Cerebrospinal Fluid Parameters Research Articles

The spectrum of cerebrospinal fluid findings in tuberculous meningitis and their relation to severity, radiological features, and outcome.

The aim of the study was to evaluate cerebrospinal fluid (CSF) findings in tuberculous meningitis (TBM) and correlate it with severity, radiological features, and outcome of TBM. In a retrospective study, data from admitted TBM patients were analyzed, and findings of CSF examinations were recorded. The CSF was categorized as typical (protein 50-500 mg/dL, cells 50-500/mm3, and glucose 50% or lower of blood sugar); those above and below these values were categorized as increased or decreased, respectively. The CSF findings were correlated with stage of TBM, and 3-month outcome and radiological features. Paradoxical response was also noted. There were 111 patients with TBM (definite 34, highly probable 77). On admission, 20 patients were in Stage I, 63 in Stage II, and 28 in Stage III TBM. CSF cells were in typical range in 73, low in 27 and increased in 11 patients. Protein was in typical range in 92 patients decreased in 11 patients and increased in eight patients. Sugar was normal in 41 and reduced in 70 patients. CSF cells, glucose, and protein did not correlate with the severity of meningitis. Fifteen patients had normal initial magnetic resonance imaging (MRI). Tuberculomas were present in 53 patients, hydrocephalus in 43 patients, basal exudates in 43 patients, and infarction in 44 patients. Mixed findings were present in 65 patients. The MRI features did not correlate with CSF. Second CSF was available after a median duration of 26 (13-276) days in 50 patients. The CSF cells were decreased in 20 and increased in 30 patients, protein increased in 30 and sugars decreased in 16 patients. Paradoxical worsening occurred in 27 patients. Fifty-one patients recovered completely, 41 partially, 15 had poor, three patients were lost to follow-up, and one died. CSF parameters did not correlate with 3-month outcome or paradoxical worsening. CSF parameters do not differ significantly between baseline and 1 month CSF, but cells and lymphocytes changed significantly between 1st month and 3rd month CSF. Typical CSF findings were present in 66% and did not correlate severity of TBM, radiological features paradoxical worsening or 3-month outcome. CSF cell count decreased within 3 months of treatment.

Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice

ObjectivesNeuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE.MethodsSerum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect.ResultsThe level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice.ConclusionGRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.

Immune profiling in multiple sclerosis: a single-center study of 65 cytokines, chemokines, and related molecules in cerebrospinal fluid and serum.

The understanding of the pathophysiology of multiple sclerosis (MS) has evolved alongside the characterization of cytokines and chemokines in cerebrospinal fluid (CSF) and serum. However, the complex interplay of pro- and anti-inflammatory cytokines and chemokines in different body fluids in people with MS (pwMS) and their association with disease progression is still not well understood and needs further investigation. Therefore, the aim of this study was to profile a total of 65 cytokines, chemokines, and related molecules in paired serum and CSF samples of pwMS at disease onset. Multiplex bead-based assays were performed and baseline routine laboratory diagnostics, magnetic resonance imaging (MRI), and clinical characteristics were assessed. Of 44 participants included, 40 had a relapsing-remitting disease course and four a primary progressive MS. There were 29 cytokines and chemokines that were significantly higher in CSF and 15 in serum. Statistically significant associations with moderate effect sizes were found for 34 of 65 analytes with sex, age, CSF, and MRI parameters and disease progression. In conclusion, this study provides data on the distribution of 65 different cytokines, chemokines, and related molecules in CSF and serum in newly diagnosed pwMS.

Impact of therapeutic and low volume plasma exchange on clinical laboratory parameters in patients treated for Alzheimer's disease from the AMBAR study.

