Global Case Fatality of Bacterial Meningitis During an 80-Year Period: A Systematic Review and Meta-Analysis.

Importance: The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. Objective: To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. Data Sources: Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality. Study Selection: Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded. Data Extraction and Synthesis: Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used. Main Outcome and Measure: Case fatality ratios of bacterial meningitis. Results: This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients' sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001). Conclusions and Relevance: In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.

Unexpected neurologic complications following a novel lymphoma treatment 'expected' to give rise to neurologic toxicity.

Chimeric antigen receptor (CAR) T-cell therapy is a novel and promising form of cellular immunotherapy using genetically engineered, tumour-specific autologous T cells. CD19-specific CAR T-cells have been shown to be very effective as a treatment for relapsed/refractory B-cell acute lymphoblastic leukaemia and aggressive B-cell non-Hodgkin's lymphoma. ICANS (immune effector cell-associated neurotoxicity syndrome) is one of the most frequently occurring toxicities of CAR T-cell treatment. We describe two cases of patients with neurologic symptoms following CAR T-cell infusion who were suspected to have ICANS, but in fact had cerebral toxoplasmosis and venous sinus thrombosis respectively. The focus on CRS and ICANS after CAR T-cell infusion may lead to less vigilance to the 'normal' threats faced by intensively pretreated patients with lymphoma such as infections and thrombosis. Both cases underscore the importance of a broad and thorough examination of patients if they experience neurologic symptoms after CAR T-cell treatment.

The FOUR score as predictor of outcome in adults with bacterial meningitis.

OBJECTIVES: To evaluate the Full Outline of Unresponsiveness (FOUR) score as a predictor of outcome in adult patients with bacterial meningitis. METHODS: We selected 427 patients from a nationwide, prospective cohort on community-acquired bacterial meningitis included from August 2011 to November 2016. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected. We compare the FOUR score with the Glasgow Coma Scale (GCS) score, performed a receiver operator characteristic curve analysis, and calculated the area under the curve (AUC) of the FOUR and GCS scores for the prediction of unfavorable outcome and mortality. RESULTS: The median FOUR score on admission was 14 (interquartile range [IQR] 12-16), and the median GCS score was 12 (IQR 9-14). The outcome was unfavorable in 135 of 427 (32%) patients, of whom 55 (13%) died. There was a strong correlation between the FOUR score and the GCS score (r = 0.85, p < 0.001). AUCs for the GCS and FOUR scores in the prediction of unfavorable outcome (both 0.64) and mortality (both 0.68) were comparable. Logistic regression analysis showed that the FOUR motor, brainstem, and respiration items were individual predictors of unfavorable outcome and mortality. For the GCS score, only the motor component was predictive, while the FOUR score provided a spectrum of clinical abnormalities in patients with a GCS score of 3. CONCLUSIONS: The FOUR score adds considerably to the prediction of outcome in patients with severe meningitis by means of better testing of the brainstem reflexes and respiration status. Future studies should consider incorporating the FOUR score into clinical assessment.