Selected publications

• Pediatric Cerebral Sinus Venous Thrombosis during the First Three Years of the SARS-CoV-2 Pandemic: A Multinational Case Series

  2025-09-05

  articleOpen access

  Background: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has been associated with thrombotic complications in adults and children. Cerebral sinovenous thrombosis (CSVT) has also been described in adults with SARS-CoV-2, though rarely rep

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• Evidence of Varicella Zoster Virus Reactivation in Children With Arterial Ischemic Stroke: Results of the VIPS II Study.

  PubMed · 2025-03-18 · 10 citations

  articleOpen access

  BACKGROUND: Varicella zoster virus (VZV) has historically been associated with focal cerebral arteriopathy and arterial ischemic stroke (AIS) in children, and risk of AIS and myocardial infarction in adults. The VIPS (Vascular Effects of Infection in Pediatric Stroke) II study aimed to determine whether VZV remains a pediatric stroke trigger in an era of routine VZV vaccination. METHODS: This 22-center prospective cohort study enrolled 205 patients (28 days to 18 years; median, 11.6 years) with spontaneous AIS (December 2016 to January 2022) in North America and Australia, performed parental interviews, and collected baseline (hyperacute [≤72 hours; n=194] and acute [4-6 days; n=181]) and convalescent (1-6 weeks; n=74) serum samples. A virology research laboratory measured VZV IgM and IgG titers by an in-house ELISA in patients with AIS and 95 unmatched well control children. RESULTS: Baseline serologies indicated prior VZV exposure in 198 patients (97%). Parents recalled prior VZV vaccination in 160 (78%) and remote chickenpox in 3 (1.4%). Twenty patients (9.8%) had serologic evidence of recent VZV reactivation at the time of their stroke; all were asymptomatic. All had remote VZV exposure with VZV vaccination (median) 6.1 years prior. We observed recent VZV reactivation in patients with focal cerebral arteriopathy (4/32 [12.5%]) but not with arterial dissection or moyamoya. All 95 controls had serologic evidence of prior VZV exposure and 3 (3.1%) had recent VZV reactivation. CONCLUSIONS: One in 10 patients with childhood AIS had recent, asymptomatic VZV reactivation. In a vaccinated population, VZV may continue to play a modest role in childhood stroke pathogenesis.

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• The International Pediatric Stroke Study: Insight into Childhood Stroke from a Developmental Perspective

  The Journal of Pediatrics · 2025-12-17 · 1 citations

  article
  PublisherDOI

• Changing Management of Focal Cerebral Arteriopathy of Childhood From 2010 to 2022

  Stroke · 2025-05-12 · 2 citations

  article

  BACKGROUND: The most common cause of arterial ischemic stroke in healthy children, focal cerebral arteriopathy (FCA), can progress rapidly over days with worsening brain injury. A 2017 retrospective Swiss study of corticosteroid treatment for FCA changed practice. To assess its impact, we compared the FCA cohorts from the 2 VIPS (Vascular Effects of Infection in Pediatric Stroke) prospective cohort studies. METHODS: The VIPS II study prospectively enrolled 205 children (29 days to 18 years) with arterial ischemic stroke at 22 centers, December 2016 to January 2022. The local team measured 12-month outcomes using the pediatric stroke outcome measure. A neuroradiologist and pediatric vascular neurologist independently reviewed all clinically obtained imaging and clinical data to classify the cause of arterial ischemic stroke. The neuroradiologist measured the FCA Severity Score on vascular imaging performed at any time poststroke. We compared the VIPS II FCA cohort to the previously published FCA cohort from VIPS I (2010–2014; 37 centers). RESULTS: Of 75 children with definite arteriopathy enrolled in VIPS II, 32 (43%) had FCA, compared with 41 of 127 (32%) of definite arteriopathy cases in VIPS I. The median age was 11.3 years (56% male) in VIPS I and 11.4 years (55%) in VIPS II. Treatment with intravenous corticosteroids increased from 2 of 41 (5%) of FCA patients in VIPS I to 18 of 32 (56%) in VIPS II. The VIPS II FCA cases were more severe at baseline (median FCA Severity Score 6 versus 4; P =0.006). There were no significant differences in either the change in FCA Severity Score (baseline to maximum) or the 12-month neurological outcomes. CONCLUSIONS: Treatment of FCA with corticosteroids increased dramatically between the VIPS I and VIPS II studies. VIPS II cases were more severe at baseline, but we observed no significant difference in disease progression or neurological outcomes. Given the low level of evidence supporting corticosteroid therapy, pediatric stroke centers should enroll FCA patients into ongoing FCA corticosteroid treatment trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT04873583 and NCT06040255.

