Describe the presentation of refractory amyloid β-related angiitis (ABRA) and response to cyclophosphamide and tocilizumab.

Retrospective chart review of single patient’s brain MRI, clinical course, neuropathology, and medical management.

A 70-year-old female presented with first-time seizure and subacute cognitive changes with imaging showing diffuse T2/FLAIR hyperintensities, cortical microhemorrhages, and no infarction. Despite high-dose glucocorticoids and a prednisone taper, interval brain MRIs showed interval vasogenic edema, accrual of microhemorrhages, new leptomeningeal enhancement, and uncal and subfalcine herniation. Brain biopsy confirmed ABRA. The vasogenic edema was refractory to steroids, maximal hyperosmolar therapy, and cyclophosphamide. Tocilizumab, an IL-6 receptor antagonist, administration led to rapid reduction in edema and improvement in her left sided hemiparesis.

We describe the first case to our knowledge of steroid refractory ABRA responsive to tocilizumab. ABRA is a rare CNS vasculitis caused by an inflammatory reaction to intravascular amyloid deposition. There is debate on whether ABRA and cerebral amyloid angiopathy-related inflammation (CAA-ri) exist on a spectrum of amyloid-related neuroinflammatory disorders or are distinct entities. We highlight their pathologic differences, as ABRA involves transmural inflammation of the vessel wall, while CAA-ri involves perivascular inflammation with vessel wall destruction. The precipitous progression of cortical microhemorrhages may indicate a key pathophysiologic difference between the two related disease entities. Future prospective studies are needed to investigate clinic-radiologic differences between ABRA and CAA-ri, as well as the safety, tolerability, and efficacy of IL-6 receptor blockade in addressing acute, steroid-refractory inflammation.