CSF White Blood Cell Count Research Articles

Differentiation between viral and autoimmune limbic encephalitis: a prospective cohort study with development and validation of a diagnostic model.

Distinguishing between viral encephalitis (VE) and autoimmune limbic encephalitis (ALE) presents a clinical challenge due to the overlap in symptoms. We aimed to develop and validate a diagnostic prediction model to differentiate VE and ALE. A prospective observational multicentre cohort study, which continuously enrolled patients diagnosed with either ALE or VE from October 2011 to April 2023. The demographic data, clinical features, and laboratory test results were collected and subjected to logistic regression analyses. The model was displayed as a web-based nomogram and then modified into a scored prediction tool. Model performance was assessed in both derivation and external validation cohorts. A total of 2423 individuals were recruited, and 1001 (496 VE, 505 ALE) patients were included. Based on the derivation cohort (389 VE, 388 ALE), the model was developed with eight variables including age at onset, acuity, fever, headache, nausea/vomiting, psychiatric or memory complaints, status epilepticus, and CSF white blood cell count. The model showed good discrimination and calibration in both derivation (AUC 0.890; 0.868-0.913) and external validation (107 VE, 117 ALE, AUC 0.872; 0.827-0.917) cohorts. The scored prediction tool had a total point that ranged from - 4 to 10 also showing good discrimination and calibration in both derivation (AUC 0.885, 0.863-0.908) and external validation (AUC 0.868, 0.823-0.913) cohorts. The prediction model provides a reliable and user-friendly tool for differentiating between the VE and ALE, which would benefit early diagnosis and appropriate treatment and alleviate economic burdens on both patients and society.

Improving Early Recognition of Potentially Treatable Causes of Rapidly Progressive Dementia

AbstractBackgroundRapidly progressive dementia (RPD) includes patients with less than two years from the onset of cognitive impairment to incapacitation due to dementia. Although RPD is often associated with fatal neurodegenerative diseases, including early‐onset Alzheimer disease or Creutzfeldt‐Jakob disease, treatable forms of RPD are increasingly recognized. Early recognition of patients with potentially treatable causes of RPD is key to the timely provision of therapies required to achieve the best possible long‐term outcomes.Method155 patients with RPD were prospectively enrolled from February 2016 to August 2022 via two tertiary care centers. Etiologic diagnoses were independently assigned by two neurologists with good agreement (>90%). Causes of RPD were further classified as treatment‐responsive or nonresponsive, referencing the extant literature. Demographic, clinical, and paraclinical features associated with treatable causes of RPD were identified using stepwise multivariate logistic regression and validated with 5‐fold cross validation.Result87/155 patients (56.1%) had a potentially treatable cause of RPD, including autoimmune/inflammatory disease (n = 52, 59.8%), vasculitis (n = 13, 14.9%), primary psychiatric disease (n = 4, 4.6%), or nutritional deficiency (n = 4, 4.6%). Multivariable analyses identified seven features that were independently associated with treatment‐responsiveness: age‐at‐symptom onset (OR: 0.62 per decade, 95%CI: 0.42‐0.93), seizures (OR: 9.81, 95%CI: 2.84‐33.89), MRI suggestive of autoimmune encephalitis (OR: 23.08, 95%CI: 2.28‐233.40), CSF white blood cell count ≥10 cells/mm3 (OR: 32.24, 95%CI:5.80‐179.21), movement abnormalities (OR: 4.99, 95%CI: 1.76‐14.10), presence of disease‐associated tumor (OR: 13.82, 95%CI: 2.25‐85.11), and mania (OR: 18.47, 95%CI: 1.76‐193.61). Model performance was excellent (c‐statistic = 0.88, 95%CI: 0.82‐0.94; p<0.001): 71 patients (81.6%) with potentially treatable causes of RPD and 56 patients (82.4%) with non‐treatable causes of RPD were correctly classified (PPV = 85.5%; NPV = 77.8%).ConclusionTreatment‐responsive causes of RPD were common in our series. Younger age, seizures, movement abnormalities, or mania at presentation, and paraclinical tests suggesting inflammation (MRI or CSF) or tumor in patients with RPD should prompt consideration of treatable causes of RPD and initiation of treatment when indicated.

