Brain stimulation and constraint for hemiparesis after perinatal stroke: The PLASTIC CHAMPS trial

Abstract

Background: Perinatal stroke causes hemiparetic cerebral palsy. Constraint therapy (CIMT) improves function in congenital hemiparesis and adult stroke. Repetitive transcranial magnetic stimulation (rTMS) may improve function in adult stroke. The two have not been tested in perinatal stroke. Methods: PLASTIC CHAMPS (www.clinicaltrials.gov/NCT01189058) was a controlled factorial trial of rTMS and CIMT in perinatal-stroke hemiparesis. Children 6-18 years participated in a 2 week peer-supported motor learning camp, randomized to daily inhibitory rTMS (1200 stimulations, contralesional M1), CIMT, both or neither. Primary outcomes were Assisting Hand Assessment (AHA) and Canadian Occupational Performance Measure (COPM) at 1, 8, and 24 weeks. Quality-of-life, safety and tolerability were evaluated. Change was assessed across treatment groups over time (linear mixed effects model). Results: All forty-five subjects completed the trial (median 11.4yrs). COPM scores increased >100% with maximal gains at 6 months (p<0.002). Addition of rTMS and/or CIMT doubled the chances of clinically significant gains. Combined rTMS+CIMT resulted in larger AHA gains at all time points (6 months p=0.006). CIMT or rTMS alone had more modest effects. Neither treatment decreased function in either hand. Procedures were well tolerated. Conclusions: Children with hemiparesis participating in intensive, psychosocial rehabilitation programs perceive marked increases in function. Non-invasive brain stimulation may enhance motor learning therapy in perinatal stroke hemiparesis.

Fatigue in children with perinatal stroke: clinical and neurophysiological associations

“…22 Inclusion criteria were: age 6 to 19 years; term birth; magnetic resonance imaging (MRI)-confirmed unilateral perinatal arterial ischemic stroke or periventricular venous infarction, symptomatic hemiparetic CP including Pediatric Stroke Outcome Measure>0.5; Manual Ability Classification Scale levels I to IV; both parent and child perceived functional limitations; written informed consent and/or assent. 22 Inclusion criteria were: age 6 to 19 years; term birth; magnetic resonance imaging (MRI)-confirmed unilateral perinatal arterial ischemic stroke or periventricular venous infarction, symptomatic hemiparetic CP including Pediatric Stroke Outcome Measure>0.5; Manual Ability Classification Scale levels I to IV; both parent and child perceived functional limitations; written informed consent and/or assent.…”

Mirror movements in children with unilateral cerebral palsy due to perinatal stroke: clinical correlates of plasticity reorganization

“…Arterial ischemic strokes most commonly occur near term in the middle cerebral artery territory while periventricular venous strokes occur in the fetus . As a focal injury of defined timing in an otherwise typically developing brain, perinatal stroke is an ideal human model of developmental neuroplasticity …”

“…Imaging and brain stimulation can map this complex neurophysiology in vivo, validating the model in real patients . Such modeling has direct implications for emerging treatment modalities including constraint‐induced movement therapy and non‐invasive brain stimulation but is both cumbersome and expensive. A clinical assessment that could assess this motor organization at the bedside could be a useful tool for implementing more personalized approaches to neurorehabilitation.…”

“…2 As a focal injury of defined timing in an otherwise typically developing brain, perinatal stroke is an ideal human model of developmental neuroplasticity. 3 The most common morbidity after perinatal stroke is motor disability, typically unilateral spastic CP. Emerging evidence from preclinical and human studies have informed models of developmental motor system organization.…”

Current therapies and therapeutic decision making for childhood‐onset movement disorders

“…Repetitive TMS (rTMS) techniques have been shown to be safe in children . rTMS has been shown to produced noticeable neurological benefit in poststroke patients, including children with perinatal or neonatal stroke . The magnitude of effects noted may vary, but the main challenges are immobility of equipment and the requirement for sustained repetitive stimulation to maintain benefits.…”