INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial.

BACKGROUND: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. METHODS: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1-7.8 mmol/L and 7.8-10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. DISCUSSION: As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established. TRIAL REGISTRATION: ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017.

Prognostic Factors for Long-Term Recovery of Homonymous Visual Field Defects After Posterior Circulation Ischemic Stroke.

OBJECTIVES: Ischemic stroke (IS) is the main cause of homonymous visual field defects (HVFDs) in adults. Some reports suggest recovery even in late-phase strokes, but data is sparse. This study examines the frequency of long-term recovery from HVFDs in patients with posterior circulation infarction (POCI) and evaluates whether demographic or clinical characteristics are prognostic factors of perimetric recovery. MATERIALS AND METHODS: Our study included patients with HVFDS due to POCI who had undergone 2 or more kinetic perimetric evaluations at least 6 months after the index IS. Clinical and imaging data were systematically reviewed and we performed univariate and multivariate logistic regression analyses to determine whether demographic, stroke etiology (TOAST classification), and initial perimetric patterns were prognostic factors of visual recovery occurring 6 months and beyond from POCI. RESULTS: One hundred one patients with POCI were included. Median subject age was 60 years and 54.4% were female. After a median perimetric follow-up time of 13.5 months, spontaneous visual improvement was observed in 15.8% of patients. Prognostic factors for visual improvement were age < 50 years (OR 4.6; P = 0.093), POCI associated with hypercoagulable states (OR 12.3; P = 0.048), and vertebral artery dissection (OR 12.6; P = 0.048), while the presence of complete homonymous hemianopia was a negative predictor of recovery (OR 0.2; P = 0.048). CONCLUSION: Partial visual recovery in HVFDs is observed even 6 months and beyond POCI. Age < 50 years and stroke etiology were predictors of recovery.

Blue Rubber Bleb Nevus Syndrome With Multiple Cavernoma-Like Lesions on MRI: A Familial Case Report and Literature Review.

Blue rubber bleb nevus syndrome (BRBNS), also called Bean's syndrome, is a rare disease associated with multiple venous malformations in the skin and gastrointestinal (GI) tract. Dermatological lesions, which are the first clinically visible manifestations, appear as skin-colored compressible protuberances or as dark-blue venous nodules, rubbery in consistency. Central nervous system (CNS) manifestations are rare, variable, non-specific, and tend to occur late in the disease, mainly reported as seizures and focal neurological deficits secondary to compression. Most cases occur sporadically, however, an autosomal dominant inheritance pattern has been reported. A 74-year-old male with history of focal epilepsy secondary to possible neurocysticercosis presented at the emergency department due to sudden onset of aphasia, left central facial paralysis, and dysphagia secondary to catastrophic intracerebral hemorrhage. Cerebral MRI showed multiple cerebral cavernous malformations (CCM)-like lesions and, on the general exploration, multiple dark-blue nodules, rubbery in consistency. One week later he died due to complicated pneumonia; a brain autopsy was performed showing multiple vascular malformations. His son had a history of focal epilepsy presumed to be related to neurocysticercosis. He had the same skin lesions and brain MRI pattern. Histological analysis of the skin lesions of the two cases showed venous vascular malformations. A non-systematic review was carried out, in which all case reports of blue nevus syndrome with neurological manifestations in adults were included.

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. RESULTS: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. CONCLUSION: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. TRIAL REGISTRATION: ISRCTN25765518.