Abstract 38: Herpes Viruses in Childhood Arterial Ischemic Stroke: Interim Results of the VIPS Study

Background: Varicella zoster virus (VZV) is a known cause of cerebral arteriopathy and arterial ischemic stroke (AIS) in children, and scant evidence suggests other herpes viruses may also play a role. An objective of the Vascular effects of Infection in Pediatric Stroke (VIPS) study was to determine whether recent infection with herpes viruses_as measured by serologies_is associated with childhood AIS. Methods: VIPS is an international prospective 35-center case-control study enrolling 350 children (28 days-18 years) with AIS and 120 unmatched trauma controls. Case confirmation and vascular imaging review are performed centrally. Acute blood samples are collected ≤3 weeks after stroke/trauma; convalescent samples 7-28 days after the acute draw in cases only. Samples were tested for IgG and IgM antibodies to herpes simplex virus (HSV) 1 and 2, cytomegalovirus (CMV), Epstein Barr virus (EBV), and VZV. An algorithm developed a priori by a pediatric infectious disease expert (C.A.G.) classified acute infection as a dichotomous variable. Results: Of 310 cases enrolled thus far, 141 cases with paired samples and 44 controls underwent serologic analysis. Median age (IQR) was 7.0 years (2.9, 14.3) for cases and 8.3 (3.3, 13.3) for controls (P=0.90). Evidence of an acute herpes infection was found in 41% of cases versus 9% of controls (P<0.0001; Table). The most commonly identified virus was HSV-1. After adjusting for age in a multivariable logistic regression analysis, herpes exposure remained a significant predictor of AIS (OR 9.0, 95% CI 3.1, 38.7; P=0.0004). Of the 58 cases positive for herpes, 36% had a definite arteriopathy, and 33% a possible arteriopathy, compared to 34% and 24%, respectively, of 83 negative cases. Conclusions: In this interim analysis, acute exposure to a herpes virus appears associated with childhood AIS, present in 41% of cases that were tested.

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Abstract 39: Infection, Vaccination, and Childhood Stroke: Preliminary Results of the Vascular Effects of Infection in Pediatric Stroke (VIPS) Study

Stroke ◽

10.1161/str.45.suppl_1.39 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Nancy K Hills ◽

Gabrielle A DeVeber ◽

Carol A Glaser ◽

Max Wintermark ◽

Mitchell S Elkind ◽

...

Keyword(s):

Acute Infection ◽

Arterial Ischemic Stroke ◽

Vascular Effects ◽

Recent Infection ◽

Time Period ◽

Increased Risk ◽

Childhood Vaccines ◽

A Prospective Study ◽

Parental Interviews ◽

Control Study

Background: Acute minor infection was associated with childhood arterial ischemic stroke (AIS) in a retrospective study. In a prospective study, we tested the hypothesis that acute infection increases stroke risk, while vaccination against infection is protective. Methods: VIPS is an international multi-center prospective case-control study with a target enrollment of 350 cases of AIS (28 days-18 years old); parental interviews were conducted within 3 weeks of stroke occurrence in cases. Unmatched controls were identified and interviewed within 3 weeks of routine clinic visits for annual check-ups, migraine, or developmental delay, or urgent visits for trauma. Data were collected on recent infections and routine childhood vaccines. We explored attitudes toward vaccination by asking if the child had received all, most, some, few, or none of the routine vaccines expected for his/her age. Results: Data were available for 310 cases and 289 controls. Median (IQR) age was 7.5 (2.8, 14.2) and 8.2 (3.3, 12.8) years respectively (p=0.96). Infection ≤1week prior to stroke/interview date conferred a 6.5-fold risk of AIS (p<0.0001); the most common type of infection reported in this time period was upper respiratory (75% of controls and 50% of cases). In general, cases were under-vaccinated compared to controls (Table). Children reported to have had some/few/no routine vaccinations were at higher risk of AIS than those receiving all or most (OR 6.72, 95% CI 2.30, 19.6, p<0.0001). In logistic regression adjusted for age, ever having received an MMR, polio, or pneumococcus vaccine were each significantly protective against stroke. Conclusions: Recent infection confers an increased risk of childhood AIS, while routine vaccinations appear protective. This finding has positive implications for both primary and secondary stroke prevention.

