Amyloid Angiopathy

To the Editor: The recent article by Fountain and Eberhard ^[1] discusses the association, in some patients, between granulomatous angiitis of the CNS (GANS) and CAA. These authors suggest that symptoms may reflect the presence of the angiitis in this setting and that steroid treatment may be beneficial in treating the angiitis and ameliorating the symptoms. This opinion is supported by the case described below.

This case has been reported on two previous occasions as simply a case of granulomatous angiitis with cerebral hemorrhage. ^[6,7] The case was of interest because the patient's history supported an association between the varicella virus and GANS and because the patient's symptoms waxed and waned in parallel with the institution, tapering and reinstitution of steroid therapy. ^[6,7] This led to the suggestion that prednisone was appropriate therapy for GANS.

The original histopathologic description of the patient's disease ^[1] was based on a brain biopsy of a lesion for which a preoperative diagnosis of tumor was considered. This biopsy was performed over 17 years ago, a time preceding the great interest in CAA. The patient died of a cerebral hemorrhage 15 years later, having been placed on maintenance prednisone ^[7] for that entire period. Examination of over 24 samples of cerebral hemisphere obtained at autopsy, as well as samples of brainstem and cerebellum, failed to reveal even the suggestion of an inflammatory process. But I was immediately struck by the widespread CAA, an impression confirmed by green birefringence of the Congo Redstained slides.

Samples were sent to David Nochlin, MD, at the University of Washington (Seattle, WA) for immunohistochemistry, and the affected vessels were shown to be strongly positive for beta/A₄ amyloid. There were insufficient numbers of senile plaques or neurofibrillary tangles to suggest Alzheimer's disease. Review of the material from the 15-year-old biopsy also showed marked CAA, a finding originally overlooked. The amyloid in the biopsy contained beta/A₄, but none of the giant cells in the inflammatory response contained beta/A₄.

Like Fountain and Eberhard, we do not know whether GANS and CAA are unrelated or whether GANS is an inflammatory response to the beta/A₄. In either event, this case provides not only "anecdotal" clinical evidence ^[6,7] of the benefits of steroids in at least one variant of GANS but histologic proof at autopsy that the inflammatory response was totally suppressed by the steroids. The CAA remained, and after 15 years the patient clearly died as a result of hemorrhage from that disease. Nevertheless, the histology of the biopsy and the parallel ^[6,7] between periods of exacerbation and reduction of sterodis suggests that if GANS can be caused by beta/A₄, the GANS itself may be responsible for lesions and symptoms that can be held in check and reversed by prednisone.

William I. Rosenblum, MD

Richmond, VA