare medical condition in children. Based on the different radiological findings reported in various studies in pediatric IIH, this study was conducted to determine the diagnostic value of MRI findings in diagnosing IIH in children. Methods: In this retrospective study, the medical records of all children aged 1 to 18 years who visited Ghaem Hospital in Mashhad, Iran, between 2012 and 2022 and were diagnosed with IIH were gathered. Forty-nine cases of children with IIH and 48 control cases of children with the first unprovoked seizure with no indications of increased intracranial pressure for comparison were selected. Patient demographic information and MRI findings were extracted. The comparison between different MRI findings in the case and control groups was conducted using statistical tests. Results: In the case group, the mean diameter of the subarachnoid space expansion around the optic nerve was 5.96 ± 1.21, compared to 4.79 ± 0.33 in the control group, with statistically significant difference (P < 0.001). All the patients with flattening of the posterior globe or transverse sinus stenosis were in the case group, and the frequency of these findings in the case group was significantly higher than in the control group (P < 0.001). The majority of patients (95.5%) classified under category 3 and 4 of empty sella were part of the case group, and the statistical test results indicated a significant difference between the two groups (P < 0.001). The optic nerve sheath diameter cut-off of 5.35 mm, when used for expansion of the subarachnoid space around the optic nerve, with a sensitivity of 82% and a specificity of 100% in diagnosing IIH. Conclusion: The most reliable diagnostic indicators for diagnosing IIH in children are perioptic subarachnoid space expansion with high sensitivity, and posterior globe flattening and transverse sinus stenosis with high specificity. [ABSTRACT FROM AUTHOR]

It is generally accepted that hydrocephalus is a consequence of the disbalance between cerebrospinal fluid (CSF) secretion and absorption which should in turn lead to CSF pressure gradient development and ventricular enlargement. To test CSF pressure gradient role in hydrocephalus development, we experimentally caused CSF system impairment at two sites in cats. In the first group of animals, we caused Sylvian aqueduct obstruction and recorded CSF pressure changes pre and post obstruction at three measuring sites (lateral ventricle -LV, cortical-CSS and lumbar subarachnoid space -LSS) during 15 min periods and in different body positions over 360 degrees. In the second group of experiments, we caused cervical stenosis by epidural plastic semiring implantation and monitored CSF pressure changes pre and post stenosis implantation at two measuring sites (lateral ventricle and lumbar subarachnoid space) during 15 min periods in different body positions over 360 degrees. Both groups of experimental animals had similar CSF pressures before stenosis or obstruction at all measuring points in the horizontal position. During head-up verticalization, CSF pressures inside the cranium gradually became more subatmospheric with no significant difference between LV and CSS, as they are measured at the same hydrostatic level, while CSF pressure inside LSS became more positive, causing the development of a large hydrostatic gradient between the cranial and the spinal space. With cervical stenosis, CSF pressure inside the cranium is positive during head-up verticalization, while in cats with aqueductal obstruction CSF pressure inside the CSS remains negative, as it was during control period. Concomitantly, CSF pressure inside LV becomes less negative, thus creating a small hydrostatic gradient between LV and CSS. Since CSF pressure and gradient changes occur only by shifting body position from the horizontal plane, our results indicate that cervical stenosis in a head-up vertical position reduces blood perfusion of the whole brain, while aqueductal obstruction impairs only the perfusion of the local periventricular brain tissue. It seems that, for evolutionary important bipedal activity, free craniospinal communication and good spinal space compliance represent crucial biophysical parameters for adequate cerebral blood perfusion and prevention of pathophysiological changes leading to the development of hydrocephalus. [ABSTRACT FROM AUTHOR]

Bing–Neel syndrome (BNS) is a rare condition that may occur in patients with Waldenstrom macroglobulinemia (WM) and is caused by lymphoplasmacytic infiltration into the central nervous system. BNS is an extramedullary manifestation of WM which may present with various neurological signs and symptoms that make the diagnosis difficult to achieve. We present a case of BNS in a 60-year-old patient diagnosed 6 years after recovering from Waldenstrom's macroglobulinemia. We observed the patient for a secondary generalized focal motor seizure. Unenhanced brain CT revealed slight hyperdensity of left parietal subarachnoid spaces. The MRI of the brain and spinal cord showed leptomeningeal enhancement in both parietal lobes. The presence of monoclonal bands (light chain k and IgM) was found in cerebrospinal fluid, leading to the diagnosis of BNS. The patient started treatment with ibrutinib and remains clinically stable during a 1-year follow-up. However, the MRI showed the appearance of a new subcortical left parietal lesion. BNS is an extremely rare presentation of WM that should be recognized and considered early in the presence of unexplained neurological symptoms in patients with a history of WM, even if the patient appears to have recovered. [ABSTRACT FROM AUTHOR]

