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Relationship of Modic Changes, Disk Herniation Morphology, and Axial Location to Outcomes in Symptomatic Cervical Disk Herniation Patients Treated With High-Velocity, Low-Amplitude Spinal Manipulation: A Prospective Study

Published:September 27, 2016DOI:https://doi.org/10.1016/j.jmpt.2016.08.004

      Abstract

      Objective

      The purpose of this study was to evaluate whether cervical disk herniation (CDH) location, morphology, or Modic changes (MCs) are related to treatment outcomes.

      Methods

      Magnetic resonance imaging (MRI) and outcome data from 44 patients with CDH treated with spinal manipulative therapy were evaluated. MRI scans were assessed for CDH axial location, morphology, and MCs. Pain (0-10 for neck and arm) and Neck Disability Index (NDI) data were collected at baseline; 2 weeks; 1, 3, and 6 months; and 1 year. The Patient’s Global Impression of Change data were collected at all time points and dichotomized into “improved,” yes or no. Fischer’s exact test compared the proportion improved with MRI abnormalities. Numerical rating scale and NDI scores were compared with MRI abnormalities at baseline and change scores at all time points using the t test or Mann-Whitney U test.

      Results

      Patients who were Modic positive had higher baseline NDI scores (P = .02); 77.8% of patients who were Modic positive and 53.3% of patients who were Modic negative reported improvement at 2 weeks (P = .21). Fifty percent of Modic I and 83.3% of Modic II patients were improved at 2 weeks (P = .07). At 3 months and 1 year, all patients with MCs were improved. Patients who were Modic positive had higher NRS and NDI change scores. Patients with central herniations were more likely to improve only at the 2-week time point (P = .022).

      Conclusions

      Although patients who were Modic positive had higher baseline NDI scores, the proportion of these patients improved was higher for all time points up to 6 months. Patients with Modic I changes did worse than patients with Modic II changes at only 2 weeks.