Little is known about the impact of plasma exchange (PE) on clinical laboratory parameters in Alzheimer's disease (AD) patients. AD patients in the AMBAR trial (N = 322) received weekly therapeutic PE (TPE) for 6 weeks followed by monthly low-volume PE (LVPE) for12 months. Treatment were placebo (sham PE), low-albumin, low-albumin + IVIG (i.e., albumin alternated with intravenous immunoglobulin) and high-albumin + IVIG. Coagulation parameters transiently increased post-TPE. Blood calcium, platelets, and albumin levels decreased but remained within the reference range. Leukocyte counts increased. Fibrinogen, hemoglobin, total protein, gamma globulin, and IgG, transiently dipped below the reference range. Hypogammaglobulinemia (7.2 g/L) persisted in pre-TPE measurements. No changes were observed during the LVPE period. Cerebrospinal fluid parameters and vital signs were unchanged throughout. Laboratory parameters of AD patients were affected by TPE similarly to effects of PE-treatment for other pathologies. These effects were less pronounced or non-existent for LVPE.

Comparative Analysis of Diagnostic Criteria for Radiologically Isolated Syndrome (S31.009)

<h3>Objective:</h3> This study aimed to analyze the factors that predict the conversion of radiologically isolated syndrome (RIS) patients to multiple sclerosis (MS), and the validity of the two RIS diagnostic criteria. <h3>Background:</h3> Okuda et al. introduced the RIS criteria for the first time in 2009. In 2018, the MAGNIMS group proposed less stringent criteria. There are no studies comparing these two criteria. <h3>Design/Methods:</h3> All participants with suspected demyelinating brain MRI lesions were included in this study. Patient data was collected including demographics, clinical and cerebrospinal fluid (CSF) parameters, and MRI lesion characteristics. All MRI images were reevaluated by two MS specialists and a neuroradiologist. Multi-parameter Cox-regression method was used during the analyses. <h3>Results:</h3> A total of 130 patients (30 mRIS, 65 Okuda and mRIS, 35 nonRIS) from seven centers were included into the study. Fifty percent of the patients converted into MS after 8.59 years (95% CI: 3.95–13.22). The conversion rate of the three groups were comparable (p=0.18). Presence of oligoclonal bands in the CSF (OCB) (HR=0.09, p=0.02), elevated IgG index (HR=0.08, p=0.02), and presence of spinal MRI lesion (HR= 0.23, p=0.001) predicted conversion to MS. Male gender (HR=1.05, p=0.89) and age less than 37 (HR=0.56, p=0.21) were not predictive of conversion to MS. <h3>Conclusions:</h3> Our findings indicates that baseline spinal lesions, an elevated IgG index, and OCB are the best predictors of conversion to MS. Considering conversion to MS, we found no difference between patients who fulfilled the Okuda or modified RIS criteria. It is necessary to explore new parameters that will improve the sensitivity and specificity of the present diagnostic criteria for RIS. <b>Disclosure:</b> Tuncay Gunduz has nothing to disclose. Dr. Ciftci has nothing to disclose. Bilge Piri Cinar has nothing to disclose. Mr. Baba has nothing to disclose. MERAL SEFEROGLU has nothing to disclose. Dr. SIVACI has nothing to disclose. Dr. Cilingir has nothing to disclose.ÖZLEM ETHEMOGLU has nothing to disclose. LEVENT OCEK, 4284 has nothing to disclose. Dr. Barburoglu has nothing to disclose. Dr. Ozakbas has nothing to disclose. Dr. Eraksoy has nothing to disclose. Dr. Kurtuncu has nothing to disclose.

Review of Risk Factors Associated With Biomarkers for Alzheimer Disease.

BACKGROUND: Alzheimer disease (AD) is a neurodegenerative disease with no cure. The number of individuals living with AD doubles every 5 years. The current clinical practice relies on clinical history, mental status tests, cerebrum imaging, and physical and neurological examinations; however, recent advances in the field of biomarkers have provided clues for the early detection of AD. High levels of tau and low levels of amyloid-β (Aβ) in cerebrospinal fluid are well-known biomarkers for AD. METHODS: A database search of PubMed, Ovid MEDLINE, and CINAHL was conducted to identify relevant articles published within the last 5 years. The search was limited to articles concerning adults 65 years or older and published in the English language. Twelve articles were included in the review. RESULTS: Risk factors of sleep disruption, depression, and motor function are implicated. Cerebrospinal fluid parameters for biomarkers of tau and Aβ were universally lower among Blacks compared with Whites, raising concern that norm reference may not be accurate for all populations. Older adults are more at risk for AD. Results are inconclusive regarding whether depression is related to Aβ and tau pathology. CONCLUSION: Nurses should screen for sleep architecture, depression, and motor function in their patients and educate them on good sleep hygiene. Sleep studies should be advocated for people with suspected sleep apnea to mitigate the risk factor related to abnormal Aβ and tau pathology. Falls and decreased motor function require screening because they may be early indicators of abnormal biomarkers leading to AD.