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Abstract WMP111: Socioeconomic Determinants of Outcome After Childhood Arterial Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.wmp111 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Lori C Jordan ◽

Nancy K Hills ◽

Warren Lo ◽

Rebecca N Ichord ◽

Christine K Fox ◽

...

Keyword(s):

Ischemic Stroke ◽

Maternal Education ◽

Recurrent Stroke ◽

Pediatric Population ◽

Neurological Deficits ◽

Pediatric Stroke ◽

Arterial Ischemic Stroke ◽

Vascular Effects ◽

Middle Income ◽

Poor Outcome

Introduction: Lower socioeconomic status (SES) is associated with poorer outcome after adult stroke. In a large cohort of children with arterial ischemic stroke (AIS), we determined 12-month neurological outcome and tested the hypothesis that SES is a determinant of outcome in children. Methods: From 2009-2014, the Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS (29 days-18 years) at 37 international centers, including 3 in lower and middle income (LAMI) countries. Outcome was assessed at 12 months via the recurrence and recovery questionnaire (RRQ) parental report of the pediatric stroke outcome measure (PSOM). Poor outcome was defined as a PSOM of ≥1. Results: Of 355 children, outcome was available for 310 (87%) at a median of 12 months (IQR 11-13). Ten children died prior to hospital discharge and 4 by 12 months. Outcomes improved from discharge to 12 months (Figure). Of 23 cases in LAMI countries, 88% had an income <USD$10,000, compared to 11% of 287 cases in non-LAMI countries. Overall, only 39% LAMI cases had a good outcome, versus 61% of non-LAMI cases (p=0.052). There were too few cases to analyze outcome predictors in LAMI countries. However, in non-LAMI countries, income did not independently predict poor outcome (OR 1.7, 95% CI 0.57, 4.8, for income <$10,000 vs. >$100,000). Other markers of SES (maternal education level and rural/suburban/urban residence) also did not predict outcome. Independent predictors of poor outcome included moderate (OR 4.6, 95% CI 2.0, 11) or severe (OR 21, 95% CI 7.1, 60) neurological deficits at discharge (compared to no deficits) and recurrent stroke (OR 3.5, 95% CI 1.5, 8.3). Conclusion: Outcomes after childhood stroke may be worse in LAMI countries, although we were underpowered to study this subgroup. Within non-LAMI countries, SES does not appear to impact outcome in children, unlike reports in adults, perhaps reflecting better access to rehabilitation services in the pediatric population.

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Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults

10.1007/82_2021_236 ◽

2021 ◽

Author(s):

Charles Grose ◽

Amir Shaban ◽

Heather J. Fullerton

Keyword(s):

Ischemic Stroke ◽

Herpes Zoster ◽

Trigeminal Ganglion ◽

Cerebral Arteries ◽

Varicella Vaccine ◽

Arterial Ischemic Stroke ◽

Varicella Zoster ◽

Common Features ◽

Afferent Fibers ◽

Cervical Ganglion

AbstractThe cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.

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Biological Plausibility of a Link Between Arterial Ischemic Stroke and Infection With Varicella-Zoster Virus or Herpes Simplex Virus

Circulation ◽

10.1161/circulationaha.116.021459 ◽

2016 ◽

Vol 133 (8) ◽

pp. 695-697 ◽

Cited By ~ 7

Author(s):

Charles Grose

Keyword(s):

Ischemic Stroke ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Varicella Zoster Virus ◽

Biological Plausibility ◽

Arterial Ischemic Stroke ◽

Varicella Zoster ◽

Simplex Virus

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Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke

Annals of Neurology ◽

10.1002/ana.23688 ◽

2012 ◽

Vol 72 (6) ◽

pp. 850-858 ◽

Cited By ~ 59

Author(s):

Nancy K. Hills ◽

S. Claiborne Johnston ◽

Stephen Sidney ◽

Brandon A. Zielinski ◽

Heather J. Fullerton

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Acute Infection ◽

Arterial Ischemic Stroke

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Abstract 174: Headache Presentation in Childhood Arterial Ischemic Stroke Differs by Arteriopathy Subtype

