CSF Leukocyte Count Research Articles

Validation of the encephalitis criteria in adults with a suspected central nervous system infection: An updated score

ObjectivesWe aimed to validate and refine the encephalitis criteria proposed by the International Encephalitis Consortium in a cohort of adults initially suspected of a central nervous system (CNS) infection. MethodsWe included patients from two prospective cohort studies consisting of adults suspected of a CNS infection whom underwent a diagnostic lumbar puncture. We evaluated the test characteristics of the criteria for both possible and probable encephalitis. The reference standard was a final clinical diagnosis of encephalitis. Recalibration of the criteria was done by adjusting the weight of each criterion based on their respective odds. ResultsIn total 1446 episodes were evaluated, of whom 162 (11%) had a clinical diagnosis of encephalitis. Possible encephalitis had a sensitivity of 41% (95% CI 33-49) and a specificity of 88% (95% CI 86-90). Probable encephalitis had a sensitivity and specificity of respectively 27% (95% CI 20-34) and 95% (95% CI 94-96). Through odds-based weighting we recalibrated the weight of each individual criterion, resulting in a model consisting of an altered mental status (weight of 2), seizures (weight of 3), elevated CSF leukocyte count (weight of 5) and abnormalities on neuroimaging (weight of 9). We proposed a cut-off at 5 for possible encephalitis, (sensitivity 93% [95% CI 88-96]; specificity 51% [95% 49-54]), and at 8 for probable encephalitis (sensitivity 51% [95% CI 44-59]; specificity 91% [95% CI 89-92]). ConclusionsWe validated and refined the existing diagnostic criteria for encephalitis, leading to a substantially enhanced sensitivity. These updated criteria hold promise to facilitate the accurate identification of encephalitis.

CSF Findings in Chinese Patients with NMDAR, LGI1 and GABABR Antibody-Associated Encephalitis.

CSF inflammation in subtypes of antibody-defined autoimmune encephalitis (AE) ranges in intensity from moderate to severe. In a retrospective, cross-sectional study, we characterized CSF findings in Chinese patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E), anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E), and anti-gamma aminobutyric acid-B receptor encephalitis (GABABR-E). The AE cases, including 102 NMDAR-E, 68 LGI1-E and 15 GABABR-E, were included. CSF inflammatory parameters consisted primarily of CSF leukocytes, oligoclonal bands (OCBs), and CSF/serum albumin ratios (QAlb). Ten serum cytokines were evaluated in order to classify AE subtypes. 88% of NMDAR-E, 80% of GABABR-E, and 51% of LGI1-E patients had aberrant CSF features. In NMDAR-E, the CSF leukocyte count, CSF protein concentration, and age-adjusted QAlb were significantly higher than in LGI1-E, but did not differ from GABABR-E. Blood-CSF barrier dysfunction was less common in NMDAR-E patients with >40 years old. On admission, inflammatory CSF response was more prevalent in NMDAR-E patients with a higher CASE score. With age <60 years, CSF inflammatory changes were less frequent in LGI1-E patients, but more common in GABABR-E patients. MCP-1, IL-10, IL-1β, and IL-4 were potential classifiers for NMDAR-E, LGI1-E, and GABABR-E, and correlated substantially with CSF leukocyte count and QAlb. Subtype-specific patterns are formed by the various inflammatory CSF parameters in NMDAR-E, LGI1-E, and GABABR-E, and their correlation with disease severity, age, and disease duration. CSF inflammatory characteristics associated with MCP-1, IL-10, IL-1β, and IL-4 may be potential immunopathogeneses targeting markers for these AE subtypes.

Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections

We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis. We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis. We included 738 episodes between 2017 and 2022, split into a derivation (n=450) and validation cohort (n=288). Of these patients, 224 (30%) were diagnosed with CNS infection, of which 81 (11%) with bacterial meningitis, 107 (14%) with viral meningitis or encephalitis, and 35 patients (5%) with another CNS infection. Diagnostic accuracy of CRP, IL-6, and Il-1β in CSF was high, especially for diagnosing bacterial meningitis. Combining these biomarkers in a multivariable model increased accuracy and provided excellent discrimination between bacterial meningitis and all other disorders (AUC=0.99), outperforming all individual biomarkers as well as CSF leukocytes (AUC=0.97). When applied to the population of patients with a CSF leukocyte count of 5-1000 cells/mm3, accuracy of the model also provided a high diagnostic accuracy (AUC model=0.97 vs. AUC CSF leukocytes=0.80) with 100% sensitivity and 92% specificity. These results remained robust in a temporal validation cohort. Inflammatory biomarkers in CSF are able to differentiate CNS infections and especially bacterial meningitis from other disorders. When these biomarkers are combined, their diagnostic accuracy exceeds that of CSF leukocytes alone and as such these markers have added value to current clinical practice.

