What does Peul et al suggest?

Sciatica: Background

 Sciatica is relatively common; lifetime incidence is 13% to 40% (Frymoyer, 1992)  Annual incidence of an episode of sciatica is 1% to 5% (Frymoyer, 1988)  Ancient Greeks used the term sciatica to describe pains or “ischias” (Stafford et al, 2007)  Initially known as Cotugno’s Disease after the anatomist who wrote the first book on the condition in the 1700’s (Delaney, 1980)

Sciatica: Epidemiology

Source: Stafford et al, 2007 Source: www.google.com/health

Sciatica: Pathophysiology

 Several etiologies proposed: (1) (1) (2) Inflammatory Phospholipase A 2 (Saal et al, 1990; Franson et al, 1992) TNF-α (Karppinen et al, 2003) (2) (3) Immune-mediated Mechanical

Sciatica: Inflammatory?

Stafford et al, 2007

Sciatica: Immune-mediated?

 Raised antibody levels to glycosphingolipids were detected in (Brisby et al, 2002):  71% of patients with acute sciatica  61% at 4 yr follow-up  54% of those undergoing discectomy

Peul et al, 2007, New England Journal of Medicine

Background

 No consensus on how long non-surgical (“conservative”) therapy should be tried prior to surgery (Luijsterburg et al, 2004)  Authors suggest “sociocultural preferences” account for differences  Dutch guidelines: after 6 weeks of conservative treatment, offer surgery  In the US, largely practitioner dependent in terms of referral to physical therapy vs. referral to surgery  US vs. Switzerland expert panels differ little (Vader et al, 2000)

Methods: Eligibility

 Multicenter, prospective, randomized trial  Inclusion Criteria: (1) 18 to 65 years (2) radiologically confirmed disc herniation (3) sciatica lasting 6-12 weeks  Exclusion Criteria: (1) Cauda equina (2) Muscle paralysis (3) Absent movement against gravity (4) Similar sciatica episode within 12 months (5) Previous spine surgery (6) Bony stenosis (7) Spondylolisthesis (8) Pregnancy (9) Severe co-existing disease  Randomization via computer-generated block scheme

Methods: Treatment

 General or spinal anesthesia  Minimal, unilateral transflaval approach  Annular fenestration with curettage and removal of disk material  No attempt to perform a subtotal diskectomy  Home rehabilitation supervised by physiotherapists using standardized protocol

Methods: Conservative

 GP informed patients of favorable prognosis and encouraged them to visit website with more information  Pain medication was adjusted according to previous study protocol (Peul et al, 2005)  Patients fearful of moving were referred to physiotherapists  Microdiskectomy was offered to patients with sciatica persisting for 6 months  Patients with (1) increasing leg pain non-responsive to pain meds (2) progressive neurologic deficits were offered surgery earlier than 6 months

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Methods: Surveys

Roland Disability Questionnaire for Sciatica (Ostelo et al, 2003) Visual Analogue Scale for Leg Pain (Capodaglio, 2001) Likert Self-Rating (Dawes, 2008) Primary outcomes: (1) Functional disability (2) Intensity of leg pain (3) Global perceived recovery Secondary outcomes: recorded at 8, 26, and 52 weeks Secondary outcome visits: (1) neuro exam (2) independent research nurse made (a) functional (b) economic observations SF-36 Sciatica Frequency and Bothersomeness Index (Grovle et al, 2008)

Methods: Surveys Cont’d

 Prolo functional observational assessment  Prolo economic observational assessment  McGill affective score

Methods: Stats

 Primary aims:  Disease specific disability with respect to daily functioning (Roland and VAS)  Median time to recovery (Likert scale as a function of time)  Power of .9 with two-tailed significance at .05 level to detect at least a 3 point difference on Roland  SPSS version 12  Hazard ratio to compute speed of recovery

