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Introduction: HaNDL syndrome is a transient and rare condition that presents with neurological deficit and headache accompanied by lymphocytosis on cerebrospinal fluid (CSF) analysis. It is usually characterized by spontaneous recovery without neurological sequelae. This is a benign condition, which has not yet been adequately defined and includes many diseases in the differential diagnosis. We indicated 2 different cases that applied with acute neurological findings., Case Report: Two patients who were admitted to our hospital with transient neurological deficits and headaches were evaluated. There was no significant pathology in cranial imaging and EEG reports. Lymphocytic pleocytosis was observed in CSF. Patients were followed up with attacks but were discharged without deficits. We diagnosed the patients with HaNDL syndrome with clinical features, imaging, and laboratory findings., Conclusion: HaNDL is an underdiagnosed syndrome and it should be considered especially for young patients with headaches is prominent without a risk factor for ischemia, recurrent episodes with neurological symptoms, CSF pleocytosis, and normal imaging findings.Therefore, we wanted to raise awareness for the existence of this rare disease which is a waste of time by performing unnecessary tests and therapies during the diagnosis period., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: There 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., Methods: A 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., Results: The 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)., Conclusion: Overall, 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., (© 2023. The Author(s).)

Background: Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease., Methods: Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation., Results: Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis., Conclusion: EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Difficulty in interpreting white blood cell (WBC) counts in cerebrospinal fluid (CSF) complicates the diagnosis of neonatal meningitis in traumatic lumbar punctures (LP). The aim of our study was to determine the correction factor for WBC counts in traumatic LP that offers the greatest diagnostic efficacy in meningitis., Methods: We conducted a retrospective observational study of LP in neonates between January 2014 and December 2020. Traumatic LP was defined as a red blood cell (RBC) count ≥ 1,000 cells/mm 3 CSF and pleocytosis as WBCs ≥ 20 cells/mm 3 CSF. The CSF RBC:WBC ratio was analyzed by linear regression to determine a new correction factor. Cell count adjustments were also studied using the 500:1, the 1,000:1 ratio method, and the peripheral blood RBC:WBC ratio, using ROC curves and studies of accuracy (sensitivity and specificity)., Results: Overall, 41.0% of the 1,053 LPs included in the study were traumatic. The best results for effective WBC correction were the method based on the peripheral blood ratio (sensitivity = 1.0 and specificity = 0.9 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.9 for viral meningitis) and the 400:1 ratio (sensitivity = 1.0 and specificity = 0.8 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.8 for viral meningitis) obtained from linear regression (95% CI 381.7-427.4; R2 = 0.7)., Conclusion: Both the peripheral blood correction and the 400:1 correction reduce the number of neonates classified with pleocytosis who were not eventually diagnosed with meningitis. Both methods might be a useful tool to clarify the neonatal meningitis diagnosis, offering neonatologists the possibility to assess the WBC count in traumatic LP., (© 2022. The Author(s).)

Objectives: Many patients with meningitis have no aetiology identified leading to unnecessary antimicrobials and prolonged hospitalisation. We used viral capture sequencing to identify possible pathogenic viruses in adults with community-acquired meningitis., Methods: Cerebrospinal fluid (CSF) from 73 patients was tested by VirCapSeq-VERT, a probe set designed to capture viral targets using high throughput sequencing. Patients were categorised as suspected viral meningitis - CSF pleocytosis, no pathogen identified (n = 38), proven viral meningitis - CSF pleocytosis with a pathogen identified (n = 15) or not meningitis - no CSF pleocytosis (n = 20)., Results: VirCapSeq-VERT detected virus in the CSF of 16/38 (42%) of those with suspected viral meningitis, including twelve individual viruses. A potentially clinically relevant virus was detected in 9/16 (56%). Unexpectedly Toscana virus, rotavirus and Saffold virus were detected and assessed to be potential causative agents., Conclusion: VirCapSeq-VERT increases the probability of detecting a virus. Using this agnostic approach we identified Toscana virus and, for the first time in adults, rotavirus and Saffold virus, as potential causative agents in adult meningitis. Further work is needed to determine the prevalence of atypical viral candidates as well as the clinical impact of using sequencing methods in real time. This knowledge can help to reduce antimicrobial use and hospitalisations leading to both patient and health system benefits., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Status epilepticus (SE) has traditionally been thought to cause cerebrospinal fluid (CSF) pleocytosis. However, attributing CSF pleocytosis solely to SE without addressing the underlying etiology may lead to poor outcomes. Leukocyte recruitment to CSF has been shown to peak around 24 hours after prolonged seizures in animal studies, suggesting that CSF pleocytosis within the first 24 hours of SE onset may be due to underlying causes. The goal of this study is to assess if SE is associated with CSF pleocytosis, independent of other causes within the first 24 hours of onset., Methods: We completed a historical cohort study of adult patients with SE admitted to the intensive care unit of Vancouver General Hospital between March 2010 and May 2019., Results: Of the 441 patients admitted with SE during the study period, 107 met our inclusion criteria leading to 111 lumbar punctures (LPs), with 4 patients receiving two LPs. CSF pleocytosis was seen in 12 of 72 patients who underwent an LP within the first 24 hours of SE onset. In all 12 patients, a secondary etiology for the pleocytosis was observed aside from SE. Of the six CSF samples collected after 24 hours of onset that demonstrated pleocytosis, four had no cause for pleocytosis other than SE., Conclusions: In all 12 patients with CSF pleocytosis in the first 24 hours of onset of SE, an underlying etiology was identified. Therefore, any pleocytosis noticed within the first 24 hours of onset of refractory SE should not be attributed solely to SE.

