Cerebrospinal Fluid Research Articles

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Directional flow in perivascular networks: mixed finite elements for reduced-dimensional models on graphs

AbstractFlow of cerebrospinal fluid through perivascular pathways in and around the brain may play a crucial role in brain metabolite clearance. While the driving forces of such flows remain enigmatic, experiments have shown that pulsatility is central. In this work, we present a novel network model for simulating pulsatile fluid flow in perivascular networks, taking the form of a system of Stokes–Brinkman equations posed over a perivascular graph. We apply this model to study physiological questions concerning the mechanisms governing perivascular fluid flow in branching vascular networks. Notably, our findings reveal that even long wavelength arterial pulsations can induce directional flow in asymmetric, branching perivascular networks. In addition, we establish fundamental mathematical and numerical properties of these Stokes–Brinkman network models, with particular attention to increasing graph order and complexity. By introducing weighted norms, we show the well-posedness and stability of primal and dual variational formulations of these equations, and that of mixed finite element discretizations.

Multi-Omic Characterization of Single Cells and Cell-Free Components Detected in the Cerebrospinal Fluid of Patients with Leptomeningeal Disease

Background/Objectives: Up to 30% of patients with breast cancers will develop brain or leptomeningeal metastases, and this risk is especially high with HER2-positive cancers. For patients with central nervous system metastases, cerebrospinal fluid (CSF) liquid biopsies are a promising opportunity to monitor disease, inform treatment, and predict prognosis. This pilot study investigated CSF liquid biopsy analytes from three patients diagnosed with central nervous system metastases based on imaging but not confirmed via clinical cytology. Methods: The detection of cellular analytes with the non-enrichment high-definition single-cell assay (HDSCA3.0) workflow was compared between the CSF and matched peripheral blood (PB) samples. Results: Circulating tumor cells (CTCs) were detected in the CSF but not the PB and were subsequently molecularly characterized using single-cell genomics and targeted multiplexed proteomics to reveal a clonal population of phenotypically heterogeneous cells. There was a lack of concordance in the copy number alteration profiles between CTCs and cell-free DNA (cfDNA) in the CSF. Extracellular vesicle surface marker analysis in CSF revealed a prominent signal among tetraspanins (CD9/CD63/CD81), with CD81 exhibiting the highest signal across all patients. Conclusions: The data presented suggest that CSF could be a useful tool for diagnosing and assessing disease severity.

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.

A sex-dependent algorithm including kappa free light chain for multiple sclerosis diagnosis.

Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist. We aim to evaluate these and to compare the diagnostic accuracy of KFLC concentrations and their related indexes versus OCB. For that purpose, paired CSF and serum samples were collected and immediately processed for albumin, total protein, immunoglobulins and OCB, then frozen at -20°C. KFLC was measured in a BN II (Siemens Healthineers, Germany). KFLC-derived indexes were calculated. Diagnostic accuracy was evaluated by the area under the curve (AUC), Youden's index and odds ratio. From the 193 patients included, 56 were classified as MS according to the 2017 McDonald criteria. K-index, Q KFLC and Reiber's diagram showed good accuracy in MS diagnosis when studied distinguishing between sexes, similar to OCB. Cut-offs for K-index and Q KFLC change substantially between sex having the highest AUC similar than OCB. A sex-dependent algorithm combining the use of K-index, Q KFLC and OCB yields the highest diagnostic accuracy. In conclusion, CSF KFLC measurement is a rapid, quantitative and easy-to-standardize tool that used through the proposed sex-dependent algorithm may reduce the number of manual OCB tests performed.

Elevated serum sodium is linked to increased amyloid-dependent tau pathology, neurodegeneration, and cognitive impairment in Alzheimer's disease.

