Subarachnoid hemorrhage and diffuse vasculopathy in an adult infected with HIV

Case report

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✓This 34-year-old man with a 10-year history of HIV infection presented with an acute onset of severe headache, fever, nausea, vomiting, and left-sided weakness. Computed tomography (CT) scanning demonstrated diffuse subarachnoid hemorrhage (SAH), and subsequent CT angiography revealed multiple large and giant intracranial aneurysms with diffuse vasculopathy. The patient's CD4-positive cell count was low, although he had been receiving combination antiret-roviral therapy and his viral load was undetectable.

The preponderance of the literature on HIV-infected patients with intracranial vascular involvement has concerned children in whom there is a high viral load. In such children, appropriate antiretroviral therapy may result in the complete resolution of these vascular abnormalities. In the present study, the authors report on the unique case of an HIV-infected adult patient who presented with SAH, diffuse intracranial vasculopathy, and multiple giant and fusiform aneurysms, despite having received adequate antiretroviral treatment and demonstrating an undetectable viral load. Intracranial vascular involvement in these patients may become increasingly common as the management of HIV infection continues to improve and afflicted patients survive for longer periods.

Abbreviations used in this paper:CT = computed tomography; SAH = subarachnoid hemorrhage.

Abstract

✓This 34-year-old man with a 10-year history of HIV infection presented with an acute onset of severe headache, fever, nausea, vomiting, and left-sided weakness. Computed tomography (CT) scanning demonstrated diffuse subarachnoid hemorrhage (SAH), and subsequent CT angiography revealed multiple large and giant intracranial aneurysms with diffuse vasculopathy. The patient's CD4-positive cell count was low, although he had been receiving combination antiret-roviral therapy and his viral load was undetectable.

The preponderance of the literature on HIV-infected patients with intracranial vascular involvement has concerned children in whom there is a high viral load. In such children, appropriate antiretroviral therapy may result in the complete resolution of these vascular abnormalities. In the present study, the authors report on the unique case of an HIV-infected adult patient who presented with SAH, diffuse intracranial vasculopathy, and multiple giant and fusiform aneurysms, despite having received adequate antiretroviral treatment and demonstrating an undetectable viral load. Intracranial vascular involvement in these patients may become increasingly common as the management of HIV infection continues to improve and afflicted patients survive for longer periods.

As a result of great improvements in medical therapy, new complications are increasingly being detected in patients with HIV and/or AIDS. The occurrence of cerebral aneurysms in HIV-infected children has been well-documented,2–6,8,10,11,13–17,19 and there appears to be a high proportion of fusiform aneurysms in this population. Aneurysms in children with HIV may improve or even resolve in response to appropriate antiretroviral therapy.13 Intracranial aneurysms have rarely been reported in adult patients with HIV.12 The cases that have been reported have largely consisted of patients harboring berry aneurysms. In the present report, we discuss the unique case of a patient with HIV infection in whom SAH, diffuse intracranial vas-culopathy, and multiple giant and fusiform aneurysms developed, despite his having received such effective antiret-roviral treatment that his viral load was undetectable.

Case Report

This 34-year-old man with a 10-year history of HIV infection presented to our institution after the acute onset of severe headache, fever, nausea, vomiting, and left-sided weakness. He had been treated with lamivudine, nevirapine, and nelfinavir mesylate over the previous 6 months and this regimen had rendered his viral load undetectable. However, he had a CD4-positive cell count of 66/μl (reference range 400–1500/μl). His medical history was significant for end-stage renal disease and severe cardiomyopathy (ejection fraction 20%). During the neurological examination a mild left hemiparesis was demonstrated. An unenhanced CT scan showed diffuse SAH (Fig. 1), and subsequent CT angiography revealed diffuse vasculopathy with vessel irregularity and multiple fusiform and giant saccular aneurysms (Fig. 2).

Fig. 1.
Fig. 1.

