Department of Neurology, Salford Royal NHS Foundation Trust, Manchester, United Kingdom.
Department of Neurology, Royal Hallamshire Hospital, Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
Front Immunol. 2020 May 5;11:668. doi: 10.3389/fimmu.2020.00668. eCollection 2020.
Complications involving the central nervous system (CNS) occur in 9-14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and "domino" autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with confusion, slurred speech, left sided facial weakness and ataxia. A magnetic resonance imaging brain scan showed multiple enhancing tumefactive lesions. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. After extensive investigations for infections, autoimmune disorders and recurrence of malignancy, he underwent brain biopsy, which showed a macrophage rich lesion with severe myelin loss but axonal preservation indicating a demyelinating pathology. Although his symptoms improved with corticosteroids, he relapsed five months later. In the absence of any systemic features suggesting graft versus host disease (GvHD), his presentation was thought to be compatible with MS. The illness followed an aggressive course that did not respond to glatiramer acetate and natalizumab. He was therefore treated with "domino" autologous HSCT, which also failed to induce long-term remission. Despite further treatment with ocrelizumab, he died of progressive disease. An autopsy limited to the examination of brain revealed multifocal destructive leukoencephalopathy with severe myelin and axonal loss. Immunohistochemistry showed macrophage located in the perivascular area, with no T or B lymphocytes. The appearance was unusual and not typical for chronic MS plaques. Reported cases of CNS demyelination following allogeneic HSCT are very limited in the literature, especially in relation to histopathological examination. Although the clinical disease course of our patient following allogeneic HSCT resembled an "MS-like" relapsing remitting encephalomyelitis, the autopsy examination did not show any evidence of active inflammation. The impact of DMTs and HSCT on the histological appearance of "MS-like" CNS pathologies is unknown. Therefore, reporting this and similar cases will improve our awareness and understanding of underlying disease mechanisms.
异基因造血干细胞移植（HSCT）后，中枢神经系统（CNS）并发症发生在 9-14%的患者中，包括中风样发作、脱髓鞘、脑炎和非特异性神经症状。在这里，我们报告了一例异基因 HSCT 后多发性硬化（MS）样复发缓解性脑脊髓炎的病例，该病例对疾病修饰疗法（DMT）和“多米诺骨牌”自体 HSCT 均无反应。一名 53 岁男性因慢性髓性白血病的淋巴母细胞转化接受异基因 HSCT 治疗。10 个月后，他出现意识模糊、言语不清、左侧面部无力和共济失调。磁共振成像脑扫描显示多发强化肿块样病变。视神经脊髓炎（NMO）和髓鞘少突胶质细胞糖蛋白（MOG）抗体均为阴性。在广泛调查感染、自身免疫性疾病和恶性肿瘤复发后，他接受了脑活检，活检显示巨噬细胞丰富的病变，严重的髓鞘丢失，但轴突保留，表明脱髓鞘病理。尽管他的症状在皮质类固醇治疗后有所改善，但他在 5 个月后复发。由于没有任何提示移植物抗宿主病（GvHD）的全身特征，他的表现被认为与 MS 相符。该疾病呈侵袭性病程，对醋酸格拉替雷和那他珠单抗无反应。因此，他接受了“多米诺骨牌”自体 HSCT 治疗，但也未能诱导长期缓解。尽管进一步接受奥瑞珠单抗治疗，他仍死于进行性疾病。尸检仅限于大脑检查，显示多发性破坏性脑白质病，伴有严重的髓鞘和轴突丢失。免疫组化显示巨噬细胞位于血管周围区域，无 T 或 B 淋巴细胞。该表现不寻常，不符合慢性 MS 斑块的典型表现。文献中报道的异基因 HSCT 后 CNS 脱髓鞘病例非常有限，特别是在组织病理学检查方面。虽然我们的患者在异基因 HSCT 后的临床疾病过程类似于“MS 样”复发缓解性脑脊髓炎，但尸检检查未显示任何活动性炎症的证据。DMT 和 HSCT 对“MS 样”CNS 病变的组织学表现的影响尚不清楚。因此，报告此类病例将提高我们对潜在疾病机制的认识和理解。
