Cerebrospinal Fluid Cell Count Research Articles

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.

Prognostic Factors for Japanese Adults With Acute Community-Acquired Bacterial Meningitis: A Retrospective Study.

Background This study aimed to determine if the cerebrospinal fluid (CSF) cell count is useful for predicting the infection severity or prognosis in Japanese adults with community-acquired bacterial meningitis. Methodology This study retrospectively evaluated the prognosis of patients diagnosed with community-acquired bacterial meningitis at our hospital from January 2004 to December 2021 using the modified Rankin scale (mRs) (Showa General Hospital; N = 39). Patients were classified into the following two groups: (i) favorable (mRs: 0-3) and (ii) unfavorable (mRs: 4-6). Eight factors were selected and compared with outcomes, and then two factors were evaluated from those, and a multivariate logistic regression was used to determine the significant variables. Results CSF cell count was observed to be associated with poor prognoses (odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.99995-0.99999, p = 0.0012). Glasgow coma scale (GCS) score on admission was also observed to be associated with poor prognoses (OR = 0.93, 95% CI = 0.89145-0.97290, p = 0.0029). Conclusions Low CSF cell count and low GCS on admission were observed as risk factors for poor prognoses in patients with bacterial meningitis.

An Observational Study on Clinical Profile and Outcome of Japanese Encephalitis Patients Admitted in the Department of Medicine of a Tertiary Care Hospital of North Bank of Assam, India

Background: A significant public health issue in India is Japanese encephalitis (JE), which has a high fatality rate and causes residual neurological damage in survivors. The goal of the current study was to examine JE positive among patients who had been admitted with acute encephalitis syndrome (AES) and to analyse the differences in clinical profile, disease severity, neurological consequences, and mortality rate in Tezpur Medical College and Hospital. Methods: This study is a retrospective observational study in a patients who were diagnosed as Japanese encephalitis on the basis of JEV-specific IgM antibodies in blood and cerebrospinal fluid (CSF) samples. The study included 32 Japanese Encephalitis positive patients admitted in Tezpur Medical College and Hospital (who met the clinical case definition of AES) and thus, their clinical profile and outcome were analysed. Result: A total 32 JE cases were enrolled in the study diagnosed with CSF and Serum IgM ELISA antibody test. All of them were Serum IgM ELISA antibody positive, 9(28%) cases were both Serum and CSF IgM antibody positive. Most common age group affected was 12-20 years(31%). 59.37% cases recovered completely, 21.87% had neurological sequelae at the time of discharge and 18.75% died at ward. Conclusion: Japanese Encephalitis is one of the leading cause of AES in India. In our study it has been seen that GCS score on presentation and CSF cell counts has positive association with mortality and disease sequale. Adequate care and treatment should be provided in order to avoid subsequent complications/sequale. Proper vaccination and vector control can prevent or mitigate this disease.

Association between clinical characteristics, acute steroid treatment and oligoclonal bands result in multiple sclerosis: A retrospective study

BackgroundDetection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is important for diagnosis of multiple sclerosis (MS). Previous studies reported that treatment with intravenous methylprednisolone (IVMP) before lumber puncture (LP) could suppress OCBs production. The aim of this study was to assess whether IVMP initiation prior to CSF collection affects OCBs results in patients with an acute demyelinating event. Additionally, we examined which clinical characteristics are associated with the presence of OCBs in the CSF. MethodsWe retrospectively evaluated patients admitted to the neurology department at rabin medical center (RMC) between 2010 and 2022 who underwent LP with OCBs analysis as part of their demyelinating attack workup. Patients were divided into OCB-positive and OCB-negative groups and demographical and clinical characteristics (including timing and duration of acute steroid treatment and history of prior demyelinating attacks) were analyzed for association with OCBs results. ResultsA total of 342 patients were included with a median age of 35 years (IQR, 27–46). Two hundred thirty-eight (69.6 %) were OCB-positive. Initiation of IVMP before LP was not associated with negative OCBs (11.8 % Vs. 13.5 %, P = 0.721), nor was it correlated with OCBs positivity (OR=0.86, P = 0.66). CSF cell count was higher in OCB-positive patients (5 Vs. 3, P = 0.001), and a history of prior demyelinating attacks was associated with- (33.6 % Vs. 20.2 %, P = 0.014) and predictive of OCBs positivity (OR=2, P = 0.013). ConclusionsTiming of steroids was not associated with OCB positivity. However, pleocytosis and a prior attack were associated with OCB positivity in this cohort. Our results suggest that steroid treatment is unlikely to affect OCBs results. Ideally, larger prospective studies would be needed to confirm our observations.

