Single-nucleus RNA-seq dissection of choroid plexus tumor cell heterogeneity.

The genomic, genetic and cellular events regulating the onset, growth and survival of rare, choroid plexus neoplasms remain poorly understood. Here, we examine the heterogeneity of human choroid plexus tumors by single-nucleus transcriptome analysis of 23,906 cells from four disease-free choroid plexus and eleven choroid plexus tumors. The resulting expression atlas profiles cellular and transcriptional diversity, copy number alterations, and cell-cell interaction networks in normal and cancerous choroid plexus. In choroid plexus tumor epithelial cells, we observe transcriptional changes that correlate with genome-wide methylation profiles. We further characterize tumor type-specific stromal microenvironments that include altered macrophage and mesenchymal cell states, as well as changes in extracellular matrix components. This first single-cell dataset resource from such scarce samples should be valuable for divising therapies against these little-studied neoplasms.

Therapeutic Effect of Boron Neutron Capture Therapy on Boronophenylalanine Administration via Cerebrospinal Fluid Circulation in Glioma Rat Models.

In recent years, various drug delivery systems circumventing the blood-brain barrier have emerged for treating brain tumors. This study aimed to improve the efficacy of brain tumor treatment in boron neutron capture therapy (BNCT) using cerebrospinal fluid (CSF) circulation to deliver boronophenylalanine (BPA) to targeted tumors. Previous experiments have demonstrated that boron accumulation in the brain cells of normal rats remains comparable to that after intravenous (IV) administration, despite BPA being administered via CSF at significantly lower doses (approximately 1/90 of IV doses). Based on these findings, BNCT was conducted on glioma model rats at the Kyoto University Research Reactor Institute (KUR), with BPA administered via CSF. This method involved implanting C6 cells into the brains of 8-week-old Wistar rats, followed by administering BPA and neutron irradiation after a 10-day period. In this study, the rats were divided into four groups: one receiving CSF administration, another receiving IV administration, and two control groups without BPA administration, with one subjected to neutron irradiation and the other not. In the CSF administration group, BPA was infused from the cisterna magna at 8 mg/kg/h for 2 h, while in the IV administration group, BPA was intravenously administered at 350 mg/kg via the tail vein over 1.5 h. Thermal neutron irradiation (5 MW) for 20 min, with an average fluence of 3.8 × 1012/cm2, was conducted at KUR's heavy water neutron irradiation facility. Subsequently, all of the rats were monitored under identical conditions for 7 days, with pre- and post-irradiation tumor size assessed through MRI and pathological examination. The results indicate a remarkable therapeutic efficacy in both BPA-administered groups (CSF and IV). Notably, the rats treated with CSF administration exhibited diminished BPA accumulation in normal tissue compared to those treated with IV administration, alongside maintaining excellent overall health. Thus, CSF-based BPA administration holds promise as a novel drug delivery mechanism in BNCT.

A Rare Case of Meningitis: Can Cellulosimicrobium cellulans Cause Meningitis in a Non-immunocompromised Person?

Infections with Gram-positive soil-dwelling Cellulosimicrobium cellulans bacterium are sporadic. Rarely, do patients with indwelling medical devices or those who suffer from immunosuppression get infected by this pathogen. However, based on routine clinical and laboratory procedures, it is hard to distinguish between the meningitis caused by C. cellulans and that from other bacteria. Here, we report a unique case of C. cellulans infection in a 37-year-old immunocompetent man presenting with meningitis associated with encephalopathy and headache. He presented with severe headaches, altered sensorium, reduced sleep, photophobia, and restlessness, with a feeling of impending doom, but with no neck rigidity and fever. Trans-axial T1 and T2/FLAIR head MRI showed diffused cerebral edema, with bilateral high frontoparietal sulcal enhancement, hyperintensity along the right posterior insula-temporal region, and left parietal deep white matter. Lumbar puncture CSF examination indicated bacterial meningitis, and C. cellulans was identified on culture. The patient was administered intravenous ceftriaxone for seven days and dexamethasone for three days. A follow-up lumbar puncture CSF examination showed no signs of the pathogen, indicating its eradication. To our knowledge, this is the first case of C. cellulans causing meningitis in an otherwise healthy man with no history of indwelling medical devices or immunosuppression. This rare case of meningitis suggests that C. cellulans can infect healthy humans and cause meningitis.

