Cerebrospinal Fluid Cell Count Research Articles

Evaluation of the Microscanner C3 for Automated Cell Counting in Cerebrospinal Fluid Analysis

Background: Cerebrospinal fluid (CSF) analysis is essential for diagnosing various disorders affecting the central nervous system (CNS). Traditionally, CSF cell count analysis is performed manually using a Neubauer chamber hemocytometer, which is labor-intensive and prone to subjective interpretation. Methods: In this study, we evaluated the analytical and clinical performance of the Microscanner C3, an automated cell counting system, for CSF analysis using artificially prepared samples and 150 clinical CSF samples. Results: The lowest detectable white blood cell (WBC) count was 3.33 cells/µL, and the lowest detectable red blood cell (RBC) count was 3.67 cells/µL. The coefficients of variation (CV%) for the Microscanner C3 were lower than those for the Neubauer chamber at all cell concentrations. The correlation coefficients (R) between the Microscanner C3 and conventional methods were high: 0.9377 for WBCs and 0.9952 for RBCs when compared with the Neubauer chamber, and 0.8782 for WBCs and 0.9759 for RBCs when compared with the flow cytometer. Additionally, the Microscanner C3 showed good agreement with both the Neubauer chamber and flow cytometer in the Passing–Bablok regression analysis and Bland–Altman analysis for WBC count at all concentrations and RBC count at concentrations of 0–1000 cells/µL. Conclusions: The Microscanner C3 proved to be more sensitive, precise, and consistent compared to the conventional hemocytometer. The new system is also compact, convenient, and cost-effective, making it a valuable option for clinical laboratories.

A-140 Reducing cell count bias with the GloCyte® Automated Cell Counter for CSF: an observational study at Loyola University Medical Center

Abstract Background Accurate STAT cerebrospinal fluid (CSF) cell counts are critical in supporting diagnoses of meningitis, malignancy, demyelinating disease, and hemorrhage. Limitations of automated analyzers to achieve acceptable linearity for the clinically relevant range has maintained manual CSF cell counting as the preferred method. Manual cell counting, performed with a hemocytometer and bright field microscope, is time-consuming, requires specialized skills and depends on human interpretation. This subjectivity inherently introduces the potential for non-random error in the enumeration of both total nucleated cells (TNC) and red blood cells in CSF by manual methods. The purpose of this study was to evaluate and compare the level of bias inherent in manual determination (TNC) in CSF as compared to the GloCyte Automated Cell Counter. Methods Result bias data for CSF specimens processed in the hematology lab at Loyola University Medical Center, a quaternary care 547-bed academic medical center in Maywood, IL, was analyzed for manual cell counting using a Neubauer-improved hemocytometer and GloCyte, an FDA-cleared cell counting device employing fluorescence technology to automate RBC and TNC counts in under 5 minutes, with linearity down to 0 cells/µL. Result bias was determined by defining the “expected result” for both GloCyte and hemocytometer as the initial cell count determined at a 1:5 dilution of a freshly-collected CSF sample and calculating the expected cell count for subsequent serial dilutions of 1:10, 1:20, 1:50, 1:100 for each method. The actual TNC count and the disparity of the actual result from the expected result was recorded as bias. Results Data are summarized below in the Table, and indicate a lower bias for GloCyte compared to manual counts across the range of dilutions. Conclusions This study demonstrates that GloCyte can be implemented as a means of effectively mitigating the reporting bias of CSF TNC counts performed with a Neubauer-improved hemocytometer.

Cognitive impairments in autoimmune encephalitis: the role of autoimmune antibodies and oligoclonal bands.

