Non-organic Signs to Predict Outcomes for Neck Pain

Prospective Study to Determine Evaluate the Validity and Predictive Ability of Physical Exam Signs for Cervical Radiculopathy to Predict Epidural Steroid Injection (ESI) Treatment Outcomes.

Neck pain is the 4th leading cause of disability in the world, with approximately 50% being neuropathic in nature. Epidural steroid injections (ESI) are one of the most commonly used treatments for cervical radiculopathy. Physical exam signs, including non-organic signs, have been shown to predict outcomes for low back pain treatments, but have yet to be adequately studied for neck pain.

In this prospective, observational study, 72 patients with cervical radiculopathy undergoing an initial ESI for this pain episode will undergo a comprehensive history and physical examination that includes the presence of Spurling test, midline and paraspinal tenderness, 9 non-organic tests in 5 categories, and 3 questionnaires to assess depression, anxiety, sleep, and somatization. The investigators will also evaluate patients' MRI results to determine patients' precise pathology. Patients will then receive interlaminar cervical ESI. The primary outcome measure will be the difference in the proportion of people with a positive categorical outcome, defined as a >/= 2-point decrease in arm pain 4 weeks post-procedure coupled with a score >/= 5 on a 7-point patient global impression of change (PGIC) scale 4 weeks post-treatment, indicating subjective improvement.

The main objectives of this study are to:

1. Determine the ability of physical exam, including non-organic signs, to predict ESI outcomes in individuals with cervical radicular pain.
2. Determine the prevalence of different non-organic signs, and the association with other factors that may be associated with non-organic illness such as psychopathology and multiple unrelated pain conditions.

Study Overview

• Status: Completed
• Conditions: Cervical Radiculopathy; Cervical Radicular Pain
• Intervention / Treatment: Procedure: Cervical epidural steroid injection

Detailed Description

Seventy-two patients with cervical radiculopathy undergoing an initial ESI for this pain episode will undergo a comprehensive history and physical examination that includes the presence of Spurling test, midline and paraspinal tenderness, 9 non-organic tests in 5 categories, and 3 questionnaires to assess depression, anxiety, sleep, and somatization.

Non-organic signs that the investigators will evaluate are:

1. Tenderness

   1. Superficial
   2. Non-anatomical (e.g. cervical radicular pain causing tenderness in the arm or mid-back)

2. Sham stimulation

   1. Downward pressure on head elicits neck pain
   2. With hands clasped behind neck, passive rotation of shoulders elicits neck pain

3. Distraction

   a. Inability to rotate head > 45 degrees during overt range-of-motion testing, but significantly greater range of motion when patient is lying prone and asked to turn head to respond to physician request (e.g. sign paper, count fingers, answer question).

4. Regional disturbances

   1. Sensory disturbances that deviate from normal neuroanatomy or pathology (e.g. single herniated disc causing pain throughout entire arm or radiating into lower back)
   2. Motor disturbances that deviate from normal neuroanatomy or pathology (e.g. dramatic non-neurological weakness, give-away weakness)

5. Overreaction

   1. Verbal (e.g. crying, screaming)
   2. Non-verbal (e.g. exaggerated grimacing, clutching affected area, abnormally slow or rigid movements)

The investigators will evaluate MRI results to determine the precise pathology. Patients will then receive interlaminar cervical ESI. In accordance with standard practice, a Tuohy needle will be directed towards the side of the radicular pain, with correct needle position in the epidural space being confirmed with real-time contrast injection. Once the physician is satisfied with the spread, a 3 mL solution consisting of depo-methylprednisolone 40 mg + 2 mL normal saline will be injected. At Seoul National University, due to Korean healthcare regulations, the mixture will be a 3 mL solution containing 10 mg of dexamethasone and 2 mL saline. The primary outcome measure will be the difference in the proportion of people with a positive categorical outcome, defined as a >/= 2-point decrease in average arm pain 4 weeks post-procedure coupled with a score >/= 5 on a 7-point patient global impression of change (PGIC) scale 4 weeks post-treatment, indicating subjective improvement. Secondary outcome measures will include mean reductions in average and worst 0-10 numerical rating scale (NRS) arm pain scores over the past 7 days, mean reduction in average and worst neck pain scores, neck disability index (NDI) score, medication usage, patient global impression of change (PGIC), Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), Somatic Symptom Scale-8 (SSS-8), and side effects. Individuals who experience a positive categorical outcome at 4 weeks will continue to be evaluated at 12 weeks, while those with a negative outcome will exit the study.

