Elevated Cerebrospinal Fluid Research Articles

Elevated cerebrospinal fluid galectin-3 and associated cytokines after severe traumatic brain injury in patients.

This study aimed to investigate the galectin-3 and associated cytokines levels in the cerebrospinal fluid (CSF) of severe traumatic brain injury (sTBI) patients. Temporal CSF expression of galectin-3 and associated cytokines levels in sTBI patients within 1-week post-injury were studied using the multiplex bead array. STBI patient group was stratified using the Modified Rankin Score (mRS) into 3 groups: mRS 6 (died), mRS 5 (severely disabled) and mRS 1-4 (mild-to-moderately disabled) group. Analysis for bead array data using Kruskal-Wallis test with post hoc Dunn's multiple comparisons test, and temporal changes and correlation analysis using Spearman's correlation were carried out. At day 1 post-injury, CSF galectin-3 and interleukin-6 (IL-6), interleukin-10 (IL-10), cysteine-cysteine motif chemokine ligand-2 (CCL-2), and cysteine-cysteine motif chemokine ligand-20 (CCL-20), but not interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) levels were significantly elevated in mRS 5 group compared to non-TBI controls. Temporal correlation analysis at 1-7 days showed decreased IL-10 level in the mRS 6 group, decreased IL-10 and CCL-2 levels in mRS 5 group, and decreased IL-6, CCL-2, and CCL-20 levels in the mRS 1-4 group. Receiver operating characteristic curve analyses revealed a significant area under the curve for comparison between mRS 6 and mRS 5 groups for galectin-3 and IL-6. No significant differences in sex, age, Glasgow Coma Scale score, C-reactive protein levels and types of TBI-induced hemorrhages were observed between the groups. CSF galectin-3 and associated cytokines, especially IL-6, CCL-2 and CCL-20 levels were different within sub-groups of sTBI patients, suggesting their potential use in sTBI prognostics.

Osteopontin: A novel marker of pre-symptomatic sporadic Alzheimer's disease.

We investigate the role of osteopontin (OPN) in participants with Pre-symptomatic Alzheimer's disease (AD), mild cognitive impairment (MCI), and in AD brains. Cerebrospinal fluid (CSF) OPN, AD, and synaptic biomarker levels were measured in 109 cognitively unimpaired (CU), parental-history positive Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) participants, and in 167 CU and 399 participants with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. OPN levels were examined as a function of amyloid beta (Aβ) and tau positivity. Survival analyses investigated the link between OPN and rate of conversion to AD. In PREVENT-AD, CSF OPN was positively correlated with synaptic biomarkers. In PREVENT-AD and ADNI, OPN was elevated in CSF Aβ42/40(+)/total tau(+) and CSF Aβ42/40(+)/phosphorylated tau181(+) individuals. In ADNI, OPN was increased in Aβ(+) positron emission tomography (PET) and tau(+) PET individuals, and associated with an accelerated rate of conversion to AD. OPN was elevated in autopsy-confirmed AD brains. Strong associations between CSF OPN and key markers of AD pathophysiology suggest a significant role for OPN in tau neurobiology, particularly in the early stages of the disease. In the Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease cohort, we discovered that cerebrospinal fluid (CSF) osteopontin (OPN) levels can indicate early synaptic dysfunction, tau deposition, and neuronal loss in cognitively unimpaired elderly with a parental history. CSF OPN is elevated in amyloid beta(+) positron emission tomography (PET) and tau(+) PET individuals. Elevated CSF OPN is associated with an accelerated rate of conversion to Alzheimer's disease (AD). Elevated CSF OPN is associated with an accelerated rate of cognitive decline on the Alzheimer's Disease Assessment Scale-Cognitive subscale 13, Montreal Cognitive Assessment, Mini-Mental State Examination, and Clinical Dementia Rating Scale Sum of Boxes. OPN mRNA and protein levels are significantly upregulated in the frontal cortex of autopsy-confirmed AD brains.

Ubiquitin-Proteasome System in the Different Stages of Dominantly Inherited Alzheimer's Disease.

