RESUMO
Cerebrovascular events in pediatric population are very rare. Up to 30% may result from varicella zoster (VZV) arteriopathy, usually as a delayed complication of varicella primary infection. The most typical pattern includes involvement of anterior brain circulation arteries, probably by VZV migration from the trigeminal ganglia. Strokes related with VZV usually have a good prognosis, but risk of recurrence is greater when compared to other stroke etiologies in this age group. We report the case of a 4-year-old boy, immunocompetent, who presented a basilar artery stenosis and a cerebellar stroke, an extremely rare presentation of VZV arteriopathy. The investigation workup and treatment are detailed, as the clinical and imaging follow-up after one year.
Assuntos
Cerebelo/irrigação sanguínea , Artérias Cerebrais/virologia , Varicela/virologia , Herpesvirus Humano 3/patogenicidade , AVC Isquêmico/virologia , Insuficiência Vertebrobasilar/virologia , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Artérias Cerebrais/diagnóstico por imagem , Varicela/complicações , Varicela/diagnóstico , Varicela/tratamento farmacológico , Pré-Escolar , Glucocorticoides/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , Masculino , Resultado do Tratamento , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/tratamento farmacológicoRESUMO
The purpose of this study was to assess whole brain and regional patterns of cerebrovascular reactivity (CVR) abnormalities in HIV-infected women using quantitative whole brain arterial spin labeling (ASL). We hypothesized that HIV-infected women would demonstrate decreased regional brain CVR despite viral suppression. This cross-sectional study recruited subjects from the Bay Area Women's Interagency Health Study (WIHS)-a cohort study designed to investigate the progression of HIV disease in women. In addition to conventional noncontrast cerebral MRI sequences, perfusion imaging was performed before and after the administration of intravenous acetazolamide. CVR was measured by comparing quantitative ASL brain perfusion before and after administration of intravenous acetazolamide. In order to validate and corroborate ASL-based whole brain and regional perfusion, phase-contrast (PC) imaging was also performed through the major neck vessels. FLAIR and susceptibility weighted sequences were performed to assess for white matter injury and microbleeds, respectively. Ten HIV-infected women and seven uninfected, age-matched controls were evaluated. Significant group differences were present in whole brain and regional CVR between HIV-infected and uninfected women. These regional differences were significant in the frontal lobe and basal ganglia. CVR measurements were not significantly impacted by the degree of white matter signal abnormality or presence of microbleeds. Despite complete viral suppression, dysfunction of the neurovascular unit persists in the HIV population. Given the lack of association between CVR and traditional imaging markers of small vessel disease, CVR quantification may provide an early biomarker of pre-morbid vascular disease.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Gânglios da Base/patologia , Artérias Cerebrais/patologia , Transtornos Cerebrovasculares/patologia , Lobo Frontal/patologia , Infecções por HIV/patologia , Substância Branca/patologia , Acetazolamida/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Gânglios da Base/irrigação sanguínea , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/virologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/virologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/tratamento farmacológico , Estudos Transversais , Progressão da Doença , Feminino , Lobo Frontal/irrigação sanguínea , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/virologia , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Humanos , Angiografia por Ressonância Magnética/métodos , Pessoa de Meia-Idade , RNA Viral/genética , Marcadores de Spin , Substância Branca/irrigação sanguínea , Substância Branca/diagnóstico por imagem , Substância Branca/virologiaAssuntos
Isquemia Encefálica/diagnóstico por imagem , Artérias Cerebrais/diagnóstico por imagem , Gadolínio , Imageamento por Ressonância Magnética/métodos , Infecção pelo Vírus da Varicela-Zoster/diagnóstico por imagem , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/virologia , Artérias Cerebrais/virologia , Humanos , Infecção pelo Vírus da Varicela-Zoster/complicaçõesRESUMO
We aimed to test the hypothesis that brain large artery diameters relate to distal downstream arteriolar diameters. In a sample of 110 autopsied individuals (69% men, 76% HIV+, mean age 51), we used multilevel models to relate large artery lumen and lumen-to-wall ratio to left frontal lobe arteriolar lumen and lumen-to-wall ratio adjusting for demographics and vascular risk factors. Comparing the large artery characteristics of the whole brain did not disclose significant associations with frontal lobe arteriolar characteristics. However, restricting the comparison to large arteries upstream of the studied arterioles demonstrated an independent association between left-sided frontal lobe arteriolar luminal diameter with large artery luminal diameters (B = 1.82 ± 0.77, P = 0.01) and with large artery lumen-to-wall ratio (B = 0.58 ± 0.29, P = 0.05). In stratified models, the point estimates in the HIV+ subsample were larger than in the HIV- subsample. These finding suggest coupling between higher proximal blood flow represented by large artery diameter and lower distal resistance represented by arteriolar dilatation. The relationship between arteriolar dilatation and brain parenchyma homeostasis should be further studied.
