Felicia C. Chow

Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system.

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-infected versus non-HIV-infected 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 (HRs). Results: The incidence rate of ischemic stroke was 5.27 per 1000 person-years in HIV-infected compared with 3.75 in non-HIV-infected patients, with an unadjusted HR of 1.40 [95% confidence interval (CI): 1.17 to 1.69, P < 0.001]. HIV remained an independent predictor of stroke after controlling for demographics and stroke risk factors (HR: 1.21, 95% CI: 1.01 to 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 to 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 (95% CI: 1.53 to 3.04) for women vs. HR: 1.18 (95% CI: 0.95 to 1.47) for men]. Among HIV patients, increased HIV RNA (HR: 1.10, 95% CI: 1.04 to 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.

La cuerda dulce – a tolerability and acceptability study of a novel approach to specimen collection for diagnosis of paediatric pulmonary tuberculosis

BackgroundRecent data demonstrate the utility of the string test for the diagnosis of sputum-scarce HIV-associated TB in adults. We hypothesized that, if well-tolerated by children, this simple tool might offer a breakthrough in paediatric TB diagnosis. Thus the objective of this study, undertaken in the paediatric service of the Hospital Nacional Dos de Mayo, Lima, Perú, was to determine the tolerability and acceptability of the string test to paediatric TB suspects, their parents and nursing staff.Methods22 paediatric subjects aged 3–14 years (median 8) under investigation for TB were invited to undergo 2 string tests (four-hour downtime each). Subjective and objective pain and discomfort rating scales were used to assess the perception of the subject, parent and attending nurse.ResultsPatients as young as 4 years tolerated the procedure extremely well with 84% willing to undergo a second procedure. Peak discomfort at the time of swallowing and of string retrieval was mild (30% of maximum possible score) and brief as judged by visual analogue ratings and objective indicators. Good concordance of parent/child and objective/subjective ratings strengthened the validity of these findings.ConclusionThe string test is well tolerated and achievable for most paediatric TB suspects as young as 4 years. A formal prospective paediatric efficacy study is now needed.

HIV infection and incidence of ischemic stroke.

Objective:To determine the association of HIV infection and immunodeficiency with incidence of ischemic stroke. Design:Cohort study of HIV-positive and matched HIV-negative adult Kaiser Permanente Northern and Southern California (KPNC and KPSC, respectively) members during 1996–2011 (KPNC) or 2000–2011 (KPSC). Methods:We used Poisson models to obtain rate ratios for incident ischemic stroke associated with HIV infection, both overall and stratified by CD4+ cell counts (cells/&mgr;l) and HIV RNA copies (copies/ml), with HIV-negative individuals as the reference group. We also obtained rate ratios for risk factors in the HIV-positive subset. Results:Among 24 768 HIV-positive and 257 600 HIV-negative individuals, the ischemic stroke rate per 100 000 person-years was 125 (n = 151 events) for HIV-positive and 74 (n = 1128 events) for HIV-negative individuals, with an adjusted rate ratio of 1.4 [95% confidence interval (CI) 1.2–1.7). Compared with HIV-negative individuals, HIV-positive individuals with recent CD4+ cell counts of 500 cells/&mgr;l at least (rate ratio 1.0, 95% CI 0.8–1.4) or recent HIV RNA less than 500 copies/ml (rate ratio 1.1, 95% CI 0.9–1.4) had no excess risk of ischemic stroke, with similar results for HIV-positive individuals with nadir CD4+ cell counts of 500 cells/&mgr;l at least (rate ratio 1.4, 95% CI 0.8–2.2) or 200–499 cells/&mgr;l (rate ratio 1.2, 95% CI 0.9–1.5). Among HIV-positive individuals only, recent CD4+ cell count less than 200 cells/&mgr;l (rate ratio 2.5, 95% CI 1.3–4.6) was associated with an increased risk of ischemic stroke after adjustment for recent HIV RNA and nadir CD4+ cell count, whereas recent HIV RNA and nadir CD4+ were not independent risk factors. Conclusion:Ischemic stroke incidence in HIV-positive individuals with high CD4+ cell count or low HIV RNA is similar to that of HIV-negative individuals.