This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating® (CDR®). Using the SOMAscan assay, we detected subtle increases in specific ubiquitin enzymes associated with proteostasis in mutation carriers (MCs) up to two decades before the estimated symptom onset. This was followed by more pronounced elevations of UPS-activating enzymes, including E2 and E3 proteins, and ubiquitin-related modifiers. Our findings also demonstrated consistent correlations between UPS proteins and CSF biomarkers such as Aβ42/40 ratio, total tau, various phosphorylated tau species to total tau ratios (ptau181/T181, ptauT205/T205, ptauS202/S202, ptauT217/T217), and MTBR-tau243, alongside Neurofilament light chain (NfL) and the CDR®. Notably, a positive association was observed with imaging markers (PiB PET, tau PET) and a negative correlation with markers of neurodegeneration (FDG PET, MRI), highlighting a significant link between UPS dysregulation and neurodegenerative processes. The correlations suggest that the increase in multiple UPS proteins with rising tau levels and tau-tangle associated markers, indicating a potential role for the UPS in relation to misfolded tau/neurofibrillary tangles (NFTs) and symptom onset. These findings indicate that elevated CSF UPS proteins in DIAD MCs could serve as early indicators of disease progression and suggest a link between UPS dysregulation and amyloid plaque, tau tangles formation, implicating the UPS as a potential therapeutic target in AD pathogenesis.

Comparison of Clinical Outcomes between Microscopic and Endoscopic Transsphenoidal Pituitary Tumor Resection

Abstract Objectives In recent years, the transnasal endoscopic method for transsphenoidal pituitary tumor resection (eTSR), alongside the conventional sublabial microscopic transsphenoidal resection (mTSR) method, has gained popularity due to advancements in imaging and instrumentation. The current study sought to elucidate whether the trend toward eTSR was associated with changes in clinical outcomes at a single institution's multidisciplinary pituitary surgery program. Setting and Participants The Virginia Commonwealth University (VCU) Brain Tumor Database was queried for patients who underwent either transnasal or sublabial pituitary tumor resection of pituitary tumors between 2009 and 2021. Design Clinical outcomes were compared between the two groups. Main Outcome Measures Surgical outcomes like estimated blood loss (EBL), cerebrospinal fluid (CSF) leak rates, hospital length of stay (LOS), and extent of resection were studied. Results A total of 93 patients (57 mTSR, 36 eTSR) underwent review, revealing that mTSR was associated with a higher average intraoperative blood loss (310.5 ± 48.6 mL) than eTSR (160.0 ± 30.7 mL; p = 0.012). eTSR demonstrated an elevated intraoperative CSF leak incidence (36.1 vs. 15.8%; p = 0.043), but no difference in postoperative CSF leak requiring intervention. Hospital LOS and extent of resection showed no significant differences between the approaches. Conclusion This single-institution, retrospective study suggests that, in experienced hands, both eTSR and mTSR approaches are effective with comparable risk profiles. The approach may be best determined by the surgical team's evaluation of the tumor's imaging features, paying attention to the patient's preoperative hematologic status due to the greater propensity for blood loss with the microscopic approach.

Association of elevated cerebrospinal fluid levels of the longevity protein α‐Klotho with a delayed onset of cognitive impairment in Parkinson's disease patients

AbstractBackground and PurposeParkinson's disease (PD) is an age‐related condition characterized by substantial phenotypic variability. Consequently, pathways and proteins involved in biological aging, such as the central aging pathway comprising insulin‐like growth factor 1–α‐Klotho–sirtuin 1–forkhead box O3–peroxisome proliferator‐activated receptor γ, may potentially influence disease progression.MethodsCerebrospinal fluid (CSF) levels of α‐Klotho in 471 PD patients were examined. Of the 471 patients, 96 carried a GBA1 variant (PD GBA1), whilst the 375 non‐carriers were classified as PD wild‐type (PD WT). Each patient was stratified into a CSF α‐Klotho tertile group based on the individual level. Kaplan–Meier survival curves and Cox regression analysis stratified by tertile groups were conducted. These longitudinal data were available for 255 patients. Follow‐up times reached from 8.4 to 12.4 years. The stratification into PD WT and PD GBA1 was undertaken to evaluate potential continuum patterns, particularly in relation to CSF levels.ResultsHigher CSF levels of α‐Klotho were associated with a significant later onset of cognitive impairment. Elevated levels of α‐Klotho in CSF were linked to higher Montreal Cognitive Assessment scores in male PD patients with GBA1 mutations.ConclusionsOur results indicate that higher CSF levels of α‐Klotho are associated with a delayed cognitive decline in PD. Notably, this correlation is more prominently observed in PD patients with GBA1 mutations, potentially reflecting the accelerated biological aging profile characteristic of individuals harboring GBA1 variants.

Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.

Molecularly targeted immunotherapy used to treat a novel overlap syndrome of pediatric N‐methyl‐d‐aspartate receptor encephalitis (NMDARE) and possible neurosarcoidosis

AbstractObjectiveOverlap syndromes have been described between N‐methyl‐ d‐aspartate receptor encephalitis (NMDARE) and other neuroinflammatory conditions, although rarely involving neurosarcoidosis. Molecularly targeted immunotherapy may be helpful in the empiric treatment of these conditions.MethodsWe describe a 9‐year‐old boy with new‐onset seizures and worsening encephalopathy.ResultsInitial evaluation was concerning for neurosarcoidosis, including elevated cerebrospinal fluid (CSF) and serum angiotensin‐converting enzyme and leptomeningeal with multiple cranial nerve enhancement on magnetic resonance imaging. CSF and serum cytokine profiles were used to choose targeted empiric immunotherapy, and the boy's seizure burden and encephalopathy improved after treatment with tocilizumab. The NMDA receptor antibody titer was later found to be elevated, raising suspicion for a novel overlap syndrome.InterpretationOur patient met the criteria for definite NMDARE and possible neurosarcoidosis. Given the mixed radiographic and serologic markers in this child, cytokine levels were used to direct the choice of empiric treatment, resulting in excellent clinical response. This case suggests that targeted immunotherapy informed by cytokine testing may be helpful in cases of high‐acuity pediatric neuroinflammatory disease with limited diagnostic clarity.

Exploring the diagnostic potential of cerebrospinal fluid (CSF) IL-10:IL-6 ratio in patients with primary central nervous system lymphoma (PCNSL).

e14041 Background: Primary Central Nervous System Lymphomas (PCNSL) present significant diagnostic challenges due to their aggressive nature. Current diagnostic methods include neuroimaging, CSF cytology, FDG-PET scans, and biopsies. Building upon the success of the IL-10:IL-6 ratio as a diagnostic biomarker in intraocular lymphoma, this study investigates its potential in PCNSL diagnosis. CSF IL-10:IL-6 ratio emerges as a promising, easily accessible biomarker for early PCNSL detection. Methods: Fifteen histopathologically confirmed PCNSL patients were compared with fifteen CNS inflammatory condition patients and ten patients with other CNS malignancies. Detailed clinical assessments were conducted, and IL-10:IL-6 levels were measured in serum and CSF using Flow cytometry. Results: The CSF IL-10:IL-6 Ratio was elevated (> 1) compared to serum levels in PCNSL patients in contrast to other control groups. The mean age ± SD of PCNSL patients was 55.47 ± 17.29, with a male-to-female ratio of 8:7. The mean (SD) for CSF IL-10:IL-6 ratio in PCNSL was 3.35 (3.88), while the mean (SD) for serum IL-10:IL-6 ratio was 0.438 (1.54). The statistical analysis revealed a significant difference (P = 0.0058 < 0.05). Conversely, comparing the CSF IL-10:IL-6 ratio with serum levels in controls with CNS inflammatory conditions and CNS malignancies showed no statistical significance (P > 0.05). Conclusions: Elevated CSF IL-10 and CSF IL-10/IL-6 ratios suggest their potential as early diagnostic markers for large B cell PCNSL. The IL-10:IL-6 ratio holds promise as a novel, easily accessible biomarker in readily available body fluids for PCNSL diagnosis.

What Is Brain Damage and Does Electroconvulsive Therapy Cause It?

Surveys show public misperceptions and confusion about brain damage and electroconvulsive therapy (ECT). Fictional movies have misrepresented ECT to suggest brain damage and to ridicule mental illness and psychiatric patients. "Brain damage" has become a colloquial expression without consistent meaning. In contrast, brain injury is the medical term for destruction of brain cells, such as from kinetic impact (concussion), hypoxia, or infection. Studies of both high-resolution magnetic resonance imaging (MRI) and enzyme assays find that causes of brain injury are accompanied by observable structural changes on MRI and elevated blood and cerebrospinal fluid levels of brain enzymes that leak from injured brain cells. Concussion is also followed by intracerebral bleeding, progressive brain atrophy, diffuse axonal injury, cranial nerve injury, and 2-4 fold increased risk for dementia. In contrast, there is no evidence that ECT produces any of these. Studies of ECT patients find no brain edema, structural change persisting 6 months, or elevated levels of leaked brain enzymes. Statistical comparisons between brain injury and ECT effects indicate no similarity ( P < 0.00000001). Moreover, the kinetic, thermal, and electrical effects of ECT are far below levels that could possibly cause harm. This robust evidence shows that there is no basis to claim that ECT causes brain injury.

Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia.

Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise. We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n = 6, 2: n = 17, 3: n = 6). pNF-H levels before and during treatment were compared with the levels of controls (n = 22), patients with Duchenne muscular dystrophy (n = 17), myotonic dystrophy type 1 (n = 11), untreated SMA individuals with chronic type 3 disease (n = 8), and children with presymptomatic SMA (n = 3). SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment. Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration.

Autoimmune Nodopathy

Autoimmune nodopathy (AN), a newly established category of autoimmune disease, refers to an immune-mediated neuropathy associated with development of autoantibodies against membrane proteins, including neurofascin 186, neurofascin 155, contactin-1, and contactin-associated protein 1 located in the nodes of Ranvier or paranodes. Subclass analysis of these autoantibodies reveals predominant elevation of immunoglobulin (G4. Patients with AN show clinical and laboratory characteristics such as distal-predominant sensorimotor disturbance, sensory ataxia, poor response to intravenous immunoglobulin, and highly elevated cerebrospinal fluid protein levels. B cell-depletion therapy using an anti-CD20 monoclonal antibody is effective for patients with AN. Autoantibody measurement is beneficial not only for diagnosis but also for deciding treatment strategies for AN.

Clinical characteristics of patients with autoimmune nodopathy with anti-neurofascin155 antibodies.

According to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies. Nine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed. Compared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor-sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy. Patients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

Clinical features, cerebrospinal fluid changes, and prognosis in Chinese patients with autoimmune encephalitis.

Autoimmune encephalitis (AE) is a rare, treatable disease of the central nervous system (CNS) caused by an antibody-related immune response. This study is to investigate the correlation of clinical features, cerebrospinal fluid (CSF) characteristics, and prognosis in patients with AE. A total of 71 patients diagnosed with antibody-positive AE were retrospectively analyzed. The patients were divided into three groups: anti-NMDAR group, anti-LGI1 group, and other types. Clinical data were collected to analyze clinical features and CSF results, and prognosis was determined by modified Rankin Scale (mRS). There was statistical difference in the incidences of decreased consciousness level (P < 0.001), memory loss (P = 0.017), speech disorders (P = 0.035), and dyskinesia (P = 0.001) in different antibodies groups. Younger age (P = 0.018), elevated CSF chloride content (P = 0.006), and white blood cells > 50/mm3 (P = 0.026) were highly correlated with ICU admission. Anti-LGI1 encephalitis had a relatively small risk for ICU admission (P = 0.034), and a lower risk of poor functional recovery (P = 0.048) and recurrence (P = 0.041). Patients with first-line treatment failure (P = 0.021) had an increased risk of poor functional recovery. Delayed treatment (P = 0.011) would increase the risk of recurrence. There are differences in age, gender, clinical characteristics, and CSF results in different subtypes of AE. First-line therapy failure would have poor functional recovery, and delayed therapy would increase the risk of relapse. Chloride ion content and white blood cell count in cerebrospinal fluid are positively correlated with the patient's exacerbation and admission to ICU. These indicators have certain clinical value for the prognosis of AE patients.

Thecaloscopy Reduces the Risk of Recurrent Perineural (Tarlov) Cysts after Microsurgical Resection.

Sacral Tarlov cysts (TCs), often asymptomatic, can cause significant pain and severe neurological dysfunction. Conventional treatments are generally associated with high recurrence and complication rates. Specifically, the substantial recurrence rates, which can reach as high as 50%, significantly impact long-term outcomes. Recent evidence increasingly supports the hypothesis that the formation of Tarlov cysts (TCs) may be associated with inflammatory processes within the nerve root sheath, further exacerbated by elevated cerebrospinal fluid (CSF) pressure. This retrospective study explores thecaloscopy, combined with surgical techniques, as a more effective alternative. We observed a total of 78 patients, 48 of whom underwent endoscopic fenestration of the arachnoid sheath in addition to microsurgical resection of the TC. We found that the fenestration of the arachnoid sheath at the level of lumbosacral spinal nerve root entry led to a significantly decreased risk of developing recurrent TCs (5/48 vs. 9/30). Only one of the patients suffered from a persistent new bladder dysfunction after microsurgical resection. This presented technique provides a promising treatment path for the future management of TCs, offering a safe and more effective treatment option compared to previous methods. Additionally, the advantages of the thecaloscopy provide pathophysiological implications regarding the development of perineural cysts.

Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

CSF N-acylethanolamine acid amidase level and Parkinson's disease risk: A mendelian randomization study

BackgroundNeuroinflammation is involved in the progression of Parkinson's disease (PD), and N-acylethanolamine acid amidase (NAAA) is involved in regulating inflammation by hydrolyzing bioactive lipid mediators called N-acylethanolamines (NAEs). However, the causal relationship between cerebrospinal fluid (CSF) NAAA protein levels and the risk of PD remains unclear. This study aimed to explore the causal effect of CSF NAAA levels on PD risk through Mendelian randomization (MR) analysis. MethodGenome-wide association study (GWAS) summary statistics for CSF NAAA protein quantitative trait loci (pQTL) and GWAS summary statistics for PD were obtained from publicly available databases. Inverse-variance weighted (IVW) was the main causal estimation method for MR analysis. In addition, the maximum likelihood, MR Egger regression, and weighted median were used to supplement the IVW results. Finally, various sensitivity tests were performed to verify the reliability of the MR findings. ResultsIn the initial MR analysis, the IVW showed that CSF NAAA protein levels significantly increased PD risk (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.01–1.35, P = 0.031). This finding was further validated in a replicate MR analysis (OR = 1.20, 95% CI: 1.02–1.41, P = 0.027). Sensitivity analysis showed that MR results were stable and not affected by heterogeneity and horizontal pleiotropy. ConclusionThe present MR study supports a causal relationship between elevated CSF NAAA protein levels and increased PD risk.

Interactions Between Endocannabinoid and Endogenous Opioid Systems Prospectively Influence Postoperative Opioid Use in Pregnant Patients Undergoing Cesarean Delivery

Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This study evaluated the interactive effects of preoperative beta-endorphin (BE) concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol and plasma anandamide) on postoperative opioid use and pain intensity in a prospective cohort of n = 112 pregnant patients undergoing scheduled cesarean delivery. Maternal blood and CSF samples were collected preoperatively for BE and EC assays. Patients completed measures of outpatient opioid use (number of tablets used and days of use) and average pain intensity at 2 weeks postoperatively. Results of general linear model analyses controlling for maternal age, body mass index at time of delivery, and race revealed significant multiplicative interactions between EC and BE concentrations on number of opioid tablets used (based on pill count), days of opioid use, and total milligram morphine equivalents used in the 2-week follow-up period. Elevated preoperative plasma and CSF 2-arachidonoylglycerol predicted reduced outpatient opioid analgesic use, particularly for patients low in CSF BE. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (P < .02) characterized by higher preoperative BE concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma anandamide concentrations. Further exploration of interactions between EC and endogenous opioid inhibitory systems as they influence responses to opioid analgesics in other clinical pain populations may help guide the development of precision pain management approaches. PerspectiveIn the postoperative setting of patients undergoing cesarean delivery, elevated ECs were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in CSF. Further exploration of interactions between these 2 inhibitory systems as they impact responses to pain management interventions appears warranted.

Granulocytes in cerebrospinal fluid of adults suspected of a central nervous system infection: a prospective study of diagnostic accuracy.

