1. Degenerative Marrow (Modic) Changes on Cervical Spine MRI Scans Prevalence, Inter- and Intra-examiner Reliability and Link to Disc Herniation Eugen Mann, final year medical student (current Radiol Resident) Cynthia Peterson, RN, DC, DACBR, M.Med.Ed Jürg Hodler, MD, MBA Published in SPINE 2011;36:1081-1085 Department of Radiology, Orthopaedic University Hospital Balgrist Zürich, Switzerland

2. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 2 BACKGROUND  Types I, II and III were first described by Dr. Michael Modic  I = low SI on T1 and high SI on T2  II = high SI on T1 and either isointense or high on T2  III = low SI on both T1 and T2 (sclerosis on x-rays)  Most of the literature focuses on the lumbar spine  Type I changes (at least) appear linked with pain  Appears to be a genetic predisposition to Modic changes  Jensen et al found a link between new Modic changes (type I) and disc herniation in the lumbar spine

3. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 3 MODIC TYPE I

4. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 4 MODIC TYPE II + HERNIATION

5. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 5 RATIONALE FOR STUDY  Only one previous study on Modic changes in the cervical spine.  Prevalence study only.  Appears different from findings in lumbar spine. Type I were most prevalent.  Experience suggested that disc herniations and Modic changes were often seen at the same level. Is this true?

6. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 6

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9. 9 METHODS  Cervical MRI scans of 500 consecutive pts age 50 and over were retrospectively evaluated by a final year medical student trained specifically in MRI diagnosis of Modic changes and disc herniations.  200 of these same scans were independently evaluated by a radiologist for inter-examiner reliability.  100 of the 200 scans were re-evaluated one month later by the same radiologist for intra-examiner reliability.  Age and gender of the patients was recorded

10. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 10  Motion segments C3/4 – C6/7 were assessed for:  Presence/Absence of Modic changes at segmental levels  Type of Modic change if present (Types I and II only)  Presence/Absence of disc herniation at segmental levels  Category of disc herniation if present  Type I = diffuse or broad-based without cord or root compression (Bulge)  Type II = focal protrusion usually with cord or nerve root compromise METHODS (cont)

11. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 11 EXCLUSION CRITERIA  Recent fractures  Surgical fusions  Acute Schmorl‘s nodes  Spinal infections  Tumours  Inflammatory arthropathy  Haemodialysis spondyloarthropathy  Congenital block vertebra

12. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 12 STATISTICAL ANALYSIS  Descriptive statistics for prevalence data  Number of patients  Number of motion segments  Age and gender  Risk ratios (95% CI) for association between disc herniations and Modic changes  Kappa statistics for reliability data  SPSS and CIA were used for data analysis  (Thanks to Prof. Jennifer Bolton for her help with the risk ratio calculations.)

13. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 13 RESULTS  Prevalence  Association with disc herniation  Reliability of diagnosis  Inter-observer reliability  Intra-observer reliability

14. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 14 RESULTS 1 Prevalence  426 patients met inclusion criteria (85.2%)  Mean age = 61.7 (SD = 9.12)  Male:Female ratio = 48:52  172 out of 426 pts had Modic changes at one or more levels (40.4%).  30% = Modic I  70% = Modic II  51% of Modic changes were seen in females  No significant age difference between pts with and without Modic changes

15. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 15  C6/7 was most common level for Modic changes, followed by C5/6.  245 out of 1704 motion segments had Modic changes (14.4%).  74 motion segments = Type I  171 motion segments = Type II  Disc herniations type I and II were noted in 333 pts (78.2%)  242 pts (56.8%) had DH at more than 1 level  Of 1704 motion segments, 226 (13.3%) had disc bulge and 493 (28.9%) had true herniation.  C5/6 followed by C6/7 were most commonly involved

16. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 16 RESULTS 2 Modic changes and disc herniation  Only Type II disc herniations were considered. Modic I and II were pooled  RR = 2.42 (95% CI = 1.93 – 3.04) overall for both Modic changes and disc herniation at the same level.  Highest RR was at the C4/5 level (RR = 3.3. 95% CI = 1.8 – 6.05)

17. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 17 RESULTS 3 Reliability of diagnosis  Inter-Examiner reliability of identifying and categorizing Modic changes  K = 0.54 (95% CI = 0.43 – 0.65) Moderate  73%  Intra-Examiner reliability  K = 0.89 (95% CI = 0.72 – 0.92) Almost perfect  89%

18. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 18 DISCUSSION  Reliability between experienced and novice reader is acceptable.  A large percentage of pts over age 50 have Modic changes at this Hospital.  Modic type II changes were predominate.  Similar to findings in the lumbar spine  However….Did we miss the Modic I pts because these happen earlier?

19. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 19 DISCUSSION (cont)  No age difference found between those with and without Modic changes may be due to excluding pts under age 50.  High prevalence of DH in this population likely due to type of Hospital  Patients with Disc herniations are 2.42 times more likely to also have Modic changes at the same level.  However, the majority of DH pts did not have Modic changes  Genetic predisposition?

20. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 20 FURTHER STUDIES  Look at patients younger than age 50  Compare pain and disability levels between patients with Modic I vs. Modic II in the cervical spine  How do these patients respond to chiropractic care? Or to other treatments?  Currently collecting data for nerve root injections.

21. The Evolution of Degenerative Marrow (Modic) Changes on Cervical Spine MRI Scans  Eugen Mann, M.D.(current Radiol Resident)  Cynthia Peterson, RN, DC, DACBR, M.Med.Ed  Jürg Hodler, MD, MBA  Christian Pfirrmann, MD, MBA Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 21

22. Purpose of Study  Evaluate the course and development of Modic changes in the cervical spine in neck pain patietns and compare the findings with similar studies done on the lumbar spine. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 22

23. METHODS  From the original 500 patients in the previous study, 64 had follow-up MRI scans (after applying the exclusion criteria).  Retrospective analysis of sagittal and axial T1 and T2-weighted cervical MRI scans.  Presence or absence of Modic changes and type (Modic 1 and 2 only) recorded as well as segmental level/s.  Age and gender also recorded Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 23

24. Statistical Analysis  Descriptive statistics  Prevalence rates in relation to the number of affected segmental levels.  Prevalence rates in relation to MC type, gender and mean age. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 24

25. Results  Baseline MRI:  37/64 patients (58%) had Modic changes on 1st MRI study.  This corresponded to 21.9% of motion segments.  Follow-up MRI:  46/64 patients (72%) had Modic changes at follow-up.  This corresponded to 30.5% of motion segments. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 25

26. Results Continued  Baseline:  19 segments with MC 1  37 segments with MC 2  Follow-up:  21 segments with MC 1  57 segments with MC 2  ‘New’ Modic changes in 22 segments (MC 1 in 14 segments and MC 2 in 8 segments) Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 26

27. Results Continued  Change of Modic 1 to Modic 2 occurred in 12 segments (4.7%).  No cases of Modic 2 changing to Modic 1 or a disappearing Modic change.  Average time between MRI exams for ‘new’ MC 1 was 2.4 years.  ‘New’ MC 2 average time was 5.0 years  MC 1 changing to MC 2 average time was 3.1 years. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 27

28. Conclusions:  Modic changes in the cervical spine are dynamic in nature, like in the lumbar spine.  Their relevance to patient symptoms and prognosis is currently unknown. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 28

29. Symptomatic, MRI Confirmed Lumbar Disc Herniation Patients: A Comparative Effectiveness Observational Study of Two Age and Gender Matched Cohorts Treated with either Spinal Manipulative Therapy or Imaging-Guided Lumbar Nerve Root Injections Cynthia Peterson, DC, DACBR, M.Med.Ed Serafin Leemann, DC Marco Lechmann, B.Med Christian W.A. Pfirrmann, MD, MBA Jürg Hodler, MD, MBA B. Kim Humphreys, BSc, DC, PhD Departments of Radiology and Chiropractic, Orthopaedic University Hospital Balgrist, Zürich, Switzerland

30. Christian Pfirrmann, MD, MBA Jürg Hodler, MD, MBA Marco Lechmann B.Med. Serafin Leemann, DC, Cynthia Peterson DC, DACBR, M.Med.Ed, Kim Humphreys, DC, PhD

31. Background  Lumbar nerve root injections are an accepted treatment for patients with radiculopathy from LDH.  More supporting literature.  SMT remains more controversial.  Less supporting literature.