The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a pivotal diagnostic marker for multiple sclerosis (MS). These bands play a crucial role in the diagnosis and understanding of a wide array of immune diseases. In this study, we explore the relationship between the cognitive profile of autoimmune encephalitis (AIE) and the presence of OCBs in CSF, with a particular emphasis on NMDA receptor antibodies. We studied a cohort of 21 patients across five tertiary centers, segregated into two distinct categories. One group comprised individuals who tested positive only for autoimmune encephalitis antibodies indicative of encephalitis, while the other group included patients whose CSF was positive for both autoimmune encephalitis antibodies and OCBs. Our investigation focused primarily on cognitive functions and behavioral alterations, supplemented by auxiliary diagnostic assessments such as CSF cell count, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results, evaluated for the two patient groups. To validate our findings, we employed statistical analyses such as Fisher's exact test with Benjamini-Hochberg correction. Our study included 21 patients, comprising 14 who were presented with only autoimmune encephalitis antibodies, and 7 who were dual-positive. Among these patients, we focused on those with NMDA receptor antibodies. Of these, five were dual positive, and nine were positive only for NMDA receptor antibodies. The dual-positive NMDA group, with an average age of 27 ± 16.47 years, exhibited significantly higher CSF cell counts (p=0.0487) and more pronounced language and attention deficits (p= 0.0264). MRI and EEG results did not differ significantly between the groups. Our results point to OCBs as an additional marker of disease severity in AIE, especially in NMDA receptor-antibody positive patients, possibly indicating a broader inflammatory process, as reflected in elevated CSF lymphocytes. Regular testing for OCBs in cases of suspected AIE may aid in disease prognosis and identification of patients more prone to language and attention disorders, improving diagnosis and targeting treatment for these cognitive aspects.

The value of the systemic immune-inflammation index in assessing disease severity in autoimmune encephalitis

Background Autoimmune encephalitis (AE) is a group of autoimmune diseases targeting the central nervous system, characterized by severe clinical symptoms and substantial consumption of medical resources. Neuroinflammation plays a crucial role in disease progression, and detecting inflammatory responses can provide insights into disease status and disease severity. The systemic immune-inflammation index (SII), a novel marker of inflammatory status, has been rarely studied in AE. Methods Retrospective analysis of data from AE patients admitted to the First Affiliated Hospital of Zhengzhou University between January 2019 and September 2023 was conducted. Univariate analysis and logistic regression were used to assess the association between SII and patient severity. Nomograms for predicting AE severity were established, and receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis were employed to evaluate predictive accuracy. Additionally, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was used to assess patient severity. Results This study enrolled 157 patients, of whom 57 were classified as severe according to the CASE score. SII, cerebrospinal fluid (CSF) cell counts, disturbance of consciousness, and behavioural abnormalities independently associated with the occurrence of severe cases. The C-index of the nomograms was 0.87, indicating strong association with disease severity, as supported by the calibration. Additionally, SII levels were highest within seven days of onset and decreased after one month. In subgroup analyses of different antibodies, SII also associations with severe cases in NMDAR encephalitis. Conclusions Higher SII levels are associated with an increased likelihood of developing severe AE, peaking within 7 days of disease onset and decreasing thereafter, potentially offering a prognostic marker to assess disease progression early in its course.

Cerebrospinal fluid soluble CD27 is a sensitive biomarker of inflammation in autoimmune encephalitis

BackgroundAutoimmune encephalitis (AE) comprises a group of rare, severe neuroinflammatory conditions. Current biomarkers of neuroinflammation are often normal in AE which therefore can be difficult to rule out in patients with seizures, cognitive and/or neuropsychiatric symptoms. Cerebrospinal fluid (CSF) soluble CD27 (sCD27) and soluble B-cell maturation antigen (sBCMA) have high sensitivity for neuroinflammation in other neuroinflammatory conditions. In this exploratory study we investigate the potential of sCD27 and sBCMA in CSF as biomarkers of neuroinflammation in AE. MethodsConcentrations of sCD27 and sBCMA were measured in CSF from 40 AE patients (20 patients were untreated (12 with anti-N-Methyl-d-Aspartate receptor antibodies (NMDA) and 8 with anti-Leucine-rich Glioma-Inactivated 1 antibodies (LGI1)), and 37 symptomatic controls (SCs). ResultsCSF concentrations of sCD27 were increased in untreated NMDA AE patients (median 1571 pg/ml; p < 0.001) and untreated LGI1 AE patients (median 551 pg/ml; p < 0.05) compared to SCs (median 250 pg/ml). CSF sBCMA was increased in untreated NMDA AE patients (median 832 pg/ml) compared to SCs (median 429 pg/ml). CSF sCD27 and sBCMA correlated with the CSF cell count. Receiver operating characteristic curve analysis of untreated AE patients versus SCs showed an area under the curve of 0.97 for sCD27 and 0.76 for sBCMA. ConclusionCSF sCD27 is a suitable biomarker of neuroinflammation in AE with an ability to discriminate patients with NMDA AE and LGI1 AE from symptomatic controls. CSF sCD27 may be suited for ruling out AE and other neuroinflammatory conditions in the early phase of the diagnostic work-up.

