Kuroda Hiroshi, Fujihara Kazuo, Kushimoto Shigeki, Aoki Masashi
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Japan.
Neurotoxicology. 2015 May;48:35-43. doi: 10.1016/j.neuro.2015.03.002. Epub 2015 Mar 7.
Delayed neurologic sequelae (DNS) after carbon monoxide (CO) poisoning manifest as a relapse of neurologic deficits. However, the long-term outcome of DNS has not been fully clarified. Myelin basic protein (MBP) levels in the cerebrospinal fluid (CSF) have been reported to be elevated in DNS. However, the precise timing and clinical value of the CSF examination have not been fully evaluated. We aimed to clarify the long-term outcome and the factors predicting the outcome of DNS and to evaluate the utility of CSF-MBP for predicting the development and severity of DNS.
This work was designed as a single-center, prospective, observational study. We graded DNS severity as Grade 1 (consistent independence), Grade 2 (temporary dependence), or Grade 3 (persistent dependence). We analyzed the percentage categorized in each grade and the parameters associated with outcome.
Of 100 patients experiencing acute CO poisoning (median age: 46 years; 69% male), 20 (20%) developed DNS, including six Grade 1 (30%), ten Grade 2 (50%), and four Grade 3 (20%) cases. The Grade 3 patients [median: 77 years; interquartile range (IQR): 76-82] were older than the Grade 1 patients [42; 30-46] (P<0.01); the DNS onset of the Grade 1 patients [median interval after poisoning: 35 days; IQR: 32-56] occurred later than that of the Grade 3 patients [10; 9-13] P<0.001) and the Grade 2 patients [25; 23-27] (P<0.05). The CSF-MBP levels of the DNS patients were higher than those of the non-DNS patients (P<0.0001). The 1-month CSF-MBP levels of the Grade 3 patients were higher than those of the Grade 1 patients (P<0.05); the MBP index, defined as [(Age)×(1-month CSF-MBP)], was higher in the Grade 3 patients than in the Grade 1 patients (P<0.01). Severe DNS were associated with advanced age (>72.5 years), earlier onset (<18 days), higher 1-month CSF-MBP (>252 pg/ml), and higher MBP index (>20.9 year × ng/ml).
Poor DNS outcomes were associated with advanced age and earlier onset. CSF-MBP can serve as a sensitive predictor of both the development and outcomes of DNS.
一氧化碳（CO）中毒后的迟发性神经后遗症（DNS）表现为神经功能缺损的复发。然而，DNS的长期预后尚未完全明确。据报道，DNS患者脑脊液（CSF）中的髓鞘碱性蛋白（MBP）水平升高。然而，CSF检查的确切时机和临床价值尚未得到充分评估。我们旨在阐明DNS的长期预后以及预测其预后的因素，并评估CSF-MBP对预测DNS发生和严重程度的效用。
本研究设计为单中心、前瞻性观察性研究。我们将DNS严重程度分为1级（持续独立）、2级（暂时依赖）或3级（持续依赖）。我们分析了各等级的占比以及与预后相关的参数。
100例急性CO中毒患者（中位年龄：46岁；69%为男性）中，20例（20%）发生DNS，包括6例1级（30%）、10例2级（50%）和4例3级（20%）病例。3级患者[中位年龄：77岁；四分位间距（IQR）：76 - 82]比1级患者[42岁；30 - 46]年龄更大（P<0.01）；1级患者DNS发病时间[中毒后中位间隔时间：35天；IQR：32 - 56]比3级患者[10天；9 - 13]更晚（P<0.001），也比2级患者[25天；23 - 27]更晚（P<0.05）。DNS患者的CSF-MBP水平高于非DNS患者（P<0.0001）。3级患者1个月时的CSF-MBP水平高于1级患者（P<0.05）；MBP指数定义为[(年龄)×(1个月时的CSF-MBP)]，3级患者的MBP指数高于1级患者（P<0.01）。严重DNS与高龄（>72.5岁）、发病早（<18天）、1个月时CSF-MBP水平高（>252 pg/ml）以及MBP指数高（>20.9岁×ng/ml）相关。
DNS预后不良与高龄和发病早有关。CSF-MBP可作为DNS发生和预后的敏感预测指标。
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