Neurodegenerative Langerhans cell histiocytosis: long-term follow-up of 63 patients from the Italian Registry

: Neurodegenerative Langerhans cell histiocytosis (ND-LCH) is a potentially devastating complication of LCH. We analyzed the natural history and the long-term outcome of patients with ND-LCH enrolled in the Italian LCH registry. ND-LCH was diagnosed in 63/637 patients with LCH (10%). Overall, at ND-LCH diagnosis 60% (38/63) patients were asymptomatic, 24% (15/63) had mild clinical manifestations including abnormal neurological examination and/or evoked potentials, and 16% (10/63) had overt symptoms. Brain MRI showed progressive structural changes in 13/63 (21%) patients over a median time of 1.5 years. Clinical ND-LCH developed after a median of 2.5 years since ND-LCH diagnosis. 30/63 patients (17 pauci-symptomatic, 11 symptomatic, two asymptomatic but with severe brain MRI) received treatment, and 17/30 (57%) were stable or improved at the last follow-up). 33/63 patients (mostly asymptomatic) were not treated and 31/33 (94%) remained stable through follow-up. At univariable analysis, the risk of developing overt clinical symptoms increased with LCH reactivations (OR 6.40, p=0.018), severe brain MRI abnormalities at ND-LCH diagnosis (OR 10.40, p.