Cerebrospinal fluid indices as predictors of treatment response in autoimmune encephalitis

BackgroundCerebrospinal fluid (CSF) indices reflecting intrathecal antibody production and blood-brain barrier impairment are not routinely assessed in patients with autoimmune encephalitis (AE). We aimed to study CSF indices and their association with the prognosis of AE. MethodsThis retrospective cohort study conducted at Amrita Institute of Medical Sciences (AIMS), Kochi, India, included 60 patients aged more than 18 years with definite/probable/possible AE admitted to the Department of Neurology from August 2016 to November 2021. We introduced a classification of treatment response based on modified Rankin Scale change over time and treatment modalities. ResultsIn our cohort of 60 patients (six [10%] seropositive cases), a good rapid treatment response was associated with CSF white blood cell count of more than 4 cells/mm3 (OR, 4.57; 95% CI 1.31–15.96; P = .02) and positive immunoglobulin G (IgG) Local Synthesis (OR, 7.27; 95% CI 1.56–33.86; P = .01). Albumin Index had association with a poor Glasgow Coma Scale score at the nadir of the disease (OR, 1.17; 95% CI 1.01–1.34; P = .04). Similar results were yielded in the seronegative cohort. IgG Local Synthesis appeared to be a strong predictor for good rapid treatment response in both univariate and multivariate (adjusted OR, 28.71; 95% CI 2.12–389.22; P= .01) analysis. Time to immunotherapy was reversely correlated with good response overall (in the cohort with outliers removed [N = 49]: unadjusted OR 0.97, 95% CI 0.95–0.99; P= .01; adjusted OR 0.97; 95% CI 0.95–0.99; P= .008). ConclusionCSF indices reflecting intrathecal antibody production and blood-brain barrier impairment appear to be promising predictors of disease severity and therapeutic response in patients with autoimmune encephalitis.

Therapeutic Lumbar Punctures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Should Opening Pressure Direct Management?

BackgroundIncreased intracranial pressure (ICP) frequently complicates cryptococcal meningitis. Therapeutic lumbar punctures (LPs) have acute survival benefits in the first week, and we sought to understand the longer-term survival impact of therapeutic LPs.MethodsWe prospectively enrolled human immunodeficiency virus (HIV)–seropositive adults with cryptococcal meningitis from 2013 to 2017 in Uganda. We assessed the association between clinical characteristics, CSF parameters, and 14- and 30-day mortality by baseline ICP. We also assessed 30-day mortality by number of follow-up therapeutic LPs performed within 7 days.ResultsOur analysis included 533 participants. Participants with baseline ICP >350 mm H2O were more likely to have Glasgow Coma Scale (GCS) score <15 (P < .001), seizures (P < .01), and higher quantitative cryptococcal cultures (P < .001), whereas participants with ICP <200 mm H2O were more likely to have baseline sterile CSF cultures (P < .001) and CSF white blood cell count ≥5 cells/µL (P = .02). Thirty-day mortality was higher in participants with baseline ICP >350 mm H2O and ICP <200 mm H2O as compared with baseline ICP 200–350 mm H2O (hazard ratio, 1.55 [95% confidence interval, 1.10–2.19]; P = .02). Among survivors at least 7 days, the 30-day relative mortality was 50% higher among participants who did not receive any additional therapeutic LPs compared to those with ≥1 additional follow-up LP (33% vs 22%; P = .04), irrespective of baseline ICP.ConclusionsManagement of increased ICP remains crucial in improving clinical outcomes in cryptococcal meningitis. Guidelines should consider an approach to therapeutic LPs that is not dictated by baseline ICP.

