J Manipulative Physiol Ther. 2016 (Mar); 39 (3): 210-217 ~ FULL TEXT
Cynthia K. Peterson, RN, DC, MMedEd, Christian W.A. Pfirrmann, MD, MBA,
Jürg Hodler, MD, MBA, Serafin Leemann, DC, Christof Schmid, DC,
Bernard Anklin, DC, B. Kim Humphreys, DC, PhD
Orthopaedic University Hospital Balgrist,
University of Zürich, Switzerland;
Professor, Chiropractic Medicine Department,
Orthopaedic University Hospital Balgrist,
University of Zürich, Switzerland.
OBJECTIVE: The purpose of this study was to compare the outcomes of overall improvement, pain reduction, and treatment costs in matched patients with symptomatic, magnetic resonance imaging-confirmed cervical disk herniations treated with either spinal manipulative therapy (SMT) or imaging-guided cervical nerve root injection blocks (CNRI).
METHODS: This prospective cohort comparative-effectiveness study included 104 patients with magnetic resonance imaging-confirmed symptomatic cervical disk herniation. Fifty-two patients treated with CNRI were age and sex matched with 52 patients treated with SMT. Baseline numerical rating scale (NRS) pain data were collected. Three months after treatment, NRS pain levels were recorded and overall "improvement" was assessed using the Patient Global Impression of Change scale. Only responses "much better" or "better" were considered "improved." The proportion of patients "improved" was calculated for each treatment method and compared using the χ2 test. The NRS and NRS change scores for the 2 groups were compared at baseline and 3 months using the unpaired t test. Acute and subacute/chronic patients in the 2 groups were compared for "improvement" using the χ2 test.
RESULTS: "Improvement" was reported in 86.5% of SMT patients and 49.0% of CNRI patients (P = .0001). Significantly more CNRI patients were in the subacute/chronic category (77%) compared with SMT patients (46%). A significant difference between the proportion of subacute/chronic CNRI patients (37.5%) and SMT patients (78.3%) reporting "improvement" was noted (P = .002).
CONCLUSION: Subacute/chronic patients treated with SMT were significantly more likely to report relevant "improvement" compared with CNRI patients. There was no difference in outcomes when comparing acute patients only.
KEYWORDS: Cervical Spine; Comparative-Effectiveness Research; Disk Herniation; Injections; Manipulation, Spinal; Nerve Root; Outcomes Assessment; Radiculopathy
From the Full-Text Article:
Cervical nerve root compression (radiculopathy) can be severely disabling in some patients and is caused by either disk herniation or more commonly spinal degeneration affecting the intervertebral foramina and subsequent exiting nerve root.  The most common nerve roots to be involved are the C6 and C7 levels, with the symptoms arising because of compression of the nerve root, inflammation of the nerve root, or both. [1, 2] Typical clinical signs and symptoms of cervical radiculopathy include pain in the distribution of the involved nerve root, paresthesias in a dermatomal pattern, weakness of the muscles innervated by the involved nerve root, and/or a decrease in the reflex.  In some patients, arm pain predominates over the neck pain. [3, 4]
The diagnosis of cervical nerve root compression is made with magnetic resonance imaging (MRI) scans. It is important, however, to recognize that disk protrusions seen on MRI are not always symptomatic, so it is critical that imaging abnormalities are linked to patient symptoms to determine whether or not the imaging findings are clinically relevant. [5–7] However, more severe disk herniations such as extruded disks with compression of the spinal cord are uncommon in asymptomatic people.7
Patients with symptomatic cervical disk herniations are initially treated conservatively, with surgery reserved for those cases that remain unresponsive to conservative care. [2–4, 8] A variety of different conservative treatments are used for these patients, including pain medications, physiotherapy treatment, lifestyle changes, nerve root injections, or even spinal manipulative therapy (SMT). However, most treatments, other than cervical transforaminal epidural steroid injections (cervical nerve root injections [CNRIs]), are not well documented with research evidence. [2, 3, 8–13] Recently, the use of imaging-guided CNRIs has come under scrutiny because of rare but extremely serious adverse events in some patients including ischemic myelopathy, transient or permanent tetraplegia, brain infarctions leading to death, and arterial dissections or cortical blindness. [14, 15] Because of the risk of such serious adverse events, a few institutions have modified the procedure to significantly reduce these risks to the new procedure called the imaging-guided indirect CNRI. [14, 16] Comparing short-term outcomes of this new indirect approach with the traditional direct nerve root injection showed no significant differences in the level of pain reduction.  The research evidence for SMT as a treatment for patients with symptomatic cervical disk herniations is sparse but slowly increasing, with a recent cohort outcomes study showing that more than 3/4 of patients with subacute and chronic symptoms reported clinically relevant improvement at 3 months after start of treatment. [10–13, 17] However, SMT to the cervical spine is not without controversy either. The issue of vertebral artery dissection and stroke after manipulation is often quoted. [18, 19] Unfortunately, accurate estimations of the frequency of this association cannot be calculated because of its rarity but are estimated at 1 of 200,000 treatments to 1 in several million treatments. [18, 19]
It is also important to recognize that the natural history for patients with acute symptoms from disk herniation (less than 4–8 weeks) is reported to be favorable, and thus, it is difficult to determine whether or not improvement in acute patients undergoing various treatments including CNRIs or SMT is due to the treatment or to the natural history of the condition. [19, 20] Randomized, controlled, clinical trials (RCTs) would be considered the “criterion standard” to compare specific treatments with patients not treated at all. However, subacute and especially chronic patients should have passed the time point for the effects of natural history to have occurred. Thus, evaluating the outcomes of these patients treated with various conservative therapies could provide useful evidence for clinicians.