Assuntos
Arteríolas/patologia , Artérias Carótidas/patologia , Artérias Cerebrais/patologia , Lobo Frontal/patologia , Infecções por HIV/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteríolas/anatomia & histologia , Arteríolas/virologia , Autopsia , Artérias Carótidas/anatomia & histologia , Artérias Carótidas/virologia , Estudos de Casos e Controles , Artérias Cerebrais/anatomia & histologia , Artérias Cerebrais/virologia , Feminino , Lobo Frontal/anatomia & histologia , Lobo Frontal/irrigação sanguínea , Lobo Frontal/virologia , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Vascular , VasodilataçãoAssuntos
Isquemia Encefálica/tratamento farmacológico , Doenças Arteriais Cerebrais/diagnóstico por imagem , Doenças Arteriais Cerebrais/patologia , Infecções por HIV/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Adulto , Isquemia Encefálica/virologia , Angiografia Cerebral , Doenças Arteriais Cerebrais/virologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/patologia , Artérias Cerebrais/virologia , Feminino , Humanos , Acidente Vascular Cerebral/virologiaAssuntos
Isquemia Encefálica/patologia , Encéfalo/patologia , Artérias Cerebrais/patologia , Infecções por HIV/patologia , Acidente Vascular Cerebral/patologia , Hemorragia Subaracnóidea/patologia , Fármacos Anti-HIV/uso terapêutico , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/virologia , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/virologia , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/patogenicidade , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esteroides/uso terapêutico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/virologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/virologia , Carga Viral/efeitos dos fármacosRESUMO
With a decline in varicella zoster virus (VZV)-specific cell-mediated immunity, VZV can reactivate, infect cerebral arteries and cause stroke. Previous studies of cerebral arteries from subjects without a history of transient ischemic attacks or stroke revealed no VZV DNA or VZV antigen; however, VZV DNA and VZV antigen were found in the cerebral arteries of a subject with diabetes, a known risk factor for VZV reactivation and zoster. The present study analyzed an additional 55 cerebral arteries from 18 subjects with co-morbidities that may increase risk of VZV reactivation: a history of alcohol abuse, tricyclic antidepressant intoxication, cocaine abuse, HIV or being over age 70 years. VZV antigen was detected in 24 (44%) cerebral arteries from 14 (78%) subjects.
Assuntos
Artérias Cerebrais/patologia , Artérias Cerebrais/virologia , Herpesvirus Humano 3/fisiologia , Ativação Viral/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/virologiaRESUMO
Varicella zoster virus (VZV) vasculopathy is caused by productive virus infection of cerebral arteries, leading to inflammation, pathological vascular remodeling, and ischemic or hemorrhagic stroke. VZV vasculopathy occurs in immunocompetent and immunocompromised individuals and involves both large and small vessels. MRI abnormalities include more deep-seated than superficial lesions, particularly at gray-white matter junctions, and lesions may enhance. Diagnosis is challenging, since stroke can occur months after zoster rash and in the absence of rash or CSF pleocytosis. The best virological test for diagnosis is detection of anti-VZV IgG antibody in the CSF. Pathological studies of VZV-infected arteries from patients with VZV vasculopathy reveal that the arterial adventitia is the initial site of infection, after which virus spreads transmuraly towards the lumen. Histological and immunohistochemical studies of VZV-infected arteries show a thickened intima, disrupted internal elastic lamina, and loss of smooth muscle cells, that likely contribute to weakening of the vessel wall and occlusion. Early in disease, VZV-infected arteries contain CD4+ and CD8+ T cells, macrophages, and rare B cells, in addition to abundant neutrophils in early disease. Importantly, perivascular inflammatory cells underlie the areas of thickened intima, raising the possibility that soluble factors secreted by these cells contribute to arterial remodeling. This review discusses the clinical features of VZV vasculopathy and potential mechanisms of VZV-induced cerebrovascular remodeling and stroke.
Assuntos
Anticorpos Antivirais/sangue , Artérias Cerebrais/patologia , Endotélio Vascular/patologia , Herpes Zoster/patologia , Acidente Vascular Cerebral/patologia , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Artérias Cerebrais/imunologia , Artérias Cerebrais/virologia , Endotélio Vascular/imunologia , Endotélio Vascular/virologia , Herpes Zoster/diagnóstico , Herpes Zoster/imunologia , Herpes Zoster/virologia , Herpesvirus Humano 3/imunologia , Humanos , Imunoglobulina G/sangue , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/virologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/virologiaRESUMO
Virological confirmation of varicella zoster virus (VZV) vasculopathy is provided by presence of virus in the cerebral arteries, frequently associated with inflammation. Yet, cerebral arteries from normal subjects have never been studied for VZV DNA or antigen. We analyzed 63 human cerebral arteries from 45 subjects for VZV DNA and antigen, control herpes simplex virus (HSV)-1 DNA and antigen, and leukocyte-specific CD45 antigen. No cerebral arteries contained VZV or HSV-1 DNA or antigen; eight arteries from seven subjects contained leukocytes expressing CD45. Thus, the presence of VZV antigen in cerebral arteries of patients with stroke is likely to be clinically significant.
