7. Whiplash-Associated Disorders

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1 papr_ EVIDENCE-BASED MEDICINE Evidence-based Interventional Pain Medicine according to Clinical Diagnoses 7. Whiplash-Associated Disorders Hans van Suijlekom, MD, PhD*; Nagy Mekhail, MD, PhD, FIPP ; Nileshkumar Patel, MD, MBA ; Jan Van Zundert, MD, PhD, FIPP ; Maarten van Kleef, MD, PhD, FIPP ; Jacob Patijn, MD, PhD *Department of Anesthesiology and Pain Management, Catharina Ziekenhuis, Eindhoven, The Netherlands; Department of Anesthesiology and Pain Management, Maastricht University Medical Centre, Maastricht, The Netherlands; Pain Management Department, Anesthesiology Institute, Cleveland, Ohio, USA; Pain and Rehabilitation, Coastal Orthopedics, Cleveland Clinic, Bradenton, Florida, U.S.A.; Department of Anesthesiology and Multidisciplinary Pain Centre, Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: Whiplash-associated disorders are comprised of a range of symptoms of which neck complaints and headaches are the most significant spine related. In the acute and sub-acute stage of the disorder, conservative treatment for minimally 6 months is recommended, active mobilization is slightly better than passive treatment. Thereafter, interventional treatment may be considered. The available evidence for injection of Botulinum toxin A (2 B-) and intra-articular corticosteroid injections (2 C-) supports a negative recommendation. Radiofrequency treatment of the ramus medialis (medial branch) of the ramus dorsalis is recommended (2 B+). Key Words: evidence-based medicine, pain, facet joint, whiplash, interventional management Address correspondence and reprint requests to: Maarten van Kleef, MD, PhD, Department of Anesthesiology and Pain Management, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. maarten.van.kleef@mumc.nl DOI /j x 2010 World Institute of Pain, /10/$15.00 Pain Practice, Volume 10, Issue 2, INTRODUCTION This review on whiplash is part of the series Evidence- Based Interventional Pain Medicine According to Clinical Diagnoses. Recommendations formulated in this article are based on grading strength of recommendations and quality of evidence in clinical guidelines described by Guyatt et al. 1 and adapted by van Kleef et al. in the editorial accompanying the first article of this series 2 (Table 1). The latest literature update was performed in November Whiplash-associated disorder (WAD) is the official name for the constellation of symptoms affecting the neck that are triggered by an accident with an acceleration deceleration mechanism. The occurrence of WAD is typical in motor vehicle accidents specifically with an impact from behind or from the flanks, but WAD can also result from other injuries including diving. Research in Europe shows that the prevalence of neck pain caused by car accidents has risen from 3.4 per 100,000 in 1970 to 1974, to 40.2 per 100,000 in 1990 to In 1995, the Quebec Task Force made a theoretical classification of WADs, 4 which was recently

2 132 van suijlekom et al. Table 1. Summary of Evidence Scores and Implications for Recommendation Score Description Implication 1A+ Effectiveness demonstrated in various RCTs of good quality. The benefits clearly outweigh risk and burdens 1B+ One RCT or more RCTs with methodologic weaknesses, demonstrate effectiveness. The benefits clearly outweigh risk and burdens 2B+ One or more RCTs with methodologic weaknesses, demonstrate effectiveness. Benefits closely balanced with risk and burdens 2B Multiple RCTs, with methodologic weaknesses, yield contradictory results better or worse than the control treatment. Benefits closely balanced with risk and burdens, or uncertainty in the estimates of benefits, risk and burdens. 2C+ Effectiveness only demonstrated in observational studies. Given that there is no conclusive evidence of the effect, benefits closely balanced with risk and burdens 0 There is no literature or there are case reports available, but these are insufficient to suggest effectiveness and/or safety. These treatments should only be applied in relation to studies. 2C- Observational studies indicate no or too short-lived effectiveness. Given that there is no positive clinical effect, risk and burdens outweigh the benefit 2B- One or more RCTs with methodologic weaknesses, or large observational studies that do not indicate any superiority to the control treatment. Given that there is no positive clinical effect, risk and burdens outweigh the benefit 2A- RCT of a good quality which does not exhibit any clinical effect. Given that there is no positive clinical effect, risk and burdens outweigh the benefit Positive recommendation Considered, preferably study-related Only study-related Negative recommendation RCT, randomized controlled trial. updated. 