Vascular dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). While sodium is essential for maintaining vascular function, its role in AD pathology remains unclear. We included 353 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), assessing serum sodium levels, cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, magnetic resonance imaging (MRI), and cognitive function. An independent sample (N = 471) with available CSF sodium-related proteins and AD biomarkers was also included. Associations between serum sodium levels and AD pathology, neurodegeneration, and cognition were evaluated using linear regression models. Spearman's correlation analyses assessed the relationships between CSF sodium-related proteins and AD biomarkers. Higher serum sodium levels were associated with increased AD pathology, reduced hippocampal volume, and greater cognitive decline (all p < 0.05). The relationship between serum sodium and amyloid PET was evident in several AD-susceptible brain regions, including the neocortex and limbic system. Individuals with high serum sodium exhibited higher tau pathology, lower hippocampal volume, and more severe cognitive decline per unit increase in amyloid PET compared to those with low serum sodium (all p < 0.05). Among the 14 CSF sodium-related proteins, which were inter-correlated, six were significantly correlated with CSF AD pathology and amyloid PET, while two were correlated with hippocampal volume and cognitive function, with sodium channel subunit beta-2 (SCN2B) and sodium channel subunit beta-3 (SCN3B) showing the strongest correlations. These findings underscore the crucial role of serum sodium in AD progression, highlighting a potential network of sodium dysregulation involved in AD pathology. Targeting sodium may offer a novel therapeutic approach to slowing AD progression, particularly by impeding the progression of amyloid-related downstream events.

CSF flow measurement in the mesencephalic aqueduct using 2D cine phase-contrast MRI in dogs with communicating internal hydrocephalus, ventriculomegaly, and physiologic ventricular spaces

BackgroundBrachycephalic dogs are overrepresented with ventricular enlargement. Cerebrospinal fluid (CSF) flow dynamics are not completely understood. MRI techniques have been used for the visualization of CSF dynamics including phase-contrast imaging.ObjectivesThis study aimed to determine a causality between CSF flow and ventriculomegaly or hydrocephalus and to compare CSF flow dynamics among dogs with ventriculomegaly, internal hydrocephalus, and physiologic ventricles.AnimalsA total of 51 client-owned dogs were included in the study.MethodsMagnetic resonance imaging (MRI)-based FLASH sequences and phase-contrast images of the brain were obtained, and the ROI was placed at the level of the mesencephalic aqueduct. ECG monitoring was performed parallel to MRI acquisition. Evaluation of flow diagrams and processing of phase-contrast images were performed using commercially available software (Argus VA80A, Siemens AG Healthcare Sector, Erlangen, Germany). Dogs were divided into three groups: Group 1 consisted of brachycephalic dogs with ventriculomegaly (group 1A) or internal hydrocephalus (group 1B), group 2 consisted of brachycephalic dogs with normal ventricles, and group 3 consisted of meso- to dolichocephalic dogs with normal ventricles.ResultsGroup 1 had a higher median Vrost (4.32 cm/s; CI: 2.94–6.33 cm/s) and Vcaud (−6.1 cm/s, CI: 3.99–9.33 cm/s) than group 2 (Vrost: 1.99 cm/s; CI 1.43–2.78 cm/s; Vcaud: 2.91 cm/s, CI: 2.01–4.21 cm/s; p = 0.008; p = 0.03) and group 3 (Vrost:1.85 cm/s, CI: 1.31–2.60 cm/s; Vcaud − 2.46 cm/s, CI 1.68–3.58 cm/s; p = 0.01; p = 0.02). The median Volcaud of group 1 (−0.23 mL/min, CI: 0.13–0.42 mL/min) was higher than that of group 2 (−0.09 mL/min, CI: 0.05 mL/min and 0.15 mL/min) (p = 0.03). Groups 1A and 1B did not differ in Vcaud, Vrost, Volcaud, and Volrost. Group 1A and 1B showed a higher median Vrost (4.01 cm/s, CI: 2.30–7.05 cm/s; 5.94 cm/s, CI: 2.16–7.88 cm/s) than group 2 (1.85 cm/s, CI: 1.24–2.80 cm/s.) (p = 0.03; p = 0.004).Conclusion and clinical importanceIncreased CSF flow velocities in rostral and caudal directions are present in dogs with ventriculomegaly and internal hydrocephalus compared to normal controls.

The "Hedgehog-Halo Sign" Is Associated with Gait Symptom Severity and Tap Response in Normal Pressure Hydrocephalus.

