Location of Childhood Arterial Ischemic Stroke Influences Recurrence

Ischemic stroke of the posterior circulation is rare, accounting for only 20% of all episodes of childhood arterial ischemic stroke (CAIS), and yet it is associated with 80% of all CAIS recurrence in pediatric patients, according to a new study in JAMA Neurology.¹

As an estimated 20% of all patients who experience CAIS are likely to have a recurrence within 5 years,^2,3 the current study was designed to identify features of CAIS most likely to carry risk.

The investigators retrospectively evaluated a cohort of 107 pediatric patients (75 male, 32 female, median age 7.7 years) who presented to the Children’s Hospital of Philadelphia between January 2006 and January 2015 with confirmed CAIS. The diagnoses were subclassified using the Childhood AIS Standardized Classification System and Diagnostic Evaluation (CASCADE) criteria according to CAIS isolated to the anterior (ACAIS) or posterior (PCAIS) circulation in 2 groups of 61 patients (57%) and 46 patients (43%), respectively, who were followed up at a median of 20.9 months.

“It is standard clinical practice to evaluate children in a comprehensive manner for all types of risk factors when they have a stroke,” explained study co-investigator Rebecca Ichord, MD, director of the Pediatric Stroke Program of the Children’s Hospital of Philadelphia, Pennsylvania. “This typically includes vascular imaging, cardiac evaluation, and lab evaluation for prothrombotic disorders.”

The PCAIS group comprised the majority (81.8%) of all recurrences in the cohort, which showed a total estimated recurrence of 10.3% at 3 years. Patients with ACAIS remained free of recurrence at 1 month and 96% free (95% CI, 85%-99%) at follow-up at 1 and 3 years. Recurrence-free survival was significantly lower in the PCAIS group:  88% (95% CI, 75%-95%) at 1 month and 81% (95% CI, 66%-90%) at 1 and 3 years.

At 1- and 3-year follow-up, 9 and 2 episodes of recurrence occurred in patients with PCAIS and ACAIS, respectively. Recurrences were most likely to occur within 6 months of the original stroke event. After univariate analysis (hazard ratio (HR) = 6.4 [95% CI, 1.429.8; P =.02]) and adjusting for sex and cervical dissection (HR = 5.3 [95% CI, 1.1-26.4; P =.04]), PCAIS remained the only risk factor for CAIS recurrence compared with ACAIS.

Of 11 recurrences, 10 (90.9%) were in male patients. This may have been due to an overrepresentation of male participants in the study who made up 70.1% of the cohort, although the investigators pointed out that the rate of arterial dissection has also been shown to be higher in males.^4,5 Of 19 patients with cervical vertebral artery dissection, 5 (26.3%) had recurrences, although this was also not identified as an independent risk factor for recurrence.

The investigators suggested that the substantially greater risk of recurrence in PCAIS compared with ACAIS may point to differences in underlying mechanisms in the two kinds of stroke, and that closer monitoring in children with PCAIS may be warranted.

Of note, the majority of patients (92.5%) were treated with antithrombotic therapies. Although, “some patients did ultimately receive dual antiplatelet and anticoagulation therapy under the umbrella of different prevention strategies,” Dr Ichord emphasized that the current study was performed as a descriptive and “fact-finding” study. “It was not designed in a way that would provide evidence to support a recommendation about standard of care.” She and her colleagues concluded that such treatment in PCAIS also warrants further investigation.

References

1. Uohara MY, Beslow LA, Billinghurst L, et al. Incidence of recurrence in posterior circulation childhood arterial ischemic stroke [published online January 23, 2017]. JAMA Neurol. doi:10.1001/jamaneurol.2016.5166
2. Fullerton HJ, Wu YW, Sidney S, Johnston SC. Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics. 2007;119:495-501.
3. Mackay MT, Wiznitzer M, Benedict SL; International Pediatric Stroke Study Group. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol. 2011;69:130-140.
4. Fullerton HJ, Johnston SC, SmithWS. Arterial dissection and stroke in children. Neurology. 2001;57:1155-1160.
5. Golomb MR, Fullerton HJ, Nowak-Gottl U, et al; International Pediatric Stroke Study Group. Male predominance in childhood ischemic stroke: findings from the International Pediatric Stroke Study. Stroke. 2009;40:52-57.