The relationship between blood–brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis

Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood-brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.

SEGMENTATION OF SPINAL SUBARACHNOID LUMEN WITH 3D ATTENTION U-NET

Phase Contrast Magnetic Resonance Image (PC-MRI) is an emerging noninvasive technique that contains pulsatile information by measuring the parameters of cerebrospinal fluid (CSF) flow. As CSF flow quantities are measured from the selected region on the images, the accuracy in the identification of the interested region is the most essential, and the examination requires a lot of time and experience to analyze and for accurate CSF flow assessment. In this study, a three-dimensional (3D)-Unet architecture, including pulsatile flow data as the third dimension, is proposed to address the issue. The dataset contains 2176 phase and rephase images from 57 slabs of 39 3-tesla PC-MRI subjects collected from the lower thoracic levels of control and Idiopathic Scoliosis (IS) patients. The procedure starts with labeling the CSF containing spaces in the spinal canal. In the preprocessing step, unequal cardiac cycle images (i.e., frame) and the numbers of MRIs in cases are adjusted by interpolation to align the temporal dimension of the dataset to an equal size. The five-fold cross-validation procedure is used to evaluate the 3D Attention-U-Net model after training and achieved an average weighted performance of 97% precision, 95% recall, 98% F1 score, and 95% area under curve. The success of the model is also measured using the CSF flow waveform quantities as well. The mean flow rates through the labeled and predicted CSF lumens have a significant correlation coefficient of 0.96, and the peak CSF flow rates have a coefficient of 0.65. To our knowledge, this is the first fully automatic 3D deep learning architecture implementation to segment spinal CSF-containing spaces that utilizes both spatial and pulsatile information in PC-MRI data. We expect that our work will attract future research on the use of PC-MRI temporal information for training deep models.

Association between cerebrospinal fluid parameters and developmental and neurological status in glucose transporter 1 deficiency syndrome.

In glucose transporter 1 deficiency syndrome (Glut1DS), cerebrospinal fluid glucose (CSFG) and CSFG to blood glucose ratio (CBGR) show significant differences among groups classified by phenotype or genotype. The purpose of this study was to investigate the association between these biochemical parameters and Glut1DS severity. The medical records of 45 patients who visited Osaka University Hospital between March 2004 and December 2021 were retrospectively examined. Neurological status was determined using the developmental quotient (DQ), assessed using the Kyoto Scale of Psychological Development 2001, and the Scale for the Assessment and Rating of Ataxia (SARA). CSF parameters included CSFG, CBGR, and CSF lactate (CSFL). CSF was collected from 41 patients, and DQ and SARA were assessed in 24 and 27 patients, respectively. Simple regression analysis showed moderate associations between neurological status and biochemical parameters. CSFG resulted in a higher R2 than CBGR in these analyses. CSF parameters acquired during the first year of life were not comparable to those acquired later. CSFL was measured in 16 patients (DQ and SARA in 11 and 14 patients, respectively). Although simple regression analysis also showed moderate associations between neurological status and CSFG and CSFL, the multiple regression analysis for DQ and SARA resulted in strong associations through the use of a combination of CSFG and CSFL as explanatory variables. The severity of Glut1DS can be predicted from CSF parameters. Glucose and lactate are independent contributors to the developmental and neurological status in Glut1DS.

The Diagnostic Value of Cerebrospinal Fluid Lactate for Detection of Sepsis in Community-Acquired Bacterial Meningitis.

