Infratentorial progressive multifocal leukencephalopathy in a patient with pulmonary sarcoidosis
Infratentorial progressive multifocal leukencephalopathy in a patient with pulmonary sarcoidosis
复制标题
肺结节病患者幕下进行性多灶性白质脑病
作者：
L. Neeb;S. Diekmann;C. Blechschmidt;H. Meisel;J. Hofmann;L. Harms;M. Endres
先生，一位56岁女性于2007年7月因小脑性共济失调、四肢轻瘫、吞咽困难和构音障碍转介到我院。1988年，患者被诊断为肺结节病，此后接受不同剂量的糖皮质激素治疗。2007年2月的脑部磁共振成像（MRI）扫描显示左侧脑桥T2加权高信号病变（图1a）。患者被诊断为可能的神经结节病，并接受静脉注射甲泼尼龙（500 mg/天，连续5天），随后口服泼尼松龙（40- 100 mg/天，在接下来的几周内）治疗。然而，尽管进行了治疗，但神经系统症状进一步进展，患者被转移到我们的神经科病房。实验室检查显示血细胞分类计数中淋巴细胞减少（相对：3%，绝对：0.31/nl），白细胞水平正常。可能的自身免疫性和感染性病因的血清学检测为阴性。脑脊液（CSF）检查正常，仅在CSF中检测到寡克隆带。分子检测显示多克隆T和B细胞群。为了排除Whipple病，进行了十二指肠粘膜活检，发现正常。胸部CT符合肺结节病。MRI扫描显示脑桥和小脑T2加权和液体衰减反转恢复高信号（图1b，c），无钆增强。在幕上两侧的额叶皮质下白色物质中发现较小的（7 mm）相似信号强度（图1d）。静脉注射甲泼尼龙500 mg/天，连续5天，然后口服甲氨蝶呤10 mg一次。此后不久，患者发生细菌性肺炎，被转移到神经重症监护室，接受了呼吸治疗和机械通气。小脑的立体定向脑活检显示脱髓鞘区域，另外以几个泡沫状巨噬细胞的存在为标志。通过免疫组织化学在活检样品中检测到JC病毒（JCV）（图2）。此外，通过聚合酶链反应（PCR）检测小脑组织、CSF、血清和尿液中的JCV DNA，建立进行性多灶性白质脑病（PML）的诊断。立即停止口服泼尼松龙治疗。开始用西多福韦5 mg/kg加丙磺舒治疗，1周后重复。然而，患者发生细菌性脓毒症伴多器官衰竭。她在首次出现神经症状后11个月死于心血管衰竭。本例显示结节病患者的PML脑干/小脑表现。PML是一种由潜伏性JCV L再活化引起的脱髓鞘性CNS疾病。尼卜属哈姆斯湾Endres神经内科，Charite Universitaetsmedizin柏林，Chariteplatz 1，10117柏林，德国电子邮件：lars. charite.de
Sirs, A 56-year-old woman was referred to our hospital in July 2007 because of cerebellar ataxia, tetraparesis, dysphagia and dysarthrophonia which had progressed over the last 9 months. In 1988 the patient was diagnosed with pulmonary sarcoidosis and since treated with varying doses of glucocorticoids. A magnetic resonance imaging (MRI) scan of the brain from February 2007 showed a left pontine T2 weighted hyperintense lesion (Fig. 1a). The patient was diagnosed with probable neurosarcoidosis and treated with a pulse of i.v. methylprednisolone (500 mg/day for 5 consecutive days) followed by oral prednisolone (40– 100 mg/day over the next weeks). However, despite treatment neurological symptoms further progressed and the patient was transferred to our neurological ward. Laboratory testing revealed lymphocytopenia in differential blood count (relative: 3%, absolute: 0.31/nl) with normal leukocyte levels. Serological tests for possible autoimmune and infective etiologies were negative. Cerebral spinal fluid (CSF) examination was normal besides detection of oligoclonal bands only in CSF. Molecular testing revealed a polyclonal Tand B-cell population. To exclude Whipple0s disease a biopsy of duodenal mucosa was performed and found normal. Thorax-CT was consistent with pulmonary sarcoidosis. MRI scans showed T2-weighted and fluid-attenuated inversion recovery hyperintensities in pons and cerebellum (Fig. 1b, c) without Gadolinium enhancement. Smaller (7 mm), similar signal intensities were found supratentorially in the frontal subcortical white matter on both sides (Fig. 1d). Intravenous methylprednisolone at 500 mg/day was administered for 5 consecutive days followed by administration of methotrexate at 10 mg orally once. Soon thereafter, the patient developed bacterial pneumonia, was transferred to the neurointensive care unit, antibiotically treated and mechanically ventilated. Stereotactic brain biopsy of the cerebellum showed areas of demyelination additionally marked by the presence of several foamy macrophages. JC virus (JCV) was detected in biopsy sample by immunohistochemistry (Fig. 2). In addition, JCV DNA was detected by polymerase chain reaction (PCR) in cerebellar tissue, CSF, serum and later in urine, establishing the diagnosis of progressive multifocal leukoencephalopathy (PML). Therapy with oral prednisolone was immediately stopped. Treatment with cidofovir 5 mg/kg plus probenicid was initiated and repeated 1 week later. However, the patient developed bacterial sepsis with multi-organ failure. She died of cardiovascular failure 11 months after first neurological symptoms occurred. This case shows a brainstem/cerebellar manifestation of PML in a patient with sarcoidosis. PML is a demyelinating CNS disease caused by re-activation of a latent JCV L. Neeb (&) L. Harms M. Endres Department of Neurology, Charite Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany e-mail: lars.neeb@charite.de