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Objectives Status epilepticus (SE) can be associated with neuronal surface antibodies (NS-Abs) but NS-Ab detection rate remains unknown in patients with SE of unclear etiology at symptom presentation but suspected of having an autoimmune etiology (SE suspected autoimmune). We aimed to determine the NS-Ab detection rate and the clinical features that predict the presence of NS-Abs in patients with SE suspected autoimmune. Methods We retrospectively reviewed the clinical information of 137 patients with SE suspected autoimmune who underwent testing for NS-Abs between January 2007 and September 2020. NS-Abs were examined in both serum and cerebrospinal fluid (CSF) obtained at symptom onset with established assays. We classified brain magnetic resonance imaging (MRI) findings into unremarkable, autoimmune limbic encephalitis (ALE) (bilateral abnormalities highly restricted to the medial temporal lobes), ALE-Plus (ALE pattern and additional extramedial temporal lobe abnormalities), multifocal cortico-subcortical (MCS), or other pattern. We compared the clinical features between patients with and without NS-Abs. Results Forty-four patients (32.1%) had NS-Abs, including 35 N-methyl-d-aspartate receptor (NMDAR) (one with concurrent γ-aminobutyric acid B receptor [GABAbR] and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor [AMPAR]), 5 γ-aminobutyric acid A receptor (GABAaR), 2 leucine-rich glioma-inactivated 1(LGI1), 1 GABAbR, and 1 unknown antigens. Compared with NS-Ab-negative patients, NS-Ab-positive patients were more likely to have a preceding headache (56.8% vs 26.7%), preceding psychobehavioral or memory alterations (65.9% vs 20.4%), involuntary movements (79.5% vs 16.1%), CSF pleocytosis (81.8% vs 62.0%), elevated immunoglobulin G (IgG) index (45.2% vs 15.6%), oligoclonal bands (51.5% vs 9.5%), tumor (47.7% vs 8.6%), and higher APE2 score (median of 9 vs 7), and they were less likely to have an ALE-Plus pattern (2.3% vs 23.7%). However, preceding fever and ALE or MCS pattern were not different between the two groups of patients. Significance When an autoimmune etiology was suspected, there was a relatively high likelihood (one of three patients) of identifying NS-Abs. Some clinical features (preceding symptoms, inflammatory CSF) predict a higher likelihood of finding NS-Ab positivity, but the ALE-Plus MRI pattern is more likely suggestive of NS-Ab negativity.

Neurological symptoms are frequently reported in patients suffering from COVID‐19. Common CNS‐related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID‐19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID‐19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with the detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID‐19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS‐CoV‐2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood–brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare and often of uncertain significance. In this review, we provide an overview of the neurological impact that occurs in the acute phase of COVID‐19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well‐characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID‐19., Neurological symptoms are common during COVID‐19. Proposed mechanisms of neuropathogenesis include indirect consequences of systemic immune activation, viral interaction with the vascular endothelium inducing a pro‐thrombotic state, and direct CNS damage by viral neuroinvasion. Immune activation has been detected using cerebrospinal fluid (CSF) biomarkers, and microvascular injuries in pathological and neuroimaging studies. Active viral CNS invasion remains questionable, and virus detection in CSF is rare and of uncertain significance. Moreover, typical distinguishing features of neurotropic infections are mild or absent in CSF during SARS‐CoV‐2 infection. We highlight the potential importance of CSF biomarkers to characterize neuropathogenic processes related to COVID‐19.

Tick-borne encephalitis (TBE) is caused by the neurotropic tick-borne encephalitis virus (TBEV). In dogs, this virus may affect the central nervous system (CNS), causing meningoencephalitis, meningomyelitis, radiculitis or any combination of these. Diagnosis of TBE relies on a combination of clinical signs of CNS disease and laboratory findings, including CSF pleocytosis and serum TBEV antibody titers. Exposure to TBEV does not necessarily cause clinical disease, and seroprevalence has been reported as high as 40% in endemic areas. This causes concerns of over-diagnosing TBE in dogs with CNS disease. By examining TBEV antibodies in dogs with and without neurological disease in a TBEV endemic area, this study aimed to evaluate the diagnostic value of TBEV antibodies in the cerebrospinal fluid (CSF) in dogs. Eighty-nine dogs were included in the study, 56 with neurological disease and 33 neurologically normal control dogs. A positive TBEV CSF and serum IgG antibody titer (> 126 U/mL) was found in 3/89 dogs (3.4%). A positive serum TBEV antibody titer was found in 11 of the 89 dogs (12.4%). None of the control dogs showed a positive CSF antibody titer, whilst two showed positive serum concentrations. A positive CSF IgG antibody titer supports a clinical diagnosis of TBE in patients with acute onset of CNS disease and may help reduce the risk of over-diagnosis.

