Meredith R. Golomb

Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young

PURPOSE The purpose of this statement is to review the literature on childhood stroke and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are responsible for diagnosing and treating infants, children, and adolescents with cerebrovascular disease. METHODS The Writing Group members were appointed by the American Heart Association Stroke Councils Scientific Statement Oversight Committee. The panel included members with several different areas of expertise. Each of the panels recommendations was weighted by applying the American Heart Association Stroke Councils Levels of Evidence grading algorithm. After being reviewed by panel members, the manuscript was reviewed by 4 expert peer reviewers and by members of the Stroke Council Leadership Committee and was approved by the American Heart Association Science Advisory and Coordinating Committee. We anticipate that this statement will need to be updated in 4 years. RESULTS Evidence-based recommendations are provided for the prevention of ischemic stroke caused by sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and cardiogenic embolism. Recommendations on the evaluation and management of hemorrhagic stroke also are provided. Protocols for dosing of heparin and warfarin in children are suggested. Also included are recommendations on the evaluation and management of perinatal stroke and cerebral sinovenous thrombosis in children.

Presumed pre- or perinatal arterial ischemic stroke : Risk factors and outcomes

A subgroup of children with arterial ischemic stroke in the pre‐ or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after 2 months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); 6 of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in 5, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.

Male Predominance in Childhood Ischemic Stroke Findings From the International Pediatric Stroke Study

Background and Purpose— Previous studies suggested a male predominance in childhood ischemic stroke, mirroring gender differences in adults but were limited by small sample sizes or unconfirmed diagnoses. We sought to study gender within a large international series of confirmed cases of pediatric ischemic stroke. Methods— From January 2003 to July 2007, the International Pediatric Stroke Study enrolled children (0 up to 19 years) with arterial ischemic stroke or cerebral sinovenous thrombosis at 30 centers in 10 countries. Neonates were those <29 days of age. We calculated the “expected” gender ratio for our study as the weighted average of population-based childhood gender ratios in enrolling countries weighted by the number of subjects enrolled in each country. &khgr;2 tests were used to compare the observed gender ratios in our series with this expected ratio (51.7%). Results— Among 1187 children with confirmed ischemic stroke, 710 were boys (60%, P<0.0001). Male predominance persisted after stratification by age (61% for neonates, P=0.011; 59% for later childhood, P=0.002) and stroke subtype (58% for arterial ischemic stroke, P=0.004; 65% for cerebral sinovenous thrombosis, P=0.002). The greatest proportion of males occurred among children with arterial ischemic stroke and a history of trauma (75%, P=0.008), although boys were also overrepresented among those with arterial ischemic stroke and no trauma (57%; P=0.07). There were no gender differences in case fatality or deficits at discharge. Conclusions— Childhood ischemic stroke appears to be more common in boys regardless of age, stroke subtype, or history of trauma. Further exploration of this gender difference could shed light on stroke mechanisms in both children and adults.

In-Home Virtual Reality Videogame Telerehabilitation in Adolescents With Hemiplegic Cerebral Palsy

UNLABELLED Golomb MR, McDonald BC, Warden SJ, Yonkman J, Saykin AJ, Shirley B, Huber M, Rabin B, AbdelBaky M, Nwosu ME, Barkat-Masih M, Burdea GC. In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy. OBJECTIVE To investigate whether in-home remotely monitored virtual reality videogame-based telerehabilitation in adolescents with hemiplegic cerebral palsy can improve hand function and forearm bone health, and demonstrate alterations in motor circuitry activation. DESIGN A 3-month proof-of-concept pilot study. SETTING Virtual reality videogame-based rehabilitation systems were installed in the homes of 3 participants and networked via secure Internet connections to the collaborating engineering school and childrens hospital. PARTICIPANTS Adolescents (N=3) with severe hemiplegic cerebral palsy. INTERVENTION Participants were asked to exercise the plegic hand 30 minutes a day, 5 days a week using a sensor glove fitted to the plegic hand and attached to a remotely monitored videogame console installed in their home. Games were custom developed, focused on finger movement, and included a screen avatar of the hand. MAIN OUTCOME MEASURES Standardized occupational therapy assessments, remote assessment of finger range of motion (ROM) based on sensor glove readings, assessment of plegic forearm bone health with dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), and functional magnetic resonance imaging (fMRI) of hand grip task. RESULTS All 3 adolescents showed improved function of the plegic hand on occupational therapy testing, including increased ability to lift objects, and improved finger ROM based on remote measurements. The 2 adolescents who were most compliant showed improvements in radial bone mineral content and area in the plegic arm. For all 3 adolescents, fMRI during grip task contrasting the plegic and nonplegic hand showed expanded spatial extent of activation at posttreatment relative to baseline in brain motor circuitry (eg, primary motor cortex and cerebellum). CONCLUSIONS Use of remotely monitored virtual reality videogame telerehabilitation appears to produce improved hand function and forearm bone health (as measured by DXA and pQCT) in adolescents with chronic disability who practice regularly. Improved hand function appears to be reflected in functional brain changes.

Early Stroke and Cerebral Vasculopathy in Children With Facial Hemangiomas and PHACE Association

PHACE association is a rare neurocutaneous syndrome that may include posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, and sternal defects. The arterial abnormalities may be developmental or acquired and usually involve the cervical and cerebral vasculature. We believe that infants with PHACE association are at increased risk of arterial ischemic stroke and describe 5 infants with facial hemangiomas and structural and acquired arterial anomalies, all of whom suffered an arterial ischemic stroke during infancy.