Diagnostic accuracy of clinical and laboratory characteristics in suspected non-surgical nosocomial central nervous system infections

BackgroundThe diagnosis of meningitis in nonsurgical hospitalised patients is often difficult and diagnostic accuracy of clinical, laboratory, and radiological characteristics is unknown. MethodsIn a prospective multi-centre cohort study in the Netherlands with adults suspected of central nervous system (CNS) infections, we included consecutive patients who underwent a lumbar puncture for the suspicion of a nonsurgical nosocomial CNS infection. All episodes were categorized into five final clinical diagnosis categories, as reference standard: CNS infection, CNS inflammatory disease, systemic infection, other neurological disease, or non-systemic, non-neurological disease. Diagnostic accuracy of clinical characteristics, the index test, was assessed by determining sensitivity, specificity, and positive and negative predictive values (PPV; NPV). ResultsBetween 2012-2022, 114 of 1275 (9%) patients included in the cohort had suspected nonsurgical nosocomial CNS infection. Sixteen (14%) patients had a confirmed diagnosis of nonsurgical nosocomial CNS infection, including 4 (25%) with bacterial meningitis, 9 (56%) with viral CNS infections, 2 (13%) fungal meningitis and 1 (6%) parasitic meningitis. Diagnostic accuracy of individual clinical characteristics was generally low. Elevated CSF leukocyte count had the highest sensitivity (81%; 95% CI 54-96) and NPV (96%; 95% CI 90-99). When combining the presence of abnormalities in neurological or CSF examination, sensitivity for diagnosing a CNS infection was 100% (95% CI 79-100) and NPV 100% (95% CI 78-100). CSF examination changed clinical management in 47% of patients. ConclusionOf patients suspected of nonsurgical nosocomial CNS infections, 14% were diagnosed with such infections. Diagnostic accuracy for individual clinical characteristics was low, with elevated CSF leukocyte count having the highest sensitivity and NPV.

A Multicenter Epidemiological and Pathogenic Characteristics Study of Community-Acquired Bacterial Meningitis Children in China: Results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

To explore the epidemiological and pathogenic characteristics of children with community-acquired bacterial meningitis. A multicenter, retrospective study was conducted among CABM patients under 15 years old from 33 hospitals in China from 2019 to 2020. The medical record, laboratory, and microbiological data were collected and analyzed. A total of 1610 children with CABM were identified and presented at a median onset age of 45 days of whom 955 (59.3%) were males. CABM occurred mostly in infants <1 year of age (84.0%, 1352/1610). In etiology-confirmed cases, the pathogens were isolated from CSF culture in 515 (32.0%), 400 (24.8%) in blood culture, and 186 (11.6%) both in CSF and blood culture. In total, 126 pathogens were identified through CSF mNGS in 330 CABM cases; 21 S. pneumoniae isolates were detected in 83 CABM cases by antigen detection method. Major pathogens were E. coli (195, 24.7%), GBS (170, 21.5%), and S. pneumoniae (157, 19.9%). GBS (29.3%, 22/75) was the first pathogen of CABM in neonates aged 0-6 days old, while E. coli (44.7%, 76/170) in 7 to 28 days of age; S. pneumoniae (96.2%, 151/157) was the most common pathogen in >3 months old cases. About 9.7% (19/195) strains of E. coli produced ultra‑broad‑spectrum β‑lactamases. The common intracranial imaging complications were subdural effusion and (or) empyema in 349 (21.7%), hydrocephalus in 233 (14.5%), and cerebral abscess in 178 (11.1%). A total of 389 (24.2%) cases were completely cured and 1088 (67.6%) cases improved. Among 166 patients (10.3%) with adverse outcomes, 32 cases (2.0%) died, and 37 cases (2.3%) relapsed. The onset age of CABM in children is usually within 1 year of age, especially <3 months. The primary pathogens in infants less than 3 months old are E. coli and GBS, and the dominant pathogen in children older than 3 months old is S. pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. CABM should not be excluded even if CSF leukocyte counts are within normal range. Due to the low detection rate of pathogens in children with CABM, standardized CSF bacteriological examination should be paid more attention to increase the pathogen detection rate. Non‑culture CSF detection methods may facilitate pathogenic diagnosis.

Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis, Already at Diagnosis: The NEOS2 Model. (P5-5.009)

Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis, Already at Diagnosis: The NEOS2 Model. (P5-5.009)

Neurosyphilis among people with and without HIV infection: A Danish nationwide prospective, population-based cohort study 2015–2021

Comparative data on clinical presentation, laboratory characteristics, treatment, and outcome of neurosyphilis (NS) in people living with HIV (PLWH) and NS patients without HIV are scarce. Nationwide, population-based, prospective cohort study on all adults with NS diagnosed between 2015 and 2021 at departments of infectious diseases in Denmark. We identified 108 patients with NS, which equals a yearly incidence of 0.3/100,000 adults. The median age was 49 years, 85 (79%) were male, 43 (40%) were men having sex with men and 20 (22%) were PLWH. Ninety-five (88%) had early NS, 37 (34%) had ocular or ocular and otogenic NS, and 27 (25%) had symptomatic meningitis. Most common symptoms were visual disturbance (44%), skin rash (40%), fatigue (26%) and chancre (17%). Median CSF leukocyte count was 27×106 cells/L. PLWH less often had neurological deficits (p=0.02). Unfavorable outcome was observed in 23 (21%) at discharge of whom 0 were PLWH (p=0.01). Among the 88 NS patients without HIV a CSF leukocyte count of ≥30×106 cells/L was associated with unfavorable outcome (OR=3.3 (95% confidence interval: 1.1-10.4)). PLWH with NS have better outcomes than NS patients without HIV infection.

Clinical features and prognostic factors in adults with viral meningitis.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

Diagnostic Accuracy of Clinical Signs and Biochemical Parameters for External Ventricular CSF Catheter-Associated Infection.

Few prospective well-designed diagnostic accuracy studies have been performed to study the parameters of infection in patients suspected for external ventricular catheter-associated infection. Our objective was to analyze the diagnostic accuracy of clinical characteristics and biochemical and microbiological parameters in diagnosing external ventricular CSF catheter-associated infection. From 2014 to 2017, we performed a single-center cohort study in consecutive patients at the intensive care unit who required an external ventricular CSF catheter in the Hague, the Netherlands. CSF was sampled and analyzed daily. Ventricular catheter-associated infection was defined according to the 2017 Infectious Diseases Society of America's Clinical Practice Guidelines. We compared clinical characteristics and biochemical parameters between patients with and without infection from 3 days before to 3 days after the day the CSF sample was collected that grew bacteria. A total of 103 patients were included of whom 15 developed a catheter-associated infection (15%). The median day cultures were positive was 3 days after CSF collection (interquartile range [IQR] +2 to +4). On day 0, none of the tests could differentiate between patients with and without infection. The CSF leukocyte count was increased in patients with ventricular catheter-associated infection as compared with patients without on days +2 and +3. The difference was most prominent on day +2 (1,703 × 106/L [IQR 480-6,296] vs 80 × 106/L [IQR 27-251]; p < 0.001; area under the curve [AUC] 0.87 [95% confidence interval (CI) 0.71-1.00]). Sensitivity for the CSF leukocyte count at a cutoff level >1,000 × 106/L was 67% (95% CI 30-93), and specificity was 100% (95% CI 90-100); the positive predictive value was 100%, and the negative predictive value was 92% (95% CI 83-97). The percentage of polymorphonuclear cells (PMNs) was higher in patients with infection on days +1 and +2 (day +2 89% [IQR 78-94] vs 59% [IQR 39-75]; p < 0.01; AUC 0.91 [95% CI 0.81-1.0]). An elevated CSF leukocyte count and increased percentage of PMNs are the strongest indicators for external catheter-associated infections on the days before culture positivity. New CSF markers of drain-associated infection should be studied to enable earlier diagnosis and treatment in patients with an infection and reduce antibiotic treatment in those with no infection. This study provides Class I evidence that in individuals requiring an external ventricular CSF catheter, an elevated CSF leukocyte count and an increased percentage of PMNs are the strongest indicators of catheter-associated infections in the days before CSF culture positivity.