Community-acquired bacterial meningitis conveys significant morbidity and mortality due to intracranial and systemic complications, and sepsis is a major contributor to the latter. While cerebrospinal fluid (CSF) analysis is essential in the diagnosis of bacterial meningitis, its predictive utility for detection of sepsis is unknown. We investigated the diagnostic performance of CSF parameters for sepsis defined by the Sepsis-3 criteria in a retrospective cohort of patients with community-acquired bacterial meningitis. Among 103 patients, 69.5% developed sepsis. CSF lactate was associated with sepsis with an odds ratio of 1.11 (p = 0.022), while CSF cell counts, glucose and protein levels were not (all p > 0.4). Employing the optimal cutoff of 8.2 mmol/L, elevated CSF lactate resulted in a sensitivity of 81.5% and specificity of 61.5% for sepsis. In exploratory analyses, CSF lactate was also associated with in-hospital mortality with an odds ratio of 1.21 (p = 0.011). Elevated CSF lactate might contribute to early diagnosis of sepsis as well as prognostication in patients with community-acquired bacterial meningitis.

Assessment of disorders of hemodynamics and csf dynamics in idiopathic intracranial hypertension syndrome according to MRI data

Highlights. An increase in the pulsatility index of intracranial venous blood flow and cerebrospinal fluid flow at the foramen magnum level, and a decrease in arteriovenous delay and an intracranial compliance index indicate disturbances in the pulse wave distribution, and a decrease in compliance/extensibility of the brain due to increased intracranial pressure.Aim. To assess the parameters of hemodynamics and cerebrospinal fluid dynamics in patients with idiopathic intracranial hypertension syndrome according to phase-contrast MRI.Methods. The study included 18 patients with idiopathic intracranial hypertension syndrome and 20 controls, all patient were examined using the Ingenia 3,0T MRI scanner. The analysis was performed using phase-contrast MRI to assess quantitative parameters of hemodynamics and cerebrospinal fluid (CSF) dynamics in 14 different structures. The blood and CSF volumes, pulsatility index (PI), arterio-venous delay, and intracranial compliance index were calculated. The Mann-Whitney U-test reliability was used to assess the differences between the controls and patients.Results. The group of patients had an increased CSF systolic peak at the foramen magnum without significant changes in CSF volume, and significantly increased CSF PI at the cervical level by 11.88% (p&lt;0,05). There was a tendency toward an increase in the intracranial venous blood volume, as well as a tendency toward significant increase in PI at the straight and superior sagittal sinuses by 1,3 times (p&gt;&lt;0,01, p&gt;&lt;0,05). Moreover, there was a reduction of intracranial arterio-venous delay by 1,9 times (p&gt;&lt;0,05), and a significant decrease in the intracranial compliance index by 1,2 times (p&gt;&lt;0,05). Conclusion We have assessed the parameters of hemodynamics and CSF dynamics in patients with idiopathic intracranial hypertension and revealed disturbances in CSF dynamics and pulse wave propagation in the intracranial regions. Such changes may indicate a decrease in compliance/increase in stiffness of the brain tissue due to an increase in intracranial pressure and a possible diffuse stagnation of interstitial fluid. Keywords Phase-contrast magnetic resonance imaging • Central nervous system • Idiopathic intracranial hypertension • Hemodynamics • Cerebrospinal fluid dynamics • Intracranial compliance index&gt;˂0,05). There was a tendency toward an increase in the intracranial venous blood volume, as well as a tendency toward significant increase in PI at the straight and superior sagittal sinuses by 1,3 times (p˂0,01, p˂0,05). Moreover, there was a reduction of intracranial arterio-venous delay by 1,9 times (p˂0,05), and a significant decrease in the intracranial compliance index by 1,2 times (p˂0,05).Conclusion. We have assessed the parameters of hemodynamics and CSF dynamics in patients with idiopathic intracranial hypertension and revealed disturbances in CSF dynamics and pulse wave propagation in the intracranial regions. Such changes may indicate a decrease in compliance/increase in stiffness of the brain tissue due to an increase in intracranial pressure and a possible diffuse stagnation of interstitial fluid.