      Key Indexing Terms

      Introduction

      After low back pain, neck pain is the second most common complaint of patients presenting to a chiropractic practice.
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      Prevalence and predictors of intense, chronic, and disabling neck and back pain in the UK general population.
      A relatively common subgroup of neck pain is cervical radiculopathy (CR), with an annual incidence of about 80 cases per 100 000 people.
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      Patients with CR present with neck pain, arm pain in a dermatomal pattern, and neurologic deficits, including motor weakness, decreased deep tendon reflexes, or dermatomal sensory loss.
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      Neck pain, cervical radiculopathy, and cervical myelopathy: pathophysiology, natural history, and clinical evaluation.
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      Posterior-lateral foraminotomy as an exclusive operative technique for cervical radiculopathy: a review of 846 consecutively operated cases.
      The nerve roots of C6 and C7 are the most commonly affected.
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      • Litchy WJ
      • O’Fallon WM
      • Kurland LT
      Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990.
      Clinically, the best tests to diagnose CR are
      • Fejer R
      • Kyvik KO
      • Hartvigsen J
      The prevalence of neck pain in the world population: a systematic critical review of the literature.
      the upper limb tension test A,
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      The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults.
      <60° of cervical rotation,
      • Webb R
      • Brammah T
      • Lunt M
      • Urwin M
      • Allison T
      • Symmons D
      Prevalence and predictors of intense, chronic, and disabling neck and back pain in the UK general population.
      positive Spurling test, and
      • Radhakrishnan K
      • Litchy WJ
      • O’Fallon WM
      • Kurland LT
      Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990.
      pain relief with cervical distraction.
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      Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy.
      These tests seem to have the best diagnostic accuracy. If 3 of the 4 are positive, there is a 65% probability that CR is present; with all 4 tests positive, the probability increases to 90%.
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      Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy.
      For further investigation, magnetic resonance imaging (MRI) is the most commonly used imaging modality to detect CR because it detects neural structures, such as cervical nerve roots, directly.
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      The diagnosis and treatment of cervical radiculopathy.
      MRI has been reported to have better accuracy in the prediction of cervical disk herniation (CDH) causing CR compared with other imaging modalities such as computed tomography or plain films.
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      Preoperative evaluation of cervical radiculopathy and myelopathy by surface-coil MR imaging.
      In addition, MRI can also rule out unusual cases of a pathologic condition as a cause of CR, such as intra- or extradural spinal tumors or epidural abscess.
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      Neck pain, cervical radiculopathy, and cervical myelopathy: pathophysiology, natural history, and clinical evaluation.
      In unclear cases, for the differentiation of other neurologic conditions that may imitate CR, electrodiagnostic studies have been reported to be very useful as a further investigation method.
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      The diagnosis and treatment of cervical radiculopathy.
      Thus, it is important to link the clinical findings with the findings on the MRI study because degenerative disk changes, including CDH, are often seen in asymptomatic persons.
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      Correlation between operative outcomes of cervical compression myelopathy and MRI of the spinal cord.
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      • Williams AL
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      • Gabriel Rothman SL
      • Sze GK
      Lumbar disc nomenclature: version 2.0: Recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology.
      The exact pathogenesis of CR is still not clear. Some of the causes of CR are degenerative changes such as CDH, spondylotic spurring of the uncovertebral or facet joints, or a combination of these that lead to compression of the nerve root in the intervertebral foramen.
      • Rao R
      Neck pain, cervical radiculopathy, and cervical myelopathy: pathophysiology, natural history, and clinical evaluation.
      In addition to the mechanical compression, inflammatory changes in the nerve root and in the dorsal root ganglion seem to play an important role in pain generation. Neurogenic chemical mediators of pain can be released by the neural cell bodies and nonneurogenic mediators of pain by the disk tissue.
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      • Montgomery D
      The pathophysiology of axial and radicular neck pain.
      To further complicate matters, recent studies have reported that Modic changes (MCs) are commonly associated with disk herniations in both the lumbar and cervical spine.
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      • Peterson CK
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      • Pfirrmann CW
      The evolution of degenerative marrow (Modic) changes in the cervical spine in neck pain patients.
      MCs are specific endplate signal changes in the spine categorized into 3 types: MC type I (bone marrow edema), II (fat), and III (subchondral bone sclerosis).
      • Modic MT
      • Steinberg PM
      • Ross JS
      • Masaryk TJ
      • Carter JR
      Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging.
      In published reports, they are associated with nonspecific spinal pain syndromes, especially type I.
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      • et al.
      Association between changes in lumbar Modic changes and low back symptoms over a two-year period.
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      • et al.
      Modic changes in endplates of lumbar vertebral bodies: prevalence and association with low back and sciatic pain among middle-aged male workers.
      There are 2 main theories about the pathophysiology of MCs: a biomechanical theory and an infection theory. The biomechanical theory explains the MC as a result of mechanical stress at the vertebral endplate.
      • Albert HB
      • Kjaer P
      • Jensen TS
      • Sorensen JS
      • Bendix T
      • Manniche C
      Modic changes, possible causes and relation to low back pain.
      • van Dieën JH
      • Weinans H
      • Toussaint HM
      Fractures of the lumbar vertebral endplate in the etiology of low back pain: a hypothesis on the causative role of spinal compression in aspecific low back pain.
      • Schmid G
      • Witteler A
      • Willburger R
      • Kuhnen C
      • Jergas M
      • Koester O
      Lumbar disk herniation: correlation of histologic findings with marrow signal intensity changes in vertebral endplates at MR imaging.
      Because disk degeneration is also a result of improper loading of the disk, published reports support this theory with studies that have identified an increased incidence of MCs in patients with disk degeneration.
      • Albert HB
      • Manniche C
      Modic changes following lumbar disc herniation.
      • Jensen TS
      • Kjaer P
      • Korsholm L
      • et al.
      Predictors of new vertebral endplate signal (Modic) changes in the general population.
      The infection theory implies that the edema in the vertebral endplate is caused by pyogenic infection of the disk and adjacent endplates. However, controversy about this theory exists in the published reports.
      • Stirling A
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      • Rafiq M
      • Lambert PA
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      Association between sciatica and Propionibacterium acnes.
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      Propionibacterium acnes contamination in lumbar disc surgery.
      • Wedderkopp N
      • Thomsen K
      • Manniche C
      • Kolmos HJ
      • Secher Jensen T
      • Leboeuf YC
      No evidence for presence of bacteria in modic type I changes.
      For disk herniation patients it has been reported that patients with MC have a slower resorption of the discus hernia.
      • Shan Z
      • Fan S
      • Xie Q
      • et al.
      Spontaneous resorption of lumbar disc herniation is less likely when modic changes are present.
      In addition, studies often report a poorer outcome with various treatments of individuals who are MC positive.
      • Jensen RK
      • Leboeuf-Yde C
      Is the presence of modic changes associated with the outcomes of different treatments? A systematic critical review.
      • Peterson CK
      • Pfirrmann CW
      • Hodler J
      Are Modic changes related to outcomes in lumbar disc herniation patients treated with imaging-guided lumbar nerve root blocks?.
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      However, spinal manipulative therapy (SMT) is not one of the treatments evaluated in patients who are MC positive.
      The treatment of CR can be divided into conservative and surgical treatment methods.
      • Decker RC
      Surgical treatment and outcomes of cervical radiculopathy.
      • Murphy DR
      • Hurwitz EL
      • Gregory A
      • Clary R
      A nonsurgical approach to the management of patients with cervical radiculopathy: a prospective observational cohort study.
      Surgical treatment options contain several different methods and are generally considered in the absence of success with conservative treatment.
      • Alentado VJ
      • Lubelski D
      • Steinmetz MP
      • Benzel EC
      • Mroz TE
      Optimal duration of conservative management prior to surgery for cervical and lumbar radiculopathy: a literature review.
      The pool of conservative treatment methods for CR includes different manual and physical therapies as well as oral or invasive application of anti-inflammatory medication. There is good evidence that many patients with CR benefit, in both short-term and long-term outcomes, from epidural or nerve root infiltration.
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      • Kolstad F
      • Leivseth G
      • Nygaard OP
      Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study.
      • Vallée JN
      • Feydy A
      • Carlier RY
      • Mutschler C
      • Mompoint D
      • Vallée CA
      Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid injection.
      The evidence for SMT as a treatment method for CDH with CR is sparse in the published reports. Murphy et al
      • Murphy DR
      • Hurwitz EL
      • Gregory A
      • Clary R
      A nonsurgical approach to the management of patients with cervical radiculopathy: a prospective observational cohort study.
      studied 35 patients with CR who were treated conservatively with an individualized combination of high-velocity, low-amplitude (HVLA) manipulation; muscle energy techniques; neural mobilization techniques; traction treatment; nonsteroidal anti-inflammatory medication; oral corticosteroids; epidural steroid injection; and different types of rehabilitation exercises. They reported a mean self-rated improvement of 88% and a mean reduction in pain of 72% at 3 months after the initial treatment.
      • Murphy DR
      • Hurwitz EL
      • Gregory A
      • Clary R
      A nonsurgical approach to the management of patients with cervical radiculopathy: a prospective observational cohort study.
      Although this study used cervical HVLA manipulation as the central part of their treatment, the other modalities were added individually. This means that the outcome cannot be related only to the HVLA manipulation. Peterson et al
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      looked at the effect of HVLA alone for the treatment of patients with MRI-confirmed CDH with radiculopathy. They examined the effect of HVLA manipulation at the level of the symptomatic CDH combined with local ice application. At 3 months after the initial treatment, the patients had a mean reduction in pain scores of 66%. In addition, 93% of the acute patients (symptoms duration <4 weeks) and 76% of the chronic patients (symptoms duration >12 weeks) reported their global impression of change as better or much better.
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      There is some research evidence supporting the use of HVLA SMT for patients with symptomatic CDHs, but the importance of specific MRI findings relevant to the treatment outcomes has not been studied. Therefore, the purposes of this study were to
      • Fejer R
      • Kyvik KO
      • Hartvigsen J
      The prevalence of neck pain in the world population: a systematic critical review of the literature.
      compare the specific MRI CDH findings of location in the axial plane, morphology, CDH level, and presence or absence and type of MCs to treatment outcomes; and
      • Côté P
      • Cassidy JD
      • Carroll L
      The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults.
      examine the inter-rater reliability of using the accepted nomenclature for CDH as well as for MC.

      Methods

      Ethics approval was obtained from the hospital and Canton ethics committees before the start of the study (EK 21/2009).

      Patients

      Inclusion Criteria

      This is a retrospective analysis of the MRI scans from patients included in a previous prospective, cohort, outcome study about symptomatic CDH treated by SMT done by Peterson et al in 2013.
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      The patients had been recruited from a single chiropractic practice in Zurich, Switzerland, from January 2010 to April 2013. The participants were aged between 24 and 66 years. Inclusion criteria had been the following: neck pain and moderate to severe arm pain in a dermatomal pattern and sensory, motor, or reflex alterations corresponding to the involved MRI-confirmed nerve root level. In addition, at least one of the following clinical tests for radiculopathy had been required
      • Fejer R
      • Kyvik KO
      • Hartvigsen J
      The prevalence of neck pain in the world population: a systematic critical review of the literature.
      : positive upper limb tension test,
      • Côté P
      • Cassidy JD
      • Carroll L
      The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults.
      positive cervical traction test,
      • Webb R
      • Brammah T
      • Lunt M
      • Urwin M
      • Allison T
      • Symmons D
      Prevalence and predictors of intense, chronic, and disabling neck and back pain in the UK general population.
      positive Spurling test, and
      • Radhakrishnan K
      • Litchy WJ
      • O’Fallon WM
      • Kurland LT
      Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990.
      cervical rotation <60°. Those tests were considered by Wainner et al
      • Wainner RS
      • Fritz JM
      • Irrgang JJ
      • Boninger ML
      • Delitto A
      • Allison S
      Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy.
      as the most reliable and accurate for the evaluation of CR. In addition, an MRI-proven CDH at the corresponding level was required.

