Amyloid beta-related angiitis--a case report and comprehensive review of literature of 94 cases.
Cerebral amyloid angiopathy (CAA) most frequently presents with recurrent intracerebral lobar hemorrhage in the elderly. There is, however, an important subset of patients who present instead with subacute cognitive decline, seizures, headaches and radiological as well as neuropathological evidence of CAA-associated perivascular inflammation [1, 2]. Here we report the first case of a patient with CAArelated vasculitis in which azathioprine has been associated with sustained clinical and radiological remission. A 70-year-old left-handed women with long-standing temporal lobe seizures presented with cognitive decline over 2 years. Examination revealed left homonymous hemianopia, gaze-evoked nystagmus, left upper limb ataxia and left-sided sensory inattention. She had difficulty following commands and her affect was altered. She scored 22/30 points on mini-mental state examination (MMSE). Brain MRI revealed a large area of increased T2 signal in the right hemisphere. An autoimmune screen, serum inflammatory markers and CSF analysis were unremarkable. EEG showed asymmetrical right-sided disorganization of background activity and mild slowing. Neuropathologic examination showed severe leptomeningeal and parenchymal amyloid angiopathy with evidence of predominately perivascular inflammation around the walls of many amyloid-laden blood vessels (Fig. 1). The patient was treated with a 5-day course of intravenous methylprednisolone (500 mg/day), which led to some improvement. MRI at 3 months showed improvement of the abnormalities in the right hemisphere, but repeat MRI at 9 months revealed progression of the white matter changes. Thirteen months after the initial presentation she noticed worsening visual problems as well as stiffness and weakness in her right leg. Her cognitive function had declined to 17/30 on MMSE. MRI showed clear disease progression (Fig. 2a–c). A second course of intravenous methylprednisolone resulted in symptomatic improvement. A further relapse at 15 months necessitated a third course of intravenous methylprednisolone. This led to a dramatic improvement in her walking and memory. At this point she was started on azathioprine, 75 mg once daily (lymphocyte counts maintained in the range of 0.8–1.1/ml). She remained neurologically stable with a partial resolution of her initial hemianopia. MRI 23 months after the initial presentation, when she had been on azathioprine for 8 months, confirmed partial resolution of the white-matter changes (Fig. 2d–f). At 25 months she was readmitted with a 2-week history of cognitive decline (MMSE 16/30), recurrence of her left hemianopia and left upper limb ataxia. It became clear that she had stopped taking her medication following the death of her husband 2 months earlier. Azathioprine treatment was reinstated and her symptoms started to improve again. At 45 months, 20 months after initiation of azathioprine, S. Luppe (&) N. Scolding A. Wilkins Department of Neurology, Frenchay Hospital, Bristol BS16 1LE, UK e-mail: Sebastian.Luppe@bristol.ac.uk