Reduced cerebrospinal fluid (CSF) clearance may play a vital role in the pathogenesis of normal pressure hydrocephalus (NPH), but the radiologic marker is yet to be elucidated. This open-label study presents two novel neuroimaging biomarkers based on enlarged perivascular spaces (ePVS) of the sub-insular territory: the Hedgehog and Hedgehog-Halo (H-H) sign, designed to predict gait symptom severity and tap response in NPH. We retrospectively reviewed 203 patients with possible NPH with baseline magnetic resonance imaging and gait analyses before and after lumbar puncture (LP). The Hedgehog/H-H sign was scored using T2-weighted images. The clinical severity at baseline and post-tap gait improvement was compared in patients with and without Hedgehog/H-H sign. The association between Hedgehog/H-H sign and post-tap gait outcomes was assessed using multivariate regression. The diagnostic performance of Hedgehog/H-H sign was compared with conventional radiological markers. Patients with H-H showed higher global disability and more severe gait impairment than those without any signs. Following LP, patients with Hedgehog/H-H sign significantly improved in various gait parameters, unlike those with neither sign. Additionally, sub-insular ePVS was significantly associated with post-tap gait improvement after adjusting covariates. Finally, the Hedgehog/H-H sign showed a higher performance than conventional markers in predicting post-tap gait response. The Hedgehog/H-H sign is a useful neuroimaging biomarker related to the severity and tap response in NPH. This biomarker can be readily applied in clinical practice before undergoing LP, independent of conventional radiological signs. Further research is warranted to determine applicability in predicting post-shunt gait response.

Multi-scenario refractive index sensor based on merging BIC in an all-dielectric metasurface

In recent years, bound states in the continuum (BICs) in the all-dielectric metasurfaces have attracted considerable attention due to the low radiation loss and large quality factor (Q-factor). In this study, we design a highly sensitive refractive index sensor working in multi-scenario based on merging quasi-BIC in the silicon nitride metasurface. By adjusting the thickness of the metasurface and keeping the structural symmetry, nine BICs distributed in momentum space form the merging BIC at the Γ point with significantly enhanced Q-factor. The transmission spectra of the metasurface sensor disperse with the refractive index in multi-scenario. The modulation depth of the Fano resonance spectrum can exceed 99.9%. The sensitivity and figure of merit of the refractive index sensor based on the merging quasi-BIC can reach 41.35 nm/RIU and 13,389.1 RIU-1 for gas, 59.05 nm/RIU and 8,415.9 RIU-1 for blood, and 66.08 nm/RIU and 8,845.8 RIU-1 for cerebrospinal fluid, respectively. Furthermore, we investigate the influence of the structural deviations on the Q-factor, which of the merging quasi-BIC maintains higher than that of the isolated quasi-BIC. Our work offers a method for designing high-sensitivity sensors working in multi-scenarios, which may hold significant potential for enhancing device performance in gas and biological detection.

The Impact of Venous Stenting for Patients with Idiopathic Intracranial Hypertension and Spontaneous Cerebrospinal Fluid Leak on Symptoms and Quality of Life

BACKGROUND: Elevated intracranial pressure can cause skull base defects and a spontaneous cerebrospinal fluid leak (CSF). Venous sinus stenting (VSS) has emerged as a promising treatment option for patients with a CSF leak in the setting of idiopathic intracranial hypertension (IIH). There is a lack of literature on symptomatology and quality of life (QOL) after VSS for IIH patients with a CSF leak. This study explores the effects of VSS on symptoms and QOL in IIH patients with a CSF leak. METHODS: This is a retrospective study on patients who have IIH complicated by a CSF leak and underwent VSS. A QOL questionnaire was developed from the migraine disability assessment test and the PROMIS-PI was given to patients included in this study. RESULTS: Ten patients were included in this study. Nine patients underwent endoscopic closure of CSF prior to stent placement and one patient was treated with VSS only. There was no evidence of CSF leak recurrence in this population following VSS. Headaches improved in 5/8, tinnitus in 5/6, and visual disturbance in 4/5 patients. Diamox was discontinued in 7 out of 8 patients after VSS. There was an improvement in headache (p=0.0140) specific questions and overall QOL (p=0.0061) on the QOL questionnaire. DISCUSSION: This preliminary study demonstrates that VSS is effective in alleviating many symptoms in IIH patients with a CSF leak, especially headaches. Diamox may be able to be discontinued in many patients following VSS. No CSF leak recurrence was noted in this patient population.

Neurocutaneous Melanocytosis-Associated Hydrocephalus: The Memorial Sloan Kettering Experience from 2001 to 2022.

