Poor Outcomes Related to Anterior Extension of Large Hemispheric Infarction: Topographic Analysis of GAMES-RP Trial MRI Scans.

BACKGROUND: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI). METHODS: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate. RESULTS: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016). CONCLUSIONS: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Long-Term Outcomes in Patients Aged ≤70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction: An Exploratory Analysis.

BACKGROUND AND PURPOSE: We aimed to determine whether subjects aged ≤70 years who were treated with intravenous glyburide (RP-1127; BIIB093; glibenclamide) would have better long-term outcomes than those who received placebo. METHODS: GAMES-RP (Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals) was a prospective, double-blind, randomized, placebo-controlled phase 2 clinical trial. Eighty-six participants, aged 18 to 80 years, who presented to 18 centers with large hemispheric infarction (baseline diffusion-weighted imaging volumes, 82-300 cm3) randomized within 10 hours of symptom onset were enrolled. In the current exploratory analysis, we included participants aged ≤70 years treated with intravenous glyburide (n=35) or placebo (n=30) who met per-protocol criteria. Intravenous glyburide or placebo was administered in a 1:1 ratio. We analyzed 90-day and 12-month mortality, functional outcome (modified Rankin Scale, Barthel Index), and quality of life (EuroQol group 5-dimension). Additional outcomes assessed included blood-brain barrier injury (MMP-9 [matrix metalloproteinase 9]) and cerebral edema (brain midline shift). RESULTS: Participants ≤70 years of age treated with intravenous glyburide had lower mortality at all time points (log-rank for survival hazards ratio, 0.34; P=0.04). After adjustment for age, the difference in functional outcome (modified Rankin Scale) demonstrated a trend toward benefit for intravenous glyburide-treated subjects at 90 days (odds ratio, 2.31; P=0.07). Repeated measures analysis at 90 days, 6 months, and 12 months using generalized estimating equations showed a significant treatment effect of intravenous glyburide on the Barthel Index (P=0.03) and EuroQol group 5-dimension (P=0.05). Participants treated with intravenous glyburide had lower plasma levels of MMP-9 (189 versus 376 ng/mL; P<0.001) and decreased midline shift (4.7 versus 9 mm; P<0.001) compared with participants who received placebo. CONCLUSIONS: In this exploratory analysis, participants ≤70 years of age with large hemispheric infarction have improved survival after acute therapy with intravenous glyburide. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.

BACKGROUND: Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction. METHODS: GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusion-weighted image lesion between 82 and 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was ≤10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. RESULTS: The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies.

Lumbar disc nomenclature: version 2.0: Recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology.

BACKGROUND CONTEXT: The paper ''Nomenclature and classification of lumbar disc pathology, recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology,'' was published in 2001 in Spine (© Lippincott, Williams & Wilkins). It was authored by David Fardon, MD, and Pierre Milette, MD, and formally endorsed by the American Society of Spine Radiology (ASSR), American Society of Neuroradiology (ASNR), and North American Spine Society (NASS). Its purpose was to promote greater clarity and consistency of usage of spinal terminology, and it has served this purpose well for over a decade. Since 2001, there has been sufficient evolution in our understanding of the lumbar disc to suggest the need for revision and updating of the original document. The revised document is presented here, and it represents the consensus recommendations of contemporary combined task forces of the ASSR, ASNR, and NASS. This article reflects changes consistent with current concepts in radiologic and clinical care. PURPOSE: To provide a resource that promotes a clear understanding of lumbar disc terminology amongst clinicians, radiologists, and researchers. All the concerned need standard terms for the normal and pathologic conditions of lumbar discs that can be used accurately and consistently and thus best serve patients with disc disorders. STUDY DESIGN: This article comprises a review of the literature. METHODS: A PubMed search was performed for literature pertaining to the lumbar disc. The task force members individually and collectively reviewed the literature and revised the 2001 document. The revised document was then submitted for review to the governing boards of the ASSR, ASNR, and NASS. After further revision based on the feedback from the governing boards, the article was approved for publication by the governing boards of the three societies, as representative of the consensus recommendations of the societies. RESULTS: The article provides a discussion of the recommended diagnostic categories pertaining to the lumbar disc: normal; congenital/developmental variation; degeneration; trauma; infection/inflammation; neoplasia; and/or morphologic variant of uncertain significance. The article provides a glossary of terms pertaining to the lumbar disc, a detailed discussion of these terms, and their recommended usage. Terms are described as preferred, nonpreferred, nonstandard, and colloquial. Updated illustrations pictorially portray certain key terms. Literature references that provided the basis for the task force recommendations are included. CONCLUSIONS: We have revised and updated a document that, since 2001, has provided a widely acceptable nomenclature that helps maintain consistency and accuracy in the description of the anatomic and physiologic properties of the normal and abnormal lumbar disc and that serves as a system for classification and reporting built upon that nomenclature.