Pattern and course of neurodegeneration in Langerhans cell histiocytosis

To explore the frequency and course of neurodegenerative central nervous system (CNS) disease in Langerhans cell histiocytosis (ND-LCH).

We studied 83 patients with LCH in whom magnetic resonance imaging (MRI) of the brain was performed at least twice for various clinical indications. We defined radiologic ND-LCH as an MRI pattern comprising bilateral symmetric lesions in the dentate nucleus of the cerebellum or basal ganglia.

Forty-seven of 83 patients (57%) had radiologic ND-LCH, at a median of 34 months (range 0-16 years) from the diagnosis of LCH. The MRI findings deteriorated in 31/47 (66%) patients over a median of 3 years (range 2 months to 12 years 6 months) and did not reverse in any patient. In 12 patients with radiologic ND-LCH (25%), clinical ND-LCH with overt symptoms were found 3 to 15 years (median 6 years) after initial LCH diagnosis. These symptoms included intention tremor, cerebellar ataxia, dysarthria, dysdiadochokinesis, concentration deficits, psychomotor retardation, severe headaches, and psychosis.

We conclude that radiologic ND-LCH is serious, not uncommon in patients studied by MRI, irreversible, and may be followed by severe clinical ND-LCH many years after the initial diagnosis of LCH.