Neurointensive Care Unit, University Hospital Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neurocrit Care. 2017 Dec;27(3):447-457. doi: 10.1007/s12028-017-0413-8.
Chikungunya fever is a globally spreading mosquito-borne disease that shows an unexpected neurovirulence. Even though the neurological complications have been a major cause of intensive care unit admission and death, to date, there is no systematic analysis of their spectrum available.
To review evidence of neurological manifestations in Chikungunya fever and map their epidemiology, clinical spectrum, pathomechanisms, diagnostics, therapies and outcomes.
Case report and systematic review of the literature followed established guidelines. All cases found were assessed using a 5-step clinical diagnostic algorithm assigning categories A-C, category A representing the highest level of quality. Only A and B cases were considered for further analysis. After general analysis, cases were clustered according to geospatial criteria for subgroup analysis.
Thirty-six of 1196 studies were included, yielding 130 cases. Nine were ranked as category A (diagnosis of Neuro-Chikungunya probable), 55 as B (plausible), and 51 as C (disputable). In 15 cases, alternative diagnoses were more likely. Patient age distribution was bimodal with a mean of 49 years and a second peak in infants. Fifty percent of the cases occurred in patients <45 years with no reported comorbidity. Frequent diagnoses were encephalitis, optic neuropathy, neuroretinitis, and Guillain-Barré syndrome. Neurologic conditions showing characteristics of a direct viral pathomechanism showed a peak in infants and a second one in elder patients, and complications and neurologic sequelae were more frequent in these groups. Autoimmune-mediated conditions appeared mainly in patients over 20 years and tended to show longer latencies and better outcomes. Geospatial subgrouping of case reports from either India or Réunion revealed diverging phenotypic trends (Réunion: 88% direct viral vs. India: 81% autoimmune).
Direct viral forms of Neuro-Chikungunya seem to occur particularly in infants and elderly patients, while autoimmune forms have to be also considered in middle-aged, previously healthy patients, especially after an asymptomatic interval. This knowledge will help to identify future Neuro-Chikungunya cases and to improve outcome especially in autoimmune-mediated conditions. The genetics of Chikungunya virus might play a key role in determining the course of neuropathogenesis. With further research, this could prove diagnostically significant.
基孔肯雅热是一种在全球范围内传播的蚊媒疾病，具有出乎意料的神经毒力。尽管神经系统并发症一直是重症监护病房入院和死亡的主要原因，但迄今为止，尚无针对其谱的系统分析。
综述基孔肯雅热的神经表现证据，并绘制其流行病学、临床谱、发病机制、诊断、治疗和结局图谱。
遵循既定指南，采用病例报告和文献系统评价。使用 5 步临床诊断算法对所有发现的病例进行评估，将病例分为 A-C 类，A 类代表最高质量级别。只有 A 和 B 类病例才被考虑进一步分析。在进行一般分析后，根据地理空间标准对病例进行聚类，进行亚组分析。
从 1196 项研究中筛选出 36 项研究，共纳入 130 例病例。其中 9 例被评为 A 级（神经基孔肯雅病可能诊断），55 例为 B 级（合理），51 例为 C 级（可疑）。在 15 例病例中，更可能存在其他替代诊断。患者年龄分布呈双峰模式，平均年龄为 49 岁，婴儿期出现第二个高峰。50%的病例发生在<45 岁的患者中，且无报告合并症。常见的诊断为脑炎、视神经病变、神经视网膜炎和格林-巴利综合征。表现出直接病毒发病机制特征的神经系统疾病在婴儿和老年患者中发病率较高，且并发症和神经系统后遗症在这些患者中更为常见。自身免疫介导的疾病主要发生在>20 岁的患者中，潜伏期较长，结局较好。来自印度或留尼汪岛的病例报告地理空间亚组分析显示出不同的表型趋势（留尼汪岛：88%为直接病毒型，印度：81%为自身免疫型）。
神经基孔肯雅病的直接病毒形式似乎特别发生在婴儿和老年患者中，而自身免疫形式也应考虑在中年、既往健康的患者中，尤其是在无症状间隔期后。这一知识将有助于识别未来的神经基孔肯雅病病例，并改善结局，尤其是在自身免疫介导的疾病中。基孔肯雅病毒的遗传学可能在决定神经发病机制的过程中发挥关键作用。随着进一步的研究，这可能具有诊断意义。