      Exclusion Criteria

      Initial exclusion criteria for the first study done in 2013 were contraindication to SMT such as tumors, infections, inflammatory arthropathies, acute fractures, Paget disease, anticoagulation therapy, cervical spondylotic myelopathy, known unstable congenital anomalies, and severe osteoporosis.
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      Also, patients with previous spinal surgery, a history of strokes, signs of cervical spondylotic myelopathy, spinal stenosis, or pregnancy had been excluded. In addition to these exclusions, patients whose MRIs were no longer available to analyze were excluded from the current study.

      Baseline Data and Outcome Measures

      In the study from 2013, patients first completed a demographic information questionnaire and a baseline questionnaire, including the numerical rating scale (NRS) for pain and the Neck Disability Index (NDI) as secondary outcome measurements.
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      The NRS for pain is an 11-point rating scale with 0 being no pain and 10 being the worst pain imaginable. It is an accurate, reliable, repeatable, and sensitive measurement for pain intensity assessment.
      • Cleland JA
      • Childs JD
      • Whitman JM
      Psychometric properties of the Neck Disability Index and Numeric Pain Rating Scale in patients with mechanical neck pain.
      Patients completed separate NRS scales for neck and arm pain. The NDI was also included; it is a commonly used questionnaire for measuring self-rated disability caused by pain, and it has been reported to be valid and reliable.
      • Vernon H
      The Neck Disability Index: state-of-the-art, 1991-2008.
      At 2 weeks, 1 month, 3 months, 6 months, and 1 year after the initial consultation, a trained research assistant who was independent from the treating practice interviewed all patients by telephone to collect the NDI, both NRSs, and the Patient’s Global Impression of Change (PGIC) data. The PGIC is considered to be the primary outcome measurement for this study. It consists of a 7-point verbal scale containing the following responses: much worse, worse, slightly worse, no change, slightly better, better, and much better. Only the responses much better and better were considered to be clinically relevant improvement, as was determined in previous studies.
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.

      Treatment Procedure

      The patients had been treated by a standardized single HVLA cervical SMT at the level of the symptomatic CDH (Fig 1). Treatments were repeated 3 to 5 times per week during the first 2 to 4 weeks and 1 to 3 times per week afterward until the patients were asymptomatic. These treatments had been administered by 3 different doctors of chiropractic. All had been working in the same practice for several years. They had between 6 and 30 years of clinical experience. Because the senior doctor of chiropractic educated the younger chiropractors during their postgraduate residency programs, the SMT method can be seen as standardized. Patients had been allowed to take pain medications if needed, but this was not evaluated in the study. If patients wanted to have additional treatment modalities such as surgery or nerve root infiltration, these options were discussed with the chiropractor. If one of these treatments had been administered, the patient would have been removed from the study. This did not happen in any of the cases.
      Figure thumbnail gr1
      Fig 1Doctor and patient set up for the high-velocity, low-amplitude spinal manipulative procedure to the level of cervical disk herniation.

      MRI Analysis

      All MRIs of the included patients were analyzed for MCs and intervertebral disk herniation. The MRIs were read independently by 2 chiropractors in the government-accredited postgraduate program (residents) for the reliability part of this study and by a professor with a special education in musculoskeletal imaging with 28 years of experience. A consensus reading among the 3 evaluators was then used for the outcome evaluations.
      For MCs, the type (MC I or II) and the spinal level in which they were present for each patient was assessed and recorded. All CDHs in the MRI studies of the included patients were evaluated and recorded according to the latest update on spinal disk nomenclature. Although the recommendations used were designed for the lumbar spine, the authors stated that these could be easily extrapolated to the cervical spine.
      • Fardon DF
      • Williams AL
      • Dohring EJ
      • Murtagh FR
      • Gabriel Rothman SL
      • Sze GK
      Lumbar disc nomenclature: version 2.0: Recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology.
      The spinal level of the CDH, the location category, and the type classification were identified. By location category, the DH was labeled as central, paramedian/paracentral, foraminal, or extraforaminal. Relating to the type of classification, these were labeled as disk bulge, disk protrusion, disk extrusion, or disk sequestration, as described by Fardon et al.
      • Fardon DF
      • Williams AL
      • Dohring EJ
      • Murtagh FR
      • Gabriel Rothman SL
      • Sze GK
      Lumbar disc nomenclature: version 2.0: Recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology.
      A disk bulge is described as a widening of more than 25% of the disk’s circumference. A disk herniation is defined as a disk displacement that is less than 25% of its circumference. The difference between an extrusion and a protrusion is that, in an extrusion, the base of the disk herniation has a smaller diameter than the widest diameter of the disk herniation, whereas in a protrusion, the base diameter is bigger than the widest diameter of the herniation (Fig 2). A sequester describes a part of the disk material that has lost its contact to the disk and floats freely in the spinal canal.
      • Fardon DF
      • Williams AL
      • Dohring EJ
      • Murtagh FR
      • Gabriel Rothman SL
      • Sze GK
      Lumbar disc nomenclature: version 2.0: Recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology.
      Figure thumbnail gr2
      Fig 2T2-weighted axial (A) and parasagittal (B) magnetic resonance imaging slices showing a left paramedian C5-C6 cervical disk extrusion (arrows) with posterior displacement of the spinal cord.
      Finally, whether MCs and CDHs were at the same level was recorded.

      Statistical Analysis

      Primary Outcome Statistics

      The PGIC scale was dichotomized into improved and not improved patients as described earlier. The percentage of patients improved or not improved was calculated for all time points. Fischer’s exact test was used to compare the proportion of patients improved for the various categories of MRI abnormalities. A P value <.05 was considered statistically significant. Unfortunately, the number of patients with MC type I was small and did not reach the required minimum of 5 patients for 3 of the data collection time points required to perform the χ2 test for this particular MRI finding. Only the time points of 3 months and 1 year met the minimum requirement.