ObjectivesTo report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP).MethodsThis was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed.ResultsOne hundred five patients were included; their median age was 30 (range 14–75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features).ConclusionsNMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.

Purpose of ReviewTo describe the clinical presentation, diagnosis, management, and outcomes of 4 confirmed Eastern equine encephalitis (EEE) cases and a review of the literature.Recent FindingsThere was a sharp rise in the number of EEE cases in the United States in 2019, with 38 confirmed cases and 15 deaths. Our institution cared for 10% of patients with neuroinvasive EEE nationwide. These were the first cases seen locally since 2010.SummaryEEE virus causes one of the most lethal types of arboviral encephalitis in the United States with a mortality of 30%–40%. Manifestations of EEE infections can range from mild encephalopathy to coma. Common findings include CSF pleocytosis and involvement of the basal ganglia on MRI. Given the rarity of this disease and nonspecific findings, diagnosis can be challenging, and a high clinical suspicion is important. Management is mainly supportive, and the use of IV immunoglobulin remains controversial. Two of our 4 patients died; these patients had coma within 48 hours, hyponatremia, involvement of bilateral thalami and brainstem, status epilepticus, and severe brain dysfunction in EEG.

Background: Cerebral amyloid angiopathy with related inflammation (CAA-ri) is a rare age-associated disorder characterized by an inflammatory response to amyloid in cerebral blood vessels. CAA-ri is often treated with corticosteroids, but response to treatment is variable. Objective: To assess the relationship between clinical and paraclinical measures and outcomes in patients with CAA-ri treated with high doses of methylprednisolone. Methods: Longitudinal clinical course, and results from serum and cerebrospinal fluid (CSF) testing, electroencephalography, and neuroimaging were reviewed from 11 prospectively-accrued CAA-ri patients diagnosed, treated, and followed at Barnes Jewish Hospital (St. Louis, MO, USA). Magnetic resonance imaging (MRI) changes were quantified using a scoring system validated in cases of amyloid related imaging abnormality (ARIA-E). Clinical outcomes were assessed as change in modified Rankin Scale (ΔmRS) from baseline to final assessment (median 175 days from treatment with high doses of methylprednisolone; range, 31–513). Results: Worse outcomes following methylprednisolone treatment were associated with requirement for intensive care unit admission (median ΔmRS, 5 versus 1.5; p = 0.048), CSF pleocytosis (median ΔmRS 4.5 versus 1; p = 0.04), or lower CSF Aβ40 at presentation (rho = –0.83; p = 0.02), and diffusion restriction (median ΔmRS 4 versus 1.5; p = 0.03) or higher late ARIA-E scores (rho = 0.70; p = 0.02) on MRI, but not preexisting cognitive decline (median ΔmRS 2 versus 2; p = 0.66). Conclusion: Clinical and paraclinical measures associated with outcomes may inform clinical counseling and treatment decisions in patients with CAA-ri. Baseline cognitive status was not associated with treatment responsiveness.

We report a 57-year-old man with recurrent meningoencephalitis resulting in bouts of altered consciousness, encephalopathy, tremors, focal seizures, and paraparesis. The neurological manifestations were accompanied by fever and leukocytosis in the absence of other systemic manifestations. MRI abnormalities of the brain, brainstem, spinal cord and meninges and CSF pleocytosis and elevated protein were observed. Exhaustive studies failed to reveal an etiology. Brain biopsy revealed nodules of neutrophils and macrophages, but no vasculitis. The lesions were not vasocentric as would be expected with neuro-Behcet's disease and neuro-Sweet's disease. The disorder was responsive to high-dose corticosteroid therapy and, ultimately, to anakinra, an IL-1α and IL-1β receptor antagonist.

The role of biological sex on clinical outcomes and the pathogenesis of AIDS-related opportunistic infections is unknown. We assessed baseline biomarkers and outcomes between 577 men and 400 women in HIV-related cryptococcal meningitis cohorts in Uganda and South Africa from 2010 to 2017. We compared 10-week mortality by sex via Cox proportional hazards models. The 10-week mortality for women was 50% (198/400) and 43% (247/577) for men. Women had higher risk of death in an unadjusted model (Hazard Ratio (HR) = 1.20; 95%CI, 1.00–1.45; P = .05). Women maintained a higher risk when adjusting for quantitative CSF culture, altered mental status, CSF pleocytosis, age, and antiretroviral status (HR = 1.31; 95%CI, 1.07–1.59; P Lay Summary We examined the role of biological sex in cryptococcal meningitis mortality in a large cohort. Our findings reveal significant differences in inflammatory markers by biological sex. Women have significantly higher mortality due to cryptococcal meningitis that is attributable to anemia at baseline.

