Department of Neurology, Montefiore Medical Center, Bronx, NY, USA.
Department of Pediatrics, Albert Einstein College of Medicine, Children's Hospital at Montefiore, Bronx, NY, USA.
BMC Neurol. 2024 Oct 21;24(1):404. doi: 10.1186/s12883-024-03840-8.
Hemophagocytic lymphohistiocytosis (HLH) is an inherited syndrome characterized by immune dysregulation. Central nervous system (CNS)-isolated disease is a rare presentation of familial HLH. We present a case of pediatric CNS-isolated HLH with a presentation complicated by unusual hemorrhagic intraparenchymal lesions.
A 15-year-old male presented with ataxia and MRI findings of multiple hemorrhagic lesions in his cerebral white matter, brainstem, and cerebellum, suggestive of vasculitis. After failing to improve with steroids and plasmapheresis, and progression to acute neurologic decompensation, new brainstem hemorrhages were noted. Further workup revealed 2 PRF1 mutations, confirming a diagnosis of familial CNS-HLH. He was later found to have a platelet granule defect, explaining his atypical neuroradiologic findings. The patient received treatment per the HLH-1994 protocol and underwent stem cell transplantation. Two years post-transplant, his perforin expression is nearly normal and his neurologic deficits have significantly improved.
This case illustrates the variability in presentation of isolated CNS-HLH. Although rare, it is important to include this diagnosis on the differential in patients with CNS hemorrhagic lesions. If initial diagnostic studies remain inconclusive or response to early treatments is poor, CNS-HLH should be considered, as delay in diagnosis and treatment significantly affects morbidity and mortality.
噬血细胞性淋巴组织细胞增生症（HLH）是一种以免疫失调为特征的遗传性综合征。中枢神经系统（CNS）孤立性疾病是家族性 HLH 的罕见表现。我们报告了一例儿科 CNS 孤立性 HLH 病例，其表现复杂，伴有不常见的出血性脑实质病变。
一名 15 岁男性因共济失调和 MRI 发现大脑白质、脑干和小脑多处出血性病变就诊，提示血管炎。在类固醇和血浆置换治疗无效并进展为急性神经功能恶化后，注意到新的脑干出血。进一步检查发现 2 个 PRF1 突变，确诊为家族性 CNS-HLH。后来发现他有血小板颗粒缺陷，解释了他不典型的神经放射学发现。患者按照 HLH-1994 方案接受治疗，并进行了干细胞移植。移植后 2 年，他的穿孔素表达几乎正常，神经功能缺损显著改善。
本病例说明了孤立性 CNS-HLH 的表现多样性。尽管罕见，但在有 CNS 出血性病变的患者中，应将此诊断纳入鉴别诊断。如果初始诊断性研究仍不明确或早期治疗反应不佳，应考虑 CNS-HLH，因为诊断和治疗的延迟会显著影响发病率和死亡率。
