Intracerebral hemorrhage causes 15% of strokes annually in the United States, and there is currently no effective therapy.Aims and hypothesis
This is a clinical trial designed to study the safety, feasibility, and efficacy of a protocol of targeted temperature management to moderate hypothermia in intracerebral hemorrhage patients.Methods
The targeted temperature management after intracerebral hemorrhage trial is a prospective, single-center, interventional, randomized, parallel, two-arm (1:1) phase-II clinical trial with blinded end-point ascertainment. Intracerebral hemorrhage patients will be randomized within 18 h of symptom onset to either 72 h of targeted temperature management to moderate hypothermia (32–34°C) followed by a controlled rewarming at of 0·05–0·1°C per hour or 72 h of targeted temperature management to normothermia (36–37°C) using endovascular or surface cooling.Outcomes
The primary outcome is the development of serious adverse events possibly and probably related to treatment. Secondary outcomes include in-hospital neurological deterioration between day 0–7, in-hospital mortality, functional outcome measured by the modified Rankin scale at discharge and 90 days, and effect of treatment allocation on cerebral edema and hematoma volume.Discussion
Intracerebral hemorrhage remains the most severe form of stroke with limited options to improve survival. As the early resuscitation phase in the intensive care unit represents the greatest opportunity for impact on clinical outcome, it also appears to be the most promising window of opportunity to demonstrate a benefit when investigating aggressive treatments.Conclusion
More research of novel therapies to improve outcomes after intracerebral hemorrhage is desperately needed. The results of the targeted temperature management after intracerebral hemorrhage clinical trial may provide additional information on the applicability of targeted temperature management after intracerebral hemorrhage.
The associations between the CHADS2 score/CHA2DS2-VASc score, and the presence of cerebral vessel occlusion on admission were examined in cardioembolic stroke patients with nonvalvular atrial fibrillation.Methods
The subjects were 546 consecutive patients hospitalized between April 2007 and December 2012 with onset of cardioembolic stroke associated with nonvalvular atrial fibrillation within 24 h. The associations between the CHADS2 score/CHA2DS2-VASc score and the presence of occluded cerebral vessels on magnetic resonance angiography were evaluated retrospectively. Occluded cerebral vessels were classified into the internal carotid artery, middle cerebral artery (M1, M2), basilar artery, and other (anterior cerebral artery [A1], posterior cerebral artery [P1], vertebral artery).Results
Major artery occlusion was seen in 52% of patients with CHADS2 score 0, 52% of patients with score 1, 57% with score 2, 75% with score 3, and 75% with score ≥4. As for the CHA2DS2-VASc score, major artery occlusion was seen in 62% of patients with score 0, 49% with score 1, 53% with score 2, 53% with score 3, 65% with score 4, 71% with score 5, and 82% with score ≥6. The incidence of concurrent major arterial occlusion increased as both scores rose. When classified by occluded blood vessel, the incidence of concurrent internal carotid artery occlusion increased as both the CHADS2 and CHA2DS2-VASc scores increased.Conclusion
As the CHADS2 and CHA2DS2-VASs scores increased, the incidence of concurrent major arterial occlusion, particularly internal carotid artery occlusion, increased in patients with cardioembolic stroke associated with nonvalvular atrial fibrillation.
Although free fatty acids have been positively associated with risk factors for stroke, the role of plasma free fatty acids in the development of stroke has not been elucidated in older adults.Aims
We sought to examine the association between plasma free fatty acids and incident stroke.Methods
Prospective cohort of 4369 men and women ≥65 years of age in the Cardiovascular Health Study. Plasma levels of free fatty acids were measured at the 1992–1993 examination and stroke events were adjudicated by a committee of experts including neurologists and neuroradiologists. Cox regression was used to estimate the relative risk of stroke associated with free fatty acids concentrations.Results
The average age among participants was 75 ± 5·2 years. During a median follow-up of 11·4 years, 732 incident strokes occurred. The crude incidence rates of stroke were 14·5, 14·9, and 17·6 per 1000 person-years across increasing tertiles of plasma free fatty acids. The adjusted hazard ratio (95% confidence interval) for incident stroke was 1·05 (0·97–1·14) per standard deviation increase in plasma free fatty acids. Restriction to ischemic stroke did not alter the results [hazard ratio (95% confidence interval): 1·04 (0·96–1·14) per standard deviation higher free fatty acids], and there was no effect modification by adiposity (P interaction = 0·18) or by diabetes (P interaction = 0·15).Conclusion
Our data did not show an association of plasma free fatty acids with incident stroke among community dwelling older adults.
In acute stroke, the volume of salvageable brain tissue is maximal at onset and declines rapidly with time. Prehospital start of clinical trial interventions would enable delivery of neuroprotective agents, such as magnesium sulfate, to stroke patients in the hyperacute period when they are potentially most effective.Aims
A broad aim of the FAST-MAG study is to develop and validate techniques to perform pivotal trials of neuroprotective therapies for acute stroke in the prehospital setting. In tandem with an accompanying general trial design article, this manuscript provides a detailed overview of several novel prehospital study methods employed in the NIH FAST-MAG Trial.Design
Multicenter, randomized, double-blinded, placebo-controlled, pivotal clinical trial.
Special Prehospital Procedures Distinctive prehospital methods deployed in FAST-MAG include: identifying likely stroke patients using the Los Angeles Prehospital Stroke Screen; eliciting explicit informed consent from patients or on scene legally authorized representatives via cellphone discussion with off-scene physicians; paramedic rating of pretreatment stroke severity using the Los Angeles Motor Scale; assigning patients to a study arm using blinded, pre-encounter randomization; facilitating continuity of study infusion from the field to the ED by stocking ambulances with study kits including both field and hospital doses; and electronic fax consent signature documentation by geographically separated subjects and enrolling physicians.Discussion
The suite of prehospital trial methods developed for the FAST-MAG Trial enable enrollment of patients in very early time windows, including the hyperacute, ‘golden hour’ period immediately after stroke onset.
Stroke is a life-altering event that potentially affects stroke survivors, their families, healthcare resources, and society in general. Stroke has often been described as ‘brain attack’, denoting emergency emphasis on the vascular pathology. Consequently, many national and provincial stroke strategies have emphasized vascular care through primary prevention strategies and thrombolysis. Despite being important initiatives, this has resulted in a stroke system that emphasizes the frontloading of stroke care, focusing on the vascular pathology. The advent of thrombolysis therapy has benefited a small proportion of patients while a vast majority are still affected by stroke-related impairments. Management of the vascular elements of stroke is important; however, the impact of rehabilitation on stroke recovery has been relatively undervalued. Stroke care is in need of a revolution toward a more comprehensive and balanced approach. It is anticipated that the major focus of stroke care will include promoting recovery, in line with the growing evidence on stroke rehabilitation interventions. A paradigm shift is necessary to ensure that comprehensive and balanced stroke care which incorporates rehabilitation is taken into account, leading to a stroke care system where patient needs are managed both as a ‘brain attack’ and an ‘injured brain’.