1. Cortico-spinal tract integrity measured using magnetic resonance imaging and transcranial magnetic stimulation in neuromyelitis optica and multiple sclerosis Praveena Manogaran 1, Irene Vavasour 2, Michael Borich 3, Shannon Kolind 1, William Regan 1, Alex MacKay 2,4, Lara Boyd 3, David Li 1,2, and Anthony Traboulsee 1 1 Divison of Neurology, Department of Medicine 2 Department of Radiology 3 Brain Behaviour Lab, Department of Physical Therapy 4 Department of Physics & Astronomy The University of British Columbia, Vancouver IntroductionMethodsResultsConclusion

2. Multiple Sclerosis (MS) Central: Fatigue Cognitive Impairment Depression Visual: Optic neuritis Diplopia Musculoskeletal: Weakness Spasms Ataxia Sensation: Pain Bowel: Incontinence Diarrhea Urinary: Incontinence Frequency Retention http://www.rethinkmsrelapses.com/pages/understand_ms_relapses/ what_causes_an_ms_relapse Barkhof F et al. Brain 1997; 11: 2059-2069 T 2 -weighted - 4 hyperintense lesions IntroductionMethodsResultsConclusion Axon Myelin Damaged Myelin

3. 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 IntroductionMethodsResultsConclusion

4. 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 IntroductionMethodsResultsConclusion

5. METHODS IntroductionMethodsResultsConclusion

6. Study Population 30 subjects age and gender matched MRI protocol performed on Philips 3.0T Achieva system Study Group Total Male Total Female Mean Age (yr) Age Range (yr) EDSS Range Mean Disease Duration (yr) NMO374328-552.0-6.08.7 MS374224-600.0-6.07.4 Control284222-58N/A IntroductionMethodsResultsConclusion

7. 0 10 20 30 40 50 60 70 80 10 100 1000 T 2 Time (ms) Amplitude 40 ms500 ms Fit T 2 data with NNLS to obtain T 2 relaxation of MRI signal Time (ms) Signal Amplitude T 2 Relaxation and Myelin Water Fraction Images courtesy of Sandra Meyers, UBC MRI Research Group IntroductionMethodsResultsConclusion

8. 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 bilaterally IntroductionMethodsResultsConclusion

9. 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) MEP Test Stimulus Paired pulse TMS evaluates ICI and ICF pathwaysPP ratio = conditioned MEP/unconditioned mean MEP IntroductionMethodsResultsConclusion Transcranial Magnetic Stimulation (TMS)

10. RESULTS IntroductionMethodsResultsConclusion

11. Myelin water fraction is decreased in neuromyelitis optica compared to multiple sclerosis and healthy controls ** p < 0.01*** p < 0.001 IntroductionMethodsResultsConclusion

12. Lower intracortical inhibition in multiple sclerosis compared to neuromyelitis optica and healthy controls ** p < 0.01 IntroductionMethodsResultsConclusion

13. No significant correlations were found between myelin water fraction and intracortical excitability measures IntroductionMethodsResultsConclusion

14. 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 IntroductionMethodsResultsConclusion

15. Conclusions These neurophysiological and neuroanatomical changes may offer a novel biomarker to distinguish between individuals with MS and NMO IntroductionMethodsResultsConclusion

16. Acknowledgements MRI Research Group Anthony Traboulsee Shannon Kolind Irene Vavasour Sandra Meyers Alex MacKay Eric Zhao Nolan Shelley David Li Alex Rauscher UBC’s MRI Technologists Brain Behaviour Lab Michael Borich Marjan Zakeri Lara Boyd Tamara Koren Andrej Satara MS/MRI Research Group William Regan Annie Kuan Rachel Kim Study subjects