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Stroke Caused by Human Immunodeficiency Virus–Associated Intracranial Large-Vessel Aneurysmal Vasculopathy
Brent Tipping, MBChB;
Linda de Villiers, MBChB;
Sally Candy, MBChB;
Helen Wainwright, MBChB
Arch Neurol. 2006;63:1640-1642.
ABSTRACT
Background Intracranial aneurysms related to human immunodeficiency virus (HIV) infection have been well described in pediatric patients but not in adults.
Objective To describe a case of intracranial large-vessel aneurysmal vasculopathy causing stroke in a 27-year-old HIV-infected woman.
Design Comparison of clinical and histological data with previously published cases.
Setting A referral hospital stroke unit.
Patient A 27-year-old HIV-infected woman presenting with stroke; neuroimaging demonstrated fusiform aneurysmal dilation of the left internal carotid and the left middle cerebral artery and its branches.
Results Autopsy showed degeneration of the elastic lamina, myxoid degeneration, and medial atrophy, causing consequent ectasia of the involved intracranial vessels.
Conclusion Aneurysmal dilation of the intracranial arteries occurs in HIV-infected adults, but the pathogenic role of HIV remains unknown.
INTRODUCTION
Human immunodeficiency virus (HIV) infection is associated with vascular disease and an increased incidence of stroke in adults.1 In addition, childhood HIV–associated intracranial aneurysmal vasculopathy has been described.2-16 This report describes an adult HIV-infected woman who had a cerebral infarct caused by aneurysmal dilatation of the arteries in the circle of Willis. To the best of our knowledge, this is the first description of HIV-associated intracranial aneurysmal vasculopathy in an adult with postmortem histopathology.
CASE REPORT
A 27-year-old woman with World Health Organization stage IV HIV infection17 and a CD4 count of 14 cells/µL presented with a right hemiparesis. Computed tomography with intravenous contrast (Figure 1A) showed an infarct of the left basal ganglia and fusiform dilation of the left middle and anterior cerebral arteries, as well as the distal basilar artery (Figure 1B). The extracranial carotid and vertebral arteries appeared normal on computed tomography angiography. Cerebrospinal fluid analysis showed a protein level of 1.0 g/L; cerebrospinal fluid glucose level of 41 mg/dL (2.3 mmol/L); blood glucose level of 72 mg/dL (4.0 mmol/L); 7 lymphocytes per cubic millimeter; 3 polymorphs per cubic millimeter; negative cryptococcal latex antigen fixation; negative rapid plasma reagin; and negative culture for bacteria, fungi, and tuberculosis.
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Figure 1. A, Contrast-enhanced computed tomography (CT) scan and 3-dimensional reconstruction (B) of the CT angiogram showing fusiform dilation of the left internal carotid artery, left anterior cerebral, and left middle cerebral artery (long arrows), as well as dilation of the tip of the basilar artery (short arrows).
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The patient died of bacterial pneumonia 25 days after her initial presentation.
Cranial autopsy examination showed fusiform dilation of the left internal carotid, and of the left middle cerebral artery and branches (Figure 2). Thrombus was present in the left middle cerebral artery, including the anterior branch. Histological examination of the left internal carotid and middle cerebral arteries showed luminal thrombosis, concentric intimal fibrosis with hyalinization, atrophic media, and fragmentation and thinning of the elastic lamina. Neutrophils were present on the luminal surface related to the thrombus (Figure 3). Arteries on the nonsymptomatic right side had thickened internal elastic lamina with fragmentation and focal intimal proliferation with calcification. The media was preserved. Alcian blue staining of vessels on the right as well as severely affected vessels on the left showed deposition of mucopolysaccharides in the intima and media of the arteries with splaying of the myocytes (Figure 4). No microorganisms or cytopathic changes were observed and immunoperoxidase stains showed moderate numbers of CD68 + macrophages and some CD3 + lymphocytes. Human immunodeficiency virus p24 antigen staining of the vessel sections was negative. Sections of the left caudate infarct showed liquefactive necrosis and perivascular chronic inflammation.
