Central nervous system disease associated with Langerhans' cell histiocytosis

To study the pathogenesis of central nervous system (CNS) lesions in Langerhans' cell histiocytosis (LCH), discuss their differential diagnosis and suggest guidelines for their management.

Central nervous system (CNS) disease with Langerhans' cell histiocytosis (LCH) is a poorly understood disorder. Most commonly, the hypothalamic-pituitary region is involved, leading to diabetes insipidus (DI) or other endocrinopathies. We report four patients in whom lesions in the pons, cerebellum, basal ganglia, cerebral white matter, or optic nerve and tract were demonstrated by magnetic resonance imaging (MRI).

Three developed a progressive neurological disorder with cerebellar and pontine symptoms leading to severe disability--in one patient to blindness and death--in spite of various treatment approaches. In the fourth patient, who had MRI examinations to evaluate long-standing DI, CNS lesions were detected in the absence of neurological symptoms. There was no correlation between activity of LCH, severity and course of the CNS disease, or morphology of the lesions on MRI. Brain biopsy was performed in the three symptomatic patients and revealed cerebellar atrophy in one. Normal brain tissue was obtained from two patients. In none of the patients could autoantibodies to nervous system tissue be detected in serum or cerebrospinal fluid.

Based on clinical, pathological, and MRI findings in our four patients and on information in the literature, we conclude that the CNS disease associated with LCH, although insufficiently understood, is likely to be a manifestation of histiocytosis in the brain, and we propose guidelines for the management of patients with this disorder.