Effects of r TMS on Ipsilateral Corticomotor Projections

Effects of r. TMS on Ipsilateral Corticomotor Projections in Children with Perinatal Stroke: Neuromodulation feasibility in the PLASTIC CHAMPS trial Damji O, Kotsovsky O, Chen R, Kirton A

Disclosures • No conflicts • Non-invasive brain stimulation is experimental in kids

Stroke Can Happen in Kids? • Common – >1: 2500 live births = >1000 Alberta children. – #1 cause hemiplegic CP • Poorly understood • Poor outcomes • No prevention or treatment • Ideal model for studying neuroplasticity in children

Perinatal Stroke = Motor System Injury = Hemiparetic CP Symptomatic Neonatal AIS (NAIS) Arterial Presumed Perinatal Ischemic Stroke (APPIS) Periventricular Venous Infarction (PVI)

PVI Ipsilateral Projections > 0. 05 m. V at 120% RMT in >5/20 trials AIS-MCA

Aims • Determine the neurophysiology of ipsilateral connections in perinatal stroke – Hypothesis: The unlesioned hemisphere controls both contraand ipsi-lateral physiology • Investigate the effects of inhibitory r. TMS on ipsilateral projections in perinatal stroke – Hypothesis: r. TMS inhibits ipsilateral corticomotor projections

Faraday's Law of Magnetic Induction TMS Neurophysiology • Rest Motor Threshold (RMT) • Stimulus Response Curve (SRC) – 100 / 110 / 120 / 130 / 140 / 150% • Paired-Pulse Methods – Short Interval Intracortical Inhibition (SICI) – Intracortical Facilitation (ICF)

www. clinicaltrials. gov. NCT 01189058 PLASTIC CHAMPS Brain Camp r. TMS: 1 Hz x 20 minutes OR sham CIMT: Cast x 90% waking hours

Results • • Interim analysis of 35 children Mean age 11. 25 years, 20 male 55% arterial, 45% PVI 15 r. TMS versus 20 sham N = 18 excluded N = 35 N = 17 Met ipsi criteria

Results – Ipsilateral Projections • 17 (49%) of children had ipsilateral projections • Presence and intensity correlated with disability – AHA (r=-0. 58; p=0. 004) and MA (r=-0. 45; p=0. 013). • Ipsi SRC slope was lower than contra (p=0. 01). • SICI was present bilaterally – contra -38. 5%, ipsi -30. 7% • ICF was present bilaterally – contra +15. 4%, ipsi +23. 1% • SICI and ICF differed between sides (p= 0. 004)

Results Non-lesional r. TMS affected contralateral as expected: Increased RMT and lowered SRC slope

Results Non-lesional r. TMS had less effect on ipsilateral physiology: No change in ICF Trends to lower SRC slope and increased SICI Ipsilateral SRC Slope Ipsilateral SICI

Results Children with ipsilateral projections did not show a decrease in motor function with r. TMS MA improved, AHA unchanged

Results Changes cortical physiology correlated between contralateral and ipsilateral sides SICI ICF

Conclusions • Contralesional inhibitory r. TMS is feasible in kids with perinatal stroke and ipsilateral projections • r. TMS effects on corticomotor neurophysiology are more predictable on the contralateral side • r. TMS shifts in corticomotor neurophysiology correlate between contra and ipsi-lateral systems

Acknowledgements PLASTIC CHAMPS APSP Stollery Edmonton Dr. Jerome Yager APSP Glenrose Edmonton Dr. John Andersen Kathleen O’Grady Sick. Kids Stroke Program Dr. Gabrielle de. Veber Neuroimaging Dr. Xing-Chang Wei Dr. Jayme Kosior Clinical Research Unit Christina Ma TMS Dr. Aleks Mineyko Taryn Bemister Jessica Denys Jacquie Hodge Jenny Saunders Jamie Roe Helen Carlson Siddharth Shinde Dave Czank ACH Pediatric TMS Laboratory Oleg Kotsovsky Omar Damji Dr. Thilinie Rajapakse Toronto Western Research Institute Dr. Robert Chen Carolyn Gunraj Calgary Stroke Program Dr. Michael Hill Dr. Sean Dukelow ACH RMT Dr. Alberto Nettel-Aguirre Dr. Brent Hagel ACH CIMT Program / Rehab Tamara Thicke Gillian Hoyt-Hallett Clare O’ O’Byrne Colleen Lane, Mia Herrero

www. perinatalstroke. ca