PDF(Pubmed)
Abstract：
ABSTRACTBorna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies.ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum.
摘要：
博尔纳病病毒1（BoDV-1）最近才被证明主要导致人类致命的脑炎。尽管它很罕见,bornavirus脑炎（BVE）可以被认为是由嗜神经病毒引起的脑炎感染的模型疾病，了解其病理机制至关重要。这项研究的目的是比较大脑炎症的程度和分布模式与临床病程，和单独的治疗程序。为此，这项研究包括7例致命BVE患者的自体脑材料。对组织进行全淋巴细胞标记CD45、BoDV-1核蛋白以及神经胶质标记GFAP和小神经胶质标记Iba1的免疫组织化学染色。将切片数字化并计数CD45阳性细胞和BoDV-1阳性细胞。对于GFAP和Iba1,确定半定量评分。此外，我们以标准化的方式检索并总结了有关个体临床疗程和治疗的详细信息.淋巴细胞分布的分析显示了个体间的模式。相比之下,当观察BoDV-1阳性的神经胶质细胞和神经元时，脑干中大量的病毒参与是显而易见的。七名患者中有三名接受了早期高剂量类固醇治疗，与在病程后期接受类固醇治疗的患者相比，这导致中枢神经组织的淋巴细胞浸润显着降低，生存期更长。这项研究强调了早期大剂量免疫抑制治疗在BVE中的潜在重要性。我们的发现暗示了一个有希望的治疗选择，应该在未来的观察性或前瞻性治疗研究中得到证实。
