Steven K. Feske

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.

Posterior reversible encephalopathy syndrome: a review.

Encephalopathy due to reversible cerebral edema is an important cause of neurologic morbidity accompanying many disorders. Although controversy remains concerning the pathophysiologic trigger, the mechanism of this disorder ultimately depends on failure of the blood-brain barrier to maintain the compartmentalization of intravascular fluid. This failure of the blood-brain barrier depends primarily on the capillary hydrostatic pressure, under the influence of the systemic blood pressure, and on the integrity of the structures that make up the blood-brain barrier, most importantly the vascular endothelium, under the influence of various diseases and toxic medications. Although typical clinical contexts and presentations have been well defined, many patients have atypical features that pose a diagnostic challenge. Therefore, awareness of this clinical variability is important for prompt diagnosis. This review discusses the history and pathophysiology of posterior reversible encephalopathy syndrome and then addresses its clinical diagnosis and management.

Predicting Hematoma Expansion After Primary Intracerebral Hemorrhage

IMPORTANCE Many clinical trials focus on restricting hematoma expansion following acute intracerebral hemorrhage (ICH), but selecting those patients at highest risk of hematoma expansion is challenging. OBJECTIVE To develop a prediction score for hematoma expansion in patients with primary ICH. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study at 2 urban academic medical centers among patients having primary ICH with available baseline and follow-up computed tomography for volumetric analysis (817 patients in the development cohort and 195 patients in the independent validation cohort). MAIN OUTCOMES AND MEASURES Hematoma expansion was assessed using semiautomated software and was defined as more than 6 mL or 33% growth. Covariates were tested for association with hematoma expansion using univariate and multivariable logistic regression. A 9-point prediction score was derived based on the regression estimates and was subsequently tested in the independent validation cohort. RESULTS Hematoma expansion occurred in 156 patients (19.1%). In multivariable analysis, predictors of expansion were as follows: warfarin sodium use, the computed tomography angiography spot sign, and shorter time to computed tomography (≤ 6 vs >6 hours) (P < .001 for all), as well as baseline ICH volume (<30 [reference], 30-60 [P = .03], and >60 [P = .005] mL). The incidence of hematoma expansion steadily increased with higher scores. In the independent validation cohort (n = 195), our prediction score performed well and showed strong association with hematoma expansion (odds ratio, 4.59; P < .001 for a high vs low score). The C statistics for the score were 0.72 for the development cohort and 0.77 for the independent validation cohort. CONCLUSIONS AND RELEVANCE A 9-point prediction score for hematoma expansion was developed and independently validated. The results open a path for individualized treatment and trial design in ICH aimed at patients at highest risk of hematoma expansion with maximum potential for therapeutic benefit.

Stroke in pregnancy.

Although pregnancy-associated stroke is uncommon, the risk of stroke is greatly increased above the low baseline rate in young patients during late pregnancy and, even more so, during the puerperium. Stroke is a major contributor to the serious morbidity and mortality of pregnancy. The physiological hormonally mediated changes in circulation, vascular tissue structure, and coagulability, and the pathological state of pre-eclampsia-eclampsia contribute to this increased risk of stroke. Pregnancy-associated strokes are roughly evenly divided among hemorrhagic strokes, mainly from rupture of aneurysms and arteriovenous malformations (AVMs); ischemic strokes, mainly from late pregnancy and postpartum cerebral venous thrombosis; and strokes associated with pre-eclampsia-eclampsia, with a contribution from cardioembolism, especially in populations at risk from a high rate of underlying rheumatic valvular heart disease. Awareness of the types of stroke to expect during pregnancy will facilitate early diagnosis. This article discusses the pathogenesis of pregnancy-associated stroke, its epidemiology, and some diagnostic and therapeutic issues unique to pregnancy.

Increased leukocyte ROCK activity in patients after acute ischemic stroke

BACKGROUND Rho-kinase (ROCK) is a downstream effector of Rho GTPase that is known to regulate various pathological processes important to the development of ischemic stroke, such as thrombus formation, inflammation, and vasospasm. Inhibition of ROCK leads to decreased infarct size in animal models of ischemic stroke. This study tests the hypothesis that ROCK activity increases during the acute phase of ischemic stroke. METHODS Serial blood samples were drawn from 10 patients with acute ischemic stroke presenting within 24 h of symptom onset and with NIHSS scores >or=4. Samples were taken at 24, 48, and 72 h. Leukocyte ROCK activity was determined by immunoblotting leukocyte lysates with antibodies to the phosphorylated form of myosin-binding subunit (P-MBS) of myosin light chain phosphatase (MLCP). MBS and P-MBS contents were normalized to alpha-tubulin, and ROCK activity was expressed as the ratio of P-MBS to MBS. ROCK activities in these 10 patients were compared to baseline ROCK activities in 10 control subjects without acute illness and matched for sex, age, and number of vascular risk factors using a two-tailed Students t-test. RESULTS The mean NIHSS score in patients with stroke was 15.4. ROCK activity was significantly increased at 24 and 48 h in patients after acute ischemic stroke when compared to control values, with peak elevations at 48 h after stroke onset. There was no apparent correlation between ROCK activity and stroke severity based on NIHSS. CONCLUSIONS Leukocyte ROCK activity is increased in patients after acute ischemic stroke with maximal activity occurring about 48 h after stroke onset. These findings suggest that activation of ROCK may play a role in the pathogenesis of ischemic stroke in humans.