CSF Neopterin Levels Are Elevated in Various Neurological Diseases and Aging.

Background/Objectives: Cerebrospinal fluid (CSF) neopterin reflects inflammation of the central nervous system (CNS) and is a potentially useful biomarker for neuroinflammatory assessment and differential diagnosis. However, its optimal cut-off level in adult patients with neurological disease has not been established and it has not been adequately studied in controls. We aimed to determine its usefulness as a biomarker of neuroinflammation and the effect of age on its level. Methods: In this retrospective study, CSF neopterin was evaluated in 652 patients in 38 disease groups. Its levels were analyzed with high-performance liquid chromatography with fluorometric detection. Results: A receiver operating characteristic analysis revealed that the optimal cut-off value of 33.57 pmol/mL for CSF neopterin distinguished the control and meningitis/encephalitis groups with a sensitivity of 100.0% and specificity of 94.4%. In the control group, which consisted of 170 participants (99 men and 71 women; mean ± standard deviation age, 52.56 ± 17.99 years), age was significantly positively correlated with CSF protein (r = 0.474, p < 0.001) and CSF neopterin (r = 0.476, p < 0.001) levels but not with CSF cell count (r = 0.144, p = 0.061). Both male and female controls exhibited significant increases in CSF neopterin levels with age. Similarly, the CSF neopterin level was significantly positively correlated with age in patients with amyotrophic lateral sclerosis, independently of disease duration and respiratory function. Conclusions: CSF neopterin levels were elevated in patients with various CNS diseases, reflecting CNS inflammation; they were also elevated with age. Prospective studies are required to establish CSF neopterin as a sensitive biomarker of neuroinflammation.

Targeted metabolomics identifies accurate CSF metabolite biomarkers for the differentiation between COVID-19 with neurological involvement and CNS infections with neurotropic viral pathogens