Bacterial meningitis presenting with a normal cerebrospinal fluid leukocyte count

ObjectivesWe describe clinical characteristics and outcome of adults with bacterial meningitis presenting with a normal CSF leukocyte count. MethodsWe studied community-acquired bacterial meningitis with a normal CSF leukocyte count (≤ 5 per mm3) in adults from a prospective nationwide cohort study. ResultsFrom 2006 through 2020, 39 of 2,357 (2%) episodes presented with a normal CSF leukocyte count. Immunocompromising conditions were present in 19 of 39 patients (49%), compared to 690 of 2303 (30%) in patients with elevated leukocytes (P = 0.02). The triad of fever, neck stiffness, and altered consciousness was present in 6 of 34 patients (18%). CSF protein was abnormal in 25 of 37 patients (68%). We identified 3 clinical subgroups: those with severe pneumococcal meningitis (20 patients [51%]), with mainly sepsis (8 [21%]), and a miscellaneous group (11 [28%]). All patients with severe pneumococcal meningitis presented with high CSF protein levels and 18 of 19 (95%) had bacteria in the CSF Gram stain. Outcome was unfavorable in 23 of 39 (59%) patients and 12 (31%) died. ConclusionPatients with bacterial meningitis may present with normal CSF leukocyte counts. In these patients, CSF protein levels and Gram staining are important diagnostic parameters.

Next-generation sequencing of cerebrospinal fluid for diagnosis of atypical herpes simplex encephalitis.

ObjectivesHerpes simplex encephalitis (HSE) is one of the most common causes of severe viral encephalitis. The characteristic manifestations of HSE include cerebrospinal fluid with mild cytopenia, dominated by lymphocytes, elevated protein, and normal blood glucose values (3.9–6.1 mmol/L). Although it is not difficult to diagnose classical HSE, diagnosing clinically atypical cases is more difficult.MethodsWe reviewed the results of next-generation sequencing (NGS) of CSF in a series of patients diagnosed with atypical HSE.ResultsFour patients lacking classical clinical manifestations of HSE, including no fever, headache, or other typical neurological deficit symptoms, 1–2 × 106 cells/L CSF leucocyte count, and no typical imaging features, were diagnosed with atypical HSE by NGS of CSF. The NGS reads corresponding to herpes simplex virus type 1 ranged from 2 to 13,174.ConclusionsMild HSE may not present with classic frontotemporal lobe syndrome and fever may not be an inevitable symptom in patients with immunosuppression. However, the possibility of HSE should be considered in patients with atypical intracranial infection, and these patients should be tested by NGS.

Microbial aspects and potential markers for differentiation between bacterial and viral meningitis among adult patients.

ObjectivesMeningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for differentiation between bacterial and viral meningitis.MethodologyAdult patients with acute meningitis were subjected to lumber puncture. Cerebrospinal fluid (CSF) microorganisms were identified using Real-time PCR. PCT and CRP levels, peripheral and CSF-leucocyte count, CSF-protein and CSF-glucose levels were assessed.ResultsOut of 80 patients, infectious meningitis was confirmed in 75 cases; 38 cases were bacterial meningitis, 34 cases were viral meningitis and three cases were mixed infection. Higher PCT, peripheral and CSF-leukocytosis, higher CSF-protein and lower CSF-glucose levels were more significant in bacterial than viral meningitis patients. Neisseria meningitides was the most frequent bacteria and varicella-zoster virus was the most common virus. Using ROC analyses, serum PCT and CSF-parameters can discriminate bacterial from viral meningitis. Combined ROC analyses of PCT and CSF-protein significantly improved the effectiveness in predicting bacterial meningitis (AUC of 0.998, 100%sensitivity and 97.1%specificity) than each parameter alone (AUC of 0.951 for PCT and 0.996 for CSF-protein).ConclusionCSF-protein and serum PCT are considered as potential markers for differentiating bacterial from viral meningitis and their combination improved their predictive accuracy to bacterial meningitis.

Enterovirus Meningitis in Adults: A Prospective Nationwide Population-Based Cohort Study.