Objectives: To describe the epidemiology, age at infection, clinical characteristics and outcome of listeria infection in young infants to inform management and empiric antibiotic choice in young infants., Design: Prospective 2-year surveillance of Listeria monocytogenes infection in young infants detected through the British Paediatric Surveillance Unit 'orange card' system and triangulated with the public health laboratories., Setting: National population study (England, Wales, Scotland and the Ireland) PATIENTS: All infants under 90 days with proven or probable invasive listeriosis MAIN OUTCOME MEASURES: Incidence, mortality, age of infection, clinical characteristics and outcome RESULTS: During a 2-year period (2017-2019), 27 cases of listeriosis in infants <90 days of age were reported. The incidence of listeriosis in this study was 1.8 per 100 000 live births with 7% mortality (2/27). Nearly all cases presented within the first 24 hours of life (26/27). The majority (20/27, 74%) were born preterm and 16/24 (67%) were born to women from ethnic minority backgrounds., Conclusions: Invasive listeriosis in young infants in the UK and Ireland is rare and presents early in the neonatal period. National guidelines that recommend the use of amoxicillin as part of empiric regimes for sepsis and meningitis in infants over 1 month of age should be modified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection., Methods: In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively., Results: Of all infants included, 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43)., Conclusions: A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Andrea Cruz is an associate editor for Pediatrics. The other authors have no relevant conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Rationale: Aseptic meningoencephalitis is a rare central nervous system complication of relapsing polychondritis (RP)., Patient: We report a 61-year-old Japanese male patient with spiking fever and impaired consciousness. Neurological examination revealed meningealirritation, and cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis with elevated protein (199 mg/dL) and interleukin-6 (3810 pg/mL). Serological analysis showed high levels of anti-type II collagen antibodies, and the result of auricular biopsy was consistent with the diagnosis of RP showing cartilage degeneration surrounded by inflammatory cell infiltrations., Diagnosis: A clinical diagnosis of RP was made according to the diagnostic criteria established by MacAdams et al., Intervention: Steroid pulse therapy (methylprednisolone 1000 mg, consecutive 3 days) followed by oral prednisolone (60 mg/day) resolved the patient's high fever and disturbance of consciousness., Outcomes: The patient rapidly improved after steroid treatments and has a normal quality of life under the maintenance dose of steroid plus methotrexate (4 mg/week)., Lessons: RP-associated meningoencephalitis is a rare complication with significant morbidity and mortality. It should be considered and differentiated in patients with RP with unexplained spiking fever and impaired consciousness. In addition, the assessment of cerebrospinal fluid interleukin-6 levels may be useful to investigate the disease activity of RP-related meningoencephalitis. Further prospective studies are required to confirm this result., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The outcome of neuroborreliosis (NB) is variable and may partially depend on host-related immune factors. In NB, the cerebrospinal fluid (CSF) contains a large population of T lymphocytes, but the mechanisms and consequences of their recruitment have not been fully elucidated. We have studied expression of T lymphocyte chemoattractant cytokines in association with CSF cytometric parameters and clinical data in NB patients., Methods: The blood and CSF of 17 patients with NB and blood of 12 patients with erythema migrans (EM) were obtained before the antibiotic administration, and in fraction of NB patients during and/or after antibiotic treatment. The control samples came from blood donors (blood) and patients in whom neuroinfection was excluded by a lumbar puncture (CSF). Concentrations of IL-16, CXCL9, CXCL10, CXCL11, CCL2 and CCL5 in serum and CSF were measured with commercial ELISA. Data were analyzed with non-parametric tests, p < 0.05 considered significant., Results: The serum concentrations of IL-16, CXCL9, CXCL10 and CCL5 were increased, higher in NB than in EM. In CSF all the cytokines were upregulated, CXCL10, CXCL9 and IL-16 over ten-fold. The CSF concentration index favored the intrathecal synthesis of all the cytokines except CCL5, for which it could not be reliably estimated. CCL2, CXCL10 and CXCL9 created concentration gradients towards CSF. The intrathecal expression of IL-16, CCL5 and CXCL9 correlated with CSF lymphocyte counts, of IL-16, CXCL9 and CXCL10 - with a blood-brain barrier disruption, and of CXCL9 and CXCL10 with intrathecal specific IgG synthesis. The expression of CCL2, CXCL10 and CXCL11 peaked early after NB onset and decreased naturally afterwards. High initial CSF CXCL9, CXCL10 and CXCL11 levels associated with a persistent CSF pleocytosis and BBB disruption after treatment, but no cytokine was predictive of clinical outcome. In follow up (post-treatment) examinations, CSF CXCL10 and CCL5 associated positively and CCL2 negatively with a protracted lymphocytic pleocytosis., Conclusions: Several cytokines chemotactic for T lymphocytes are upregulated intrathecally in NB, with different dynamics and relation to other inflammatory parameters, suggesting their distinct pathogenetic roles. CXCL10 and CXCL9 are vividly upregulated and seem deeply involved in the pathogenesis of the intrathecal inflammation. IL-16 and CCL5 may directly drive T lymphocyte migration from periphery, but their ability to create an adequate chemotactic gradient remains to be confirmed. A delayed normalization of pleocytosis is accompanied by higher intrathecal expression of Th1-related and lower of Th2-related chemokines, in agreement with the protective role of Th1 to Th2 transition in the course of NB., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations., Methods: Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated., Results: Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients., Conclusions: In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Background: Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of CSF findings in patients with COVID-19 to understand prognosis and explore therapeutic options., Methods: We searched PubMed, Google Scholar, and Scopus databases using the keywords "SARS-CoV-2 in cerebrospinal fluid" and "SARS-CoV-2 and CNS Complications"" for reports of CSF findings in COVID-19 related neurological manifestations. Descriptive analyses were conducted to observe the CSF protein and cell counts based on age, gender, severity, fatality of COVID-19, and whether central (CNS) or peripheral nervous system (PNS) was associated., Results: A total of 113 patients were identified from 67 studies. Of these, 7 patients (6.2%) were fatal COVID-19 cases and 35 patients (31%) were considered severe COVID-19 cases. CSF protein was elevated in 100% (7/7) of the fatal cases with an average of 61.28 mg/dl and in 65.0% (52/80) in non-fatal cases with an average 56.73 mg/dl. CSF protein levels were elevated in 74.5% (38/51) patients with non-severe COVID-19 and 68.6% (24/35) in those with a severe COVID-19 infection. CSF cell count was increased in 43% of fatal cases, 25.7% severe cases, and 29.4% of non-severe cases., Conclusion: Our analysis showed that the most common CSF findings situation in COVID-19 infection is elevated protein with, very occasionally, mild lymphocyte predominant pleocytosis. Further studies to elucidate the pathophysiology of neurological complications in COVID-19 are recommended., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We report a 60-year-old woman who developed spinal cord infarction (SCI) with anti-aquaporin (AQP) 4 antibody seropositive. She was admitted to our hospital with acute onset of flaccid paraparesis and urinary disturbances that completed within a few minutes after acute pain in her lower back. Neurological examination revealed flaccid paraparesis, bladder and bowel dysfunction and dissociated sensory loss below the level of Th11 spinal cord segment. Diffusion weighted imaging (DWI) and T 2 -wighted imaging (T 2 WI) of thoracic spine MRI showed high signal intensity in the spinal cord between Th9 and Th12 vertebral levels with decreased apparent diffusion coefficient (ADC). We diagnosed her as having SCI. Thereafter the serum examination on admission was reported as positive for anti-aquaporin 4 (AQP4) antibody. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, and the spinal cord lesions became enlarged in MRI on 12 days after the onset. We, therefore, suspected that the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) accompanied SCI. The patient underwent two courses of high dose intravenous methylprednisolone (IVMP) for three days (1 g/day). Her neurological symptoms did not improve significantly, but the size of T 2 WI MRI high signal lesion improved to that of the initial MRI scan. Anti-AQP4 antibody seropositivity may have modified the SCI pathology in the present patient.