Nanopore-targeted sequencing (NTS) for intracranial tuberculosis: a promising and reliable approach.

BACKGROUND: The World Health Organization predicted 10.6 million new tuberculosis cases and 1.5 million deaths in 2022. Tuberculous meningitis, affecting 1% of active TB cases, is challenging to diagnose due to sudden onset, vague symptoms, and limited laboratory tests. Nanopore-targeted sequencing (NTS) is an emerging third-generation sequencing technology known for its sequencing capabilities. We compared its detection efficiency with Xpert, MTB culture, PCR, and AFB smear in cerebrospinal fluid samples to highlight the substantial potential of NTS in detecting intracranial tuberculosis. METHODS: This study included 122 patients suspected of having intracranial tuberculosis at the Second Hospital of Nanjing in Jiangsu Province, China, between January 2021 and January 2024. The Univariate logistic regression and random forest regression identified risk factors and clinical markers. A chi-square test evaluated diagnostic accuracy for different image types of intracranial tuberculosis. RESULTS: The research involved 100 patients with intracranial tuberculosis. Among them, 41 had tuberculous meningitis, 27 had cerebral parenchymal tuberculosis, and 32 had mixed intracranial tuberculosis. Besides, 22 patients were diagnosed with other brain conditions. In diagnosing intracranial tuberculosis, NTS demonstrated a sensitivity of 60.0% (95% CI: 49.7-69.5%) and a specificity of 95.5% (95% CI:75.1-99.8%), with an AUC value of 0.78 (95% CI: 0.71 to 0.84), whose overall performance was significantly better than other detection methods. There was no notable difference (P > 0.05) in diagnostic accuracy between NTS and the final diagnosis for intracranial tuberculosis patients with varying imaging types. Furthermore, patients who tested positive had a 31.500 (95% CI: 6.205-575.913) times higher risk of having intracranial tuberculosis compared to those with negative results. CONCLUSION: Due to its convenience, efficiency, quick turnaround time, and real-time sequencing analysis, NTS might become a promising and reliable method for providing microbiological diagnoses for patients with intracranial tuberculosis and for screening populations at risk.

Sex-specific age-related differences in cerebrospinal fluid clearance assessed by resting-state functional magnetic resonance imaging.

Cerebrospinal fluid (CSF) flow may assist the clearance of brain wastes, such as amyloid-ß (Aß) and tau, and thus play an important role in aging and dementias. However, a lack of non-invasive tools to assess the CSF dynamics-related clearance in humans hindered the understanding of the relevant changes in healthy aging. The global infra-slow (<0.1 Hz) brain activity measured by the global mean resting-state fMRI signal (gBOLD) was recently found to be coupled by large CSF movements. This coupling has been found to correlate with various pathologies of Alzheimer's disease (AD), particularly Aß pathology, linking it to waste clearance. Using resting-state fMRI data from a group of 719 healthy aging participants, we examined the sex-specific differences of the gBOLD-CSF coupling over a wide age range between 36-100 years of age. We found that this coupling index remains stable before around age 55 and then starts to decline afterward, particularly in females. Menopause may contribute to the accelerated decline in females.

Modified rat pup cerebrospinal fluid collection method.

BACKGROUND: Cerebrospinal fluid (CSF) reflects biochemical changes in the brain due to its direct contact with brain interstitial fluid, making it a valuable tool for diagnosing and monitoring disease progression and therapeutic effectiveness in clinical practice. However, collecting CSF in animal studies, particularly from small animals like rat pups or mice, poses significant challenges. NEW METHOD: After attempting various reported protocols, we encountered difficulties in consistently obtaining sufficient CSF from rat pups (P7-P42). Consequently, we modified these methods and developed a protocol with controllable and precise parameters for each step, enhancing reproducibility across different researchers. RESULTS: The newly developed method enables rapid, single-operator, and reproducible CSF extraction while ensuring high-quality (the absorbance of the "quality control solution" at 415 nm < 0.05 AU, an indicator of oxyhemoglobin contamination for the collected CSF samples) and high-yield samples (33 ± 2.128 µL for P7 pups, 34.10 ± 2.747 µL for P8 pups, 36.67 ± 3.997 µL for P9 pups, 36.90 ± 1.946 µL for P10 pups, 35.11 ± 3.285 µL for P10 hypoxic-ischemic brain damage (HIBD) pups and 51.70 ± 5.256 µL for P42 pups, respectively). COMPARISON WITH EXISTING METHODS: Unlike existing methods of CSF extraction in rat pups, our protocol has reproducible capillary pipette pulling parameters, controllable CSF quality indexes, and can be operated by a single person with high yield in a short time. CONCLUSIONS: This paper provides a step-by-step comparison and discussion of the CSF collection process, establishing a method that enables a single operator to collect CSF rapidly, consistently, sufficiently, and with controlled quality.