      Secondary Outcome Statistics

      To assess differences in NRS neck pain, NRS arm pain, and NDI scores between patients who were MC positive and MC negative at each time point, the Mann-Whitney U test was performed (nonparametric data). The change scores for NRS neck pain, NRS arm pain, and NDI scores between baseline and all time points were calculated separately for the MC-positive and MC-negative groups (normally distributed data) and compared using the unpaired Student t test. The unpaired t test was also used to compare differences in NRS neck pain change scores, NRS arm pain change scores, and NDI change scores between MC type I and MC-negative groups at each time point.

      Interexaminer Reliability Analysis

      The κ reliability test and percentage calculation according to Landis and Koch
      • Landis JR
      • Koch GG
      An application of hierarchical kappa-type statistics in the assessment of majority agreement among multiple observers.
      were used to evaluate the interexaminer reliability between the independent readings of the MRI by the main author and a coauthor, both chiropractic residents in the postgraduate program. The κ test labels reliability in the following levels: poor (0-0.2), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and almost perfect (0.81-1.00).
      • Landis JR
      • Koch GG
      An application of hierarchical kappa-type statistics in the assessment of majority agreement among multiple observers.
      In addition, κ values were obtained for the following MRI findings: whether MCs were present, categorization of MCs, spinal level of MCs, CDH level, location category of the CDH (central, paramedian, foraminal, or extraforaminal), type classification of the CDH (bulge, protrusion, extrusion, or sequester), and whether MCs and CDH were at the same spinal level.

