Ventricular System Research Articles

A PREMATURIDADE ASSOCIADA A FATORES NEUROLÓGICOS: UMA REVISÃO INTEGRATIVA DE LITERATURA

The risk factors associated with prematurity include a series of significant neurological complications, including periventricular leukomalacia, encephalopathy of prematurity, seizures, intraventricular hemorrhage and cerebellar lesions. Periventricular leukomalacia is characterized by necrosis of the cerebral white matter near the lateral ventricles and is strongly associated with motor and cognitive deficits. Encephalopathy of prematurity refers to a variety of brain lesions resulting from the immaturity and vulnerability of the premature brain, impacting long-term neurological development. Seizures in premature newborns are often indicative of significant brain insults and can lead to permanent neurological damage. Intraventricular hemorrhage, a condition in which bleeding occurs within the ventricles of the brain, is associated with an increased risk of developing hydrocephalus and permanent brain damage. Finally, cerebellar lesions, which affect the cerebellum, impair motor coordination and balance, contributing to difficulties in motor and cognitive development. These risk factors highlight the need for early interventions and intensive care strategies to mitigate the adverse impacts of prematurity on children's neurological development. Therefore, the aim of this study is to condense and understand the neurological factors involved in prematurity in the Brazilian context.

Top stories on advances in understanding ventricular conduction system development, physiology, arrhythmogenesis, and therapeutics

Top stories on advances in understanding ventricular conduction system development, physiology, arrhythmogenesis, and therapeutics

Leonardo da Vinci as a Neurologist

In addition to his versatility in painting and art, Leonardo da Vinci was extremely passionate about medicine, particularly the study of the brain. He investigated the ventricles of the brain in great detail in an attempt to locate the seat of the soul in the brain (senso comune). Pathography on Leonardo da Vinci suggests that his ability to use mirror writing and supposed attention-deficit/hyperactivity disorder may have contributed to his extraordinary creativity and tendency to be unable to complete his work. It is presumed that Leonardo da Vinci died of a stroke; however, it is speculated that ulnar or median nerve palsy led to right upper limb paralysis that prevented him from painting in his later years.

Morphometry of choroid plexus epithelial cells in neurodegenerative diseases.

The choroid plexus not only secretes the majority of cerebrospinal fluid but also controls the circadian rhythm, which can be impaired in the presence of neurodegenerative diseases. In addition, many studies have reported the contribution of choroid plexus abnormalities to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Formalin-fixed paraffin-embedded blocks were obtained from the lateral ventricles of the brains of four subjects with AD, four with vascular dementia, four with Parkinson's disease, three with multiple system atrophy, and five control patients with unremarkable neuropathological findings. They were sectioned and routinely stained with hematoxylin and eosin. Morphological analysis of epithelial cells in 10 high-power fields or a total area per case was conducted using digital images. There were no significant changes in any of the measurements: epithelial cell area, long and short axes, and ratio of the epithelial cell area to total stained area among the five groups. However, a simple linear regression analysis of epithelial cells in 20 patients showed that age was significantly correlated with the cell area, long axis, and short axis but not ratio. There were no effects of hypertension, diabetes mellitus, or calcification in the stroma on the measurements. These findings indicate that age was associated with the cell area and size in choroid plexus epithelial cells, whereas no significant changes in any epithelial cell measurements were present in neurodegenerative diseases.

Administration of monophosphoryl lipid A shortly after traumatic brain injury blocks the following spatial and avoidance memory loss and neuroinflammation

Traumatic brain injury (TBI) frequently leads to cognitive impairments. The toll-like receptor 4 (TLR4) ligand, Monophosphoryl lipid A (MPL), has shown promise in modulating neuroinflammatory responses after TBI. We investigated the effects of MPL on spatial memory, passive avoidance memory, neuronal survival, and inflammatory/anti-inflammatory cytokines in rat brain following mild-to-moderate TBI. Rats underwent a learning period in the Morris water maze and shuttle box, followed by TBI induction by controlled cortical impact. MPL was administered into the cerebral ventricle 20 min after TBI. Spatial memory was assessed 7 and 28 days later. Passive avoidance memory was assessed 2 and 6 days after TBI. MPL significantly improved the spatial memory deficit at 7 days but not 28 days after TBI. It also improved impairment of the avoidance memory at both 2 and 6 days after TBI. MPL prohibited the TBI-induced TNF-α increase and IL-10 decrease in the injured region at 7 days post-TBI period. MPL prevented the neuronal loss induced by TBI in the hippocampus. A single administration of MPL shortly after TBI alleviates short-term memory deficits, through anti-inflammatory and anti-cell loss activities. Repeated MPL administration may also inhibit the long-term memory deficits after TBI.

