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Cortico-spinal tract integrity measured using magnetic resonance imaging and
transcranial magnetic stimulation in neuromyelitis optica and multiple sclerosis
Praveena Manogaran1, Irene Vavasour2, Michael Borich3, Shannon Kolind1, William Regan1, Alex MacKay2,4, Lara Boyd3, David Li1,2, and Anthony
Traboulsee1
1Divison of Neurology, Department of Medicine 2Department of Radiology 3Brain Behaviour Lab, Department of Physical Therapy 4Department of Physics & Astronomy
The University of British Columbia, Vancouver
Introduction Methods Results Conclusion
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Multiple Sclerosis (MS)
Central:FatigueCognitive ImpairmentDepression
Visual:Optic neuritisDiplopia
Musculoskeletal:WeaknessSpasmsAtaxia Sensation:
Pain
Bowel:IncontinenceDiarrhea
Urinary:IncontinenceFrequencyRetention
http://www.rethinkmsrelapses.com/pages/understand_ms_relapses/what_causes_an_ms_relapseBarkhof F et al. Brain 1997; 11: 2059-2069
T2-weighted - 4 hyperintense lesions
Introduction Methods Results Conclusion
Axon
Myelin
Damaged Myelin
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Neuromyelitis Optica (NMO)
Optic Neuritis
Myelitis
http://www.unitedspinal.org/msscene/2008/02/04/neuromyelitis-optica/
• Characterized by damage to astrocytes
• Usually presents with severe axonal degeneration
• Shows similar clinical and radiological features to MS but treatment and prognosis differ significantly
Introduction Methods Results Conclusion
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Objective
1. Characterize differences in cortical excitability and myelin status of descending motor output pathways
2. Evaluate the relationships between these measures in individuals with MS and NMO compared to healthy controls
Introduction Methods Results Conclusion
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METHODS
Introduction Methods Results Conclusion
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Study Population
• 30 subjects age and gender matched• MRI protocol performed on Philips 3.0T Achieva
system
Study Group
TotalMale
Total Female
Mean Age (yr)
Age Range (yr)
EDSS Range
Mean Disease Duration (yr)
NMO 3 7 43 28-55 2.0-6.0 8.7
MS 3 7 42 24-60 0.0-6.0 7.4
Control 2 8 42 22-58 N/A N/A
Introduction Methods Results Conclusion
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0 1
0 2
0 3
0 4
0 5
0 6
0 7
0
80
10 100 1000T2 Time (ms)
Am
plit
ude
40 ms 500 ms
Fit T2 data with NNLS to obtain
T2 relaxation of MRI signal
Time (ms)
Sig
nal
Am
plit
ude
T2 Relaxation and Myelin Water Fraction
Images courtesy of Sandra Meyers, UBC MRI Research Group
Introduction Methods Results Conclusion
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Image courtesy of the Brain Behaviour Lab
TMS is a non-invasive, safe, and quick measure of cortical-spinal excitability
Motor Evoked Potential
(MEP)
Transcranial Magnetic Stimulation (TMS)
Figure-of-eight coil attached to a Magstim 200 stimulator targeting motor
cortex
MEPs recorded with surface electromyography of extensor carpi
radialis bilaterallyIntroduction Methods Results Conclusion
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Strafella AP & Paus T. J Neurophysiol 2001; 85(6): 2624-2629
Test Response
2 ms interstimulus interval = Intracortical Inhibition
(ICI)
12 ms interstimulus interval = Intracortical Facilitation
(ICF)
MEPTest Stimulus
Paired pulse TMS evaluates ICI and ICF pathways
PP ratio = conditioned MEP/unconditioned mean MEP
Introduction Methods Results Conclusion
Transcranial Magnetic Stimulation (TMS)
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RESULTS
Introduction Methods Results Conclusion
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Myelin water fraction is decreased in neuromyelitis optica compared to multiple
sclerosis and healthy controlsM
WF
0.12
0.14
0.16
0.18
0.20
0.22
0.24***
**
** p < 0.01*** p < 0.001
Introduction Methods Results Conclusion
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Lower intracortical inhibition in multiple sclerosis compared to neuromyelitis optica
and healthy controls
** p < 0.01
ICF
rat
io
Control
MS
NMO
0.0
0.5
1.0
1.5
2.0
2.5
ICI r
ati
o
0.0
0.5
1.0
1.5**
**
Introduction Methods Results Conclusion
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No significant correlations were found between myelin water fraction and intracortical excitability measures
ICF
rat
io
0.12 0.14 0.16 0.18 0.200.0
0.5
1.0
1.5
2.0
2.5 r = -0.165, p = 0.6
0.12 0.14 0.16 0.18 0.200.0
0.5
1.0
1.5
2.0
2.5 r = -0.188, p = 0.6
0.12 0.14 0.16 0.18 0.200.0
0.5
1.0
1.5
2.0
2.5 r = 0.408, p = 0.2
MWF CST
ICI r
atio
0.12 0.14 0.16 0.18 0.200.0
0.5
1.0
1.5
r = -0.028, p = 0.9
MWF CST0.12 0.14 0.16 0.18 0.20
0.0
0.5
1.0
1.5
r = 0.052, p = 0.9
MWF CST0.12 0.14 0.16 0.18 0.20
0.0
0.5
1.0
1.5
r = -0.039, p = 0.9
Control NMO MS
Introduction Methods Results Conclusion
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Conclusions• Structural changes found in the
descending motor output pathway white matter of NMO patients
• Cortical excitability changes were observed in MS patients that were specific to intracortical inhibitory pathways
• Intracortical inhibition may not be directly linked to myelination
Introduction Methods Results Conclusion
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Conclusions
These neurophysiological and neuroanatomical changes may offer a
novel biomarker to distinguish between individuals with MS and NMO
Introduction Methods Results Conclusion
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AcknowledgementsMRI Research GroupAnthony TraboulseeShannon KolindIrene VavasourSandra MeyersAlex MacKayEric ZhaoNolan ShelleyDavid LiAlex Rauscher
UBC’s MRI Technologists
Brain Behaviour LabMichael BorichMarjan ZakeriLara BoydTamara KorenAndrej Satara
MS/MRI Research GroupWilliam ReganAnnie KuanRachel Kim
Study subjects