In December 2019, a new coronavirus infection was identified in China. Although the clinical presentation of COVID-19 is predominantly respiratory, more than 35%% of patients have neurological symptoms. We report an elderly female with asthenia, dry cough, anosmia, ageusia, fever, nausea, and a severe and persistent headache. She had confirmed COVID-19 using the nasal swab RT-PCR technique. Her cranial tomography was normal. The CSF analysis demonstrated a cell count of 21 cells/mm 3 (80% lymphocytes and 20% monocytes), 34 mg/dl protein, and 79 mg/dl glucose. She improved after 4 days. Our report draws attention to the meningeal involvement of SARS-Cov-2.

To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes ( p < 0.01) and a more frequent quantitative intrathecal IgM synthesis ( p = 0.001 and p < 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included ( p < 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present.

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed longitudinally. We suggest that HZ provides a 'model' of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology provoked local HIV-1 production by enhanced trafficking or activation of HIV-1-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determined the plasma HIV-1 RNA concentrations, in this setting the CSF WBC counts established the relation of the CSF HIV-1 RNA levels to this plasma set-point., Competing Interests: LH, RWP, DF, MG no competing interests. HZ has served at scientific advisory boards for Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Biogen and Alzecure, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg (all outside submitted work). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Meningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of hours to several days. Delay in treatment can lead to serious outcomes. Inflammation of the meninges is assessed by analysing cerebrospinal fluid. Identifying the pathogen in cerebrospinal fluid is another way to diagnose meningitis. Cerebrospinal fluid is collected by doing a lumbar puncture, which is an invasive test, and can be avoided if a physical examination excludes the diagnosis of meningitis. However, most physical examinations, such as nuchal rigidity, Kernig's test, and Brudzinski's test, are not sufficiently sensitive to exclude meningitis completely. Jolt accentuation of headache is a new and less well-recognised physical examination, which assesses meningeal irritation. It is judged as positive if the headache is exacerbated by rotating the head horizontally two or three times per second. A 1991 observational study initially reported high sensitivity of this examination to predict pleocytosis. Pleocytosis, an abnormally high cerebrospinal fluid sample white cell count, is an accepted indicator of nervous system infection or inflammation. Jolt accentuation of headache may therefore accurately rule out meningitis without the use of lumbar puncture. However, more recent cross-sectional studies have reported variable diagnostic accuracy., Objectives: To estimate the diagnostic accuracy of jolt accentuation of headache for detecting acute meningitis in emergency settings. Secondary objectives: to investigate the sources of heterogeneity, including study population, patient condition, and types of meningitis., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Elsevier) to 27 April 2020. We searched ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web Version 5.0 to 28 April 2020., Selection Criteria: We included cross-sectional studies that assessed the diagnostic accuracy of jolt accentuation of headache for people with suspected meningitis in emergency settings. We included participants of any age and any severity of illness. Meningitis should be diagnosed with any reference standard, such as cerebrospinal fluid pleocytosis, proof of causative agents, or autopsy., Data Collection and Analysis: Two review authors independently collated study data. We assessed methodological quality of studies using QUADAS-2 criteria. We used a bivariate random-effects model to determine summary estimates of sensitivity and specificity where meta-analysis was possible. We performed sensitivity analyses to validate the robustness of outcomes. We assessed the certainty of the evidence using the GRADE approach., Main Results: We included nine studies (1161 participants). Five studies included only adults. Four studies included both adults and children; however, the proportion was not reported in three of these studies. The youngest child reported in the studies was aged 13 years. There was no study including only children. The reference standard was pleocytosis in eight studies, and the combination of pleocytosis and increased protein in the cerebrospinal fluid in one study. Two studies also used smear or positive culture of cerebrospinal fluid. Risk of bias and concern about applicability was high in the participant selection domain for all included studies and the consciousness subgroup. Overall, pooled sensitivity was 65.3% (95% confidence interval (CI) 37.3 to 85.6), and pooled specificity was 