Differentiating neurosarcoidosis from multiple sclerosis using combined analysis of basic CSF parameters and MRZ reaction.

Neurosarcodosis is one of the most frequent differential diagnoses of multiple sclerosis (MS) and requires central nervous system (CNS) biopsy to establish definite diagnosis according to the latest consensus diagnostic criteria. We here analyzed diagnostic values of basic cerebrospinal fluid (CSF) parameters to distinguish neurosarcoidosis from MS without CNS biopsy. We retrospectively assessed clinical, radiological and laboratory data of 27 patients with neurosarcoidosis treated at our center and compared following CSF parameters with those of 138 patients with relapsing-remitting MS: CSF white cell count (WCC), CSF/serum albumin quotient (Qalb), intrathecal production of immunoglobulins including oligoclonal bands (OCB), MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of 3 the viruses measles (M), rubella (R), and zoster (Z) virus, and CSF lactate levels. Additional inflammatory biomarkers in serum and/or CSF such as neopterin, soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were assessed. There was no significant difference in the frequency of CSF pleocytosis, but a CSF WCC > 30/μl was more frequent in patients with neurosarcoidosis. Compared to MS, patients with neurosarcoidosis showed more frequently an increased Qalb and CSF lactate levels as well as increased serum and CSF levels of sIL-2R, but a lower frequency of intrathecal IgG synthesis and positive MRZ reaction. Positive likelihood ratio (PLR) of single CSF parameters indicating neurosarcoidosis was highest, if (a) CSF WCC was >30/μl (PLR 7.2), (b) Qalb was >10 × 10-3 (PLR 66.4), (c) CSF-specific OCB were absent (PLR 11.5), (d) CSF lactate was elevated (PLR 23.0) or (e) sIL-2R was elevated (PLR>8.0). The combination of (a) one of three following basic CSF parameters, i.e., (a.1.) CSF WCC >30/ul, or (a.2.) QAlb >10 × 10-3, or (a.3.) absence of CSF-specific OCB, and (b) absence of positive MRZ reaction showed the best diagnostic accuracy (sensitivity and specificity each >92%; PLR 12.8 and NLR 0.08). Combined evaluation of basic CSF parameters and MRZ reaction is powerful in differentiating neurosarcoidosis from MS, with moderate to severe pleocytosis and QAlb elevation and absence of intrathecal IgG synthesis as useful rule-in parameters and positive MRZ reaction as a rule-out parameter for neurosarcoidosis.

Clinical and Diagnostic Study of Cerebrospinal Fluid Parameters in the Laboratory of the Regional Children’s Hospital

The aim of the work is to analyze the morbidity of children who underwent CSF research for the period 2019-2021, as well as to consider the dynamics of the development of the disease picture with purulent and serous meningitis (against the background of anti-intoxication and antibacterial therapy) and to assess the condition of a sick child. The contingent of subjects is an experimental group of children under 14 years old with a diagnosis of purulent and serous meningitis who were being treated at the Penza regional Hospital. The main results of the work showed that in three years the number of children in need of cerebrospinal fluid examination has decreased. However, the number of pathological studies in children with meningitis remained at a fairly high level. In children during the newborn period with a diagnosis of purulent meningitis, there is a positive dynamic of indicators against the background of anti-intoxication and antibacterial therapy. In children diagnosed with serous meningitis, there was a slight lymphocytic pleocytosis, in several cases of the disease there is an increase in neutrophils. This indicates the most severe course of the disease and has a less favorable prognosis.

Blood–brain barrier dysfunction and folate and vitamin B12 levels in first-episode schizophrenia-spectrum psychosis: a retrospective chart review

Vitamin deficiency syndromes and blood–brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture, blood-based vitamin status diagnostics and neuroimaging within the clinical routine. 222 FEP patients were included in our analyses. We report an increased CSF/serum albumin quotient (Qalb) as a sign of BBB dysfunction in 17.1% (38/222) of patients. White matter lesions (WML) were present in 29.3% of patients (62/212). 17.6% of patients (39/222) showed either decreased vitamin B12 levels or decreased folate levels. No statistically significant association was found between vitamin deficiencies and altered Qalb. This retrospective analysis contributes to the discussion on the impact of vitamin deficiency syndromes in FEP. Although decreased vitamin B12 or folate levels were found in approximately 17% of our cohort, we found no evidence for significant associations between BBB dysfunction and vitamin deficiencies. To strengthen the evidence regarding the clinical implications of vitamin deficiencies in FEP, prospective studies with standardized measurements of vitamin levels together with follow-up measurements and assessment of symptom severity in addition to CSF diagnostics are needed.

Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19.Materials and methodsRetrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay.Results442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH.DiscussionAIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.

Efficacy and safety of lenalidomide in HIV-associated cryptococcal meningitis patients with persistent intracranial inflammation: an open-label, single-arm, prospective interventional study

BackgroundPatients with human immunodeficiency virus-associated cryptococcal meningitis (HIV-CM) have persistent intracranial inflammation despite negative cerebrospinal fluid (CSF) fungal cultures after optimal treatment for CM, which could be devastating for the central nervous system. However, a definitive treatment strategy for persistent intracranial inflammation despite optimal antifungal therapies is undefined.MethodsWe identified 14 HIV-CM patients with persistent intracranial inflammation and conducted a 24-week, prospective, interventional study. All participants received lenalidomide (25 mg, p.o.) on days 1 to 21 of a 28-day cycle. Follow-up lasted for 24 weeks with visits at baseline and weeks 4, 8, 12, and 24. The primary endpoint was the change in clinical manifestations, routine CSF parameters, and MRI findings after lenalidomide treatment. An exploratory analysis was made on changes in cytokine levels in CSF. Safety and efficacy analyses were undertaken in patients who received at least one dose of lenalidomide.ResultsOf 14 participants, 11 patients completed the 24 weeks of follow-up. Rapid clinical remission following lenalidomide therapy was observed. Clinical manifestations (fever, headache, altered mentation) were reversed fully by week-4 and remained stable during follow-up. A significant reduction in white blood cell (WBC) count in CSF was noted occurred at week-4 (P = 0.009). The median protein concentration in CSF decreased from 1.4 (0.7–3.2) g/L at baseline to 0.9 (0.6–1.4) at week-4 (P = 0.004). The median albumin concentration in CSF decreased from 79.2 (48.4–149.8) mg/L at baseline to 55.3 (38.3–89.0) mg/L at week-4 (P = 0.011). The WBC count, protein level, and albumin level in CSF remained stable and approached a normal range through week-24. There was no significant change in immunoglobulin-G, intracranial pressure (ICP), or chloride-ion concentration at each visit. Brain MRI demonstrated multiple lesions to be absorbed post-therapy. Levels of tumor necrosis factor-α granulocyte colony stimulating factor, interleukin (IL)-6, and IL-17A decreased significantly during 24-week follow-up. Two (14.3%) patients had mild skin rash, which resolved spontaneously. Lenalidomide-related serious adverse events were not observed.ConclusionLenalidomide could improve persistent intracranial inflammation in HIV-CM patients significantly and was well tolerated without serious adverse events observed. And the additional randomized controlled study is required to further validate the finding.

Elevated neurofilament light chain CSF/serum ratio indicates impaired CSF outflow in idiopathic intracranial hypertension

BackgroundImpaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.MethodsNfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.ResultsCSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = − 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.ConclusionsThe observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.

Clinical Value of Glycan Changes in Cerebrospinal Fluid for Evaluation of Post-Neurosurgical Bacterial Meningitis with Hemorrhagic Stroke Patients.