5 This makes it easier to compare international research. Grade 0: No complaints in the neck. No physical signs. Grade I neck pain: no symptoms indicating serious pathology and minimal influence on daily activities. Grade II neck pain: no symptoms indicating serious pathology, but having influence on daily activities. Grade III neck pain: no symptoms indicating serious pathology, presence of neurological disorders such as decreased reflexes, muscle weakness, or decreased sensory function. Grade IV neck pain: indications of serious underlying pathology such as fracture, myelopathy, or neoplasm. This article will primarily cover the current understanding of the pathophysiology and pain intervention approach for patients with WAD I and II. Spitzer et al. 4 indicates that the natural course of whiplash is fairly favorable. Approximately 85% of the patients resumed their activities within 6 months after an accident. It is generally assumed that the symptoms become chronic in 15% to 30% of the WAD patients. 6 I. DIAGNOSIS I.A HISTORY Typical symptoms of acute whiplash injury include: (1) pain in the neck, shoulders, and, potentially, in the arms; (2) headache, particularly in the occipital area, sometimes radiating to the forehead above both eyes; and (3) restricted mobility of the neck as a result of neck stiffness immediately after the accident. Concomitant symptoms include dizziness, visual impairments, nausea, tinnitus, deafness, paresthesias in the hands, localized spasm and tenderness, unilateral brachialgia due to shoulder complaints, lower back pain, posttraumatic stress disorder (depression), and cognitive function disorders. The importance of history taking is to be able to rule out grades III and IV neurological symptoms that can indicate damage to the nervous system and skeletal structures. The term acute whiplash syndrome applies to the first 3 weeks after the accident. Thereafter, a subacute stage starts during which most of the symptoms disappear while administering conservative therapy. If the symptoms persist after 3 months, it is considered chronic whiplash syndrome. 6 I.B PHYSICAL EXAMINATION The physical examination aims to either exclude or demonstrate nervous system damage. At the same time,

3 7. Whiplash-Associated Disorders 133 fractures should be ruled out. A thorough neurological examination of the neck should be carried out, focusing on the sensibility and motor function of the arms and hands, and radicular provocation tests (Spurling). Clinical signs of WAD typically include localized spasm and tenderness as well as limitation in the active range of motion, including lateroflexion and extension. Patients with neck pain have tenderness and spasms that are not evident in the asymptomatic individuals. 7 Even so, palpation may reveal localized tenderness, and range of motion may be restricted, but neither of these features yield a definitive diagnosis in the WAD I and II patients. They merely point to some abnormality that warrants further interventions. I.C ADDITIONAL TESTS The objective of physical examination is to pinpoint the source of pain, and hopefully, the information obtained from the assessments will direct to effective treatments. Additional tests should be carried out when indicated. A magnetic resonance imaging scan (MRI) of the neck is not useful with WAD I and II, but can still be considered in case of suspected neurological problems. 6 Research has demonstrated that an MRI scan during the chronic stage of a whiplash injury rarely shows a traumatic defect. 8 Choosing an MRI is guided by clinical evaluation in case of unexplained neurologic abnormalities and in preparation of surgical intervention. MRI is perhaps the best screening tool for missed and occult fractures, infections, and tumors. Apart from these criteria, utility of MRI is limited. Electrophysiologic examination by electromyography (EMG) and nerve conduction velocity (NCV) tests are not justified in WAD I and II given the absence of radicular pain. Even for the assessment of radiculopathy, electrophysiologic tests are not more valuable than a careful neurologic evaluation. Hence, forced by the overwhelming lack of evidence for the conventional investigational approach (use of X-rays, MRI, EMG/NCVs), one has to resort to physiologic tests. Pain is a sensory experience. As such, in dealing with WAD I and II patients, imaging and electrophysiologic investigations cannot reliably diagnose the source of pain. Rather, these latter tests are useful corollaries to physiologic tests, to confirm the findings of the physiologic tests and clinical evaluation. In the chronic whiplash patients, where conservative treatment has failed and physical examination reveals possible dysfunction of the cervical facet joints, a diagnostic blockade of these joints is appropriate. 