Solomon Tom, Dung Nguyen Minh, Kneen Rachel, Thao Le Thi Thu, Gainsborough Mary, Nisalak Ananda, Day Nicholas P J, Kirkham Fenella J, Vaughn David W, Smith Shelagh, White Nicholas J
Department of Neurological Science, University of Liverpool, Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
Brain. 2002 May;125(Pt 5):1084-93. doi: 10.1093/brain/awf116.
Japanese encephalitis (JE) causes at least 10 000 deaths each year. Death is presumed to result from infection, dysfunction and destruction of neurons. There is no antiviral treatment. Seizures and raised intracranial pressure (ICP) are potentially treatable complications, but their importance in the pathophysiology of JE is unknown. Between 1994 and 1997 we prospectively studied patients with suspected CNS infections referred to an infectious disease referral hospital in Ho Chi Minh City, Vietnam. We diagnosed Japanese encephalitis virus (JEV), using antibody detection, culture of serum and CSF, and immunohistochemistry of autopsy material. We observed patients for seizures and clinical signs of brainstem herniation, measured CSF opening pressures (OP) and, on a subset of patients, performed EEGs. Of 555 patients with suspected CNS infections, 144 (26%) were infected with JEV (134 children and 10 adults). Seventeen (12%) patients died and 33 (23%) had severe sequelae. Of the 40 patients with witnessed seizures, 24 (62%) died or had severe sequelae, compared with 26 (14%) of 104 with no witnessed seizures [odds ratio (OR) 4.50, 95% confidence interval (CI) 1.94-10.52, P < 0.0001]. Patients in status epilepticus (n = 25), including 15 with subtle motor seizures, were more likely to die than those with other seizures (P = 0.003). Patients with seizures were more likely to have an elevated CSF OP (P = 0.033) and to develop brainstem signs compatible with herniation syndromes (P < 0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80 patients with lower pressures [OR 8.69, 95% CI 1.73-45.39, P = 0.005). Of the 50 patients with a poor outcome, 35 (70%) had signs compatible with herniation syndromes (including 19 with signs of rostro-caudal progression), compared with nine (10%) of those with better outcomes (P < 0.0001). Of 11 patients with CSF OP > or =25 cm, five (46%) died, compared with seven (9%) of 80 patients with lower pressures (OR 8.69, 95% CI 1.73-45.39, P = 0.005). The combination of coma, multiple seizures, brainstem signs and illness for 7 or more days was an accurate predictor of outcome, correctly identifying 42 (84%) of 50 patients with a poor outcome and 82 (87%) of 94 with a better outcome. These findings suggest that in JE, seizures and raised ICP may be important causes of death. The outcome may be improved by measures aimed at controlling these secondary complications.
日本脑炎（JE）每年至少导致10000人死亡。死亡被认为是由神经元的感染、功能障碍和破坏所致。目前尚无抗病毒治疗方法。癫痫发作和颅内压（ICP）升高是潜在可治疗的并发症，但其在日本脑炎病理生理学中的重要性尚不清楚。1994年至1997年期间，我们对越南胡志明市一家传染病转诊医院收治的疑似中枢神经系统感染患者进行了前瞻性研究。我们通过抗体检测、血清和脑脊液培养以及尸检材料的免疫组织化学方法诊断日本脑炎病毒（JEV）。我们观察患者是否有癫痫发作和脑干疝的临床体征，测量脑脊液初压（OP），并对一部分患者进行脑电图检查。在555例疑似中枢神经系统感染的患者中，144例（26%）感染了JEV（134例儿童和10例成人）。17例（12%）患者死亡，33例（23%）有严重后遗症。在40例有癫痫发作记录的患者中，24例（62%）死亡或有严重后遗症，而在104例无癫痫发作记录的患者中，有26例（14%）死亡或有严重后遗症[比值比（OR）4.50，95%置信区间（CI）1.94 - 10.52，P < 0.0001]。癫痫持续状态的患者（n = 25），包括15例有轻微运动性癫痫发作的患者，比其他癫痫发作患者更易死亡（P = 0.003）。有癫痫发作的患者脑脊液初压升高的可能性更大（P = 0.033），且更易出现与疝综合征相符的脑干体征（P < 0.0001）。在脑脊液初压≥25 cm的11例患者中，5例（46%）死亡，而在初压较低的80例患者中有7例（9%）死亡[OR 8.69，95% CI 1.73 - 45.39，P = 0.005]。在50例预后不良的患者中，35例（70%）有与疝综合征相符的体征（包括19例有头 - 尾进展体征的患者），而在预后较好的患者中有9例（10%）有此类体征（P < 0.0001）。在脑脊液初压≥25 cm的11例患者中，5例（46%）死亡，而在初压较低的80例患者中有7例（9%）死亡（OR 8.69，95% CI 1.73 - 45.39，P = 0.005）。昏迷、多次癫痫发作、脑干体征以及病程7天或更长时间这一组合是预后的准确预测指标，正确识别出了50例预后不良患者中的42例（84%）以及94例预后较好患者中的82例（87%）。这些发现表明，在日本脑炎中，癫痫发作和颅内压升高可能是重要的死亡原因。针对控制这些继发性并发症的措施可能会改善预后。