A Trespasser in Lymph Node: A Case Report.

Cryptococcal meningitis is a prevalent, opportunistic fungal disease seen in human immunodeficiency virus (HIV)-infected individuals. A lymph node is an unusual presentation site for Cryptococcus and can mimic tuberculosis. Disseminated cryptococcosis is a life-threatening disease that is seen commonly in acquired immunodeficiency syndrome (AIDS). We report a case of an HIV patient who presented with mild pleural effusion, multiple mediastinal, axillary lymphadenopathy with a low CD4:CD8 lymphocyte ratio, and favored clinically disseminated tuberculosis. Further cerebrospinal fluid (CSF) and tracheal aspirate have been done. Tracheal aspirate culture shows a fungal organism resembling Cryptococcus. Later, India ink staining on CSF highlighted the fungal organism Cryptococcus. Cytopathological investigation showed necrotizing inflammation along with fungal organisms, confirming the presence of cryptococcal lymphadenitis.

Perspective: Risks/adverse events for epidural spinal injections.

Background: Despite the lack of FDA (Food and Drug Administration) approval, cervical and lumbar epidural spinal injections are frequently performed in the US to address back pain and/or painful radiculopathy. The three major types of injections include; interlaminar/translaminar (ESI), transforaminal (TFESI), or caudal injections. Notably, most studies document little to no clear short-term, and no long-term benefits/efficacy for these injections vs. various placebos. Methods: More adverse events (AE) occurred with cervical© rather than lumbar (L) injections, and more severe AE were attributed to C-TFESI vs. CESI injections. Results: Acute post injection AE symptoms were observed immediately or within 72 post-injection hours. These symptoms included; hypotension, acute respiratory distress, chest pain, upper extremity numbness, weakness, paresthesias, paralysis, and fevers. More AE were attributed to cervical C-TFESI vs. cervical CESI. These AE included; intramedullary/cord injections, intravascular injections (i.e. vertebral artery) resulting in brain stem/cerebellar/cord strokes, epidural abscess/infection, confusion, epidural hematomas, intracranial hypotension, and/or 6th nerve cranial palsies. AE for lumbar LESI/L-TFESI included; infections/abscess, epidural hematomas/subdural hematomas, intravascular injections, cerebrospinal fluid (CSF) leaks/dural tears (DT), and intracranial/postural hypotension. Notably, the vast majority of studies showed little to no short-term, and no long-term benefits for cervical or lumbar ESI/TFESI vs placebos (i.e. mostly consisting of normal saline alone, or saline plus local anesthesia). Conclusion: Epidural cervical and lumbar ESI or TFESI spinal injections demonstrated minimal to no short-term, and no long-term benefits for the treatment of cervical and/or lumbar pain/radiculopathy vs. placebos. Further, more AE were observed for cervical vs. lumbar epidural injections overall, with more AE usually seen with TFESI vs. ESI procedures.

Numerical analysis of the effect of Syringomyelia on cerebrospinal fluid dynamics.

Spinal cord enlargement (SCE) includes conditions such as Syringomyelia, tumors, and tumor-like cases of demyelination, edema, or inflammation. These conditions involve fluid-filled cysts, known as syrinx, or masses of tissue, referred to as tumors, which cause increased pressure within the spinal cord (SC) and obstruct cerebrospinal fluid (CSF) circulation. To assess the impact of SCE location and diameter, we constructed fifteen computational SC models, each featuring a SCE placed in one of five probable locations with 20 %, 40 %, and 60 % stenosis. Our objective was to investigate how the location, diameter, and length of the SCE influence CSF velocity pattern and to identify the most critical location in the SC associated with this condition. The results indicated a velocity increase of 0.5 cm/(s) near models with 60 % stenosis. Importantly, SCE located from T1 to T5 exhibit a more pronounced reduction, exceeding 6.5, in the Womersley number. Our finding suggests that this region is the most vulnerable for SCE formation due to its significant impact on fluid circulation. The identification of specific locations within the SC associated with heightened risk can contribute to an improved understanding, treatment and management of SCE.

