Cerebrospinal Fluid Protein Levels Research Articles

Prediction of Serum-Free and Cerebrospinal Fluid Valproic Acid Levels in Patients With Hypoalbuminemia After Craniotomy.

In patients with hypoalbuminemia after craniotomy, total serum concentrations of valproic acid (VPA) may provide poor clinical insights, owing to saturated protein binding and increased unbound fractions. However, very few clinical laboratories routinely analyze free concentrations of the drug. The aim of this study was to develop a model to predict serum-free and cerebrospinal fluid (CSF) levels of VPA based on its total concentration and to investigate the model's applicability. Total serum and CSF concentrations of VPA in 79 patients were measured using a validated immunoassay between January 2015 and December 2015. The demographic, clinical, and laboratory information of patients were retrieved from medical records. A multiple linear regression analysis was adopted to determine the potential variations and establish the functional relationship between CSF concentration and significant clinical factors. Based on the stepwise multiple linear regression analysis performed using the natural logarithm of the concentration of VPA in the CSF as the dependent variable, serum concentrations of VPA (X1, β' = 0.844), serum albumin concentration (X2, β' = -0.393), and CSF protein concentration (X3, β' = 0.098) were identified as the 3 variables that significantly predicted the dependent variable: (Equation is included in full-text article.), with a coefficient of determination (R) of 0.874. As the CSF protein level is often unavailable, the model was redefined to include 2 variables-serum concentrations of VPA (X1, β' = 0.840) and serum albumin concentration (X2, β' = -0.359): (Equation is included in full-text article.), with R = 0.813. Based on total VPA and serum albumin concentrations, we developed a model to predict serum-free and CSF levels of VPA. This model is useful for correcting dose adjustment in patients with hypoalbuminemia after craniotomy.

Prediction Rule for Scrub Typhus Meningoencephalitis in Children: Emerging Disease in North India.

To evaluate the proportion of scrub typhus meningoencephalitis among children with acute encephalitis syndrome and to outline its differentiating features. To develop a prediction rule for scrub typhus meningoencephalitis. A prospective cohort study was conducted at a tertiary care public hospital in Northern India. Consecutive patients of acute encephalitis syndrome who met our inclusion criteria were enrolled over 2 years. Standardized workup including serum IgM against Orientia tsutsugamushi was performed. Clinical and laboratory features were compared between IgM-positive and IgM-negative patients. The area under the receiver operating characteristic curve of the score derived from "independent predictors" was measured. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated at different cut-offs of the score. Scrub typhus IgM enzyme-linked immunosorbent assay was positive in 66/352 patients (18.8%). Longer duration of fever and prodromal stage along with eschar, hepatomegaly, lymphadenopathy, and pneumonia were significantly more prevalent in scrub typhus meningoencephalitis. However, petechiae were frequent in non-scrub typhus patients. Leucocytosis, lymphocytosis, thrombocytopenia, hypoalbuminemia, and elevated levels of serum bilirubin, serum transaminases, and cerebrospinal fluid protein were associated with scrub typhus meningoencephalitis. Logistic regression revealed fever for >8 days, pneumonia, absence of petechiae, cerebrospinal fluid protein >1000 mg/L, and serum glutamic oxaloacetic transaminase >100 IU/L as independent "predictors" of scrub typhus meningoencephalitis. The area under the receiver operating characteristic curve (95% confidence interval) of the prediction score was 0.832 (0.78-0.89). Score at cutoff ≥1 had 91% sensitivity, 96.1% negative predictive value, and at cutoff ≥4 had 99.7% specificity, 88.9% positive predictive value, 83.1% negative predictive value, 40.3 positive likelihood ratio, 0.88 negative likelihood ratio for identifying scrub typhus meningoencephalitis. Prediction score may help physicians in peripheral areas to identify and treat scrub typhus meningoencephalitis, an emerging cause of acute encephalitis syndrome in India.

Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers

BackgroundThe clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers.MethodsAntibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD (bvFTD, n = 16) and progressive primary aphasia (PPA, n = 13), as well as presymptomatic mutation carriers (PMC, n = 16) and non-carriers (NC, n = 8). A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples. The findings were further examined in an independent cohort including 13 FTD patients, 79 patients with Alzheimer’s disease and 18 healthy controls.ResultsWe found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals (PMC and NC) for 26 proteins. The analysis show patterns of separation between unaffected individuals and FTD patients, especially for those with a clinical diagnosis of bvFTD. The most statistically significant differences in protein levels were found for VGF, TN-R, NPTXR, TMEM132D, PDYN and NF-M. Patients with FTD were found to have higher levels of TN-R and NF-M, and lower levels of VGF, NPTXR, TMEM132D and PDYN, compared to unaffected individuals. The main findings were reproduced in the independent cohort.ConclusionIn this pilot study, we show a separation of FTD patients from unaffected individuals based on protein levels in CSF. Further investigation is required to explore the CSF profiles in larger cohorts, but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.

Cerebrospinal fluid myelin basic protein is elevated in multiple system atrophy

IntroductionParkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging an early diagnosis. Diagnostic accuracy is important because PD and MSA have a different prognosis and response to treatment. Here, we aimed to evaluate the diagnostic value of brain-specific structural proteins in cerebrospinal fluid (CSF) of PD and MSA patients, as well as their association with cognitive decline. MethodsCSF samples were collected from patients with clear signs of parkinsonism, but with uncertain diagnosis at the time of inclusion. Clinical diagnoses of PD (n = 55) and MSA (n = 22) were established after 3 and 10 years of follow-up and re-evaluated after 12 years, according to the most updated clinical criteria. CSF from controls (n = 118) was studied for comparison. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B) and myelin basic protein (MBP) levels in CSF were measured using ELISA. Protein levels were also correlated with cognitive decline, i.e. worsening of the mini mental state examination (MMSE) over a period of three years. ResultsMBP concentrations were increased in MSA compared to PD and controls (p < 0.005) and could differentiate MSA and PD with high accuracy (AUC = 0.781; p < 0.001). Concentrations of MPB, GFAP and S100B, but not NSE, were significantly elevated in PD patients compared to controls (p = 0.05). None of the brain-specific structural proteins correlated with MMSE progression. ConclusionsOur results demonstrate that MBP differentiates PD from MSA at early stages of the disease, indicating that demyelination and axonal damage may already occur in early stages of MSA.

Clinical characteristics of GAD 65-associated autoimmune encephalitis.

To examine the clinical characteristics of autoimmune encephalitis associated with the glutamate decarboxylase 65 (GAD 65) antibody. Medical records of all patients that diagnosed with GAD 65 antibody-associated encephalitis were retrospectively analyzed. Data regarding demographics and symptoms, neurological signs, laboratory and imaging results, treatment and prognosis were collected. We collected a total of seven patients, mainly young or middle-aged women with a subacute or chronic course. The main clinical symptoms mainly included chronic epilepsy, cerebellar ataxia, stiff-person syndrome, and limbic encephalitis. Three of seven (43%) patients had high CSF (cerebrospinal fluid) protein levels. Oligoclonal IgG bands (including IgG 1) and 24hours intrathecal synthesis of IgG were detected in CSF and serum in six patients, five patients (83%) reported increased distribution of oligoclonal IgG bands (including IgG 1) and 24hours intrathecal synthesis of IgG in serum and CSF. And six of seven patients (86%) had abnormal thyroid function or were positive for thyroid antibodies. By electroencephalogram examination, sharp or slow waves in the temporal region were often observed for six of seven patients (86%). Abnormal imaging signals (six of seven patients, 86%) of the temporal lobe and hippocampus were detected by brain magnetic resonance imaging, and decreased metabolism of the temporal lobe was detected by positron emission tomography/computed tomography (six of six patients, 100%). These patients were mainly treated with corticosteroid and gamma globulin. The clinical symptoms of the patients were alleviated. The course of GAD 65 antibody-associated encephalitis is longer than other autoimmune encephalitides. The clinical symptoms of GAD 65 autoimmune encephalitis mainly manifested as chronic epilepsy, cerebellar ataxia, stiff-person syndrome, and limbic encephalitis, and combined with or without thyroid autoimmune diseases, type 1 diabetes, and thymoma. A comprehensive understanding of the disease is a way to prevent misdiagnosis and delayed treatment.

