A 26-year-old man of Portuguese descent with no significant past medical history presents with subacute onset of right-sided hemiparesis and aphasia, with marked expressive aphasia, word-finding difficulty, and rare paraphrasic errors.

Examination demonstrated right central facial weakness, 2–3/5 strength in the right arm and leg, and dysmetria in the right upper and lower extremities.

Reflexes were hyperactive on the right with a right-sided Babinski response.

MRI of the brain showed multiple bilateral concentric ring-like structures in the centrum semiovale and the corona radiata on T2 imaging (figure,A), consistent with the pattern of Balo concentric sclerosis.

There was associated restricted diffusion in 3 lesions and incomplete ring enhancement in 1 lesion.

CSF analysis showed 30 leukocytes (79% lymphocytes, 4% monocytes), erythrocyte count was 850, and oligoclonal bands were absent.

He was treated with 1 g of IV methylprednisolone daily for 5 days, with little improvement.

He then underwent 5 plasmapheresis exchanges, with significant improvement of motor, sensory, speech deficits, and gait.

Forty-five days after discharge, his examination showed 4+/5 strength in the right intrinsic muscles of the hand and a right-sided positional tremor.

Gait and tandem gait were normal.

He was placed on β-interferon-1a 44 μg subcutaneously 3 times a week, for treatment of presumed clinically isolated syndrome, with good response.

One year later, his neurologic examination was essentially normal.

There was no family history of demyelinating or autoimmune disorders.

His mother has a significant history of headaches and early-onset strokes, and was found to be a carrier of the Notch3 mutation consistent with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

His sister had a stroke in her 30s, and a history of migraine headaches, but has not undergone medical evaluation.

Testing for CADASIL in the patient showed the Notch3 mutation associated with CADASIL (transition C>T, nucleotide position 1750, codon 558).

Skin biopsy showed electron-dense extracellular material in close apposition to the smooth muscle of the vascular media1 (figure, B).