Vogt-Koyanagi-Harada disease developed during chemotherapy for Hodgkin lymphoma: a case report

BackgroundOcular manifestations are known for non-Hodgkin lymphoma, but are rare for Hodgkin lymphoma. We report a case of Vogt-Koyanagi-Harada (VKH) disease presenting as serous retinal detachment and uveitis in both eyes in a child undergoing chemotherapy for Hodgkin lymphoma.Case presentationThe patient was a 7-year-old boy with stage IIB Hodgkin lymphoma (nodular lymphocyte predominant type) who was undergoing chemotherapy, including 2 cycles of the OEPA regimen and 1 cycle of the COPDAC regimen. Two days after the end of the COPDAC regimen, the patient complained of headache and of blurred and decreased vision in both eyes. On the basis of optic symptoms, such as uveitis and serous retinal detachment in both eyes, increased cell counts in cerebrospinal fluid, and positivity for human leukocyte antigen (HLA)-DR4 in peripheral blood cells, incomplete VKH disease was diagnosed. Intravenous treatment with high-dose prednisolone (60mg/m2/day) for 7 days improved both visual acuity and serous retinal detachment and enabled the remains of the COPDAC chemotherapy cycle to be administered. With prednisolone treatment, visual acuity improved from 20/500 to 20/20 in the right eye and from 20/63 to 20/25 in the left eye. Because multiple vitiligo lesions later appeared in the abdomen, complete VKH disease was finally diagnosed.ConclusionThe onset of VKH disease occurred during chemotherapy for Hodgkin lymphoma. The patient was HLA-DR4-positive and might have had a predisposition to develop autoimmune diseases, including VKH disease. However, the anticancer drugs administered to this patient have not been reported to cause uveitis. Whether Hodgkin lymphoma triggered the development of VKH remains unclear. Early diagnosis of VKH disease and prompt treatment with high-dose prednisone enabled the patient to maintain good visual function despite chemotherapy for Hodgkin lymphoma.

Adult-onset COVID-19-associated Fulminant Acute Encephalopathy with Elevated Cerebrospinal Fluid Interleukin-8: A Case Report

A 26-year-old woman receiving immunosuppressive therapy for polymyositis was infected with COVID-19 (an omicron mutant strain) and presented with fever. On the second day after the onset, she was admitted to our hospital and developed status epilepticus. Brain magnetic resonance imaging on admission revealed abnormal symmetric hyperintensities in the bilateral putamen and around the dorsal horns of the lateral ventricle. Three days after admission, brain computed tomography revealed marked cerebral edema and herniation. The cerebrospinal fluid (CSF) cell count was normal, and the reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was negative. Interleukin (IL)-2, 6, and 10 levels were within the normal range in both serum and CSF, whereas IL-8 levels in the CSF were markedly higher compared to serum levels. She had fulminant acute encephalopathy, suspected to be in the early stages of acute necrotizing encephalopathy (ANE). Steroid pulse therapy and intravenous infusions of remdesivir were ineffective, and the patient died of sepsis on the 26th day after admission. We demonstrated that ANE may occur even in patients infected with Omicron strains and speculated that the pathogenesis in this case might be associated with intrathecal IL-8 production by microglial activation.

Accuracy of automated analyzers for the estimation of CSF cell counts: A systematic review and meta-analysis.

This systematic review evaluates the evidence for accuracy of automated analyzers that estimate cerebrospinal fluid (CSF) white blood cell counts (WBC) compared to manual microscopy. Inclusion criteria of original research articles included human subjects, English language, and manual microscopy comparator. PUBMED, EMBASE and Cochrane Review databases were searched through 2019 and QUADAS-2 Tool was used for assessment of bias. Data were pooled and analyzed by comparison method, using random effects estimation. Among 652 titles, 554 abstracts screened, 104 full-text review, 111 comparisons from 41 studies were included. Pooled estimates of sensitivity and specificity (n = 7) were 95% (95%-CI 93%-97%) and 84% (95%-CI: 64%-96%), respectively. Pooled R2 estimates (n = 29) were 0.95 (95%-CI: 0.95-0.96); Pooled spearman rho correlation (n = 27) estimates were 0.95 (95% CI 0.95-0.96). Among those comparisons using Bland-Altman analysis (n = 11) pooled mean difference was estimated at 0.98 (95% CI-0.54-2.5). Among comparisons using Passing-Bablok regressions (n = 14) the pooled slope was estimated to be 1.05 (95% CI 1.03-1.07). Q tests of homogeneity were all significant with the exception of the Bland-Altman comparisons (I2 10%, p value 0.35). There is good overall accuracy for CSF WBC by automated hematologic analyzers. These findings are limited by the small sample sizes and inconsistent validation methodology in the reviewed studies.