Paclitaxel triggers molecular and cellular changes in the choroid plexus.

Paclitaxel is a widely used chemotherapeutic agent for treating various solid tumors. However, resulting neuropathic pain, often a lifelong side effect of paclitaxel, can limit dosing and compromise optimal treatment. The choroid plexus, located in the brain ventricles, spreads peripheral inflammatory reactions into the brain. Our study is the first to analyze the effects of paclitaxel on inflammatory alterations in the choroid plexus. We hypothesized that the choroid plexus could respond directly to paclitaxel and simultaneously be indirectly altered via circulating damage-associated molecular patterns (DAMPs) produced by paclitaxel application. Using immunohistochemical and Western blot analysis, we examined the levels of toll-like receptor 9 (TLR9) and formyl peptide receptor 2 (FPR2), along with the pro-inflammatory cytokines interleukin 6 (IL6) and tumor necrosis factor α (TNFα) in choroid plexus epithelial cells of male Wistar rats following paclitaxel treatment. Moreover, we utilized an in vitro model of choroid plexus epithelial cells, the Z310 cells, to investigate the changes in these cells in response to paclitaxel and DAMPs (CpG ODN). Our results demonstrate that paclitaxel increases TLR9 and FPR2 levels in the choroid plexus while inducing IL6 and TNFα upregulation in both acute and chronic manners. In vitro experiments further revealed that paclitaxel directly interacts with epithelial cells of the choroid plexus, leading to increased levels of TLR9, FPR2, IL6, and TNFα. Additionally, treatment of cells with CpG ODN, an agonist of TLR9, elicited upregulation of IL6 and TNFα. Our findings determined that paclitaxel influences the choroid plexus through both direct and indirect mechanisms, resulting in inflammatory profile alterations. Given the pivotal role of the choroid plexus in brain homeostasis, a compromised choroid plexus following chemotherapy may facilitate the spread of peripheral inflammation into the brain, consequently exacerbating the development of neuropathic pain.

Focused Ultrasounds as an Adeno-Associated Virus Gene Therapy-Empowering Tool in Juvenile Mice via Intracerebroventricular Administration.

Systemic delivery of adeno-associated virus (AAV) vectors targeting the central nervous system has the potential to solve many neurodevelopmental disorders, yet it is made difficult by the filtering effect of the blood-brain barrier and systemic complications. To overcome this limitation, we attempted to inject a Venus-expressing, oligodendrocyte-selective AAV9 viral vector in the ventricles together with lipid microbubbles and subjected them to focused ultrasound (FUS); the resulting mechanical stimulation on the brain ventricles is able to open small, temporary gaps from which vector particles can leak and spread. Our findings indicate that FUS can increase viral vector diffusion across both the anteroposterior and left-right axes without influencing cell tropism; significant effects were found with 60 and 90 s exposure time, but no effects were observed with longer intervals. Taken together, these results highlight a new strategy for the safe and effective delivery of viral vectors and offer new perspectives for the development and application of gene therapies for central nervous system diseases.

