Blum Corinna, Single Constanze, Laichinger Kornelia, Hofmann Anna, Rattay Tim W, Adeyemi Kamaldeen, Riessen Reimer, Haap Michael, Häberle Helene, Ziemann Ulf, Mengel Annerose, Feil Katharina
Department of Neurology & Stroke, University Hospital Tübingen, Tübingen, Germany.
Department of Neurology/Neurodegenerative Diseases, University Hospital Tübingen, Tübingen, Germany.
Front Neurol. 2025 Jan 6;15:1512227. doi: 10.3389/fneur.2024.1512227. eCollection 2024.
Disorders of consciousness (DoC) in non-traumatic ICU-patients are often treated with amantadine, although evidence supporting its efficacy is limited.
This retrospective study analyzed non-traumatic DoC-patients treated with amantadine between January 2016 and June 2021. Data on patient demographics, clinical characteristics, treatment specifications, and outcomes were extracted from electronic medical records. Patients were classified as responders if their Glasgow Coma Scale (GCS) improved by ≥3 points within 5 days. Good outcome was defined as a modified Rankin Scale (mRS) of 0-2. Machine learning techniques were used to predict response to treatment.
Of 442 patients (mean age 73.2 ± 10.7 years, 41.0% female), 267 (60.4%) were responders. Baseline characteristics were similar between groups, except that responders had lower baseline GCS (7 [IQR 5-9] vs. 8 [IQR 5-10], = 0.030), better premorbid mRS (2 [IQR 1-2] vs. 2 [IQR 1-3], < 0.001) and fewer pathological cerebral imaging findings (45.7% vs. 61.1%, OR 0.56, 95% CI: 0.36-0.86, = 0.008). Responders exhibited significantly lower mortality at discharge (13.5% vs. 27.4%, OR 0.41, 95% CI: 0.25-0.67, < 0.001) and follow-up (16.9% vs. 32.0%, OR 0.43, 95% CI: 0.24-0.77, = 0.002). Good outcomes were more frequent in responders at follow-up (4.9% vs. 1.1%, OR 6.14, 95% CI: 1.35-28.01, = 0.004). In multivariate analysis higher premorbid mRS (OR 0.719, 95% CI 0.590-0.875, < 0.001), pathological imaging results (OR 0.546, 95% CI 0.342-0.871, = 0.011), and experiencing cardiac arrest (OR 0.542, 95% CI 0.307-0.954, = 0.034) were associated with lower odds of response. Machine learning identified key predictors of response, with the Stacking Classifier achieving the highest performance (accuracy 64.5%, precision 66.6%, recall 64.5%, F1 score 61.3%).
This study supports the potential benefits of intravenous amantadine in non-traumatic DOC-patients. Higher premorbid mRS, and pathological cerebral imaging were key predictors of non-response, offering potential avenues for patient selection and treatment customization. Findings from this study informed the design of our ongoing prospective study, which aims to further evaluate the long-term efficacy of amantadine.
非创伤性重症监护病房（ICU）患者的意识障碍（DoC）常使用金刚烷胺治疗，但其疗效的证据有限。
这项回顾性研究分析了2016年1月至2021年6月间接受金刚烷胺治疗的非创伤性DoC患者。从电子病历中提取患者人口统计学、临床特征、治疗规范及预后的数据。若患者格拉斯哥昏迷量表（GCS）在5天内改善≥3分，则分类为有反应者。良好预后定义为改良Rankin量表（mRS）评分为0 - 2分。采用机器学习技术预测治疗反应。
442例患者（平均年龄73.2±10.7岁，41.0%为女性）中，267例（60.4%）有反应。两组间基线特征相似，但有反应者基线GCS较低（7[四分位间距5 - 9]对8[四分位间距5 - 10]，P = 0.030），病前mRS较好（2[四分位间距1 - 2]对2[四分位间距1 - 3]，P < 0.001），脑部病理影像学表现较少（45.7%对61.1%，比值比0.56，95%置信区间：0.36 - 0.86，P = 0.008）。有反应者出院时死亡率显著较低（13.5%对27.4%，比值比0.41，95%置信区间：0.25 - 0.67，P < 0.001），随访时死亡率也较低（16.9%对32.0%，比值比0.43，95%置信区间：0.24 - 0.77，P = 0.002）。随访时有反应者良好预后更常见（4.9%对1.1%，比值比6.14，95%置信区间：1.35 - 28.01，P = 0.004）。多因素分析显示，较高的病前mRS（比值比0.719，95%置信区间0.590 - 0.875，P < 0.001）、病理影像学结果（比值比0.546，95%置信区间0.342 - 0.871，P = 0.011）以及发生心脏骤停（比值比0.542，95%置信区间0.307 - 0.954，P = 0.034）与反应几率较低相关。机器学习确定了反应的关键预测因素，堆叠分类器表现最佳（准确率64.5%，精确率66.6%，召回率64.5%，F1分数61.3%）。
本研究支持静脉注射金刚烷胺对非创伤性DoC患者的潜在益处。较高的病前mRS和脑部病理影像学表现是无反应的关键预测因素，为患者选择和治疗定制提供了潜在途径。本研究结果为我们正在进行的前瞻性研究设计提供了依据，该前瞻性研究旨在进一步评估金刚烷胺的长期疗效。