Plasma-Type Gelsolin Is Decreased in Human Blood and Cerebrospinal Fluid After Subarachnoid Hemorrhage

Background and Purpose— Subarachnoid hemorrhage (SAH) pathophysiology involves neurovascular proteolysis and inflammation. How these 2 phenomena are related remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the depletion of anti-inflammatory plasma-type gelsolin (pGSN). Methods— We enrolled 42 consecutive SAH subjects and sampled cerebrospinal fluid (CSF) and blood on post-SAH Days 2 to 3, 4 to 5, 6 to 7, and 10 to 14. Control subjects were 20 consecutive non-SAH hydrocephalus patients with lumbar drains. Enzyme-linked immunosorbent assay, Western blotting, and zymography were used to quantify pGSN and MMP-9. Results— In CSF, pGSN was lower in SAH compared with control subjects on post-SAH Days 2 to 3 (P=0.0007), 4 to 5 (P=0.041), and 10 to 14 (P=0.007). In blood, pGSN decreased over time (P=0.001) and was lower in SAH compared with control subjects on post-SAH Days 4 to 5 (P=0.037), 6 to 7 (P=0.006), and 10 to 14 (P=0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and 46 kDa, representing cleaved pGSN fragments. Gelatin zymography showed that CSF MMP-9 was elevated in SAH compared with control subjects. Higher CSF MMP-9 correlated with lower CSF pGSN on post-SAH Day 7 (r=−0.38; P=0.05). Conclusions— SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN cleavage by MMPs. Because pGSN is known to inhibit inflammatory mediators, these findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH. Further studies are warranted to investigate the mechanisms underlying MMP–pGSN signaling in SAH.

Emerging Cases of Powassan Virus Encephalitis in New England: Clinical Presentation, Imaging, and Review of the Literature

BACKGROUND Powassan virus (POWV) is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits Lyme disease. The prevalence of POWV among animal hosts and vectors has been increasing. We present 8 cases of POWV encephalitis from Massachusetts and New Hampshire in 2013-2015. METHODS We abstracted clinical and epidemiological information for patients with POWV encephalitis diagnosed at 2 hospitals in Massachusetts from 2013 to 2015. We compared their brain imaging with those in published findings from Powassan and other viral encephalitides. RESULTS The patients ranged in age from 21 to 82 years, were, for the most part, previously healthy, and presented with syndromes of fever, headache, and altered consciousness. Infections occurred from May to September and were often associated with known tick exposures. In all patients, cerebrospinal fluid analyses showed pleocytosis with elevated protein. In 7 of 8 patients, brain magnetic resonance imaging demonstrated deep foci of increased T2/fluid-attenuation inversion recovery signal intensity. CONCLUSIONS We describe 8 cases of POWV encephalitis in Massachusetts and New Hampshire in 2013-2015. Prior to this, there had been only 2 cases of POWV encephalitis identified in Massachusetts. These cases may represent emergence of this virus in a region where its vector, I. scapularis, is known to be prevalent or may represent the emerging diagnosis of an underappreciated pathogen. We recommend testing for POWV in patients who present with encephalitis in the spring to fall in New England.

COMA AND CONFUSIONAL STATES: EMERGENCY DIAGNOSIS AND MANAGEMENT

Coma and confusion signal a failure of brain function with many possible causes. Since many of the potential causes may quickly lead to death or severe disability, it is important to develop a focused and ordered approach to facilitate the rapid diagnosis and early institution of proper therapies. This requires an understanding of the localizing features of the neurologic examination and of the syndromes likely to cause coma and confusion, a predetermined plan for empiric therapies in certain cases of doubt when diagnostic confirmation will be delayed, and a careful consideration of cases when the diagnosis is not revealed by the initial neuroimaging, lumbar puncture, or EEG.

Cerebral hemorrhage in a patient taking fenfluramine and phentermine for obesity

Obesity affects approximately 58 million people in the United States and is the second leading cause of preventable death after cigarette smoking.1 Recently, the poor results of dietary and behavioral therapy for obesity have led to renewed interest in the use of appetite suppressants.1,2 One particularly popular regimen consists of the combination of sympathomimetic amines d,l-fenfluramine and phentermine. D,l-fenfluramine decreases appetite by stimulating serotonin release and inhibiting its reuptake by presynaptic neurons, whereas phentermine decreases appetite by modulating noradrenergic neurotransmission. Several studies suggest that the combination of d,l-fenfluramine and phentermine in low doses produces greater appetite suppression with fewer side effects than higher doses of individual drugs and may be a more effective treatment for obesity.2,3 Sympathomimetic amines such as amphetamines and phenylpropanolamine have a well-documented association with stroke and cerebral hemorrhage.4 Phentermine and d,l-fenfluramine have been associated with cases of cerebral infarction,5,6 but they have not been implicated as a cause …

Cerebrovascular complications of pregnancy and the postpartum period.

Cerebrovascular complications of pregnancy, though uncommon, threaten women with severe morbidity or death, and they are the main causes of major long-term disability associated with pregnancy. In this review, we discuss the epidemiology, pathophysiology, presentation and diagnosis, and management and outcomes of ischemic and hemorrhagic stroke and cerebral venous thrombosis. We also discuss the posterior reversible encephalopathy syndrome, the reversible cerebral vasoconstriction syndrome including postpartum cerebral angiopathy, and their relationship as overlapping manifestations of pre-eclampsia-eclampsia.