Assuntos
Antígenos Virais/análise , Artérias Cerebrais/química , DNA Viral/análise , Herpesvirus Humano 1/genética , Herpesvirus Humano 3/genética , Antígenos Comuns de Leucócito/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/genética , Artérias Cerebrais/virologia , DNA Viral/genética , Feminino , Humanos , Antígenos Comuns de Leucócito/genética , Leucócitos/citologia , Leucócitos/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Varicella zoster virus (VZV) has been known to cause cerebral arterial vasculopathy and an acquired antibody-mediated coagulopathy associated with purpura fulminans and generalized thromboembolism. There are no published reports of cerebral venous sinus thrombosis (CVST) associated with primary VZV infection. We report 2 cases that highlight an unusual presentation of VZV infection: CVST with primary varicella infection. One patient had extensive CVST with coexistent middle cerebral artery involvement. Primary VZV infection can be associated with thrombosis of cerebral arteries and venous sinuses.
Assuntos
Artérias Cerebrais/virologia , Herpes Zoster/virologia , Herpesvirus Humano 3/isolamento & purificação , Trombose dos Seios Intracranianos/virologia , Adolescente , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Angiografia Cerebral/métodos , Artérias Cerebrais/patologia , Imagem de Difusão por Ressonância Magnética , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Humanos , Infarto da Artéria Cerebral Média/virologia , Angiografia por Ressonância Magnética , Masculino , Flebografia/métodos , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. No animal model exists for stroke caused by VZV infection of cerebral arteries. Thus, we analyzed cerebral and temporal arteries from 3 patients with VZV vasculopathy to identify features that will help in diagnosis and lead to a better understanding of VZV-induced vascular remodeling. METHODS: Normal and VZV-infected cerebral and temporal arteries were examined histologically and by immunohistochemistry using antibodies directed against VZV, endothelium, and smooth muscle actin and myosin. RESULTS: All VZV-infected arteries contained 1) a disrupted internal elastic lamina; 2) a hyperplastic intima composed of cells expressing α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-myosin) but not endothelial cells expressing CD31; and 3) decreased medial smooth muscle cells. The location of VZV antigen, degree of neointimal thickening, and disruption of the media were related to the duration of disease. CONCLUSIONS: The presence of VZV primarily in the adventitia early in infection and in the media and intima later supports the notion that after reactivation from ganglia, VZV spreads transaxonally to the arterial adventitia followed by transmural spread of virus. Disruption of the internal elastic lamina, progressive intimal thickening with cells expressing α-SMA and SM-MHC, and decreased smooth muscle cells in the media are characteristic features of VZV vasculopathy. Stroke in VZV vasculopathy may result from changes in arterial caliber and contractility produced in part by abnormal accumulation of smooth muscle cells and myofibroblasts in thickened neointima and disruption of the media.
Assuntos
Artérias Cerebrais/patologia , Herpesvirus Humano 3/imunologia , Acidente Vascular Cerebral/patologia , Túnica Íntima/patologia , Viroses/patologia , Actinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias Cerebrais/metabolismo , Artérias Cerebrais/virologia , Humanos , Hiperplasia/patologia , Masculino , Miócitos de Músculo Liso/patologia , Cadeias Pesadas de Miosina/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Acidente Vascular Cerebral/virologia , Túnica Íntima/metabolismo , Viroses/metabolismoRESUMO
OBJECTIVE: HIV enters the brain soon after infection causing neuronal damage and microglial/astrocyte dysfunction leading to neuropsychological impairment. We examined the impact of HIV on resting cerebral blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC). METHODS: This cross-sectional study used arterial spin labeling MRI (ASL-MRI) to measure rCBF within 33 HIV+ and 26 HIV- subjects. Nonparametric Wilcoxon rank sum test assessed rCBF differences due to HIV serostatus. Classification and regression tree (CART) analysis determined optimal rCBF cutoffs for differentiating HIV serostatus. The effects of neuropsychological impairment and infection duration on rCBF were evaluated. RESULTS: rCBF within the LN and VC were significantly reduced for HIV+ compared to HIV- subjects. A 2-tiered CART approach using either LN rCBF < or =50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF < or =37.05 mL/100 mL/min yielded an 88% (29/33) sensitivity and an 88% (23/26) specificity for differentiating by HIV serostatus. HIV+ subjects, including neuropsychologically unimpaired, had reduced rCBF within the LN (p = 0.02) and VC (p = 0.001) compared to HIV- controls. A temporal progression of brain involvement occurred with LN rCBF significantly reduced for both acute/early (<1 year of seroconversion) and chronic HIV-infected subjects, whereas rCBF in the VC was diminished for only chronic HIV-infected subjects. CONCLUSION: Resting cerebral blood flow (rCBF) using arterial spin labeling MRI has the potential to be a noninvasive neuroimaging biomarker for assessing HIV in the brain. rCBF reductions that occur soon after seroconversion possibly reflect neuronal or vascular injury among HIV+ individuals not yet expressing neuropsychological impairment.
