P 168. TMS neurophysiology and interventional rTMS in children with perinatal stroke: Safety and tolerability in the PLASTIC CHAMPS trial

Abstract

Perinatal stroke causes hemiplegic cerebral palsy and lifelong disability. TMS can define neurophysiology and central therapeutic targets while rTMS carries therapeutic potential in adult stroke but have not been applied to the more plastic developing brain. Ipsilateral projections from the unlesioned hemisphere to the affected hand are prominent in this population and the effects of non-lesioned inhibitory rTMS are unknown. PLASTIC CHAMPS is a randomized, blinded, factorial clinical trial of rTMS and constraint therapy (CIMT) to enhance upper extremity function in children (6–18 years) with perinatal stroke hemiparesis. Thirty-five children (mean age 11.25 y, 20 males) attended a 2-week intensive motor learning camp, randomized 1:1 to daily non-lesioned M1 inhibitory (1 Hz, 1200 stimulations) rTMS or sham. TMS neurophysiology mapping lasting 90–120 min (baseline and 1 week post-camp) included RMT, AMT, stimulus response curves, iSP, SICI, ICF, and IHI. Primary safety outcomes were decreased function in: (1) affected hand in children with ipsilateral projections (Assisting Hand Assessment (AHA), Melbourne Assessment (MA)) and (2) unaffected hand in all children (grip strength [GS], pinch strength [PS]). The Pediatric TMS Tolerability Evaluation was administered at 4 timepoints: 2 TMS neurophysiology sessions (pre and post camp) and 2 rTMS treatments (days 1 and 10). This measure characterizes any adverse events and subjectively ranks TMS against 7 common childhood experiences. Differences in hand function and tolerability scores were compared between rTMS and sham and over time (paired t -tests, ANOVA). TMS and rTMS procedures were well tolerated with no serious adverse events and no drop-outs. Affected hand function in children with ispsilateral projections did not decrease between rTMS and sham (AHA no change, MA increased). Unaffected hand function did not decrease with rTMS (GS and PS same). TMS and rTMS tolerability scores were favourable, scoring better than “a long car ride” on average. All side effects were mild, brief (minutes), and self-limiting with none requiring medication. Headache was common (43% during 1st TMS session) but resolved with removal of the swim cap used for mapping. Headache rates decreased (20%) with the same protocol 3 weeks later. Headache was uncommon during rTMS (11%) with tolerance (0% at 2nd session) and comparable rates between rTMS and sham. Other side-effects (neck pain, tingling, nausea, presyncope) were infrequent (<5% on final TMS session). Non-invasive brain stimulation trials are safe and feasible in children with perinatal stroke. Inhibitory rTMS over the non-lesioned M1 does not negatively affect normal hand function or affected hand function in children with ipsilateral projections. Headaches are common but mild and self-limiting.