77. Opportunity for Improved Use of a Commercially Available Meningitis/Encephalitis Panel in Pediatric Patients

Abstract Background The BioFire® FilmArray Meningitis/Encephalitis (ME) panel delivers timely CSF analysis when meningitis or encephalitis is suspected and has the potential for earlier optimization of patient care. It is unclear if the M/E panel provides incremental benefit over standard microbiologic methods such as culture and cell counts, especially in the absence of significant pleocytosis. We evaluated the clinical utility of the ME panel with respect to CSF white blood cell count per high power field (WBC/hpf) and patient age. Methods We identified paired CSF ME panels and CSF cultures collected throughout a large healthcare system from 2016–May 2021 in children &amp;lt; 18 years of age. CSF results from the same calendar day were included in the dataset. We reviewed standalone HSV and Enterovirus (EV) CSF studies to determine frequency of duplicative testing. Results were stratified by CSF WBC/hpf and patient age (&amp;lt; 14 days, 14–60 days, &amp;gt; 60 days and &amp;lt; 5 years, and &amp;gt; 5 years). Results 1045 paired cultures and ME panels were identified. Of those, 921 (88%) ME panels were negative, but 5 of those cultures grew bacteria. Of 124 (12%) positive ME panel results, 66% were viral: 46 (37%) EV, 22 (18%) HHV-6 and 6 (5%) parechovirus. In 498 cases, ME panels were sent when CSF had &amp;lt; 10 WBC/hpf, resulting in only 2 (0.4%) PCRs positive for bacteria, one which was gram stain positive and the other was considered a false positive (Table 1). In addition to a ME panel, standalone PCRs for enterovirus and HSV were sent in 134 (13%) and 213 (20%) of cases, respectively, with &amp;lt; 2% discordance. Pathogen distribution by ME panel did not vary with age (Table 2). Meningitis and encephalitis panel, standalone PCR and culture results overall and by age group. Conclusion In our cohort, the ME panels were overwhelmingly negative. Only 12% of ME panels were positive, mostly with self-limited viral pathogens (e.g., EV, parechovirus). Performance was worse when samples had &amp;lt; 10 WBC/hpf. Duplicative testing was common and had no benefit. Performance was similar across age groups. More targeted use of the ME panel could improve the utility and efficacy of this test. Disclosures Anne Bonkowsky, MD/PhD, BioFire Diagnostics (Consultant, Grant/Research Support, Other Financial or Material Support, I have intellectual property through the University of Utah in BioFire Diagnostics and the FilmArray and receive royalties through the University of Utah.)Merck (Advisor or Review Panel member)

A.1 CSF Findings in Early Active Autoimmune Encephalitis

Background: Treatment decisions for patients with autoimmune encephalitis (AE) frequently need to be made before results from autoantibody testing are available, as early treatment is associated with better outcomes. Cerebrospinal fluids (CSF) white blood cell (WBC) count and protein concentration measured early on in the disease process is often used, in combination with other clinical factors, to evaluate the likelihood that a patient has AE. Methods: CSF characteristics (WBC count, protein concentration, and oligoclonal banding) measured in a first AE presentation, prior to results of autoantibodies being available, were retrospectively analyzed at two tertiary care centers. Results: Ninety-five patients were included in the study. CSF WBC counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). Conclusions: A substantial proportion of patients with early active AE had a CSF WBC count or protein concentration within the normal. Inclusion of CSF oligoclonal banding may help identify a higher proportion of patients with an inflammatory CSF profile early in the disease process.

Bing-Neel Syndrome: A Rare Mimic of Secondary Normal Pressure Hydrocephalus.

An 80-year-old man, in remission from Waldenström macroglobulinemia (WM), presented with 6-month cognitive decline, broad-based shuffling gait, and nocturia. Serial CT head demonstrated progressive ventriculomegaly. MRI revealed abnormal fluid-attenuated inversion recovery signal in the lateral ventricles with fluid–fluid levels and in peripheral sulci/basal cisterns. Pachymeningeal thickening/enhancement was noted at the frontal dura, cavernous sinus, and Meckel caves (Figure). Spinal MRI revealed enhancement along the thoracic spinal cord/conus with a thickened cauda equina. Highly proteinaceous CSF (7.01 g/L) formed a jelly-like precipitate moments after lumbar puncture (Video 1). CSF white blood cell count was 27 × 106/L (92% lymphocyte) and flow cytometric analysis confirmed recurrent CNS WM (Bing-Neel syndrome).1,2

Reader Response: CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series.