We report two neurocutaneous melanocytosis (NCM) patients who required ventriculoperitoneal shunt placement and subsequently developed intraperitoneal melanoma. These patients with NCM are at an increased risk for developing NRAS-associated melanomas in the central nervous system, which in turn may lead to symptomatic hydrocephalus requiring cerebrospinal fluid diversion. Due to the rarity of NCM, current knowledge on disease progression and appropriate management is limited. Ongoing studies aiming to better understand this condition and inform its clinical management may help to identify risk factors for developing more severe complications.

Exploring the appropriate situation of performing CSF mNGS in patients with proposed intracranial infections

BackgroundIdentifying the responsible pathogen is crucial for precision medicine in intracranial infections, and Cerebrospinal Fluid (CSF) Metagenomic Next-Generation Sequencing (mNGS) is a reliable method for this detection. However, the indiscriminate utilization of this approach may impose a financial burden on both patients and society. The study aims to investigate the optimal conditions for applying CSF mNGS in patients with suspected intracranial infections, offering valuable references for precision medicine of intracranial infections.MethodsA total of 175 hospitalized patients presenting with suspected intracranial infections were selected for retrospective analysis. Base on the detection of responsible pathogens using CSF mNGS, the patients were categorized into two groups, responsible pathogens in Group A were detected but not in Group B. The types of responsible pathogens in group A and the final diagnosis of patients in group B were analyzed. Demographic data, clinical presentation, CSF analysis, imaging results, and electroencephalography (EEG) findings were analyzed for both groups. Finally, a scoring system was established to promptly assess the appropriateness of CSF mNGS for patients with suspected intracranial infections. Each independent predictor was assigned a score of 1, and the patients were subsequently scored. We advocate sending patients’ CSF for mNGS when the cumulative score is ≥ 2.ResultsIn Group A, the predominant responsible pathogen was the varicella-zoster virus (VZV), while Group B exhibited the highest proportion of final diagnoses related to epilepsy. The logistic regression model indicates that headache [OR = 2.982, 95% CI (1.204–7.383), p = 0.018], increased cerebrospinal fluid white cell count [OR = 4.022, 95% CI (1.331–12.156), p = 0.014], and decreased cerebrospinal fluid glucose levels [OR = 9.006, 95% CI (2.778–29.194), P < 0.001] are independent predictive factors for intracranial infection pathogens detected by CSF mNGS. Under this scoring system, the sensitivity for detecting the responsible pathogen was 57.5%, and the specificity was 87.4%.ConclusionThe likelihood of detecting the responsible pathogen through CSF mNGS in patients with suspected intracranial infections can be evaluated using the scoring system. Furthermore, it is crucial to consider the possibility of another condition, such as epilepsy, when the responsible pathogen is not detected using cerebrospinal fluid mNGS.

Cerebrospinal fluid neurofilament light chain levels in children with acquired demyelinating syndrome

ObjectiveTo study the cerebrospinal fluid (CSF) neurofilament light chain (NfL) in pediatric acquired demyelinating syndrome (ADS) and its association with factors of laboratory and imaging results.MethodsWe analyzed clinical data from children with ADS collected from May 2020 to January 2021 at the Department of Neurology of Guangzhou Women and Children's Medical Center. Enzyme-linked immunosorbent assays were used to detect the CSF NfL of patients.ResultsThirty pediatric ADS patients (17 male, 13 female) were included in the study. The most frequent diagnosis was uncategorized ADS (36.7%, 11/30), followed by acute disseminating encephalomyelitis (ADEM) (23.3%, 7/30), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) (20.0%, 6/30), NMO (6.7%, 2/30), multiple sclerosis (MS) (6.7%, 2/30), and neuromyelitis optic spectrum disorders (NMOSD) (6.7%, 2/30). The median CSF NfL for the first time was 7,425.28 pg/ml (interquartile range, 1,273.51, &amp;gt;10,000 pg/ml). CSF NfL increase over normal value (&amp;lt;290.00 pg/ml for people younger than 30 years old) was seen in 98.7% of patients. Patients were divided into uncategorized ADS, ADEM, MOGAD, and MS/NMO/NMOSD groups, with no significant difference in CSF NfL between each group. The CSF NfL positively correlated with the immunoglobulin (Ig) G (ρ = 0.473) and IgE (ρ = 0.366). However, the CSF NfL did not correlate with CSF white blood count and CSF protein. Furthermore, there was no significant difference between patients with oligoclonal bands positive and without. The CSF NfL negatively correlated with interferon γ (ρ = −0.501), CD45 + CD3+ T (ρ = −0.466), CD45 + CD3 + CD4+ T (ρ = −0.466), and CD45 + CD3 + CD8+ T cells (ρ = −0.521). However, it did not correlate with CD45 + CD19+ B cells. CSF NfL in patients with cerebral white matter lesions in MRI was higher than in patients without. Moreover, the CSF NfL positively correlated with the number of brain MRI locations (ρ = 0.362). Nine patients underwent multiple detections of CSF NfL, and their CSF NfL for the last detection was not significantly different from the first.ConclusionsThe CSF NfL increases significantly in pediatric ADS, and it can be a biomarker of neuro-axonal injury and a good indication of the extent of lesions.