Factors Associated with the Need for Ventriculoperitoneal Shunting in Patients with Spontaneous Intracerebral Hemorrhage Requiring Emergency Cerebrospinal Fluid Diversion

Abstract Introduction Intracerebral hemorrhage (ICH) is a serious medical condition that is frequently complicated by acute hydrocephalus, necessitating emergency cerebrospinal fluid (CSF) diversion in a subset of patients, ultimately requiring long-term treatment via placement of permanent ventricular shunts. The present study aimed to determine factors associated with the need for permanent ventricular shunt placement in these patients. Methods A total of 309 consecutive patients who underwent emergent CSF diversion with external ventricular drain (EVD) as a treatment for ICH between July 2009 and July 2018 were studied retrospectively to assess the factors that might be correlated with shunt-dependent chronic hydrocephalus. A binary logistic regression model was designed to identify independent related factors of shunt-dependent hydrocephalus after ICH. Results Of 309 patients included in this study, 102 (33.00%) required permanent ventricular CSF shunting before discharge. In univariate analysis, age,ventriculitis, ICP elevation &gt;30 mm Hg, ICH evacuation, the Graeb score, days of EVD in place, and CSF protein levels were significantly associated with the requirement for permanent CSF diversion (p &lt; 0.05). The age and ICH evacuation were protective variables and the ventriculoperitoneal (VP) shunt possibility was reduced by 22.6 and 63.5%, respectively. Conclusion Our results showed that higher Graeb score, ICP elevation &gt;30 mm Hg, more days of EVD in place, and higher CSF protein levels were associated with permanent CSF diversion in these patients. Advanced age and ICH evacuation decreased the possibility of VP shunting in our study.These factors may help in predicting which patients will need permanent CSF diversion and could ultimately lead to improvements in the management of these patients.

Searching for autoimmune encephalitis: Beware of normal CSF

ObjectiveTo determine the prevalence of cerebrospinal fluid (CSF) markers associated with inflammation (i.e., elevated white blood cell count, protein concentration, and CSF-specific oligoclonal bands) in patients with early active autoimmune encephalitis (AE). MethodsCSF characteristics, including WBC count, protein concentration, and oligoclonal banding, were analyzed in patients diagnosed with AE at two tertiary care centers. ResultsNinety-five patients were included in the study. CSF white blood cell counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients with AE had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). ConclusionsWhite blood cell counts and protein levels were within normal limits in the CSF of a substantial proportion of patients with early active AE. Inclusion of CSF oligoclonal banding identified a higher proportion of patients with an inflammatory CSF profile, especially when CSF was sampled early in the disease process.

Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease

Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems‐wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)‐based proteomics workflow for the in‐depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1,000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature.

Inflammation-related plasma and CSF biomarkers for multiple sclerosis

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (P CSF < 4 × 10-5, P plasma < 4 × 10-5), and plasma CCL20 was associated with disease severity (P = 4 × 10-5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

Increased apolipoprotein E and decreased TNF-α in the cerebrospinal fluid of nondemented APOE-ε4 carriers.

AimThe ε4 allele of apolipoprotein E gene (APOE) is a well‐known risk factor of late‐onset Alzheimer's disease. However, little is known why this variant confers a risk for Alzheimer's disease. The aim of this study was to examine the influence of the APOE genotype on cerebrospinal fluid (CSF) protein levels.MethodsThe present study performed a secondary analysis on our previously generated database to compare the CSF levels of 1128 proteins between APOE‐ε4 carriers (28 subjects) and noncarriers (104 subjects). All subjects were physically healthy Japanese individuals without dementia.ResultsCSF levels of apoE2, apoE3, and apoE4 were significantly higher (all nominal P < 10 × 10−5, false discovery rate < 0.001) and those of tumor necrosis factor‐α (TNF‐α) were significantly lower (nominal P = 1.39 × 10−6, false discovery rate < 0.001) in APOE‐ε4 carriers than in noncarriers. No significant correlation was observed between the CSF levels of TNF‐α and any of the apoE proteins.ConclusionsOur findings indicate the possible roles of apoE and TNF‐α in the pathogenesis of APOE‐ε4‐associated Alzheimer's disease.

Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of 18F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake.We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and <contralateral gray matter; 2, = contralateral gray matter; 3, >contralateral gray matter). Grades 0–2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions.Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007).This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection.