      Results

      A total of 44 patients were available at baseline for the analysis. The mean age was 44.73 years with a standard deviation (SD) of 7.9 years. The sample size changed between the different time points, as a result of the relatively narrow time frames allowed for the follow-up telephone calls. Although for some patients some telephone calls were missing, they remained in the study unless 3 consecutive telephone calls were missed. The mean age of patients with MCs was 47.69 years (SD 8.9 years); the mean age of patients without MCs was 43.35 years (SD 7.3 years) (P = .099). Like the total sample size, the number of patients who were MC positive and MC negative also fluctuated slightly between the different time points.
      There were 51 cervical motion segments with CDH: 7 classified as bulge, 25 classified as protrusion, and 19 classified as extrusion and no sequestrations.
      At 2 weeks, 56.3% of all patients had clinically significant improvement. This number increased gradually until reaching 100% at 1 year after start of treatment (Table 1).
      Table 1Percentage of Patients With Clinically Significant Improvement (ie, Much Better or Better on the 7-Point Likert Scale) at Different Time Points for Patients With and Without MCs and Total Number of the Different Groups at Each Time Point
      All (%)No.MC+ (%)No.MC– (%)No.MC I (%)No.MCII (%)No.
      2 wk56.33277.8953.33050.02
      Insufficient number of patients to perform χ2 test.
      83.36
      1 mo68.34190.91168.438100.04
      Insufficient number of patients to perform χ2 test.
      100.05
      3 mo86.745100.01385.742100.05100.06
      6 mo88.44391.71290.241100.04
      Insufficient number of patients to perform χ2 test.
      100.06
      1 y100.041100.011100.040100.05100.06
      All, all patients; MC, Modic change; MC+, patients with MC; MC–, patients without MC; No. total number of patients in the corresponding group.
      a Insufficient number of patients to perform χ2 test.
      There were no significant differences in treatment outcomes for any of the data collection time points for MC spinal level, CDH spinal level, CDH type (ie, morphology) classification, and whether MC and CDH were at the same level. In the CDH location in the axial plane classification, 77.8% of patients with central herniations reported improvement at the 2-week time point compared with 44.4% of patients with paracentral herniations and 20.0% of patients with foraminal herniations (P = .022). However, no significant difference in the proportion of patients improved at the other data collection time points was found.
      Table 1 shows the number of patients with MCs and their types for the various data collection time points. In 3 cases, T1-weighted MR images were not available to classify patients who were Modic positive as type I or II and were only assessed with the T2-weighted slices as Modic positive. In patients with MCs (both type I and II), although not statistically significant, 77.8% reported clinically relevant improvement at 2 weeks, whereas 53.3% of patients without MC had clinically relevant improvement (χ2 [1, N = 31] = 0.30; P = .21). With the exception of the 6-month time point for the patients who were MC positive, both MC-positive and MC-negative groups had a gradual increase in proportion of patients with clinically significant improvement until reaching 100% at 1 year after treatment. From 3 months after treatment, all patients with MC type I and II reported clinically significant improvement.
      Comparison of patients with MC and without MC in relation to NRS for neck pain, NRS for arm pain, and NDI total score indicated a statistically significant difference for NDI total score at baseline (P = .04) and a trend at 6 months after treatment (P = .07) (Table 2), with patients who were Modic positive having higher scores.
      Table 2Median Score Comparisons Between Patients Who Were MC Positive and MC Negative at Baseline and All Time Points Regarding NRS Neck Pain, NRS Arm Pain, and NDI Total Score
      MC (Y/N)No.Median (Interquartile Range)P
      Baseline NRS neckY137.0 (4.0).08
      N315.5 (2.5)
      Baseline NRS armY138.0 (4.75).30
      N316.5 (4.5)
      Baseline NDI totalY1323.0 (15.0).04
      P < .05.
      N3115.0 (11.0)
      2 wk NRS neckY93.0 (1.5).92
      N223.5 (1.88)
      2 wk NRS armY93.0 (0.75).54
      N225.0 (1.88)
      2 wk NDI totalY913.0 (9.0).75
      N2213.5 (8.0)
      1 mo NRS neckY113.0 (0.0).72
      N292.0 (0.75)
      1 mo NRS armY110.5 (0.0).21
      N292.0 (1.0)
      1 mo NDI totalY118.0 (4.0)>.99
      N298.0 (4.0)
      3 mo NRS neckY131.0 (0.0).94
      N311.0 (0.0)
      3 mo NRS armY130.0 (0.0).34
      N311.0 (0.0)
      3 mo NDI totalY135.0 (1.5).48
      N313.75 (2.0)
      6 mo NRS neckY122.0 (0.25).09
      N311.0 (0.0)
      6 mo NRS armY120.25 (0.0).57
      N310.0 (0.0)
      6 mo NDI totalY124.0 (2.4).07
      N312.0 (0.0)
      1 y NRS neckY111.0 (0.0).46
      N290.0 (0.0)
      1 y NRS armY110.0 (0.0).81
      N290.0 (0.0)
      1 y NDI totalY111.10 (0.0).91
      N291.00 (0.0)
      MC, Modic change; N, no; NDI total, Neck Disability Index total score; No., number of patients; NRS arm, numerical rating scale for arm pain; NRS neck, numerical rating scale for neck pain; SD, standard deviation; Y, yes.
      a P < .05.
      Differences in change scores for NRS neck pain, NRS arm pain, and NDI total scores between patients who were MC positive and MC negative indicated that for all time points except NRS arm pain at 6 months, the patients who were MC positive had higher change scores (ie, more pain relief and greater reductions in disability). However, this did not reach statistical significance (Table 3). Similarly, when comparing the patients who were MC negative with only patients with MC type I, the patients with MC type I had higher NRS neck pain and arm pain change scores and higher NDI change scores at all time points. However, this also did not reach statistical significance (Table 4).
      Table 3Differences for NRS Neck Pain, Arm Pain, and NDI Total Change Scores Between Patients Who Were MC Positive and MC Negative for All Time Points
      MC (Y/N)No.Mean (SD)t Test Statistics
      2 wk NRS neck changeY92.89 (2.77)P = .20
      N221.66 (2.22)t
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      = 1.30
      d = 0.49
      2 wk NRS arm changeY93.00 (2.49)P = .30
      N221.77 (3.10)t
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      = 1.05
      d = 0.44
      2 wk NDI changeY95.56 (3.40)P = .20
      N223.39 (4.38)t
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      = 1.32
      d = 0.56
      1 mo NRS neck changeY113.86 (3.56)P = .19
      N292.48 (2.78)t
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.
      = 1.30
      d = 0.44
      1 mo NRS arm changeY114.14 (3.82)P = .75
      N293.79 (2.62)t
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.
      = 0.33
      d = 0.11
      1 mo NDI changeY119.91 (6.70)P = .73
      N296.36 (4.95)t
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.
      = 1.84
      d = 0.61
      3 mo NRS neck changeY134.61 (3.65)P = .22
      N313.24 (2.83)t
      • Schistad EI
      • Espeland A
      • Rygh LJ
      • Røe C
      • Gjerstad J
      The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.
      = 1.35
      d = 0.43
      3 mo NRS arm changeY135.31 (3.31)P = .38
      N314.32 (3.41)t
