Khasnavis Siddharth, Belliveau Timothy, Arnsten Amy, Fesharaki-Zadeh Arman
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Neurotrauma Rep. 2024 Mar 13;5(1):226-231. doi: 10.1089/neur.2023.0124. eCollection 2024.
Traumatic Brain Injury (TBI) is a significant contributor to disability across the world. TBIs vary in severity, and most cases are designated mild TBI (mTBI), involving only brief loss of consciousness and no intracranial findings on imaging. Despite this categorization, many persons continue to report persistent cognitive changes in the months to years after injury, with particular impairment in the cognitive and executive functions of the pre-frontal cortex. For these persons, there are no currently approved medications, and treatment is limited to symptom management and cognitive or behavioral therapy. The current case studies explored the use of the alpha-2A adrenoreceptor agonist, guanfacine, combined with the antioxidant, -acetylcysteine (NAC), in the treatment of post-TBI cognitive symptoms, based on guanfacine's ability to strengthen pre-frontal cortical function, and the open-label use of NAC in treating TBI. Two persons from our TBI clinic were treated with this combined regimen, with neuropsychological testing performed pre- and post-treatment. Guanfacine + NAC improved attention, processing speed, memory, and executive functioning with minimal side effects in both persons. These results encourage future placebo-controlled trials to more firmly establish the efficacy of guanfacine and NAC for the treatment of cognitive deficits caused by TBI.
创伤性脑损伤(TBI)是全球致残的一个重要原因。TBI的严重程度各不相同,大多数病例被定为轻度TBI(mTBI),仅涉及短暂的意识丧失,影像学检查无颅内异常发现。尽管有这种分类,但许多人在受伤后的数月至数年仍报告持续存在认知变化,前额叶皮质的认知和执行功能尤其受损。对于这些人,目前没有获批的药物,治疗仅限于症状管理以及认知或行为疗法。基于胍法辛增强前额叶皮质功能的能力以及N-乙酰半胱氨酸(NAC)在治疗TBI方面的开放标签使用,当前的病例研究探讨了α-2A肾上腺素能受体激动剂胍法辛与抗氧化剂NAC联合用于治疗TBI后认知症状的情况。我们TBI诊所的两名患者接受了这种联合治疗方案,并在治疗前后进行了神经心理学测试。胍法辛+NAC在两名患者中均改善了注意力、处理速度、记忆力和执行功能,且副作用最小。这些结果促使未来开展安慰剂对照试验,以更确切地确定胍法辛和NAC治疗TBI所致认知缺陷的疗效。