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

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

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

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

METHODS

Introduction Methods Results Conclusion

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

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

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

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)

RESULTS

Introduction Methods Results Conclusion

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

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

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

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

Conclusions

These neurophysiological and neuroanatomical changes may offer a

novel biomarker to distinguish between individuals with MS and NMO

Introduction Methods Results Conclusion

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