Hazard Ratio

“A hazard ratio of 2 means that treatment will cause the patient to heal faster, but in a very specific sense. In the context of hazard ratio, “fast” means that a treated patient who has not yet healed by a certain time has twice the chance of being healed at the next point in time compared to someone in the control group” (Spruance et al, 2004)

Discussion

 Microdiskectomy technique  Subgroups: sciatica when sitting  Adequate reflection of productivity costs and quality of life missing for the “conservative” group  Objective information on the course of symptoms  Limited generalizability: (1) (2) (3) Nurses guided pain management in conservative group Lack of blinding of patient and practitioner Sampling timepoints may have underestimated time to recovery

Critique

 Blinding and the Placebo Effect?  Patients  Independent research nurse  Scale to analyze “median time to recovery”  Limited generalizability (Netherlands vs. US)  Intention to treat (Hollis et al, 1999)  Hazard ratio (Spruance et al, 2004)  Physiologic mechanisms behind sciatica

Implications and Future Directions

 Health reform and rationing  Epidural injections for sciatica?

 Does type of surgery (e.g. MIS) influence the outcome?

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References

Frymoyer J. Lumbar disc disease: epidemiology. Instr Course Lect 1992; 41: 217–23 Frymoyer JW. Back pain and sciatica. N Engl J Med 1988; 318: 291–300 Stafford MA, Peng P Hill DA Sciatica: a review of history, epidemiology, pathogenesis, and the role of epidural steroid injection in management. Br J Anaesth. 2007 Oct;99(4):461-73. Epub 2007 Aug 17. Delaney TJ, Rowlingson JC, Carron H, Butler A. Epidural steroid effect in nerves ad meninges. Anesth Analg 1980; 59: 610–4 Saal JS, Franson RC, Dobrow R, White AH, Goldthwaite N. High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine 1990; 15: 674–8 Franson RC, Saal JS, Saal JA. Human disc phospholipase A2 is inflammatory. Spine 1992; 17: 5129–32 Karppinen J, Korhonen T, Malmivaara A, et al. Tumor necrosis factor-a monoclonal antibody, infliximab, used to manage severe sciatica. Spine 2003; 28: 750–4 Brisby H, Balague F, Schafer D, et al. Glycosphingolipid antibodies in serum in patients with sciatica. Spine 2002; 27: 380–6 Peul WC, van Houwelingen HC, van den Hout WB, Brand R, Eekhof JA, Tans JT, Thomeer RT, Koes BW; Leiden-The Hague Spine Intervention Prognostic Study Group. Surgery versus prolonged conservative treatment for sciatica.N Engl J Med. 2007 May 31;356(22):2245-56.

Luijsterburg PA, Verhagen AP, Braak S, Oemraw A, Avezaat CJ, Koes BW Neurosurgeons' management of lumbosacral radicular syndrome evaluated against a clinical guideline. Eur Spine J. 2004 Dec;13(8):719-23. Epub 2004 Apr 29. Ostelo RW, de Vet HC, Vlaeyen JW, Kerckhoffs MR, Berfelo WM, Wolters PM, van den Brandt PA. Behavioral graded activity following first-time lumbar disc surgery: 1-year results of a randomized clinical trial. Spine (Phila Pa 1976). 2003 Aug 15;28(16):1757-65.

Capodaglio EM. Comparison between the CR10 Borg's scale and the VAS (visual analogue scale) during an arm-cranking exercise. J Occup Rehabil. 2001 Jun;11(2):69-74 Grøvle L, Haugen AJ, Keller A, Natvig B, Brox JI, Grotle M. Reliability, validity, and responsiveness of the Norwegian versions of the Maine-Seattle Back Questionnaire and the Sciatica Bothersomeness and Frequency Indices. Spine (Phila Pa 1976). 2008 Oct 1;33(21):2347-53.

Spruance, Spotswood L., Reid, Julia E., Grace, Michael, Samore, Matthew Hazard Ratio in Clinical Trials Antimicrob. Agents Chemother. 2004 48: 2787-2792 Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ. 1999 Sep 11;319(7211):670 4.