Objective To compare the demographical, clinical and laboratory features, and outcomes of neonates with enteroviral meningitis (EVM) with those with bacterial meningitis (BM). Methods A retrospective two-center study was performed in La Réunion Island between January 2008 and December 2018 in hospitalized neonates aged less than 29 days. Patients positive for enterovirus real-time polymerase chain reaction from the cerebrospinal fluid (CSF) were diagnosed with EVM. Neonates with positive CSF culture results for a potentially pathogenic bacterium were diagnosed with BM. Results Compared with their EVM peers (n = 20), BM-infected neonates (n = 14) had lower birth weight, and were more likely to present hypotension and neurological symptoms on admission. Thrombocytopenia, elevated serum procalcitonin, hyperproteinorachia, hypoglycorrhachia, CSF pleocytosis, a bacterial meningitis score >0 were more frequent in the BM-infected group. All BM-infected neonates had at least one abnormal cutoff value in the CSF, while nine neonates (45%) in the EVM group had no CSF abnormality (p = 0.004). BM-infected neonates also had a longer length of hospital stay, needed more supportive care, received more prolonged antimicrobial courses, and developed respiratory and neurological complications. Conclusion Recognition of some clinical and laboratory features can help clinicians in differentiating BM from EVM when managing this high-risk patient group.

Rhombencephalitis (RE) refers to inflammatory diseases involving the brainstem and cerebellum. Although RE is a rare entity, it is associated with high morbidity and mortality. The management of such patients is often challenging in terms of identifying the etiology and defining prognosis. Infections, autoimmune and paraneoplastic conditions are commonly implicated. Patients with RE often present with a biphasic illness with an initial flu-like syndrome followed by brainstem dysfunction. CSF pleocytosis, abnormal brain MRI findings, isolation of organism or molecular (PCR/antigen) detection in CSF/blood cultures/stool samples and nasal/rectal swabs help in arriving at a definitive or probable diagnosis. Prompt aggressive treatment with antibacterial and antiviral drugs and/or immunoglobulins along with supportive therapy is crucial for avoiding a poor outcome. We present a case report of a 28-year old female patient who developed RE and myelitis in the third trimester of pregnancy. We aim to highlight the highly suggestive radiological findings which corroborated with the clinical diagnosis of enterovirus infection. The patient's radiological follow-up and neurological sequalae are also described. To the best of our knowledge, ours is the first report which describes the MRI features of this clinical scenario in the third trimester of pregnancy, and also the subsequent clinico-radiological follow up.

OBJECTIVE The Bacterial Meningitis Score (BMS) is recommended by pediatric academic societies to rule out the diagnosis of bacterial meningitis. The aim of this study was to evaluate the performance of the BMS to identify adults at no risk for bacterial meningitis. METHODS We conducted a multicentric retrospective study including adults who consulted the emergency department (ED) for meningitis [cerebrospinal fluid (CSF) white blood cells ≥5/mm with a ratio of white blood cells/red blood cells

The aim of our study was to compare the course of TBE in children and adults. A retrospective analysis of the medical records of 669 patients was performed. The patients were categorized into 2 groups: Group I with 68 children and group II with 601 adults. TBE symptoms in children were milder compared with adults, with meningitis in 97% of cases. In adults, meningoencephalitis and meningoencephalomyelitis made up 49.26% of cases. Nausea and vomiting are more frequent in children, while neurological manifestations are more frequent in adults. There were no differences in CSF pleocytosis at the onset of disease in both groups, while CSF protein concentration was higher in adults. Children treated with corticosteroids over 7 days had higher checkup pleocytosis than pleocytosis at the onset of disease compared with adults. Corticosteroid use prolongs the disease duration but does not influence the development of TBE sequelae. Children had more favourable outcomes than adult patients.

Background Lyme neuroborreliosis (NB) is a tick-borne infectious disorder of the nervous system caused by Borrelia burgdorferi spirochetes. There are not many data available regarding the differences in the course of NB in children and adults. The aim of our study was to compare the clinical course of NB between children and adults. Methods Retrospective analysis of medical documentation of 181 patients with NB was performed. The patients were divided into 2 groups: Group I: 57 children with NB; Group II: 124 adults with NB. Medical data, such as patients' age, sex, place of living (residence), time from a tick bite, subjective complaints, general examination results, laboratory parameters and treatment were analyzed. Results In children, the most common symptoms were headache (89.5%), neck stiffness (64.9%) and nausea and vomiting (56.1%). In adults, the most common symptoms were headache (77.4%), facial nerve palsy (59.7%), neck stiffness (59.7%), vertigo (41.9%) and lumbosacral region pain (37.1%). Bannwarth's syndrome was observed in 10.5% of children and 36.3% of adults. In cerebrospinal fluid (CSF) in children, the pleocytosis at admission was higher than in adults, but protein concentration was significantly lower. There were no differences in percentage of mononuclear cells in CSF smear between the groups. In CSF examination after treatment, a decrease in pleocytosis and protein concentration was observed in both groups. Analysis of effectiveness of treatment mostly with third generation cephalosporins (defined as complete recovery) between the groups, calculated by the Kaplan-Meier method and compared with the use of the log-rank test, showed no significant differences between children and adults (log-rank P = 0.619). Conclusions In children, NB more frequently presented as meningitis, and in adults in the form of Bannwarth's syndrome. CSF pleocytosis in children with NB was higher than in adults, while the protein concentration in children was lower. Outcomes in children and adults were favorable and did not differ after standard NB treatment.

Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVID-19 who developed subacute cognitive disturbances.Methods: From June 1 to August 15, 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation, were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA, and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Clock Drawing Test (CDT).Results: All but one of our patients were female, and the mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15–33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of six words/min (IQR 5.25–10.75) and altered visuospatial construction with a median of four points (IQR 4–9) (CDT). CSF pleocytosis was not detected, and only one patient was positive for SARS-CoConclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.

BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

Guillain-Barré syndrome (GBS) is a rare complication of chickenpox. All cases of post-varicella GBS published in the literature have been associated with the classical albuminocytological dissociation. We report the case of a 48-year-old male with flaccid areflexic quadriparesis and bilateral seventh, ninth, tenth, and twelfth cranial nerve palsies 10 days after chickenpox. Cerebrospinal fluid (CSF) analysis done in the second week showed marked lymphocytic pleocytosis. Electroneurographic studies were suggestive of acute inflammatory demyelinating polyradiculopathy. He had near-total neurological recovery with intravenous immunoglobulin. Our case demonstrates that GBS can occur after primary varicella infection, and marked CSF pleocytosis can be an additional feature.

We report a case of a 27-year-old obese female presenting with headache, blurry and double vision. She was found to have bilateral papilledema by an ophthalmologist and sent to the emergency department (ED). Cerebrospinal fluid (CSF) analysis showed elevated opening pressure and lymphocytic pleocytosis. Symptoms improved significantly after lumbar puncture (LP). Subsequently, polymerase chain reaction (PCR) for herpes simplex virus-2 (HSV-2) came back positive. This case represents an unusual presentation of HSV-2 meningitis, where the clinical picture was suggestive of pseudotumor cerebri or idiopathic intracranial hypertension (IIH), but CSF analysis revealed HSV-2. Papilledema and elevated intracranial pressure has not previously been described in association with HSV-2. Therefore, patients presenting with typical signs and meeting all diagnostic criteria for IIH in the presence of CSF pleocytosis may represent a distinct group of viral-induced intracranial hypertension. In these cases, an investigation of viral etiologies should be conducted.

Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with central nervous system (CNS) infections. Methods We conducted a prospective multisite study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to 1 of 3 tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. Metagenomic next-generation sequencing of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusions Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections., We examined the utility of next-generation sequencing in comparison to usual care in detecting a pathogenic organism in children with central nervous system infections.

Background: Cerebro Spinal Fluid (CSF) examination is very useful in patients of suspected CNS disease and the necessity of correlating it with the clinico-pathologic findings which will help in early diagnosis of CNS diseases and guide the further management of the disease. CSF examination with quantification of leukocytes and differential count of cellular subsets in the cerebrospinal fluid is a standard procedure in cases of suspected infectious conditions. Present study emphasises pleocytosis in the cerebrospinal fluid along with other laboratory parameters. Materials and Methods: The study is consisting of 295 CSF samples from patients with clinically suspected CNS infections. The CSF findings were evaluated in all age group patients in relation to cell counts and pleocytosis. Results: In Physical examination of CSF colour, appearance and received quantity were evaluated. Maximum specimen was received in 1 year to 18 year age group. CSF pleocytosis (>5cells/µl) was present maximum (48%) in 1 month to less than 1 year age. Pleocytosis >5 leucocytes/µl was found in 121 (41%) samples out of 295 samples. Conclusion: CSF cell count examination is very common and useful investigation done for suspected various CNS diseases. Infectious and non-infectious diseases of CNS can cause pleocytosis of the cerebrospinal fluid. The type of cells depends mainly on the clinical scenario. However it seems to vary with total cell count also, such as lymphocytes predominating at lower total cell counts while neutrophils are at higher total counts.

