ObjectiveTo assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.MethodsENOS randomized 4,011 patients with acute stroke (<48 hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90. Cognition was assessed via telephone at day 90. Stroke syndrome was classified with the Oxfordshire Community Stroke Project classification. Brain imaging was adjudicated masked to clinical information and treatment and assessed SVD (leukoaraiosis, old lacunar infarcts/lacunes, atrophy) and brain frailty (leukoaraiosis, atrophy, old vascular lesions/infarcts). Analyses used ordinal logistic regression adjusted for prognostic variables.ResultsIn all participants and those with lacunar syndrome (LACS; 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07–1.24; brain frailty score OR 1.25, 95% CI 1.17–1.34; those with LACS: SVD score OR 1.30, 95% CI 1.15–1.47, brain frailty score OR 1.28, 95% CI 1.14–1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS.ConclusionsBaseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making.IdentifierISRCTN99414122.

A simple, low-cost intervention in the community phase of stroke recovery aiming to promote self-directed rehabilitation improved outcomes.

T reatment options for acute ischemic stroke are limited to thrombolysis, aspirin, hemicraniectomy and stroke unit care, [1][2][3][4] and mechanical thrombectomy. [5][6][7] Although there are no definitive treatments for acute intracerebral hemorrhage, lowering blood pressure (BP) might be beneficial. 8 As a result, new interventions are still needed and, ideally, ones that are simple to administer and relevant irrespective of stroke type so that they can be given prehospital or immediately on admission to hospital before neuroimaging.Nitric oxide (NO) donors are a candidate treatment for acute stroke. [9][10][11] In preclinical studies, NO donors reduced lesion size and increased cerebral blood flow, but only if given early. 12 In multiple pilot randomized controlled trials, NO donors (specifically intravenous sodium nitroprusside and transdermal glyceryl trinitrate [GTN]) reduced BP, pulse pressure, variability, and peak systolic BP; maintained cerebral blood flow (in spite of BP reduction); and improved arterial compliance. [13][14][15][16][17] Although sodium nitroprusside attenuated platelet function, GTN had no effect on platelets, 13,14 suggesting that it could be given to patients whether they had ischemic or hemorrhagic stroke. In a small trial of GTN administered by paramedics before hospital admission (with median time toBackground and Purpose-Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset. Methods-Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset.Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes. Results-Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg (P<0.01, P=0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32-0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale admission of 55 minutes), GTN seemed to improve functional outcome, assessed as the modified Rankin Scale (mRS). 17When assessed in a large international trial involving patients with stroke within 48 hours, GTN was safe to administer but did not alter mRS, the primary outcome. 18The potential benefit of GTN when administered early 17 suggested that the...