Acute hyperglycemia is associated with intraventricular extension among patients with spontaneous intracerebral hemorrhage

ObjectiveAcute hyperglycemia following intracerebral hemorrhage (ICH) is associated with poor functional outcomes and may result from a neuroendocrine stress response. Given the proximity of neuroendocrine structures to the cerebral ventricles, we tested the hypothesis that intraventricular hemorrhage (IVH) is associated with hyperglycemia. Materials and methodsA post-hoc analysis of the ICH Deferoxamine (i-DEF) trial was conducted to determine predictors of IVH. Variables with significant differences (p < 0.1) in univariable tests between patients with and without IVH were entered into a logistic regression model along with age, sex, diabetes, hyperglycemia (admission glucose ≥140 mg/dL), and baseline intraparenchymal hemorrhage (IPH) volume. This model was then applied to an independent cohort of consecutive non-traumatic ICH patients admitted to a single referral center (2007 to 2018). ResultsAmong 294 patients in the i-DEF cohort with mean age 60 ± 12 years (IVH in 41 %), hyperglycemia (aOR 1.90, 95 % CI [1.06–3.38]), smoking history (aOR 1.90, 95 % CI [1.11–3.27]), and non-lobar ICH location (aOR 3.38, 95 % CI [1.49–7.69]) were independently associated with IVH. In the independent cohort consisting of 856 patients with mean age 71 ± 12 years (IVH in 37 %), hyperglycemia (aOR 2.23, 95 % CI [1.55–3.20]), non-lobar ICH location (aOR 2.50, 95 % CI [1.75–3.59]), and IPH volume (aOR 1.02, 95 % CI [1.01–1.02]) were associated with IVH. ConclusionsHyperglycemia is associated with IVH and may be a peripheral marker for the inflammatory response to hemorrhage within the ventricles. Further translational studies are needed to elucidate the pathophysiological basis for this phenomenon.

Neuroendoscopic Lavage in Hydrocephalus with Ventricular Empyema: A Case Report

Introduction: Ventricular empyema, or pyogenic ventriculitis, is a severe condition characterized by pus accumulation in the cerebral ventricles due to intracranial infection, often caused by Gram-negative bacteria. Early diagnosis and treatment are crucial to prevent fatal neurological damage. Case Report: A 3-month-old infant with severe hydrocephalus and ventricular empyema was admitted with symptoms of seizures, fever, and diarrhea. Initial examination showed decreased consciousness and significant leukocytosis. CT scans confirmed severe hydrocephalus and ventricular empyema. Despite resistance to standard antibiotics, neuroendoscopic lavage (NEL) and bilateral external ventricular drainage (EVD) were performed, leading to substantial improvement. Discussion: The patient’s condition improved significantly post-surgery, with a decrease in leukocyte count and resolution of empyema as shown in follow-up imaging. This case demonstrates the efficacy of NEL in treating complex pediatric neurosurgical conditions. Conclusion: NEL proves to be an effective treatment for intraventricular empyema in pediatric patients, improving clinical outcomes and reducing hospital stays. The success of this approach emphasizes the need for tailored neurosurgical interventions and regular follow-ups to ensure patient recovery and prevent recurrence.

Real-time volumetric imaging of cells and molecules in deep tissues with Takoyaki ultrasound.

Acoustic contrast agents and reporter genes play a critical role in allowing ultrasound to visualize blood flow, map molecules and track cellular function in opaque living organisms. However, existing ultrasound methods to image acoustic contrast agents predominantly focus on 2D planar imaging, while the biological phenomena of interest unfurl in three dimensions. Here, we introduce a method for efficient, dynamic imaging of contrast agents and reporter genes in 3D using multiplexed matrix array transducers. Our "Takoyaki" pulse sequence uses the simultaneous scanning of multiple focal points to excite contrast agents with sufficient acoustic pressure for nonlinear imaging while efficiently covering 3D space. Through in vitro experiments, we first show that the Takoyaki sequence produces highly sensitive volume images of gas vesicle contrast agents and compare its performance with alternative imaging schemes. We then establish its utility in cellular imaging in vivo by visualizing acoustic reporter gene-expressing tumors in a mouse model of glioblastoma. Finally, we demonstrate real-time volumetric imaging by tracking the dynamics of fluid motion in brain ventricles after intraventricular contrast injection. Takoyaki imaging enables a more comprehensive understanding of biological processes by providing spatiotemporal information in 3D within the constraints of accessible multiplexed matrix array systems.

Anatomical Characteristics of Cervicomedullary Compression on MRI Scans in Children with Achondroplasia.

