卒中后疲劳相关危险因素的研究
Study on Risk Factors of Fatigue after Stroke
DOI: 10.12677/ACM.2022.125650, PDF, HTML, XML, 下载: 85  浏览: 109 
作者: 孟会娟:青海大学研究生院,青海 西宁;刘 冀:青海大学附属医院,青海 西宁
关键词: 脑卒中卒中后疲劳相关危险因素Stroke Post-Stroke Fatigue Related Risk Factors
摘要: 脑卒中(Stroke)是常见的心脑血管疾病,严重威胁着人类的健康。流行病学研究显示,脑卒中是我国居民首位致死、致残的疾病。脑卒中患者的临床并发症很多,其中卒中后疲劳是中风最常见且持久的后遗症,卒中后疲劳(fatigue after stroke, PSF)的病因尚不清楚,治疗也相对局限。本综述旨在研究卒中后疲劳的相关危险因素,为脑卒中患者的临床康复提供帮助。
Abstract: Stroke is a common cardiovascular and cerebrovascular disease that seriously threatens human health. Epidemiological studies have shown that stroke is the first fatal and disabling disease in Chinese residents. There are many clinical complications in stroke patients, of which post-stroke fa-tigue is the most common and long-lasting sequela of stroke, and the etiology of post-stroke fatigue (PSF) is still unclear and the treatment is relatively limited. The aim of this review was to determine the risk factors associated with studying post-stroke fatigue and provide help for the clinical reha-bilitation of stroke patients.
文章引用:孟会娟, 刘冀. 卒中后疲劳相关危险因素的研究[J]. 临床医学进展, 2022, 12(5): 4496-4502. https://doi.org/10.12677/ACM.2022.125650

1. 引言

卒中后疲劳是中风幸存者普遍经历的障碍 [1]。最近的一项荟萃分析包含50%的合并患病率估计值 [2]。疲劳可以被定义为一种主观上缺乏体力或脑力(或两者兼而有之),个人认为这会干扰正常或期望的活动。卒中后疲劳与较差的生活质量显著相关,即考虑了年龄、残疾和抑郁 [3],但这对患者也很重要,40%的患者表示疲劳是他们最严重的症状或最严重的症状之一 [4]。卒中后疲劳会降低功能独立性,限制社会参与,并与死亡率增加有关 [5] [6]。这会对患者的生活质量和日常生活活动产生负面影响 [7] [8],也会加重家庭成员和护理人员的负担,尽管研究人员试图解释PSF的机制 [9],但其病因仍不清楚。这在一定程度上是因为PSF [10] 有许多影响因素,因此,本研究针对卒中后躯体疲劳的流行病学、相关危险因素等方面展开综述,为脑卒中患者找到预防、治疗或管理PSF的途径。

2. 流行病学

疲劳是脑卒中常见且持续的后遗症 [11],占所有脑卒中 [12] 患者的39%至79%。大约40%的患者报告疲劳是中风最严重的后遗症之一 [13]。林晓琼等 [14] 调查发现,随着时间间隔的延长,疲劳得分呈现逐渐增高的趋势,在患病后1年疲劳得分达到了峰值。然而,王敏 [15] 研究发现患者发病后2周、1个月、3个月、6个月的疲劳得分随时间呈现出逐渐下降趋势。卒中后疲劳(fatigue after stroke, PSF)对老年卒中幸存者的短期功能结果有负面影响。在年轻中风患者中,这种影响可能更为深远,因为他们面临着来自工作和家庭的要求更高 [16]。然而,导致卒中后疲劳发病率差异性较大的原因可能与纳入人群、样本量和测量工具有关。研究者采用不同的疲劳量表可导致不同的疲劳患病率,其中最常用的疲劳评价量表有疲劳严重度量表、个人疲劳强度问卷和疲劳影响量表 [17]。

3. 影响因素

3.1. 一般因素

有研究考察了PSF的潜在决定因素(如种族差异) [18]。许多因素已被证明与PSF有关,包括年龄 [19]、性别 [20]、中风严重程度 [21]、抑郁 [21]、中风类型和病变部位 [19]。然而,这些风险因素在所有研究中并不一致 [18]。关于哪种预测因子可以准确预测卒中患者PSF风险增加,仍有许多不确定性,事实上,对于临床实践来说,识别那些PSF风险高的患者更为关键。促发风险因素,无论是可控制的还是不可控制的,都值得研究,以便更好地指导PSF的管理。近年来,随着对PSF的日益重视,来自不同地区的研究人员进行了一些临床研究,以确定PSF的预测因素,在按地区分层的亚组分析中,在欧洲和亚洲人群中,女性和抑郁症与PSF显著相关,研究中分别没有异质性和中高度异质性。