We read with interest the article by Edén et al.1 assessing the CSF biomarkers of intrathecal inflammation (CSF white blood cell counts, neopterin, β2-microglobulin [β2M], and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in COVID-19 patients with neurologic symptoms. The results illustrate evidence of significant CSF inflammation with raised soluble markers without any cellular response, unlike other viral CNS infections. As far as intrathecal markers such as neopterin and β2M are concerned, these are nonspecific and are produced by macrophages during the activation of cell-mediated immune response. These are often found significantly raised in various conditions such as HIV infection,2 relapsing-remitting or chronic progressive multiple sclerosis,3 and head trauma,4 putting forth questions about its value as a disease-specific marker.

Determinants of cognition in autoimmune limbic encephalitis-A retrospective cohort study.

Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE. Hence, we here investigate major determinants of cognitive functioning in ALE. In a retrospective analysis of 102 patients with ALE, we first compared verbal learning capacity, nonverbal learning capacity, and attentional and executive functioning by absence or presence of different types of neural autoantibodies (AABs). Subsequently we established three linear regression models including 63, 38, and 61 patients, respectively to investigate how cognitive functioning in these domains may depend on common markers of ALE such as intrathecal inflammation, blood-cerebrospinal fluid (CSF)-barrier function, mesiotemporal epileptiform discharges and slowing, determined by electroencephalography (EEG) and structural mesiotemporal changes, measured with magnetic resonance imaging (MRI). We also accounted for possible effects of cancer- and immunotherapy and other centrally effective medication. There was no effect of AAB status on cognitive functioning. Although the regression models could not predict verbal and nonverbal learning capacity, structural mesiotemporal neural network alterations on T2-/fluid attenuated inversion recovery (FLAIR)-signal-weighted MRI and mesiotemporal epileptiform discharges or slowing on EEG exerted a significant impact on memory functions. In contrast, the regression model significantly predicted attentional and executive functioning with CSF white blood cell count and centrally effective medication being significant determinants. In this cohort, cognitive functioning in ALE does not depend on the AAB status. Common markers of ALE cannot predict memory functioning that only partially depends on structural and functional alterations of mesiotemporal neural networks. Common markers of ALE significantly predict attentional and executive functioning that is significantly related to centrally effective medication and CSF white blood cell count, which may point toward inflammation affecting brain regions beyond the limbic system.

CSF shunt valve occlusion-does CSF protein and cell count matter?

Shunt obstruction is a common cause of shunt failure in the treatment of hydrocephalus. Valve occlusion is traditionally believed to originate from elevated CSF protein or cellular components, although detailed evidence is scarce and contradictory. Therefore, this study aimed to examine CSF protein and cell count as risk factors for valve obstruction. We retrospectively examined 274 patients who underwent shunt placement for hydrocephalus between 2009 and 2018 and had at least 1year follow-up. Age, aetiology of hydrocephalus, valve type, occurrence of revision, reason for revision and CSF protein and cell count at the time of shunt insertion and revision surgery were analysed. Thirty-two of 274 patients (11.7%) required revision surgery due to valve occlusion. Mean time to revision was 143days. CSF white blood cell (WBC) count but not protein was associated with valve occlusion overall. Of all obstructed valve patients, 25% showed CSF protein level within the normal range, whereas 13.6% of the patients overall showed greatly elevated CSF protein level without evidence of valve obstruction. Persistently elevated CSF protein level at the time of shunt revision was significantly associated with valve obstruction within 90days of initial insertion (early occlusion). Children with congenital malformations and post-haemorrhagic patients were significantly overrepresented in the occlusion group, particularly in the early occlusion group. Pathological CSF values such as WBC count and persistently elevated protein level serves as a risk factor for early valve obstruction. Late obstruction occurs independent of normal CSF values. Infants are particularly prone to early and late valve obstructions. CSF protein level at shunt insertion is not predictive of valve occlusion.

Comparison of children with acute flaccid myeltis before and after 2014.