      • Schistad EI
      • Espeland A
      • Rygh LJ
      • Røe C
      • Gjerstad J
      The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.
      = 0.88
      d = 0.29
      3 mo NDI changeY1315.15 (6.80)P = .20
      N3110.87 (6.98)t
      • Schistad EI
      • Espeland A
      • Rygh LJ
      • Røe C
      • Gjerstad J
      The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.
      = 1.87
      d = 0.62
      6 mo NRS neck changeY124.00 (2.85)P = .07
      N312.63 (3.24)t
      • Bianchi M
      • Peterson CK
      • Pfirrmann C
      • Hodler J
      • Bolton J
      Are the presence of Modic changes on MRI scans related to "improvement" in low back pain patients treated with lumbar facet joint injections?.
      = 0.35
      d = 0.12
      6 mo NRS arm changeY124.21 (2.86)P = .45
      N314.94 (2.81)t
      • Bianchi M
      • Peterson CK
      • Pfirrmann C
      • Hodler J
      • Bolton J
      Are the presence of Modic changes on MRI scans related to "improvement" in low back pain patients treated with lumbar facet joint injections?.
      = –0.76
      d = –0.26
      6 mo NDI changeY1214.32 (6.71)P = .07
      N3112.06 (7.92)t
      • Bianchi M
      • Peterson CK
      • Pfirrmann C
      • Hodler J
      • Bolton J
      Are the presence of Modic changes on MRI scans related to "improvement" in low back pain patients treated with lumbar facet joint injections?.
      = 0.87
      d = 0.31
      1 y NRS neck changeY115.36 (2.61)P = .39
      N294.16 (2.79)t
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.
      = 1.25
      d = 0.45
      1 y NRS arm changeY115.50 (3.69)P = .94
      N295.41 (2.81)t
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.
      = 0.08
      d = 0.03
      1 y NDI changeY1114.48 (7.21)P = .52
      N2912.97 (5.95)t
      • Hurst H
      • Bolton J
      Assessing the clinical significance of change scores recorded on subjective outcome measures.
      = 0.66
      d = 0.23
      MC, Modic changes; N, no; NDI change, Neck Disability Index change score; No., patient number; NRS neck/arm change, numerical rating scale for neck pain/arm pain change score; SD, standard deviation; Y, yes.
      Table 4Differences for NRS Neck Pain, Arm Pain, and NDI Total Change Scores Between Patients Who Were MC Negative and Patients With Type I MC for All Time Points
      MC (0/I)No.Mean (SD)t Test Statistics
      2 wk NRS neck change0221.66 (2.22)P = .27
      I23.50 (2.12)t
      • Jensen TS
      • Kjaer P
      • Korsholm L
      • et al.
      Predictors of new vertebral endplate signal (Modic) changes in the general population.
      = 1.12
      d = 0.85
      2 wk NRS arm change0221.77 (3.10)P = .24
      I24.50 (0.71)t
      • Jensen TS
      • Kjaer P
      • Korsholm L
      • et al.
      Predictors of new vertebral endplate signal (Modic) changes in the general population.
      = 1.22
      d = 1.43
      2 wk NDI change0223.39 (4.38)P = .40
      I26.50 (2.12)t
      • Jensen TS
      • Kjaer P
      • Korsholm L
      • et al.
      Predictors of new vertebral endplate signal (Modic) changes in the general population.
      = .98
      d = 0.96
      1 mo NRS neck change0292.48 (2.78)P = .06
      I43.88 (4.77)t
      • Kolstad F
      • Leivseth G
      • Nygaard OP
      Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study.
      = .86
      d = 0.37
      1 mo NRS arm change0293.79 (2.62)P = .14
      145.87 (2.17)t
      • Kolstad F
      • Leivseth G
      • Nygaard OP
      Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study.
      = 1.51
      d = 0.78
      1 mo NDI change0296.36 (4.95)P = .44
      I410.00 (6.98)t
      • Kolstad F
      • Leivseth G
      • Nygaard OP
      Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study.
      = 1.32
      d = 0.61
      3 mo NRS neck change0313.24 (2.83)P = .12
      I56.00 (3.74)t
      • Cleland JA
      • Childs JD
      • Whitman JM
      Psychometric properties of the Neck Disability Index and Numeric Pain Rating Scale in patients with mechanical neck pain.
      = 1.94
      d = 0.84
      3 mo NRS arm change0314.32 (3.41)P = .10
      157.10 (2.92)t
      • Cleland JA
      • Childs JD
      • Whitman JM
      Psychometric properties of the Neck Disability Index and Numeric Pain Rating Scale in patients with mechanical neck pain.
      = 1.72
      d = 0.88
      3 mo NDI change03110.87 (9.98)P = .34
      I516.00 (7.71)t
      • Cleland JA
      • Childs JD
      • Whitman JM
      Psychometric properties of the Neck Disability Index and Numeric Pain Rating Scale in patients with mechanical neck pain.
      = 1.51
      d = 0.70
      6 mo NRS neck change0313.63 (3.24)P = .20
      I45.00 (3.56)t
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      = .79
      d = 0.40
      6 mo NRS arm change0314.94 (2.81)P = .53
      145.88 (2.39)t
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      = .64
      d = 0.36
      6 mo NDI change03112.06 (7.92)P = .14
      I415.75 (8.50)t
      • Peterson CK
      • Schmid C
      • Leemann S
      • Anklin B
      • Humphreys BK
      Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.
      = .87
      d = 0.45
      1 y NRS neck change0294.16 (2.79)P = .39
      I56.30 (2.86)t
      • Vallée JN
      • Feydy A
      • Carlier RY
      • Mutschler C
      • Mompoint D
      • Vallée CA
      Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid injection.
      = 1.58
      d = 0.76
      1 y NRS arm change0295.41 (2.81)P = .10
      157.70 (2.68)t
      • Vallée JN
      • Feydy A
      • Carlier RY
      • Mutschler C
      • Mompoint D
      • Vallée CA
      Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid injection.
      = 1.69
      d = 0.83
      1 y NDI change02912.97 (5.95)P = .07
      I518.40 (6.27)t
      • Vallée JN
      • Feydy A
      • Carlier RY
      • Mutschler C
      • Mompoint D
      • Vallée CA
      Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid injection.
      = 1.87
      d = 0.89
      0, no Modic change; I, type I Modic changes; MC, Modic change; NDI change, Neck Disability Index change score; No., number of patients; NRS neck/arm change, numerical rating scale for neck pain/arm pain change score; SD, standard deviation.
      The interexaminer reliability analysis indicated a range of reliability categories between fair and perfect (Table 5). In particular, the reliability for MC present or absent, MC category, and MC and CDH at the same level revealed almost perfect to perfect κ results and also with high percent agreements. The lowest reliability was found in the CDH location and CDH level groups.
      Table 5κ and Percentage Analysis of Interexaminer Reliability of the MRI Evaluation
      MC Present/AbsentMC CatCDH LocMC LevelCDH LevelMC/CDH SameCDH Class
      κ1.000.860.420.620.290.820.60
      %100945373719368
      CDH Class, cervical disk herniation classification (bulge, protrusion, extrusion, sequester); CDH Level, spinal level of Modic change; CDH Loc, cervical disk herniation location (central, paramedian, foraminal, or extraforaminal); κ, kappa reliability value: poor (0-0.2), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and almost perfect (0.81-1.00); MC Cat, Modic change category (type I, type II); MC/CDH Same, Modic change and cervical disk herniation at the same level; MC Level, spinal level of Modic change (ie, C5/C6); MRI, magnetic resonance imaging.