3.2. 脑卒中合并相关疾病的影响

研究表明,患有糖尿病和睡眠障碍的欧洲中风患者更易患PSF,各研究的异质性较低。白质疏松症也与PSF易感性增加有关,研究中没有异质性(I2 = 0%)。令人惊讶的是,在欧洲中风患者中,只有幕下位置和PSF之间的关系发生了显著变化(OR = 2.92, p < 0.01)。在中风后的前6个月,疲劳是一种相对常见的并发症,对各种功能结果有负面影响 [22] [23]。对中风后疲劳半年多的危险因素进行了亚组分析,发现丘脑、白质疏松症、焦虑症、糖尿病,在中风存活时间超过半年的患者中,糖尿病和睡眠障碍往往与疲劳有关。与中风后不到半年的病程相比,在中风存活半年以上的患者中,抑郁与对PSF的易感性增加显著相关,研究中存在中度异质性。据报道,大约10名中风幸存者中有6名在中风发作的第1个月内出现PSF,而在指数事件发生后的几个月内,大约4名中风幸存者中有1名出现PSF [24]。PSF与中风患者的较高死亡率相关 [25]。与PSF相关的因素包括神经缺陷、睡眠障碍、抑郁和中风部位 [26] [27]。

3.3. 脑卒中部位

研究显示,对于年龄等个人因素,人们发现了相互矛盾的证据 [28] [29]。一些研究认为,疲劳的患病率随着年龄的增长而增加,但我们的结果没有显示出PSF与年龄之间的明确趋势,这可能是由于我们对老年人的限制。根据相关研究结果,社会人口因素(如年龄和独居)、既往中风和物质相关行为(如吸烟)似乎与PSF没有显著相关性,但在亚组分析中考虑的另一个研究特定因素是地理区域。无论是在欧洲还是亚洲人群中,可发现女性和抑郁症都会显著增加对PSF的易感性。在某种程度上,世界不同地区的女性通常更抑郁,与中风无关,但这取决于她们的社会经济因素 [30] [31]。到目前为止,神经影像学特征对PSF的影响仍然存在争议。虽然有几项研究强调了中风部位在疲劳发作中的重要作用,但没有证据表明,诸如大脑皮层、皮质下白质、基底节、左侧中风、右侧中风和幕下位置等危险因素与PSF密切相关。然而,病变的存在可能非常重要,因为丘脑和白质疏松症被发现是PSF的危险因素。在区域和中风亚组分析中,这些因素导致PSF增加1.73至2.92倍。有研究发现PSF与白质疏松症和丘脑等因素之间存在独立关联 [32]。以前的研究也表明,即使血管再通成功,脑白质疏松症的严重程度与缺血性卒中后的不良临床结局也存在相关性。此外,有研究结果表明,抑郁症和睡眠障碍几乎是PSF发病率的两倍。疲劳是抑郁症的症状之一。因此,这两个实体具有很强的相关性。然而,目前尚不清楚PSF是否能在将来被纳入中风后抑郁症的范畴。之前的研究发现,即使在控制了抑郁之后,PSF仍然可能发生,这表明疲劳和抑郁是两个独立的实体,并支持这两种后遗症都应该作为中风恢复的一部分独立处理的观点 [33]。按随访时间分层的亚组分析结果表明,焦虑和抑郁可在卒中后半年内加速疲劳。事实上,这些发现与之前的研究和临床实践一致。早期PSF似乎主要归因于中风的严重程度 [23],而慢性疲劳则发生在复杂的医学共病环境中。很明显,中风后残疾患者可能患有慢性共病,不仅容易产生负面情绪,而且还会恶化康复。尽管目前的研究存在一些局限性,但迄今为止的文献数据表明,中风幸存者之间存在许多相关关系,包括抑郁、睡眠障碍、糖尿病和焦虑。研究结果表明,多种因素增加了中风患者的疲劳风险,PSF的多因素基础强调,对抑郁症和睡眠障碍的适当治疗可能会减轻PSF的负担,尤其是在慢性疲劳过程中 [34]。