• Study Type: Observational
• Enrollment (Actual): 78

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • DC VA Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with clinical and MRI evidence of cervical radicular pain who are scheduled to undergo cervical epidural steroid injection

Description

Inclusion Criteria:

• Age > 18
• Cervical radicular pain based on history and physical exam (e.g. pain radiating into one or both extremities, sensory loss, muscle weakness, Spurling's test etc.)
• Pain duration > 6 weeks
• Average NRS arm pain score > 4
• MRI evidence of disc pathology consistent with symptoms

Exclusion Criteria:

• Untreated coagulopathy
• Previous spine surgery
• No MRI study
• Epidural steroid injection within past 3 years
• Radiculopathy resulting from tumor or herpes zoster
• Signs or symptoms or myelopathy or spinal cord compression
• Allergic reactions to contrast allergy including macrocyclic gadolinium or depo-methylprednisolone
• Referrals from surgery for diagnostic injections for surgical evaluation
• Serious medical (e.g. congestive heart failure) condition that might preclude optimal outcome
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cervical epidural steroid injection; This group will receive an interlaminar cervical ESI at C6-7 or C7-T1 with 1 mL steroid (depo-methylprednisolone 40 mg at Johns Hopkins and the DC VA Hospital or dexamethasone 10 mg at Seoul National University) and 2 mL normal saline.	Procedure: Cervical epidural steroid injection; Interlaminar cervical epidural steroid injection with steroid and normal saline at C6-7 and C7-T1 (standard of care).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Categorical response	Positive response is defined as a >/= 2-point reduction in average arm pain coupled with >/= 5/7 score on patient global impression of change. Anything else is a negative response.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average arm pain	Average arm pain on 0-10 numerical rating scale.	4 weeks
Worst arm pain	Worst arm pain on 0-10 numerical rating scale.	4 weeks
Average neck pain	Average neck pain on 0-10 numerical rating scale.	4 weeks
Worst neck pain	Worst neck pain on 0-10 numerical rating scale.	4 weeks
Neck disability index (NDI) score	NDI Score on 0-10 numerical rating scale.	4 weeks
Somatic Symptom Scale (SS-8) score	8-question survey, out of 32 points measuring somatization.	4 weeks
Athens Insomnia Scale (AIS) score	8-question survey, out of 24 points measuring sleep quality.	4 weeks
Hospital Anxiety and Depression Scale (HADS)	14-question survey measuring anxiety and depression (each out of 21 points).	4 weeks
Patient Global Impression of Change (PGIC) scale	7-point Likert scale measuring patient-reported improvement.	4 weeks
Patient Global Impression of Change (PGIC) scale	7-point Likert scale measuring patient-reported improvement.	12 weeks
Hospital Anxiety and Depression Scale (HADS)	14-question survey measuring anxiety and depression (each out of 21 points).	12 weeks
Athens Insomnia Scale (AIS) score	8-question survey, out of 24 points measuring sleep quality.	12 weeks
Somatic Symptom Scale (SS-8) score	8-question survey, out of 32 points measuring somatization.	12 weeks
Average arm pain	Average arm pain on 0-10 numerical rating scale.	12 weeks
Worst arm pain	Worst arm pain on 0-10 numerical rating scale.	12 weeks
Average neck pain	Average neck pain on 0-10 numerical rating scale.	12 weeks
Worst neck pain	Worst neck pain on 0-10 numerical rating scale.	12 weeks
Neck disability index (NDI) score	NDI Score on 0-10 numerical rating scale.	12 weeks
Categorical response	Positive response is a >/= 2-point reduction in average arm pain coupled with >/= 5/7 score on patient. Anything else is a negative response.	12 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Seoul National University; Washington DC VA Medical Center

Publications and helpful links

General Publications

• Fishbain DA, Cole B, Cutler RB, Lewis J, Rosomoff HL, Rosomoff RS. A structured evidence-based review on the meaning of nonorganic physical signs: Waddell signs. Pain Med. 2003 Jun;4(2):141-81. doi: 10.1046/j.1526-4637.2003.03015.x.
• Waddell G, McCulloch JA, Kummel E, Venner RM. Nonorganic physical signs in low-back pain. Spine (Phila Pa 1976). 1980 Mar-Apr;5(2):117-25. doi: 10.1097/00007632-198003000-00005.
• Jorritsma W, Dijkstra PU, De Vries GE, Geertzen JH, Reneman MF. Physical dysfunction and nonorganic signs in patients with chronic neck pain: exploratory study into interobserver reliability and construct validity. J Orthop Sports Phys Ther. 2014 May;44(5):366-76. doi: 10.2519/jospt.2014.4715. Epub 2014 Apr 14.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2020
• Primary Completion (ACTUAL): March 30, 2022
• Study Completion (ACTUAL): March 30, 2022

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (ACTUAL): March 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Neck pain; Cervical radiculopathy; Cervicalgia; Cervical radicular pain; Epidural steroid injection; Non-organic sign
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Radiculopathy
• Other Study ID Numbers: IRB00243203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon request
• IPD Sharing Time Frame: Up to 3 years after publication
• IPD Sharing Access Criteria: Upon request, contingent on objectives
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No