To observe whether cases of acute flaccid myelitis (AFM) before and since August 1, 2014, had important differences and to further characterize patients with AFM regarding clinical, laboratory, imaging, and treatment findings. All pediatric patients with AFM at our institution were reviewed. Demographic, clinical, and diagnostic data were collected through medical record review. Patients with onset before August 1, 2014, and after that date were compared and when applicable compared with Centers for Disease Control and Prevention data. Sixteen patients were included, 6 in the pre-2014 and 10 in the post-2014 group. The mean age in the pre-2014 group was 7.4 years and in the post-2014 group was 6.4 years. Initial symptoms were similar in both groups, as were functional and motor abilities at disease nadir and the most recent follow-up. Post-2014 patients had a higher mean CSF white blood cell count (57) and neutrophil count (30%) compared with pre-2014 patients (3.2 and 0.5%, respectively). Eighty percent of post-2014 patients had positive enterovirus/rhinovirus testing, with 57% of specimens positive for enterovirus D68 (EV-D68). On acute imaging, a triad of brainstem, cervical cord gray matter involvement, and ventral nerve root/cauda equina (CE) thickening/enhancement was found in 5 patients. The groups had more similarities than differences but with a more inflammatory picture in the post-2014 patients. The constellation of cervical cord gray matter, brainstem, and nerve root/CE thickening should raise suspicion for AFM in the appropriate clinical setting. Most post-2014 patients had associated enterovirus infections, and over half tested for EV-D68 were positive. There was minimal clinical improvement in both groups despite various immunotherapies.

Outcome following postneurosurgical Acinetobacter meningitis: an institutional experience of 72 cases.

The authors aimed to evaluate the antimicrobial susceptibility pattern of Acinetobacter isolates responsible for nosocomial meningitis/ventriculitis in the neurosurgical ICU. The authors also sought to identify the risk factors for mortality following Acinetobacter meningitis/ventriculitis. This was a retrospective study of 72 patients admitted to the neurosurgical ICU between January 2014 and December 2018 with clinical and microbiological diagnosis of nosocomial postneurosurgical Acinetobacter baumanii meningitis/ventriculitis. Electronic medical data on clinical characteristics, underlying pathology, CSF cytology, antibiotic susceptibilities, and mortality were recorded. To evaluate the outcome following nosocomial postneurosurgical Acinetobacter meningitis/ventriculitis, patients were followed up until discharge or death in the hospital. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to compute factors affecting survival. The study population was divided into two groups depending on the final outcome of whether the patient died or survived. Forty-three patients (59.7%) were included in the survivor group and 29 patients (40.3%) were included in the nonsurvivor group. Total in-hospital mortality due to Acinetobacter meningitis/ventriculitis was 40.3% (29 cases), with a 14-day mortality of 15.3% and a 30-day mortality of 25%. The 43 (59.7%) patients who survived had a mean length of hospital stay of 44 ± 4 days with a median Glasgow Outcome Scale-Extended score at discharge of 6. On univariate analysis, age > 40 years (p = 0.078), admission Glasgow Coma Scale (GCS) score ≤ 8 (p = 0.003), presence of septic shock (p = 0.011), presence of external ventricular drain (EVD) (p = 0.03), CSF white blood cell (WBC) count > 200 cells/mm3 (p = 0.084), and comorbidities (diabetes, p = 0.036; hypertension, p = 0.01) were associated with poor outcome. Carbapenem resistance was not a risk factor for mortality. According to a multivariable Cox proportional hazards model, age cutoff of 40 years (p = 0.016, HR 3.21), GCS score cutoff of 8 (p = 0.006, HR 0.29), CSF WBC count > 200 cells/mm3 (p = 0.01, HR 2.76), presence of EVD (p = 0.001, HR 5.42), and comorbidities (p = 0.017, HR 2.8) were found to be significant risk factors for mortality. This study is the largest case series reported to date of postneurosurgical Acinetobacter meningitis/ventriculitis. In-hospital mortality due to Acinetobacter meningitis/ventriculitis was high. Age older than 40 years, GCS score less than 8, presence of EVD, raised CSF WBC count, and presence of comorbidities were risk factors for mortality.

