Cerebral White Matter Hyperintensities Predict Functional Stroke Outcome

Background and Purpose-The integrity of white matter tracts connecting different parts of the brain is important for rapid compensation for the lost function from ischemic stroke. Impaired white matter reserve capacity secondary to leukoaraiosis may facilitate detection of new symptomatic ischemic events that would otherwise remain inconspicuous after an initial ischemic stroke. We sought to identify whether the extent of leukoaraiosis was a predictor of risk of early stroke recurrence. Methods-We used Cox regression analysis in consecutive patients with ischemic stroke to determine the relationship between leukoaraiosis burden and symptomatic stroke recurrence within 90 days. We graded total leukoaraiosis, periventricular leukoaraiosis, and subcortical leukoaraiosis using the Fazekas scale as mild (<2) and extensive (≥2) on fluid-attenuated inversion recovery images obtained within 72 hours of stroke onset in the hemisphere contralateral to acute stroke. Results-There were 106 recurrent events in 2378 patients. The cumulative incidence of recurrence was 5.9% at 90 days.Kaplan-Meier estimate of recurrence-free survival rate was lower in patients with extensive leukoaraiosis (P=0.04) and extensive periventricular leukoaraiosis (P=0.02) but not in extensive subcortical leukoaraiosis (P=0.09). Multivariable Cox regression analysis revealed a hazard ratio of 1.50 (95% confidence interval, 1.00-2.25) for extensive leukoaraiosis, 1.67 (95% confidence interval, 1.11-2.51) for extensive periventricular leukoaraiosis, and 1.42 (95% confidence interval, 0.94-2.12) for extensive subcortical leukoaraiosis. Conclusions-The extent of leukoaraiosis independently predicts 90-day recurrent stroke risk after ischemic stroke. This suggests that leukoaraiosis may be used for risk stratification in ischemic stroke.

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 59%

Extensive Leukoaraiosis Is Associated With High Early Risk of Recurrence After Ischemic Stroke

Kim

Park

Avery

et al. 2014

“…[131][132][133][134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149] Among the 19 studies that examined functional status at 30 or 90 days, none were designed to evaluate the quality of care at the hospital level or predict outcomes at the provider level. Each study examined functional status outcomes at the patient level, with 13 studies specifying an independent variable.…”

Section: Review Of Evidence On Models That Evaluate Predictors Of Funmentioning

confidence: 99%

Risk Adjustment of Ischemic Stroke Outcomes for Comparing Hospital Performance

Katzan¹,

Spertus²,

Bettger³

et al. 2014

Background and Purpose-Stroke is the fourth-leading cause of death and a leading cause of long-term major disability in the United States. Measuring outcomes after stroke has important policy implications. The primary goals of this consensus statement are to (1) review statistical considerations when evaluating models that define hospital performance in providing stroke care; (2) discuss the benefits, limitations, and potential unintended consequences of using various outcome measures when evaluating the quality of ischemic stroke care at the hospital level; (3) summarize the evidence on the role of specific clinical and administrative variables, including patient preferences, in risk-adjusted models of ischemic stroke outcomes; (4) provide recommendations on the minimum list of variables that should be included in risk adjustment of ischemic stroke outcomes for comparisons of quality at the hospital level; and (5) provide recommendations for further research. Methods and Results-This statement gives an overview of statistical considerations for the evaluation of hospital-level outcomes after stroke and provides a systematic review of the literature for the following outcome measures for ischemic stroke at 30 days: functional outcomes, mortality, and readmissions. Data on outcomes after stroke have primarily involved studies conducted at an individual patient level rather than a hospital level. On the basis of the available information, the following factors should be included in all hospital-level risk-adjustment models: age, sex, stroke severity, comorbid conditions, and vascular risk factors. Because stroke severity is the most important prognostic factor for individual patients and appears to be a significant predictor of hospital-level performance for 30-day mortality, inclusion of a stroke severity measure in risk-adjustment models for 30-day outcome measures is recommended. Risk-adjustment models that do not include stroke severity or other recommended variables must provide comparable classification of hospital performance Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/CopyrightPermission-Guidelines_UCM_300404_Article.jsp. A link to the "Copyright Permissions Request Form" appears on the right side of the page.© 2014 American Heart Association, Inc. In an effort to improve healthcare quality, regulatory bodies have begun to measure outcomes after hospitalization for several diseases, including pneumonia, myocardial infarction, and congestive heart failure. Similarly, stroke is an emerging, high-priority target for such efforts. Stroke is the fourth-leading cause of death and a cause of long-term major disability in the United States.1 It is also one of the top 10 costliest conditions for the Centers for Medicare & Medicaid Services (CMS).2 As with most disease states, accura...

“…[8][9][10] Oligodendrocytes are particularly sensitive to ischemic and oxidative stress, 7,34,35 and there is a correlation between white matter involvement and poor long-term functional outcomes after stroke. 5,6 It may be that dalfampridine is acting on demyelinated but intact pathways that are functionally impaired yet have synaptic connections in areas remote from the lesion, as Rats at the end of the dose-escalation study were larger than the rats at the end of the double cross-over study (488 vs 525 g on average, respectively). MCAO indicates middle cerebral artery occlusion.…”

Section: Strokementioning

confidence: 99%

“…2,3 Significant white matter involvement occurs in the majority of strokes 4 and has been linked to poorer long-term functional outcomes. 5,6 Additionally, oligodendrocytes have been shown to be particularly sensitive to ischemic insult. 7 The potassium channel blocker, 4-aminopyridine, known in the United States by its nonproprietary drug name dalfampridine, and in the rest of the world as fampridine, has been studied for many years for its potential to improve conduction in demyelinated axons.…”

mentioning

confidence: 99%

Dalfampridine Improves Sensorimotor Function in Rats With Chronic Deficits After Middle Cerebral Artery Occlusion

Iaci

Parry

Huang

et al. 2013

Background and Purpose-Stroke survivors often have permanent deficits that are only partially addressed by physical therapy. This study evaluated the effects of dalfampridine, a potassium channel blocker, on persistent sensorimotor deficits in rats with treatment initiated 4 or 8 weeks after stroke. Methods-Rats underwent permanent middle cerebral artery occlusion. Sensorimotor function was measured using limbplacing and body-swing symmetry tests, which normally show a partial recovery from initial deficits that plateaus ≈4 weeks after permanent middle cerebral artery occlusion. Dalfampridine was administered starting at 4 or 8 weeks after permanent middle cerebral artery occlusion in 2 blinded, vehicle-controlled studies. Plasma samples were collected and brain tissue was processed for histologic assessment. Results-Dalfampridine treatment (0.5-2.0 mg/kg) improved forelimb-and hindlimb-placing responses and body-swing symmetry in a reversible and dose-dependent manner. Plasma dalfampridine concentrations correlated with dose. Brain infarct volumes showed no differences between treatment groups. Conclusions-Dalfampridine improves sensorimotor function in the rat permanent middle cerebral artery occlusion model.Dalfampridine extended-release tablets (prolonged release fampridine outside the United States) are used to improve walking in patients with multiple sclerosis, and these preclinical data provide a strong rationale for examining the potential of dalfampridine to treat chronic stable deficits in stroke patients.