Complete neurological recovery after allogeneic hematopoietic stem cell transplantation in a child with severe central nervous system involvement of hemophagocytic lymphohistiocytosis: a case report

Background: Hemophagocytic lymphohistiocytosis (HLH) with central nervous system (CNS) involvement can cause severe and often permanent neurological sequelae. We report a child with severe CNS-HLH who achieved complete neurological recovery after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite persistent and mildly progressive radiological abnormalities. Case presentation: A 3-year-4-month-old boy presented with a 6-month history of recurrent urticarial rash, followed by fever and marked eosinophilia (peripheral blood 3.55×10⁹/L, bone marrow 42.5%). He subsequently developed seizures, persistent somnolence, and incontinence. He fulfilled all eight HLH-2004 diagnostic criteria. Cerebrospinal fluid (CSF) showed markedly elevated protein (1110.5 mg/L, later 2970 mg/L) and soluble CD25 (sCD25, 3934 pg/ml) with normal cell count. Brain MRI revealed periventricular demyelinating changes and global cerebral atrophy. Whole-exome sequencing revealed no pathogenic variant. After HLH control with teniposide, ruxolitinib, dexamethasone, emapalumab, and intrathecal methotrexate plus dexamethasone, he underwent maternal HLA 5/10-matched allo-HSCT (bone marrow plus peripheral blood stem cells and unrelated cord blood) on day 0. Neutrophil engraftment occurred on day +13 and platelet engraftment on day +39. Post-transplant complications included grade IV acute liver graft-versus-host disease (GVHD), grade III intestinal GVHD, and cytomegalovirus reactivation, all of which were controlled. Neurological recovery milestones were: normal swallowing at +2 months, independent walking at +4 months, recovery of language and eye contact at +5 months, and running with normal verbal communication at +6 months. However, follow-up brain MRI at +139 days showed mild progression of periventricular demyelinating changes with new punctate DWI hyperintensities and ventricular enlargement, while cerebral atrophy remained stable. Discussion: This case demonstrates remarkable neurological plasticity after allo-HSCT in severe CNS-HLH, with a striking "clinical-radiological dissociation" — complete functional recovery despite persistent and mildly progressive structural brain abnormalities. MRI white matter changes and atrophy reflect established structural damage (demyelination, neuronal and axonal loss), which may be irreversible, whereas functional recovery depends on inflammation control and childhood neuroplasticity. Conclusion: Complete neurological recovery can be achieved after allo-HSCT in severe CNS-HLH. Clinical improvement may occur despite persistent or mildly progressive radiological changes. Allo-HSCT should be considered for severe or refractory CNS-HLH even in the absence of an identified genetic cause.