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.1-3.6] years) and compared with scans from 37 children without achondroplasia (median age 1.5 [0-3.9] years). Mann-Whitney U testing was used for between-group comparisons. Foramen magnum diameter and area were significantly smaller in children with achondroplasia compared with the reference group (mean 10.0 vs. 16.1 mm [p < 0.001] and 109.0 vs. 160.8 mm2 [p = 0.005], respectively). The tentorial angle was also steeper in children with achondroplasia (mean 47.6 vs. 38.1 degrees; p < 0.001), while the clivus was significantly shorter (mean 23.5 vs. 30.3 mm; p < 0.001). Significant differences were also observed in myelon area, occipital angle, fourth ventricle, intracranial cerebrospinal fluid and supratentorial ventricular volumes, and the volume of brainstem protruding beyond the posterior fossa (all p < 0.05). MRI analysis of brain structures may provide a standardized value to indicate decompression surgery in children with achondroplasia.

Frontal Horn of Lateral Ventricle of Brain and Its Relation with Age, Gender and Side: Morphometric Study by Computed Tomography among Bangladeshi Population

Background: Knowledge of the baseline reference value of frontal horn size is necessary for the initial and precise analysis of ventriculomegaly. The purpose of this study was to determine the size of frontal horn of lateral ventricle and its relation with age, gender and side among adult Bangladeshi population of Chattogram district. Materials and methods: This cross-sectional analytical study was conducted during the period from July 2022 to June 2023 in the Department of Anatomy, Chittagong Medical College, Chattogram, upon 150 respondents of 20-60 years who had normal Computed Tomography (CT) scans as reported by an expert radiologist. For statistical analysis, Mann-Whitney U test, Wilcoxon signed rank test and ANOVA test were done. p-value was considered significant if it was &lt;0.05 at 95% level of confidence. Results: The mean right and left frontal horn length was 25.50 (±3.95) mm and 25.28 (±4.04) mm respectively. The length of the frontal horn of both right and left sided lateral ventricle were significantly higher in male than that of female (p&lt;0.01). Spearman's correlation coefficient indicated positive linear correlation of length of frontal horn (Right and left side) with age, insignificant in right side (p=0.061) but significant in left side (p=0.046). Conclusion: Morphometric analysis of the frontal horn of the lateral ventricles among the Bangladeshi population produced a number of significant results that may help with the early diagnosis and treatment of neurological diseases that are particular to gender and age. These findings can be validated and expanded upon in future research using bigger sample sizes and cutting-edge imaging methods. IAHS Medical Journal Vol 7(1), June 2024; 54-59

EXTH-84. A DURABLE RECURRENT INTRACEREBROVENTRICULAR INFUSION METHOD IN MICE FOR PRECLINICAL ASSESSMENT OF CELLULAR THERAPEUTICS

Abstract BACKGROUND Significant advancement in cellular treatments for glioblastoma has been made in recent years. The administration route has shifted from intravenous access to local delivery, namely intracerebroventricular (ICV) delivery, in order to prevent the injected cellular products from becoming trapped in peripheral organs such as liver and spleen. There is currently no reliable preclinical system available to accurately examine new cellular treatments that involve long-term recurrent infusion into the cerebral ventricles. METHOD We optimized the surgical device and technique by modifying a commercially available ICV device with a predetermined needle length, eliminating the requirement for spacers hence relieving the tension of the surgical wounds. To avoid skin puncture, we substituted the tunneled catheter with a silicon catheter. The surgical incisions were secured with autoclips in replacement of sutures. We administered periodic infusions of engineered monocytes on a weekly basis using the tunneled catheter for a duration of 8 weeks. The rate of wound dehiscence was monitored. RESULTS The delivery of the engineered monocytes to the cerebral ventricle via the ICV device has been confirmed using a bioluminescence-based imaging. The device and the tunneled catheter demonstrate a long-lasting durability for a minimum of 8 weeks. The optimized device and method effectively reduce the occurrence of post-operative wound dehiscence. Using a silicon catheter minimizes skin punctures. CONCLUSION Our optimized ICV device, material, and surgical approach offer a dependable preclinical instrument for the long-term and recurrent delivery of cellular therapies that reflect patients’ clinical treatment schedules and provide a more accurate evaluation of their translational potential.