9 I.D DIFFERENTIAL DIAGNOSIS The relation with the acceleration deceleration trauma is found in the medical history. Differential diagnosis that specifically must not be overlooked includes: (1) infections; (2) tumors; and (3) neurologic disorders. The red flags that will alert the clinician are unexplained fevers, night sweats, unexplained weight loss, decrease in appetite, general malaise, history of cancers, weakness, neurologic symptoms, immunosupression, illicit drug use, as well as other alerts in the evaluation of systems. II. TREATMENT OPTIONS II.A CONSERVATIVE MANAGEMENT A review article by Verhagen et al. within the Cochrane Collaboration describes the effect of conservative treatments for acute whiplash patients with WAD grades I and II. 10 The treatments in these studies varied from immobilization by means of a cervical collar to early active mobilization and multimodal treatment. These studies concluded that active treatment strategies are slightly more effective than passive treatment strategies and any treatment (whether passive or active) is more effective than no treatment at all. There is no clear evidence which treatment is better. The Dutch Institute for Healthcare Improvement working group recommends that patients with WAD (grades I to II) should be given a clear explanation about why they are experiencing the symptoms and precisely what they should expect, providing the natural course of the condition. 6 Two studies on the medical treatment of chronic WAD exemplify the lack of effectiveness of pharmaceutical interventions. In a randomized study, Schreiber et al. investigated the effect of fluoxetine vs. amitriptyline on pain in 40 patients with back pain or neck pain as a result of a whiplash accident. 11 There were no significant differences. Another study showed no significant effect of melatonin compared with placebo for sleep disorders. 12 II.B INTERVENTIONAL MANAGEMENT Interventional treatments are only considered after a minimum of 6 months because in that time period, the clinical signs have sufficiently stabilized. Interventional treatments for WAD historically include injection of steroids into the epidural space, into trigger points, or facet joints, injection of botulinum toxins in muscles with increased tenderness, and percutaneous radiofrequency (RF) treatment.

4 134 van suijlekom et al. While cervical epidural steroids appear to have shortterm benefit for the radicular symptoms, no study has demonstrated the effectiveness in an axial, nonradicular whiplash population in WAD I and II categories. A randomized study by Barnsley et al. in 1994 investigated the effect of intra-articular corticosteroid injections in the cervical facet joints of chronic whiplash patients. 9 There were no significant differences noted. Trigger point injections are as effective as simple ultrasound, but not more effective than physical therapy. 13 Freund and Schwartz 14 published a randomized, placebo-controlled pilot study in 2000 with 26 chronic whiplash patients (WAD grade II) on the effect of botulinum toxin on neck pain and neck function. The treatment group (group I) received 5 injections of 0.2-mL (20 U) botulinum toxin type A and the control group (group II) received 5 injections of 0.2-mL saline solution. The follow-up parameters were visual analog scale for neck pain and function measurements using the Vernon Mior index. After a 4-week follow-up, there was no significant difference in the effect parameters between the two groups. Likewise, others have failed to demonstrate the effectiveness of botulinum toxins in treatment of chronic neck pain even when the pain is primarily associated with myofascial spasms. 15 In a randomized, double-blind, placebo-controlled clinical trial of Padberg et al. in 2007, botulinum toxin was not proven to be effective in treatment of neck pain in chronic WAD. 16 The effect of RF treatment of the cervical facet joints is well documented. In 1996, Lord et al. published a randomized, double-blind study with 24 chronic whiplash patients on the effect of percutaneous RF treatment of the ramus medialis (medial branch) of the ramus dorsalis of the cervical facet joints. 