AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

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.

Pathophysiology

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.

Frequency

United States

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.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

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.

Physical

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

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%).¹

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Brainstem syndromes
Mitochondrial cytopathies
Vascular dementia

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• As for any stroke patient, the clinician must consider the mechanisms of stroke that are most likely and obtain the appropriate diagnostic tests.
• Blood tests
• • CBC with platelet count
  • Erythrocyte sedimentation rate (ESR)
  • Anticardiolipin antibody and lupus anticoagulant
  • Serology for specific infections
  • Blood cultures
  • Coagulation studies, including antithrombin III and protein S and C levels
  • Urine toxicology

Imaging Studies

• 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.

Other Tests

• Other tests may be appropriate for specific types of cerebrovascular disease.

Procedures

• 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.

Histologic Findings

Autopsies often reveal evidence of clinically silent cerebrovascular disease.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

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

Surgical Care

• 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.

Consultations

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.

Activity

Activity depends on severity of the neurological deficit.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• 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.

Further Outpatient Care

• Rehabilitative care often must be continued after discharge.

Prognosis

• Prognosis in an HIV-positive patient with stroke is dependent on severity of the cerebrovascular event and stage of HIV infection.

Patient Education

• For excellent patient education resources, visit eMedicine's Immune System Center and Sexually Transmitted Diseases Center. Also, see eMedicine's patient education article HIV/AIDS.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize and intervene in potentially treatable conditions such as procoagulatory states, bleeding diathesis, or aneurysmal bleeds would constitute a significant deviation from the standard of care.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Ortiz G, Koch S, Romano JG, Forteza AM, Rabinstein AA. Mechanisms of ischemic stroke in HIV-infected patients. Neurology. Apr 17 2007;68(16):1257-61. [Medline].
2. American Academy of Neurology. Evaluation and management of intracranial mass lesions in AIDS. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Jan 1998;50(1):21-6. [Medline].
3. Berger JR, Harris JO, Gregorios J. Cerebrovascular disease in AIDS: a case-control study. AIDS. Mar 1990;4(3):239-44. [Medline].
4. Calabrese LH, Furlan AJ, Gragg LA. Primary angiitis of the central nervous system: diagnostic criteria and clinical approach. Cleve Clin J Med. May-Jun 1992;59(3):293-306. [Medline].
5. Cole JW, Pinto AN, Hebel JR, et al. Acquired immunodeficiency syndrome and the risk of stroke. Stroke. Jan 2004;35(1):51-6. [Medline].
6. Connor MD, Lammie GA, Bell JE, et al. Cerebral infarction in adult AIDS patients: observations from the Edinburgh HIV Autopsy Cohort. Stroke. Sep 2000;31(9):2117-26. [Medline].
7. de Gans J, Portegies P. Neurological complications of infection with human immunodeficiency virus type 1. A review of literature and 241 cases. Clin Neurol Neurosurg. 1989;91(3):199-219. [Medline].
8. Engstrom JW, Lowenstein DH, Bredesen DE. Cerebral infarctions and transient neurologic deficits associated with acquired immunodeficiency syndrome. Am J Med. May 1989;86(5):528-32. [Medline].
9. Gendelman HE, Lipton SA, Epstein L. The Neurology of AIDS. NY: Chapman & Hall; 1998.
10. Gillams AR, Allen E, Hrieb K. Cerebral infarction in patients with AIDS. AJNR Am J Neuroradiol. Sep 1997;18(8):1581-5. [Medline].
11. Keeling DM, Birley H, Machin SJ. Multiple transient ischaemic attacks and a mild thrombotic stroke in a HIV-positive patient with anticardiolipin antibodies. Blood Coagul Fibrinolysis. Aug 1990;1(3):333-5. [Medline].
12. Kieburtz KD, Eskin TA, Ketonen L. Opportunistic cerebral vasculopathy and stroke in patients with the acquired immunodeficiency syndrome. Arch Neurol. Apr 1993;50(4):430-2. [Medline].
13. Kumwenda JJ, Mateyu G, Kampondeni S, et al. Differential diagnosis of stroke in a setting of high HIV prevalence in Blantyre, Malawi. Stroke. May 2005;36(5):960-4. [Medline].
14. Pinto AN. AIDS and cerebrovascular disease. Stroke. Mar 1996;27(3):538-43. [Medline].
15. Roquer J, Palomeras E, Knobel H. Intracerebral haemorrhage in AIDS. Cerebrovasc Dis. Jul-Aug 1998;8(4):222-7. [Medline].
16. Said G, Saimont AG, Lacroix C. Neurological complications of HIV and AIDS. Philadelphia: WB Saunders Co; 1998.
17. Tipping B, de Villiers L, Candy S, Wainwright H. Stroke caused by human immunodeficiency virus-associated intracranial large-vessel aneurysmal vasculopathy. Arch Neurol. Nov 2006;63(11):1640-2. [Medline].
18. Woods GL, Goldsmith JC. Aspergillus infection of the central nervous system in patients with acquired immunodeficiency syndrome. Arch Neurol. Feb 1990;47(2):181-4. [Medline].

Article Last Updated: Aug 28, 2007