Post-neurosurgical bacterial meningitis (PNBM) is one of the severe complications in patients receiving neurosurgical procedures. Recent studies have found microbe-related glycans play important roles in adhesion, invasion, and toxicity toward innate immunological reactions. In this study, we aimed to investigate the glycomic profile and its potential diagnostic efficacy in post-neurosurgical bacterial meningitis (PNBM) patients with hemorrhagic stroke. A total of 136 cerebrospinal fluid (CSF) samples were recruited and divided into a PNBM group and a non-PNBM group based on the clinical diagnostic criteria. A lectin biochip-based method was established for the detection of glycans in CSF. The clinicopathological data and biochemical parameters in CSF from all patients were analyzed. Two models for multivariate analysis investigating glycan changes in the CSF were conducted, aiming at determining the specific expression and diagnostic efficacy of lectin-probing glycans (LPGs) for PNBM. In univariate analysis, we found that 8 out of 11 LPGs were significantly correlated with PNBM. Model 1 multivariate analysis revealed that PNA (p = 0.034), Jacalin (p = 0.034) and LTL (p = 0.001) were differentially expressed in the CSF of PNBM patients compared with those of non-PNBM patients. Model 2 multivariate analysis further disclosed that LTL (p = 0.021) and CSF glucose (p &lt; 0.001) had independent diagnostic efficacies in PNBM, with areas under the curve (AUC) of 0.703 and 0.922, respectively. In summary, this study provided a new insight into the subject of CSF glycomics concerning bacterial infection in patients with hemorrhagic stroke.

Comparison of Treponema-specific immunoglobulin G (IgG) index with Treponema pallidum particle agglutination (TPPA) index for detection of intrathecal Treponema-specific antibody synthesis for serological diagnosis of neurosyphilis.

The determination of Treponema-specific intrathecal immunoglobulin synthesis with the Treponema pallidum particle agglutination (TPPA) index is a well-established method recommended in German guidelines for the diagnosis of neurosyphilis. However, the TPPA test is no longer available. The aim of this study was to evaluate whether the determination of a Treponema-specific immunoglobulin G (IgG) index can substitute the TPPA index. Serum and cerebrospinal fluid (CSF) samples from patients with confirmed (n=6) and probable (n=3) neurosyphilis as well as patients with adequately treated syphilis without neurosyphilis (n=4) were investigated. In addition to index calculation further CSF parameters were determined. The results of the Treponema IgG and the TPPA index were consistent in all patients with confirmed neurosyphilis and non-neurosyphilis patients. In two patients with probable neurosyphilis the IgG index appeared more plausible than the TPPA index when taking into account all available laboratory and clinical data of the patients. In conclusion, the determination of Treponema-specific intrathecal immunoglobulin synthesis with the IgG index appears to be a suitable alternative to the TPPA index.

Outcome of tuberculous meningitis in children aged 9 months to 12 years at the end of intensive phase of treatment

BackgroundTuberculous meningitis (TBM) is associated with high morbidity and mortality. Most of the literature focuses on outcomes at the end of therapy when it may be too late for intervention to improve the outcomes. So, the present study addresses outcomes by the end of intensive course of therapy. MethodsIt was a prospective cohort observational study that enrolled 80 patients with TBM between 9 months and 12 years of age. Participants were classified into Definite, Probable and Possible TBM using Marais criteria. Survival/Mortality was evaluated at the end of hospital stay. Demographic, clinical, cerebrospinal fluid and radiological parameters were evaluated for predictors of morbidity and mortality. Standardized tools were used to assess possible impairments in different domains at the end of intensive phase of treatment, namely Gross Motor Functional Classification System for motor functional ability, Pediatric-Mini Mental score examination (MMSE), Blantyre Coma Scale (BCS) score and Vineland Social Maturity Scale (VSMS) for cognitive outcome, Auditory Brainstem Evoked Responses for hearing outcome and using Teller's/Snellen's visual acuity charts to assess visual impairment. ResultsA high Mortality rate of 42.5% was seen in the enrolled patients. Out of the total 80 patients, 20% recovered completely while 36.25% survived with disability (morbidity). Motor, Hearing, Cognitive and Vision impairment was present in 33.3%, 4%, 33.3% and 48.9% of the survivors respectively. On multivariate regression, raised intracranial tension and stage III disease were significantly associated with mortality. Morbidity was significantly associated with Stage III disease on multivariate analysis. ConclusionsDespite advances in treatment, Tuberculous meningitis is associated with high burden of deaths and devastating neurological sequelae. Timely diagnosis and intervention of neurological impairments is needed to improve the outcome of TBM in survivors.