Jarrahi Abbas, Shah Manan, Ahluwalia Meenakshi, Khodadadi Hesam, Vaibhav Kumar, Bruno Askiel, Baban Babak, Hess David C, Dhandapani Krishnan M, Vender John R
Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Front Neurosci. 2022 May 12;16:791035. doi: 10.3389/fnins.2022.791035. eCollection 2022.
Spontaneous Intracerebral hemorrhage (ICH) is a devastating injury that accounts for 10-15% of all strokes. The rupture of cerebral blood vessels damaged by hypertension or cerebral amyloid angiopathy creates a space-occupying hematoma that contributes toward neurological deterioration and high patient morbidity and mortality. Numerous protocols have explored a role for surgical decompression of ICH craniotomy, stereotactic guided endoscopy, and minimally invasive catheter/tube evacuation. Studies including, but not limited to, STICH, STICH-II, MISTIE, MISTIE-II, MISTIE-III, ENRICH, and ICES have all shown that, in certain limited patient populations, evacuation can be done safely and mortality can be decreased, but functional outcomes remain statistically no different compared to medical management alone. Only 10-15% of patients with ICH are surgical candidates based on clot location, medical comorbidities, and limitations regarding early surgical intervention. To date, no clearly effective treatment options are available to improve ICH outcomes, leaving medical and supportive management as the standard of care. We recently identified that remote ischemic conditioning (RIC), the non-invasive, repetitive inflation-deflation of a blood pressure cuff on a limb, non-invasively enhanced hematoma resolution and improved neurological outcomes anti-inflammatory macrophage polarization in pre-clinical ICH models. Herein, we propose a pilot, placebo-controlled, open-label, randomized trial to test the hypothesis that RIC accelerates hematoma resorption and improves outcomes in ICH patients. Twenty ICH patients will be randomized to receive either mock conditioning or unilateral arm RIC (4 cycles × 5 min inflation/5 min deflation per cycle) beginning within 48 h of stroke onset and continuing twice daily for one week. All patients will receive standard medical care according to latest guidelines. The primary outcome will be the safety evaluation of unilateral RIC in ICH patients. Secondary outcomes will include hematoma volume/clot resorption rate and functional outcomes, as assessed by the modified Rankin Scale (mRS) at 1- and 3-months post-ICH. Additionally, blood will be collected for exploratory genomic analysis. This study will establish the feasibility and safety of RIC in acute ICH patients, providing a foundation for a larger, multi-center clinical trial.
自发性脑出血（ICH）是一种严重的损伤，占所有中风的10%-15%。高血压或脑淀粉样血管病损伤的脑血管破裂会形成占位性血肿，导致神经功能恶化以及患者的高发病率和死亡率。许多方案都探讨了ICH手术减压的作用，包括开颅手术、立体定向引导内窥镜检查以及微创导管/引流管血肿清除术。包括但不限于STICH、STICH-II、MISTIE、MISTIE-II、MISTIE-III、ENRICH和ICES在内的研究均表明，在某些有限的患者群体中，血肿清除可以安全进行，死亡率可以降低，但与单纯的药物治疗相比，功能结局在统计学上并无差异。基于血凝块位置、合并症以及早期手术干预的局限性，只有10%-15%的ICH患者是手术候选者。迄今为止，尚无明确有效的治疗方案可改善ICH的预后，因此药物治疗和支持性治疗仍是标准的治疗方法。我们最近发现，远程缺血预处理（RIC），即对肢体上的血压袖带进行无创、重复的充气-放气，在临床前ICH模型中可无创地增强血肿吸收并改善神经功能结局，其机制为促进抗炎性巨噬细胞极化。在此，我们提出一项先导性、安慰剂对照、开放标签、随机试验，以检验RIC可加速ICH患者血肿吸收并改善预后这一假设。20例ICH患者将被随机分组，在中风发作后48小时内开始接受模拟预处理或单侧手臂RIC（4个周期，每个周期充气5分钟/放气5分钟），并持续每天两次，共一周。所有患者将根据最新指南接受标准医疗护理。主要结局将是ICH患者单侧RIC的安全性评估。次要结局将包括血肿体积/血凝块吸收速率以及功能结局，通过ICH后1个月和3个月时的改良Rankin量表（mRS）进行评估。此外，还将采集血液进行探索性基因组分析。本研究将确定RIC在急性ICH患者中的可行性和安全性，为更大规模的多中心临床试验奠定基础。
