Recanalization Treatment in Pediatric Arterial Ischemic Stroke

Dr. Knox is Pediatric Neurology Resident, Department of Pediatrics, Division of Child Neurology, Weill Cornell Medicine/New York Presbyterian Hospital. Dr. Kosofsky is Professor of Pediatrics and Neurology, Weill Cornell Medical College.

Dr. Knox reports no financial relationships relevant to this field of study. Dr. Kosofsky reports he is a major stockholder in b2d2, a biotechnology company.

SYNOPSIS: In a population-based study from Switzerland, the authors found that recanalization treatment (intravenous thrombolysis or endovascular treatment) overall was safe without significant side effects or increased mortality compared to standard care.

SOURCE: Bigi S, Dulcey A, Gralla J, et al. Feasibility, safety, and outcome of recanalization treatment in childhood stroke. Ann Neurol 2018;83:1125-1132.

The incidence of pediatric arterial ischemic stroke (AIS) is about two per 100,000. Up to half of pediatric stroke patients subsequently have neurologic deficits or epilepsy. The American Heart Association guidelines on infant and pediatric stroke give recommendations based on etiology. Treatment options include intravenous thrombolysis (IVT), intra-arterial thrombolysis (IAT), and mechanical thrombectomy. However, use of these interventions varies by center, and, often, the appropriate diagnosis is made late and outside the window for intervention. Several groups have published small series about pediatric stroke patients detailing their experience with IVT, IAT, and mechanical thrombectomy. Using the International Pediatric Stroke Study (IPSS), Amlie-Lefond et al found that 15 patients receiving alteplase over a four-year period tolerated the treatments.¹ However, most patients (12/13) had neurologic deficits at the time of discharge. Tabone et al created a stroke protocol for two regional centers in France, and published their experience with 13 children receiving recanalization therapy. They also found these procedures were tolerated without significant side effects, and 11/12 survivors had modified Rankin Scale of 0-2.² Tatum et al published results on four pediatric stroke cases who underwent mechanical embolectomy using FDA-approved devices over a six-year period.³ Three out of four of these cases had improved pediatric modified Rankin scale scores, which were ≤ 2. These studies demonstrate that recanalization procedures are tolerated, but not frequently used, in diverse pediatric stroke populations.

Bigi et al published the first population-based cohort to assess the safety of recanalization in pediatric AIS. The cohort was drawn from a nationwide registry in Switzerland of all pediatric stroke cases, and they reported on data from 2000 to 2015. There were 150 AIS cases with a pediatric NIH Stroke Scale (NIHSS) ≥ 4. Sixteen of these cases underwent recanalization, which was defined as IVT, IAT, or mechanical recanalization. Mean age was 7 years. Etiology was unknown in 40% of cases, 18% were cardioembolic, and 17% were focal cerebral arteriopathy. Four patients died secondary to stroke. Only two complications were noted: asymptomatic intracerebral hemorrhage and mucosal bleeding. Five patients developed malignant middle cerebral artery infarctions. Complete recanalization was achieved in 25% of cases, and partial recanalization in 38%, with 25% having no recanalization. Of note, they found that patients receiving recanalization therapy had higher PedNIHSS scores, were older, and had a shorter time interval from symptom onset to diagnosis. A multiple regression analysis showed that higher baseline PedNIHSS was associated with higher morbidity six months after treatment. Overall, these investigators concluded that recanalization is well tolerated, but stressed the importance of needing larger studies.

COMMENTARY

The research by Bigi et al adds to the rich emerging literature regarding improvements in the diagnosis and treatment of pediatric stroke, which in part has resulted from, as well as contributed to, the establishment of regional centers of excellence. Although randomized, controlled trials and larger studies are needed, this study adds further evidence that recanalization should be considered and performed more frequently. In their cohort, at most, four children per year underwent recanalization treatment. They also noted that more strokes were recognized between 2011 and 2015 than previous time periods, highlighting the importance of education and awareness of strokes in the pediatric population. Without recognition of stroke and appropriate imaging early in the course, children are not candidates for these potentially life-saving interventions. More research into this important area is necessary to continue to make therapeutic advances and determine potential differences in the best practices for pediatric and adult patients following stroke, as is greater participation in multisite clinical trials and registries, such as those that have been conducted by the International Pediatric Stroke Society.

REFERENCES

1. Amlie-Lefond C, deVeber G, Chan AK, et al; International Pediatric Stroke Study. Use of alteplase in childhood arterial ischaemic stroke: A multicenter, observational, cohort study. Lancet Neurol 2009;8:530-536.
2. Tabone L, Mediamolle N, Bellesme C, et al. Regional pediatric acute stroke protocol: Initial experience during 3 years and 13 recanalization treatments in children. Stroke 2017;48:2278-2281.
3. Tatum J, Farid H, Cooke D, et al. Mechanical embolectomy for treatment of large vessel acute ischemic stroke in children. J Neurointerven Surg 2013;5:128-134.