Unenhanced CT images of the head showing diffuse SAH. Within the subarachnoid clot, there appears to be negative filling defects suggesting multiple aneurysms of the circle of Willis.

Fig. 2.
Fig. 2.

Three-dimensional reconstructions of the CT angiogram. A: Posterior view demonstrating a diffuse irregularity of the basilar artery trunk with multiple areas of vessel wall dilation. Note the absence of the left P1 segment (as there is a fetal origin of the left posterior cerebral artery) and the fusiform appearance of the right posterior cerebral artery. B: Right lateral view revealing fusiform dilations of the right cavernous, supraclinoid, anterior cerebral, and middle cerebral arteries. The right internal carotid artery (RICA) bifurcation and giant anterior communicating artery aneurysms are visualized, and involvement of the left supraclinoid carotid artery can be seen in the background. C: Posterior and superior views showing fusiform dilations of both supraclinoid carotid arteries, anterior cerebral arteries, and middle cerebral arteries, and the left posterior cerebral artery, a giant anterior communicating artery aneurysm, and a giant right carotid artery bifurcation aneurysm. RT-PCOM = right posterior communicating artery.

The patient's intracranial vascular disease was not deemed amenable either to microsurgical or endovascular intervention. He was treated conservatively and discharged from the hospital after 7 days.

Discussion

In the present study, we document diffuse vasculopathy involving all major cerebral vessels with the development of multiple fusiform and giant intracranial aneurysms in an HIV-infected adult despite an undetectable viral load and long-term treatment with a multidrug antiretroviral therapy regimen.

Intracranial vascular abnormalities including aneurysms are well established in children infected with HIV.2–6,8,10,11,13–17,19 Saccular and/or fusiform aneurysms have been reported in these cases, usually in association with a high viral load.14 Vascular abnormalities under these conditions may completely resolve with appropriate antiretroviral therapy.13

Although multiple cases of isolated saccular aneurysms have been reported in the HIV-infected adult population,12 diffuse arterial involvement with multiple intracranial aneurysms has not been clearly described previously. Berkefeld and colleagues1 described two adult patients who presented with ischemia and apparent intracranial vasculitis (with aneurysmal dilation). The vasculitis appeared to improve with antiviral and corticosteroid therapy.

Presently, the mechanism by which HIV infection contributes to aneurysm formation is unclear. The HIV itself may cause the damage; however, viral proteins or toxic factors may also contribute.7,9,18 A destructive proliferative process associated with panarteritis and involvement of the vasa vasorum has been postulated and supported by autopsy findings.19 Alternatively, bacterial infection of the blood vessel wall in the setting of immunosuppression may lead to the development of aneurysms or other vasculopathy.3,20

As the medical management and overall survival of patients with HIV infection continues to improve, further investigation into the association of HIV infection with intracranial vasculopathy and aneurysms will be important as these challenging sequelae are increasingly encountered.

References

  • 1

    Berkefeld JEnzensberger WLanfermann H: MRI in human immunodeficiency virus-associated cerebral vasculitis. Neuroradiology 42:5265282000

  • 2

    Bonkowsky JLChristenson JCNixon GWPavia AT: Cerebral aneurysms in a child with acquired immune deficiency syndrome during rapid immune reconstitution. J Child Neurol 17:4574602002

  • 3

    Bulsara KRRaja AOwen J: HIV and cerebral aneurysms. Neurosurg Rev 28:92952005

  • 4

    Dubrovsky TCurless RScott GChaneles MPost MJAltman N: Cerebral aneurysmal arteriopathy in childhood AIDS. Neurology 51:5605651998

  • 5

    Elfenbein DSEmmanuel PJ: Radiological case of the month. Aneurysmal dilation of cerebral arteries associated with HIV infection. Arch Pediatr Adolesc Med 155:8498502001

  • 6

    Fulmer BBDillard SCMusulman EMPalmer CAOakes J: Two cases of cerebral aneurysms in HIV+ children. Pediatr Neurosurg 28:31341998