17 Patients (n = 54) were selected double-blindly for this study. Each patient underwent 3 blocks of the rami mediales (medial branches) of the 2 rami dorsales supplying the putatively symptomatic facet joint. The blocks were performed with lidocaine 2%, bupivacaine 0.5%, or a saline solution, and were randomly administered (double blind, placebo controlled). Patients with complete relief of pain for the duration of the local anesthetic and those who reported no relief with normal saline were deemed to have true facetogenic pain. Twenty-four such patients were included in the study. Patients were randomized in two groups of 12 patients: Group I underwent RF treatment at multiple levels of the cervical ramus medialis (medial branch) of the ramus dorsalis. Group II received a sham treatment. After 27 weeks, 7 (58%) of the patients from group I and 1 (8%) from group II were pain free. The mean time of pain symptom recurrence to at least 50% of the preoperative level was 263 days in 12 patients in group I and 8 days in 12 patients in group II. Others have also demonstrated the utility of cervical RF treatment, in litigant and nonlitigant populations. 18,19 Prushansky et al. 20 conducted a prospective study of 40 patients with chronic whiplash injuryassociated disorders who underwent RF treatment. The authors found an improvement in 70% of patients based on a number of parameters including the Neck Disability Index and cervical range of motion. In 1999, McDonald et al. 21 published a prospective long-term follow-up study of the long-term effect of RF treatment of the ramus medialis (medial branch) of the ramus dorsalis of the cervical facet joints in 28 chronic whiplash patients with neck pain. Twenty patients (71%) reported complete pain reduction. The mean time of pain symptom recurrence to at least 50% of the preoperative level was 219 days (0 to 1,095 days) in all 28 patients and 422 days if only the positive results were evaluated. In 11 patients (55%), the procedure was repeated for the recurrence of the pain symptoms, resulting in complete pain reduction. Several procedures were carried out in 4 patients (20%) who reported complete pain reduction lasting a minimum of 90 days in each case. As the treated nerves regenerate, the complete relief can be reinstated by repeating the procedure. 22 Psychological disorders are a characteristic of many chronic pain syndromes. Wallis et al. showed that in the above-mentioned patient group, the psychological stress factors, measured using the McGill Pain Questionnaire and the SCL-90-R (Symptom Checklist-90 Revised), entirely normalized in the patients in which the pain after the RF treatment had completely disappeared. 19 II.C COMPLICATIONS OF INTERVENTIONAL MANAGEMENT Complications of RF treatment of the ramus medialis (medial branch) of the cervical ramus dorsalis are described in article 5 of this series on cervical facet pain. 23 II.D EVIDENCE FOR INTERVENTIONAL MANAGEMENT A summary of the available evidence is given in Table 2.

5 7. Whiplash-Associated Disorders 135 Table 2. Evidence for Interventional Management Technique Whiplash-associated disorders (WAD) Red flags ruled out Evaluation Botulinum toxin type A 2 B- Intra-articular injection 2 C- Radiofrequency treatment of the ramus medialis 2B+ (medial branch) of the cervical ramus dorsalis IV. SUMMARY WADs are comprised of a range of symptoms of which the neck complaints and headaches are the most significant spine-related symptoms. Six months of conservative treatment are recommended. The prevalence of cervical facetogenic pain is high in the whiplash population. If the facet joints are painful, a RF treatment of the ramus medialis (medial branch) of the ramus dorsalis at the cervical facets joints can be recommended. Yes Selective diagnostic block 50% pain reduction Yes RF cervical facet / ramus medialis (medial branch) of the cervical ramus dorsalis Conservative treatment effectively carried out during a minimum of 6 months without sufficient result (VAS 4) Painful cervical facet joints III. RECOMMENDATIONS RF lesions of the ramus medialis (medial branch) of the ramus dorsalis of the cervical segmental nerves are recommended for therapy-resistant neck complaints when there is an indication for involvement of the cervical facet joints