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

Symptomatic Neonatal AIS

(NAIS)

Arterial Presumed Perinatal Ischemic

Stroke (APPIS)

Periventricular Venous Infarction

(PVI)

Perinatal Stroke = Motor System Injury = Hemiparetic CP

AIS-MCA

PVI

Ipsilateral Projections

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

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 on ipsilateral projections in perinatal stroke– 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)

PLASTIC CHAMPS trial

Plastic Adapatation Stimulated by TMS and Induced Constraint for

Congenital Hemiplegia After Motor Perinatal Stroke

PLASTIC CHAMPS Brain CamprTMS: 1Hz x 20 minutes OR shamCIMT: Cast x 90% waking hours

www.clinicaltrials.govNCT01189058

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 = 17Met 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

Dr. Aleks MineykoTaryn Bemister

Jessica DenysJacquie Hodge

Jenny Saunders Jamie Roe

Helen CarlsonSiddharth Shinde

Dave CzankTMS

ACH Pediatric TMS LaboratoryOleg KotsovskyOmar DamjiDr. Thilinie Rajapakse

Toronto Western Research Institute Dr. Robert ChenCarolyn Gunraj

PLASTIC CHAMPS

Calgary Stroke Program Dr. Michael HillDr. Sean Dukelow

ACH RMTDr. Alberto Nettel-AguirreDr. Brent Hagel

ACH CIMT Program / Rehab Tamara ThickeGillian Hoyt-HallettClare O’ByrneColleen Lane, Mia Herrero

APSP Stollery Edmonton Dr. Jerome Yager

APSP Glenrose Edmonton Dr. John AndersenKathleen O’Grady

SickKids Stroke Program Dr. Gabrielle deVeber

NeuroimagingDr. Xing-Chang WeiDr. Jayme Kosior

Clinical Research UnitChristina Ma

www.perinatalstroke.ca