  PublisherDOI

• Assessing the Impact of the COVID-19 Pandemic on Childhood Arterial Ischemic Stroke: An Unanticipated Natural Experiment

  Stroke · 2025-04-02 · 5 citations

  articleOpen access

  BACKGROUND: The VIPS (Vascular Effects of Infection in Pediatric Stroke) II prospective cohort study aimed to better understand published findings that common acute infections, particularly respiratory viruses, can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through enrollment, creating an opportunity to assess its impact. METHODS: Twenty-two sites (North America, Australia) prospectively enrolled 205 children (aged 28 days to 18 years) with AIS from December 2016 to January 2022, including 100 cases during the COVID-19 pandemic epoch, defined here as January 2020 to January 2022. To assess background rates of subclinical infection, we enrolled 100 stroke-free well children, including 39 during the pandemic. We measured serum SARS-CoV-2 nucleocapsid total antibodies (present after infection, not vaccination; half-life of 3–6 months). We assessed clinical infection via parental interview. RESULTS: The monthly rate of eligible AIS cases declined from spring through fall 2020, recovering in early 2021 and peaking in the spring. The prepandemic and pandemic cases were similar except pandemic cases had fewer clinical infections in the prior month (17% versus 30%; P =0.02) and more focal cerebral arteriopathy (20% versus 11%; P =0.09). Among pandemic cases, 26 of 100 (26%) had positive antibodies, versus 4 of 39 (10%) of pandemic-era well children ( P =0.04). The first SARS-CoV-2 positive case occurred in July 2020. Ten of the 26 (38%) positive cases had a recent infection by parental report, and 7 of those 10 had received a diagnosis of COVID-19. Only 1 had multisystem inflammatory syndrome in children. Median (interquartile range) nucleocapsid IgG total levels were 50.1 S/CO (specimen to calibrator absorbance ratio; 26.9–95.3) in the positive cases and 18.8 (12.0–101) in the positive well children ( P =0.33). CONCLUSIONS: The COVID-19 pandemic may have had dual effects on childhood AIS: an indirect protective effect related to public health measures reducing infectious exposure in general, and a deleterious effect as COVID-19 emerged as another respiratory virus that can trigger childhood AIS.

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• Abstract 133: Asymmetry of Arteriopathy in Pediatric Moyamoya