  • 7

    Gavin PYogev R: Central nervous system abnormalities in pediatric human immunodeficiency virus infection. Pediatr Neurosurg 31:1151231999

  • 8

    Husson RNSaini RLewis LLButler KMPatronas NPizzo PA: Cerebral artery aneurysms in children infected with human immunodeficiency virus. J Pediatr 121:9279301992

  • 9

    Kanmogne GDKennedy RCGrammas P: HIV-1 gp120 proteins and gp160 peptides are toxic to brain endothelial cells and neurons: possible pathway for HIV entry into the brain and HIV-associated dementia. J Neuropathol Exp Neurol 61:99210002002

  • 10

    Kure KPark YDKim TSLyman WDLantos GLee S: Immunohistochemical localization of an HIV epitope in cerebral aneurysmal arteriopathy in pediatric acquired immunodeficiency syndrome (AIDS). Pediatr Pathol 9:6556671989

  • 11

    Lang CJacobi GKreuz WHacker HHerrmann GKeul HG: Rapid development of giant aneurysm at the base of the brain in an 8-year-old boy with perinatal HIV infection. Acta Histochem Suppl 42:83901992

  • 12

    Maniker AHHunt CD: Cerebral aneurysm in the HIV patient: a report of six cases. Surg Neurol 46:49541996

  • 13

    Martinez-Longoria CAMorales-Aguirre JJVillalobos-Acosta CPGomez-Barreto DCashat-Cruz M: Occurrence of intracerebral aneurysm in an HIV-infected child: a case report. Pediatr Neurol 31:1301322004

  • 14

    Mazzoni PChiriboga CAMillar WSRogers A: Intracerebral aneurysms in human immunodeficiency virus infection: case report and literature review. Pediatr Neurol 23:2522552000

  • 15

    Nunes MLPinho APSfoggia A: Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV infection and HSV encephalitis. Arq Neuropsiquiatr 59:1161182001

  • 16

    Patsalides ADWood LVAtac GKSandifer EButman JAPatronas NJ: Cerebrovascular disease in HIV-infected pediatric patients: neuroimaging findings. AJR Am J Roentgenol 179:99910032002

  • 17

    Petropoulou FMostrou GPapaevangelou VTheodoridou M: Central nervous system aneurysms in childhood AIDS. AIDS 17:2732752003

  • 18

    Ren ZYao QChen C: HIV-1 envelope glycoprotein 120 increases intercellular adhesion molecule-1 expression by human endothelial cells. Lab Invest 82:2452552002

  • 19

    Shah SSZimmerman RARorke LBVezina LG: Cerebrovascular complications of HIV in children. AJNR Am J Neuroradiol 17:191319171996

  • 20

    Sinzobahamvya NKalangu KHamel-Kalinowski W: Arterial aneurysms associated with human immunodeficiency virus (HIV) infection. Acta Chir Belg 89:1851881989

Article Information

Address reprint requests to: Aaron S. Dumont, M.D., Box 800212, Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia 22908. email: asd2f@virginia.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Unenhanced CT images of the head showing diffuse SAH. Within the subarachnoid clot, there appears to be negative filling defects suggesting multiple aneurysms of the circle of Willis.

  • View in gallery

    Three-dimensional reconstructions of the CT angiogram. A: Posterior view demonstrating a diffuse irregularity of the basilar artery trunk with multiple areas of vessel wall dilation. Note the absence of the left P1 segment (as there is a fetal origin of the left posterior cerebral artery) and the fusiform appearance of the right posterior cerebral artery. B: Right lateral view revealing fusiform dilations of the right cavernous, supraclinoid, anterior cerebral, and middle cerebral arteries. The right internal carotid artery (RICA) bifurcation and giant anterior communicating artery aneurysms are visualized, and involvement of the left supraclinoid carotid artery can be seen in the background. C: Posterior and superior views showing fusiform dilations of both supraclinoid carotid arteries, anterior cerebral arteries, and middle cerebral arteries, and the left posterior cerebral artery, a giant anterior communicating artery aneurysm, and a giant right carotid artery bifurcation aneurysm. RT-PCOM = right posterior communicating artery.

