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

Abstract

Objective: To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis.

Methods: A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model).

Results: All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand.

Conclusions: Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement.

Classification of evidence: This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy.

© 2016 American Academy of Neurology.

Figures

Figure 1. Recruitment, randomization, and flow

(A) Screening sampled the eligible population across the study period grouped by age and developmental level. Most were excluded by age or ability to attend the program. Intention-to-treat groups are shown as analyzed. (B) Study flow began with baseline motor function and neurophysiology outcome measures within 2 weeks of starting therapy. Daily programming for 2 weeks (days 1–10) included goal-directed, intensive motor learning therapy. Participants randomly received daily contralesional rTMS, CIMT, neither, or both. Outcome measures were repeated at 1 week, 2 months, and 6 months. APSP = Alberta Perinatal Stroke Project; CIMT = constraint-induced movement therapy; rTMS = repetitive transcranial magnetic stimulation; TMS = transcranial magnetic stimulation.

Figure 2. Primary outcomes

(A) AHA scores across time and treatment. Largest changes at 6 months were observed with rTMS + CIMT. Top dashed line indicates clinically significant change of ≥5 logit units. (B) COPM satisfaction and performance increased at 1 week with sustained or further elevations at 2 and 6 months across all participants. (C) Change in COPM by treatment group. Clinically significant gains (≥2 units, top dashed line) were associated with CIMT, rTMS, or both. Open circles = outliers. AHA = Assisting Hand Assessment; CIMT = constraint-induced movement therapy; COPM = Canadian Occupational Performance Measure; rTMS = repetitive transcranial magnetic stimulation.

Figure 3. Secondary outcomes

(A) Mean MA scores increased from baseline at 1 week with greater effects in the rTMS group. (B) By 6 months, no change in mean MA score was observed across groups. PedsQL CP–measure parent scores for child daily activity (C) and school activity (D) increased at 6 months with treatment effects similar to those seen in motor function scores (*p < 0.05). Open circles = outliers. CIMT = constraint-induced movement therapy; CP = cerebral palsy; MA = Melbourne Assessment; PedsQL = Pediatric Quality of Life Inventory; rTMS = repetitive transcranial magnetic stimulation.

Figure 4. Safety

Unaffected hand function did not decrease with any interventions. (A) Box and blocks performance at 6 months was unchanged except for an increase in function associated with CIMT (p = 0.03). (B) Grip strength of the unaffected hand was maintained and increased in those receiving rTMS (p = 0.008). (C) In participants with prominent ipsilateral corticospinal tract arrangements (n = 20), no decrease in hand function was associated with rTMS where MA gains were actually larger. Open circles = outliers. CIMT = constraint-induced movement therapy; MA = Melbourne Assessment; rTMS = repetitive transcranial magnetic stimulation.