Use of Clinical and Neuroimaging Characteristics to Distinguish Temporal Lobe Herpes Simplex Encephalitis From Its Mimics

BACKGROUND We describe the spectrum of etiologies associated with temporal lobe (TL) encephalitis and identify clinical and radiologic features that distinguish herpes simplex encephalitis (HSE) from its mimics. METHODS We reviewed all adult cases of encephalitis with TL abnormalities on magnetic resonance imaging (MRI) from the California Encephalitis Project. We evaluated the association between specific clinical and MRI characteristics and HSE compared with other causes of TL encephalitis and used multivariate logistic modeling to identify radiologic predictors of HSE. RESULTS Of 251 cases of TL encephalitis, 43% had an infectious etiology compared with 16% with a noninfectious etiology. Of infectious etiologies, herpes simplex virus was the most commonly identified agent (n = 60), followed by tuberculosis (n = 8) and varicella zoster virus (n = 7). Of noninfectious etiologies, more than half (n = 21) were due to autoimmune disease. Patients with HSE were older (56.8 vs 50.2 years; P = .012), more likely to be white (53% vs 35%; P = .013), more likely to present acutely (88% vs 64%; P = .001) and with a fever (80% vs 49%; P < .001), and less likely to present with a rash (2% vs 15%; P = .010). In a multivariate model, bilateral TL involvement (odds ratio [OR], 0.38; 95% confidence interval [CI], .18-.79; P = .010) and lesions outside the TL, insula, or cingulate (OR, 0.37; 95% CI, .18-.74; P = .005) were associated with lower odds of HSE. CONCLUSIONS In addition to HSE, other infectious and noninfectious etiologies should be considered in the differential diagnosis for TL encephalitis, depending on the presentation. Specific clinical and imaging features may aid in distinguishing HSE from non-HSE causes of TL encephalitis.

Burden of neuroinfectious diseases on the neurology service in a tertiary care center.

Background: Neurologic infections have the potential to cause death and suffering. These disorders often go unrecognized or are misdiagnosed. There has yet not been a census of neurologic infections conducted in a hospital setting. We aimed to determine the burden of neurologic infections on the neurology service in a tertiary care center and identify challenges in the diagnosis and treatment of these infections. Methods: We reviewed retrospectively all inpatients diagnosed with any neuroinfectious disease evaluated at Johns Hopkins Medical Institutions between October 2004 and December 2005. We recorded information on hospital admission, clinical features, microbiologic analysis, neuroimaging, EEG, pathology, treatment, and outcome. Results: A total of 116 of 4,225 patients admitted to or consulted on by the neurology service were identified. Eighty percent of patients were aged between 18 and 65 years. Fifty-two patients were immunocompromised, of which 28 patients had HIV infection. Overall, 86 microbiologic agents were identified in 80 patients. The commonest causes were viral, followed by bacterial and fungal infections. However, 31% of patients remained without an identifiable microbiologic etiology. Hospitalization periods were long, with 43% of patients staying beyond 2 weeks. There was significant morbidity: 28% of patients required rehabilitation or long-term care, and 12% died. Conclusions: Neurologic infections have a major socioeconomic impact because they result in prolonged hospitalizations, expensive diagnostic tests and treatments, and long-term debilitation or death in young patients. Though potentially curable conditions, the burden of undiagnosed infections remains high.

Cerebrovascular Disease in Central Nervous System Infections

Cerebrovascular disease is a complication of a variety of infections affecting the central nervous system (CNS). Infection may cause vasculitis affecting primarily the vessels at the base of the brain in the setting of meningitis; an immune-mediated parainfectious process leading to vasospasm or thrombosis; or a hypercoagulable state in combination with endothelial dysfunction resulting from activation of inflammatory and procoagulant cascades. Although systemic signs and symptoms may be present to aid in the diagnosis, cerebral infarction secondary to infection may be indistinguishable from more typical causes of stroke. Confirmation of an infectious vasculitis may also be challenging, as brain biopsy, the gold standard for diagnosis, is rarely pursued. In many CNS infections, vascular complications portend a poor prognosis as they are often associated with devastating neurologic outcomes, including death, underscoring the importance of early recognition and appropriate therapy. In this review, we address bacterial, viral, fungal, and parasitic causes of cerebrovascular disease.

