Arteriopathy in pediatric stroke: an underestimated clinical entity

Abstract

Background: Pediatric arterial ischemic stroke (AIS), which was thought to be a rare disorder, is being increasingly recognized as an important cause of neurological morbidity, thanks to new advances in neuroimaging. Objective: The aim of this study was to review the main etiologies of stroke due to arteriopathy in children. Methods: Using a series of cases from our institution, we addressed its epidemiological aspects, physiopathology, imaging findings from CT, MR angiography, MR conventional sequences and MR DWI, and nuclear medicine findings. Results: Through discussion of the most recent classification for childhood AIS (Childhood AIS Standardized Classification and Diagnostic Evaluation, CASCADE), we propose a modified classification based on the anatomical site of disease, which includes vasculitis, varicella, arterial dissection, moyamoya, fibromuscular dysplasia, Takayasu's arteritis and genetic causes (such as ACTA-2 mutation, PHACE syndrome and ADA-2 deficiency). We have detailed each of these separately. Conclusions: Prompt recognition of AIS and thorough investigation for potential risk factors are crucial for a better outcome. In this scenario, neurovascular imaging plays an important role in diagnosing AIS and identifying children at high risk of recurrent stroke.

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

“…Deficiency of ADA-2 can lead to vasculopathy and inflammation through the macrophages and the polarization of monocytes onto proinflammatory cells, resulting in damage to the endothelial integrity. Vasculopathy, associated with hemorrhagic and ischemic strokes in ADA2 deficiency, has an early-onset as well as clinical and histopathological characteristics of polyarteritis nodosa (PAN) [79]. DADA2 is predominately expressed in childhood.…”

Pediatric Stroke: A Review of Common Etiologies and Management Strategies

“…Children with predisposing factors such as genetic or acquired connective tissue disorders (e.g., copper deficiency) may be more susceptible to dissection; however, the absence of these risks does not rule out the possibility of an ensuing vascular insult [54,57]. The risk of dissection due to connective tissue disorders such as Marfan's and Ehler-Danlos syndrome is not well elucidated, but it is not negligible and can lead to multiple dissections [58]. The male gender is also a reported risk factor for AIS from craniocervical arterial dissection [57].…”

“…However, whiplash injuries are another mechanism by which dissections can occur-there have been some reports of strokes in children after amusement park rides [60]. Additionally, while adult dissections are nearly all traumatic in nature, there is in children a substantial incidence of spontaneous dissections without preceding trauma [58]. Approximately 5-20% of children with a spontaneous dissection have an underlying connective tissue or genetic disorder, or bony or vascular anatomic variations [56].…”

“…Approximately 5-20% of children with a spontaneous dissection have an underlying connective tissue or genetic disorder, or bony or vascular anatomic variations [56]. Most spontaneous dissections occur in the anterior circulation vessels, and cases involving the posterior circulation are more likely to be traumatic [58].…”

“…Within their cohort, 20.8% of children with dissections had stroke recurrence, which is a significantly higher figure than the rate seen in the adult population. Additionally, long-term effects of strokes in children are significant, and up to 75% of children affected by stroke can experience lasting neurological deficits [58]. This may be linked to misdiagnosis or an unidentified etiology.…”