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Figure 2. Fusiform dilation of the left internal carotid and the left middle cerebral arteries and its branches (arrows).
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Figure 3. Microscopic examination of left internal carotid artery with intimal hyperplasia, luminal neutrophilic infiltrate, fibrosis, and thickened, beaded internal elastic lamina (arrow) with fragmentation (hematoxylin-eosin, original magnification x100).
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Figure 4. Microscopic examination of mucopolysaccharide deposition in the intima and media (arrow) with splaying of smooth muscle cells, medial atrophy, and fragmentation of the elastic lamina (Alcian blue, original magnification x100).
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COMMENT
Fusiform dilation of intracranial arteries has been described in HIV-positive children (32 cases)2-16 and in only 2 studies of HIV-positive adults (5 cases).18-19 Clinical manifestations varied from cerebral infarcts (14 children), transient ischemic attacks (2 adults), intracranial hemorrhages (5 children), subarachnoid hemorrhage (3 adults), seizures (3 children), and movement disorders (3 children). One study reports an incidence of fusiform intracranial artery dilation of 1.9% in 426 HIV-positive children.4
The pathogenesis of intracranial aneurysms in HIV infection is postulated to be caused by immune activation in response to transendothelial migration of HIV strains with tropism for cerebral mononuclear cells,9 and an alteration of dynamic vascular responsiveness to pulsatile blood flow regulated by alterations in circulating cytokines and growth factors leading to vascular remodelling.20 Opportunistic infections associated with HIV that are known to involve vessels—such as varicella-zoster virus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus, Treponema pallidum, Candida albicans, Cryptococcus neoformans, and Mycobacterium tuberculosis—may contribute to the production of these cytokines and growth factors.1 Repeated infections may contribute to an increase in elastases, leading to the fragmentation and thinning of the internal elastic lamina, an early histological finding in the development of fusiform aneurysms.6, 15 Although it was absent in our patient, HIV glycoprotein 41 has been demonstrated in mononuclear cells within the intima of aneurysmal intracranial arteries in 1 case.12 Extracranial aneurysms in HIV-positive patients are due to vasculitis of the vasa vasora, which are absent in the intracranial arteries, implying that the pathogenesis is different.21
The survival of patients with aneurysmal HIV-associated vasculopathy prior to the availability of highly active antiretroviral therapy was less than 1 year.5-7,12, 15-16 Stabilization of intracranial aneurysms has been reported in 3 patients after 4 months of highly active antiretroviral therapy,9, 17 and in 1 case of resolution after 15 months of highly active antiretroviral therapy.3 It remains to be seen whether highly active antiretroviral therapy will arrest progression or promote resolution of intracranial aneurysms in adults, thereby confirming the role of HIV in the pathogenesis of intracranial arterial aneurysm formation.
AUTHOR INFORMATION
Correspondence: Brent Tipping, MBChB, Institute of Ageing in Africa, Division of Geriatric Medicine, University of Cape Town, L51, Old Main Bldg, Groote Schuur Hospital, Observatory, 7925 Cape Town, South Africa (btipping{at}mweb.co.za).
Accepted for Publication: May 22, 2006.
Author Contributions: Study concept and design: Tipping and de Villiers. Acquisition of data: Tipping, Candy, and Wainwright. Analysis and interpretation of data: Tipping and Candy. Drafting of the manuscript: Tipping, de Villiers, Candy, and Wainwright. Critical revision of the manuscript for important intellectual content: de Villiers and Candy. Administrative, technical, and material support: Tipping. Study supervision: de Villiers and Candy. Microscopy: Wainwright.
Financial Disclosure: None reported.
Author Affiliations: Stroke Unit, Division of Geriatrics, Department of Medicine (Drs Tipping and de Villiers), and Departments of Radiology (Dr Candy) and Anatomical Pathology (Dr Wainwright), Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
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