Seeley W W, Marty F M, Holmes T M, Upchurch K, Soiffer R J, Antin J H, Baden L R, Bromfield E B
Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA.
Neurology. 2007 Jul 10;69(2):156-65. doi: 10.1212/01.wnl.0000265591.10200.d7.
Acute limbic encephalitis has been reported in the setting of treatment-related immunosuppression and attributed to human herpesvirus-6 (HHV6) infection. Clinical and laboratory features of the syndrome, however, have not been well characterized.
We describe the clinical, EEG, MRI, and laboratory features of nine patients with acute limbic encephalitis after allogeneic hematopoietic stem cell transplantation (HSCT). To explore the relationship between HHV6 and this syndrome, we reviewed available CSF HHV6 PCR results from all HSCT patients seen at our center from March 17, 2003, through March 31, 2005.
Patients displayed a consistent and distinctive clinical syndrome featuring anterograde amnesia, the syndrome of inappropriate antidiuretic hormone secretion, mild CSF pleocytosis, and temporal EEG abnormalities, often reflecting clinical or subclinical seizures. MRI showed hyperintensities within the uncus, amygdala, entorhinal area, and hippocampus on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences. CSF PCR assays for HHV6 were positive in six of nine patients on initial lumbar puncture. All patients were treated with foscarnet or ganciclovir. Cognitive recovery varied among long-term survivors. The one brain autopsy showed limbic gliosis and profound neuronal loss in amygdala and hippocampus. Among 27 HSCT patients with CSF tested for HHV6 over a 2-year period, positive results occurred only in patients with clinical limbic encephalitis.
Patients undergoing allogeneic hematopoietic stem cell transplantation are at risk for post-transplant acute limbic encephalitis (PALE), a distinct neurologic syndrome. Treatment considerations should include aggressive seizure control and, possibly, antiviral therapy. PALE can be associated with the CSF presence of human herpesvirus-6, but the pathogenic role of the virus requires further exploration.
急性边缘叶脑炎已在治疗相关免疫抑制的情况下被报道，并归因于人类疱疹病毒6型（HHV6）感染。然而，该综合征的临床和实验室特征尚未得到很好的描述。
我们描述了9例异基因造血干细胞移植（HSCT）后发生急性边缘叶脑炎患者的临床、脑电图、磁共振成像（MRI）和实验室特征。为了探讨HHV6与该综合征之间的关系，我们回顾了2003年3月17日至2005年3月31日在我们中心就诊的所有HSCT患者的脑脊液HHV6聚合酶链反应（PCR）结果。
患者表现出一种一致且独特的临床综合征，其特征为顺行性遗忘、抗利尿激素分泌不当综合征、脑脊液轻度淋巴细胞增多以及颞叶脑电图异常，常反映临床或亚临床癫痫发作。MRI在T2加权像、液体衰减反转恢复（FLAIR）序列和扩散加权成像（DWI）序列上显示钩回、杏仁核、内嗅区和海马内有高信号。9例患者中有6例初次腰椎穿刺时脑脊液HHV6 PCR检测呈阳性。所有患者均接受了膦甲酸钠或更昔洛韦治疗。长期存活者的认知恢复情况各不相同。1例脑尸检显示边缘叶胶质增生以及杏仁核和海马中神经元大量丢失。在2年期间接受脑脊液HHV6检测的27例HSCT患者中，阳性结果仅出现在有临床边缘叶脑炎的患者中。
接受异基因造血干细胞移植的患者有发生移植后急性边缘叶脑炎（PALE）的风险，这是一种独特的神经综合征。治疗考虑应包括积极控制癫痫发作，可能还需进行抗病毒治疗。PALE可能与脑脊液中存在人类疱疹病毒6型有关，但该病毒的致病作用需要进一步探索。
