Niranjan N Singh, MD, DNB,
Assistant Professor of Neurology, University
of Missouri Columbia
Nothing to disclose.
Coauthor(s)
Florian P Thomas, MD, MA, PhD,
Drmed,,
Director, Spinal Cord Injury Service, St
Louis Veterans Affairs Medical Center; Director, National MS
Society Multiple Sclerosis Center; Director, Neuropathy
Association Center of Excellence, Professor, Department of
Neurology and Psychiatry, Associate Professor, Institute for
Molecular Virology, and Department of Molecular Microbiology
and Immunology, St Louis University
Nothing to disclose.
Specialty Editor(s)
Francisco Talavera, PharmD, PhD,
Senior Pharmacy Editor,
eMedicine
eMedicine Salary Employment
Howard S Kirshner, MD,
Professor of Neurology, Psychiatry and
Hearing and Speech Sciences, Vice Chairman, Department of
Neurology, Vanderbilt University School of Medicine;
Director, Vanderbilt Stroke Center; Program Director, Stroke
Service, Vanderbilt Stallworth Rehabilitation Hospital;
Consulting Staff, Department of Neurology, Nashville Veterans
Affairs Medical Center
BMS/Sanofi Honoraria Speaking and
teaching
Ronald A Greenfield, MD,
Professor, Department of Internal Medicine,
Section of Infectious Diseases, University of Oklahoma
College of Medicine
Pfizer Honoraria Speaking
and
teaching; Gilead Honoraria Speaking
and teaching; Ortho
McNeil Honoraria Speaking and
teaching; Wyeth Honoraria Speaking
and
teaching; Abbott Honoraria Speaking
and
teaching; Astellas Honoraria Speaking
and teaching; Cubist Speaking and
teaching
Selim R Benbadis, MD,
Professor, Director of Comprehensive Epilepsy
Program, Departments of Neurology and Neurosurgery,
University of South Florida School of Medicine, Tampa General
Hospital
Specific types of cerebrovascular disease are associated with HIV infection. In addition, with improved treatment and prolonged survival, more HIV-infected patients reach an older age and are at risk for cerebrovascular diseases unrelated to HIV infection. HIV-positive patients may suffer transient ischemic attacks (TIAs) or hemorrhagic, thrombotic, or embolic strokes.
AIDS seems to confer additional risk for ischemic and hemorrhagic stroke independent of other stroke-related risk factors. Some mechanisms responsible for strokes, both nonspecific and specific to HIV include hypertension, hypotension, cardiac disease, illicit drug use, coagulopathy, vasculitis (infectious, autoimmune), and hemorrhage (including hemorrhage into neoplasms and abscesses), but other mechanisms may be operative that are less well understood.
Premature atherosclerotic cerebral arteriopathy associated with HAART-induced metabolic disorders has become an additional risk factor in patients with AIDS.
Several studies have documented subclinical cervical artery atherosclerosis, as assessed by intima-media thickness, ultrasound detection of carotid artery plaques, and intracerebral small-vessel disease, all being associated with the induced metabolic changes.[1]
The incidence of stroke is approximately 0.5-7% of AIDS patients in clinical studies, but an 11-34% prevalence has been observed in autopsy studies. Thus, most lesions are apparently clinically silent. Most strokes in AIDS are occlusive; only about 1% are hemorrhagic.
Mortality/Morbidity
Stroke increases both morbidity and mortality in patients with HIV/AIDS. The degree of the increase is related to the specific type of cerebrovascular disease encountered and to the stage of HIV infection.
Age
HIV-positive patients are at risk for strokes at much younger ages than typically are associated with stroke. As in the HIV-seronegative population, age itself is a risk factor for stroke in HIV-infected individuals.
Cerebrovascular events are defined by the abrupt onset of a focal neurological deficit in an awake patient. The exact time course and symptoms are dependent on the location and nature of the cerebrovascular disorder (ie, TIA vs hemorrhagic stroke vs occlusive stroke) as well as the patient's underlying condition.
The physical examination of the patient with HIV and cerebrovascular disease usually reveals a focal neurological deficit in addition to the stigmata of HIV itself.
Causes of stroke not related to HIV are those seen in the general population, including atherosclerosis of large arteries with resultant TIA and stroke; hypertensive small-vessel disease with lacunar strokes; and hemorrhage secondary to hypertension, aneurysm, or arteriovenous malformations.
In a population-based retrospective study of the pathomechanisms of stroke among 82 HIV-seropositive patients, cardioembolism and small vessel disease accounted for 18% each, followed by large vessel disease (12%), vasculitis (13%) and hypercoagulability (9%).[2]
Causes of cerebrovascular disorders specific to HIV are numerous and variable.
Hypertension due to HIV nephropathy can lead to hypertensive intraparenchymal hemorrhage or to lacunar infarctions, just as in HIV-seronegative patients.
Hypotension in severely ill patients (eg, septic shock) can lead to hypotensive encephalopathy or watershed infarctions. Cachexia and dehydration also can cause hypotension.
Coagulopathies are common in HIV infection and can lead to occlusive strokes and intracerebral or subarachnoid hemorrhage.
