BACKGROUND Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, .)

Background Cardiovascular disease is increased among HIV-infected patients, but little is known regarding ischemic stroke rates. We sought to compare stroke rates and determine stroke risk factors in HIV versus non-HIV patients. Methods An HIV cohort and matched non-HIV comparator cohort seen between 1996 and 2009 were identified from a Boston health care system. The primary endpoint was ischemic stroke, defined using International Classification of Diseases (ICD) codes. Unadjusted stroke incidence rates were calculated. Cox proportional hazards modeling was used to determine adjusted hazard ratios (HR). Results The incidence rate of ischemic stroke was 5.27 per 1000 person years (PY) in HIV compared with 3.75 in non-HIV patients, with an unadjusted HR of 1.40 (95% confidence interval [CI] 1.17-1.69, P<0.001). HIV remained an independent predictor of stroke after controlling for demographics and stroke risk factors (1.21, 1.01-1.46, P=0.043). The relative increase in stroke rates (HIV vs. non-HIV) was significantly higher in younger HIV patients (incidence rate ratio 4.42, 95% CI 1.56-11.09 age 18-29; 2.96, 1.69-4.96 age 30-39; 1.53, 1.06-2.17 age 40-49), and in women (HR 2.16 [1.53-3.04] for women vs. 1.18 [0.95-1.47] for men). Among HIV patients, increased HIV RNA (HR 1.10, 95% CI 1.04-1.17, P=0.001) was associated with an increased risk of stroke. Conclusions Stroke rates were increased among HIV-infected patients, independent of common stroke risk factors, particularly among young patients and women.

Ischemic stroke incidence in HIV-positive individuals with high CD4 cell count or low HIV RNA is similar to that of HIV-negative individuals.

Improvements in the immunologic tests performed on cerebrospinal fluid have increased the sensitivity and reduced the turnaround time for diagnosis of central nervous system histoplasmosis over prior antigen and antibody detection methods and culture.

Objective: To compare rates of intracerebral hemorrhage (ICH) in HIV-infected and uninfected individuals in a large clinical care cohort and to assess risk factors associated with ICH. Methods:We identified incident ICH in HIV-infected and uninfected control cohorts from the Partners Health Care system using ICD-9-CM codes. We constructed Cox proportional hazards models to estimate adjusted hazard ratios for HIV infection and other predictors of ICH.Results: The incidence rate of ICH was 2.29 per 1,000 person-years in HIV-infected individuals compared with 1.23 per 1,000 person-years in uninfected individuals, with an unadjusted incidence rate ratio of 1.85 (95% confidence interval 1.37-2.47, p , 0.001). In a multivariable model, HIV infection was independently associated with a higher hazard of ICH, although its effect diminished with increasing age. Female sex was associated with a lower hazard of ICH in the uninfected cohort but not in the HIV cohort. CD4 count ,200 3 10 6 cells/L and anticoagulant use were predictive of ICH.Conclusions: HIV infection conferred an increased adjusted hazard of ICH, which was more pronounced in young patients and in women. Cardiovascular and cerebrovascular event rates are increased in HIV infection. [1][2][3][4][5][6][7] Several studies pointing to an elevated risk of cerebrovascular disease in HIV-infected individuals have focused on ischemic stroke and excluded intracranial hemorrhage. 5,8,9 Whereas ischemic stroke and cardiovascular disease often coexist and share a similar risk profile and underlying mechanism, the association between HIV and intracerebral hemorrhage (ICH), which has mechanisms distinct from ischemic stroke, is less clear. We examined the association of HIV with the risk of ICH by comparing the incidence of ICH in HIV-infected and uninfected individuals in a large US clinical care cohort. Our primary hypothesis was that the rate of ICH in HIV-infected individuals would be higher than in uninfected individuals. We further controlled for potential confounders and identified predictors of ICH in HIV-infected individuals.METHODS Study design and patient population. We conducted an observational study of an HIV cohort derived from the Partners HealthCare System Research Patient Data Registry (RPDR), a clinical care database of all inpatient and outpatient encounters from Massachusetts General Hospital and Brigham and Women's Hospital. Other vascular outcomes have been studied in this cohort.3,5 HIV-infected individuals were identified from the RPDR using ICD-9-CM codes 042 or V08, previously validated in the cohort. 5 The HIV cohort was matched by age, race, and sex in a 1:10 ratio to HIV-uninfected individuals, who constituted the control cohort. The control cohort was intentionally overpopulated to allow for the possibility of missing data and application of the exclusion criteria. Within the cohorts, individuals who were at least 18 years of age at the beginning of the observation period and who had at least 1 inpatient or 2 outpatient clinical encou...

The increased risk of ischemic stroke among WLWH compared with HIV-uninfected women persisted after adjusting for both traditional and sex-specific stroke risk factors. Further investigation into the mechanisms of elevated stroke risk among WLWH, including immunologic factors, will be key for developing targeted preventive strategies for this at-risk population.

Stroke in PLWH in SSA occurs at a young age, in those with advanced disease, and is associated with worse outcomes than in HIV-uninfected comparators. Stroke in young individuals in the region should prompt HIV testing, and ongoing efforts to promote early antiretroviral therapy initiation might also help decrease stroke incidence, morbidity, and mortality in the region.

PURPOSE OF REVIEW Brain abscesses and spinal epidural abscesses are serious, potentially life-threatening infections of the central nervous system. This article outlines the clinical presentation, evaluation, and management of brain abscesses and spinal epidural abscesses, with a specific focus on bacterial infections. RECENT FINDINGS The overall incidence of brain abscesses has declined, in part because of fewer brain abscesses associated with otogenic infections. However, emerging patient populations at high risk for brain abscess include those with a history of penetrating head trauma, neurosurgery, or immunodeficiency. Improved mortality rates for brain abscess are attributable to modern diagnostic imaging, stereotactic-guided aspiration, and newer antimicrobials that readily penetrate into the central nervous system and abscesses. Brain MRI is more sensitive than CT for brain abscess, particularly in the early stages, but CT remains more widely available and can adequately identify potential abscesses and confirm response to treatment. With the advent of minimally invasive neurosurgical techniques, surgical excision is often employed only for posterior fossa, multiloculated, or superficial well-circumscribed abscesses. In select clinical scenarios, conservative medical management may be a safe alternative to a combined surgical and medical approach. Unlike brain abscess, the incidence of spinal epidural abscess is on the rise and has been attributed to higher prevalence of predisposing factors, including spinal procedures and instrumentation. SUMMARY Successful diagnosis and management of brain abscess and spinal epidural abscess requires a collaborative approach among neurologists, neurosurgeons, radiologists, and infectious disease physicians. The foundation of management of brain abscess includes surgical intervention for diagnostic purposes if a pathogen has not been identified or for decompression of larger abscesses or those with mass effect and significant surrounding edema; appropriate dosing and adequate duration of an antimicrobial regimen tailored to the presumptive source of infection and available culture data, and eradication of the primary source of infection. For spinal epidural abscesses, neurologic status at the time of presentation is directly related to outcomes, underscoring the importance of prompt recognition and intervention.