Targeted proteomics of cerebrospinal fluid in treatment naïve multiple sclerosis patients identifies immune biomarkers of clinical phenotypes.

Multiple sclerosis (MS) is an inflammatory demyelinating disease with heterogeneous clinical presentations and variable long-term disability accumulation. There are currently no standard criteria to accurately predict disease outcomes. In this study we investigated the cross-sectional relationship between disease phenotype and immune-modulating cytokines and chemokines in cerebrospinal fluid (CSF). We analyzed CSF from 20 DMT-naïve MS patients using Olink Proteomics' Target 96 Inflammation panel and correlated the resulting analytes with respect to (1) disease subtype, (2) patient age and sex, (3) extent of clinical disability, and (4) MRI segmental brain volumes. We found that intrathecal IL-4 correlated with higher Expanded Disability Status Scale (EDSS) scores and longer 25-foot walk times, and CD8A correlated with decreased thalamic volumes and longer 9-hole peg test times. Male sex was associated with higher FGF-19 expression, and Tumefactive MS with elevated CCL4. Several inflammatory markers were correlated with older age at the time of LP. Finally, higher intrathecal IL-33 correlated with increased MS lesion burden and multi-compartment brain atrophy. This study confirms immune heterogeneity underlying CSF profiles in MS, but also identifies several inflammatory protein biomarkers that may be of use for predicting clinical outcomes in future algorithms.

Functional MRI study with conductivity signal changes during visual stimulation.

BACKGROUND: Although blood oxygen level-dependent (BOLD) functional MRI (fMRI) is a standard method, major BOLD signals primarily originate from intravascular sources. Magnetic resonance electrical properties tomography (MREPT)-based fMRI signals may provide additional insights into electrical activity caused by alterations in ion concentrations and mobilities. PURPOSE: This study aimed to investigate the neuronal response of conductivity during visual stimulation and compare it with BOLD. MATERIALS AND METHODS: A total of 30 young, healthy volunteers participated in two independent experiments using BOLD and MREPT techniques with a visual stimulation paradigm at 3 T MRI. The first set of MREPT fMRI data was obtained using a multi-echo spin-echo (SE) echo planar imaging (EPI) sequence from 14 participants. The second set of MREPT fMRI data was collected from 16 participants using both a single-echo SE-EPI and a single-echo three-dimensional (3D) balanced fast-field-echo (bFFE) sequence. We reconstructed the time-course Larmor frequency conductivity to evaluate hemodynamics. RESULTS: Conductivity values slightly increased during visual stimulation. Activation strengths were consistently stronger with BOLD than with conductivity for both SE-EPI MREPT and bFFE MREPT. Additionally, the activated areas were always larger with BOLD than MREPT. Some participants also exhibited decreased conductivity values during visual stimulations. In Experiment 1, conductivity showed significant differences between the fixation and visual stimulation blocks in the secondary visual cortex (SVC) and cuneus, with conductivity differences of 0.43 % and 0.47 %, respectively. No significant differences in conductivity were found in the cerebrospinal fluid (CSF) areas between the two blocks. In Experiment 2, significant conductivity differences were observed between the two blocks in the SVC, cuneus, and lingual gyrus for SE-EPI MREPT, with differences of 0.90 %, 0.67 %, and 0.24 %, respectively. Again, no significant differences were found in the CSF areas. CONCLUSION: Conductivity values increased slightly during visual stimulation in the visual cortex areas but were much weaker than BOLD responses. The conductivity change during visual stimulation was less than 1 % compared to the fixation block. No significant differences in conductivity were observed between the primary visual cortex (PVC)-CSF and SVC-CSF during fixation and visual stimulations, suggesting that the observed conductivity changes may not be related to CSF changes in the visual cortex but rather to diffusion changes. Future research should explore the potential of MREPT to detect neuronal electrical activity and hemodynamic changes, with further optimization of the MREPT technique.

Optimization of the Diagnosis of Central Nervous System Infections in Vietnamese Hospitals: Results From a Retrospective Multicenter Study.

