ABSTRACT
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.
Subject(s)
Cerebellum/blood supply , Cerebral Arteries/virology , Chickenpox/virology , Herpesvirus 3, Human/pathogenicity , Ischemic Stroke/virology , Vertebrobasilar Insufficiency/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Cerebral Arteries/diagnostic imaging , Chickenpox/complications , Chickenpox/diagnosis , Chickenpox/drug therapy , Child, Preschool , Glucocorticoids/therapeutic use , Host-Pathogen Interactions , Humans , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/drug therapy , Male , Treatment Outcome , Vertebrobasilar Insufficiency/diagnostic imaging , Vertebrobasilar Insufficiency/drug therapyABSTRACT
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.
Subject(s)
Anti-HIV Agents/therapeutic use , Basal Ganglia/pathology , Cerebral Arteries/pathology , Cerebrovascular Disorders/pathology , Frontal Lobe/pathology , HIV Infections/pathology , White Matter/pathology , Acetazolamide/administration & dosage , Antiretroviral Therapy, Highly Active , Basal Ganglia/blood supply , Basal Ganglia/diagnostic imaging , Basal Ganglia/virology , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/virology , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/drug therapy , Cross-Sectional Studies , Disease Progression , Female , Frontal Lobe/blood supply , Frontal Lobe/diagnostic imaging , Frontal Lobe/virology , HIV/drug effects , HIV/pathogenicity , HIV Infections/complications , HIV Infections/diagnostic imaging , HIV Infections/drug therapy , Humans , Magnetic Resonance Angiography/methods , Middle Aged , RNA, Viral/genetics , Spin Labels , White Matter/blood supply , White Matter/diagnostic imaging , White Matter/virologySubject(s)
Brain Ischemia/diagnostic imaging , Cerebral Arteries/diagnostic imaging , Gadolinium , Magnetic Resonance Imaging/methods , Varicella Zoster Virus Infection/diagnostic imaging , Adult , Brain/blood supply , Brain/diagnostic imaging , Brain/virology , Brain Ischemia/etiology , Brain Ischemia/virology , Cerebral Arteries/virology , Humans , Varicella Zoster Virus Infection/complicationsABSTRACT
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.
Subject(s)
Arterioles/pathology , Carotid Arteries/pathology , Cerebral Arteries/pathology , Frontal Lobe/pathology , HIV Infections/pathology , Adult , Aged , Aged, 80 and over , Arterioles/anatomy & histology , Arterioles/virology , Autopsy , Carotid Arteries/anatomy & histology , Carotid Arteries/virology , Case-Control Studies , Cerebral Arteries/anatomy & histology , Cerebral Arteries/virology , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/blood supply , Frontal Lobe/virology , Histocytochemistry , Humans , Male , Middle Aged , Vascular Resistance , VasodilationSubject(s)
Brain Ischemia/drug therapy , Cerebral Arterial Diseases/diagnostic imaging , Cerebral Arterial Diseases/pathology , HIV Infections/complications , Stroke/drug therapy , Thrombolytic Therapy/adverse effects , Adult , Brain Ischemia/virology , Cerebral Angiography , Cerebral Arterial Diseases/virology , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/pathology , Cerebral Arteries/virology , Female , Humans , Stroke/virologySubject(s)
Brain Ischemia/pathology , Brain/pathology , Cerebral Arteries/pathology , HIV Infections/pathology , Stroke/pathology , Subarachnoid Hemorrhage/pathology , Anti-HIV Agents/therapeutic use , Brain/blood supply , Brain/drug effects , Brain/virology , Brain Ischemia/complications , Brain Ischemia/drug therapy , Brain Ischemia/virology , Cerebral Arteries/drug effects , Cerebral Arteries/virology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/pathogenicity , HIV-1/physiology , Humans , Male , Middle Aged , Steroids/therapeutic use , Stroke/complications , Stroke/drug therapy , Stroke/virology , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/virology , Viral Load/drug effectsABSTRACT
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.
Subject(s)
Cerebral Arteries/pathology , Cerebral Arteries/virology , Herpesvirus 3, Human/physiology , Virus Activation/physiology , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Registries , Risk Factors , Substance-Related Disorders/diagnosis , Substance-Related Disorders/virologyABSTRACT
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.
Subject(s)
Antibodies, Viral/blood , Cerebral Arteries/pathology , Endothelium, Vascular/pathology , Herpes Zoster/pathology , Stroke/pathology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , B-Lymphocytes/virology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/virology , Cerebral Arteries/immunology , Cerebral Arteries/virology , Endothelium, Vascular/immunology , Endothelium, Vascular/virology , Herpes Zoster/diagnosis , Herpes Zoster/immunology , Herpes Zoster/virology , Herpesvirus 3, Human/immunology , Humans , Immunoglobulin G/blood , Macrophages/immunology , Macrophages/pathology , Macrophages/virology , Stroke/immunology , Stroke/virologyABSTRACT
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.