Online supplemental material is available for this article.

Reactive increase of cerebrospinal fluid white blood cell count after lumbar puncture: Fact or fiction?

Lumbar puncture (LP) is commonly used in the diagnostic workup of neurological patients, often to exclude inflammatory diseases of the central nervous system. In clinical practice, an increase of white blood cell count (WBC) in the cerebrospinal fluid (CSF) after a LP is often assumed as reactive to the first puncture. Scientific evidence of this hypothesis, however, is lacking.Retrospective review of laboratory parameters was done by analyzing CSF of patients who had at least two LPs between 2012 and 2016 in a single center. Inclusion criteria were a normal CSF WBC in the first LP as well as absence of any underlying disease typically associated with increased CSF WBC.A total of 176 patients (age 57.0 ± 17.6) with 260 serial LPs were included. No significant effect on the CSF WBC (1.2 ± 1.1 vs 1.4 ± 1.4/μl, p = .17), lactat and protein level between consecutive punctures was found after a second LP. In the subgroup of 104 patients who had two LPs within ten days, only one (0.96%) showed a mild abnormal CSF WBC (9 leukocytes/μl) in the second LP.A raise of CSF WBC after LP is rare and not commonly found; therefore, it should lead to careful exclusion of other, especially inflammatory diseases. The needle size is important to minimize the trauma during LP and seems to have an influence on the rate of reactive increase of CSF WBC after LP.

CYFRA 21-1 levels in cerebrospinal fluid as a putative therapeutic monitoring biomarker for patients with leptomeningeal carcinomatosis: A pilot study.

To investigate the feasibility of cerebrospinal fluid (CSF) CYFRA 21-1 levels as a therapeutic monitoring biomarker in leptomeningeal carcinomatosis (LMC) patients undergoing ventriculo-lumbar perfusion (VLP) chemotherapy. The levels of CYFRA 21-1 in 42 CSF samples from 15 LMC patients were analyzed using an electrochemiluminescence immunoassay. Samples were collected at individual time points during VLP chemotherapy. Therapeutic outcomes were measured as improvements in the Karnofsky Performance Status (KPS) score and decreasing intracranial pressure (ICP) as the main endpoint of VLP chemotherapy. Changes in CSF CYFRA 21-1 levels, protein levels, and cytology results were also investigated. We subsequently evaluated whether these changes were correlated with KPS score and ICP. The CSF CYFRA 21-1 levels at individual time points were associated with KPS score and ICP. The KPS scores (p= 0.007) and ICP (p= 0.018) of patients with high CSF CYFRA 21-1 levels were significantly different from those of patients with low CSF CYFRA 21-1 levels. By contrast, CSF protein levels and cytological responses were not significantly associated with KPS scores and ICP. CSF CYFRA 21-1 may have utility as a therapeutic monitoring biomarker to design personalized therapeutic strategies in LMC patients undergoing VLP chemotherapy.

Extremely Elevated Cerebrospinal Fluid Protein and Glucose Level in a Neonate with Hypernatremic Dehydration

AbstractWe describe the case of a term newborn who presented with hypernatremic dehydration on day 19 of life. The baby was otherwise hemodynamically stable with no evidence of focal or asymmetric neurological signs. The laboratory tests at the time of admission were negative except for hypernatremia and the extremely elevated levels of cerebrospinal fluid (CSF) protein (717 mg/dL) and glucose levels (97 mg/dL). The hypernatremic dehydration was corrected as per the unit protocol over 48 hours. Repeat CSF analysis done after 5 days showed normalization of the protein and glucose levels. Serial follow-up and neuroimaging showed no evidence of neurological sequelae. Unique feature of our case is this is the first case reporting such an extreme elevation of CSF protein and glucose levels that have had no bearing on neurodevelopmental outcome at 1 month and 3 months of follow-up.

