Outcome of Therapies for Ischemic Cerebrovascular Disease in Children

Outcome after surgery

Endovascular

Endovascular treatment of pediatric ischemic stroke is rare. An analysis of 7341 patients with pediatric ischemic stroke revealed that only 2.6% of patients were treated with thrombectomy (258). Despite its rarity, endovascular treatment of pediatric ischemic stroke cases achieves functional outcomes similar to those of adult stroke cases.

• Functional outcomes: A study of 190 patients who underwent endovascular treatment for pediatric ischemic stroke reported that 55.3% of patients had favorable functional outcomes at discharge (258). A smaller study of only 21 children found that 66% and 86% of patients had a modified Rankin Scale score of 0 to 2 at 30-day and 90-day follow-ups, respectively (274). Furthermore, in a cohort of 40 children treated with thrombectomy, 62.5% and 79.5% of patients had a modified Rankin Scale score of 0 to 2 at 90-day and 1-year follow-ups, respectively (215).
• Clinical scores and outcomes: A study of 73 children from 27 centers reported an improvement from admission to day 7 in median PedNIHSS scores from 14.0 to 4.0, with a median modified Rankin Scale score of 1 at 6-month and 24-month follow-ups (92). A retrospective case review of 24 children treated with intra-arterial fibrinolysis only and 44 children treated with thrombectomy found that only 13.4% of patients in the former group, versus 52.2% of patients in the latter group, had good clinical outcomes (275).

Decompressive Craniectomy

Decompressive craniectomy is rare and applied only in severe cases, so there are very few reports of outcomes following this procedure for children with arterial ischemic stroke. This lack of reporting makes the outcome difficult to compare to cases without decompressive surgery.

• Rare procedure with low mortality, but patients often have severe neurological deficits at discharge: Of the 4294 children in the IPSS, 38 patients (less than 1%) underwent craniectomy; the mortality rate was 8%, and 62% of patients who underwent decompressive hemicraniectomy had severe deficits at time of discharge (224).
• May improve survival in children with malignant strokes: A review of 97 cases reported in the literature revealed a 95.4% survival rate with craniectomy for malignant ischemic stroke, as compared to a 67% mortality rate without craniectomy (276).  This review reported a median modified Rankin Scale score of 2 after craniectomy with a mean follow-up of 31.8 months .

Outcome after nonsurgical treatments

• Medical management only is very common and very effective: An analysis of 7341 patients with pediatric ischemic stroke revealed that 97.4% of patients were treated with medical management only (258). Of these patients, 83.7% had favorable functional outcomes at discharge. It should be noted that in this study, outcomes of medical management cannot reasonably be compared to those of endovascular thrombectomy (also reported in this study) given the confounding variable of stroke severity, which affects both patient selection and outcomes.
• IV tPA is used less commonly in children than in adults but achieves similar results: In a study of 2904 children with ischemic stroke, only 24 (less than 1%) received IV tPA (277). Compared with patients who did not receive tPA, these patients had higher mortality rates and were more likely to be discharged to a long-term facility, but this does not control for stroke severity. In a cohort of 28 children treated with IV tPA, 77.8% of patients had a modified Rankin Scale score of 0 to 2 at both 90-day and 1-year follow-ups (215).

Outcome after multimodal therapies

Two factors limit the analysis of outcomes following either endovascular or open surgical intervention and adjuvant therapies.

• Limited number of patients: The remarkably low percentage of patients who undergo endovascular or open surgical intervention for pediatric ischemic stroke limits the number of patients reported in the literature.
• Reporting inadequacies: Reporting inadequacies hinder the determination of what adjuvant therapies, if any, were employed during a given patient’s admission for stroke. As there are many adjuvant therapies, even within the same broad category of intervention, future reports should attempt to clearly define the nature of multimodal therapy to enable comparison and determine optimal strategies for individual patients.

Outcomes: General/Overall

Mortality

Recent mortality rate estimates — which include both stroke-specific mortality and mortality due to underlying systemic illness — have decreased to around 10% (268,269).

• Older studies report higher mortality: Estimates of stroke-specific mortality may be complicated by the presence of an underlying systemic illness (62). Perhaps due to improved specificity of reporting and/or more effective stroke care, older studies report higher mortality (range of 7% to 28%) for pediatric ischemic stroke (265,266).
• Recent studies report lower mortality: More recent analyses have reported stroke-specific mortality to be between 4% and 5% (10,267). When mortality due to underlying systemic illness is included, rates of 10% and 14% have been reported (268,269).

Recurrence

Recent estimates of stroke recurrence have decreased to approximately 7% in the 2 years following the initial stroke.

• Older studies report higher recurrence rates: Studies using data from 1978 to 2004 have reported stroke recurrence rates of nearly 20% (270,271).
• Recent studies report lower recurrence rates: In a 2016 study involving 37 international centers and 355 children with ischemic stroke, the cumulative stroke recurrence rate was 6.8%, with a median follow-up time of 2.0 years and only one predictor of recurrence (the presence of an arteriopathy) (272).
• Secondary stroke prevention strategies have improved: Recent estimates of stroke recurrence rates are remarkably lower than those previously reported. This decrease may be explained by improvements in secondary stroke prevention strategies for children, perhaps due to increased use of antithrombotic medications (272).

Neurological Outcomes

Several studies have reported neurological outcomes after pediatric ischemic stroke. However, analysis of these outcomes is hindered by lack of standardization in how neurological outcomes are assessed and reported.

• An estimated 60% to 70% of children have neurological deficits at discharge and follow-up: One large study reported that neurological deficits were present in 60% of neonates and almost 70% of older children at ≥29-day follow-up: 33% of neonates and 36% of older children had mild deficits, 19% of neonates and 23% of older children had moderate deficits, and 8% of neonates and 10% of older children had severe deficits (10). In a cohort of 124 children who presented with ischemic stroke, 66% were reported to have neurological deficits at discharge (267).
• Several predictors of poor neurological outcomes have been identified: Predictors of poor neurological outcomes include infarct size, multiple infarcts, involvement of both cortical and subcortical regions, involvement of the basal ganglia and posterior limb of the internal capsule, hyperglycemia in the acute poststroke period, and seizures in the acute poststroke period (62).

Cognitive and Functional Outcomes

Cognitive and functional outcomes of children who suffered ischemic stroke have been reported extensively in the literature. However, as with neurological outcomes, the methodology for evaluating these outcomes is not standardized. Moreover, scores and scales used for the assessment of cognitive and functional outcomes may not be applicable for children of all ages.

• Cognitive outcomes: One study of cognitive outcomes after stroke analyzed measures of overall intelligence, verbal ability, working memory, and processing speed. The investigators found that all of these measures were significantly lower in children who suffered an ischemic stroke compared with the normative sample, and that younger age at the time of stroke was associated with poorer performance (273).
• Functional outcomes: One study reported that 50% of children had a good outcome at 12-month follow-up (Pediatric Stroke Outcome Measure score <1), and 38% of children were judged by their caretakers as having fully recovered (269). Another study with a median follow-up time of 6.9 years found that 56% of children and 55% of young adults had a favorable outcome (modified Rankin Scale score 0 or 1) (268).