70.4% (95% CI 47.7 to 86.1) (very low-certainty evidence). We established the possibility of heterogeneity from visual inspection of forest plots. However, we were unable to conduct further analysis for study population, types of meningitis, and participants' condition, other than disturbance of consciousness (a secondary outcome). Amongst participants whose consciousness was undisturbed (8 studies, 921 participants), pooled sensitivity and specificity were 75.2% (95% CI 54.3 to 88.6) and 60.8% (95% CI 43.4 to 75.9), respectively (very low-certainty evidence)., Authors' Conclusions: Jolt accentuation for headache may exclude diagnoses of meningitis in emergency settings, but high-quality evidence to support use of this test is lacking. Even where jolt accentuation of headache is negative, there is still the possibility of acute meningitis. This review identified the possibility of heterogeneity. However, factors that contribute to heterogeneity are incompletely understood, and should be considered in future research., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Raised white cell count (WCC) in lumbar CSF is a commonly used marker of meningitis. The effect of cranial neurosurgery per se on lumbar WCC is not established. At this single centre, many patients undergo ICPM followed by lumboperitoneal shunt (LPS), with lumbar CSF WCC samples taken during insertion. We aimed to determine the effect of ICP bolt insertion on lumbar CSF WCC. We undertook a retrospective analysis of lumbar CSF samples in patients who had recently undergone 24-h ICPM. Thirty-three patients (16F:7M) aged 43.31 ± 12.1 years (mean ± SD) had lumbar CSF samples after ICPM. Fourteen had CSF sampled within 6 weeks and 19 after 6 weeks of ICPM. Twenty-five samples were taken during LPS insertion, 5 during lumbar drainage/puncture and 3 during LPS revision. All 33 patients were afebrile at the point of CSF sampling. The mean lumbar WCC within 6 weeks of ICPM was significantly higher than the mean lumbar WCC after 6 weeks, being 15.4 ± 18.0 and 2.32 ± 1.79 cells/microlitre respectively respectively. There was no significant increase in RBC. In patients with raised CSF WCC, 60% of raised WCC were predominantly lymphoctyes and 40% predominantly neutrophils. Only one patient grew an organism (S. aureus). We conclude that lumbar CSF WCC can be raised following minor intracranial surgery, despite no clinical sign of infection. We caution against using lumbar CSF WCC values independently as the only marker of infection following neurosurgery., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon., Methods: Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR., Results: Twenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae., Conclusion: VZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the characteristic clinical and spinal MRI phenotypes of sarcoidosis-associated myelopathy (SAM), we analyzed a large cohort of patients with this disorder., Methods: Patients diagnosed with SAM at a single center between 2000 and 2018 who met the established criteria for definite and probable neurosarcoidosis were included in a retrospective analysis to identify clinical profiles, CSF characteristics, and MRI lesion morphology., Results: Of 62 included patients, 33 (53%) were male, and 30 (48%) were African American. SAM was the first clinical presentation of sarcoidosis in 49 patients (79%). Temporal profile of symptom evolution was chronic in 81%, with sensory symptoms most frequently reported (87%). CSF studies showed pleocytosis in 79% and CSF-restricted oligoclonal bands in 23% of samples tested. Four discrete patterns of lesion morphology were identified on spine MRI: longitudinally extensive myelitis (n = 28, 45%), short tumefactive myelitis (n = 14, 23%), spinal meningitis/meningoradiculitis (n = 14, 23%), and anterior myelitis associated with areas of disc degeneration (n = 6, 10%). Postgadolinium enhancement was seen in all but 1 patient during the acute phase. The most frequent enhancement pattern was dorsal subpial enhancement (n = 40), followed by meningeal/radicular enhancement (n = 23) and ventral subpial enhancement (n = 12). In 26 cases (42%), enhancement occurred at locations with coexisting structural changes (e.g., spondylosis)., Conclusions: Recognition of the clinical features (chronically evolving myelopathy) and distinct MRI phenotypes (with enhancement in a subpial and/or meningeal pattern) seen in SAM can aid diagnosis of this disorder. Enhancement patterns suggest that SAM may have a predilection for areas of the spinal cord susceptible to mechanical stress., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Neurotuberculosis usually responds well to standard antitubercular therapy. Some; patients have prolonged course A 11 year old boy diagnosed TBM, an immunocompetent patient, had an unusual course of illness in the form of prolonged fever, persistent hyponatremia and CSF; pleocytosis despite adequate treatment. Clinical course in the management of TBM can be; protracted with complications despite adequate therapy., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