Etiology, Clinical Presentation, and Outcomes of Bacterial Meningitis in Adult Patients: A Retrospective Study in Lithuania (2018-2021).

BACKGROUND Bacterial meningitis is a serious and life-threatening condition that requires prompt diagnosis and treatment. This retrospective study aimed to identify causes, presentation, and predictive factors for outcomes of community-acquired bacterial meningitis in 86 adults in Vilnius, Lithuania between 2018 and 2021. MATERIAL AND METHODS We performed a retrospective study of demographic, clinical, and laboratory records of 86 adult patients admitted to Vilnius University Hospital Santaros Clinics with a diagnosis of acute bacterial meningitis during the period of 2018-2021. RESULTS Of 86 patients, 54 (62.79%) were men. The median (Md) age of patients was 58 (range, 18-83) years and the median duration of hospitalization was 20 (range, 3-92) days. Patients were first hospitalized in the Intensive Care Unit (ICU) in 59.3% of cases. The most prevalent concerns were headache (66.28%), febrile temperature (56.98%), general fatigue (53.49%), and confusion/sleepiness (52.33%). Of 57 (66.28%) etiologically confirmed cases, the most prevalent agent was Listeria monocytogenes (29.82%), followed by Streptococcus pneumoniae (28.07%) and Neisseria meningitidis (28.07%). Patients with meningitis caused by L. monocytogenes were the oldest (P=0.003) and had the longest hospitalization (P<0.001). Fatigue was the prominent symptom in patients with meningococcal meningitis (81.2%, P=0.010). Twelve patients (13.95%) have died. Advanced age and low (<100 cells per μL) white blood cell (WBC) count in cerebrospinal fluid (CSF) were associated with lethal outcome, whereas headache was associated with favorable outcome. CONCLUSIONS Clinical characteristics of community-acquired acute bacterial meningitis differ based on etiological factors. Patient age, CSF WBC count, and headache may be significant predictive factors for outcomes of bacterial meningitis.

Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis

BackgroundA comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking. MethodsMultiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included. ResultsA total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, −0.04 to 0.32). ConclusionsThe results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking.

Broad Range Eubacterial Polymerase Chain Reaction of Cerebrospinal Fluid Reduces the Time to Exclusion of and Costs Associated with Ventriculostomy-Related Infection in Hemorrhagic Stroke.

Patients with hemorrhagic stroke and an external ventricular drain in situ are at risk for ventriculostomy-related-infections (VRI). Because of the contamination of the cerebrospinal fluid (CSF) with blood and the high frequency of false negative CSF culture, the diagnosis of VRI remains challenging. This study investigated the introduction of CSF broad range eubacterial polymerase chain reaction (ePCR) and its effect on frequency and duration of antibiotic therapy for VRI, neurocritical care unit (NCCU) length of stay, related costs, and outcome. Between 2020 and 2022, we prospectively included 193 patients admitted to the NCCU of the University Hospital of Zürich with hemorrhagic stroke and an external ventricular drain for more than 48 h. Patient characteristics, serum inflammatory markers, white blood cell count in CSF, use and duration of antibiotic treatment for VRI, microbiological findings (CSF cultures and ePCR tests), and NCCU length of stay were compared in patients with no infection, noncerebral infection, suspected VRI, and confirmed VRI. Data of patients with suspected VRI of this cohort were compared with a retrospective cohort of patients with suspected VRI treated at our NCCU before the introduction of CSF ePCR testing (2013-2019). Out of 193 patients, 12 (6%) were diagnosed with a confirmed VRI, 66 (34%) with suspected VRI, 90 (47%) with a noncerebral infection, and 25 (13%) had no infection at all. Compared with the retrospective cohort of patients, the use of CSF ePCR resulted in a reduction of patients treated for suspected VRI for the whole duration of 14 days (from 51 to 11%). Furthermore, compared with the retrospective group of patients with suspected VRI (n = 67), after the introduction of CSF ePCR, patients with suspected VRI had shorter antibiotic treatment duration of almost 10 days and, hence, lower related costs with comparable outcome at 3 months. The use of CSF ePCR to identify VRI resulted in shorter antibiotic treatment duration without changing the outcome, as compared with a retrospective cohort of patients with suspected VRI.

