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Progressive leukoencephalopathy developed in a patient with adult celiac disease. Neurologic abnormalities appeared 4 years after the gastrointestinal manifestations despite a gluten-free diet and replacement of vitamins. Brain MRI showed marked confluent white matter abnormalities, and stereotactic brain biopsy revealed chronic leukoencephalopathy. Treatment with IV steroids and immunoglobulins did not stop disease progression. Celiac disease should be considered in the differential diagnosis of the leukoencephalopathies.