Effects of rTMS 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

Perinatal Stroke = Motor System Injury = Hemiparetic CP

Symptomatic Neonatal AIS (NAIS) Arterial Presumed Perinatal Ischemic Stroke (APPIS) Periventricular Venous Infarction (PVI)

Ipsilateral Projections

> 0.05mV at 120% RMT in >5/20 trials

PVI AIS-MCA

Aims

• Determine the neurophysiology of ipsilateral connections in perinatal stroke – Hypothesis: The unlesioned hemisphere controls both contra and ipsi-lateral physiology • Investigate the effects of inhibitory rTMS projections in perinatal stroke – on ipsilateral Hypothesis: rTMS 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

NCT01189058

PLASTIC CHAMPS trial

Pl

astic

A

dapatation

S

timulated by

T

MS and

I

nduced

C

onstraint for

C

ongenital

H

emiplegia

A

fter

M

otor

P

erinatal

S

troke

PLASTIC CHAMPS Brain Camp rTMS

: 1Hz 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 rTMS versus 20 sham N = 35 N = 18 excluded 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 rTMS affected contralateral as expected: Increased RMT and lowered SRC slope

Results

Non-lesional rTMS 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 rTMS MA improved, AHA unchanged

Results

Changes cortical physiology correlated between contralateral and ipsilateral sides

SICI ICF

Conclusions

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

Acknowledgements

APSP Stollery Edmonton

Dr. Jerome Yager

APSP Glenrose Edmonton

Dr. John Andersen Kathleen O’Grady

SickKids Stroke Program

Dr. Gabrielle deVeber

Neuroimaging

Dr. Xing-Chang Wei Dr. Jayme Kosior

Clinical Research Unit

Christina Ma TMS

ACH Pediatric TMS Laboratory

Oleg Kotsovsky Omar Damji Dr. Thilinie Rajapakse

Toronto Western Research Institute

Dr. Robert Chen Carolyn Gunraj Dr. Aleks Mineyko Taryn Bemister Jessica Denys Jacquie Hodge Jenny Saunders Jamie Roe Helen Carlson Siddharth Shinde Dave Czank PLASTIC CHAMPS

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 ’ Byrne Colleen Lane, Mia Herrero

www.perinatalstroke.ca