Oculomotor nerve palsy can be a strong indicator of an internal carotid artery aneurysm, specifically of the posterior communicating artery, due to the anatomical positioning within the basal cisterns of the subarachnoid space, which allows for nerve compression. This condition can predict an acute subarachnoid haemorrhage, associated with a high mortality rate, often presenting with sudden, severe headaches, with or without deficits. The pathophysiology theories include direct mechanical compression by the aneurysmal sac, arterial pulsations, and nerve tissue oedema from venous obstruction. In cases of unruptured aneurysms, nerve irritation is less common. This palsy occurs in about one-third of cases. Aneurysmal orientation can vary (lateral, superior, inferior, medial, posterior), and due to the nerve’s anatomical position, aneurysms in the postero-lateral-inferior position are more likely to cause nerve damage. Treatment opinions vary from observation to intervention, with options including traditional neurosurgery and endovascular embolization. The latter is increasingly preferred due to its efficacy and lower risk profile. A clinical case involves a 56-year-old female presenting with ptosis, diplopia, and ipsilateral mydriasis. Imaging confirmed a posterior communicating artery aneurysm with a maximum diameter of 5.3 mm and a 3 mm bleb. Endovascular coiling was performed successfully, excluding the aneurysm from circulation without complications. Post-treatment, the patient was discharged in good condition with recommendations for periodic monitoring. In conclusion, while no single best treatment exists for posterior communicating artery aneurysms with oculomotor nerve palsy, early intervention (surgical or endovascular) and patient monitoring are crucial for preventing complications and ensuring quality of life. [ABSTRACT FROM AUTHOR]

Patients with leptomeningeal carcinomatosis (LMC) experience a poor prognosis and rapid progression, and cerebrospinal fluid drainage (CSFD) is used to manage intracranial hypertension and hydrocephalus in LMC patients. This study aims to describe a novel discovery of preoperative radiological features in patients who underwent CSFD for LMC. A retrospective review was conducted during the past 5 years of LMC patients with intracranial hypertension and hydrocephalus who underwent CSFD. We evaluated the patients' preoperative radiological features, clinical characteristics, and survival times. A total of 36 patients were included. Of the 36 patients, 34 underwent ventriculoperitoneal shunting, and 2 patients underwent only external ventricular drainage due to rapid progression. The median preoperative Karnofsky performance scale score was 40.0 (interquartile range [IQR], 20.0–40.0). The median survival time after surgery was 5 months (IQR, 0.00–10.43 months). Of the 36 patients, 24 (66.7%) had supratentorial cerebral edema before surgery, including 14 patients (38.9%) with features of disproportionately enlarged subarachnoid space hydrocephalus (DESH). Four patients (11.1%) exhibited cerebellar swelling and had a median survival time of 0.27 month (IQR, 0.00–0.56 month). Nine patients (25%) have enhancement lesions on the cerebellum. The survival curve analysis shows that patients with features of cerebellar enhancement have shorter survival times than other patients. Patients with DESH features have longer survival times compared with those with global cerebral edema. Patients with radiological features of cerebellar enhancement have shorter postoperative survival than other patients; however, those with supratentorial cerebral edema, especially features of DESH, could benefit from CSFD. Patients with cerebellar swelling should avoid undergoing CSFD. [ABSTRACT FROM AUTHOR]

Background Large pituitary adenoma often pushes the diaphragma sella and extends to the suprasellar compartment. The thinned out diaphragma may get opened during endonasal endoscopic surgery and pose high risk for cerebrospinal fluid (CSF) leak. Such larger defects are difficult to plug with fat graft that tends to slip in to the subarachnoid space. Here, we describe a unique technique of closure of diaphragma sella that augment repair of the skull base in such cases. Materials and Method The free edge of diaphragma sella was sutured with the anterior tuberculum sella dura in five cases of large pituitary adenoma that needed extra arachnoidal resection. Suturing was done with 6-0 prolene using endoscopic needle holder that converted a large diaphragm defect in to a smaller arachnoid rent and was easily plugged with fat graft. Result None of these patients had postoperative CSF leak. Conclusion Though technically difficult, direct repair of the diaphragma sella is possible. This augments the skull base reconstruct and effectively reduces the chances of postoperative CSF leak. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. While new therapeutic modalities have been available for Alzheimer's disease, there is currently no effective treatment for VaD. We encountered two cases with VaD who recovered their cognitive function to normal levels after ventriculoatrial shunt (VA shunt). Both cases complained cognitive impairment shortly after cerebral infarctions. Their brain images showed ventricular dilatation without the findings of disproportionately enlarged subarachnoid space hydrocephalus, which is regarded as characteristic for idiopathic normal pressure hydrocephalus (iNPH). Both cases were initially diagnosed as VaD by board neurosurgeons. However, since they showed positive response to lumbar tap test, VA shunts were performed. Both cases recovered their cognitive function to normal level. Their excellent cognitive outcomes after VA shunts indicate that many iNPH patients with lacunar infarcts may possibly be misdiagnosed as VaD. [ABSTRACT FROM AUTHOR]