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Role of Nuclear Medicine in Complex Regional Pain Syndrome

Musculoskeletal · 3 min read

The three-phase bone scan supports a clinical diagnosis; it neither makes nor excludes it

Complex regional pain syndrome (CRPS) is persistent regional pain, usually in a distal limb, out of proportion to the inciting event, with sensory, vasomotor, sudomotor or motor and trophic change. It is diagnosed at the bedside, not in the scanner. The three-phase bone scan can support an uncertain diagnosis or point to another cause of pain, but a normal scan does not exclude CRPS.

Diagnosis is clinical

  • The Budapest criteria are the standard: continuing disproportionate pain; at least one symptom in three of four categories (sensory, vasomotor, sudomotor/oedema, motor/trophic); at least one sign in two or more categories on examination; and no other diagnosis that better explains them.
  • Imaging is not part of the criteria. In validation, the clinical criteria had a sensitivity of 0.99 and a specificity of 0.68.
  • The European Pain Federation standards (2019) state that diagnosis requires no tests except to exclude other diagnoses. The task force was divided on bone scintigraphy, and the majority did not consider it useful for diagnosis.
  • Type I has no major nerve injury; type II follows one. The distinction matters little for treatment.

The three-phase study and its time course

A ⁹⁹ᵐTc-diphosphonate is injected with the camera over both limbs, and the affected side is compared with the other. Flow images are acquired during injection, blood-pool images within about 10 minutes, and delayed images at 2–4 hours. The pattern changes with time from onset.

Phase0–20 weeks20–60 weeks60–100 weeks
1 FlowIncreasedNormalReduced
2 Blood poolIncreasedNormalReduced
3 DelayedIncreased, diffuse and periarticularStill increasedNormal, or reduced
Pearl

The delayed phase carries the diagnosis. Diffuse periarticular uptake, often around several joints of the hand or foot, is the classic pattern; flow and blood pool normalise first.

How accurate is it?

  • A 2012 meta-analysis of 12 studies gave pooled sensitivity 87% and specificity 69%, with wide confidence intervals.
  • A 2017 Bayesian meta-analysis found that, against the Budapest criteria, sensitivity fell to about 55% while specificity was about 94%. Positive scans were commoner in shorter disease.
  • In upper-limb CRPS, blinded visual reading was specific (83–100%) but insensitive (31–50%); quantitative delayed-phase analysis performed best within 5 months of onset.
  • After wrist fracture, no imaging test reliably separated CRPS from normal post-traumatic change.

When it helps, and the pitfalls

  • Most useful early, when the clinical picture is incomplete, and to look for an alternative cause: occult or stress fracture, osteomyelitis, arthritis.
  • SPECT/CT localises focal uptake and clarifies a separate bone or joint disorder.
  • Uptake is non-specific. Recent fracture, surgery, arthritis and infection all raise it; read the scan with the history.
  • Reduced uptake does not exclude CRPS. Late disease can be cold, and children most often show diffusely decreased uptake on the affected side.
  • PET has no established diagnostic role in CRPS.
Take home
  • CRPS is diagnosed with the Budapest criteria; imaging is not one of them.
  • The classic scan is increased flow and blood pool with diffuse periarticular delayed uptake, but it fades with time and may be reduced in late disease and in children.
  • The scan is specific but insensitive against the Budapest criteria: a normal scan does not exclude CRPS, and uptake must be read with the history.
Sources
  1. Harden RN, Bruehl S, Perez RSGM, et al. Validation of proposed diagnostic criteria (the "Budapest Criteria") for complex regional pain syndrome. Pain. 2010;150(2):268-74.
  2. Goebel A, Barker C, Birklein F, et al. Standards for the diagnosis and management of complex regional pain syndrome: results of a European Pain Federation task force. Eur J Pain. 2019;23(4):641-51.
  3. Bartel TB, Kuruva M, Gnanasegaran G, et al. SNMMI procedure standard for bone scintigraphy 4.0. J Nucl Med Technol. 2018;46(4):398-404.
  4. Demangeat JL, Constantinesco A, Brunot B, et al. Three-phase bone scanning in reflex sympathetic dystrophy of the hand. J Nucl Med. 1988;29(1):26-32.
  5. Howard BA, Roy L, Kaye AD, Pyati S. Utility of radionuclide bone scintigraphy in complex regional pain syndrome. Curr Pain Headache Rep. 2018;22(1):7.
  6. Ringer R, Wertli M, Bachmann LM, et al. Concordance of qualitative bone scintigraphy results with presence of clinical complex regional pain syndrome 1: meta-analysis of test accuracy studies. Eur J Pain. 2012;16(10):1347-56.
  7. Wertli MM, Brunner F, Steurer J, Held U. Usefulness of bone scintigraphy for the diagnosis of complex regional pain syndrome 1: a systematic review and Bayesian meta-analysis. PLoS One. 2017;12(3):e0173688.
  8. Wüppenhorst N, Maier C, Frettlöh J, et al. Sensitivity and specificity of 3-phase bone scintigraphy in the diagnosis of complex regional pain syndrome of the upper extremity. Clin J Pain. 2010;26(3):182-9.
  9. Schürmann M, Zaspel J, Löhr P, et al. Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods. Clin J Pain. 2007;23(5):449-57.
  10. Kwon HW, Paeng JC, Nahm FS, et al. Diagnostic performance of three-phase bone scan for complex regional pain syndrome type 1 with optimally modified image criteria. Nucl Med Mol Imaging. 2011;45(4):261-7.
  11. Goldsmith DP, Vivino FB, Eichenfield AH, et al. Nuclear imaging and clinical features of childhood reflex neurovascular dystrophy: comparison with adults. Arthritis Rheum. 1989;32(4):480-5.
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