Abstract
BACKGROUND: Leukoencephalopathy with calcifications and cysts is a rare, autosomal recessive cerebral microangiopathy that causes progressive white matter disease, calcifications, and cysts within the brain. It is typically associated with slowly progressive psychomotor regression, seizures, and movement disorders. Although leukoencephalopathy with calcifications and cysts affects only the central nervous system, it demonstrates remarkable neuropathologic and radiologic overlap with Coats plus, a disorder of small vessels of the brain, eyes, gastrointestinal tract, and bone. Coats disease without extraocular involvement, a genetically distinct disorder from Coats plus, is characterized by retinal telangiectasias and exudative retinopathy, accompanied by neovascularization. Inhibition of vascular endothelial growth factor (VEGF) signaling with the monoclonal anti-VEGF antibody bevacizumab can improve retinal edema and exudates in Coats disease. Given these observations, we reasoned that VEGF inhibition might also be effective in treating leukoencephalopathy with calcifications and cysts and Coats plus, neither of which has any known therapy. METHODS: We treated an 18-year-old man with leukoencephalopathy with calcifications and cysts using biweekly infusions of the VEGF inhibitor bevacizumab for more than one year and performed clinical examinations and brain imaging at three month intervals. RESULTS: After treatment for more than one year, the patient showed improved bradykinesia and range of motion, and brain magnetic resonance imaging demonstrated a marked reduction in cyst volume and white matter lesions. CONCLUSIONS: Further studies in a cohort of patients are warranted to investigate the efficacy of VEGF inhibition as a treatment for leukoencephalopathy with calcifications and cysts.