Corrected white blood cell count, cell index, and validation of a clinical model for the diagnosis of health care-associated ventriculitis and meningitis in adults with intracranial hemorrhage

ObjectivesTo evaluate the utility of the corrected CSF white blood cell (WBC) count, cell index, CSF lactate, CSF glucose and a newly developed diagnostic model for the diagnosis of healthcare-associated ventriculitis or meningitis (HCAVM) in the setting of intracranial hemorrhage (ICH). Patients and methodsA case-control study of 111 adult patients with ICH with HCAVM (cases) or without HCAVM (controls) matched 1:2 by age, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II (APACHE II) score enrolled in a large tertiary care center from 2003 to 2016. ResultsSubjects were appropriately matched by age, GCS, and APACHE II score (P > 0.2). Cases had significantly higher CSF WBC count (uncorrected and corrected), cell index, and CSF lactate, but lower CSF glucose levels than controls (P < 0.05). There were no differences between CSF protein, CSF neutrophilic pleocytosis, and serum C-reactive protein between cases and controls (P > 0.1). The diagnostic accuracy as analyzed by the area under the receiver operating characteristic curve (AUC of ROC) was found to be good for the cell index (0.825), fair for the corrected CSF WBC count (0.770), and poor for the diagnostic model and uncorrected CSF WBC count (0.652 and 0.653, respectively). ConclusionThe diagnosis of HCAVM in patients with ICH remains challenging and although no single parameter is sufficient for diagnosis the cell index proved to be an important indicator of infection in our study.

A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis.

ObjectiveTo construct a grading score that predicts neurologic function 1 year after diagnosis of anti-NMDA receptor (NMDAR) encephalitis.MethodsThree hundred eighty-two patients with detailed information and functional status at 1 year were studied. Factors associated with poor status (defined as modified Rankin Scale score ≥3) were identified and incorporated into a multivariate logistic regression model. This model was used to develop a 5-point prediction score, termed the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score.ResultsIntensive care unit admission (p < 0.001), treatment delay >4 weeks (p = 0.012), lack of clinical improvement within 4 weeks (p < 0.001), movement disorder (p = 0.001), central hypoventilation (p < 0.001), elevated CSF white blood cell count (p < 0.001), elevated CSF protein level (p = 0.027), and abnormal MRI (p = 0.002) were associated with 1-year functional status in univariate analysis. Intensive care unit admission, treatment delay >4 weeks, lack of clinical improvement within 4 weeks, abnormal MRI, and CSF white blood cell count >20 cells/μL were independent predictors for outcome in multivariate regression modeling. These 5 variables were assigned 1 point each to create the NEOS score. NEOS score strongly associated with the probability of poor functional status at 1 year (3% for 0 or 1 point to 69% for 4 or 5 points, p < 0.001).ConclusionsThe NEOS score accurately predicts 1-year functional status in patients with anti-NMDAR encephalitis. This score could help estimate the clinical course following diagnosis and may aid in identifying patients who could benefit from novel therapies.

Cerebrospinal fluid protein and glucose levels in neonates with a systemic inflammatory response without meningitis

BackgroundIt has been estimated that paediatric meningitis without elevated CSF white cell count (pleocytosis) accounts for 0.5–12% of all cases of bacterial meningitis. CSF protein and glucose measurements are therefore essential in management but may be neglected in clinical practice. In order to improve recognition of bacterial meningitis in neonates and to enable adequate management and audit, we investigated whether a systemic inflammatory response in the absence of meningitis is associated with elevated CSF protein and reduced CSF glucose levels. A further aim was to determine whether abnormal levels of these parameters were associated with increased incidence of neurological damage.MethodsAs part of an audit into management of abnormal CSF findings in neonates, we conducted a retrospective analysis of neonates without meningitis as evident from normal CSF white blood cell counts and negative CSF culture. We compared data from neonates with fever (temperature > 38.0 °C) and/or elevated C-reactive protein (CRP) levels (> 5 mg/l) (possible sepsis) with data from neonates without fever or CRP elevation.ResultsWe analysed results from a total of 244 neonates. CSF protein levels were 0.89 g/l (SD 0.37) in neonates without fever or elevated CRP (n = 26) and not significantly different from neonates with possible sepsis (n = 218) with 0.92 g/l (SD 0.40). CSF glucose levels in infants with possible sepsis were 2.71 (SD 0.83) mmol/l and not significantly different from infants without sepsis with 2.55 mmol/l (SD 0.34).ConclusionsCSF protein and glucose levels are not affected by a systemic inflammatory response syndrome if there is no meningitis.