Clinical Course of Adult T-Cell Leukemia-Lymphoma with Central Nervous System Involvement

Background: Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma with a highly diverse clinical presentation. Although central nervous system (CNS) involvement is common, the detailed clinical presentation of CNS-ATL needs to be clarified. Objective: This study aims to clarify the clinical course of ATL with CNS involvement. CNS involvement was classified according to the criteria of JALSG202 for acute lymphocytic leukemia as follows: Grade I: no symptoms and cerebrospinal fluid (CSF)cell count less than 5/μl and presence of abnormal lymphocytes; Grade II: asymptomatic and CSF cell count 5-50/μl and presence of abnormal lymphocytes; Grade III: symptomatic or CSF cell counts &amp;gt; 50 cells/μl and presence of abnormal lymphocytes. Results: The analysis included 213 cases of ATL treated at Kagoshima University Hospital from 2002 to 2021. Of these aggressive ATL cases, the clinical subtypes at initial presentation were as follows: acute type 109, lymphoma type 54, chronic type 30, smoldering type 18, and 2 cases were unclassifiable. The median age of the patients was 63 years, and 96 cases (45.1%) were women. Sixty patients had received allogeneic hematopoietic stem cell transplants. During the clinical course, 28 patients (13.1%) with a median age of 61 years and 13 women（46.4%）had CNS involvement. Two cases were classified as Grade I, six as Grade II, and 20 as Grade III. Among them, nine patients (4.2%) showed neurological symptoms at the initial ATL diagnosis, and 1 patient presented with neurological findings at the time of chronic to acute transformation. Of the remaining 203 patients, prophylactic intrathecal chemotherapy was administered in 101 cases, at which time CNS involvement was diagnosed in 9 cases (8.9%). Three patients developed symptomatic involvement while responding to chemotherapy. One patient developed symptomatic involvement when refractory to chemotherapy. Four cases were CNS recurrence with systemic disease progression after remission. Two cases were identified as primary CNS-ATL. The simplified ATL-PI (Prognostic Index) at initial ATL diagnosis for the 28 patients with CNS involvement revealed four cases with high-risk, thirteen with intermediate-risk, two with low-risk, six not eligible due to indolent ATL subtypes, and three cases with unknown risk. The incidence of CNS involvement by ATL subtype was 17.8% (19/107) for acute type, 1.8% (1/54) for lymphoma type, 16.7% (5/30) for chronic type, and 0% for smoldering type (excluding 1 case of unknown subtype and 2 cases of primary CNS-ATL) at ATL diagnosis. At the diagnosis of CNS involvement, 15 (53.6％) patients showed at least 5% of ATL cells in the peripheral blood. During a median observation period of 429 days, the 1-year cumulative incidence of CNS involvement was 12.3% (95% CI 8.3-17.1%). High-dose methotrexate-based therapy was administered to 5 patients with CNS involvement, which had a certain effect on CNS lesions but had limited efficacy for other lesions. All of these cases were treated with concomitant intrathecal chemotherapy. The 2-year overall survival rate after diagnosis of CNS involvement was 16.9% (95% CI 4.9-35.2%). The CNS-IPI (International Prognostic Index) did not predict CNS involvement in ATL. Conclusions: This is the largest study to examine the clinical course of CNS involvement of ATL. The 1-year cumulative incidence of CNS involvement was 12.3%, indicating that CNS involvement is an early complication after diagnosis of aggressive ATL, especially in leukemic subtypes. The prognosis after the diagnosis of CNS involvement was also clarified. The high frequency of CNS involvement during prophylactic intrathecal chemotherapy in patients with ATL without neurological symptoms suggests that it is an important clinical question that needs to be addressed.