32. Methods Comparative effectiveness outcomes study. (Tinetti ME, Studenski SA, N Engl J Med 2011, 364:2478-2481.) Comparative effectiveness outcomes study. (Tinetti ME, Studenski SA, N Engl J Med 2011, 364:2478-2481.) Two age, gender and diagnosis matched cohorts (+/- 2 years). Two age, gender and diagnosis matched cohorts (+/- 2 years). 51 patients who received an imaging-guided lumbar nerve root injection at the level of the radiculopathy. 51 patients who received an imaging-guided lumbar nerve root injection at the level of the radiculopathy. 51 patients who received lumbar SMT at the site of disc herniation. 51 patients who received lumbar SMT at the site of disc herniation.

33. Methods cont.  Patients clinical sx (dermatome, myotome, reflex) had to correspond to the level of disc herniation noted on MRI scans.  Exclusion criteria for SMT patients (tumors, infections, SSAs, acute fxs, Paget’s disease, severe OP, previous spinal surgery, S/S of cauda equina, body mass index >30, spondylolisthesis, neurogenic claudication, pregnancy).  Exclusion criteria for NRI patients (pregnancy, anticoagulation therapy, overlying skin infections).

34. Methods cont Pain evaluated immediately prior to both treatments using the NRS (0 – 10). Pain evaluated immediately prior to both treatments using the NRS (0 – 10). 1 month after the first SMT treatment and NRI, follow-up data was collected by telephone interviews. 1 month after the first SMT treatment and NRI, follow-up data was collected by telephone interviews. NRS and Patient’s Global Impression of Change (PGIC) data (7 point scale) were collected at 1 month. NRS and Patient’s Global Impression of Change (PGIC) data (7 point scale) were collected at 1 month. Only ‘Much better’ and ‘Better’ were considered clinically relevant ‘Improvement’. Only ‘Much better’ and ‘Better’ were considered clinically relevant ‘Improvement’. ‘Slighty Worse’, ‘Worse’ and ‘Much Worse’ were all counted at ‘Worse’. ‘Slighty Worse’, ‘Worse’ and ‘Much Worse’ were all counted at ‘Worse’.

35. Methods: Statistical Analysis  The % of patients ‘Improved’ and ‘Worse’ with each treatment was calculated.  Pre-TX and 1 Month mean NRS scores were compared within each group using the paired Student’s t-test.  Mean NRS and NRS change scores for the NRI and SMT groups were compared at baseline and 1 month using the unpaired t-test.  The NRI and SMT groups were also compared for ‘improvement’ using the Chi Squared test.  Odds Ratios and 95% C.I.s were calculated

36. Cost Comparison  Mean treatment costs between the two groups were compared (excluding the MRI costs).

37. Results  Mean patient age was 47.56 (SD = 10.62)  62.7% were male  The L5 and S1 nerve root levels were the most commonly involved.  76.5% of the SMT patients reported clinically relevant improvement (OR 1.40, 95% CI = 0.85-2.30).  62.7% of NRI patients reported clinically relevant improvement (OR = 0.75, 95% CI = 0.51-1.09). (p =0.15 )  5.9% of the NRI patients (3) were ‘worse’ compared to 2.0% (1) of SMT patients. All cases were ‘slightly worse’.

38. Results cont  Both treatment groups had significant decreases in their NRS scores at 1 month (p = 0.0001).  The NRI group had significantly higher baseline NRS scores (7.36 (1.77) vs. 6.34 (2.55) (p = 0.02).  No significant differences between the groups for the 1 month NRS, 1 month NRS change score or the PGIC score at 1 month  No serious Adverse events in either group.

39. NRI (Mean and SD)SMT (Mean and SD) Pre NRS score7.36 (1.77)6.34 (2.55) (P = 0.02) 1 month NRS score 3.40 (2.81)2.52 (1.87) 1 month PGIC 2.25 (1.38)1.94 (1.04) NRS Change score 3.89 (2.836)3.79 (2.80)

40. SMT group Chronicity Results  29 Acute and 15 chronic SMT patients  22/29 acute pts (75%) ‚improved‘  8/15 chronic (53%) ‚improved‘

41. Cost Comparison  Average cost in the SMT group was CHF 533.77 (SD = 177.67, range = 176.00 – 1056.00). (Average number of Txs was 11.20, SD 3.61. Range = 5-20.)  NRI treatment costs were CHF 697.00 (fixed costs include one ‘simple’ pre- injection physician consultation plus the injection procedure).

