Background: Familial Hemophagocytic lymphohistiocytosis (FHL) is a lethal disease characterized by the occurence of an hemophagocytic syndrome characterized by high fever, hepatosplenomegaly, pancytopenia, low fibrinogen level, hemodilution, elevation of the liver enzymes and hypertriglyceridemia. Neurological manifestations of FHL have been recognized but their frequencies, characteristics and influence on the outcome remain relatively ill-defined.

Subject: We have retrospectively assessed the neurological manifestations in 34 patients with FHL in a single center. Clinical, radiological and cerebrospinal fluid cytology data were analysed according to treatment modalities.

Interventions: All patients were initially treated by chemotherapy, 13 underwent also a Bone Marrow Transplantation (BMT) while 16 were treated by chemotherapy alone

Results: Twenty five patients had evidence of Central Nervous System (CNS) disease at time of diagnosis stressing the frequency of CNS involvement early in the time course of FHL. Four additional patients who did not have initial CNS disease, who did not die early from FHL complications and were not transplanted, also developed a specific CNS disease. Therefore all evaluable patients had CNS involvement. Initially, CNS manifestations were isolated lymphocytic meningitis in 20, meningitis with clinical and radiological neurologic symptoms in 9. Outcome of patients treated by systemic and intrathecal chemotherapy and/or immunosuppression only (n=16) was poor since all died following occurence of multiple relapses or CNS disease progression in most cases. Thirteen patients were treated by BMT(HLA-identical in 6 cases and HLA -nonidentical in 7 cases). Seven are long term survivors including 3 who received an HLA partially identical marrow, off treatment with normal neurological function and cognitive development as well.

Conclusion: This study emphazises the high frequency and severity of CNS manifestations in FHL. To perform a BMT in FHL patients before the occurence of CNS parenchymal lesions appears to be crucial even when no HLA-identical donor is available.