另有研究发现,情绪健康(应对策略和控制点)、临床因素(睡眠、疼痛、中风特征、生物学和免疫学因素)、社会因素(社会支持、残疾和日常生活功能)和认知功能等均与PSF相关。在调查与PSF相关的个人特征(即年龄、性别、婚姻状况)和控制点,以及抑郁、中风特征、中风损伤和认知缺陷时,观察到年龄、性别、抑郁和控制点解释了20%的疲劳变异 [35]。社会支持在Michael等人 [36] 的一项研究中,与非疲劳个体相比,疲劳个体的社会支持显著减少。他们还发现疲劳的受试者在不摔倒的情况下进行日常生活活动的信心较低,事实上这是疲劳的最强预测因子。Wang等人 [37] 还调查了中国中风样本(N = 265)中疲劳与社会支持之间是否存在关联。在他们的研究中,对家庭功能的满意度与中风后急性期的PSF相关。他们进一步报告说,那些疲劳的人来自功能失调家庭的可能性是正常家庭的两倍多。同样,Wei等人 [38] 还发现,社会利用程度低是与PSF相关的风险因素。在卒中患者入院时和3个月随访时都发现了这种关联。在Wei等人 [38] 的一项研究中,脑卒中3个月后,基底节、放射冠或内囊与PSF独立相关。Mutai等人 [39] 发现,右侧病变、丘脑和脑干病变与急性卒中后期的PSF相关(在卒中后两周内进行的测量)。在另一项研究中,与基线检查时(中风后6至8周)的所有其他梗死区域相比,幕下梗死与PSF风险增加显著相关 [40]。此外,当Naess等人 [41] 在分析中排除抑郁症患者时,观察到中风部位与疲劳之间存在关联 [42]。Tang及其同事 [43] 的几项研究结果强调了疲劳与中风特征之间的关系,他们的研究中,发现急性尾状核梗死独立预测中风后3个月的疲劳,而壳核或苍白球梗死则没有。此外,一些研究观察到,在长期随访测量中,白质高信号(WMH)与PSF独立相关 [41]。

3.4. 免疫炎症

Ormstad等人 [44] 从中风患者中采集血液样本,以确定犬尿氨酸途径是否可以预测随后的疲劳和抑郁,此外还测量了急性血清色氨酸分解代谢产物和竞争性氨基酸水平,然而没有观察到抑郁症的预测因子,研究结果还表明,中风后12个月FSS评分升高的患者急性色氨酸指数显著降低,血清犬尿氨酸水平较高。因此,急性细胞因子水平与疲劳评分之间的显著关系在卒中后18个月不再存在。此外,最近的一项研究表明,PSF与全身炎症有关,而全身炎症又与影响免疫反应的两个基因有关。研究发现IL1RN (白细胞介素-1受体激动剂) C等位基因携带者更容易发生PSF,而TLR4 (toll样受体4基因)携带者似乎对PSF有保护作用。IL1RN的C等位基因与更高的促炎细胞因子循环浓度有关 [45]。Choi Kwon等人 [46] 最近的一项研究也表明,血清素合成相关的基因多态性与PSF相关。另外,一些观察性研究表明,PSF的发生涉及心理、生物、行为和环境因素的相互作用 [47],更全面地了解PSF的机制可能有助于早期发现和开发有效的治疗方法策略。PSF的发展通常与全身炎症和免疫反应紊乱有关 [48],随着对大量炎症生物标志物的研究,hs-CRP因其在动脉粥样硬化和脑血管疾病中的应用而受到广泛关注。一项荟萃分析发现,hs-CRP水平升高与缺血性中风风险独立相关 [49],最近的研究表明,hs-CRP的升高可以预测中风患者的临床结果、死亡率和复发事件 [50] [51] [52],同时,尼娜·格罗文报道,与健康对照组相比,慢性疲劳综合征与hs-CRP水平升高密切相关。综合以上多项研究结果,hs-CRP作为急性期反应物和非特异性炎症指标,参与调节中风和疲劳的病理生理学,hs-CRP是一种敏感的炎症标志物。因此,它被认为是一种敏感和可靠的指标,反映潜在的炎症活动。一些学者报道,与健康对照组相比,慢性疲劳综合征患者的hs-CRP升高 [53]。此外,一系列研究也已经证实了hs-CRP与冠心病 [54]、高血压 [55]、中风等疾病之间的关系。这些发现表明,免疫炎症改变可能是PSF发病机制发展的原因 [56]。

4. 小结与展望

随着PSF的发病率逐年增加,我们对卒中后疲劳的危害越发重视,它不仅影响患者的康复进程,还会增加脑卒中患者死亡的风险以及再次入院的可能。但PSF发病机制极其复杂并且涉及多个学科领域,对其病因学的分析仍需大量研究,而对于影响因素而言,虽然本综述中很多研究结果表明年龄、性别、疼痛、睡眠障碍与卒中后疲劳有关,但有些机制尚不完全清楚。目前关于卒中后疲劳发病机制、影响因素的相关研究仍有限,因此,还需进一步探索。

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