The aetiologies of central nervous system infections in hospitalised Cambodian children

BackgroundCentral nervous system (CNS) infections are an important cause of childhood morbidity and mortality. The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia.MethodsWe did a one year prospective study of children hospitalised with suspected CNS infection at Angkor Hospital for Children, Siem Reap. Cerebrospinal fluid specimens (CSF) samples underwent culture, multiplex PCR and serological analysis to identify a range of bacterial and viral pathogens. Viral metagenomics was performed on a subset of pathogen negative specimens.ResultsBetween 1st October 2014 and 30th September 2015, 284 analysable patients were enrolled. The median patient age was 2.6 years; 62.0% were aged <5 years. CSF white blood cell count was ≥10 cells/μL in 116/272 (42.6%) cases. CNS infection was microbiologically confirmed in 55 children (19.3%). Enteroviruses (21/55), Japanese encephalitis virus (17/55), and Streptococcus pneumoniae (7/55) accounted for 45 (81.8%) of all pathogens identified. Of the pathogens detected, 74.5% (41/55) were viruses and 23.6% (13/55) were bacteria. The majority of patients were treated with ceftriaxone empirically. The case fatality rate was 2.5%.ConclusionsEnteroviruses, JEV and S. pneumoniae are the most frequently detected causes of CNS infection in hospitalised Cambodian children.

Aseptic meningitis in adults and children: Diagnostic and management challenges

BackgroundAseptic meningitis represents a common diagnostic and management dilemma to clinicians. ObjectivesTo compare the clinical epidemiology, diagnostic evaluations, management, and outcomes between adults and children with aseptic meningitis. Study designWe conducted a retrospective study from January 2005 through September 2010 at 9 Memorial Hermann Hospitals in Houston, TX. Patients age≥2months who presented with community-acquired aseptic meningitis with a CSF white blood cell count >5cells/mm3 and a negative Gram stain and cultures were enrolled. Patients with a positive cryptococcal antigen, positive blood cultures, intracranial masses, brain abscesses, or encephalitis were excluded. ResultsA total of 509 patients were included; 404 were adults and 105 were children. Adults were most likely to be female, Caucasian, immunosuppressed, have meningeal symptoms (headache, nausea, stiff neck, photophobia) and have a higher CSF protein (P <0.05). In contrast, children were more likely to have respiratory symptoms, fever, and leukocytosis (P <0.05). In 410 (81%) patients, the etiologies remained unknown. Adults were more likely to be tested for and to have Herpes simplex virus and West Nile virus while children were more likely to be tested for and to have Enterovirus (P <0.001). The majority of patients were admitted (96.5%) with children receiving antibiotic therapy more frequently (P <0.001) and adults receiving more antiviral therapy (P=0.001). A total of 384 patients (75%) underwent head CT scans and 125 (25%) MRI scans; all were normal except for meningeal enhancement. All patients had a good clinical outcome at discharge. DiscussionAseptic meningitis in adults and children represent a management challenge as etiologies remained unknown for the majority of patients due to underutilization of currently available diagnostic techniques.

Prediction of Outcome From Adult Bacterial Meningitis in a High-HIV-Seroprevalence, Resource-Poor Setting Using the Malawi Adult Meningitis Score (MAMS).

Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates >50%. To improve outcome, interventional trials and standardized clinical algorithms are urgently required. To optimize these processes, we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian patients with ABM (n = 523 [65%] cerebrospinal fluid [CSF] culture positive). We validated the nomogram internally using a bootstrap procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dexamethasone and glycerol using clinical trial data from Malawi. ABM mortality at 6-week follow-up was 54%. Five of 15 variables tested were strongly associated with poor outcome (CSF culture positivity, CSF white blood cell count, hemoglobin, Glasgow Coma Scale, and pulse rate), and were used in the derivation of the Malawi Adult Meningitis Score (MAMS) nomogram. The C-index (area under the curve) was 0.76 (95% confidence interval, .71-.80) and calibration was good (Hosmer-Lemeshow C-statistic = 5.48, df = 8, P = .705). Harmful effects of adjunctive glycerol were observed in groups with relatively low predicted risk of poor outcome (25%-50% risk): Case Fatality Rate of 21% in the placebo group and 52% in the glycerol group (P < .001). This effect was not seen with adjunctive dexamethasone. MAMS provides a novel tool for predicting prognosis and improving interpretation of ABM clinical trials by risk stratification in resource-poor settings. Whether MAMS can be applied to non-HIV-endemic countries requires further evaluation.

Circulating Memory T Follicular Helper Cells in Patients with Neuromyelitis Optica/Neuromyelitis Optica Spectrum Disorders.

Objective. This study aimed to examine the potential role of memory T follicular helper (Tfh) cells in patients with neuromyelitis optica/neuromyelitis optica spectrum disorders (NMO/NMOSD). Methods. The percentages of different subsets of circulating memory Tfh cells in 25 NMO/NMOSD patients before and after treatment as well as in 17 healthy controls were examined by flow cytometry. The levels of IL-21 and AQP4 Ab in plasma and CSF were measured by ELISA. Results. The percentages and numbers of circulating memory Tfh cells, ICOS+, CCR7−, CCR7−ICOS+, CCR7+, CCR7+ICOS+ memory Tfh cells, and the levels of IL-21 in plasma and CSF were significantly increased in NMO/NMOSD patients. The percentages of CCR7− and CCR7−ICOS+ memory Tfh cells were positively correlated with ARR, plasma IL-21, and AQP4 Ab levels. The percentages of CCR7+ and CCR7+ICOS+ memory Tfh cells were positively correlated with CSF white blood cell counts, proteins, and IL-21 levels. Treatment with corticosteroids significantly reduced the numbers of CCR7−ICOS+ and CCR7+ICOS+ memory Tfh cells as well as plasma IL-21 levels in patients with partial remission. Conclusions. Our findings indicate that circulating memory Tfh cells may participate in the relapse and development of NMO/NMOSD and may serve as a new therapeutic target.

Cerebrospinal fluid white blood cell counts in infants with myelomeningoceles

The authors undertook this study to determine white blood cell (WBC) counts in CSF obtained from lateral ventricles and myelomeningoceles (MMCs) in infants in a developing country at the time of their initial presentation for medical evaluation. CSF was aspirated from the lateral ventricles and from MMC sacs of 100 consecutive infants at Kijabe Hospital, Kijabe, Kenya. Peripheral blood WBC counts and CSF WBC counts were determined in the laboratory. CSF with WBC counts of 5 cells/mm(3) or greater was cultured. The mean WBC count in ventricular CSF was 16 cells/mm(3), with a median and mode of 0 cells/mm(3). The mean WBC count of CSF in MMC sacs was 141 cells/mm(3) (median 15 cells/mm(3)). No child had both a positive culture from ventricular CSF and a negative culture from MMC CSF. There was no correlation between age at presentation and WBC counts in the MMCs. Infants younger than 8 days old were as likely to have high WBC counts in CSF from their MMC sacs as were older children; 7 of 12 infants with 500 WBCs or more in CSF from their MMCs were younger than 8 days old. Only 5 of 58 CSF specimens from MMC sacs with 5 or more WBCs/mm(3) had positive bacterial cultures, which may be a reflection of CSF specimen processing rather than of true culture negativity. CSF from ventricular fluid of infants presenting with MMCs infrequently has high WBC counts, so infrequently that it does not need to be evaluated routinely. CSF in MMC sacs often has high WBC counts that suggest the presence of bacterial infection. In developing countries where culture reliability is questionable, intravenous administration of antibiotics before MMC closure for infants with high MMC WBC counts may diminish postoperative meningitis/ventriculitis.