Kogelnik Andreas M, Loomis Kristin, Hoegh-Petersen Mette, Rosso Fernando, Hischier Courtney, Montoya Jose G
Stanford University School of Medicine, Stanford, CA, USA.
J Clin Virol. 2006 Dec;37 Suppl 1:S33-8. doi: 10.1016/S1386-6532(06)70009-9.
Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.
We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.
Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.
Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.
These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.
发现12例有长期中枢神经系统(CNS)功能障碍症状的患者,其抗人疱疹病毒6型(HHV - 6)和爱泼斯坦 - 巴尔病毒(EBV)的抗体滴度升高。所有患者均有以下四种或更多种神经认知症状:认知功能受损、处理速度减慢、睡眠障碍、短期记忆缺陷、疲劳以及与抑郁相符的症状。
我们试图确定EBV和HHV - 6抗体升高是否表明CNS功能障碍患者存在慢性病毒激活,以及口服缬更昔洛韦抑制病毒活性是否能改善他们的症状。
在一项开放标签研究中,对12例抗HHV - 6和EBV的IgG抗体滴度高、患有中枢神经系统功能障碍且疲劳衰弱超过一年(中位时间3年,范围1 - 8年)的患者,给予6个月的缬更昔洛韦治疗。
12例患者中有9例(75%)症状几乎完全缓解,全部能够重返工作岗位或恢复全职活动。在9例对治疗有症状反应的患者中,EBV VCA IgG滴度从1:2560降至1:640(p = 0.008),HHV - 6 IgG滴度从中位值1:1280降至1:320(p = 0.271)。12例患者中未观察到具有临床意义的血液学毒性或严重不良事件。
这些初步的临床和实验室观察结果值得进一步研究,以确定这种临床反应是由药物的抗病毒作用介导,还是通过免疫调节间接介导,亦或是由安慰剂效应介导。