The aims of this study were to investigate the frequency of HIV-1 RNA level discordance between the cerebrospinal fluid (CSF) and plasma and of CSF viral escape (CVE) in patients with HIV-1 subtype C on antiretroviral therapy, and evaluate the CSF white blood cell (WBC) performance characteristics in predicting CSF discordance in HIV+ group and the frequency of cognitive impairment in individuals with CSF HIV discordance or escape. HIV-1 RNA levels were assessed in plasma and CSF samples from 68 HIV+ participants without opportunistic infection. CSF discordance was found in 7.4% and CVE in 10%, with comparable frequencies between HIV-1B and C. Twenty samples (29%) showed increased CSF WBC counts. This group had higher CSF and plasma HIV-1 RNA levels than the group with normal WBC counts (p < 0.0001 and 0.006, respectively). The odds of CSF discordance were 18 times higher for a person with CSF WBC count of > 5 cells/mm 3 than the group with normal CSF WBC count. CSF WBC counts (cut-off of 15 cells/mm 3 ) showed high-performance characteristics as a predictive biomarker of CSF discordance (AUC the ROC curve 0.98). The frequency of cognitive impairment for CSF escape or discordance was 83% and 80%. The odds of cognitive impairment in these groups were 19 and 15 times higher than those for an HIV(-) person. Viral discordance or escape in the CNS occurs at a comparable frequency for HIV-1C and HIV-1B. The CSF WBC count was effective as a predictive biomarker of CSF and plasma discordance.

Narcolepsy-type 1 is a neurological sleep-disorder caused by a selective loss of hypothalamic orexin/hypocretin-producing neurons whose underlying mechanism is considered to be immune-mediated. We report the case of a 16 year-old girl with excessive daytime sleepiness, hypnagogic/hypnopompic hallucinations and cataplexy, fulfilling narcolepsy-type 1 diagnostic criteria. She was HLA-DQB1*06:02/DQA1*01:02 positive. CSF analysis demonstrated positive IgG oligoclonal bands, pleocytosis and hypocretin-1 below detection limit. Other autoimmune processes were excluded, including autoimmune encephalitis. After treatment with intravenous immunoglobulins sleep-related hallucinations transiently improved for a month. This case's CSF inflammatory findings support the role of neuroinflammation in narcolepsy-type 1 development in genetically predisposed patients., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To investigate the association of serum neurofilament light chain (sNfL) levels with CSF parameters in clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS), taking into account radiologic and clinical parameters of disease activity., Methods: Simultaneously collected serum and CSF samples of 112 untreated patients newly diagnosed with CIS or RRMS were included in this cross-sectional study. CSF parameters were obtained as part of routine diagnostic tests. sNfL levels of patients and of 62 healthy donors were measured by highly sensitive single molecule array (SiMoA) immunoassay., Results: Patients with RRMS (n = 91, median 10.13 pg/mL, interquartile range [IQR] 6.67-17.77 pg/mL) had higher sNfL levels than healthy donors (n = 62, median 5.25 pg/mL, IQR 4.05-6.81 pg/mL, p < 0.001) and patients with CIS (n = 21, median 5.69 pg/mL, IQR 4.73-9.07 pg/mL, p < 0.001). Patients positive for oligoclonal bands (OCBs) (n = 101, median 9.19 pg/mL, IQR 6.34-16.38 pg/mL) had higher sNfL levels than OCB-negative patients (n = 11, median 5.93 pg/mL, IQR 2.93-8.56 pg/mL, p = 0.001). sNfL levels correlated with CSF immunoglobulin G (IgG) levels ( r = 0.317, p = 0.002), IgG ratio (QIgG) ( r = 0.344, p < 0.001), and CSF leukocyte count ( r = 0.288, p = 0.002). In linear regression modeling, the CSF leukocyte count combined with the number of contrast-enhancing lesions in MRI predicted sNfL levels best., Conclusions: In active MS, sNfL levels correlate with intrathecal pleocytosis and IgG synthesis, indicating that axonal damage is associated with both acute and chronic CNS-intrinsic inflammation., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Cryptococcal meningitis commonly affects immunocompromised cases and can have varied presentation. In some instances, the presence of a plethora of inflammatory cells on cerebrospinal fluid (CSF) in an immunosuppressed patient can lead to further investigations, which unravel the presence of cryptococcal meningitis. The aim of this retrospective study was to analyze the spectrum of CSF findings of immunosuppressed patients who were diagnosed to have cryptococcal meningitis. Retrospective analysis of CSF cytospin slides exhibiting pleocytosis and belonging to immunocompromised patients was performed, and these cases were found to have cryptococcal meningitis. Out of 932 cases of CSF (January 2016-July 2017), 10 had pleocytosis and 5 of these 10 cases demonstrated spores of Cryptococcus. Male-to-female ratio was 1:1.5. All the patients were immunocompromised and had CSF leukocytosis. Lymphocytes and monocytes were present in all samples while only one case showed plasma cells. Spores of Cryptococcus were also noted in all the cases and highlighted on India Ink Preparation and Gomori Methenamine Silver stain. All the cases were positive for agglutination-based cryptococcal antigen assay, except one where the test was not done. All immunosuppressed patients having pleocytosis in CSF were found to have cryptococcal infection. Therefore, pleocytosis in CSF in any immunosuppressed patient should raise the suspicion of cryptococcal meningitis. The pathologist and the clinician need to be vigilant in such scenarios to rule out any opportunistic infection and investigate the patient thoroughly for any underlying immunosuppression., (© 2019 Wiley Periodicals, Inc.)