BackgroundCOVID-19 is primarily considered a respiratory tract infection, but it can also affect the central nervous system (CNS), which can result in long-term sequelae. In contrast to CNS infections by classic neurotropic viruses, SARS-CoV-2 is usually not detected in cerebrospinal fluid (CSF) from patients with COVID-19 with neurological involvement (neuro-COVID), suggesting fundamental differences in pathogenesis.MethodsTo assess differences in CNS metabolism in neuro-COVID compared to CNS infections with classic neurotropic viruses, we applied a targeted metabolomic analysis of 630 metabolites to CSF from patients with (i) COVID-19 with neurological involvement [n = 16, comprising acute (n = 13) and post-COVID-19 (n = 3)], (ii) viral meningitis, encephalitis, or myelitis (n = 10) due to herpes simplex virus (n = 2), varicella zoster virus (n = 6), enterovirus (n = 1) and tick-borne encephalitis virus (n = 1), and (iii) aseptic neuroinflammation (meningitis, encephalitis, or myelitis) of unknown etiology (n = 21) as additional disease controls.ResultsStandard CSF parameters indicated absent or low neuroinflammation in neuro-COVID. Indeed, CSF cell count was low in neuro-COVID (median 1 cell/µL, range 0–12) and discriminated it accurately from viral CNS infections (AUC = 0.99) and aseptic neuroinflammation (AUC = 0.98). 32 CSF metabolites passed quality assessment and were included in the analysis. Concentrations of differentially abundant (fold change ≥|1.5|, FDR ≤ 0.05) metabolites were both higher (9 and 5 metabolites) and lower (2 metabolites) in neuro-COVID than in the other two groups. Concentrations of citrulline, ceramide (d18:1/18:0), and methionine were most significantly elevated in neuro-COVID. Remarkably, triglyceride TG(20:1_32:3) was much lower (mean fold change = 0.09 and 0.11) in neuro-COVID than in all viral CNS infections and most aseptic neuroinflammation samples, identifying it as highly accurate biomarker with AUC = 1 and 0.93, respectively. Across all samples, TG(20:1_32:3) concentration correlated only moderately with CSF cell count (ρ = 0.65), protein concentration (ρ = 0.64), and Q-albumin (ρ = 0.48), suggesting that its low levels in neuro-COVID CSF are only partially explained by less pronounced neuroinflammation.ConclusionsThe results suggest that CNS metabolite responses in neuro-COVID differ fundamentally from viral CNS infections and aseptic neuroinflammation and may be used to discover accurate diagnostic biomarkers in CSF and to gain insights into differences in pathophysiology between neuro-COVID, viral CNS infections and aseptic neuroinflammation.

Breaking Barriers: Unveiling Sex-Related Differences in Cerebrospinal Fluid Analysis-A Narrative Review.

(1) Background: The recent emphasis on sexual and gender diversity's impact on human health underscores the need for tailored diagnostic and therapeutic approaches in neurology. The aim of this article is to conduct a narrative review of the available scientific literature on sex differences in cerebrospinal fluid analysis. (2) Methods: The literature search encompassed PubMed databases, focusing on cerebrospinal fluid analysis and sex differences, considering parameters like cerebrospinal fluid protein content, cell count, albumin quotient (QAlb) and intrathecal IgG synthesis. (3) Results: Nine articles from the past two decades were identified, revealing limited research in this area. Males consistently exhibited higher cerebrospinal fluid protein content and albumin quotient values across various pathologies and age groups. Consequently, males more frequently manifested blood-cerebrospinal fluid barrier dysfunction than females. No significant sex differences were observed in cerebrospinal fluid leukocyte count or intrathecal IgG synthesis. (4) Conclusions: This review highlights the dearth of research on sex differences in cerebrospinal fluid analysis, despite consistent findings of higher protein content and albumin quotient values in males. Revisiting current diagnostic thresholds based on sex is crucial for accurate prognosis and personalised treatment strategies in neurological disorders. Moving towards sex-specific approaches in clinical practice is imperative for advancing personalised medicine.

Red blood cell count in cerebrospinal fluid was correlated with inflammatory markers on the seventh postoperative day and all associated with the outcome of aneurysmal subarachnoid hemorrhage patients.

Exploring factors associated with the outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) has become a hot focus in research. We sought to investigate the associations of inflammatory markers and blood cell count in cerebrospinal fluid with the outcome of aSAH patients. We carried a retrospective study including 200 patients with aSAH and surgeries. The associations of neutrophil, lymphocyte, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII), system inflammation response index (SIRI), and blood cell count in cerebrospinal fluid on the 1st and 7th postoperative days with the outcome of aSAH patients were investigated by univariate analysis and multivariate logistic regression model. According to the modified Rankin scale (mRS) score, there were 147 patients with good outcome and 53 patients with poor outcome. The neutrophil, NLR, SIRI, and SII levels on the seventh postoperative day in patients with poor outcome were all significantly higher than patients with good outcome, P < 0.05. The multivariate logistic regression model including inflammatory markers and blood cell counts in cerebrospinal fluid on the 1st postoperative day confirmed that red blood cell count in cerebrospinal fluid (≥177 × 109/L; OR: 7.227, 95% CI: 1.160-45.050, P = 0.034) was possibly associated with poor outcome of aSAH patients, surgical duration (≥169 min), Fisher grade (III-IV), hypertension, and infections were also possibly associated with the poor outcome. The model including inflammatory markers and blood cell counts in cerebrospinal fluid on the 7th postoperative day confirmed that red blood cell count in cerebrospinal fluid (≥54 × 109/L; OR: 39.787, 95% CI: 6.799-232.836, P < 0.001) and neutrophil-lymphocyte ratio (≥8.16; OR: 6.362, 95% CI: 1.424-28.428, P = 0.015) were all possibly associated with poor outcome of aSAH patients. The NLR (r = 0.297, P = 0.007) and SIRI (r = 0.325, P = 0.003) levels were all correlated with the count of red blood cells in cerebrospinal fluid. Higher neutrophil-lymphocyte ratio and higher red blood cell count in cerebrospinal fluid were all possibly associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage. However, we need a larger sample study.

