文献精读|慢性酒精相关性脑损害的中国诊疗指南(2024)

文摘   健康   2024-12-16 13:40   湖北  

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引用本文:国家重点研发计划《酒精、吗啡依赖关键诊疗技术的推广应用研究》项目专家组, 中国医师协会神经内科分会. 慢性酒精相关性脑损害的中国诊疗指南(2024 [J] . 中华医学杂志, 2024, 104(19) : 1663-1679. DOI: 10.3760/cma.j.cn112137-20230923-00534.
通信作者:彭英,中山大学孙逸仙纪念医院神经科
观点提炼:

1.慢性酒精相关性脑损害(ARBD)患者几乎都存在慢性酒精依赖综合征发病机制。

2. 适当而有效的神经保护治疗有助于改善慢性ARBD的各种症状。

3. 鼠神经生长因子的神经营养治疗可减少慢性ARBD患者的酒精渴求、抑郁情绪和睡眠障碍。

4. 旨在帮助医师选择合适的诊疗方法提高ARBD患者临床预后。

慢性ARBD概述

慢性酒精相关性脑损害(alcohol‑related brain damage, ARBD),是一组由长期酒精摄入导致人大脑慢性损害的重要疾病谱。由于长期饮酒造成酒精作用于脑组织产生的慢性、容易复发的脑部疾病,是长期过量饮酒导致的中枢神经系统中毒,而且几乎所有患者都存在慢性酒精依赖综合征发病机制。《慢性酒精相关性脑损害的中国诊疗指南(2024)》共形成了28条推荐意见,为提高慢性ARBD的临床疗效提供参考和指导。

结合病理表现与临床表现,慢性ARBD的临床分类主要分为以下10种综合征[1‑3,18‑19]:酒精相关性认知障碍(alcohol-related cognitive impairment,ARCI)、酒精相关性痴呆(alcohol-related dementia,ARD)、韦尼克脑病(Wernicke′s encephalopathy,WE)、柯萨可夫综合征(Korsakoff syndrome,KS)、酒精性小脑变性(alcoholic cerebellar degeneration,ACD)、Marchiafava-Bignami病(MBD)、脑桥中央髓鞘溶解(central pontine myelinolysis,CPM)、酒精性癫痫、酒精性震颤-谵妄(delirium tremens,DT)和酒精性精神行为障碍等。

慢性ARBD的病理和影像学表现


各型综合征可能存在不同程度的病理表现。最常见出现的病理改变为白质脱髓鞘和灰质萎缩。白质脱髓鞘的易感部位包括前额叶皮质下、胼胝体、脑桥等,严重的脱髓鞘病变后可继发轴索损伤;而灰质萎缩主要由于神经元丢失所致,最常发生于额叶上部皮质、小脑和下丘脑,颞叶海马也可受累,引起皮质、小脑萎缩[45‑47]


推荐意见1:MRI可检测到慢性ARBD特定临床综合征的特征性影像学改变,并一定程度反映了的病理变化特征和严重程度,可辅助诊断慢性ARBD和鉴别其他脑疾病。(1B)


推荐意见 2:fMRI或 PET‑CT 检查可一定程度反映慢性ARBD的病理生理变化特征,可辅助分析慢性ARBD的功能改变和严重程度。(1C)

慢性ARBD的筛查、评估和临床诊断


推荐意见 3AUDIT量表用于评估慢性 ARBD患者的酒精使用障碍及其严重程度具有良好的信度和效度。(1B


推荐意见4OCDS用于评估慢性ARBD患者酒精渴求的程度,可用于临床评估和临床研究的随访,具有良好的信度和效度。(1B


推荐意见 5MoCA 用于评估慢性 ARBD 患者的认知功能和不同认知域的改变,并可较好地检测视空间和执行能力水平,未矫正的MoCA<26分作为酒精使用障碍合并认知障碍的分界值,具有良好的信度和效度。(1B) 

慢性ARBD的治疗


(一)戒酒

慢性ARBD的首要治疗方法就是戒酒。治疗一般分为2个阶段:一是戒酒阶段,也称作解毒阶段;另一阶段是康复治疗阶段。戒酒阶段可使用的方法包括:药物治疗和非药物治疗。

1.药物治疗:积极的药物治疗能够帮助患者戒断对酒精的依赖,防止疾病复发。

推荐意见6:可选择纳曲酮作为戒酒治疗的一线治疗药物,但纳曲酮在我国病例人群中的有效性和安全性仍需进一步明确。(2A)


推荐意见7:可选择纳美芬作为戒酒治疗的一线治疗药物,但纳美芬在我国病例人群中的有效性和安全性仍需进一步明确。(1B)


推荐意见 8:戒酒治疗药物双硫仑、阿坎酸虽然有戒酒疗效,但由于药物的可及性、安全性问题,我国病例人群临床应用少。(2A)


推荐意见9:可选择苯二氮䓬类药物作为戒酒治疗的二线治疗药物,尽可能短期使用以减少出现药物成瘾和依赖。(2A)


推荐意见10:巴氯芬、托吡酯和三环类抗抑郁药作为戒酒治疗的二线治疗药物,需充分评估患者获益‑风险比并严密随访用药安全性的情况下慎重选择使用。(2B)