Background No widely accepted gold standard for diagnosis of shunt infection exists, with definitions variable among clinicians and publications. This article summarizes the utility of commonly used diagnostic tools and provides a comprehensive review of optimal measures for diagnosis. Methods A query of PubMed was performed extracting articles related to shunt infection in children. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, resulting in 1756 articles related to shunt infection, 49 of which ultimately met inclusion criteria. Results Of the 49 articles included in the analysis, 9 did not define infection, 9 used culture alone, 9 used cultures and/or symptomatology, and 4 used a combination of cultures, cerebral spinal fluid (CSF) pleocytosis and symptomatology. The remainder of the studies used definitions from the Centers for Disease Control and Prevention (n = 2) and the Hydrocephalus Clinical Research Network (n = 2) or borrowed elements from these definitions. Variation in definition stems from the lack of sensitivity and specificity of commonly used signs, symptoms, and tests. Shunt tap alone is considered half as sensitive as hardware culture. Fever upon presentation was present in 16% to 42% of cases. CSF pleocytosis combined with fever has a sensitivity of 82% and specificity of 99%. CSF eosinophilia, lactic acid, serum anti-Staphylococcus epidermidis titer, procalcitonin, and C-reactive protein are non-specific and their utility is not well established. Conclusions The definition of shunt infection is variable across studies, with CSF culture and/or symptomatology being the most commonly utilized parameters.

Background Several types of physical examinations are used in the diagnosis of meningitis, including nuchal rigidity, jolt accentuation, Kernig's sign, and Brudzinski's sign. Jolt accentuation was reported to have sensitivity of nearly 100% and to be highly efficient for excluding meningitis, but more recent studies showed that a number of patients with meningitis may present negative in this test. Methods We systematically reviewed studies on the above‐mentioned physical examination tests and performed meta‐analysis of their diagnostic characteristics to evaluate the clinical usefulness. Nine studies, comprising a total of 599 patients with pleocytosis in the cerebrospinal fluid (CSF) and 1216 patients without CSF pleocytosis, were enrolled in the analysis. Results Jolt accentuation showed a decent level of odds ratio (3.62; 99% confidence interval (CI): 1.13‐11.60, P = 0.004) comparable to that in nuchal rigidity (2.52; 1.21‐5.27, P = 0.001) for the correct prediction of CSF pleocytosis among subjects with suspected meningitis. The estimated sensitivity was relatively high (40%‐60%) in nuchal rigidity or jolt accentuation tests. On the other hand, Kernig's and Brudzinski's signs exhibited relatively low sensitivity (20%‐30%). The estimated specificity was higher in Kernig's and Brudzinski's signs (85%‐95%) than in nuchal rigidity or jolt accentuation tests (65%‐75%). Conclusion Approximately half of the patients with meningitis may not present typical meningeal signs upon physical examination. Combining several examinations for the detection of meningeal signs may decrease the risk of misdiagnosis.

Herpes simplex virus (HSV) infection in infants is a devastating disease with an often subtle presentation. We examined cerebrospinal fluid (CSF) HSV PCR (polymerase chain reaction) testing and empiric acyclovir therapy in young febrile infants. Chart review identified hospitalized infants aged ≤60 days with fever ≥38°C who had undergone lumbar puncture. Previously published criteria were used to define patients at high risk for HSV. Primary outcomes were CSF HSV PCR testing and empiric acyclovir therapy. Of 536 febrile infants, 23% had HSV testing; empiric acyclovir was started in 15%. HSV testing and therapy were associated with younger age, seizure, maternal vaginal lesions, postnatal HSV contact, vesicles, poor tone, CSF pleocytosis, and enteroviral testing. Sixty-two percent of high-risk infants did not undergo HSV testing, and 75% did not receive acyclovir. High-risk infants were untested and untreated at relatively high rates. Evidence-based criteria to guide HSV testing and treatment are needed.

Central nervous system infection may be associated with oxidative stress and may influence clinical severity and outcome. We report oxidative stress markers in the patients with tuberculous meningitis (TBM) and correlate these with clinico-radiological severity and outcome. Fifty-six patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF), and magnetic resonance (MRI) were included. Plasma glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in the patients and 55 matched healthy controls. Hospital death was noted. Disabilities at 3 and 6 months were categorized using the modified Rankin Scale (mRS) as poor (mRS > 2) or good (mRS ≤ 2). The patients had lower levels of GSH (1.49 ± 0.49 vs 2.57 ± 0.39 mg/dL, p ˂ 0.001) and TAC (0.25 ± 0.17 vs 2.20 ± 0.31 mmol Trolox Eq/L, p ˂ 0.001), and higher level of MDA (6.61 ± 1.72 vs 3.09 ± 0.38 nmol/mL, p