Degree of genetic liability for Alzheimer's disease associated with specific proteomic profiles in cerebrospinal fluid

Genetic factors play a major role in Alzheimer's disease (AD) pathology, but biological mechanisms through which these factors contribute to AD remain elusive. Using a cerebrospinal fluid (CSF) proteomic approach, we examined associations between polygenic risk scores for AD (PGRS) and CSF proteomic profiles in 250 individuals with normal cognition, mild cognitive impairment, and AD-type dementia from the Alzheimer's Disease Neuroimaging Initiative. Out of 412 proteins, 201 were associated with PGRS. Hierarchical clustering analysis on proteins associated with PGRS at different single-nucleotide polymorphism p-value inclusion thresholds identified 3 clusters: (1) a protein cluster correlated with highly significant single-nucleotide polymorphisms, associated with amyloid-beta pathology and complement cascades; (2) a protein cluster associated with PGRS additionally including variants contributing to modest risk, involved in neural injury; (3) a protein cluster that also included less strongly associated variants, enriched with cytokine-cytokine interactions and cell adhesion molecules. These findings suggest that CSF protein levels reflect varying degrees of genetic liability for AD and may serve as a tool to investigate biological mechanisms in AD.

Cerebrospinal Fluid Findings Are Poor Predictors of Appropriate FilmArray Meningitis/Encephalitis Panel Utilization in Pediatric Patients.

Molecular testing of cerebrospinal fluid (CSF) using the BioFire FilmArray meningitis/encephalitis (FA-M/E) panel permits rapid, simultaneous pathogen detection. Due to the broad spectrum of targeted organisms, FA-M/E testing may be restricted to patients with abnormal CSF findings. We sought to determine if restriction is appropriate in our previously healthy and/or immunocompromised pediatric patients. FA-M/E was ordered on 1,025 CSF samples from 948 patients; 121 (11.8%) specimens were FA-M/E positive. Of these, 89 (73.6%) were virus positive, and 30 (24.8%) were bacterium positive. The most common targets detected were enterovirus (n = 38), human herpesvirus 6 (HHV-6) (n = 30), and Streptococcus pneumoniae (n = 14). Pleocytosis with white blood cell (WBC) levels of ≥5 cells/mm3 and ≥10 cells/mm3 were found in 33.1% and 24.3% of all specimens, respectively. Using WBC levels of ≥5 cells/mm3, 63.4% (59/93) of positive specimens exhibited pleocytosis, compared to 29.5% (233/789) of negative specimens. Among positive specimens, 54.4% (37/68) of viral and 87% (20/23) of bacterial cases had pleocytosis. The use of a pleocytosis cutoff of ≥10 cells/mm3 would have missed an additional enterovirus, one cytomegalovirus (CMV), and two HHV-6 diagnoses. CSF glucose and protein levels were normal for 83/116 (75.2%) and 51/116 (44%) positive specimens. Abnormal glucose in combination with WBC levels of ≥10 cells/mm3 showed high specificity (94.5%) and was a better predictor of FA-M/E positivity than abnormal protein. Sensitivity and positive predictive values were <90% for all biomarkers. CSF pleocytosis and abnormal glucose/protein were poor predictors of FA-M/E. Restricting FA-M/E orders based on pleocytosis or other abnormal parameters would have resulted in missed diagnostic opportunities, particularly for the detection of viruses in both previously healthy and immunocompromised patients.

Aseptic meningitis as an atypical manifestation of neuromyelitis optica spectrum disorder flare

BackgroundInflammatory demyelinating disease of the central nervous system characterized by aseptic meningitis is rare and can be easily confused with intracranial infection. Here, we investigated the clinical features of neuromyelitis optica spectrum disorder (NMOSD) patients with a meningitis-like presentation. MethodsFrom a total of six attacks, five patients were identified. Their demographic, clinical, and magnetic resonance imaging (MRI) findings, as well as treatments and prognoses were retrospectively analyzed. ResultsFive patients (two males with myelin oligodendrocyte glycoprotein [MOG] antibody and three females with aquaporin-4 [AQP4] antibody) experienced six attacks. Average age at onset was 31.5 ± 3.5 years-old. The earliest clinical manifestations included fever (6/6), headache (5/6), and meningeal irritation (6/6) accompanied by leukocytosis and elevated protein levels (6/6) in cerebrospinal fluid. Two attacks initially manifested as meningitis alone. Meanwhile, following the onset of meningitis-like symptoms, four attacks were accompanied by transverse myelitis on the same day. One attack was associated with leptomeningeal enhancement on MRI, four attacks with spinal meninges enhancement, and one with both leptomeningeal and spinal meninges enhancement. All patients were considered to have an intracranial infection at onset and consequently treated with anti-infective drugs. As the symptoms continuously deteriorated, flare-up of NMOSD was considered a more reasonable diagnosis. Application of glucocorticoids (with or without intravenous immunoglobulin therapy) quickly relieved the symptoms. Subsequent re-examination of cerebrospinal fluid and MRI showed significant improvements. ConclusionAseptic meningitis may be an atypical phenotype of NMOSD flare that is easily confused with specific infection. Comprehensive evaluation to exclude an infective etiology and enable accurate diagnosis and timely immunotherapy are critical to prognosis.