References

1

Berkefeld JEnzensberger WLanfermann H: MRI in human immunodeficiency virus-associated cerebral vasculitis. Neuroradiology 42:5265282000

2

Bonkowsky JLChristenson JCNixon GWPavia AT: Cerebral aneurysms in a child with acquired immune deficiency syndrome during rapid immune reconstitution. J Child Neurol 17:4574602002

3

Bulsara KRRaja AOwen J: HIV and cerebral aneurysms. Neurosurg Rev 28:92952005

4

Dubrovsky TCurless RScott GChaneles MPost MJAltman N: Cerebral aneurysmal arteriopathy in childhood AIDS. Neurology 51:5605651998

5

Elfenbein DSEmmanuel PJ: Radiological case of the month. Aneurysmal dilation of cerebral arteries associated with HIV infection. Arch Pediatr Adolesc Med 155:8498502001

6

Fulmer BBDillard SCMusulman EMPalmer CAOakes J: Two cases of cerebral aneurysms in HIV+ children. Pediatr Neurosurg 28:31341998

7

Gavin PYogev R: Central nervous system abnormalities in pediatric human immunodeficiency virus infection. Pediatr Neurosurg 31:1151231999

8

Husson RNSaini RLewis LLButler KMPatronas NPizzo PA: Cerebral artery aneurysms in children infected with human immunodeficiency virus. J Pediatr 121:9279301992

9

Kanmogne GDKennedy RCGrammas P: HIV-1 gp120 proteins and gp160 peptides are toxic to brain endothelial cells and neurons: possible pathway for HIV entry into the brain and HIV-associated dementia. J Neuropathol Exp Neurol 61:99210002002

10

Kure KPark YDKim TSLyman WDLantos GLee S: Immunohistochemical localization of an HIV epitope in cerebral aneurysmal arteriopathy in pediatric acquired immunodeficiency syndrome (AIDS). Pediatr Pathol 9:6556671989

11

Lang CJacobi GKreuz WHacker HHerrmann GKeul HG: Rapid development of giant aneurysm at the base of the brain in an 8-year-old boy with perinatal HIV infection. Acta Histochem Suppl 42:83901992

12

Maniker AHHunt CD: Cerebral aneurysm in the HIV patient: a report of six cases. Surg Neurol 46:49541996

13

Martinez-Longoria CAMorales-Aguirre JJVillalobos-Acosta CPGomez-Barreto DCashat-Cruz M: Occurrence of intracerebral aneurysm in an HIV-infected child: a case report. Pediatr Neurol 31:1301322004

14

Mazzoni PChiriboga CAMillar WSRogers A: Intracerebral aneurysms in human immunodeficiency virus infection: case report and literature review. Pediatr Neurol 23:2522552000

15

Nunes MLPinho APSfoggia A: Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV infection and HSV encephalitis. Arq Neuropsiquiatr 59:1161182001

16

Patsalides ADWood LVAtac GKSandifer EButman JAPatronas NJ: Cerebrovascular disease in HIV-infected pediatric patients: neuroimaging findings. AJR Am J Roentgenol 179:99910032002

17

Petropoulou FMostrou GPapaevangelou VTheodoridou M: Central nervous system aneurysms in childhood AIDS. AIDS 17:2732752003

18

Ren ZYao QChen C: HIV-1 envelope glycoprotein 120 increases intercellular adhesion molecule-1 expression by human endothelial cells. Lab Invest 82:2452552002

19

Shah SSZimmerman RARorke LBVezina LG: Cerebrovascular complications of HIV in children. AJNR Am J Neuroradiol 17:191319171996

20

Sinzobahamvya NKalangu KHamel-Kalinowski W: Arterial aneurysms associated with human immunodeficiency virus (HIV) infection. Acta Chir Belg 89:1851881989

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