Neurodegeneration was suspected in 23/478 patients (16/23 male, mean age at diagnosis 49 years [5 - 68 years]). Diagnoses were ECD (13/23), Langerhans cell histiocytosis (LCH) (7/23), mixed LCH/ECD (2/23), and RDD (1/23). Median time from diagnosis to suspicion of neurodegeneration was 1.3 years (range 0-19 years). Median follow-up from histiocytic neoplasm diagnosis was 4.5 years (range 1 month- 20.5 years). Symptoms included ataxia (18/23), dysarthria (16/23), urinary dysfunction (16/23), cognitive impairment (14/23), and dysphagia (14/23).  

A progressive neurologic disorder was confirmed in 15/23, of which all were associated with an underlying active (12/15) or inactive (3/15) histiocytic neoplasm, (7/15 ECD, 5/15 LCH, 2/15 mixed, and 1/15 RDD). Of the 8 patients without a progressive neurologic disorder, diagnoses included fixed deficit from histiocytic neoplasm (3/8), depression (2/8), fatigue (1/8), pain (1/8), and stroke (1/8). Of the 3/15 patients with progressive neurologic dysfunction and inactive CNS histiocytic neoplasm, all had progressive pontocerebellar dysfunction. Progressive pontocerebellar atrophy on MRI was present in 10/13 patients with progressive symptoms, and 2/6 patients with no progressive symptoms.

Progressive neurologic dysfunction in adult patients with histiocytic neoplasms is most frequently due to an active histiocytic neoplasm, or non-histiocytic etiology. A minority of patients have a presumed non-neoplastic progressive neurologic dysfunction, primarily associated with pontocerebellar atrophy.