Cerebral aneurysmal arteriopathy in childhood AIDS

Dubrovsky, T.; Curless, Richard G.; Scott, Glynis; Chaneles, M.; Post, M. Judith Donovan; Altman, Nolan; Petito, Carol K.; Start, David; Wood, Charles

doi:10.1212/wnl.51.2.560

Cited by 124 publications

(127 citation statements)

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“…A thinner media has been reported in entities associated with arterial dilatation in patients with and without HIV. 1,2,6,7 The lymphocytes in the adventitia were seen in equal proportions among groups, making vasculitis a less likely explanation to our results. Disruption of the IEL has been reported in HIV vasculopathy, 1,2,4 but we failed to reproduce this finding.…”

Section: Discussionmentioning

confidence: 52%

“…[1][2][3] Pathological studies on arteries affected by HIV vasculopathy have demonstrated significant arterial media (ie, muscularis) layer disruption characterized by atrophy, fibrosis, and fragmentation of the internal elastic lamina (IEL). 1,2,4 The HIV infection of the smooth muscle cells may underlie the subsequent deterioration of the media. 5 Little is known about arterial wall changes that could precede the development of clinical cerebrovascular events, particularly those related to HIV vasculopathy.…”

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confidence: 99%

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Thinning of the Arterial Media Layer as a Possible Preclinical Stage in HIV Vasculopathy

Gutierrez

Glenn

Isaacson

et al. 2012

Stroke

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Background and Purpose-The purpose of this study was to determine if postmortem intracranial arteries from donors with HIV without stroke have thinner media layers compared with patients without HIV and without stroke. Methods-Cross-sectional cuts from intracranial arteries were stained with van Gieson and hematoxylin and eosin. Arteries were examined for thickness of each arterial layer. Univariable and multivariable models were used for statistical analyses with probability values Ͻ0.05 considered significant. Results-A total of 18 brains were analyzed, 5 with HIV and 13 without. Fifty-five arteries were collected, 15 from HIV brains and 40 from unaffected controls. In univariable analysis, in arteries from HIV-infected brains, the media to wall thickness ratio was smaller than in donors without HIV (0.496 versus 0.563, Pϭ0.017). In multivariable analysis, HIV infection was the only independent predictor of smaller media ratios compared with the same-aged control subjects (Pϭ0.049) but not with aged control subjects (Pϭ0.081). Conclusions-In patients with HIV without clinical stroke, the media arterial layer is thinner than in patients without HIV. This suggests that a thinner media layer might be a preclinical stage in the development of HIV-related vasculopathy. (Stroke. 2012;43:1156-1158.)

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Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 99%

Thinning of the Arterial Media Layer as a Possible Preclinical Stage in HIV Vasculopathy

Gutierrez

Glenn

Isaacson

et al. 2012

Stroke

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“…Both large and small vessels display marked endothelial hyperproliferation, death, and monolayer disorganization, leading to aneurysms, occlusions, and telangiectasias (3)(4)(5)(6)(7). Strikingly, HIV-1-infected patients also develop an unusually aggressive form of the vascular neoplasm Kaposi sarcoma, suggesting a prominent contribution of HIV-1 in determining the behavior of Kaposi sarcoma cells.…”

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confidence: 99%

HIV-1 Tat Activates Dual Nox Pathways Leading to Independent Activation of ERK and JNK MAP Kinases

Myers

et al. 2007

Journal of Biological Chemistry

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Human immunodeficiency virus, type 1 Tat is known to exert pleiotropic effects on the vascular endothelium through mitogen-activated protein (MAP) kinases, although the signaling pathways leading to MAP kinase activation are incompletely understood. We focused on proximal pathways potentially governing downstream MAP kinase activity by Tat. Within 2 min, Tat activated both Ras and Rho GTPases in endothelial cells, leading to ERK phosphorylation by 10 min. Notably, Rac1 was necessary for downstream activation of RhoA and both Rac1 and RhoA acted upstream of the Ras/ERK cassette. Antioxidants and the oxidase inhibitor diphenylene iodonium blocked ERK phosphorylation, but specific interference with the canonical Nox2 oxidase had no effect on ERK. Instead, knock down of the novel oxidase Nox4 completely suppressed Tat-dependent Ras and ERK activation downstream of Rac1 and RhoA. Conversely, interference with Rac1, PAK1, and Nox2 blocked JNK phosphorylation, whereas RhoA(N19) and Nox4 knock down did not. Further, knock down of Nox2, but not Nox4, blocked Tat-induced cytoskeletal rearrangement, whereas knock down of Nox4, but not Nox2, blocked Tat-dependent proliferation. Rac1, therefore, bifurcates Tat signaling, leading to concurrent but separate Nox4-dependent Ras/ERK activation, and Nox2-dependent JNK activation. Tat signaling, therefore, provides an example of Nox-specific differential control of MAP kinase pathways.