Human herpesvirus 6 (HHV-6) encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapy.

Human herpesvirus (HHV)-6 encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapyis relatively rare in clinical practice and needs to be differentiated from immune effector cell-associatedneurotoxicity syndrome (ICANS). We retrospectively reported a case of HHV-6 encephalitis secondary to CAR-T cell therapy. A male patient from China with diffuse large B-cell lymphoma underwent chimeric CAR-T cell therapy anddeveloped a generalized rash on the 8th day, followed by cognitive changes, memory loss, and disorientation onthe 14th day after CAR-T cell therapy. Initially, ICANS was suspected. A lumbar puncture was performed on the 18th day. The cerebrospinal fluid (CSF) analysis revealed slightly elevated protein levels and a high presence of HHV-6B sequences by mNGS. Brain MRI showed bilateral hippocampal abnormalities. The patient was ultimatelydiagnosed with HHV-6 encephalitis and treated with ganciclovir and dexamethasone. After one week of treatment,follow-up CSF analysis showed a reduction in HHV-6B sequences. The patient was discharged with improvedmemory and orientation. HHV-6 encephalitis secondary to CAR-T cell therapy may be easily confused with ICANS. Timely andaggressive diagnostic procedures, such as mNGS of CSF and cranial imaging, along with prompt antiviral therapy,are crucial for improving patient outcomes.

Psychrobacter sanguinis infection in a pediatric patient with craniopharyngioma identified in a blood culture by 16S rRNA sequencing

AbstractPsychrobacter species are gram‐negative bacteria in the Moraxellaceae family. These bacteria are considered rare opportunistic human pathogens, and the infection sites include blood, cerebral spinal fluid, wounds, urine, the ears, and the eyes. Few cases of human infection by these species have been described previously. We report a case of a 10‐year‐old boy with postneurosurgical bacteremia due to Psychrobacter sanguinis infection. This infection was difficult to identify using routine biochemical phenotypical tests. Sequencing of 16S rRNA was performed to identify this pathogen. The patient was successfully treated with antibiotics. In conclusion, P. sanguinis infections are rare but should be considered when cultures remain negative for common pathogens.

Intradural extramedullary cystic lesions: an interesting cauda equina cysticercosis case report and a literature review

BackgroundIntraspinal cysticercosis, usually with serious neurological deterioration, is rarely diagnosed because its clinical manifestations are nonspecific, and most physicians might not be familiar with its imaging features.Case presentationA 50-year-old woman presented with a 2-month history of increasing pain in her right buttock, rectal tenesmus and uncontrolled micturition. Intradural extramedullary cystic lesion was found, and the characteristic MRI findings of a living cysticercus and a dying cysticercus were presented simultaneously. Finally, the giant intraspinal cysticercus was treated by surgery and antiparasitic treatment.ConclusionsThis case emphasizes that the characteristic imaging findings of different cysticercus cysts as well as the detailed personal history usually provide useful diagnostic clues. Cerebrospinal fluid analysis may aid in confirming the diagnosis.

Varicella zoster vasculopathy causing recurrent ischaemic strokes in an immunocompetent patient.