Retrospective Review of Patients Treated with Intrathecal Rituximab for Primary and Secondary CNS Lymphoma and Leukemia

Background: Rituximab has been studied and incorporated into the treatment of primary and secondary CNS lymphoma (Grommes 2017; Bobillo 2023). Systemic rituximab, a CD20-targeting monoclonal antibody, is widely used in the treatment of various B-cell malignancies (Klein 2021); however penetration into the central nervous system (CNS) is limited (Petereit 2009; Harjunpää 2001). Although there are conflicting data regarding the efficacy of IV rituximab in primary CNS lymphoma (Schmitt 2019; Ferrari 2022; Bromberg 2019), its role in other B-cell malignancies with CNS involvement has not been adequately described. In particular, its role in treating the cerebrospinal fluid (CSF) space is unclear. The rationale for direct administration of rituximab into the CSF via lumbar puncture or Ommaya reservoir is to allow for consistent treatment of this compartment in order to effectively clear the CSF of lymphoma cells (Kadoch 2014). Limited data exist regarding the efficacy and safety of intrathecal rituximab (Bonney 2011 Aslan 2022; van de Fling 2008; Santiago 2021; Soares 2019). Current intrathecal armamentarium for leptomeningeal lymphoma is very limited and more data on the efficacy and safety of intrathecal rituximab is needed in these patients. Methods: This is a retrospective, single center study of adult patients with a diagnosis of leukemia or lymphoma who received intrathecal (IT) rituximab between 1/1/2016 and 12/31/2022 at Hackensack Meridian Health. Rituximab 25 mg IT was administered weekly either via lumbar puncture or into an Ommaya reservoir. The primary objective of this study was to evaluate the efficacy and safety of IT rituximab. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan Meier method. Descriptive statistics were used to summarize data for categorical and continuous variables. Results: Twelve patients were identified to have received IT rituximab at our institution between 1/1/2016 and 12/31/2022. Median age was 60 years (range 45-81), 54% were male, and 69% white. Disease types included primary CNS lymphoma (67%), diffuse large B-cell lymphoma (17%), PTLD of the CNS (8%), and chronic lymphocytic leukemia (8%). In regards to CNS disease involvement, 58% of patients presented with parenchymal and leptomeningeal disease, 33% with leptomeningeal disease only, and 8% with parenchymal disease only. There were 12 patients who received IT rituximab for the treatment of malignant CNS disease with characteristics and outcomes as shown in Table 1. The median number of IT rituximab treatments administered were 8 (range 2-9). Of the 10 patients evaluable for response, 92% of patients achieved complete response in the CSF following treatment with IT rituximab as evaluated by flow cytometry, cytology, cell count and protein levels in CSF. One patient that did not achieve CSF remission has an unusual case of relapsing/remitting CLL and leukemic meningitis. There were 2 patients unevaluable for response to IT rituximab: one patient received only 2 treatments prior to switching to hospice care; and the other patient had a severe adverse reaction (tightening of throat, flushing, toe numbness) after IT rituximab and was not continued on treatment. At a median follow-up of 19.7 months, median PFS was not reached (NR) (95% CI, 0.5-NR) ( Figure 1). Median OS was 70.1 months (95% CI, 1.2-NR). Six (50%) patients experienced adverse reactions from IT rituximab treatment, including perioral numbness, headache, nausea, and flushing ( Table 1). No treatment-related deaths occurred. One (8%) patient experienced a severe adverse reaction following administration of IT rituximab. This patient developed tightening of the throat, flushing, and toe numbness after the first IT rituximab and symptoms resolved with administration of hydrocortisone and diphenhydramine. No further IT rituximab doses were administered. Another patient experienced a mild reaction consisting of headache, fatigue, nausea, diaphoresis, hypotension, and bradycardia following the fourth dose of IT rituximab in combination with IV rituximab, but was able to complete his treatment course. Conclusions: The use of IT rituximab appears safe and showed promising activity in B cell malignancies, specifically as part of induction in patients with leptomeningeal disease and PCNSL as those patients achieved cytologic response.

Where to Draw Cerebrospinal Fluid from an External Ventricular Drain? Comparison of Cerebrospinal Fluid Parameters between Two Different Collection Sites

Background: High cerebrospinal fluid (CSF) sampling frequency is considered a risk factor for external ventricular drain (EVD)-associated infections. To reduce manipulation at the proximal port and potentially minimize the risk of an infection, we aimed to analyze whether CSF parameters sampled from the far distal collection bag could provide reliable results compared to the proximal port. Methods: We included patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. CSF sampling, including microbiological analysis, was performed simultaneously from the proximal port and the collection bag. Spearman’s correlation coefficients were calculated to assess the correlation of CSF cell count, protein, lactate and glucose between the two sample sites. Results: We analyzed 290 pairs of CSF samples in 77 patients. Ventriculitis was identified in 4/77 (5%) patients. In 3/4 patients, microbiological analysis showed the same bacterial species at both sample sites at the same time. Spearman’s correlation coefficient showed that CSF cell count (r = 0.762), lactate (r = 0.836) and protein (r = 0.724) had a high positive correlation between the two collection sites, while CSF glucose (r = 0.663) showed a moderate positive correlation. Conclusion: This study shows that biochemical CSF parameters can be reliably assessed from the EVD collection bag.

