Imaging Spinal Cord in MS: Current Practice & Future Directions

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1 Imaging Spinal Cord in MS: Current Practice & Future Directions Robert T. Naismith, MD Washington University St. Louis, MO PVA Summit 2013

2 Disclosures Dr. Simon has nothing to disclose. Dr. Naismith has the following disclosures: Acorda: Speaker/Consultant/Research Bayer: Speaker/Consultant Biogen: Speaker/Consultant EMD Serono: Speaker/Consultant Genzyme: Speaker/Consultant Questcor: Consultant This continuing education activity is managed and accredited by Professional Education Services Group in cooperation with the Paralyzed Veterans of America. Neither PESG nor PVA nor any accrediting organization supports or endorses any product or service mentioned in this activity. PESG Staff and the Program Planning Committee have no financial interest to disclose. Commercial Support was not received for this activity.

3 Objectives Utilize spine MRI to diagnose MS and exclude other etiologies for myelopathy. Understand how spinal cord MRI contributes to disease prognostication. Appreciate the utility of spine MRI to monitor the disease. Explain how the spinal cord MRI functions as a surrogate for axonal degeneration and progressive MS. Become familiar with spinal cord MRI research techniques in MS.

4 MRI in Multiple Sclerosis Lukas C et al. Radiology 2013.

5 Myelopathy Evaluation

6 Spine MRI in Diagnosis

7 Key Questions Should spine MRI be obtained in all patients to confirm diagnosis?

8 McDonald Criteria 2010 Polman et al. Annal Neurol 2010.

9 Neuromyelitis Optica

10 Spinal cord in Early MS Bot JC et al. Neurology 2004

11 Spinal cord in Early MS Bot JC et al. Neurology 2004

12 Case Presentation 36 y/o woman presents with migraines for the past 2 years. Migraines have been increasing in frequency. Exam was normal. MRI was obtained.

13 Case Presentation Continued

14 Radiologically-Isolated Syndrome Okuda D et al. Neurology 2011.

15 Diagnosis Summary Spinal cord imaging is frequently abnormal (~80%), even in early MS. They can be multi-focal/partial (more with RRMS) or diffuse (PPMS). One asymptomatic spinal cord lesion can count for dissemination in space for RRMS; two for PPMS. The presence of a spinal cord lesion is highly predictive of MS (RRMS and PPMS) in RIS.

16 Answers Spine MRI should be obtained in situations where the diagnosis is not conclusive. Spine MRI is not necessary for diagnosis if other clinical, imaging, and paraclinical features confirm disease.

17 Spine MRI in Prognostication

18 Prognosis Key Questions What are the implications if someone with a Clinically Isolated Syndrome has spinal cord abnormalities? How well do spinal cord abnormalities correspond to disability?

19 Natural History of MS Baseline Brain MRI and Disease Evolution Percent Patients with EDSS >3 after 14 years Percent Patients with EDSS >6 after 14 years > 10 lesions <= 10 lesions > 10 lesions <= 10 lesions Brex et al, N Eng J Med. 2002:346;

20 Fisniku et al. Brain 2008.

21 Spinal Cord Imaging in CIS Sombekke MH et al. Neurology 2012.

22 MS Conversion with Spinal Cord Lesions Sombekke MH et al. Neurology 2012.

23 Lycklama a Nijeholt GJ et al. Brain 1998.

24 Lycklama a Nijeholt GJ et al. Brain 1998.

25 Number of diffusely involved segments and number of spinal cord lesions do weakly correlate with EDSS and 25 Foot Timed Walk Lukas C et al. Radiology 2013.

26 Answers to Key Questions Presence of spinal cord abnormalities in CIS predicts faster time to McDonald criteria MS. Diffuse involvement of the cord and the number of involved segments do correlate weakly to ambulatory disability.

27 Spine MRI in Disease Monitoring

28 Practical Questions Should a baseline spinal cord MRI always be obtained for future reference? How frequent to monitor treatment for breakthough disease activity? Which sections of the spinal cord should be included and should we also get Gadolinium?

29 Early Spinal Cord MRI: Lesion Location Bot JC et al. Neurology 2004

30 MRI Frequency of Activity Brain vs. Spine Kidd D et al. JNNP 1996.

31 Monthly Imaging of Brain and Spine Brain Lesions More common: 57 (56 Gd+) of 128 brain were active, 15 (10 Gd+) of 128 spine were active. Of 167 new or enlarging brain lesions, only 1 was associated with a clear symptom. Of 19 new or enlarging spine lesions, 6 were symptomatic (5 Gd+) 27 scans around time of relapse vs. 44 while in remission. 91 new or enlarging brain lesions were observed with a relapse vs. 51 during remission. 13 of new or enlarging cord lesions observed during relapse, vs. 5 while in remission. Thorpe JW et al. Neurology 1996

32 Key Points on Monitoring Brain MRI is 10x more sensitive to detect subclinical disease activity compared to spinal cord imaging. New spinal cord activity is more likely to be clinically symptomatic. Gadolinium should be included when imaging the spinal cord. Lesions can occur anywhere within the cord, but are more common in cervical regions. Be aware of the length of imaging if acquiring brain/c/t-spine.

33 Clinical Use Summary Advantages Eloquent region of the CNS Evaluate for other diagnostic possibilities Presence of spinal cord lesions helpful in RIS and suggest faster conversion in CIS. Disadvantages Difficult to quantify Poor correlation with disability and progression Susceptible to motion and artifact Time consuming

34 Spine MRI as a Surrogate of Axonal Degeneration

35

36

37 Wallerian Degeneration I Simon JH et al. Neurology 2000;54:

38 Wallerian Degeneration II Simon JH et al. Neurology 2000;54:

39 Ferguson B et al. Brain 1997

40 Where there s smoke, there s fire.

41 Axons within the Spinal Cord Lovas G et al. Brain 2000;123:

42 Axonal Injury and Clinical Disability Bjartmar C et al. J Neurol Sci 2003.

43 Progressive MS Spinal Cord is the final common pathway for acute and chronic axonal degeneration. Spinal cord can be key to understanding progressive MS. Spinal cord may have a role in monitoring treatment effect in therapeutics proposed to remyelinate and protect axons.

44 Spinal Cord Atrophy

45

46 Correlation of EDSS and Cord Atrophy Losseff NA et al. Brain 1996

47 Rocca M et al. Neurology 2011

48

49 Spinal Cord MTR

50 Column MTR with Lower Extremity Clinical Parameters Zackowski KM et al. Brain 2009.

51 Whole Cord MTR Oh J et al. MSJ 2013

52 Spinal Cord DTI

53 Oh J et al. MSJ 2013

54 Tract-Based DTI Naismith RT et al. Neurology 2013.

55 Summary Spinal Cord Imaging can provide important information for diagnosis and prognosis in MS. Spinal Cord is a discrete tract which can inform us about axonal degeneration, ambulation, and progressive MS. While counting spinal cord plaques and enhancement may have limited utility for clinical trials, quantitative techniques (DTI, MTR, cord volume) have potential to assess therapeutics proposed to benefit axons.

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