Kerr J R, Barah F, Chiswick M L, McDonnell G V, Smith J, Chapman M D, Bingham J B, Kelleher P, Sheppard M N
Department of Microbiology, Royal Brompton and Harefield NHS Trust, Imperial College School of Medicine, London, UK.
J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):739-46. doi: 10.1136/jnnp.73.6.739.
To review the clinical and pathological features of parvovirus B19 meningoencephalitis and its sequelae in 12 previously published cases, and to perform additional tests to determine the pathogenesis of the disease.
Cases were reviewed and available serum and cerebrospinal fluid (CSF) tested for antiganglioside antibodies and a range of cytokines. In situ hybridisation for parvovirus B19 DNA was performed on postmortem brain tissue in two cases. HLA-DRB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes.
Cerebellar involvement was suggested either clinically or pathologically in four cases. In the two cases with postmortem histology, there was marked atrophy of the molecular and granular layers of the cerebellum with focal loss of Purkinje cells. Brain scanning by MRI or CT was done in six cases during the acute phase. Three were abnormal with evidence of demyelination. Three had markedly enlarged ventricles, in two of which there was high signal intensity from the white matter on both T1 and T2 weighted images. The three cases with abnormal brain scans had long term neurological sequelae (mental retardation, personality change, altered affect). In situ hybridisation on available postmortem brain tissue was negative in the two cases tested. All cases in which HLA-DR alleles were determined carried at least one of the following alleles: HLA-DRB1*01, *04, *07, *09, *15, *16. Available serum and CSF was tested for antiganglioside antibodies (all negative) and for a panel of cytokines, which had a similar profile in both serum (n = 5) and CSF (n = 1) during the acute phase. Cytokines that were consistently detectable were IL-6 (mean 726.20 pg/ml), TNFalpha (50.64 pg/ml), IFNgamma (39.64 pg/ml), GM-CSF (216.12 pg/ml), and MCP-1 (154.43 pg/ml); IL-1beta, IL-5, and IL-13 were undetectable.
HLA-DR associations, an increased cytokine response, and benefit from immunomodulatory treatment (in one case) support a role for the immune response in the pathogenesis of parvovirus B19 meningoencephalitis.
回顾12例已发表的细小病毒B19脑膜脑炎及其后遗症的临床和病理特征，并进行额外检测以确定该疾病的发病机制。
回顾病例，并检测可用血清和脑脊液（CSF）中的抗神经节苷脂抗体及一系列细胞因子。对2例病例的尸检脑组织进行细小病毒B19 DNA原位杂交。对从外周血白细胞提取的基因组DNA进行HLA - DRB1分型。
4例病例临床或病理提示有小脑受累。在2例有尸检组织学检查的病例中，小脑分子层和颗粒层明显萎缩，浦肯野细胞局灶性缺失。6例在急性期进行了MRI或CT脑部扫描。3例异常，有脱髓鞘证据。3例脑室明显扩大，其中2例在T1加权和T2加权图像上白质均有高信号强度。3例脑部扫描异常的病例有长期神经后遗症（智力发育迟缓、人格改变、情感改变）。对可用的尸检脑组织进行的2例原位杂交检测均为阴性。所有确定了HLA - DR等位基因的病例均携带至少以下等位基因之一：HLA - DRB1*01、*04、*07、*09、*15、*16。检测可用血清和脑脊液中的抗神经节苷脂抗体（均为阴性）及一组细胞因子，急性期血清（n = 5）和脑脊液（n = 1）中的细胞因子谱相似。持续可检测到的细胞因子有IL - 6（平均726.20 pg/ml）、TNFα（50.64 pg/ml）、IFNγ（39.64 pg/ml）、GM - CSF（216.12 pg/ml）和MCP - 1（154.43 pg/ml）；未检测到IL - 1β、IL - 5和IL - 13。
HLA - DR关联、细胞因子反应增强以及免疫调节治疗的获益（1例）支持免疫反应在细小病毒B19脑膜脑炎发病机制中的作用。