Effect of CD4 cell count and viral suppression on risk of ischemic stroke in HIV infection

Objectives:Evidence from the current era of combination antiretroviral therapy supports an association between HIV and cerebrovascular disease. In addition to traditional vascular risk factors, HIV-specific factors including immunodeficiency and viral replication may also predict stroke risk. The aim of this study was to determine the relationship between CD4+ cell count, viral suppression and validated ischemic stroke outcomes. Design:A single-centre, case–control study. Methods:We identified ischemic stroke cases in HIV-infected adults from an HIV clinic using International Classification of Diseases codes for cerebrovascular disease followed by validation of each case. Controls from the same HIV clinic were selected by incidence density sampling. Demographic and clinical data, including the most recent CD4+ cell count and plasma HIV RNA concentration, were abstracted from hospital and HIV clinic electronic medical records. Matched conditional logistic regression models were used to evaluate the association between CD4+ cell count, viral suppression and ischemic stroke. Results:In an adjusted model, viral suppression decreased the odds of ischemic stroke by a factor of 0.16 [95% confidence interval (95% CI) 0.05–0.50, P = 0.002]. This association, although attenuated [odds ratio (OR) 0.31, 95% CI 0.09–1.06, P = 0.062], remained after restricting the analysis to ischemic strokes due to true atherosclerotic mechanisms (i.e. excluding infection and malignancy-related strokes). Conclusion:Achieving viral suppression may reduce ischemic stroke risk, including risk of atherosclerotic strokes, in HIV-infected individuals.

Outcome in patients with H1N1 influenza and cerebrovascular injury treated with extracorporeal membrane oxygenation.

BackgroundAlthough intracranial hemorrhage and infarction have been reported in patients with H1N1 influenza infection treated with extracorporeal membrane oxygenation (ECMO), the clinical outcomes of these patients are not well described.MethodsThe authors present two patients with H1N1 influenza infection and diffuse cerebrovascular injury in the setting of ECMO.ResultsDiffuse cerebrovascular injury including intraparenchymal hemorrhage was found on head CT and brain MRI in both cases and confirmed by autopsy in one patient who died. Punctate foci of susceptibility effect were seen in both patients on T2* susceptibility-weighted or susceptibility-sensitive gradient echo sequences. These foci of susceptibility effect were consistent with infarction on histopathologic evaluation in the patient who died. The other patient made an excellent clinical recovery.ConclusionsFrequent and early surveillance imaging should be obtained in patients with H1N1 influenza infection undergoing ECMO, although the presence of diffuse cerebral injury, including intraparenchymal hemorrhage and multifocal punctate susceptibility effect, does not necessarily portend a poor prognosis.

HIV infection, vascular disease, and stroke.

With the transformation of HIV infection into a chronic disease for the majority of patients with access to combination antiretroviral therapy, HIV-infected individuals and their medical providers are facing a new set of challenges, many of which are more typical of an aging population. Accumulating evidence indicates that rates of stroke, like coronary heart disease, may be higher in HIV-infected individuals. This review will discuss the epidemiology of stroke in HIV infection, potential mechanisms underlying the pathogenesis of stroke, vascular risk and cognitive impairment, cardiovascular and stroke risk prediction, and strategies for stroke prevention in this at-risk population, with a focus on HIV-associated cerebrovascular disease in the current era of highly effective combination antiretroviral therapy.

Neurologic Complications in Treated HIV-1 Infection

Effective combination antiretroviral therapy has transformed HIV infection into a chronic disease, with HIV-infected individuals living longer and reaching older age. Neurological disease remains common in treated HIV, however, due in part to ongoing inflammation and immune activation that persist in chronic infection. In this review, we highlight recent developments in our understanding of several clinically relevant neurologic complications that can occur in HIV infection despite treatment, including HIV-associated neurocognitive disorders, symptomatic CSF escape, cerebrovascular disease, and peripheral neuropathy.