in this pain syndrome. III.A CLINICAL PRACTICE ALGORITHM The practice algorithm for the treatment of WAD is given in Figure 1. III.B TECHNIQUE(S) RF facet denervation is described in article 5 of this series on cervical facet pain. 23 No No RF lesion No No RF lesion Figure 1. Clinical Practice algorithm for the treatment of whiplash-associated disorders (WAD). RF, radiofrequency; VAS, visual analog scale. ACKNOWLEDGEMENTS This review was initially based on practice guidelines written by Dutch and Flemish (Belgian) experts that are assembled in a handbook for the Dutch-speaking pain physicians. After translation, the article was updated and edited in cooperation with U.S./international pain specialists. The authors thank José Geurts and Nicole Van den Hecke for coordination and suggestions regarding the article. REFERENCES 1. Guyatt G, Gutterman D, Baumann MH, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians Task Force. Chest. 2006;129: van Kleef M, Mekhail N, van Zundert J. Evidencebased guidelines for interventional pain medicine according to clinical diagnoses. Pain Pract. 2009;9: Versteege G. Sprain of the neck and whiplash associated disorders: anesthesiology and pain management. PhD Thesis, Groningen University, Groningen, Spitzer WO, Skovron ML, Salmi LR, et al. Scientific monograph of the Quebec Task Force on whiplash-associated disorders: redefining whiplash and its management. Spine. 1995;20:1S 73S. 5. Haldeman S, Carroll L, Cassidy JD, et al. The bone and joint decade task force on neck pain and its associated disorders: executive summary. Spine. 2008;33:S5 S7. 6. Dutch Neurology Association. [Nederlandse Vereniging voor Neurologie]. Diagnosis and Treatment of People with Whiplash Associated Disorder I/II [Diagnose en Behandeling van mensen met Whiplash Associated Disorder I/II]. Utrecht, the Netherlands: Institute for Quality in Healthcare CBO [Kwaliteitsinstituut Voor de Gezondheidszorg CBO]. Whiplash.versie.maart.2008.def.pdf (accessed May 30, 2008).

6 136 van suijlekom et al. 7. Sandmark H, Nisell R. Validity of five common manual neck pain provoking tests. Scand J Rehabil Med. 1995;27: Bonuccelli U, Pavese N, Lucetti C, et al. Late whiplash syndrome: a clinical and magnetic resonance imaging study. Funct Neurol. 1999;14: Barnsley L, Lord SM, Wallis BJ, et al. Lack of effect of intraarticular corticosteroids for chronic pain in the cervical zygapophyseal joints. N Engl J Med. 1994;330: Verhagen AP, Scholten-Peeters GG, de Bie RA, et al. Conservative treatments for whiplash. Cochrane Database Syst Rev. 2004;1:CD Schreiber S, Vinokur S, Shavelzon V, et al. A randomized trial of fluoxetine versus amitriptyline in musculoskeletal pain. Isr J Psychiatry Relat Sci. 2001;38: Wieringen S, Jansen T, Smits M, et al. Melatonin for chronic whiplash syndrome with delayed melatonin onset. Clin Drug Investig. 2001;21: Esenyel M, Caglar N, Aldemir T. Treatment of myofascial pain. Am J Phys Med Rehabil. 2000;79: Freund BJ, Schwartz M. Treatment of whiplash associated neck pain [corrected] with botulinum toxin-a: a pilot study. J Rheumatol. 2000;27: Wheeler AH, Goolkasian P, Gretz SS. Botulinum toxin A for the treatment of chronic neck pain. Pain. 2001;94: Padberg M, de Bruijn SF, Tavy DL. Neck pain in chronic whiplash syndrome treated with botulinum toxin. A double-blind, placebo-controlled clinical trial. J Neurology. 2007;254: Lord SM, Barnsley L, Wallis BJ. Percutaneous radiofrequency neurotomy in the treatment of cervical zygapophyseal joint pain. N Engl J Med. 1996;335: Sapir DA, Gorup JM. Radiofrequency medial branch neurotomy in litigant and nonlitigant patients with cervical whiplash: a prospective study. Spine (Phila Pa 1976). 2001;26: Wallis BJ, Lord SM, Bogduk N. Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy: a randomised, double-blind, placebo controlled trial. Pain. 1997;73: Prushansky T, Pevzner E, Gordon C, et al. Cervical radiofrequency neurotomy in patients with chronic whiplash: a study of multiple outcome measures. J Neurosurgery. 2006;4: McDonald GJ, Lord SM, Bogduk N. Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain. Neurosurgery. 1999;45: Husted DS, Orton D, Schofferman J, et al. Effectiveness of repeated radiofrequency neurotomy for cervical facet joint pain. J Spinal Disord Tech. 2008;21: Van Eerd M, Patijn J, Lataster A, et al. Evidencebased interventional pain medicine according to clinical diagnoses: 5. Cervical facet pain. Pain Pract. 2010;10: DOI: /j x.

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