To evaluate occurrence and extent of CSF CXCL13 elevations beyond Lyme neuroborreliosis, we investigated CXCL13 in an unselected patient cohort with neuroinflammatory disease. From March 2016 to March 2017, 180 in-patients with CSF pleocytosis were categorized into following groups: pyogenic CNS infections, aseptic meningoencephalitis, neuroimmunological diseases, and reactive pleocytosis. We provide evidence that CXCL13 elevation occurs at variable extent in the majority of neuroinflammatory diseases. The exact role of CXCL13 in CSF is elusive, but the broad occurrence in neuroinflammation points at CNS immune activation, which is not exclusive for LNB., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In 4292 infants aged ≤60 days with cerebrospinal fluid (CSF) pleocytosis, the bacterial meningitis score had excellent sensitivity (121 of 121 [100.0%] [95% confidence interval, 96.5%-100.0%]) but low specificity (66 of 4171 [1.6%] [95% confidence interval, 1.3%-2.0%]) and therefore should not be applied clinically to infants in this age group., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lyme borreliosis (LB) is a common cause of acute facial palsy in children living in endemic areas for Borrelia burgdorferi. The need for lumbar puncture in diagnostics of LB in children with facial palsy has been questioned. Our aim was to evaluate the prevalence of LB and the diagnostic value of a cerebrospinal fluid (CSF) sample among children with an acute facial palsy., Methods: We collected medical records and laboratory data of children and adolescents 0-16 years of age (n = 94) diagnosed with facial palsy between 2002 and 2016 in the Turku University Hospital. A positive B. burgdorferi serology in serum or CSF or a positive B. burgdorferi polymerase chain reaction in CSF were considered as signs of definite LB. C-X-C motif chemokine ligand 13 (CXCL13) values were measured in CSF samples from 28 children during 2014-2016., Results: Lumbar puncture was performed on 84 of 94 children with facial palsy. LB was confirmed in 29 of 42 children with, and in 4 of 42 without, pleocytosis. The sensitivity and specificity of pleocytosis to predict LB were 88% (95% confidence interval, 78%-98%) and 75% (62%-88%), respectively, and the positive and negative predictive values were 69% (55%-83%) and 90% (81%-99%), respectively. An increased CSF CXCL13 value had 67% (51%-83%) sensitivity and 100% specificity for LB., Conclusions: Because serum serology can be negative at presentation, lumbar puncture is a valuable tool when diagnosing LB among children with facial palsy. Pleocytosis and increased protein and CXCL13 values in the CSF suggest LB as the cause of facial palsy.

We reported a severe human pseudorabies encephalitis case and described a dynamic clinical manifestation with cerebrospinal fluid analyses and cytological and serological evaluation, which may elucidate the mechanism of PRV infection and facilitate clinical diagnosis and treatment in human., (© 2019 Blackwell Verlag GmbH.)

Objective: Primary CNS Vasculitis (PCNSV) is a rare disease that is often challenging to diagnose. Cerebral angiography and biopsy have been utilized in the diagnostic workup for several decades but limited literature reports on the concordance of findings of angiography and biopsy. The primary objective of this work was to examine how cerebral angiography corresponded with biopsy findings in patients with suspected PCNSV., Patients and Methods: A total of 128 patients who underwent workup for PCNSV between years 2005-2016 were identified by query of existing neurological surgery and angiography databases at University Hospitals Cleveland Medical Center (UHCMC) and the Cleveland Clinic Foundation (CCF). The primary outcome was to examine the concordance of results between angiography and cerebral biopsy. Secondary outcomes included examining concordance between results of biopsy and other commonly performed tests for diagnosis of PCNSV including Magnetic Resonance Imaging (MRI), cerebrospinal fluid white blood cell count (CSF WBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP)., Results: 128 patients underwent cerebral biopsy for diagnosis of suspected PCNSV. 93 (73%) of these patients also underwent angiography. Of the 34 patients with positive biopsy findings, only 5 also had positive angiography. Positive angiography was not found to be correlated with positive biopsy in our analysis. The only test that was significantly associated with biopsy proven vasculitis was increased CSF WBC count (P = 0.0114)., Conclusions: PCNSV is a rare disease and often requires multiple tests or procedures to obtain definitive diagnosis. These results suggest that cerebral angiography findings are not associated with biopsy findings and should be used cautiously in the diagnostic work-up of PCNSV., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: We aimed to study the prevalence of enterovirus (EV) meningitis without the presence of cerebrospinal fluid (CSF) pleocytosis and identify patient factors and clinical features associated with it., Methods: This was a retrospective analysis of patients aged < 18 years old who were diagnosed with EV meningitis by CSF reverse-transcriptase polymerase chain reaction (RT-PCR) testing between January 2015 and December 2016. Clinical variables were compared with regard to the presence of CSF pleocytosis., Results: A total of 305 patients were enrolled in study; 169 (55.4%) had no pleocytosis. Patients without pleocytosis were younger (median age 2 months vs. 67.0 months, p < 0.01) and had lower white blood cell (WBC) count (median, 8600/mm 3 vs. 10,300/mm 3 , p < 0.01). Also absolute neutrophil (ANC) count were lower than pleocytosis group (median, 4674/mm 3 vs. 7600/mm 3 , p < 0.01). Comparing three age groups, CSF apleocytosis was present in 106 of 128 patients (82.8%) aged ≤3 months, 7 of 13 patients (53.8%) aged 3 months-3 years and 56 of 164 patients (34.1%) aged > 3 years. Younger age groups had higher prevalence of CSF apleocytosis (p < 0.01). In patients aged ≤3 months, 94.5% underwent lumbar puncture within 24 h of symptom onset. The frequency of not having pleocytosis was higher than the frequency of having pleocytosis during peak EV infection prevalent months (summer and fall) (p < 0.01)., Conclusion: This study shows that EV meningitis in young infants, with early lumbar puncture, or occurring during peak EV meningitis prevalent seasons cannot be solely excluded by pleocytosis. Also, a confirmation test for EV meningitis should be performed using RT-PCR.