Elevated phospholipids and acylcarnitines C4 and C5 in cerebrospinal fluid distinguish viral CNS infections from autoimmune neuroinflammation

BackgroundViral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions.MethodsWe applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell’s palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison.ResultsOf the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89–0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89–0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial β-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation.ConclusionsChanges in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation.

The role of intrathecal free light chains kappa for the detection of autoimmune encephalitis in subacute onset neuropsychiatric syndromes

Intrathecal synthesis of free light chains kappa (FLCK) is increasingly recognized as a marker of inflammatory CNS pathologies. Here, we tested the performance of FLCK in differentiating autoimmune encephalitis (AIE) from non-inflammatory etiologies in subacute onset neuropsychiatric syndromes. Patients undergoing diagnostic work-up for suspected autoimmune encephalitis at our department between 2015 and 2020 were retrospectively assessed for definitive diagnosis, available CSF and blood samples, as well as complete clinical records. Intrathecal FLCK was measured along with established CSF markers of CNS inflammation. The study cohort consisted of 19 patients with antibody-mediated AIE (AIE+), 18 patients with suspected AIE but without detectable autoantibodies (AIE–), 10 patients with infectious (viral) encephalitis (INE), and 15 patients with degenerative encephalopathies (DGE). 25 age- and sex-matched patients with non-inflammatory neurological diseases (NIND) were used as a control group. All AIE+ patients exhibited intrathecal synthesis of FLCK compared to only 39% of AIE– patients and 81% of patients in the INE group. No intrathecal synthesis of FLCK was found in DGE and NIND patients. While intrathecal FLCK was equally specific for an inflammatory etiology as oligoclonal bands (OCB) in the cerebrospinal fluid (CSF), the sensitivity of intrathecal FLCK for any inflammatory intrathecal process was higher than that of OCB (83% vs. 38%). Intrathecal FLCK synthesis was found to discriminate AIE+ from non-inflammatory encephalopathies and AIE– when the CSF cell count was normal [receiver operating characteristic (ROC) analysis area under the curve (AUC): 0.867, p = 0.002], while it failed to differentiate between AIE+ and INE in the presence of CSF pleocytosis (AUC: 0.561, p = 0.607). In conclusion, in the absence of CSF pleocytosis, intrathecal FLCK discriminated AIE+ from competing diagnoses in our cohort of subacute onset neuropsychiatric syndromes. In addition to established markers of CSF inflammation, intrathecal FLCK might support clinical decision-making and contribute to selecting patients for (repeated) antibody testing.

A-135 Improving Cell Count Turnaround Times With the GloCyte® Automated Cell Counter for CSF: A Retrospective Study at MercyOne Des Moines Medical Center

