Sociodemographic and Clinical Factors Associated With Clinical Outcome in Neuroinfectious Diseases: A Multicenter Retrospective Cohort Study.

Objective: To evaluate sociodemographic and clinical factors associated with clinical outcomes in patients hospitalized with neuroinfectious diseases at three tertiary care centers in New York City. Methods: This retrospective cohort study was conducted at three large urban tertiary care centers between January 1, 2010 and December 31, 2017. Poor clinical outcome was defined as length of hospital stay (LOS) ≥2 weeks and/or discharge to a location other than home. Sociodemographic and clinical factors were obtained from electronic medical records and descriptively analyzed. Multivariate logistic regression analysis investigated relationships between sociodemographic and clinical factors, and outcomes. Results: Among 205 patients with definitive neuroinfectious diagnoses, older patients were more likely to have a LOS ≥2 weeks (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.05) and less likely to be discharged home (OR: 0.96; 95% CI: 0.94-0.98) than younger patients. Patients with an immunocompromised state were more likely to have a LOS ≥2 weeks (OR: 2.80; 95% CI: 1.17-6.69). Additionally, patients admitted to the intensive care unit (ICU) were more likely to have a LOS ≥2 weeks (OR: 4.65; 95% CI: 2.13-10.16) and less likely to be discharged home (OR: 0.14; 95% CI: 0.06-0.34). There were no statistically significant associations between sex, race, ethnicity, English proficiency, substance use, or poverty index, and clinical outcome. Conclusions: In this multicenter cohort of hospitalized neuroinfectious diseases, older age, history of immunocompromised state, and admission to the ICU were significantly associated with poor clinical outcome.

Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy.

The progressive neurometabolic disorder X-linked adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, which encodes the peroxisomal ATP-binding transporter for very-long-chain fatty acids. The clinical spectrum of ALD includes adrenal insufficiency, myelopathy, and/or leukodystrophy. A complicating factor in disease management is the absence of a genotype-phenotype correlation in ALD. Since 1999, most ABCD1 (likely) pathogenic and benign variants have been reported in the ABCD1 Variant Database. In 2017, following the expansion of ALD newborn screening, the database was rebuilt. To add an additional level of confidence with respect to pathogenicity, for each variant, it now also reports the number of cases identified and, where available, experimental data supporting the pathogenicity of the variant. The website also provides information on a number of ALD-related topics in several languages. Here, we provide an updated analysis of the known variants in ABCD1. The order of pathogenic variant frequency, overall clustering of disease-causing variants in exons 1-2 (transmembrane domain spanning region) and 6-9 (ATP-binding domain), and the most commonly reported pathogenic variant p.Gln472Argfs*83 in exon 5 are consistent with the initial reports of the mutation database. Novel insights include nonrandom clustering of high-density missense variant hotspots within exons 1, 2, 6, 8, and 9. Perhaps more importantly, we illustrate the importance of collaboration and utility of the database as a scientific, clinical, and ALD-community-wide resource.

Determining an infectious or autoimmune etiology in encephalitis.

OBJECTIVES: Early presentation and workup for acute infectious (IE) and autoimmune encephalitis (AE) are similar. This study aims to identify routine laboratory markers at presentation that are associated with IE or AE. METHODS: This was a multi-center retrospective study at three tertiary care hospitals in New York City analyzing demographic and clinical data from patients diagnosed with definitive encephalitis based on a confirmed pathogen and/or autoantibody and established criteria for clinical syndromes. RESULTS: Three hundred and thirty-three individuals with confirmed acute meningoencephalitis were included. An infectious-nonbacterial (NB) pathogen was identified in 151/333 (45.40%), bacterial pathogen in 95/333 (28.50%), and autoantibody in 87/333 (26.10%). NB encephalitis was differentiated from AE by the presence of fever (NB 62.25%, AE 24.10%; p < 0.001), higher CSF white blood cell (WBC) (median 78 cells/µL, 8.00 cells/µL; p < 0.001), higher CSF protein (76.50 mg/dL, 40.90 mg/dL; p < 0.001), lower CSF glucose (58.00 mg/dL, 69.00 mg/dL; p < 0.001), lower serum WBC (7.80 cells/µL, 9.72 cells/µL; p < 0.050), higher erythrocyte sedimentation rate (19.50 mm/HR, 13.00 mm/HR; p < 0.05), higher C-reactive protein (6.40 mg/L, 1.25 mg/L; p = 0.005), and lack of antinuclear antibody titers (>1:40; NB 11.54%, AE 32.73%; p < 0.001). CSF-to-serum WBC ratio was significantly higher in NB compared to AE (NB 11.3, AE 0.99; p < 0.001). From these findings, the association of presenting with fever, CSF WBC ≥50 cells/µL, and CSF protein ≥75 mg/dL was explored in ruling-out AE. When all three criteria are present, an AE was found to be highly unlikely (sensitivity 92%, specificity 75%, negative predictive value 95%, and positive predictive value 64%). INTERPRETATIONS: Specific paraclinical data at initial presentation may risk stratify which patients have an IE versus AE.