Widespread ischemic brain lesions caused by vasculopathy associated with neurofibromatosis type 1

We report the autopsy findings of a 63-year-old man with neurofibromatosis type 1 (NF1), in whom widespread ischemic brain lesions caused by vasculopathy associated with the disorder were observed. The patient, who had café au lait macules, axillary freckling, and neurofibromas, was inarticulate of speech, had difficulty in maintaining a sitting position, and was hyporeactive at the age of 57 years. He then developed autonomic dysfunction, followed by consciousness disturbance and status epilepticus. Repeated MRI studies disclosed multiple, ill-defined lesions in the brain and progressive cerebral atrophy. The histopathological features of the lesions were those of ischemia that had occurred with spatiotemporal variability in the brain. Characteristically, many arteries in the subarachnoid space manifested accumulation of cells in the intimal layer: this hyperplasia had resulted in narrowing and occlusion of the lumen. Immunoblotting demonstrated a marked decrease of neurofibromin, the NF1 product, which is known to act as a functional molecule in the normal process of vascular maintenance and repair. This case provides useful information about the pathomechanisms underlying central nervous system manifestations in patients with NF1.