Disease mechanisms include autoimmunity (eg, lupus anticoagulant, anticardiolipin antibodies), which can predispose patients to thromboembolic events.
Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation have been described.
Acquired antithrombin III and protein S and C deficiencies occur.
Hyperviscosity (eg, secondary to dehydration)
Infectious causes include hepatitis, commonly associated with HIV infection, which can impair coagulation.
Mycotic aneurysms are associated with infectious endocarditis. These can cause focal intracerebral or subarachnoid hemorrhages.
Specific forms of heart disease have been implicated in the pathogenesis of HIV-associated cerebrovascular disease. These include infectious myocarditis due to cytomegalovirus (CMV), fungi, bacteria, or toxoplasmosis; lymphocytic endocarditis; and, most commonly, marantic endocarditis. Endocarditis can result in embolic strokes with ischemic infarctions, seed infectious organisms, or lead to strokes by causing secondary hypotension.
Several types of cerebral vasculitis cause strokes in patients with HIV.
Fungi (cryptococcosis, candidiasis, aspergillosis), bacteria (syphilis, tuberculosis), viruses (CMV, varicella-zoster), and parasites (toxoplasmosis) are associated with vasculitis. Herpes zoster must be considered even in the absence of a rash (zoster sine herpete).
For some forms, no cause is identified. These cases may still be autoimmune. Histological features include granulomas, necrosis, eosinophilic infiltrates, and intimal hyperplasia.
Radiation therapy of CNS lymphoma can result in vasculopathy that can mimic an inflammatory vasculitis.
HIV-associated intracranial aneurysmal vasculopathy has been described.
The most common presentations include ischemic stroke, intracranial hemorrhage, and seizures.
Both cocaine and heroin can cause cerebrovascular disease via multiple mechanisms in addition to the infectious causes associated with drug use.
Cocaine may lead to hypertension with hemorrhage, or to vasospasm and ischemic stroke after parenteral or nonparenteral use.
Heroin can cause a vasculitis. Furthermore, nonsoluble contaminants of the drug can occlude blood vessels.
Intraparenchymal mass lesions, such as a neoplasm (Kaposi sarcoma) or infection (toxoplasmosis), can predispose to hemorrhagic strokes.
HIV infection itself may be associated with a primary vasculopathy, although only preliminary evidence exists.
CT and MRI are useful in detecting ischemic infarctions or hemorrhages into the brain parenchyma or subarachnoid space. Imaging studies often reveal evidence of clinically silent cerebrovascular disease.
MRI is superior to CT for most varieties of cerebrovascular disease, except for detection of subarachnoid hemorrhage. Diffusion- and perfusion-weighted MRI permit early identification of ischemic strokes.
Magnetic resonance angiography (MRA) is useful in detecting stenosis or occlusion in cervical or intracranial vessels as well as venous sinus thrombosis.
CT-guided angiography is an alternative to MRA but requires a helical (spiral) CT.
Doppler ultrasonography of the carotid vessels or transcranial Doppler of intracranial vessels can be performed as a less expensive alternative to MRA- or CT-guided angiography.
Cerebral angiography may be indicated in cases of suspected CNS vasculitis or aneurysm.
Echocardiography, especially via the transesophageal approach, is useful in detecting cardiac sources of cerebral emboli and infections, such as dilated cardiomyopathy, endocarditis, and other non–HIV-related causes.
Lumbar puncture (LP) with cerebrospinal fluid (CSF) analysis should be performed, if deemed safe and if subarachnoid hemorrhage or infection is a consideration.
Management of cerebrovascular disease in the HIV-positive patient is complex. In many cases, the treatments parallel those given for stroke in the non–HIV-positive population. Examples include the following:
Anticoagulation for patients with antiphospholipid antibodies or confirmed cardiac sources of embolization
Antiplatelet agents such as aspirin or clopidogrel for small vessel infarctions
Antibiotics for endocarditis or neurosyphilis
Highly active antiretroviral treatment (HAART) (Stabilization and even resolution of HIV-associated cerebral aneurysm have been demonstrated.)
Coordination of care with the primary care physician and an infectious disease specialist
Carotid endarterectomy may be indicated in patients with symptomatic narrowing of the internal carotid artery. Given the young age of most HIV-positive patients, this is an infrequent occurrence.
Occasionally, surgery may be indicated to evacuate intracerebral hematomas, clip an aneurysm, or remove an arteriovenous malformation.
Once the acute medical management of the stroke has been completed, rehabilitation treatment should be initiated. Referral to a rehabilitation hospital, skilled nursing facility, or outpatient or home health therapist should be coordinated either by the neurologist or by a physical medicine consultant.
Consideration of appropriate drug therapy, whether anticoagulant or antiplatelet drugs, antibiotics, or other medications, would depend on the cause of the stroke (see Clinical and Treatment).
In HIV-positive patients, even more than in other patients with stroke, treating the underlying disease, both HIV itself and any intercurrent infections or neoplasms that may be responsible for the cerebrovascular event, is essential.
Once the acute treatments are given and rehabilitation has begun, the neurologist should ensure that the patient has been placed on preventive treatments to reduce the risk of recurrent strokes.
