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 8 patients with ND-CNS LCH. Patients:7 male children and one young adult male with clinical and radiologic ND- CNS-LCH were treated with a regimen of vincristine 1.5 mg/m2 on day 1 and ARA-C 100 mg/m2 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 7 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 4 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.

How I treat Langerhans cell histiocytosis

“…29 If patients have refractory or recurrent disease with vinblastine/prednisone, subsequent treatment with cytarabine or clofarabine may be effective. 47,48 Special situations CNS lesions. DI is the most frequent initial sign of LCH in the CNS.…”

“…Mass lesions of the brain may respond to vinblastine/prednisone, cladribine, cytarabine, and clofarabine. 47,48,51,52 Although there has been no trial to suggest which of these regimens might be the best, cytarabine has been effective in a majority of patients and has possible benefit against ND LCH.…”

“…55,56 In an institutional series, vincristine/ cytarabine was associated with improvement in clinical symptoms and MRI images in 6 of 8 patients. 47 We therefore favor this strategy for patients with LCH ND. Some patients fail to respond to these therapies and have an inexorable decline in neurologic function over the course of years.…”

Adsorptive depletion of blood monocytes reduces the levels of circulating interleukin-17A in Langerhans cell histiocytosis

“…Cytarabine was given in parallel for 6 months based on positive reports from others. 11 Because of absence of clinical improvement and lack of alternative treatment, and considering the positive effects of natalizumab on patients with multiple sclerosis, 12 we then administered natalizumab after thorough discussions with neurologists and the parents. GMA continued once every 4 weeks.…”

Follow-up of pediatric patients treated by IVIG for Langerhans cell histiocytosis (LCH)-related neurodegenerative CNS disease

“…Of the six patients received early IVIG treatment (Cases 1, 2 and 4-7), three still have scores below 3.0 (Cases 2, 5 and 7); however, the other three (Cases 1, 4 and 6) had unfavorable results. Case 1 developed severe hydrocephalus during treatment, the outcome of which is known to be dismal [14,15]. This patient is now bedridden and IVIG treatment has been discontinued.…”