title: Neurodegenerative central nervous system Langerhans cell histiocytosis and coincident hydrocephalus treated with vincristine/cytosine arabinoside.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Texas Children's Cancer Center/Hematology Service, Houston, TX 77030, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
authors.forename: Ricardo
authors.initials: R
authors.lastname: Flores
authors.forename: Ronald
authors.initials: R
authors.lastname: Rauch
authors.forename: Robert
authors.initials: R
authors.lastname: Dauser
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Diane
authors.initials: D
authors.lastname: Puccetti
authors.forename: David A
authors.initials: DA
authors.lastname: Hsu
authors.forename: Paul
authors.initials: P
authors.lastname: Sondel
authors.forename: Maxine
authors.initials: M
authors.lastname: Hetherington
authors.forename: Stan
authors.initials: S
authors.lastname: Goldman
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McClain
mesh_terms: D002493:Central Nervous System Diseases / Q000150:complications / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000627:therapeutic use*; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006849:Hydrocephalus / Q000150:complications / Q000188:drug therapy*; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D019636:Neurodegenerative Diseases / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D003561:Cytarabine; D014750:Vincristine