Choroid plexus volume is associated with levels of CSF proteins: relevance for Alzheimer's and Parkinson's disease

The choroid plexus (ChP) is a major source of cerebrospinal fluid (CSF) production, with a direct and indirect role in protein clearance, and pathogenesis of Alzheimer's disease (AD). Here, we tested the link between the ChP volume and levels of CSF proteins in 2 data sets of (i) healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 509), and (ii) healthy controls and Parkinson's disease (PD) patients from the Parkinson's Progression Markers Initiative (N = 302). All patients had baseline CSF proteins (amyloid-β, total and phosphorylated-tau and α-synuclein (only in Parkinson's Progression Markers Initiative)). ChP was automatically segmented on 3T structural T1-weighted MRIs. We found negative associations between ChP volume and CSF proteins, which were stronger in healthy controls, early-MCI patients, and PD patients compared with late-MCI and AD patients. Further grouping of patients of ADNI dataset into amyloid-positive and amyloid-negative based on their florbetapir (AV45) PET imaging showed that the association between ChP volume and CSF proteins (t/p-tau) was lower in amyloid-positive group. Our findings support the possible role of ChP in the clearance of CSF proteins, provide evidence for ChP dysfunction in AD, and suggest the need to account for the ChP volume in future studies of CSF-based biomarkers.

Elevated Cerebrospinal Fluid Protein Is Associated with Unfavorable Functional Outcome in Spontaneous Subarachnoid Hemorrhage

Background/objective: Subarachnoid hemorrhage (SAH) is a devastating neurologic event for which markers to assess poor outcome are needed. Elevated cerebrospinal fluid (CSF) protein may result from inflammation and blood-brain barrier (BBB) disruption that occurs during SAH. We sought to determine if CSF protein level is associated with functional outcome after SAH. Methods: We prospectively collected single-center demographic and clinical data for consecutive patients admitted with spontaneous SAH. Inclusion required an external ventricular drain and daily CSF protein and cellular counts starting within 48 hours of symptom onset and extending through 7 days after onset. Seven-day average CSF protein was determined from daily measured values after correcting for contemporaneous CSF red blood cell (RBC) count. Three-month functional outcome was assessed by telephone interview with good outcome defined as modified Rankin score 0-3. Variables univariately associated with outcome at P less than .25 and measures of hemorrhage volume were included for binary logistic regression model development. Results: The study included 130 patients (88% aneurysmal SAH, 69% female, 54.8 ± 14.8 years, Glasgow Coma Scale [GCS] 14 [7-15]). Three-month outcome assessment was complete in 112 (86%) patients with good functional outcome in 74 (66%). CSF protein was lower in good outcome (35.3 [20.4-49.7] versus 80.5 [40.5-115.5] mg/dL; P < .001). CSF protein was not associated with cerebral vasospasm, but delayed radiographic infarction on 3 to 12-month neuroimaging was associated with higher CSF protein (46.3 [32.0-75.0] versus 30.2 [20.4-47.8] mg/dL; P = .023). Good 3-month outcome was independently associated with lower CSF protein (odds ratios [OR] .39 [.23-.70] for 75th versus 25th percentile of protein; P = .001) and higher admission GCS (OR 1.23 [1.10-1.37] for good outcome per GCS point increase; P < .001). Parenchymal hematoma predicted worse outcome (OR 6.31 [1.58-25.25]; P = .009). Results were similar after excluding nonaneurysmal SAH and after including CSF RBC count, CT score, and intraventricular hemorrhage volume in models. Conclusions: Elevated average CSF protein is associated with poor outcome after spontaneous SAH. Further research should investigate if elevated CSF protein identifies patients in whom mechanisms such as BBB disruption contribute to poor outcome.