42. Limitations  Not an RCT: Therefore outcomes cannot be directly attributed to the treatments.  Limited demographic information on NRI patients for more specific matching (i.e. chronicity). It appeared that perhaps a higher % of the SMT patients may have been acute.  Relative small sample sizes. Power calculation indicates that at least 50 per group are needed and we barely met that target.

43. Conclusions Most patients suffering from MRI confirmed lumbar disc herniations treated with SMT or NRIs report significant improvement in pain and functioning 1 month after start of treatment. Most patients suffering from MRI confirmed lumbar disc herniations treated with SMT or NRIs report significant improvement in pain and functioning 1 month after start of treatment. The outcomes are better than the reported natural history of this condition. The outcomes are better than the reported natural history of this condition. SMT was slightly less expensive when only evaluating the direct costs of treatment. SMT was slightly less expensive when only evaluating the direct costs of treatment.

45. Gender Differences in Pain Levels Before and After Treatment: A Prospective Outcomes Study on 3,900 Swiss Patients with MSK Complaints Cynthia Peterson DC, DACBR, M.Med.Ed. B. Kim Humphreys BSC, DC, PhD Jürg Hodler MD, MBA Christian W.A. Pfirrmann MD, MBA Department s of Radiology and Chiropractic, Orthopaedic University Hospital Balgrist, Zürich, Switzerland

46. BACKGROUND  Higher prevalence of pain in women suffering from headaches, neck and back pain as well as knee pain.  Women are more likely to experience chronic pain.  Women are more likely to receive treatment.  Women are more likely to report higher pain intensity scores.  Pain may be underdiagnosed and under treated in women??  But…  Pain intensity studies only measure pain levels at one point in time.  Is there a gender difference in response to various MSK treatments?

47. METHODS  Prospective outcomes study using several cohorts from large databases in 2 departments at the Orthopaedic University Hospital Balgrist.  1 month outcomes available.  Imaging-guided MSK therapeutic injections (sites with at least 100 patients).  Chiropractic patients treated for neck pain, low back pain or MRI confirmed lumbar disc herniation patients (at least 100 patients in each database).

48. METHODS: Imaging-guided Therapeutic MSK Injections  Inclusion Criteria  Age 18 and over  Pain strongly suspected to arise from specific joint, nerve root or spinal canal targeted for injection.  Exclusion Criteria  Overlying skin infections  Pregnancy  Anticoagulants (spine injections only)

50. METHODS: Chiropractic Patient Selection  Inclusion Criteria  Age 18 and over  No chiropractic or manual therapy in the previous 3 months.  Exclusion Criteria  tumours, infections, SSPA, acute fractures, Paget‘s disease, severe osteoporosis.

51. Department of Radiology, Orthopaedic University Hospital Balgrist. Zürich Switzerland 51

52. OUTCOME MEASURES:  NRS at baseline and 1 month after the injection procedure or 1st chiropractic treatment.  Patient‘s Global Impression of Change (PGIC) 7 point scale at 1 month.  Postal questionnaire data collection for Radiology patients  Telephone interview data collection for Chiropractic patients.

53. STATISTICAL ANALYSIS  Means + SD for NRS data at baseline and 1 month for each injection site and chiropractic treatment site.  Unpaired t-test for differences between the genders for baseline NRS, 1 month NRS and NRS change scores for each MSK region.  1 month PGIC scores for each gender were compared using the MW-U test.

54. RESULTS  3,900 total patients  1,954 from Imaging-guided injections database.  Higher female prevalence for Epidural (61%), Lumbar Facet injections (55%), GH (52%), Knee (57%), Hip (58%).  Male predominance for Cervical Nerve Root (55%), Lumbar Nerve Root (52%) injections, and Subacromial (56%).  1,946 from Chiropractic database.  62% of neck pain patients were female.  79% of lumbar disc herniation patients were male.

55. Table 1: Gender comparisons for Pain and overall Improvement for Spinal Injections. n = number of patients. NRS = Numerical Rating Scale for pain. PGIC = Patient’s global impression of change. Gender Differences for Imaging-guided Spine Injections  Cervical Indirect NRBs,Cervical Facet Injections, Lumbar Facet injections, Lumbar NRBs, Epidural injections.  No differences in baseline NRS scores.  No differences in 1 month NRS or NRS change scores.  No difference in mean PGIC scores

56. Gender Differences for Imaging-Guided Extremity Injections  Glenohumeral, Subacromial, Knee, Hip  3 of the 4 injection sites showed significantly higher baseline NRS scores for women.  However……..  At 1 month there were no significant gender differences in NRS or PGIC scores between the genders for any of these sites.