Contributions of CSF interleukin-6 elevation to the pathogenesis of myelin oligodendrocyte glycoprotein antibody–associated disease

Background: Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is a rare neuroinflammatory disorder characterized by acute episodes of central nervous system (CNS) demyelination. Previous studies have reported elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) of MOGAD patients. Objective: We examined if CSF IL-6 level increase is associated with clinical parameters in MOGAD. Methods: IL-6 levels were measured using 44 CSF samples during the acute phase and 6 samples during recovery from 34 MOGAD patients, as well as 65 CSF samples from 45 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4Ab + NMOSD), 107 samples from 76 multiple sclerosis patients, and 45 samples from neurodegenerative disease patients. Associations between IL-6 levels and clinical parameters in MOGAD were also evaluated. Results: CSF IL-6 levels were significantly comparably elevated during acute-phase in MOGAD and AQP4Ab + NMOSD, but declined following the acute phase. Among MOGAD patients, CSF IL-6 level was significantly correlated with CSF cell count, greater in patients with brain lesions than spinal cord lesions, and higher in CSF than serum, suggesting that excessive IL-6 is produced predominantly in CNS. Neurological recovery was tended to be poorer in MOGAD patients with higher CSF IL-6 level. Conclusion: CSF IL-6 may play important roles in the pathogenesis of MOGAD, especially in CNS inflammation.

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.

A Clinicopathological study of Guillain-Barrḗ Syndrome in a Tertiary Level Hospital

Background: Guillain-Barre syndrome (GBS) stands out as the most prevalent autoimmune neurological disorder. This investigation involves a comparative analysis of clinical observations, neurophysiological assessments, and cerebrospinal fluid examination, outcomes among patients with GBS. Method: A retrospective review of medical records constituted the methodology for this study, spanning from July 1, 2023, to December 31, 2023. Sociodemographic traits, antecedent illnesses, clinical progression, laboratory results, therapeutic interventions, and ultimate outcomes were assessed and compared among the study participants. Results: The study encompassed 8 patients, with an average age of 42.75 years. Respiratory complications were evident in 87.5% of the patients. In CSF analysis, 62.50% exhibited a normal cell count, while 37.50% displayed an elevated count. Elevated CSF protein levels were observed in 50% of patients, with a corresponding 50% revealing normal CSF protein levels. Increased CSF protein was associated with delayed lumbar puncture, demyelinating nerve conduction study subtype, and sensory motor variant. Regarding treatment modalities, 37.5% received intravenous immunoglobulin, and 25% underwent plasma exchange therapy. The acute phase of the disease resulted in a 25% mortality rate among patients. Conclusion: Guillain-Barre syndrome manifests diverse clinical presentations and laboratory findings. Notably, a high cerebrospinal fluid cell count challenges the widely accepted Brighton criteria for GBS diagnosis. Further investigations are warranted to elucidate the correlation between elevated CSF cell count and other factors influencing pathogenesis and outcomes in GBS patients. Bangladesh Crit Care J March 2024; 12 (1): 25-28

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.