Wernicke-Korsakoff综合征(WKS)的主要原因是硫胺素缺乏,超过90%的病例是在酒精依赖患者中报告的。虽然观察性研究显示肠胃外硫胺素的给药可显著降低WKS相关死亡率,从未进行过相关治疗试验来确定最佳硫胺素剂量.
两个双盲,平行组,进行了随机对照试验(RCT),以确定(1)预防韦尼克脑病(WE)所需的最佳硫胺素剂量,WKS的急性期,在无症状但“有风险”的酒精滥用患者中(研究1)和(2)在有症状的酒精滥用患者中使用WE治疗(研究2)。每个研究具有包括以1:1:1的比例分配的三个肠胃外硫胺素剂量的剂量方案。研究1:无症状的高危患者(N=393)每天服用100毫克,每天100毫克三次,或每天300毫克三次,3天。研究2:有症状的患者(N=127)每天接受100毫克,300毫克,每天三次,或500毫克每天三次,5天。认知功能是主要结果,使用罗兰通用痴呆症评估量表进行评估,两个Cogstate子测试,和改编的故事记忆回忆测试。次要分析检查了神经功能的差异(共济失调,动眼异常,和混乱)在后续行动中。
在认知或神经功能方面的研究1或研究2的任何剂量条件之间没有观察到显著差异。这项现实世界的研究发现,具有高合并症和多种表现的临床不适目标人群,再加上跨文化评估方面的挑战,可能会使RCT结果复杂化.
这项研究的结果表明,高剂量硫胺素对中等或较低剂量硫胺素没有明显的益处,在检查的时间间隔内,用于治疗和预防与WKS相关的认知和神经系统异常。几个研究的局限性削弱了对这些发现的解释。然而,缺乏高剂量硫胺素优势的确凿证据支持对患者特异性治疗的建议,同时确保其他生化因素的潜在影响(例如,镁和其他B族维生素缺乏症)被考虑并在必要时予以纠正。
The primary cause of Wernicke-Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose.
Two double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke\'s encephalopathy (WE), the acute phase of WKS, in asymptomatic but \"at-risk\" alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (
Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1.
Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days.
Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up.
No significant differences were observed between any of the dosage conditions for either Study 1 or
Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings.
The results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several
study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.