Dana Leifer

Cerebrovascular Reserve and Stroke Risk in Patients With Carotid Stenosis or Occlusion A Systematic Review and Meta-Analysis

Background and Purpose— Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk. Methods— We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model. Results— Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99–7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method. Conclusions— CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.

Metrics for Measuring Quality of Care in Comprehensive Stroke Centers: Detailed Follow-Up to Brain Attack Coalition Comprehensive Stroke Center Recommendations A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Background— Stroke is a major cause of disability and death. The Brain Attack Coalition has proposed establishment of primary and comprehensive stroke centers to provide appropriate care to stroke patients who require basic and more advanced interventions, respectively. Primary stroke centers have been designated by The Joint Commission since 2003, as well as by various states. The designation of comprehensive stroke centers (CSCs) is now being considered. To assist in this process, we propose a set of metrics and related data that CSCs should track to monitor the quality of care that they provide and to facilitate quality improvement. Methods and Results— We analyzed available guideline statements, reviews, and other literature to identify the major features that distinguish CSCs from primary stroke centers, drafted a set of metrics and related data elements to measure the key components of these aspects of stroke care, and then revised these through an iterative process to reach a consensus. We propose a set of metrics and related data elements that cover the major aspects of specialized care for patients with ischemic cerebrovascular disease and nontraumatic subarachnoid and intracerebral hemorrhages at CSCs. Conclusions— The metrics that we propose are intended to provide a framework for standardized data collection at CSCs to facilitate local quality improvement efforts and to allow for analysis of pooled data from different CSCs that may lead to development of national performance standards for CSCs in the future.

Clinicopathologic correlations of cranial magnetic resonance imaging of periventricular white matter

We studied clinical, imaging, and autopsy data on 7 patients who underwent magnetic resonance imaging (MRI) during life. Small periventricular zones of increased T2 signal corresponded to a periventricular cap consisting of subependymal glial accumulations, with some loss of the ependymal lining, and a surrounding pale-staining area of finely textured myelin and axons with an altered glial pattern. The fine-fiber zone is identifiable anatomically as the subcallosal fasciculus. This histologic pattern of subependymal glial accumulations and fine fibers is normal and is often associated with fibrotic small blood vessels. More extensive subcortical MRI changes corresponded, in 1 case, to multiple sclerosis, and in another to subcortical arteriosclerotic encephalopathy (Binswangers disease) with widespread fiber loss and lacunar changes. Wallerian degeneration secondary to infarction occurred in some areas of MRI abnormality.

The Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART): an adaptive design phase I dose‐escalation study of high‐dose lovastatin in acute ischemic stroke

There is growing experimental and clinical evidence that by reducing downstream products of the mevalonate pathway other than cholesterol, HMG-CoA reductase inhibitors (‘statins’) have beneficial effects on endothelial function, coronary and cerebral blood flow, inflammation, and hemostasis. Statins have been shown in rodent models of acute ischemic stroke to reduce neuronal injury and infarct size in a dose-dependent fashion. The objective of this early phase trial will be to determine the maximal-tolerated dose of lovastatin for short-term acute stroke therapy. In this multicenter phase 1B dose-escalation and dose-finding study, 33 patients with acute ischemic stroke will be administered lovastatin in increasing doses from one to 10 mg/kg daily for 3 days beginning within 24 hours after symptom onset. The primary safety outcome will be occurrence of myotoxicity

Ocular stroke and carotid artery dissection

Carotid artery dissection frequently causes transient ipsilateral visual impairment. We present 2 cases of permanent ocular vaso-occlusion sequelae consequent to dissection of the ipsilateral internal carotid, definite in one and probable in the other. In both, the ocular strokes led to the recognition of the underlying carotid vasculopathy.