Introduction: Central nervous system infections pose significant health challenges, particularly in low- and middle-income countries, because of high morbidity and mortality rates. Rapid and accurate diagnosis is essential for effective treatment to prevent adverse outcomes. Traditional culture-based diagnostics are often slow and lack specificity. This study evaluates the BioFire FilmArray Meningitis/Encephalitis (FAME) Panel against standard diagnostics in Vietnam to assess its clinical impact and suitability for local epidemiology. Methods: We conducted a prospective study involving 330 patients with suspected central nervous system infections at 4 hospitals in northern Vietnam from July 2022 to April 2023. Cerebrospinal fluid samples were analyzed using routine culture methods and FAME. We compared pathogen detection rates and assessed the potential clinical impact of FAME results on patient management. Results: Of the 330 cerebrospinal fluid specimens, 64 (19%) were positive by either conventional diagnostics (n = 48) and/or FAME (n = 33). The agreement between FAME and conventional diagnostics was 87%. Key pathogens Mycobacterium tuberculosis (n = 7), Klebsiella pneumoniae (n = 5), Streptococcus suis (n = 5), Epstein-Barr virus (n = 3), Acinetobacter baumannii (n = 1), and Trichosporon asahii (n = 1) were not detected by FAME. Classical meningitis parameter clinical symptoms, altered glucose, protein, and pleocytosis were good predictors of FAME positivity, indicating their utility in optimizing local diagnostic algorithms. Conclusions: FAME complements traditional diagnostics by offering rapid and broad pathogen detection, crucial for timely and appropriate therapy. However, its effectiveness varies with local epidemiology, and it should not replace conventional methods entirely. Tailoring diagnostic panels to regional pathogen prevalence is recommended to enhance diagnostic accuracy and clinical outcomes in low- and middle-income countries.

3D Quantitative-Amplified Magnetic Resonance Imaging (3D q-aMRI).

Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing algorithm called 3D quantitative amplified MRI (3D q-aMRI). This algorithm enables the visualization and quantification of pulsatile brain motion. 3D q-aMRI was validated and optimized on a 3D digital phantom and was applied in vivo on healthy volunteers for its ability to accurately measure brain parenchyma and CSF voxel displacement. Simulation results show that 3D q-aMRI can accurately quantify sub-voxel motions in the order of 0.01 of a voxel size. The algorithm hyperparameters were optimized and tested on in vivo data. The repeatability and reproducibility of 3D q-aMRI were shown on six healthy volunteers. The voxel displacement field extracted by 3D q-aMRI is highly correlated with the displacement measurements estimated by phase contrast (PC) MRI. In addition, the voxel displacement profile through the cerebral aqueduct resembled the CSF flow profile reported in previous literature. Differences in brain motion was observed in patients with dementia compared with age-matched healthy controls. In summary, 3D q-aMRI is a promising new technique that can both visualize and quantify pulsatile brain motion. Its ability to accurately quantify sub-voxel motion in physical units holds potential for the assessment of pulsatile brain motion as well as the indirect assessment of CSF homeostasis. While further research is warranted, 3D q-aMRI may provide important diagnostic information for neurological disorders such as Alzheimer's disease.

Hypermobile Ehlers-Danlos syndrome and spontaneous CSF leaks: the connective tissue conundrum.

Collagen, the most abundant protein in the body, is a key component of the extracellular matrix (ECM), which plays a crucial role in the structure and support of connective tissues. Abnormalities in collagen associated with connective tissue disorders (CTD) can lead to neuroinflammation and weaken the integrity of the blood-brain barrier (BBB), a semi-permeable membrane that separates the brain's extracellular fluid from the bloodstream. This compromise in the BBB can result from disruptions in ECM components, leading to neuroinflammatory responses, neuronal damage, and increased risks of neurological disorders. These changes impact central nervous system homeostasis and may exacerbate neurological conditions linked to CTD, manifesting as cognitive impairment, sensory disturbances, headaches, sleep issues, and psychiatric symptoms. The Ehlers-Danlos syndromes (EDS) are a group of heritable CTDs that result from varying defects in collagen and the ECM. The most prevalent subtype, hypermobile EDS (hEDS), involves clinical manifestations that include joint hypermobility, skin hyperextensibility, autonomic dysfunction, mast cell activation, chronic pain, as well as neurological manifestations like chronic headaches and cerebrospinal fluid (CSF) leaks. Understanding the connections between collagen, CSF, inflammation, and the BBB could provide insights into neurological diseases associated with connective tissue abnormalities and guide future research.

Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study.

INTRODUCTION: We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration. METHODS: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF-AD) study using the EPIC array. RESULTS: We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development. DISCUSSION: We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain. HIGHLIGHTS: Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)-relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels.

Perspective: Timely diagnosis and repair of intraoperative thoracic/lumbar cerebrospinal fluid (CSF) leaks.

Background: Our review of 12 articles for this perspective showed the frequency of intraoperative thoracic and/or lumbar CSF fistulas/dural tears (DT) ranged from 2.6% - 8% for primary surgical procedures. Delayed postoperative CSF leak/DT were also diagnosed in 0.83% (17/2052 patients) to 14.3% (2/14 patients) of patients undergoing thoracic and/or lumbar procedures. Further, the rate of recurrent postoperative CSF leaks/DT varied from 13.3% (2/15 patients) to 33.3% (4/12 patients). Methods: Intraoperative, postoperative delayed, and recurrent postoperative traumatic postsurgical thorac CSF leaks/DT can be limited by performing initially sufficient operative decompressions and/or decompressions/fusions (i.e., utilizing adequate open exposures vs. inadequate minimally invasive (MI) approaches). The incidence of CSF leaks/DT can be further reduced by spine surgeons' utilization of operating microscopes, and their avoiding routine attempts at total synovial cyst excision and/or complete resection of hypertrophied/ossified yellow ligament in the presence of significant dural adhesions. Results: Multiple CSF leak/CT repair techniques included; using interrupted, non-resorbable sutures for direct dural repairs (i.e. 7-0 Gore-Tex sutures where the suture is larger than the needle thus plugging needle holes), and adding where needed muscle patch grafts, microfibrillar collagen, the rotation of Multifidus muscle pedicle flaps, fibrin sealants (FS)/fibrin glues (FG), lumbar drains (LD), and/or lumbo-peritoneal (LP) shunts. Conclusion: Intraoperative, postopertive delayed, and/or recurrent postoperative thorac and/or lumbar traumatic surgical CSF leaks can be reduced by choosing to initially perform the appropriately extensive open operative decompressions and/or decompresssions/fusions. It is critical to use an operating microscope, non-resorbable interrupted sutures, and where necessary, muscle patch grafts, microfibrillar collagen, the rotation of Multifidus Muscle Pedicle Flaps, FS/FG, LD, and/or LP shunts.

Assessing Health-Related Quality of Life in Children With Spina Bifida in Lithuania.

Introduction In recent years, more emphasis has been placed on improving the health-related quality of life (HRQOL) in children with spina bifida (SB). Chronic disability is understood to impact various aspects of the person's life, family, and social functioning, in addition to the specific needs of the disease. The HRQOL is done to assess the patient's quality of life (QOL) in various domains including physical and mental. Back in the 1900s, few children survived SB, whereas today, they almost have normal life expectancy. By understanding the contributing factors to the quality of life (QOL), more targeted interventions can be put in place in order to maximize the psychological and social well-being of these patients. Aim The aim of this study is to estimate the health-related quality of life (HRQOL) in Lithuanian children with spina bifida (SB) in relation to comorbidities, level of lesions, and mobility. Objectives The objectives of this study are to investigate the HRQOL of Lithuanian children with SB born between 1999 and 2012; to analyze the relation between the HRQOL and its comorbidities, including hydrocephalus, Chiari II malformation, incontinence, and epilepsy; and to determine the relationship of health variables, the level of lesions, and mobility to the HRQOL. Methods This was a quantitative cross-sectional study on children with spina bifida across Lithuania to assess the HRQOL. Subjects were chosen and interviewed from various cities including Kaunas, Vilnius, Marijampole, Gargzdai, Birzai, Panevezys, Palanga, and Alytus. A questionnaire was used as an instrument to measure the HRQOL. The level of lesions, comorbidities, and other health variables were obtained from the medical files and directly from the patient's history. Results Regarding the HRQOL, our study population showed the highest scores in the emotional, medical, intellectual, and social domains. The lowest sub-scores were in recreational, vocational, environmental, and then physical domains. We also found that certain comorbidities including hydrocephalus, epilepsy, and incontinence negatively affected the QOL. In our study group, we also found that the ambulatory group scored significantly higher in the overall QOL. However, when comparing the level of lesions to the HRQOL, we found no statistically significant difference. Conclusion Positive results were obtained regarding the medical, emotional, intellectual, and social aspects of patients with SB in Lithuania as they scored high in this domain. However, the environmental and vocational domains scored low, suggesting that further examination needs to be carried in these domains. We concluded that having various comorbidities including hydrocephalus and incontinence has negative impacts on the QOL. Patients who suffered from epilepsy had a statistically significant lower QOL. No significant difference was found in the association between the level of lesion and the QOL in our study.

Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors.

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

Inflammatory signature in amyotrophic lateral sclerosis predicting disease progression.

Experimental studies identified a role of neuroinflammation in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the role of inflammatory molecules as diagnostic and prognostic biomarkers in patients with ALS is unclear. In this cross-sectional study, the cerebrospinal fluid (CSF) levels of a set of inflammatory cytokines and chemokines were analyzed in 56 newly diagnosed ALS patients and in 47 age- and sex-matched control patients without inflammatory or degenerative neurological disorders. The molecules analyzed included: interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-17, granulocyte colony stimulating factor (GCSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, tumor necrosis factors (TNF), eotaxin. Principal component analysis (PCA) was used to explore possible associations between CSF molecules and ALS diagnosis. In addition, we analyzed the association between CSF cytokine profiles and clinical characteristics, including the disease progression rate score, and peripheral inflammation assessed using the Neutrophil-to-lymphocyte ratio (NLR). PCA identified six principal components (PCs) explaining 70.67% of the total variance in the CSF cytokine set. The principal component (PC1) explained 26.8% of variance and showed a positive load with CSF levels of IL-9, IL-4, GCSF, IL-7, IL-17, IL-13, IL-6, IL-1ß, TNF, and IL-2. Logistic regression showed a significant association between PC1 and ALS diagnosis. In addition, in ALS patients, the same component was significantly associated with higher disease progression rate score and positively correlated with NLR. CSF inflammatory activation in present in ALS at the time of diagnosis and may characterize patients at higher risk for disease progression.

Predicting Gait Speed Improvement in Idiopathic Normal Pressure Hydrocephalus Patients: The Role of Evans Index and Ventricular Volume.

Objective This study aims to investigate the association between specific imaging parameters, namely, the Evans index (EI) and ventricular volume (VV), and the variation in gait speed observed in patients with idiopathic normal pressure hydrocephalus (iNPH) before and after cerebrospinal fluid (CSF) removal/lumbar drain (LD). Furthermore, it seeks to identify which imaging parameters are the most reliable predictors for significant improvements in gait speed post procedure. Methods In this retrospective analysis, the study measured the gait speed of 35 patients diagnosed with idiopathic normal pressure hydrocephalus (iNPH) before and after they underwent CSF removal. Before lumbar drain (LD), brain images were segmented to calculate the Evans index and ventricular volume. The study explored the relationship between these imaging parameters (the Evans index and ventricular volume) and the improvement in gait speed following CSF removal. Patients were divided into two categories based on the degree of improvement in gait speed, and we compared the imaging parameters between these groups. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal imaging parameter thresholds predictive of gait speed enhancement. Finally, the study assessed the predictive accuracy of these thresholds for identifying patients likely to experience improved gait speed post-LD. Results Following CSF removal/lumbar drain, the participants significantly improved in gait speed, as indicated by a paired sample t-test (p-value = 0.0017). A moderate positive correlation was observed between the imaging parameters (EI and VV) and the improvement in gait speed post-LD. Significant differences were detected between the two patient groups regarding EI, VV, and a composite score (statistical test value = 3.1, 2.8, and 2.9, respectively; p-value < 0.01). Receiver operating characteristic (ROC) curve analysis identified the optimal thresholds for the EI and VV to be 0.39 and 110.78 cm³, respectively. The classification based on these thresholds yielded significant associations between patients displaying favorable imaging parameters and those demonstrating improved gait speed post-LD, with chi-square (χ²) values of 8.5 and 7.1, respectively, and p-values < 0.01. Furthermore, these imaging parameter thresholds had a 74% accuracy rate in predicting patients who would improve post-LD. Conclusion The study demonstrates that ventricle volume and the Evans index can significantly predict gait speed improvement after lumbar drain (LD) in patients with iNPH.