To test the hypothesis that enterovirus meningitis (EM) is a frequent and self-limiting condition, the epidemiology of EM in adults was examined. Using a prospective, nationwide, population-based database, all adults with EM confirmed by PCR of the CSF from 2015 to 2019 were included. Unfavorable outcome was defined as Glasgow Outcome Scale scores of 1-4 at discharge. Modified Poisson regression was used to compute adjusted relative risks (RRs). A total of 419 cases of EM in 418 adults (46% female, median age 31 years [interquartile range (IQR) 27-35]) yielded an incidence of 1.80/100,000/year. Admission diagnoses included CNS infection 247/397 (62%), other neurologic conditions 89/397 (22%), and cerebrovascular diseases 33/397 (8%). Genotype was available for 271 cases, of which echovirus 30 accounted for 155 (57%). Patients presented with headache 412/415 (99%), history of fever 303/372 (81%), photophobia 292/379 (77%), and neck stiffness 159/407 (39%). Fever (≥38.0°C) was observed in 192/399 (48%) at admission. The median CSF leukocyte count was 130 106/L (range 0-2,100) with polymorphonuclear predominance (>50%) in 110/396 (28%). Cranial imaging preceded lumbar puncture in 127/417 (30%) and was associated with non-CNS infection admission diagnoses and delayed lumbar puncture (median 4.8 hours [IQR 3.4-7.9] vs 1.5 [IQR 0.8-2.8], p < 0.001). Unfavorable outcome occurred in 99/419 (24%) at discharge; more often in female patients (RR 2.30 [1.58-3.33]) and less frequent in echovirus 30 (RR 0.67 [0.46-1.00]) in adjusted analyses. Outcome remained unfavorable in 22/379 (6%) after 6 months. EM is common among young, healthy adults. Although the long-term prognosis remains reassuring, a substantial proportion have moderate disability at discharge, especially female patients.

Association of intrathecal pleocytosis and IgG synthesis with axonal damage in early MS.

ObjectiveTo 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.MethodsSimultaneously 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.ResultsPatients 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.ConclusionsIn 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.

CSF leukocyte, polykaryocyte, protein and glucose: Their cut-offs of judging whether post-neurosurgical bacterial meningitis has been cured

ObjectThis paper is aimed to explore a reasonable guideline for distinguishing whether post-neurosurgical bacterial meningitis has completely been cured, so as to avoid the deficient or excessive treatment for post-neurosurgical bacterial meningitis. Patients and methodsWe conducted a retrospective analysis of 46 patients who attended General Hospital of Chinese People’s Armed Police Force in Beijing, China, from January 1, 2014 to April 30, 2016. The CSF leukocyte, polykaryocyte, protein and glucose had been tested when their antibiotic treatments were empirically stopped. Between the non-relapse and relapse groups, Wilcoxon Rank Sum test was used to compare the differences of CSF leukocyte and polykaryocyte, and t-test was applied to contrast the distinctions of CSF protein and glucose, then, the thresholds of significant items were estimated by ROC curve. ResultsThe CSF leukocyte counts in non-relapse group are 23.72 ± 14.12/mm3, which are statistically less than the relapse group’s (47.00 ± 1.00/mm3, P = 0.014), so does the CSF polykaryocyte counts (1.74 ± 4.84/mm3 &4.67 ± 1.15/mm3, P = 0.012). Between the two groups, the AUCs of leucocyte and polykaryocyte are 0.926 (95% CI = 0.845–1.0, P = 0.014) and 0.884 (95%CI = 0.786–0.982, P = 0.028), respectively. Their critical values are 44/mm3 (sensitivity = 1, specificity = 0.907) and 3/mm3 (sensitivity = 1, specificity = 0.837). Conversely, CSF protein and glucose have no statistic differences between the two groups. ConclusionBoth CSF leukocyte and polykaryocyte can satisfactorily indicate whether the post-neurosurgical bacterial meningitis has completely been cured, 0–44/mm3 is recommended as the reference range of CSF leukocyte, and the CSF polykaryocyte’ s is 0–3/mm3.

Cerebrospinal fluid monocytes in bacterial meningitis, viral meningitis, and neuroborreliosis

ObjectiveCerebrospinal fluid (CSF) leukocytes analysis is commonly used to diagnose meningitis and to differentiate bacterial from viral meningitis. Interpreting CSF monocytes can be difficult for physicians, especially in France where lymphocytes and monocytes results are sometimes pooled. Patients and methodsWe assessed SF monocytes in patients presenting with microbiologically confirmed meningitis (CSF leukocyte count>10/mm3 for adults or >30/mm3 for children<2 months), i.e. bacterial meningitis (BM), viral meningitis (VM), and neuroborreliosis (NB). ResultsTwo-hundred patients (82 BM, 86 VM, and 32 NB) were included. The proportions of monocytes were higher in VM (median 8%; range 0–57%) than in BM (median 5%; range 0–60%, P=0.03) or NB (median 5%; range 0–53%, P=0.46), with a high value overlap between conditions. ConclusionCSF monocytes should not be used to discriminate BM from VM and NB because of value overlaps.