High-Dose Lovastatin for Acute Ischemic Stroke: Results of the Phase I Dose Escalation Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART)

Background: Hydroxymethylglutaryl coenzyme A reductase inhibitors (‘statins’) reduce the neuronal injury in dose-dependent fashion in rodent stroke models. We sought to determine whether lovastatin at doses above those currently approved can be administered safely within 24 h after an acute ischemic stroke. Methods: We conducted a phase 1B dose-finding study using an adaptive design novel to stroke trials, the continual reassessment method, to find the highest tolerated dose of lovastatin. Planned doses were 1, 3, 6, 8 and 10 mg/kg/day for 3 days. The primary safety outcomes were myotoxicity and hepatotoxicity. The model was calibrated to select a dose causing 7–13% toxicity. Results: We enrolled 33 patients (16 men/17 women, age range 23–82 years). Three patients were treated at 1 mg/kg, 10 at 3 mg/kg, 12 at 6 mg/kg, and 8 at 8 mg/kg. Thirty of the 33 patients (90.9%) completed at least 11 of 12 doses. Two patients at the 6-mg/kg dose level experienced transient mild elevations in transaminases without clinical sequelae. After an initial dose reduction, the dose was re-escalated to 8 mg/kg, and no further patients reached safety outcomes. No clinical liver disease, myopathy, or creatine phosphokinase elevations occurred. The final model-based toxicity at 8 mg/kg was 13%; no patient was treated at 10 mg/kg. Conclusions: Lovastatin at doses above those currently approved by the Food and Drug Administration is feasible for 3 days after an acute ischemic stroke and the maximum tolerated dose is estimated to be 8 mg/kg/day. Further randomized studies are warranted to confirm its safety and to demonstrate its efficacy in improving functional outcomes after stroke.

Blindness and Necrotizing Fasciitis After Liposuction and Fat Transfer

Liposuction occasionally has complications. The authors describe the symptoms, diagnosis, and treatment of necrotizing fasciitis and review the literature cases of visual loss and blindness and necrotizing fasciitis associated with liposuction surgery.

Quantitative Susceptibility Mapping of Intracerebral Hemorrhages at Various Stages.

To investigate the magnetic susceptibility of intracerebral hemorrhages (ICH) at various stages by applying quantitative susceptibility mapping (QSM).

Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults

Protein Z (PZ) is a vitamin K-dependent plasma protein that exhibits both pro- and anticoagulant properties. Both low and high PZ levels have been linked to ischaemic stroke. Although PZ-lowering gene variants have been found to be less common in ischaemic stroke, the relationship remains unclear. We investigated PZ levels and PROZ variants in a multi-ethnic case-control study of unexplained stroke in participants aged 18 to 64. Plasma PZ was measured in cases (≥2 months post-stroke) and controls. PZ polymorphisms G79A (rs3024735) and A13G (2273971) were genotyped. A combined genetic score (0-4 minor alleles) was created assuming additive effects. A total of 715 individuals (1:1.4 cases:controls) was included. Analyses revealed evidence of a non-linear association. After adjusting for demographic and clinical covariates, PZ levels >2.5 µg/ml (90th %ile) were significantly associated with cryptogenic stroke (OR 2.41 [95 % CI 1.34, 4.34]) as compared with lower levels. Higher genetic score was related to progressively lower levels of PZ, and the presence of four minor alleles was associated with lower odds of stroke (adjusted OR 0.26 [95 % CI 0.07, 0.96]) versus 0 minor alleles. In this multi-ethnic study of young and middle-aged adults, there was evidence of a non-linear positive association between PZ level and unexplained stroke, with a directionally consistent association for genetic variants related to PZ levels and cryptogenic stroke. These findings support elevated PZ levels as a risk factor for cryptogenic stroke.

Endovascular Therapy for Acute Stroke in Patients With Cancer

Intravenous thrombolysis is the standard treatment for acute ischemic stroke (AIS). However, patients with cancer who have stroke are often precluded from therapy because of coagulopathy or recent surgery. Endovascular therapy may be a more suitable recanalization strategy for some patients with cancer and stroke, but no prior detailed reports documenting its use in this population exist. We present a case series from a tertiary care referral center of 2 patients with active systemic cancer who were successfully treated with endovascular therapy for AIS. Both patients had active lung cancer with excellent premorbid functional status and presented with severe AIS from left middle cerebral artery occlusions. Intravenous thrombolysis was deferred because of absolute contraindications. Mechanical embolectomy was performed instead and revascularization was achieved within 5 hours in both patients, resulting in dramatic neurological recoveries—National Institutes of Health Stroke Scale improved from 14 to 0 and from 23 to 3 from admission to discharge, respectively. In conclusion, endovascular therapy may be beneficial for select patients with cancer and AIS who are ineligible for intravenous thrombolysis. However, further studies are needed to determine the safety and efficacy of endovascular therapy in the population with cancer.