Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features
Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features
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DOI：
10.1002/ana.25588
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发表时间：
2019-09-11
影响因子：
11.2
通讯作者：
Nath, Avindra
中科院分区：
文献类型：
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作者：
Johnson, Tory P.;Larman, H. Benjamin;Nath, Avindra
目的探讨美国国立卫生研究院未确诊疾病项目中1例伴有锥体外系症状和慢性炎症的进行性痴呆患者的病因。方法广泛的调查包括代谢谱，自身抗体面板，感染病因学，遗传筛查，全外显子测序和噬菌体展示试验，VirScan，用于病毒免疫应答。病因诊断是在死后确定的。结果与血清相比，脑脊液中登革病毒抗体明显富集。在血清或脑脊液中未检测到病毒，但尸检分析证实了登革病毒在大脑中的免疫组织化学，原位杂交，定量聚合酶链反应和测序。登革热病毒也可通过聚合酶链反应和测序从死前33个月收集的脑活检组织中检测到，证实了慢性感染，尽管针对该病毒的免疫反应很强。患者的免疫分析和全外显子组测序未显示任何免疫缺陷，病毒测序表明中枢神经系统中存在野生型登革病毒。登革热病毒是世界上最常见的虫媒病毒，是一个重大的公共卫生问题。登革热病毒感染通常是自限性的，慢性登革热感染以前没有报道。我们的研究结果表明，登革热病毒感染可能会持续在中枢神经系统引起全脑炎，并应考虑在进行性痴呆与锥体外系功能的流行地区或相关的旅行史的患者。此外，这项工作突出了全面的抗体分析测定，以帮助诊断不明病因的脑炎的效用。2019年安神经
Objective To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed Diseases Program. Methods Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing, and the phage-display assay, VirScan, for viral immune responses. An etiological diagnosis was established postmortem. Results Using VirScan, enrichment of dengue viral antibodies was detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months antemortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency, and sequencing of the virus demonstrated wild-type dengue virus in the central nervous system. Interpretation Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self-limiting, and chronic dengue infections have not been previously reported. Our findings suggest that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019