Human Immunodeficiency Virus Arteriopathy of the Adult Cerebral Circulation

Military Medicine, Jun 2007 by Statler, John D, Slaughter, Ryan C, Ronsivalle, Joseph A

Arteriopathy associated with human immunodeficiency virus infection and clinical acquired immunodeficiency syndrome is well-documented. The pathophysiology of this arteriopathy may vary in different vascular beds. Although arteriopathy of central nervous system (CNS) circulation has been recognized in pediatric patients since the late 1980s, there are no reported cases of CNS arteriopathy in adults. We present the first reported case of adult CNS arteriopathy in a human immunodeficiency virus-positive patient who succumbed to complications secondary to diffuse aneurysmal disease of the Circle of Willis.

case Report

The patient was a 36-year-old African-American female with acquired immunodeficiency syndrome diagnosed 9 years before her presentation. At presentation, she had a CD4 count of 2 cells per cubic mm and blood viral load of 18,900 copies/cc. She had no personal or family history of cerebral aneurysm or connective tissue disease. Markers typically associated with systemic vasculitis such as anti-neutrophilic cytoplasmic antibodies were negative.

The day before admission, the patient presented to the emergency room with headache. She received pain medications and was discharged to her home. The day of admission, she was found awake, but unresponsive, by her son. Lumbar puncture in the emergency room revealed 305,000 red blood cells per cubic mm. Cerebrospinal fluid cultures obtained at the time were eventually negative for bacteria (including acid-fast organisms) and fungus. Computed tomography (CT) of the brain revealed blood in the subarachnoid space (Fig. 1).

On arrival to the angiography suite, she was awake and agitated. She could follow commands, but was unable to communicate. A four-vessel cerebral arteriogram revealed aneurysmal change in the Circle of Willis with aneurysm of the proximal right middle cerebral artery (Ml) segment, proximal left anterior cerebral artery (Ml) and Al segments, and aneurysmal change of the posterior cerebral arteries (Fig. 2).

The patient was transferred to the University Hospital for neurosurgical evaluation and neurological intensive care. While there, her neurological status improved and she was discharged to her home. She had persistent neurological deficits, with lethargy, headache, diminished strength, and poor mentation.

Two months after her initial presentation, she was readmitted with another episode of subarachnoid hemorrhage (Fig. 3). Her condition deteriorated over the next 4 days due to progressively increasing intracranial pressure. She suffered an uncal herniation and care was withdrawn on hospital day 4 after she was declared clinically brain dead. The family denied requests for a postmortem examination.

Discussion

Arteriopathy associated with human immunodeficiency virus (HIV) infection was first described in children in 1987.1 A dis ease of children and young adults with HIV, it was noted to involve multiple vascular beds, manifesting variably as necrotizing vasculitis with aneurysm formation, progressive granulomatous vasculitis, and arteritis with aortic occlusive disease.2 Although considered a late complication of HIV infection,3 arteriopathy has been reported in a neonate with HFV.4 While some investigators report an association with severity of disease as manifested by CD4 count,5 others report no such correlation.3�6

Histological changes observed in the coronary circulation included fibrosis, circumferential medial calcification, and proliferation of both elastic fibers and smooth muscle.5 Large vessels demonstrate medial hypertrophy and chronic inflammation of the vasa vasorum.5�7 There is some evidence that a specific HIV envelope protein may activate smooth muscle to express the glycoprotein tissue factor. This may mediate the inflammatory response to HIV infection, leading to aneurismal dilatation and thrombosis.8 Adult patients are noted to develop rapidly progressing plexogenic pulmonary hypertension and, less commonly, in situ pulmonary artery thrombosis or pulmonary veno-occlusive disease.6

HIV arteriopathy of the cerebral circulation has been welldescribed in p�diatrie patients.9�10 Histologie findings associated with aneurysmal arteriopathy include organizing thrombus, destruction of elastic lamina, and intimai fibroplasia. The arterial wall itself may stain positive for HIV.11 The exact pathophysiologic mechanism of cerebrovascular arteriopathy in the setting of HIV infection is not well-understood. Most investigators attribute HIV arteriopathy to changes associated with chronic inflammation, either from direct infection with HIV or from infection with opportunistic organisms.2�10 Once acquired, cerebrovascular HIV arteriopathy is uniformly fatal, with death often due to aneurysm rupture or stroke.10

It is unfortunate that we were unable to obtain autopsy data from this patient. Given her clinical course, and lack of other causes for vasculitis, HIV arteriopathy is the diagnosis of exclusion for her cerebrovascular disease. Despite its recognition in p�diatrie patients, cerebral HFV arteriopathy has not been described in adults. We speculate that cerebrovascular disease may be a manifestation of long-term HIV infection (our patient had been infected for over 9 years). Heretofore, adults infected with HIV may have succumbed to opportunistic infections long before manifesting cerebrovascular disease. As better antiretroviral regimens are developed, HIV arteriopathy of the adult cerebral circulation may become commonplace.