Contributed by Zhongchuan Will Chen, MDCM*, Sean P Symons, MD**, Beverley Young, RTC*, Juan M. Bilbao, MD*
*Department of Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario
**Department of Radiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario.
A 24-year-old Caucasian man was admitted following a 10-day history of severe headache leading to collapse on the street. On presentation, he was confused and agitated with left-sided weakness and a positive left Babinski sign. His medical history was significant for asthma and non-Hodgkin's lymphoma 10 years previously treated with chemotherapy and radiation therapy with no recurrence.
Routine bloodwork, hypercoagulability and autoimmune workups including anti-neutrophil cytoplasmic antibodies were all normal. Serology was negative for Arbovirus, Bartonella, Cryptococcus and the hepatitides. Consent for HIV testing was not obtained. Blood, cerebrospinal fluid and urine cultures were all negative. Blood and urine toxicological screening was unremarkable.
CT perfusion suggested ischemia in both middle cerebral artery (MCA) and left anterior cerebral artery (ACA) territories and infarction in the left posterior cerebral artery (PCA) territory. CT angiography showed filling defects in these territories as well (Figures 1, 2, 3). Treatment with intravenous tissue plasminogen activator (TPA) and intra-arterial thrombolysis was attempted. Initial anteroposterior angiogram confirmed occlusion of the right distal M1 MCA and left A2 ACA (Figure 4). Mechanical thrombolysis and 4mg of intra-arterial TPA were unsuccessful in reopening the right MCA. The patient deteriorated and was declared brain dead 31 hours after arrival to hospital.
On post-mortem examination, the fresh brain weighed 1560g and showed oedema with bilateral transtentorial herniation and cerebellar protrusion. Coronal sections showed thromboembolic occlusion of both ACAs beyond their A2 segments and the left MCA from its origin to its bifurcation (Figure 5). All posterior fossa vessels were normal. Both common carotid and internal carotid arteries were patent, but the right external carotid artery appeared thickened with a reduced lumen. Gross examination of the remainder of the body was unremarkable.
HPS-stained permanent sections of the M1 and M2 segments of both MCAs, both ACAs beyond the anterior communicating artery and the left P2 PCA demonstrated a circumferential arteritic process composed of multi-nucleated giant cells, lymphocytes and histiocytes concentrated in the intima with fragmentation of the elastica interna (representative section; Figure 6). Elastica interna fragmentation by invading giant cells was highlighted by Elastic Van Gieson staining (Figure 7). CD68 staining revealed a sandwich-like pattern of immunoreactive cells in the intima and adventitia with relative sparing of the media (Figure 8). A CD4/CD8-positive lymphocytic and mononuclear cell infiltrate was present in the adventitia (CD4, Figure 9; CD8, Figure 10). Recent thrombosis in affected vessels caused varying degrees of corresponding neuronal ischemic change. There was no evidence of fibrinoid necrosis or previous healing lesions, but a small focus of non-fibrinoid necrosis was present. Sizes of vessels affected ranged from 2.0-3.5mm in diameter. Smaller vessels on the brain surface and the vertebrobasilar arteries were unaffected. Congo red, β-amyloid, Ziehl-Neelsen and PAS-D stains and in-situ hybridization for varicella-zoster virus were negative. Extracranially, patchy, non-thrombotic areas of a similar arteritic process involving giant cells were noted in both carotid siphons (HPS; Figure 11) and the initial segment of one renal artery (H&E; Figure 12). No other arteries or organs examined were involved.