A 66-year-old woman reported 10 days of generalised weakness, falls and memory 'glitches'. She had developed left-sided ophthalmic herpes zoster 3 months before but was otherwise well. MR scan of brain showed acute left-sided ischaemic strokes and CT cerebral angiogram identified marked stenoses of the left anterior and middle cerebral arteries. We suspected varicella-zoster virus vasculopathy, confirmed by cerebrospinal fluid analysis. Initially she had further ischaemic strokes despite intravenous acyclovir, prednisone, aspirin and clopidogrel. However, after prolonged acyclovir and prednisone, there were no new infarcts though imaging of left anterior and middle cerebral artery vessel walls showed persistent inflammation. Varicella zoster vasculopathy can cause recurrent ischaemic strokes, even in immunocompetent people with no cardiovascular risk factors, and despite long-term antiviral therapy.

Challenges and strategies toward oncolytic virotherapy for leptomeningeal metastasis.

Meningeal metastasis (LM) is commonly seen in the advanced stages of cancer patients, often leading to a rapid decline in survival time and quality of life. Currently, there is still a lack of standardized treatments. Oncolytic viruses (OVs) are a class of emerging cancer therapeutics with the advantages of selectively replicating in cancer cells, delivering various eukaryotic transgenes, inducing immunogenic cell death, and promoting anti-tumor immunity. Some studies applying OVs intrathoracically or intraperitoneally for the treatment of malignant pleural and peritoneal effusions have shown promising therapeutic effects. If OVs could be applied to treat LM, it would bring significant survival benefits to patients with LM. In this review, we analyzed past research on the use of viruses to treat meningeal metastasis, summarized the efficacy and safety demonstrated by the research results, and analyzed the feasibility of oncolytic virus therapy for meningeal metastasis. We also summarized the existing data to provide guidance for the development of OVs that can be injected into the cerebrospinal fluid (CSF).

Progressive Optic Neuropathy in Hydrocephalic Ccdc13 Mutant Mice Caused by Impaired Axoplasmic Transport at the Optic Nerve Head.

Optic nerve head (ONH) atrophy is frequently associated with hydrocephalic conditions. Cerebrospinal fluid (CSF)-containing meninges form a subarachnoid space that terminates at the ONH, which physically impacts it. This study aims to characterize optic neuropathy in congenital hydrocephalic mice with genetic disruption of the Ccdc13 gene. The ccdc13 germline knockout mice were generated. The hydrocephalus phenotype and subarachnoid space surrounding the optic nerve were evaluated using routine histology and Evans blue stain. Optic neuropathy was examined with immunohistochemistry and transmission electron microscopy (TEM). Axon transport was indicated by cholera toxin subunit B (CTB) fluorescence conjugate. Retinal function was evaluated by electroretinography (ERG), and Ccdc13 expression was revealed by a knock-in Gfp reporter. Ccdc13 mutant mice manifested hydrocephalus at birth. ONH displacement, or negative cupping, and enlarged subarachnoid space at the optic terminus occurred as early as 1 month after birth. Intraocular pressure (IOP) was normal. Optic neuropathy was first observed at the ONH, followed by a distal-to-proximal progression of optic nerve pathology indicated by alteration of axonal ultrastructure and deposition of unphosphorylated neurofilament heavy chain. Anterograde axonal transport was also hampered. Retinal ganglion cell (RGC) function was compromised as early as postnatal day 21 (P21), along with reduced neurofilament heavy chain expression. Optic neuropathy caused by disruption of Ccd13 was non-cell autonomous, stemming from hydrocephalus with presumed high intracranial pressure (ICP), which physically impacts the ONH by increasing the translaminar pressure gradient. We provided knowledge of optic neuropathy from a congenital mouse model for hydrocephalus. The hydrocephalus in mice could damage the ONH by increasing the translaminar pressure gradient and negative cupping, leading to impairment in axoplasmic transport and RGC pathology. Our findings highlight the importance of the interplay between IOP and ICP in the development of glaucoma.

Potential biomarkers of the effectiveness of pathogenetic therapy of spinal muscular atrophy in adults

The review summarizes and systematizes data on the prognostic significance of various biomarkers in determining the effectiveness of pathogenetic therapy for spinal muscular atrophy. The review includes a clinical case of a patient with type 3 spinal muscular atrophy. The case illustrates that a decrease in the level of heavy chains of neurofilaments in the cerebrospinal fluid of the patient during the use of pathogenetic therapy with nusinersen positively correlated with an improvement in motor function, assessed by standard functional scales.