2. 非药物治疗:


推荐意见 11:对左侧 DLPFC的高频重复经颅磁刺激治疗可有效改善临床预后,减少酒精渴求和复饮,以下参数具有良好的有效性和安全性[刺激部位:左侧 DLPFC 区;刺激强度:110% 运动阈值(MT);刺激频率10 Hz;刺激时间:5 s/次(循环);间歇时间:间隔20 s/次(循环);每疗程刺激次数:每天30次(循环),共10 d]。(1A)


推荐意见 12:其他脑区的重复经颅磁刺激治疗也能减少酒精渴求和复饮,但其疗效是否优于对左侧DLPFC 的高频重复经颅磁刺激治疗仍不明确。(2B)


推荐意见 13:经颅直流电刺激治疗的疗效和安全性仍需要进一步明确。(2B)


推荐意见 14:根据患者病情采取个体化的行为、心理治疗和康复治疗可提高患者临床预后,减少酒精依赖的严重程度和复饮。(2B)

(二)病因治疗


推荐意见15:纠正硫胺素(维生素B1)缺乏可改善慢性ARBD的临床预后,防止ARBD进展和加重,优先选择非肠道补充高剂量维生素B1。(1A)


推荐意见16:维生素C、维生素E对ARBD有一定的保护作用。(1C)


推荐意见 17:其他抗氧化剂的有效性和安全性仍需要进一步验证。(2D)

(三)纠正营养失调


推荐意见 18:纠正ARBD的营养失调是缓解病情、早日恢复的基础,包括给予多种维生素、必要脂肪酸、植物蛋白和植物多糖等。(1D

(四)脑保护治疗


长期酗酒的患者脑内存在过氧化物和自由基损伤及明显的神经营养因子水平低下[109‑110, 112] ,因此,适当而有效的神经保护治疗有助于改善慢性ARBD的各种症状。除使用维生素C和补充B族维生素如甲钴胺外,还可给予自由基清除剂如依达拉奉,线粒体保护剂如艾地苯醌、辅酶Q10等,以神经营养药物如鼠神经生长因子、奥拉西坦等。
本指南团队组织国内多中心临床研究的结果发现,使用依达拉奉抗氧化治疗、鼠神经生长因子的营养神经治疗可以减少慢性ARBD患者对酒精的渴求,改善抑郁情绪和睡眠障碍;

推荐意见 19:依达拉奉的抗氧化治疗可减少慢性 ARBD 患者的酒精渴求,并改善认知执行功能、抑郁情绪和睡眠障碍;鼠神经生长因子的神经营养治疗可减少慢性ARBD患者的酒精渴求、抑郁情绪和睡眠障碍。(1A)


推荐意见20:其他抗氧化、神经营养治疗慢性ARBD 的 有 效 性 和 安 全 性 仍 需 要 进 一 步 验证。(2D)

(五)各型综合征的治疗

他汀类降脂药物阿托伐他汀或瑞舒伐他汀,对酒精性脑白质脱髓鞘和酒精性认知功能障碍也可能具有一定的治疗作用[124] ,但在用药过程中应更加注意监测肝功能和肌酶。同时,可给予神经营养保护药物如鼠神经生长因子及艾地苯醌、甲钴胺等 B 族维生素以及依达拉奉等治疗。

推荐意见 21:积极非肠道补充高剂量维生素B1是KS、WE的关键病因治疗(1B)。注射甲钴胺治疗有助于提高临床预后(1D)。


推荐意见 22:胆碱酯酶抑制剂多奈哌齐可用于临床治疗 ARD的认知功能下降(1C);NMDA受体非竞争性拮抗剂美金刚可用于临床治疗ARD的认知功能下降(1D)。


推荐意见 23:短期使用苯二氮䓬类药物可稳定DT的症状(2A)。


推荐意见 24:首选苯二氮䓬类药物治疗戒断期或恢复期出现的酒精性癫痫(1C)。必要时联合丙戊酸或左乙拉西坦控制酒精性癫痫发作(2C)。


推荐意见25:可使用SSRI、SNRI或米氮平等药物减少酒精性精神和行为障碍(1B)。对于轻度焦虑、抑郁障碍,也可以联合使用中成药如舒肝解郁胶囊、乌灵胶囊等(2D)。

(六)康复治疗及其他治疗


推荐意见 26:积极的康复治疗可改善小脑性共济失调的临床症状,减少继发性运动障碍的发生和进展(1C)。


推荐意见27:针灸治疗能减轻戒断症状,有助于癫痫发作和复饮的预防(2C)。


推荐意见28:高压氧治疗能增加慢性ARBD患者脑组织的有氧代谢(2D)。

目前可证实鼠神经生长因子的营养神经治疗可以减少慢性ARBD患者对酒精的渴求,改善抑郁情绪和睡眠障碍,适当而有效的神经保护治疗有助于改善慢性ARBD的各种症状。慢性ARBD作为一组由长期酒精摄入导致人大脑慢性损害的重要疾病谱,不仅影响患者的认知、精神和行为,也对社会产生严重的疾病负担。本指南对有较多循证证据的诊断、治疗方法给予分级推荐,希望帮助广大临床医师选择合适的诊疗方法提高ARBD患者临床预后。




引用




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