Subject(s)
Antigens, Viral/analysis , Cerebral Arteries/chemistry , DNA, Viral/analysis , Herpesvirus 1, Human/genetics , Herpesvirus 3, Human/genetics , Leukocyte Common Antigens/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Viral/genetics , Cerebral Arteries/virology , DNA, Viral/genetics , Female , Humans , Leukocyte Common Antigens/genetics , Leukocytes/cytology , Leukocytes/metabolism , Male , Middle AgedABSTRACT
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.
Subject(s)
Cerebral Arteries/virology , Herpes Zoster/virology , Herpesvirus 3, Human/isolation & purification , Sinus Thrombosis, Intracranial/virology , Adolescent , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Cerebral Angiography/methods , Cerebral Arteries/pathology , Diffusion Magnetic Resonance Imaging , Herpes Zoster/complications , Herpes Zoster/diagnosis , Herpes Zoster/drug therapy , Humans , Infarction, Middle Cerebral Artery/virology , Magnetic Resonance Angiography , Male , Phlebography/methods , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/drug therapy , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Cerebral Arteries/pathology , Herpesvirus 3, Human/immunology , Stroke/pathology , Tunica Intima/pathology , Virus Diseases/pathology , Actins/metabolism , Adult , Aged , Aged, 80 and over , Cerebral Arteries/metabolism , Cerebral Arteries/virology , Humans , Hyperplasia/pathology , Male , Myocytes, Smooth Muscle/pathology , Myosin Heavy Chains/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Stroke/virology , Tunica Intima/metabolism , Virus Diseases/metabolismABSTRACT
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.
Subject(s)
AIDS Dementia Complex/physiopathology , Brain/blood supply , Brain/physiopathology , Cerebrovascular Circulation/physiology , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/physiopathology , AIDS Dementia Complex/diagnosis , Adult , Basal Ganglia/blood supply , Basal Ganglia/physiopathology , Basal Ganglia/virology , Basal Ganglia Cerebrovascular Disease/diagnosis , Basal Ganglia Cerebrovascular Disease/physiopathology , Basal Ganglia Cerebrovascular Disease/virology , Biomarkers/analysis , Brain/virology , Cerebral Arteries/pathology , Cerebral Arteries/physiopathology , Cerebral Arteries/virology , Cerebrovascular Disorders/virology , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Angiography/methods , Male , Predictive Value of Tests , Sensitivity and Specificity , Visual Cortex/blood supply , Visual Cortex/physiopathology , Visual Cortex/virologySubject(s)
Cerebral Arteries/pathology , Cerebral Arteries/virology , Encephalitis, Varicella Zoster/pathology , Encephalitis, Varicella Zoster/virology , Exanthema/complications , Frontal Lobe/blood supply , Frontal Lobe/pathology , Herpes Zoster/complications , Temporal Lobe/blood supply , Temporal Lobe/pathology , Alphaherpesvirinae/isolation & purification , Female , Frontal Lobe/virology , Hippocampus/blood supply , Hippocampus/pathology , Humans , Magnetic Resonance Imaging , Middle Aged , Polymerase Chain Reaction , Temporal Lobe/virologySubject(s)
Cerebral Arterial Diseases/virology , Herpesvirus 3, Human/pathogenicity , Ischemic Attack, Transient/etiology , Peripheral Vascular Diseases/virology , Stroke/etiology , Afferent Pathways/virology , Animals , Antiphospholipid Syndrome/complications , Cats , Cerebral Arterial Diseases/complications , Cerebral Arteries/innervation , Cerebral Arteries/virology , Ganglia, Spinal/virology , Hemiplegia/etiology , Humans , Ischemic Attack, Transient/virology , Protein S Deficiency/complications , Stroke/virology , Thrombophilia/etiology , Trigeminal Nerve/virology , Virus LatencySubject(s)
Brain Ischemia/etiology , Cerebral Arterial Diseases/virology , Herpes Zoster/complications , Herpesvirus 3, Human/pathogenicity , Peripheral Vascular Diseases/etiology , Thrombosis/etiology , Adult , Antiphospholipid Syndrome/virology , Brain Ischemia/virology , Cerebral Arterial Diseases/complications , Cerebral Arteries/virology , Hemianopsia/etiology , Hemiplegia/etiology , Humans , Male , Perceptual Disorders/etiology , Peripheral Vascular Diseases/virology , Protein S Deficiency/virology , Retinal Artery Occlusion/etiology , Retinal Artery Occlusion/virology , Thrombophilia/virology , Thrombosis/virologyABSTRACT
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.