ANGI-01. EXTRANEURAL METASTATIC EPENDYMOMA: DISTANT METASTASIS TO THE PLEURA, LUNGS, LYMPH NODES, AND BONE

Abstract Ependymomas are neuroepithelial tumors arising from ependymal cells surrounding the cerebral ventricles that account for 1.6-1.8% of primary CNS tumors. They rarely metastasize to extraneural structures, with one study reporting an incidence of 6.2% with a mean time from diagnosis to extraneural metastasis of 75.6 months. This spread, when it does occur, has been reported to occur to the lungs, lymph nodes, liver, and bone. We describe the case of a patient with recurrent WHO Grade III ependymoma, ZFTA::RELA fusion positive, with extraneural metastatic disease to the thoracic spine, lungs, and pelvic bones. He was treated with multiple surgical resections, radiation therapy, and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space, and lymph nodes. His functional and respiratory statuses declined until he ultimately developed pneumonia, status epilepticus, then spontaneous respiratory arrest, which resulted in his passing away. Salvage chemotherapy for ependymoma has unclear mortality benefit and more research must be done to determine how best to treat patients with extraneural metastases, particularly those who fail traditional treatment with resection and radiation therapy.

TMOD-07. DEVELOPMENT AND CHARACTERIZATION OF A SPINAL CORD DIFFUSE MIDLINE GLIOMA MODEL

Abstract Diffuse midline gliomas (DMGs) are very aggressive central nervous system tumors that occur mainly in children and adolescents. Most DMGs develop in the brainstem, but they can also be found in the thalamus and the spinal cord, the latter comprising 4% of all DMGs. Despite advances in current treatments, the outcome for DMG patients remains extremely poor. The success of immunotherapy in other tumors encourages its translation to DMGs, for which the understanding of the tumor immune microenvironment (TIME) is imperative. The field counts with several murine DMG models in the pontine and thalamic locations. However, there is a paucity of spinal cord models. Thus, in this work, we have generated an orthotopic syngeneic model of H3K27M spinal cord DMG by injecting the tumor cells directly into the spinal cord under the T2 vertebra. We monitored tumor growth by bioluminescence and PET using 18F-FDG and 11C-methionine. As the tumor grew, we observed human-like symptoms in the mice, such as hemiplegia and hemiparesis. TIME characterization showed that this tumor model is mainly infiltrated by macrophages and almost devoid of lymphocytes. We are currently delving into the phenotype of these populations by scRNAseq and spatial transcriptomics. In addition, we are comparing our findings with human samples (n=15) to assess whether our model mimics human disease and can serve as a bonafide model of this tumor location. As a proof of concept, treatment of spinal DMG-bearing mice with a TIM-3 antagonist antibody, previously described as effective in pontine DMG-bearing mice, increased the median overall survival. We showed by microPET imaging that anti-TIM-3 administration into the brain ventricles diffuses to the tumor. These results open a path for the characterization of the spinal cord DMG TIME and for testing preclinical treatments in this new model.

CNSC-32. CHARACTERISTIC ANALYSIS OF SPREAD AND METASTASIS OF HIGH-GRADE GLIOMA

Abstract OBJECT Exploring the clinical characteristics of spread and metastasis of high-grade glioma is helpful for clinicians to further understand high-grade glioma, optimize clinical decision-making, and make treatment plans. METHOD Clinical data of patients diagnosed with WHO Grade 4 glioma with spread and metastasis in the course of disease in Guangdong Sanjiu Brain Hospital from January 1, 2017 to December 31, 2020 were collected and analyzed. RESULTS 93 patients were included in the analysis, 59 males and 34 females, median age of 42 years (3-71 years). Tumors were located supratentorial in 78 patients (83.9%). Most patients (70, 75.3%) had tumors adjacent to the ventricular system. 28 patients (30.1%) had tumor spread at first diagnosis. All patients received surgical at first diagnosis, including total resection in 36 cases (38.7%), partial resection in 42 cases (45.2%), and biopsy in 15 cases (16.1%). In 48 patients (51.6%), ventricles were opened during operation. 69 cases (74.2%) were pathologically diagnosed with glioblastoma, 81 cases (92.0%) were IDH wild-type. MRI findings of dissemination were linear in 50.0% (46 cases), nodular type in 25.0% (23 cases), mixed type in 25.0% (23 cases), and the remaining 1 case was undetermined. Cerebrospinal fluid examination was performed in 37 cases, which 11 cases were cytological positive (29.7%). Median OS for patients with initial dissemination was 338 days. Of the 68 patients developed transmission after treatment, median OS fro initial diagnosis to transmission was 254 days, the overall median OS was 409 days. The overall median OS for all patients was 403 days. The median OS of newly diagnosed patients with tumor spread was lower than that of patients with tumor spread after treatment, but there was no statistical difference (p=0.05). CONCLUSION Most high-grade glioma patients develop tumor spread within 1 year, and these patients have unique clinical characteristics. The positive rate of cerebrospinal fluid tumor cells is low, MRI imaging is still the main diagnostic option.

Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial

Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 × 109 to 5 × 1010vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 × 109 and 1 × 1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 × 1010vp). Therefore, the maximum tolerated dose was determined to be 1 × 1010vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma.

Comprehensive Morphometric Analysis to Identify Key Neuroimaging Biomarkers for the Diagnosis of Adult Hydrocephalus Using Artificial Intelligence.

Hydrocephalus involves abnormal cerebrospinal fluid accumulation in brain ventricles. Early and accurate diagnosis is crucial for timely intervention and preventing progressive neurological deterioration. The aim of this study was to identify key neuroimaging biomarkers for the diagnosis of hydrocephalus using artificial intelligence to develop practical and accurate diagnostic tools for neurosurgeons. Fifteen 1-dimensional (1-D) neuroimaging parameters and ventricular volume of adult patients with non-normal pressure hydrocephalus and healthy subjects were measured using manual image processing, and 10 morphometric indices were also calculated. The data set was analyzed using 8 machine, ensemble, and deep learning classifiers to predict hydrocephalus. SHapley Additive exPlanations (SHAP) feature importance analysis identified key neuroimaging diagnostic biomarkers. Gradient Boosting achieved the highest performance, with an accuracy of 0.94 and an area under the curve of 0.97. SHAP analysis identified ventricular volume as the most important parameter. Given the challenges of measuring volume for clinicians, we identified key 1-D morphometric biomarkers that are easily measurable yet provide similar classifier performance. The results showed that the frontal-temporal horn ratio, modified Evan index, modified cella media index, sagittal maximum lateral ventricle height, and coronal posterior callosal angle are key 1-D diagnostic biomarkers. Notably, higher modified Evan index, modified cella media index, and sagittal maximum lateral ventricle height, and lower frontal-temporal horn ratio and coronal posterior callosal angle values were associated with hydrocephalus prediction. The results also elucidated the relationships between these key 1-D morphometric parameters and ventricular volume, providing potential diagnostic insights. This study highlights the importance of a multifaceted diagnostic approach incorporating 5 easily measurable 1-D neuroimaging biomarkers for neurosurgeons to differentiate non-normal pressure hydrocephalus from healthy subjects. Incorporating our artificial intelligence model, interpreted through SHAP analysis, into routine clinical workflows may transform the diagnostic landscape for hydrocephalus by standardizing diagnosis and overcoming the limitations of visual evaluations, particularly in early stages and challenging cases.

Choroid plexus as a mediator of CNS inflammation in multiple sclerosis.

The pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.

TMEM106B amyloid filaments in the Biondi bodies of ependymal cells

Biondi bodies are filamentous amyloid inclusions of unknown composition in ependymal cells of the choroid plexuses, ependymal cells lining cerebral ventricles and ependymal cells of the central canal of the spinal cord. Their formation is age-dependent and they are commonly associated with a variety of neurodegenerative conditions, including Alzheimer’s disease and Lewy body disorders. Here, we show that Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D. By transmission immuno-electron microscopy, Biondi bodies of choroid plexuses were decorated by TMEM239 and were associated with structures that resembled residual bodies or secondary lysosomes. By electron cryo-microscopy, TMEM106B filaments from Biondi bodies of choroid plexuses were similar (Biondi variant), but not identical, to the fold I that was previously identified in filaments from brain parenchyma.