To evaluate the infectious etiologies, clinical features, and outcomes of patients with CNS infections at a tertiary care center. Patients that present with a pleocytosis in the cerebral spinal fluid (CSF), defined as a CSF WBC count > 5 cells/mm3, from July 2015 to June 2016 at a tertiary care hospital were analyzed for this report. Data from patients with confirmed (n = 43) and presumed (n = 51) CNS infections were analyzed. CNS infection was the leading known cause of CSF pleocytosis (n = 43, 18% of all patients with a pleocytosis in the CSF), and HSV-2 was identified as the leading causative pathogen (n = 10) followed by varicella zoster virus (n = 5). Fifty-three percent of patients with a pleocytosis in the CSF did not receive a diagnosis. In the patients that did not receive a diagnosis, CNS infection was presumed to be the cause in 51 patients (21% of patients with CSF pleocytosis). The mean time to diagnosis for patients with confirmed CNS infection was 16 days, but time to diagnosis was highly variable depending on the causative pathogen. There was a significant overlap in CSF parameters and peripheral white blood cell counts in patients diagnosed with a viral, bacterial, or fungal infection. Neuroimaging changes were present in only 44% of CNS infections. The overall mortality was 7% for CNS infections, and 17% of patients with a CNS infection had a severe neurologic deficit at presentation while only 3% had a severe deficit at the last neurologic assessment. This study provides new insights into the infectious causes of disease in a cohort of patients with pleocytosis in the CSF. The study provides new insights into the time to diagnosis and outcomes in patients that present with pleocytosis in the CSF.

Purpose The exact etiology of febrile seizures (FS) is still unclear. However, it is thought that cytokine network activation may have a causative role. Therefore, this study aimed to evaluate the levels of interleukin-12 (IL-12) as a proinflammatory cytokine, interleukin-10 (IL-10) as an anti-inflammatory cytokine, and interferon-β (IFN-β), a marker of toll-like receptor-3 activation as a host response to viruses. These cytokine levels were analyzed in the cerebrospinal fluid (CSF) of children after a FS. Methods With the approval of the Human Research Ethics Committee, 76 patients with FS, who underwent lumbar puncture (LP) for the exclusion of central nervous system (CNS) infection, and who didn’t have CSF pleocytosis, were included in the study. The control group consisted of 10 patients with similar ages, with an acute febrile illness and who required LP to exclude CNS infection. The analyses were made by the enzyme-linked immunoassay method. Results Age, gender distribution and CSF IL-12 and IFN- β levels did not differ, but CSF IL-10 levels were significantly lower in the FS group as compared to the control group (0.78 ± 4.5 pg/ml, versus 27 ± 29 pg/ml, p Conclusion The low-level of CSF IL-10, considering its anti-inflammatory properties, may play a role in the etiopathogenesis of FS.

There have been suggestions that tick-borne encephalitis (TBE) may cause neurodenenerative changes in the brain. The aim of this study was the assessment of the tau protein concentration in cerebrospinal fluid (CSF) of patients with different clinical forms of TBE. The concentration of tau protein in CSF was determined using Fujirebio tests (Ghent, Belgium) in 35 patients with TBE: group I—patients with meningitis (n = 16); group II—patients with meningoencephalitis (n = 19). None of the patients reported any neurodegenerative disorder that could affect the results of the study. The control group (CG) consisted of 10 patients in whom inflammatory process in central nervous system was excluded. Tau protein concentration in CSF before treatment did not differ significantly between the examined groups, while its concentration was significantly higher in encephalitis group than in CG after 14 days of treatment. Significant increase in tau protein concentration after treatment was observed in both examined groups. The comparison between the group of patients who fully recovered and patients who presented with persistent symptoms on discharge showed significant differences in tau protein concentration before and after treatment. ROC curve analysis indicates that CSF tau protein concentration before treatment may predict complicated course of the disease with 90.9% specificity and 80% sensitivity, while after treatment, specificity became 72.7% and 71.4% for sensitivity. Correlation analysis showed that in TBE patients (both meningoencephalitis and meningitis groups), CSF pleocytosis before treatment correlated negatively with tau protein concentration in CSF. (1) Neurodegeneration process is present in TBE encephalitis. (2) Tau protein concentration may be used as a predictor of complicated course of TBE.

Given its rare incidence, there are few epidemiological case series on paraneoplastic neurologic syndromes (PNS). We present a 10-year series compiled in the Section of Neuro-Oncology, Yale Cancer Center between 2002 and 2012. 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

Background and purpose The purpose of this study was to elucidate the association between aseptic meningitis and jolt accentuation of headache (JAH) in adults. Subjects and method 87 patients with meningeal irritation (age; 35.6 ± 13.3 years old, 45 males) who were admitted to our hospital from 1st August 2013 to 31st August 2018 were included. The diagnosis was determined according to the following criteria:, aseptic meningitis was defined as cerebrospinal fluids (CSF) pleocytosis with no evidence of bacterial infection, fungal infection or carcinomatous findings; meningism was defined as the absence of CSF pleocytosis. None of these patients had consciousness disturbance and focal neurological abnormalities. The blood and CSF data were reviewed for analysis. Results 61 patients were in aseptic meningitis group, 26 patients were in meningism group. Multiple logistic regression analysis showed older age (OR 1.059, 95% Confidence interval (CI) 1.012-1.108, P = 0.013), lower CRP (OR 0.803, 95%CI 0.697-0.925, P = 0.002) and absence of JAH (OR 0.048, 95%CI 0.004-0.554, P = 0.015) were significantly associated with aseptic meningitis. The sensitivity and specificity of JAH in aseptic meningitis were 68.9%, 3.8%.

