Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

在家族性噬血细胞性淋巴组织细胞增生症 (FHL) 的病例报告中已经描述了孤立的神经炎症性疾病，但疾病表现的临床谱、对治疗的反应和预后仍不明确。我们将一项国际调查与文献搜索相结合，以确定具有以下特征的 FHL 患者：(ii) 就诊时没有血细胞减少和脾肿大；(iii) 系统性 HLH 特征不早于神经表现后 3 个月。三十八名（20 名未报告）患者的初步诊断包括急性脱髓鞘性脑病、白质脑病、中枢神经系统血管炎、多发性硬化症和脑炎。就诊时的中位年龄为 6.5 岁，最常见的是共济失调/步态障碍 (75%) 和癫痫发作 (53%)。弥漫性多灶性白质改变 (79%) 和小脑受累 (61%) 是常见的 MRI 发现。CSF 细胞计数和蛋白质分别在 22/29 和 15/29 患者中增加。14 名患者在初始神经系统表现后平均 36.9 个月进展为符合 HLH-2004 标准的全身炎症性疾病。检测到突变PRF1在23名患者（61％），RAB27A在10（26％），UNC13D在3（8％），LYST在1（3％），和STXBP2在1（3％），平均间隔的28.3个月诊断. 19例HSCT患者中，11例神经功能好转，4例稳定，1例复发，3例死亡。14例非移植患者中，仅3例病情好转或稳定，1例复发，10例死亡。孤立的 CNS-HLH 是一种罕见且经常被忽视的炎症性脑病病因。HLH 导向治疗后进行 HSCT 似乎可以提高生存率和结果。