Assuntos
Complexo AIDS Demência/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/fisiopatologia , Complexo AIDS Demência/diagnóstico , Adulto , Gânglios da Base/irrigação sanguínea , Gânglios da Base/fisiopatologia , Gânglios da Base/virologia , Doença Cerebrovascular dos Gânglios da Base/diagnóstico , Doença Cerebrovascular dos Gânglios da Base/fisiopatologia , Doença Cerebrovascular dos Gânglios da Base/virologia , Biomarcadores/análise , Encéfalo/virologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Artérias Cerebrais/virologia , Transtornos Cerebrovasculares/virologia , Estudos Transversais , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Córtex Visual/irrigação sanguínea , Córtex Visual/fisiopatologia , Córtex Visual/virologiaAssuntos
Artérias Cerebrais/patologia , Artérias Cerebrais/virologia , Encefalite por Varicela Zoster/patologia , Encefalite por Varicela Zoster/virologia , Exantema/complicações , Lobo Frontal/irrigação sanguínea , Lobo Frontal/patologia , Herpes Zoster/complicações , Lobo Temporal/irrigação sanguínea , Lobo Temporal/patologia , Alphaherpesvirinae/isolamento & purificação , Feminino , Lobo Frontal/virologia , Hipocampo/irrigação sanguínea , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Lobo Temporal/virologiaAssuntos
Doenças Arteriais Cerebrais/virologia , Herpesvirus Humano 3/patogenicidade , Ataque Isquêmico Transitório/etiologia , Doenças Vasculares Periféricas/virologia , Acidente Vascular Cerebral/etiologia , Vias Aferentes/virologia , Animais , Síndrome Antifosfolipídica/complicações , Gatos , Doenças Arteriais Cerebrais/complicações , Artérias Cerebrais/inervação , Artérias Cerebrais/virologia , Gânglios Espinais/virologia , Hemiplegia/etiologia , Humanos , Ataque Isquêmico Transitório/virologia , Deficiência de Proteína S/complicações , Acidente Vascular Cerebral/virologia , Trombofilia/etiologia , Nervo Trigêmeo/virologia , Latência ViralAssuntos
Isquemia Encefálica/etiologia , Doenças Arteriais Cerebrais/virologia , Herpes Zoster/complicações , Herpesvirus Humano 3/patogenicidade , Doenças Vasculares Periféricas/etiologia , Trombose/etiologia , Adulto , Síndrome Antifosfolipídica/virologia , Isquemia Encefálica/virologia , Doenças Arteriais Cerebrais/complicações , Artérias Cerebrais/virologia , Hemianopsia/etiologia , Hemiplegia/etiologia , Humanos , Masculino , Transtornos da Percepção/etiologia , Doenças Vasculares Periféricas/virologia , Deficiência de Proteína S/virologia , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/virologia , Trombofilia/virologia , Trombose/virologiaRESUMO
The association of atherosclerosis (AS) and Human cytomegalovirus (HCMV) infection was studied. AS plays an important role in the brain stroke and HCMV infection is supposed to be involved in the process of atherosclerotic formation. The presence of HCMV DNA and antigens was examined in the internal carotid arteries collected from 35 patients with ischemic stroke and from 20 patients from the control population. All patients belonged to the ethnic Han population in China. Three methods, immunohistochemistry (IHC), hybridization in situ (HIS), and PCR were used to detect the HCMV immediate early (IE) and late (L) antigens as well as viral DNA in vessel walls. Levels of HCMV IE gene/protein were significantly higher in the stroke group than in control group detected by the three methods (IHC 34.3% vs. 10.0%; HIS 40.0% vs. 10.0; PCR 60.0% vs. 30.0%). However, there was no significant difference in the levels of HCMV L gene/protein between these two groups of patients (IHC 11.4% vs. 5.0%; HIS 11.4% vs. 10.0%; PCR 20.0% vs. 20.0%). We concluded that the presence of HCMV IE antigen and HCMV DNA in the vessel wall was associated with the pathological process of AS formation.