Clinical and Neuroimaging Manifestations of Erdheim-Chester Disease: A Review

Erdheim-Chester disease (ECD) is a rare disorder characterized by accumulation of non-Langerhans cell histiocytes in multiple organs. The clinical manifestations are protean and vary from asymptomatic focal disease to potentially fatal multisystem disorder. The commonest presentation is symmetric osterosclerotic lesions of lower extremity long bones; other organs, including cardiovascular, nervous, and endocrine system may be affected. Central nervous system involvement can occur in up to 50% cases and is associated with poor prognosis. The disease pathogenesis involves organ involvement secondary to histiocytic infiltration and systemic inflammation driven by Th1 cytokine activation. The recent discovery of activating mutations in proto-oncogene B-rapidly accelerated fibrosarcoma (BRAF) V600E and other genes involved in mitogen-activated protein kinase (MAPK) pathways has led to redefinition of ECD as a myeloid neoplastic disorder. The diagnosis requires histochemical and molecular analysis of histiocytes in tissue biopsies in patients with compatible clinical and imaging features. The treatment options include interferon-alpha, anakinra, and immunosuppressive therapies. Better understanding of disease pathogenesis has led to development of novel targeted and effective therapies including BRAF and MEK inhibitors. The rarity of the disease and variable clinical features and course often results in diagnostic errors and delays. Rare primary neurological presentation can occur mimicking CNS inflammatory, neoplastic, or demyelinating disorders. We report an unusual case of ECD presenting with progressive encephalopathy and ataxia along with multifocal brainstem and cerebellar lesions. A comprehensive review of clinical and neuroimaging features and immunohistochemical and molecular characteristic of ECD are presented along with review of neuroimaging findings in two previously reported cases.