Background: Sudan falls in the meningitis belt where most global cases of bacterial meningitis are reported. Highly accurate decision support tools have been developed by international specialized societies to guide the diagnosis and limit unnecessary hospital admissions and prolonged antibiotic use that have been frequently reported from countries around the world. The goals of this study are to critically evaluate the clinical decision of bacterial meningitis in children in Sudan using clinical prediction rules and to identify the current bacterial aetiology., Methods: This cross-sectional hospital-based study was conducted in October to July of 2010 in a major referral pediatric hospital in Khartoum, Sudan. Febrile children age 1 day to 15 years who were provisionally diagnosed as having meningitis on admission were included (n = 503). Cerebrospinal fluid (CSF) specimens were obtained from all patients while clinical and demographic data were available for only 404. Conventional laboratory investigations were performed. The clinical decision was evaluated by the International Classification of Diseases-Clinical Modification code 320.9 and the Bacterial Meningitis Score. Ethical clearance and permissions were obtained., Results: Out of 503 provisionally diagnosed bacterial meningitis patients, the final clinical confirmation was assigned to 55.9%. When codes were applied; 5.7% (23/404) with CSF pleocytosis were re-classified as High Risk for bacterial meningitis and 1.5% (6/404) with confirmed bacterial aetiology as Proven Bacterial Meningitis. Neisseria meningitidis was identified in 0.7% (3/404) and Streptococcus pneumoniae in another 0.7%. Typical laboratory findings (i.e. CSF pleocytosis and/or low glucose and high protein concentrations, Gram positive or Gram negative diplococcic, positive bacterial culture) were seen in 5 (83%). Clinically, patients showed fever, seizures, chills, headache, vomiting, stiff neck and bulging fontanelle. All confirmed cases were less than 5 years old and were admitted in summer. All patients were prescribed with antibiotics; they were all recovered and discharged., Conclusions: Bacterial meningitis is over-diagnosed in hospitals in Khartoum therefore clinical prediction rules must be adopted and applied to guide the clinical decision. The sole bacterial aetiology in this selected group of Sudanese children remain N. meningitidis and S. pneumoniae, but with significant decrease in prevalence. Some cases showed atypical clinical and laboratory findings.

Neurosarcoidosis (NS) is a rare disease, affecting only 3%-10% of patients with sarcoidosis. The clinical presentation can be protean and often represents a diagnostic challenge. Cerebrospinal fluid (CSF) ACE level has poor sensitivity, but high specificity for establishing a diagnosis of NS. We present a case of NS in a middle-aged African American woman who presented with dysphagia and dysphonia. An extensive radiological workup was negative for structural brain disease. CSF studies demonstrated lymphocyte predominant pleocytosis with an elevated ACE level. A diagnosis of possible neurosarcoidosis was made. She responded to systemic steroid therapy with complete resolution of her symptoms over the next five months. In the appropriate clinical setting, an elevated CSF ACE level could be of paramount importance for making a diagnosis of NS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF. Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject., Methods: Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values., Results: A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases., Conclusions: Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.

Introduction: Acute flaccid myelitis (AFM) is characterized by limb weakness with spinal cord grey matter lesion on imaging or electrodiagnostic evidence of spinal cord motor neuron injury. This Poliomyelitis-like illness is rare in children, and its natural course is not yet well defined., Purpose of the Study: The purpose of the study was to report the clinical presentation, laboratory findings, management and outcome of children with AFM., Materials and Methods: This is a prospective case series study., Results: Nine children met the case definition given by CDC. All cases presented with prodromal symptoms followed by acute onset asymmetrical limb weakness. Maximum weakness is reached within 4 days from the day of onset. Cerebrospinal fluid analysis shows that pleocytosis with viral markers for arboviruses and enteroviruses was negative. Electrophysiological study revealed decreased muscle action potential in all. MRI of the spinal cord showed predominantly grey matter involvement., Conclusion: AFM should be one of the differential diagnoses in any child presenting with acute flaccid paralysis., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: MS is a demyelinating CNS disorder with a spectrum of clinical patterns regarding course and prognosis. Although several prognostic factors are considered in the initial evaluation of patients, biological markers defining the disease course and guiding treatments are currently lacking. It is unknown whether patients with CSF pleocytosis differ in regard to symptoms, disease course, and prognosis from those without. The aim of this study was to evaluate whether CSF pleocytosis during the initial presentation has an impact on the clinical course and progression of MS., Methods: We retrospectively evaluated patients attending the MS Clinic at Rabin Medical Center between January 1999 and January 2016 who underwent lumbar puncture (LP) at disease presentation, considering CSF cell count, clinical diagnosis (clinically isolated syndrome [CIS] and relapsing-remitting MS [RRMS]), annualized relapse rate (ARR), paraclinical findings (imaging, CSF oligoclonal bands, and evoked potentials), and disease progression, expressed by the Expanded Disability Status Scale (EDSS)., Results: One hundred fourteen patients (72 females) underwent LP at disease presentation (RRMS: n = 100, CIS: n = 14). Age at diagnosis was 32.4 ± 12.2 years, and the follow-up time was 9.4 ± 3.8 years. Forty-six patients showed a pleocytic CSF (≥5 cells per μL). Compared with patients with <4 cells per μL, patients with pleocytosis had a higher ARR (0.60 ± 0.09 vs 0.48 ± 0.04; p = 0.0267) and a steeper increase (slope) in the EDSS score throughout the follow-up period (correlation coefficient: r 2 = 0.04; p = 0.0251)., Conclusions: CSF pleocytosis may be considered a biological unfavorable predictive factor regarding disease course and progression in MS.