      Discussion

      In this prospective, cohort, outcome study with patients with CDH treated with HVLA cervical manipulation by 1 of 3 chiropractors, the purpose was to evaluate the outcome differences in relation to the presence or absence of MCs, as well as whether the morphology or axial location of the herniation was related to treatment outcomes. To the authors’ knowledge, no other study has looked at this previously for the cervical spine. It is known from the literature that MCs are associated with more spinal pain, particularly in patients with MC type I.
      • Peterson CK
      • Pfirrmann CW
      • Hodler J
      Are Modic changes related to outcomes in lumbar disc herniation patients treated with imaging-guided lumbar nerve root blocks?.
      • Jensen TS
      • Karppinen J
      • Sorensen JS
      • Niinimäki J
      • Leboeuf-Yde C
      Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain.
      • Bianchi M
      • Peterson CK
      • Pfirrmann C
      • Hodler J
      • Bolton J
      Are the presence of Modic changes on MRI scans related to "improvement" in low back pain patients treated with lumbar facet joint injections?.
      Consistent with this fact is that in the present study, patients with CDH with MCs reported significantly higher baseline disability scores on the NDI, which is not surprising and is consistent with published reports.
      • Schistad EI
      • Espeland A
      • Rygh LJ
      • Røe C
      • Gjerstad J
      The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.
      However, at all follow-up time points, except for arm pain at 6 months, patients who were MC positive had higher NRS and NDI change scores, meaning that their levels of pain and disability reduction were greater than patients without MC. This was also found when MC type I was compared with no MC. The results did not reach statistical significance, most likely because of the small sample size (underpowered). Some follow-up time points almost reached statistical significance, though, even with the small sample sizes (6-month NRS change score, 6-month NDI change score, and 1-year NDI change score, all with P < .10), thus indicating a trend for the patients who were MC positive to have better outcomes despite having greater disability before treatment. These results were not expected because they are contrary to those published so far for other treatments.
      • Jensen RK
      • Leboeuf-Yde C
      Is the presence of modic changes associated with the outcomes of different treatments? A systematic critical review.
      • Peterson CK
      • Pfirrmann CW
      • Hodler J
      Are Modic changes related to outcomes in lumbar disc herniation patients treated with imaging-guided lumbar nerve root blocks?.
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      For nonspecific low back pain, recent studies have reported that MCs are associated with back pain syndromes.
      • Jensen TS
      • Karppinen J
      • Sorensen JS
      • Niinimäki J
      • Leboeuf-Yde C
      Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain.
      • Schistad EI
      • Espeland A
      • Rygh LJ
      • Røe C
      • Gjerstad J
      The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.
      Also, a systematic review in 2008 reported that MCs are associated with lumbar spine pain syndromes.
      • Jensen TS
      • Karppinen J
      • Sorensen JS
      • Niinimäki J
      • Leboeuf-Yde C
      Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain.
      However, most studies do not specifically look at low back pain patients with lumbar disk herniations (LDHs) and, importantly, few have evaluated responses to specific treatments.
      A possible explanation as to why SMT may help in patients with MCs is hypothesized here. It has been reported that most MCs have a natural progression, usually from MC type I to MC type II, and may even disappear in some cases.
      • Hutton MJ
      • Bayer JH
      • Powell JM
      Modic vertebral body changes: the natural history as assessed by consecutive magnetic resonance imaging.
      • Mitra D
      • Cassar-Pullicino VN
      • McCall IW
      Longitudinal study of vertebral type-1 end-plate changes on MR of the lumbar spine.
      Because MC type I has greater association with pain syndromes, it has been determined that these pain syndromes may disappear gradually over time because of the natural progression of MCs.
      • Kuisma M
      • Karppinen J
      • Niinimäki J
      • et al.
      Modic changes in endplates of lumbar vertebral bodies: prevalence and association with low back and sciatic pain among middle-aged male workers.
      • Schistad EI
      • Espeland A
      • Rygh LJ
      • Røe C
      • Gjerstad J
      The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.
      • Mitra D
      • Cassar-Pullicino VN
      • McCall IW
      Longitudinal study of vertebral type-1 end-plate changes on MR of the lumbar spine.
      • Kääpä E
      • Luoma K
      • Pitkäniemi J
      • Kerttula L
      • Grönblad M
      Correlation of size and type of modic types 1 and 2 lesions with clinical symptoms: a descriptive study in a subgroup of patients with chronic low back pain on the basis of a university hospital patient sample.
      The theory that MCs are caused by overloading and shear forces of the vertebral disk, which lead to an inflammatory state of these structures, indicates that MCs can be an origin of spinal pain syndromes.
      • Albert HB
      • Kjaer P
      • Jensen TS
      • Sorensen JS
      • Bendix T
      • Manniche C
      Modic changes, possible causes and relation to low back pain.
      Spinal pain syndromes produce increased electromyographic activity in paraspinal muscles, which can further irritate the already inflamed joint.
      • Finneran MT
      • Mazanec D
      • Marsolais ME
      • Marsolais EB
      • Pease WS
      Large-array surface electromyography in low back pain: a pilot study.
      If the previously mentioned facts are linked with studies that report that SMT reduces paraspinal muscle activity, one can hypothesize that SMT may reduce pain in patients with MCs.
      • Pickar JG
      Neurophysiological effects of spinal manipulation.
      This can be seen as a pain-reducing treatment during the natural history of MC, or that SMT potentially supports or even accelerates the progression of MC.
      However, in a recent study by Annen et al,
      • Annen M
      • Peterson CK
      • Leemann S
      • Schmid C
      • Anklin B
      • Humphreys BK
      Comparison of outcomes in MRI confirmed lumbar disc herniation patients with and without Modic changes treated with high velocity, low amplitude spinal manipulation.
      patients with LDH with MC type I who were treated with HVLA spinal manipulation had a pattern of improvement and recurrence over time compared with patients with MC type II and patients without MCs who improved and stabilized.
      • Annen M
      • Peterson CK
      • Leemann S
      • Schmid C
      • Anklin B
      • Humphreys BK
      Comparison of outcomes in MRI confirmed lumbar disc herniation patients with and without Modic changes treated with high velocity, low amplitude spinal manipulation.
      Thus it appears, when comparing the present study on the cervical spine with the similar study on the lumbar spine, that there is a difference between the cervical and lumbar spinal regions with respect to the influence of MCs on treatment outcomes. This highlights the importance of multiple data collection time points.
      Currently, the response of patients with MC to different treatment methods remains unclear in the lumbar spinal region as well. A systematic review by Jensen and Leboeuf-Yde
      • Jensen RK
      • Leboeuf-Yde C
      Is the presence of modic changes associated with the outcomes of different treatments? A systematic critical review.
      in 2011 found 6 good quality studies that measured outcomes of patients with MC for different treatments. Two studies, 1 with intradisk steroid injection and the other with fusion surgery as treatment methods, reported a favorable outcome for patients with MC. Another study with intradisk steroid injection and 1 with epidural steroid injection, however, reported mixed results. Exercise therapy and lumbar disk replacement had negative outcomes in patients with MC. This review stated that there are too few studies on this topic to make a general opinion on how patients with MCs respond to various treatments.
      Peterson et al
      • Peterson CK
      • Pfirrmann CW
      • Hodler J
      Are Modic changes related to outcomes in lumbar disc herniation patients treated with imaging-guided lumbar nerve root blocks?.
      examined the effect of lumbar nerve root infiltration in symptomatic patients with MRI-confirmed LDH. They found that patients with LDH with MCs had significantly higher pain levels and significantly less pain reduction 1 month after treatment compared with patients with LDH without MCs. A recently published study using the same protocol was done for patients with CDH, and the results were similar.
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      To summarize, the results of the present study on patients with CDH, which indicate better treatment outcomes for patients with CDH with MCs, are generally consistent with those reported for patients with LDH, other than the fact that the patients with CDH and MC reported no relapses. However, it is in contrast to the overall results of other treatments in the published reports so far. The other treatments studied are more passive (injections, surgical fusion) compared with the active treatment of HVLA SMT, and this may be one reason for the differences in outcomes.
      This study did not find any association between the different types and axial plane locations of CDH and outcomes except at the 2-week data collection time point. A significantly higher proportion of patients with CDHs reported improvement at this time point compared with patients with either paracentral or foraminal herniations. However, because of the large variety of different types and locations (central, paramedian, foraminal, and extraforaminal for CDH location category; protrusion, extrusion, and sequester for CDH type classification), very small sample sizes resulted for the different configurations. Studies with larger sample sizes need to be done to further investigate whether CDH configurations are related to positive or negative outcomes in patients with CDH treated by cervical HVLA manipulation. However, these results are consistent with those reported for the similar study evaluating patients with LDH treated with HVLA SMT.
      • Ehrler M
      • Peterson CK
      • Leemann S
      • Schmid C
      • Anklin B
      • Humphreys BK
      Symptomatic, MRI confirmed, lumbar disc herniations: a comparison of outcomes depending on the type and anatomical axial location of the hernia in patients treated with high velocity, low amplitude spinal manipulation.
      One interesting difference between the present study and the LDH study, however, is that there were no cases of disk sequestration for the patients with CDH, whereas disk sequestration was the second most common morphology in the LDH study.
      • Ehrler M
      • Peterson CK
      • Leemann S
      • Schmid C
      • Anklin B
      • Humphreys BK
      Symptomatic, MRI confirmed, lumbar disc herniations: a comparison of outcomes depending on the type and anatomical axial location of the hernia in patients treated with high velocity, low amplitude spinal manipulation.
      Another study that examined treatment outcomes for cervical nerve root infiltration found that patients with CDH with extrusions were more likely to end up in surgical treatment.
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      It is also important to mention that none of the patients in the present study reported worsening of their condition. Cervical HVLA manipulation has been controversial, with suggestions that it can lead to vertebral artery dissection and stroke.
      • Lee KP
      • Carlini WG
      • McCormick GF
      • Albers GW
      Neurologic complications following chiropractic manipulation: a survey of California neurologists.
      • Paciaroni M
      • Bogousslavsky J
      Cerebrovascular complications of neck manipulation.
      However, in 2007, a prospective national survey by Thiel et al
      • Thiel HW
      • Bolton JE
      • Docherty S
      • Portlock JC
      Safety of chiropractic manipulation of the cervical spine: a prospective national survey.
      studied almost 20 000 patients who were treated with cervical HVLA manipulation or mechanically assisted thrust. There were no reports of serious adverse events, which were defined as symptoms with immediate onset after treatment and with persistent or significant disability. They reported frequently occurring minor adverse events such as fainting, dizziness, light-headedness, headaches, and numbness/tingling in the upper extremities. To investigate the controversy as to whether cervical HVLA manipulation is a risk factor for vertebral artery dissection, Cassidy et al
      • Cassidy JD
      • Boyle E
      • Côté P
      • et al.
      Risk of vertebrobasilar stroke and chiropractic care: results of a population-based case-control and case-crossover study.
      used a case-control research design on a huge sample size in Canada and could not find an additional risk of vertebrobasilar stroke after cervical spine manipulation by chiropractors compared with patients consulting medical doctors for the same symptoms. They reported that in the population of Ontario, Canada, during the period from 1993 to 2002, the incidence of vertebrobasilar stroke had approximately the same association with chiropractic and primary care visits. They indicated that these patients seek for care because of the prodromal symptoms of vertebrobasilar strokelike neck pain or headache.
      The results for the interexaminer reliability of diagnosing and categorizing the MRI findings in the present study were almost perfect to perfect for MC present or absent, identifying MC type, and whether MC and CDH were at the same level. Two studies that examined interexaminer reliability for the lumbar spine also reported good agreement for MC.
      • Mulconrey DS
      • Knight RQ
      • Bramble JD
      • Paknikar S
      • Harty PA
      Interobserver reliability in the interpretation of diagnostic lumbar MRI and nuclear imaging.
      • Kovacs FM
      • Royuela A
      • Jensen TS
      • et al.
      Agreement in the interpretation of magnetic resonance images of the lumbar spine.
      A third study found moderate interexaminer agreement for MC.
      • Carrino JA
      • Lurie JD
      • Tosteson AN
      • et al.
      Lumbar spine: reliability of MR imaging findings.
      For the cervical spine, the interexaminer reliability for MC has been described as substantial.
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      In the present study, substantial agreement was also achieved for identifying the level of MC. This is consistent with the previously mentioned studies that support the good results for MC.
      For CDH type classification and location category, a moderate agreement was found, and for CDH level, a fair agreement resulted. A similar study by Bensler et al
      • Bensler S
      • Sutter R
      • Pfirrmann CW
      • Peterson CK
      Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.
      also found a fair agreement for CDH location and a substantial agreement for CDH type classification. One issue that arose during the consensus reading of the images was the distinction between paramedian and foraminal CDH. It was sometimes challenging to decide which of these categories to select because often the CDH had both foraminal and paramedian components. Another problem was the distinction between protrusion and extrusion in oblique slices, because the uncinate processes tapered the disk. The low agreement for CDH level may be explained by the fact that some patients had several levels with CDH, and all disk herniations of a patient had to be rated identically by the 2 examiners to count as a positive match. In addition, the 2 examiners that performed the interexaminer reliability part of this study were 2 young chiropractors with 6 months and 1.5 years of clinical postgraduate experience. However, both had received specific training in the diagnosis and categorization of these MRI findings.