Recently, comparative-effectiveness research has been promoted rather than RCTs to compare treatment outcomes for similar patients using databases from prospective cohort studies. [21, 22] It is argued that patients in prospective cohort outcomes databases may be more representative of patients seen in daily clinical practice as compared with patients included in RCTs. Based on this premise, the purpose of this study is to compare the outcomes of overall improvement, pain reduction, and treatment costs in age- and sex-matched patients with symptomatic, MRI-confirmed cervical disk herniations who were treated with either SMT or CNRI using a comparative-effectiveness prospective cohort design.
This is the first study to have the necessary resources and databases to be able to compare the outcomes of 2 different conservative treatments for patients suffering from cervical radiculopathy. Although not a randomized, blinded, clinical trial, using these prospective cohort outcomes databases allows the inclusion of patients who are representative of those seen in routine clinical practice and follows the recommendations of Tinetti and Studenski  in performing comparative-effectiveness research.
Although the outcomes for the cervical disk herniation patients treated with SMT were markedly better than those treated with CNRI, some of this difference is due to the fact that a significantly higher proportion of patients in the CNRI cohort were subacute/chronic. Indeed, when comparing the outcomes for only the acute patients (symptoms < 4 weeks), there was no significant difference between the 2 treatments, as most of the acute patients improved. Much of this may be due to the natural history of the condition and not related to the specific treatment. [9, 20] Therefore, it was important to compare the outcomes for those patients with symptoms longer than 4 weeks. This did reveal a significant difference between the SMT- and CNRI-treated patients, with more than 78% of the SMT cohort reporting clinically relevant improvement compared with 37.5% of those treated with CNRI. However, it is important to point out that the CNRI patients only received a single nerve root block treatment, whereas the SMT patients were treated several times based on their follow-up clinical assessments during the 3–month time period from baseline to collection of the outcome data. This may have influenced the results in favor of the SMT cohort even though the literature reports that a single nerve root injection containing corticosteroid and anesthetic may result in at least a 50% reduction in pain (considered clinically relevant improvement) for 3–6 months.  However, when comparing the results of the entire CNRI cohort of 52 patients in this study where 49% were “improved” at 3 months with the shorter-term 1–month outcomes of all CNRI patients (n = 195) currently listed in the radiology database, there is surprisingly little difference, as only 43% of patients reported clinically relevant improvement even at the 1–month data collection time point.  Therefore, the longer data collection time point of 3 months does not appear to have been a negative factor in the proportion of clinically improved CNRI patients. Comparing the treatment costs between the SMT and CNRI patients shows a minimal difference of only CHF 42.47 even though the SMT patients were treated multiple times.
A recently published systematic review on the effectiveness of CNRI states that the minimal standard of a successful outcome is at least 50% relief of radicular pain that lasts a minimum of 4 weeks postinjection and further states that the quality and quantity of the research studies on direct, transforaminal nerve root injections are low.  The various studies included in this systematic review reported a range of postinjection data collection time points as well as clinically relevant improvement in as few as 20% of patients to as many as 56%. The results from this current study of 49% of CNRI patients reporting clinically relevant improvement are better than those reported in a recent retrospective practice audit where only 35.4% of patients receiving a direct transforaminal nerve root block had at least a 50% pain reduction 1 month postinjection.  A comparison of our results with those previously published is important because the method of injection in this current study is the so-called indirect nerve root block procedure, whereas the results in all previous research studies used the direct transforaminal approach.  As reported in detail in a previous publication, this indirect nerve root block procedure should have a much lower level of potential risk for serious adverse events compared with the traditional direct transforaminal approach due to the injection technique, and yet the outcomes, at least in the medium term, are comparable. 
Unfortunately, there are no similar outcome studies with which to compare the SMT patients, as spinal manipulation has often been considered a controversial treatment for patients with known cervical disk herniations and radiculopathy. There were no adverse events in either of the 2 treatment cohorts in this study, and none of the SMT patients reported that they were worse at the 3–month data collection time point.
As noted previously, this is not a randomized, blinded, clinical trial (RCT), so the outcomes cannot be directly attributed to the treatments. A follow-up RCT should be done and would be possible in the university clinical environment of this hospital which includes chiropractic medicine as an integral component of the university teaching within the faculty of medicine and the hospital therapeutic options. The sample sizes are also relatively small with 52 patients per group. However, further telephone data collection for the CNRI cohort has ceased, and thus, additional patients are not available. This factor should not have negatively influenced the results because even with these relatively small sample sizes, large statistical and more importantly clinically significant differences were found for the subacute/chronic patients.
There was no attempt to match the patients for comorbidities in this study, and that may be a limitation because many of the CNRI patients referred to this hospital are complex patients. Importantly, however, there was no difference in the baseline NRS scores between the 2 groups as was found when doing the lumbar disk herniation similar study. 
Although the treatment costs between the 2 groups were very similar, no attempt was made to collect associated costs or time off work data to do a proper cost-effectiveness comparison.
Most acute patients with MRI-confirmed symptomatic cervical disk herniations treated with either CNRI or SMT reported clinically relevant improvement at 3 months with no significant difference in outcomes between the 2 treatment methods. However, when comparing the 3–month outcomes for the subacute/chronic patients, more than 78% of patients treated with SMT reported clinically relevant improvement compared with 37.5% of patients receiving a single CNRI. The treatment costs between the 2 groups were very similar. There were no adverse events for either cohort.
Subacute and chronic patients treated with spinal manipulation
were statistically and clinically significantly more likely to
report improvement at 3 months compared with
the nerve root injection cohort.
There was no significant difference in outcomes between acute
patients treated with cervical nerve root blocks and those
treated with spinal manipulation at 3 months.
There were no adverse events for patients in either treatment group.
The cost of treatment was similar for the 2 treatment procedures.