Neonatal arterial ischemic stroke and cerebral sinovenous thrombosis are more commonly diagnosed in boys

The risk factors for arterial ischemic stroke and cerebral sinovenous thrombosis in neonates are not well understood. We looked at gender, birthweight, and gestational age in neonates with arterial ischemic stroke and cerebral sinovenous thrombosis to see if there were trends suggesting that these were risk factors. We identified neonates with a gestational age at birth ≥ 36 weeks and a diagnosis of arterial ischemic stroke or cerebral sinovenous thrombosis made by computed tomography or magnetic resonance imaging during the neonatal period from a consecutive cohort study of children with arterial ischemic stroke and cerebral sinovenous thrombosis in Ontario. Data on gender, birthweight, and gestational age were obtained by health record review. Sixty-six children with neonatal arterial ischemic stroke were identified. Forty-one (62.1%; 95% CI 49.3—73.8%) were male. Thirty-two children with neonatal cerebral sinovenous thrombosis were identified. Twenty-five (78.1%; 95% CI 60.0—90.7%) were male. One male child was identified with both arterial ischemic stroke and cerebral sinovenous thrombosis. There was a trend toward higher than average birthweights among neonates with arterial ischemic stroke and a trend toward older gestational age in female neonates with arterial ischemic stroke. Our data suggest that neonatal arterial ischemic stroke and cerebral sinovenous thrombosis are more commonly diagnosed in boys. The slightly larger size of male neonates may be contributory in arterial ischemic stroke. It is not known whether boys are at higher risk of developing arterial ischemic stroke and cerebral sinovenous thrombosis or are simply more likely to present with symptoms resulting in diagnosis. These issues need further study. (J Child Neurol 2004;19:493—497).

Cerebral Palsy After Perinatal Arterial Ischemic Stroke

The frequency of cerebral palsy, degree of disability, and predictors of disability were assessed in children in a perinatal arterial stroke database. Risk factors were assessed at the univariate level using the Pearson χ2 and Fisher exact test and at the multivariate level using logistic regression analysis. Seventy-six of 111 children with perinatal stroke (68%) had cerebral palsy, most commonly hemiplegic (66/76; 87%). Multivariate analysis of the entire cohort showed both delayed presentation (OR,9.96; 95% CI, 3.10-32.02) and male sex (OR, 2.55; 95% CI, 1.03-6.32) were associated with cerebral palsy. In subgroup multivariate analyses: in children with neonatal presentation, bilateral infarcts were associated with triplegia or quadriplegia (OR, 5.33; 95% CI, 1.28-22.27); in children with unilateral middle cerebral artery infarcts, delayed presentation (OR, 10.60; 95% CI, 2.28-72.92) and large-branch infarction (OR, 8.78; 95% CI, 2.18-43.67) were associated with cerebral palsy. These data will aid physicians in planning long-term rehabilitative care for children with perinatal stroke.

Cranial ultrasonography has a low sensitivity for detecting arterial ischemic stroke in term neonates.

The aim of this study was to investigate the sensitivity of cranial ultrasonography for detecting acute arterial ischemic stroke in term neonates. Thirty-six neonates with gestational age 36 weeks who had cranial ultrasonography followed by computed tomography (CT) or magnetic resonance imaging (MRI) confirming arterial ischemic stroke were identified from a consecutive cohort study of all children diagnosed with arterial ischemic stroke by CT or MRI and seen at Chedoke McMaster Hospital between January 1992 and December 1998 or at The Hospital for Sick Children between January 1992 and December 2000. Cranial ultrasonography demonstrated focal abnormalities in 11 patients, giving the initial cranial ultrasonography a sensitivity of 30.5% for identifying neonates with infarction (95% CI 15.5—45.5%). The sensitivity of cranial ultrasonography performed in the two pediatric referral centers (Chedoke McMaster Hospital and Hospital for Sick Children; n = 19) was higher than that in community hospitals (n = 17) (47.3% versus 11.7%; P =.031). Neonates with suspected infarction should be evaluated with CT or MRI. (J Child Neurol 2003; 18: 98—103).

PlayStation 3-based tele-rehabilitation for children with hemiplegia

The convergence of game technology (software and hardware), the Internet, and rehabilitation science forms the second-generation virtual rehabilitation framework. This reduced-cost and patient/therapist familiarity facilitate adoption in clinical practice. This paper presents a PlayStation 3-based hand physical rehabilitation system for children with hemiplegia due to perinatal brain injury (hemiplegic cerebral palsy) or later childhood stroke. Unlike precursor systems aimed at providing hand training for post-stroke adults in a clinical setting, the experimental system described here was developed for in-home tele-rehabilitation on a game console for children and adults with chronic hemiplegia after stroke or other focal brain injury. Significant improvements in Activities of Daily Living function followed three months of training at home on the system. Clinical trials are ongoing at this time.

Outcomes of perinatal arterial ischemic stroke and cerebral sinovenous thrombosis

Perinatal stroke can result in cerebral palsy, cognitive impairment, epilepsy, and sensory deficits. While some children only experience one type of disability, severe disabilities often cluster together. Death associated with perinatal stroke is rare, and often associated with other comorbidities. Clinical and radiographic factors can help predict outcome, but additional as-yet unknown factors appear to contribute to outcome as well. Rehabilitation can ameliorate deficits, and advances in rehabilitation technology and in adult stroke rehabilitation offer promise to pediatric perinatal stroke patients.