Abstract：
OBJECTIVE: The emerging zoonotic Borna disease virus 1 (BoDV-1) and the variegated squirrel bornavirus 1 (VSBV-1) cause severe and fatal human encephalitis in Germany. We conducted the first systematic clinical analysis of acute, molecularly confirmed fatal bornavirus encephalitis cases comprising 21 BoDV-1 and four VSBV-1 patients to identify options for better diagnosis and timely treatment.
METHODS: Analyses were based on medical records and, for BoDV-1, on additional medical interviews with patients\' relatives.
RESULTS: Disease onset was unspecific, often with fever and headache, inconsistently mixed with early fluctuating neurological symptoms, all rapidly leading to severe encephalopathy and progressive vigilance decline. Very shortly after seeking the first medical advice (median time interval 2 and 0 days for BoDV-1 and VSBV-1, respectively), all except one patient were hospitalised upon manifest neurological symptoms (median 10 and 16 days respectively after general symptom onset). Neurological symptoms varied, always progressing to coma and death. BoDV-1 and VSBV-1 patients required ventilation a median of three and five days, and died a median of 32 and 72 days, after hospitalisation. Death occurred mostly after supportive treatment cessation at different points in time based on poor prognosis. Disease duration therefore showed a wide, incomparable range.
CONCLUSIONS: The extremely rapid progression is the most obvious clinical characteristic of bornavirus encephalitis and the timeframe for diagnosis and targeted therapy is very short. Therefore, our results demand an early clinical suspicion based on symptomatology, epidemiology, imaging, and laboratory findings, followed by prompt virological testing as a prerequisite for any potentially effective treatment.
METHODS: Analyses were based on medical records and, for BoDV-1, on additional medical interviews with patients\' relatives.
RESULTS: Disease onset was unspecific, often with fever and headache, inconsistently mixed with early fluctuating neurological symptoms, all rapidly leading to severe encephalopathy and progressive vigilance decline. Very shortly after seeking the first medical advice (median time interval 2 and 0 days for BoDV-1 and VSBV-1, respectively), all except one patient were hospitalised upon manifest neurological symptoms (median 10 and 16 days respectively after general symptom onset). Neurological symptoms varied, always progressing to coma and death. BoDV-1 and VSBV-1 patients required ventilation a median of three and five days, and died a median of 32 and 72 days, after hospitalisation. Death occurred mostly after supportive treatment cessation at different points in time based on poor prognosis. Disease duration therefore showed a wide, incomparable range.
CONCLUSIONS: The extremely rapid progression is the most obvious clinical characteristic of bornavirus encephalitis and the timeframe for diagnosis and targeted therapy is very short. Therefore, our results demand an early clinical suspicion based on symptomatology, epidemiology, imaging, and laboratory findings, followed by prompt virological testing as a prerequisite for any potentially effective treatment.
摘要：
目的：新兴的人畜共患博尔纳病病毒1（BoDV-1）和杂色松鼠博尔纳病病毒1（VSBV-1）在德国引起严重和致命的人类脑炎。我们进行了第一次系统的临床分析急性，分子确认的致命博尔纳病毒脑炎病例包括21例BoDV-1和4例VSBV-1患者，以确定更好的诊断和及时治疗的选择。
方法：分析基于医疗记录，对于BoDV-1，在与患者亲属的额外医疗访谈中。
结果：疾病发作无特异性，经常发烧和头痛，不一致地混合了早期波动的神经症状，所有这些都迅速导致严重的脑病和逐渐的警惕性下降。在寻求第一次医疗建议后不久（BoDV-1和VSBV-1的中位时间间隔分别为2天和0天），除1例患者外,所有患者均因出现明显的神经系统症状(一般症状发作后分别为中位10日和16日)而住院治疗.神经系统症状各不相同，总是进展到昏迷和死亡。BoDV-1和VSBV-1患者需要通气的中位数为3天和5天，平均死了32天和72天,住院后。基于不良预后，死亡大多发生在不同时间点停止支持治疗后。因此，疾病持续时间显示出广泛的，无与伦比的范围。
结论：进展极快是博纳病毒性脑炎最明显的临床特征，诊断和靶向治疗的时间很短。因此,我们的结果需要基于症状学的早期临床怀疑，流行病学,成像,和实验室发现，随后进行迅速的病毒学测试，作为任何潜在有效治疗的先决条件。
方法：分析基于医疗记录，对于BoDV-1，在与患者亲属的额外医疗访谈中。
结果：疾病发作无特异性，经常发烧和头痛，不一致地混合了早期波动的神经症状，所有这些都迅速导致严重的脑病和逐渐的警惕性下降。在寻求第一次医疗建议后不久（BoDV-1和VSBV-1的中位时间间隔分别为2天和0天），除1例患者外,所有患者均因出现明显的神经系统症状(一般症状发作后分别为中位10日和16日)而住院治疗.神经系统症状各不相同，总是进展到昏迷和死亡。BoDV-1和VSBV-1患者需要通气的中位数为3天和5天，平均死了32天和72天,住院后。基于不良预后，死亡大多发生在不同时间点停止支持治疗后。因此，疾病持续时间显示出广泛的，无与伦比的范围。
结论：进展极快是博纳病毒性脑炎最明显的临床特征，诊断和靶向治疗的时间很短。因此,我们的结果需要基于症状学的早期临床怀疑，流行病学,成像,和实验室发现，随后进行迅速的病毒学测试，作为任何潜在有效治疗的先决条件。