The Neuropathology of Human Parechovirus (HPeV) is not widely described due to the relatively recent discovery of the virus combined with a limited number of autopsy case reports. We report the case of an infant boy born at 38 weeks who, six days after birth, presented with fever and severe neurological dysfunction. Human Parechovirus Type 3 (HPeV3) RNA was detected in his cerebrospinal fluid (CSF) and blood. He died five days after his initial presentation. Neuropathologic examination demonstrated multicystic encephalomalacia (ME). This case report confirms that white matter pathology is dominant in HPeV3 infection. A unique feature, of HPeV encephalomalacia is absence of CSF pleocytosis and minimal inflammation in the meninges. The findings permit comment on the pathogenesis of brain injury by this virus.

Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

ObjectiveAs autoimmune encephalitis (AIE) can resemble neurodegenerative dementia syndromes, and patients do not always present as encephalitis, this study evaluates how frequently AIE mimics dementia and provides red flags for AIE in middle-aged and older patients.MethodsIn this nationwide observational cohort study, patients with anti–leucine-rich glioma-inactivated 1 (LGI1), anti–NMDA receptor (NMDAR), anti–gamma-aminobutyric acid B receptor (GABABR), or anti–contactin-associated protein-like 2 (CASPR2) encephalitis were included. They had to meet 3 additional criteria: age ≥45 years, fulfillment of dementia criteria, and no prominent seizures early in the disease course (≤4 weeks).ResultsTwo-hundred ninety patients had AIE, of whom 175 were 45 years or older. Sixty-seven patients (38%) fulfilled criteria for dementia without prominent seizures early in the disease course. Of them, 42 had anti-LGI1 (48%), 13 anti-NMDAR (52%), 8 anti-GABABR (22%), and 4 anti-CASPR2 (15%) encephalitis. Rapidly progressive cognitive deterioration was seen in 48 patients (76%), whereas a neurodegenerative dementia syndrome was suspected in half (n = 33). In 17 patients (27%; 16/17 anti-LGI1), subtle seizures had been overlooked. Sixteen patients (25%) had neither inflammatory changes on brain MRI nor CSF pleocytosis. At least 1 CSF biomarker, often requested when dementia was suspected, was abnormal in 27 of 44 tested patients (61%), whereas 8 had positive 14-3-3 results (19%). Most patients (84%) improved after immunotherapy.ConclusionsRed flags for AIE in patients with suspected dementia are: (1) rapidly progressive cognitive decline, (2) subtle seizures, and (3) abnormalities in ancillary testing atypical for neurodegeneration. Physicians should be aware that inflammatory changes are not always present in AIE, and that biomarkers often requested when dementia was suspected (including 14-3-3) can show abnormal results. Diagnosis is essential as most patients profit from immunotherapy.

Background/Objectives: Our objectives were to determine the prevalence of co-existing bacterial meningitis (BM) and sterile cerebral spinal fluid (CSF) pleocytosis in the presence of Escherichia coli urinary tract infection (UTI) in children age zero days to two years, with the addition of CSF E. coli Polymerase Chain Reaction (PCR) analysis. Subjects/Methods: A retrospective study was conducted at a tertiary referral paediatric hospital from 1/1/2014 to 30/4/2019. Co-existing E. coli BM with UTI was defined as a pure growth E. coli from urine and a CSF culture with pure growth of E. coli and/or positive E. coli PCR. All children with a pure growth of E. coli from a urine sample and a CSF sample taken 48 hours before or after a positive urine culture were included. Further PCR analysis was carried out in cases with CSF pleocytosis. Results: There were 1911 patients that met the definition for an E. coli UTI, of which 314 had a CSF taken within 48 hours. No cases of co-existing E. coli meningitis were identified. Overall, there were 71 (23%) cases of pleocytosis, 57 (80%) of these had further PCR analysis, all of which were E. coli PCR not detected.­ Conclusion: The risk of E. coli UTI and co-existing E. coli BM is low. Routine lumber punctures (LPs) could be avoided in well-appearing infants with a diagnosis of E. coli UTI with the greatest impact seen in children up to 6 months of age. CSF E. coli PCR can help to further reduce the post-test probability of meningitis in the setting of pleocytosis. Funding Statement: None. Declaration of Interests: All authors declare that they have no conflicts of interest. Ethics Approval Statement: The study was reviewed and approved by the CHI Temple Street Scientific and Ethics Committee [REC Reference 19·007].