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“…The majority of children with human immunodeficiency virus (HIV) infection have neurologi-cal dysfunction but the development of symptomatic cerebrovascular disease is low (1.3%) 1 . Central nervous system (CNS) involvement in pediatric AIDS may be due to primary HIV infection or to secondary complications of immunodeficiency 2 .…”

mentioning

confidence: 99%

“…The proposed mechanisms for cerebrovascular disease in childhood AIDS include hypoperfusion, septic or thrombotic emboli, and infectious vasculitis of intracranial vessels 3 . It has been discussed whether the vasculitis is directed related to HIV or secondary to associated infections such as herpes simplex virus (HSV), cytomegalovirus (CMV), varicella zoster virus (VZV), mycobacteria, or fungi 1,3,4 . Cerebral artery aneurysms confined to large arteries of the circle of Willis have been previously described in HIV infected children, but a longer latency period following infection was necessary before onset of neurological symptoms.…”

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confidence: 99%

Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV infection and HSV encephalitis

Nunes

Pinho

Sfoggia

2001

Arq. Neuro-Psiquiatr.

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-Although most children with human immunodeficiency virus (HIV) infection have neurological dysfunction, in childhood the incidence of symptomatic cerebrovascular disease is low. Cerebral aneurysmal arteriopathy in childhood AIDS has been reported in the past and considered to have a relatively long latency following the primary infection. We report a 1 month-old infant with congenitally acquired HIV infection, and herpes encephalitis; she presented a sudden cardiorespiratory arrest followed by coma and was found to have a giant saccular aneurysm of the left basilar artery. Literature review showed that cerebral aneurysmal artheriopathy is an unusual manifestation in newborns and infants and this case is possibly the youngest patient reported with aneurysma, herpes encephalitis and AIDS. The role of HIV and herpes simplex infections in the pathogenesis of this lesion is discussed.KEY WORDS: AIDS, herpes simplex, cerebrovascular disease, infancy.Aneurisma cerebral sintomático precoce em lactente com infecção congênita por HIV e encefalite herpética RESUMO -A maioria das crianças com síndrome da imunodeficiência adquirida (SIDA) apresenta complicações neurológicas, mas a incidência de doença cerebrovascular sintomática nesta faixa etária é baixa. Existem relatos prévios de arteriopatia aneurismática em crianças com SIDA, mas a latência entre a infecção primária e o desenvolvimento dos sintomas geralmente é longa. Relatamos lactente com infecção congênita por HIV, que apresentou encefalite herpética e apresentou subitamente parada cardiorespiratória, seguida de coma. A investigação através de neuroimagem demonstrou aneurisma sacular gigante da artéria basilar. A revisão da literatura demonstra ser a arteriopatia aneurismática uma entidade rara no perído neonatal e em lactentes, sendo possivelmente este o caso mais jovem até o presente relatado com doença cerebrovascular aneurismática associada a herpes e SIDA. A relação da associação entre SIDA e infecção por herpes vírus na gênese da doença cerebrovascular é discutida.

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Cerebral aneurysmal arteriopathy in childhood AIDS

Cited by 124 publications

References 4 publications

Thinning of the Arterial Media Layer as a Possible Preclinical Stage in HIV Vasculopathy

Thinning of the Arterial Media Layer as a Possible Preclinical Stage in HIV Vasculopathy

HIV-1 Tat Activates Dual Nox Pathways Leading to Independent Activation of ERK and JNK MAP Kinases

Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV infection and HSV encephalitis

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