  Stroke · 2025-01-30

  articleSenior author

  Introduction: Moyamoya is a progressive steno-occlusive cerebrovascular arteriopathy of bilateral anterior circulation. The pathophysiology is elusive, and once established, moyamoya is typically inexorably progressive. Hypothesis: We hypothesized that the left-sided circulation is more vulnerable to steno-occlusive arteriopathy compared to the right, which may reflect differences in mechanical stress from blood flow. Methods: All children with moyamoya cared for between 1/1/2009 and 7/1/2024 at a single institution were identified through an IRB-approved, retrospective study. The charts and neuroimaging at the time of diagnosis were reviewed to assess symmetry of steno-occlusion. Chi-square test was used for statistical analysis, with p-value <0.05 considered statistically significant. Results: A total of 67 children (35 males) with moyamoya were identified. Steno-occlusive arteriopathy at diagnosis was assessed on head and neck MRA for all 67, as well as on cerebral catheter angiogram in the 32 patients who underwent interventional neuroimaging. Arteriopathy was more severe on the left than the right in 29 (43%), and more severe on the right than the left in 15 (22%). This left-sided predilection was statistically significant (p=0.03). Twenty-three (34%) children had complete occlusion of bilateral anterior circulation without asymmetry at diagnosis. Of the 38 (57% of the total) patients with clinical stroke at the time of presentation, 21 (55%) had right hemiplegia, 10 (26%) had left hemiplegia, and 7 (18%) presented without focal weakness. Conclusions: Moyamoya is an important cause of childhood stroke, and a risk factor for recurrent ischemic and hemorrhagic stroke throughout life. The mechanism of arteriopathy initiation and progression is unknown, and current treatment consists of palliative revascularization. The left predominance of arteriopathy with moyamoya may provide insight into underlying causes of moyamoya arteriopathy. A better understanding of moyamoya pathophysiology may also inform interventions to halt the progression of steno-occlusive arteriopathy once it has begun.

  PublisherDOI

• Tenecteplase for the Treatment of Pediatric Arterial Ischemic Stroke

  Neurology · 2025-01-13 · 5 citations

  articleCorresponding

  OBJECTIVES: Intravenous tenecteplase (TNK) is increasingly used to treat adult patients with acute arterial ischemic stroke, but the risk profile of TNK in childhood stroke is unknown. This study aims to prospectively gather safety data regarding TNK administration in children. METHODS: Since December 2023, a monthly email survey was sent to participants recruited from the International Pediatric Stroke Study and Pediatric Neurocritical Care Research Group querying recent experience with TNK in childhood stroke. Limited demographic, safety, and outcome data were collected in a secure REDCap database. Detailed clinical data were not collected. RESULTS: Eleven children were reported to have received TNK between February 2023 and January 2024. Ten were adolescents (13-17 years old), and 1 was between 5 and 12 years old. TNK was given at an outside facility before transfer to the reporting facility in 7 cases. Final diagnosis was stroke in 8 cases and stroke mimic in 3 cases. No major safety concerns or TNK-related intracranial hemorrhages on follow-up imaging were reported. DISCUSSION: Our initial data suggest that TNK may be safe in childhood arterial ischemic stroke. Strategically designed prospective studies are needed to further define safety, optimal dosage, and efficacy of TNK in acute pediatric stroke.

  PublisherDOI

• Contributors

  Elsevier eBooks · 2025-06-02

  book-chapter
  PublisherDOI

• Cerebral Arteriopathies

  Elsevier eBooks · 2024-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• Anticoagulation for Septic Cerebral Venous Thrombosis in Childhood

  Journal of Pediatric Hematology/Oncology · 2024-09-09 · 2 citations

  articleSenior author

  Anticoagulation is recommended for most children with cerebral venous thrombosis (CVT) to prevent venous infarction and promote recanalization. An exception is CVT associated with head and neck infection (septic CVT), for which treatment of infection without concomitant use of anticoagulation is recommended. Despite this, the use of anticoagulation in septic CVT is controversial, and children with septic CVT are often anticoagulated due to concerns about thrombus progression and persistence despite infection treatment. A retrospective study of children with septic CVT cared for at Seattle Children's Hospital between 2009 and 2023 was conducted to assess the safety and outcome of anticoagulation. Among 40 children with septic CVT, 25 (63%) received anticoagulation. None had bleeding complications. Performance of follow-up venous imaging was inconsistent and more commonly pursued in patients treated with anticoagulation. A total of 23/40 (58%) patients were evaluable at 1 month, among whom 26% (6/23) had resolution of thrombus and 74% (17/23) had persistence. A total of 22/40 (55%) patients were evaluable at 3 months, among whom 77% (17/22) had resolution of thrombus and 23% (5/22) had persistence. This supports the safety of anticoagulation, but further studies are needed to determine whether anticoagulation improves outcomes after septic CVT.

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