National Center on Medical Consequences of Spinal Cord Injury

 说明： 在美国，大约有25万人患有创伤性脊髓损伤(SCI)，另有至少40万人患有非创伤性原因的脊髓损伤。几十年来，由于对泌尿系统和肺部并发症的有效治疗，脊髓损伤患者的寿命有所延长。然而，脊髓损伤人口正在变得越来越老，医疗管理的成本也越来越高。因此，我们越来越迫切地需要继续了解脊髓损伤的医学后果，并寻求安全有效的治疗方案，以最大限度地减少或预防这些不良疾病。COE MCSCI的使命是通过识别和干预来减少和/或预防SCI的继发性医疗后果，从而提高SCI患者的生活质量和延长患者的寿命，这是退伍军人管理局RR&D服务的最好传统。拟议的脊髓损伤医疗后果卓越中心(COE MCSCI)将继续为医学、康复医学、神经学、神经心理学、流行病学、睡眠医学和分子生物学等几个专业领域的研究人员提供支持。COE医生/科学家-研究人员将开始对各种医疗并发症进行介入治疗，或努力更好地描述病理生理状况。将寻求的治疗或研究方法包括以下药理学和非药理学干预：伊班膦酸，以减少行走的不完全运动脊髓损伤患者的骨丢失；肠道胰岛素[胰升糖素样肽(利拉鲁肽)]，以改善碳水化合物/脂肪代谢和软组织身体成分；新的辅助方法，通过离子导入经皮给药新斯的明和葡萄糖苷，以改善常规肠道护理；口腔振动胶囊，改善肠动力和排空；外骨骼辅助行走(EAW)，通过SCI-QOL肠道管理调查、不透明放射物和高分辨率测压测量；识别和分类心血管损害的程度；用于升高血压和预防认知损害的抗低血压药物[例如，β(3)-肾上腺素能受体激动剂(Mirabegron)；阿尔法激动剂(米多君)和去甲肾上腺素前体(Droxidopa)]；一种新型膳食，具有增强的膳食诱导产热能力，以降低冷暴露时的低体温风险；成对的中枢刺激，以加强现有的神经通路到手；以及基于家庭的便携式睡眠监测，与已证实的多导睡眠图进行比较，以确定睡眠呼吸障碍。与普通人群相比，脊髓损伤患者的心血管发病率发生得更早，也更普遍。冠状动脉疾病的传统危险因素可能不能准确地预测大血管疾病的存在。因此，在我们的COE提案中，将继续研究对新出现的风险因素以及常规风险因素的测量，以及冠状动脉钙的量化，以使卫生专业人员能够更好地识别和治疗患有血管疾病的人。脊髓损伤患者的EAW已被证明是一种改变游戏规则的机械干预措施，可以改善几种与健康相关的状况，包括肠功能障碍，建议在COE进行评估。一个新的分子信号通路涉及到连接蛋白半通道的重新出现，可能是脊髓损伤后肌肉炎症和萎缩的基础，也可能是其他神经系统疾病的基础；这些半通道的抑制剂可能被证明是有效的治疗药物来减少制动后的肌肉萎缩。未来，创新的治疗方法将被纳入与内分泌代谢、呼吸、胃肠、自主神经和肌肉骨骼功能障碍相关的常规护理中，这是令人兴奋的前景。

 DESCRIPTION: Approximately 250,000 persons in the US have traumatic spinal cord injury (SCI), and at least another 400,000 individuals have spinal cord damage of non-traumatic etiologies. The longevity of those with SCI has increased over the decades because of effective treatments for urological and pulmonary complications. However, the SCI population is growing older and ever more costly to manage medically. Thus, it is increasingly imperative that we continue to understand the medical consequences of SCI and pursue safe and effective treatment options to minimize or prevent these adverse disorders. The mission of the CoE MCSCI is to improve quality of life and to increase longevity in individuals with SCI by identifying and intervening to reduce and/or prevent the secondary medical consequences of SCI, goals which are in the finest tradition of the VA's RR&D Service. The proposed Center of Excellence for the Medical Consequences of Spinal Cord Injury (CoE MCSCI) will continue to provide support for studies by investigators in several specialty areas of Medicine, Rehabilitation Medicine, Neurology, Neuropsychology, Epidemiology, Sleep Medicine, and Molecular Biology. The CoE physician/scientist-investigators will initiate interventional treatments for various medical complications, or strive o better characterize pathophysiological conditions. Therapeutic or investigational approaches that will be pursued include pharmacological and non-pharmacological interventions as follows: ibandronic acid to reduce bone loss in individuals with incomplete motor SCI who are ambulatory; a gut incretin [glucagon- like peptide (liraglutide)] to improve carbohydrate/lipid metabolism and soft tissue body composition; a novel adjunctive approach to improve routine bowel care by administering neostigmine and glycopyrrolate transdermally by iontophoresis; an oral vibrating capsule to improve bowel motility and evacuation; exoskeleton assisted walking (EAW) to improve colonic motility measured by SCI-QOL Bowel Management survey, radiopaque markers, and high resolution manometry; identification and classification of the degree of autonomic cardiovascular impairment; anti-hypotensive agents to raise blood pressure and prevent cognitive impairment [e.g., beta (3)-adrenoceptor agonist (mirabegron); an alpha agonist (midodrine), and a norepinephrine precursor (droxidopa)]; a novel meal with an enhanced ability for meal-induced thermogenesis to reduce risk of hypothermia upon cold exposure; paired central stimulation to strengthen existing neurological pathways to the hands; and home-based portable sleep monitoring compared to witnessed polysomnography for the identification of sleep disordered breathing. Compared to the general population, cardiovascular morbidity in persons with SCI occurs earlier in life and is more prevalent. Conventional risk factors for coronary artery disease may not accurately predict the presence of macrovascular disease. Thus, the measurement of emerging risk factors, as well as conventional risk factors, and the quantification of coronary artery calcium will continue to be studied in our CoE proposal to enable health professionals to better identify and treat persons with vascular disease. EAW in persons with SCI has proven to be a game-changing mechanical intervention for mobility and to improve several health- related conditions, including bowel dysfunction, which is proposed to be assessed in the CoE. A new molecular signaling pathway involving the de novo appearance of connexin hemichannels, may underlie muscle inflammation and atrophy after SCI and possibly other neurological disorders; inhibitors of these hemichannels may be proven to be potent therapeutic agents to reduce muscle atrophy after immobilization. The future holds exciting promise for innovative treatments to be incorporated into routine care associated with endocrine-metabolic, respiratory, gastrointestinal, autonomic, and musculoskeletal dysfunctions.