57. PROCEDUREDATA TIME POINT MALES Mean (SD)FEMALES Mean (SD)P- VALUE Gleno- Humeral Injections (n = 224) Baseline NRS5.79 (2.11) n = 1076.51 (2.22) n = 1170.01* 1 Month NRS2.72 (2.29)3.00 (2.62)0.40 PGIC @ 1 Month 2.65 (1.402.36 (1.51)0.14 Subacromial Injections (n = 165) Baseline NRS5.88 (2.08) n = 936.74 (1.75) n = 720.004* 1 Month NRS2.49 (2.19)2.59 (2.32)0.80 PGIC @ 1 Month 2.45 (1.49)2.20 (1.38)0.30 Knee Injections (n = 309) Baseline NRS6.10 (2.58) n = 1346.76 (2.08) n = 1750.014* 1 Month NRS4.56 (2.88)4.68 (2.95)0.73 PGIC @ 1 Month 3.43 (1.58)3.38 (1.69)0.65 Hip Injections (n = 135) Baseline NRS5.78 (2.49) n = 576.47 (1.92) n = 780.07 1 Month NRS4.11 (2.75)4.51 (2.79)0.42 PGIC @ 1 Month 3.37 (1.63)3.58 (1.61)0.45

58. Gender Differences for Chiropractic Treatment Patients  LBP Patients:  No gender difference in baseline NRS scores.  Highly significant difference in 1 month NRS and NRS Change scores between the genders. Males responded better.  Males also have a significantly lower PGIC score at 1 month (p = 0.0001).  Neck Pain Patients:  No gender differences in any of the outcome measures at any time point.  MRI Confirmed Lumbar DH Patients:  No gender differences in any of the outcome measures at any time point.

59. PROCEDUREDATA TIME POINT MALES Mean (SD) FEMALES Mean (SD) P-VALUE Low Back Pain Chiropractic Pts (n = 1065) Baseline NRS5.68 (2.12) n = 5385.91 (2.27) n = 5270.09 1 Month NRS2.29 (2.03)3.03 (2.33)0.0001* 1 Month NRS Change score 3.38 (2.62)2.82 (2.83)0.002* PGIC @ 1 Month 1.87 (1.19)2.13 (1.27)0.0001* Lumbar Disc Herniation Chiropractic Pts (n = 139) Baseline NRS LBP Baseline NRS Leg 5.84 (2.78) n = 110 5.35 (3.18) 6.06 (3.27) n = 29 5.50 (3.22) 0.71 0.82 1 Month NRS LBP 1 Month NRS Leg 2.27 (1.95) 2.31 (2.26) 2.71 (2.23) 2.17 (2.29) 0.33 0.78 1 Month NRS LBP Change score 1 Month NRS Leg Change score 3.39 (2.88) 2.97 (2.71) 3.42 (3.49) 3.62 (3.08) 0.96 0.30 PGIC @ 1 Month 1.92 (1.00)1.60 (1.00)0.10 Neck Pain Chiropractic Pts (n = 742) Baseline NRS5.56 (2.10) n = 2795.87 (2.36) n = 4630.08 1 Month NRS2.54 (2.15)2.83 (2.28)0.18 1 Month NRS Change score 2.98 (2.52)2.99 (3.01)0.96 PGIC @ 1 Month 1.93 (1.16)1.92 (1.18)0.86

60. CONCLUSIONS  Measuring pain intensity at one point in time does not give a complete clinical picture of gender differences.  Females had higher levels of pain at the GH, Subacromial and Knee anatomical regions prior to treatment but had larger NRS change scores after treatment compared to males.  The only area in these databases where males had better 1 month outcomes was LBP treated by chiropractors.  Although the majority of neck pain patients in the chiropractic database were women, their 1 month outcomes were no different compared to the men.  Why do women with neck pain respond as well as men to chiropractic treatment but women with LBP do not?

61. Departments of Radiology and Chiropractic, Orthopaedic University Hospital Balgrist. Zürich Switzerland 61 Thank You for Your Attention