Neurodegenerative central nervous system Langerhans cell histiocytosis and coincident hydrocephalus treated with vincristine/cytosine arabinoside

Pediatr Blood Cancer. 2010 Mar;54(3):416-23. doi: 10.1002/pbc.22326.


Background: Central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) include mass lesions and a neurodegenerative (ND) syndrome with ataxia, dysarthria, dysmetria, learning and behavior difficulties and/or characteristic changes on brain MRIs. Hydrocephalus has rarely been reported in LCH. LCH lesions of the orbit, mastoid and temporal bones ("CNS-Risk" lesions) and diabetes insipidus predispose patients to ND-CNS-LCH. Treatment options have been limited and only a case series using trans-retinoic acid (ATRA) and intravenous immunoglobulin (IVIG) have been published.

Methods: We have used cytosine arabinoside (ARA-C) with or without vincristine to treat eight patients with ND-CNS LCH.

Patients: Seven male children and one young adult male with clinical and radiologic ND-CNS-LCH were treated with a regimen of vincristine 1.5 mg/m(2) on day 1 and ARA-C 100 mg/m(2) daily for 5 days or ARA-C alone monthly for 4-19 months. Seven patients were evaluated with an ataxia rating scale (ARS) and all with serial MRIs of the brain.

Results: Five of seven patients had decreases in their ARS scores and/or decreased T2 hyperintense lesions on MRI images. Grade 2 neutropenia was the most frequent adverse event. Vincristine-associated neuropathy occurred in two patients. Hydrocephalus caused symptoms and signs that confounded the diagnosis and management of ND-CNS-LCH in all four patients affected with both.

Conclusions: Subtle changes in neurologic function may be complicated by hydrocephalus. Vcr/ARA-C or ARA-C were an effective therapies for some ND-CNS LCH patients. A clinical trial using this and possibly other modalities such as IVIG or ATRA should be done.

MeSH terms

  • Central Nervous System Diseases / complications
  • Central Nervous System Diseases / drug therapy*
  • Child
  • Child, Preschool
  • Cytarabine / therapeutic use*
  • Histiocytosis, Langerhans-Cell / complications
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Humans
  • Hydrocephalus / complications
  • Hydrocephalus / drug therapy*
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Neurodegenerative Diseases / complications
  • Neurodegenerative Diseases / drug therapy*
  • Retrospective Studies
  • Vincristine / therapeutic use*


  • Cytarabine
  • Vincristine