Abstract Background Accurate, STAT cerebrospinal fluid (CSF) cell counts are critical in the diagnosis of meningitis, malignancy, demyelinating disease, and hemorrhage. Due to historical limitations with the linearity of automated analyzers, CSF cell counts have traditionally been performed manually with a hemocytometer and the aid of a brightfield optical microscope. Manual cell counting is time-consuming, subjective due to reliance on human interpretation, and requires a high degree of skill. This poses significant challenges for clinical laboratories of all sizes facing unprecedented med tech shortages. The purpose of this study was to evaluate the impact of implementing the GloCyte Automated Cell Counter for CSF, an FDA-cleared device with linearity down to 0 cells/µL, on result turnaround times. Methods Result turnaround time data for CSF specimens processed in the hematology lab at MercyOne Des Moines Medical Center, a 600-bed hospital in Des Moines, Iowa, was analyzed in a retrospective study of two cell counting methods- (1) manual cell counting using a Neubauer-Improved hemocytometer and (2) GloCyte, a benchtop cell counting device that uses fluorescence technology and highly specific reagents to automate RBC and TNC cell counts in less than 5 min. Turnaround times for 227 CSF specimens counted manually during an approximately six-month period prior to the implementation of GloCyte (January 2, 2017 to June 29, 2017) were compared to those for 133 specimens analyzed on GloCyte over a similar duration (January 4, 2021 to June 30, 2021). In this study, turnaround times were defined as the time between specimen arrival in the lab and result verification. Correlation between the methods was previously established in the MercyOne Des Moines Medical Center laboratory. Results The data demonstrated a significant, 16–30-minute improvement in turnaround times with GloCyte compared to the manual hemocytometer method. Median turnaround times, analyzed to adjust for add-ons that resulted in longer turnaround times pre- and post-GloCyte implementation, were 1:38h for specimens counted manually vs 1:08 h for specimens analyzed on GloCyte. The average turnaround time for the 227 CSF specimens counted manually was 2:03 h compared to 1:46 h for the 133 samples analyzed on GloCyte. The MercyOne Des Moines Medical Center laboratory processed 456 CSF cell counts in 2022, equating to a reduction in turnaround time of 122–228 h annually with the implementation of GloCyte. Conclusion This study demonstrates that GloCyte can be implemented to significantly improve turnaround times for CSF cell counts. The MercyOne Des Moines Medical Center laboratory realized several benefits from the reduction in turnaround times- GloCyte has (1) freed up significant tech time for other tasks, (2) standardized CSF cell counting to mitigate tech to tech variability, (3) increased lab staff satisfaction and decreased stress levels, and (3) increased physician satisfaction. For MercyOne Des Moines Medical Center’s sister site, MercyOne West Des Moines Medical Center, a 146-bed hospital that infrequently performs CSF cell counts, GloCyte has provided peace of mind in performing cell counts accurately with techs of all skill levels.

A Journey from Schizophrenia to Paraneoplastic Limbic Encephalitis

A 58-year female presented with behavioral changes, dementia, and hallucinations for which she was initially treated as a case of schizophrenia. Later she developed hypersomnolence, speech difficulty and urinary incontinence. She also developed seizures later. On investigations cerebrospinal fluid (CSF) cell count was high and chest x-ray revealed homogeneous opacity over the left upper and midzone. Contrast-enhanced computerized tomography (CECT) Thorax revealed apical segment collapse consolidation with air bronchogram and bilateral pleural effusion. Multiple hepatic and bony metastasis s/o primary bronchoalveolar carcinoma. Osteolytic lesions were also found on skull x-ray and on pelvis x-ray. Tissue diagnosis couldn’t be done as the patient’s general condition deteriorated and the patient left against medical advice. From the above clinical picture and investigation findings, it was diagnosed as a case of paraneoplastic limbic encephalitis.

A hospital-based retrospective study: early recognition of neuronal surface antibodies by clinical manifestations and CSF inflammation indicators in patients with unexplained epilepsy

Background There is a lack of actual and comprehensive data on the detection rate of neuronal surface antibodies in patients with unexplained epilepsy in China. Thus, we attempted to analyze the differences in clinical manifestations, cerebrospinal fluid (CSF) characteristics, seizure types and other aspects of antibody-positive and negative patients, to identify suspected antibody-positive epilepsy patients. Methods In total, 137 inpatients with unexplained epilepsy were consecutively included, and neuronal surface antibodies (NSAbs) were detected by serological and/or CSF evaluations. The clinical features and seizure characteristics were analyzed between the NSAb-positive and negative patients. In addition, patients were divided into four groups based on CSF and blood antibody titers. CSF cell count and protein content were analyzed in relation to antibody titers. Results There were 45 (32.8%) patients tested positive for antibodies. Multivariate analyses revealed that age, mental status changes or memory deterioration, CSF protein, CSF cell count, treatment, days of hospitalization, outcome, duration of symptoms before hospitalization, status epilepticus, and number of antiepileptic drugs were significantly associated with the NSAb-positive group and changes in inflammatory indicators in routine CSF analysis were associated with antibody titers. Conclusions A relatively high proportion of patients with unexplained epilepsy have positive NSAbs. Patients with the above clinical characteristics need to be highly suspected of NSAbs positivity and should be tested for antibodies in time to assist treatment. The decrease of CSF cell count and protein content has suggestive value for the decrease of antibody titer, which should be evaluated in the follow-up.

Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis

PurposeThere is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital.MethodsA retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis.ResultsThe most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956).ConclusionOverall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making.

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.