Stroke ◽

10.1161/str.48.suppl_1.174 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Lori L Billinghurst ◽

Nancy K Hills ◽

Laura Jastrzab ◽

Max Wintermark ◽

Gabrielle A deVeber ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Analysis ◽

Arterial Ischemic Stroke ◽

Vascular Effects ◽

Afferent Activation ◽

Significant Difference ◽

Acute Headache ◽

Radiographic Classification ◽

Pathophysiologic Mechanisms

Introduction: Headache is common at onset of arterial ischemic stroke (AIS), with rates between 10-50%. Adult studies suggest that headache prevalence relates to stroke etiology, with highest rates observed in dissection. We hypothesized that children with arteriopathy-related stroke may have higher rates of headache than those without. Methods: Children (29 days -18 years) with AIS enrolled in the prospective, international Vascular Effects of Infection in Pediatric Stroke (VIPS) study were analyzed for presence of headache at stroke ictus. Cases were subjected to a rigorous, centralized process for diagnostic confirmation of AIS and radiographic classification of arteriopathy as definite, possible or absent. Site investigators abstracted data from medical records regarding stroke presentation details. Headache at stroke ictus was classified as present, absent or unclear. Results: We included all 355 VIPS cases in this secondary analysis. Headache was uncommon in subjects < 3 yo (5/90, 6%) but was present in nearly half of those ≥ 3 yo (108/265, 46%). Excluding those with an unclear headache presentation (n=31), there was no significant difference in headache at stroke ictus in children ≥ 3 yo with definite (46/92, 50%), possible (15/24, 63%) or absent (60/118, 51%) arteriopathy (p=0.53). However, in those with definite arteriopathy, a difference was found in sub-classification, with headache prevalence highest in dissection and transient cerebral arteriopathy of childhood (TCA) (70% each) (p>0.001). Acute headache was uncommon in children with moyamoya (12%). Conclusion: No difference was found in headache prevalence in children with and without definite or possible arteriopathy. However, in children with definite arteriopathy, headache was more common in TCA and dissection. This may reflect a higher degree of nociceptive afferent activation in these childhood AIS subtypes and may provide clues to underlying pathophysiologic mechanisms.

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Post Varicella Angiopathy as a Cause of Pediatric Stroke: A Case Report

International Journal of Science and Healthcare Research ◽

10.52403/ijshr.20210407 ◽

2021 ◽

Vol 6 (2) ◽

pp. 36-39

Author(s):

Anju Bala ◽

Parul Bhardwaj ◽

Vipan Garg

Keyword(s):

Ischemic Stroke ◽

Motor Neuron ◽

Varicella Zoster Virus ◽

Facial Nerve Palsy ◽

Internal Capsule ◽

Neurological Complications ◽

Arterial Ischemic Stroke ◽

Varicella Infection ◽

Varicella Zoster ◽

Double Stranded Dna

Varicella-zoster virus is a neurotropic herpes virus that contains double stranded DNA. It can cause primary, latent and reactivation infection. Chickenpox is the primary manifestation and result in life long latent infection of sensory neurons. Varicella infection is usually self limiting and complications occur mostly in immunocompromised patients. The most common neurological complications following varicella infection are cerebellar ataxia and encephalitis but arterial ischemic stroke in pediatric patient is also significant. Post varicella angiopathy also published under transient cerebral arteriopathy and is nearly always self -limited and may be the result of focal inflammation1. Arterial ischemic stroke may occur during the course of varicella infection or one week to several months after the appearance of rash. Here we present a case of 6 years old male who presented with right hemiparesis with right sided facial nerve palsy two months after chickenpox. An MRI was done which was suggestive of hyperintensities in basal ganglia and internal capsule in T-1 weighted MRI. Although the weakness was self-limiting patient was treated with aspirin in addition to supportive measures. Keywords: Arterial ischemic stroke, Post varicella angiopathy, Varicella zoster virus, Middle cerebral artery, Upper motor neuron, Lower motor neuron.

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