BACKGROUND The variability in cerebrospinal fluid (CSF) findings of myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) is not fully elucidated. OBJECTIVE AND METHODS We retrospectively analyzed 203 attack-associated CSFs from Mayo Clinic patients (2000-2019) with MOGAD. RESULTS White-blood-cell (>5/mm3) elevation was less with clinically isolated optic neuritis (23%), compared to myelitis, brain/brainstem attacks, or combinations thereof (>70%), p

In parenchymal neuro-Behcet disease (NBD), CSF opening pressure is usually normal. CSF pleocytosis is usually less than 200/mm3. Pleocytosis could be lymphocyte dominant or less frequently PMN dominant. However, CSF cytochemistry could be completely normal. CSF protein content is usually increased, but it could be normal. CSF glucose is often normal, which can be helpful in differentiation of acute NBD from infectious processes. In NBD presenting with cerebral venous sinus thrombosis, it is better to withhold the lumbar puncture; however, if CSF is taken, CSF opening pressure is elevated, but CSF constituents are usually normal. Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behcet disease. The absence of more than two oligoclonal IgG bands may help differentiate NBS from multiple sclerosis (MS). Oligoclonal bands are less stable in the setting of NBD compared with MS and can be easily suppressed by corticosteroid treatment. However, rarely in young MS patients, oligoclonal IgG bands could be absent in the early stages of the disease or can present as a weak single band. Therefore, the presence of oligoclonal bands cannot rule out NBD. CSF IL-6 might be a marker of disease activity in parenchymal NBD patients. That IL-6 is more increased in chronic progressive NBD patients is a matter of debate. Also, CSF IL-6 is not increased in patients with non-parenchymal NBD.

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 Individuals with previous syphilis may experience cognitive impairment. The goal of this study was to determine if those at high risk for laboratory-defined neurosyphilis are cognitively impaired, and whether treatment based on cerebrospinal fluid (CSF) findings results in better outcomes. Methods Participants had a new syphilis diagnosis, serum RPR titer ≥ 1:32 or peripheral blood CD4+ T cells ≤ 350/ul (in persons living with HIV) and did not endorse neurological symptoms. They underwent computerized cognitive assessment with the CogState. Thirty-two were randomized to either undergo lumbar puncture (LP) or to not undergo LP and 14 underwent LP; 64 were not randomized and 48 opted to undergo LP. Results Demographics, cognitive complaints and cognitive impairment did not differ between randomized and nonrandomized participants. Two-thirds were cognitively impaired, and impairment was not more common in those with cognitive complaints. The adjusted odds of increased severity of impairment were 3.8 times greater in those with CSF pleocytosis compared to those without. Time to cognitive normalization, improvement or decline did not differ between those who did not undergo LP and those who underwent LP and whose treatment was based on CSF analysis. Taking into account pre-treatment cognitive impairment, the risk of cognitive decline was lower in those with CSF pleocytosis treated for neurosyphilis compared to those without CSF pleocytosis not treated for neurosyphilis, (HR 0.24 (95% CI 0.07–0.88], p = 0.03). Conclusion In individuals at high risk for laboratory-defined neurosyphilis, cognitive complaints are not a good indicator of cognitive impairment. Severity of cognitive impairment was greater in those with CSF pleocytosis. Identification and treatment of those with neurosyphilis may mitigate subsequent cognitive decline.

Objectives Correction factors have been proposed for traumatic lumbar punctures (LPs) in febrile young infants. However, no studies have assessed their diagnostic utility. We sought to determine the proportion of traumatic LPs safely reclassified as low risk for bacterial meningitis using recently derived white blood cell (WBC) and protein correction factors. Methods We retrospectively analyzed traumatic LPs among all febrile infants ≤60 days old at two tertiary paediatric hospitals from 2006 through 2018. Traumatic LPs were defined as ≥10,000 RBCs/mm3. Abnormal cerebrospinal fluid (CSF) WBCs and protein were adjusted downward using a newly derived correction factor (877 red blood cells [RBCs]: 1 WBC), three commonly used correction factors (500 WBCs: 1 RBC; 1,000 WBCs: 1 WBC; peripheral RBCs: WBCs), and a newly derived protein correction factor (1,000 RBCs: 0.011 g/L protein). Results There were 437 traumatic LPs including 357 (82%) with pleocytosis and 4 (0.9%) with bacterial meningitis. Overall, fewer infants were classified as having CSF pleocytosis using 877:1 and 1,000:1 ratios (38% and 43%, respectively), with 100% sensitivity and negative predictive value, and improved specificity (63% for 877:1, 58% for 1,000:1 ratios versus 19% for uncorrected counts). Among infants with pleocytosis, 877:1 and 1,000:1 ratios reclassified 191 (54%) and 171 (48%) as normal with no misclassified bacterial meningitis cases. Ratios of 500:1 and peripheral RBC:WBC misclassified 1 infant that had bacterial meningitis. Corrected CSF protein outperformed uncorrected protein in specificity but did not add diagnostic value following WBC-based correction. Conclusions Correction ratios of 877:1 and 1,000:1 safely reclassified half of all febrile infants ≤60 days. These corrections should be considered when interpreting CSF results of traumatic LPs.