Tocilizumab reverses cerebral vasculopathy in a patient with homozygous SAMHD1 mutation

Abstract

An auto-inflammatory syndrome consequent to SAMHD1 mutations involves cerebral vasculopathy characterized by multifocal stenosis and aneurysms within large arteries, moyamoya, chronic ischemia, and early-onset strokes (SAMS). While this condition involves the innate immune system, additional clinical features mimic systemic lupus erythematosus. Mutations in this gene can also cause a subset of the rare genetic condition Aicardi-Goutières syndrome. To date, no established therapy successfully prevents disease progression. We report a corticosteroid-dependent SAMS patient, a 19-year-old male of Old Order Amish ancestry, with diffuse cerebral arteriopathy identified through contrast brain magnetic resonance arteriography (MRA) and MRI. He received subcutaneous adalimumab every 2 weeks for 9 months with minimal response. Then, he started intravenous tocilizumab (6 mg/kg/dose) every 4 weeks. He sustained steadily normalizing cerebral vasculopathy and lab abnormalities resolved, allowing prednisone reduction. We conclude that the cerebral vasculopathy of the homozygous SAMHD1 mutation-mediated auto-inflammatory disease SAMS responded favorably to tocilizumab infusion therapy.

Keywords: Aicardi-Goutières syndrome; Cerebral vasculopathy; Moyomoya; SAMHD1 mutation; Tocilizumab.

Fig. 1

Serial contrast magnetic resonance cerebral arteriography

Fig. 2

Treatment course