      Limitations

      One of the main limitations of this study is the small sample size. This was especially problematic when it came to the analysis of subgroups. This was the case for all statistics, including MC, and for the statistics of the different disk herniation classifications. Thus, this study was somewhat underpowered.
      Another limitation was that other possible causes of radiculopathy that may be visible on MRI scans were not considered. These would include nerve root compression by hypertrophy of uncinated processes or facet joints. However, because of the relatively small sample size and the fairly young age of the included patients (mean age 44.73 years), the likelihood of finding a sufficient number of these additional findings would be quite low. Additionally, the inclusion criteria were that all patients had MRI-confirmed CDHs that corresponded to the level of clinical signs of radiculopathy found on physical examination. In other words, the MRI findings could explain the clinical findings.
      The treatment method was a manual HVLA cervical manipulation performed by 3 chiropractors working in the same office. The treatment can be described as standardized because the senior chiropractor taught the younger 2 in the specific treatment method used. However, the treatment cannot be considered as standardized for all Swiss chiropractors or for chiropractors from other countries, because HVLA cervical manipulation methods can vary among different practitioners.
      Follow-up information of the outcome measures were collected by telephone calls. There was a certain time frame allocated for every follow-up time point to reach the patients. If this was not possible, the information was not available for statistical analysis. This resulted in fluctuating sample sizes between the different time points, which means that the compared groups from different time points did not include the exact same patients.
      For the reliability study, the relatively low experience level of the examiners can also be taken as a limitation.

      Conclusions

      This study identified a tendency for a higher proportion of patients who were Modic positive to report improvement after treatment with HVLA cervical SMT compared with patients who were Modic negative. This was also the case when type I MCs were compared with no MCs, although the sample size for patients with type I MCs was very small. This is in contrast to the results of most other studies on this topic to date, where patients who were Modic positive had worse responses to other nonsurgical treatments. Further research is needed to confirm these results with a larger sample size and find possible explanations. Additionally, the morphology and axial location of the cervical herniation were not related to treatment outcomes, similar to findings in patients with LDH treated with SMT. The interexaminer reliability for detecting and classifying MCs and CDH location and morphology in MRI studies had similar results as previously reported in the literature.

      Funding Sources and Conflicts of Interest

      This study was funded by the European Chiropractors Union, Balgrist Foundation, and Uniscientia Foundation. No conflicts of interest were reported for this study.

      Contributorship Information

      Concept development (provided idea for the research): C.S., S.L., B.A., C.P., B.K.H.
      Design (planned the methods to generate the results): C.P., B.K.H., S.L., C.S., B.A.
      Supervision (provided oversight, responsible for organization and implementation, writing of the manuscript): C.P.
      Data collection/processing (responsible for experiments, patient management, organization, or reporting data): C.S., S.L., B.A., C.P., M.K., K.M.
      Analysis/interpretation (responsible for statistical analysis, evaluation, and presentation of the results): M.K., C.P., K.M.
      Literature search (performed the literature search): M.K.
      Writing (responsible for writing a substantive part of the manuscript): M.K., C.P.
      Critical review (revised manuscript for intellectual content, this does not relate to spelling and grammar checking): B.K.H., K.M., S.L., C.S., B.A.

      Practical Applications

      • A higher proportion of patients who were Modic positive and had CDH reported improvement after cervical manipulation compared with patients who were Modic negative at 2 weeks, 1 month, and 3 months.
      • Patients with CDH who were Modic positive had significantly higher baseline disability scores, but at all follow-up time points other than 6 months, there were no differences compared with patients who were Modic negative.
      • Patients with central herniations were more likely to improve at the 2-week time point compared with patients with paracentral or foraminal herniations.

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