Pleocytosis is not fully responsible for low CSF glucose in meningitis.

Objective:The mechanism of hypoglycorrhachia—low CSF glucose—in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels.Methods:We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis.Results:We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2 = 36%, p < 0.001) and repeated CSF sampling (R2 = 46%, p < 0.001). Hypoglycorrhachia (<40 mg/dL) was observed in 50.1% of microbial cases, but only 9.6% of aseptic cases, most of which were neurosarcoidosis. Absolute CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used.Conclusions:The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.

The long-term outcome of tick-borne encephalitis in Central Europe

BackgroundInformation on the long-term outcome of tick-borne encephalitis (TBE) is limited. ObjectivesTo assess the frequency and severity of post-encephalitic syndrome (PES) at different time points after TBE, and to determine the parameters associated with unfavourable outcome. MethodsAdult patients diagnosed with TBE in Slovenia in the period 2007–2012 were followed-up for 12 months and also examined 2–7 years after TBE. Each patient was asked to refer a person of similar age without a history of TBE to serve as control. ResultsA total of 420 patients and 295 control persons participated in the study. The proportion of patients with PES (defined as the presence of ≥ 2 subjective symptoms that newly developed or worsened since the onset of TBE and which had no other known medical explanation, and/or ≥ 1 objective neurological sign) was higher (P < 0.001) at the follow-up visit 6 months after the acute illness (127/304, 42%, 95% CI: 36–47%) than at 12 months (68/207, 33%, 95% CI: 26–40%); the proportion at 12 months was the same as at 2–7 years after TBE (137/420, 33%, 95% CI: 28–37%). However, the proportion of severe PES at the last two time points differed (9.7% vs 4.3%, P = 0.008). Multivariate logistic regression showed that unfavourable outcome at 6 months was associated with CSF leukocyte count (OR = 1.003, 95% CI: 1.001–1.005%, P = 0.017), at 12 months with the disease outcome at 6 months (OR = 115.473, 95% CI: 26.009–512.667%, P < 0.001), and at the final visit with disease outcome at 6 months (OR = 3.808, 95% CI: 1.151–12.593%, P = 0.028) and 12 months (OR = 26.740, 95% CI: 8.648–82.680%, P < 0.001). Unspecific symptoms that occurred within the four weeks before the final examination were more frequent and more constant in patients than in the control group. ConclusionsThe frequency of PES diminished over time and stabilized 12 months after the acute illness, whereas the severity of PES continued to decline. Unfavourable outcomes at 12 months and at the final visit were strongly associated with the presence of PES at previous time points.

Tick-borne encephalitis in patients vaccinated against this disease.

Information on tick-borne encephalitis (TBE) in patients already vaccinated against the disease is limited. To compare the course and outcome in patients with vaccination breakthrough TBE with findings in patients who developed TBE without previous vaccination. All adult patients diagnosed with TBE at a single medical centre during a 16-year period and who had received at least two doses of TBE vaccine before the onset of illness qualified for the study. For each patient with breakthrough TBE, two unvaccinated sex- and age-matched patients, diagnosed with TBE in the same year, were included for comparison. Amongst 2332 patients diagnosed with TBE in the period 2000-2015, 39 (1.7%) had been vaccinated against the disease. Their median age was 59 (20-83) years; 22 of 39 (56.4%) were male. In comparison with unvaccinated patients with TBE, those with breakthrough disease more often experienced a monophasic course of illness (P = 0.006), had a higher CSF leucocyte count (P = 0.005), more often had urine retention (P = 0.012), more often needed ICU treatment (P = 0.009), were hospitalized for longer (P = 0.002) and had more severe acute illness (P = 0.004 for simple clinical assessment, P = 0.001 for severity score). In addition to several findings corroborating previous results in patients with vaccination breakthrough TBE, such as older age and the presence of a particular specific serum antibody pattern indicating anamnestic response, findings in this study indicate that the acute illness in patients with breakthrough TBE is more severe than in unvaccinated sex- and age-matched patients who develop the disease.

Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.

Objective:Although blood–brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined.Methods:BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART).Results:The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis.Conclusions:BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.