Cerebrospinal fluid (CSF) granulocytes are associated with bacterial meningitis, but information on its diagnostic value is limited and primarily based on retrospective studies. Therefore, we assessed the diagnostic accuracy of CSF granulocytes. We analyzed CSF granulocytes (index test) from all consecutive patients in two prospective cohort studies in the Netherlands. Both studies included patients ≥ 16years, suspected of a central nervous system (CNS) infection, who underwent a diagnostic lumbar puncture. All episodes with elevated CSF leukocytes (≥ 5 cells per mm3) were selected and categorized by clinical diagnosis (reference standard). Of 1261 episodes, 625 (50%) had elevated CSF leukocytes and 541 (87%) were included. 117 of 541 (22%) were diagnosed with bacterial meningitis, 144 (27%) with viral meningoencephalitis, 49 (9%) with other CNS infections, 76 (14%) with CNS autoimmune disorders, 93 (17%) with other neurological diseases and 62 (11%) with systemic diseases. The area under the curve to discriminate bacterial meningitis from other diagnoses was 0.97 (95% confidence interval [CI] 0.95-0.98) for CSF granulocyte count and 0.93 (95% CI 0.91-0.96) for CSF granulocyte percentage. CSF granulocyte predominance occurred in all diagnostic categories. A cutoff at 50% CSF granulocytes gave a sensitivity of 94% (95% CI 90-98), specificity of 80% (95% CI 76-84), negative predictive value of 98% (95% CI 97-99) and positive predictive value of 57% (95% CI 52-62). CSF granulocytes have a high diagnostic accuracy for bacterial meningitis in patients suspected of a CNS infection. CSF granulocyte predominance occurred in all diagnostic categories, limiting its value in clinical practice.

Evidence for cytokine dysregulation in schizophrenia spectrum disorders: A comparison of cerebrospinal fluid and blood samples

Abnormalities in immune function have been described in schizophrenia but few studies have investigated cytokines in cerebrospinal fluid (CSF) and their correlation with blood levels. In this cross-sectional study, cytokines were measured in CSF and plasma of 30 subjects with schizophrenia spectrum disorder (SSD) diagnosis and 23 healthy volunteers (HV). Results showed that CSF TNFα was increased in SSD subjects compared to HV and there were no correlations between CSF and plasma cytokine levels. The present findings provide evidence of dysregulation of TNFα in CSF of schizophrenia. These results identify elevated CSF TNFα levels as a potential biomarker in schizophrenia.

Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis

Biomarkers distinguishing nonrelapsing progressive disease biology from relapsing biology in multiple sclerosis (MS) are lacking. Cerebrospinal fluid (CSF) is an accessible fluid that most closely reflects central nervous system biology. To identify CSF biological measures associated with progressive MS pathobiology. This cohort study assessed data from 2 prospective MS cohorts: a test cohort provided serial CSF, clinical, and imaging assessments in a multicenter study of patients with relapsing MS (RMS) or primary progressive MS (PPMS) who were initiating anti-CD20 treatment (recruitment: 2016-2018; analysis: 2020-2023). A single-site confirmation cohort was used to assess CSF at baseline and long-term (>10 year) clinical follow-up (analysis: 2022-2023). Test-cohort participants initiated standard-of-care ocrelizumab treatment. Confirmation-cohort participants were untreated or received standard-of-care disease-modifying MS therapies. Twenty-five CSF markers, including neurofilament light chain, neurofilament heavy chain, and glial fibrillary acid protein (GFAP); 24-week confirmed disability progression (CDP24); and brain magnetic resonance imaging measures reflecting focal injury, tissue loss, and progressive biology (slowly expanding lesions [SELs]). The test cohort (n = 131) included 100 patients with RMS (mean [SD] age, 36.6 [10.4] years; 68 [68%] female and 32 [32%] male; Expanded Disability Status Scale [EDSS] score, 0-5.5), and 31 patients with PPMS (mean [SD] age, 44.9 [7.4] years; 15 [48%] female and 16 [52%] male; EDSS score, 3.0-6.5). The confirmation cohort (n = 68) included 41 patients with RMS and 27 with PPMS enrolled at diagnosis (age, 40 years [range, 20-61 years]; 47 [69%] female and 21 [31%] male). In the test cohort, GFAP was correlated with SEL count (r = 0.33), greater proportion of T2 lesion volume from SELs (r = 0.24), and lower T1-weighted intensity within SELs (r = -0.33) but not with acute inflammatory measures. Neurofilament heavy chain was correlated with SEL count (r = 0.25) and lower T1-weighted intensity within SELs (r = -0.28). Immune markers correlated with measures of acute inflammation and, unlike GFAP, were impacted by anti-CD20. In the confirmation cohort, higher baseline CSF GFAP levels were associated with long-term CDP24 (hazard ratio, 2.1; 95% CI, 1.3-3.4; P = .002). In this study, activated glial markers (in particular GFAP) and neurofilament heavy chain were associated specifically with nonrelapsing progressive disease outcomes (independent of acute inflammatory activity). Elevated CSF GFAP was associated with long-term MS disease progression.