Background: Given its rare incidence, there are few epidemiological case series on paraneoplastic neurologic syndromes (PNS)., Methods: We present a 10-year series compiled in the Section of Neuro-Oncology, Yale Cancer Center between 2002 and 2012., Results: Twenty-five cases met the PNS Euro-network criteria for definitive PNS. Most (64%; 16/25) had no known neoplasm. Cerebrospinal fluid pleocytosis declined logarithmically over time. Neuroimaging abnormalities were seen in 88% of cases (15/17), but with delayed onset. Therapeutic benefit correlated strongly to pre-treatment modified Rankin Scale (mRS) (p < 0.01), but not with time elapsed between syndrome onset to treatment (p = 0.8), first immunotherapy modality (corticosteroids: n = 10; IVIG: n = 10; PLEX: n = 3; p = 0.37), or number of immunotherapy modalities provided (p = 0.17). PNS-related mortality was high (24%; 6/25). Nonetheless, 16% (3/18; 7 living patients censored) survived over 6 times the anticipated median expected by tumor type and stage., Conclusions: PNS are rare, at an estimated incidence of 3.1 cases per million-person-years. Detection of CSF pleocytosis and MRI abnormalities depend on time of analysis. While PNS-related mortality was high, immunotherapy benefit correlated strongly with pre-treatment mRS and long-term survival is possible.

Anti-Borrelia antibodies in the cerebrospinal fluid (CSF) are required for definite diagnosis of Lyme neuroborreliosis (LNB). However, children often present with early LNB, and antibody production in the CSF may not be demonstrated. Recent studies have suggested the chemokine CXCL13 to be an early marker for LNB. The aim of the study was to evaluate CXCL13 for laboratory diagnosis in pediatric LNB patients and to evaluate the association with pleocytosis in CSF, clinical features, and recovery. CSF samples were collected from LNB patients, classified as definite LNB (n = 44) or possible LNB (n = 22), and controls classified as non-LNB (n = 102) or other specific diagnoses (n = 23). CSF samples were analyzed with the recomBead CXCL13 assay (Mikrogen Diagnostik, Germany), cut-off 160 pg/mL. CXCL13 was significantly higher in LNB patients compared to controls (p < 0.001). Among LNB patients, 58/66 had elevated CXCL13, and among controls, 111/125 had CXCL13 levels under cut-off (sensitivity 88%, specificity 89%). In LNB patients with pleocytosis but no detectable anti-Borrelia antibodies in CSF (possible LNB), CXCL13 was elevated in 16/22 (73%). A weak correlation between CXCL13 and pleocytosis in CSF was found in LNB patients (Rho = 0.46, p < 0.01), but no differences in CXCL13 levels in relation to specific clinical features. In conclusion, CXCL13 is elevated in CSF in children with LNB, showing acceptable sensitivity and specificity. In patients with possible LNB, CXCL13 was elevated in a majority of cases (73%) and is suggested as a complementary diagnostic tool in pediatric LNB patients. CXCL13 was not associated with specific clinical features or recovery.

Objective: Define the etiologies, clinical features, time to diagnosis, and outcomes of patients that present with cerebral spinal fluid (CSF) pleocytosis., Patients and Methods: This is retrospective cohort study of patients with CSF pleocytosis, defined as WBC count >5 cells/mm 3 in the CSF, from July 2015 to June 2016 at a large tertiary care hospital. The proportion of patients within specific diagnostic categories were analyzed for differences in diagnostic testing and outcomes., Results: 53% of patients had CSF pleocytosis due to an unknown etiology. The leading known cause of neuroinflammation was CNS infection (n = 43/244, 18%), followed by malignancy (n = 28/244, 11%). Mean time to diagnosis was 125 days in patients with autoimmune neuroinflammation and was 16 days in patients with an infection or malignancy. CSF parameters and peripheral white blood cell counts did not distinguish between categories of disease. The presence of CSF oligoclonal bands or a positive biopsy result most commonly supported a diagnosis of an autoimmune disease or malignancy, respectively. Neuroimaging changes were present in only 44% of infections but were found in 80-90% of other categories of neuroinflammation. Patients presenting with a severe neurologic deficit had 22.29 higher odds of a severe deficit at the last neurologic assessment, and mortality was highest (29%) in patients with malignancy-associated neuroinflammation., Conclusions: This study to defines general diagnostic categories of neuroinflammatory disease in patients and provides new insight on the value of specific diagnostic testing, time to diagnosis, and outcomes in these patient populations., (Published by Elsevier B.V.)