Motor Pathway Changes assoc with Upper Limb BTX-A in Hemiplegic Cerebral Palsy
Dr Toni Redman University of Western Australia Princess Margaret Hospital, Perth
Background
Cerebral Palsy most common cause physical disability in children Spasticity - ↓ function - contractures - bony malalignment Botulinum Toxin - spasticity management
Botulinum Toxin A (BTX-A)
Neurotoxin Clostridium difficile Binds motor nerve ending Reversible Peak 3-4 weeks
Motor Pathways in Hemiplegic CP
Abnormal motor pathways Neural plasticity affected side Ipsilateral corticomotor +/- Contralateral corticomotor
Unaffected Hemisphere
Affected Hemisphere
Ipsilateral
Contralateral
Affected Side
Unaffected Side
Motor Pathway - BTX-A
Adult studies
- cervical dystonia, writer’s cramp - 12 week follow up - corticomotor reorganisation with BTX-A therapy
Study Hypothesis Corticomotor reorganisation will occur with BTX-A therapy for upper limb spasticity in children with hemiplegic CP
Secondary Aim
Document change over time in corticomotor pathways in children with hemiplegic CP
Participants
Inclusion Criteria - hemiplegic CP - age 7y0m – 13y11m - dynamic spasticity UL Exclusion Criteria - significant cognitive impairment - poorly controlled epilepsy - unable to attend all assessments
Setting
Recruitment - Spasticity Management Clinic, PMH - Cerebral Palsy Assoc of WA Assessments - Centre for Neuromuscular and Neurological Disorders, Perth Ethical Approval - PMH, CPWA, UWA Ethics Committees
Design
Treatment Group (12) Control Group (11)
One series UL BTX-A
- Muscle selection individualised +/- LL BTX-A
No UL BTX-A
+/- LL BTX-A
Community OT and Physio Community OT and Physio
Assessments
Baseline, 1, 3, 6 months Transcranial magnetic stimulation (TMS)
TMS
Cortical stimulation – EMG response Cortical threshold higher in children Facilitation – no EMG response at 80%
Statistical Analysis
SPSS Student t tests – group comparison Linear mixed model analysis – covariates age, gender, treatment group, day, day*day Descriptive analysis – group and pathway type Statistical significance p<0.05
Results
Follow-up attendance 97% 2 participants attended 3 of 4 assessments. Remaining participants attended all assessments. 0 lost to follow up
Group Comparison
Mean Std Dev Sig. (2 sided p value) 0.823
Age (years)
Control Treatment
10.55 10.72 0.38 0.56
2.16 1.81 0.48 0.49
Gender M 1/ F 2
Control Treatment
0.578
Motor Pathways
11 participants – ipsilateral affected Unaffected Hemisphere side Ipsilateral 7 participants – contralateral affected side 4 participants – not able to be determined
Affected Side
Affected Hemisphere
Contralateral
Unaffected Side
Results
Observations : Poor tolerance TMS >80% stimulus Max TMS stimulus 80% +/- facilitation
Cortical Threshold
Threshold <50% 50-60% 60-70% 70-80% >80% Age (yr) n/a 12,14 11,12,12,13,14 11,11 7 – 13 Affected Side 0 2 4 2 14 Unaffected Side 0 2 5 2 13
Pathway shift
No statistically significant shift in treatment group pathways
-TMS map shift maximal 1-3 month post BTX-A (clinical effect) - Ipsilateral affected side pathways lay significantly closer to unaffected side pathway at 3 months (p 0.04)
Trend
Baseline (M.D)
R fDI
L fDI (aff)
3 months post BTX-A
R fDI
L fDI (aff)
6 months post BTX-A
R fDI
L fDI (aff)
Baseline (J.C)
R fDI (aff)
L fDI
1 month post BTX-A
R fDI (aff)
L fDI
3 months post BTX-A
R fDI (aff)
L fDI
6 months post BTX-A
R fDI (aff)
L fDI
Pathway variability Significant variability in control participants
Up to 67% - ipsilateral affected side Up to 33% - contralateral affected side Up to 34% - unaffected side
Conclusion
Central motor pathway reorganisation occurs with BTX-A therapy Changes in both affected and unaffected side pathways (systemic BTX-A effect?) Significant variability over time in motor pathways (implications?) Poor tolerance of TMS procedure limits its usefulness as investigatory tool in paediatrics
Recommendations
Larger study needed to confirm trends : - persistent pathway shift at 6 month - max pathway shift at 1-3 month c/w clinical effect of BTX-A Alternative tools to investigate corticomotor pathway – corticospinal tractography
Acknowledgements
Telethon Research Institute, Perth Co-investigator: Noula Gibson, PMH Supervisors: Dr Judith Finn, SPH, UWA Dr Gary Thickbroom, CNND Dr Jane Valentine, Dept Paed Rehab, PMH Dr Alexandra Bremner, SPH, UWA
Future…