Complex regional pain syndrome

Diagnostic workup
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By Steven H Horowitz MD

There are no gold-standard diagnostic tests in CRPS; the diagnosis is clinical. However, the following tests can be helpful in supporting the clinical diagnosis or ruling out other clinical entities.

Neurophysiological studies. Nerve conductions and electromyography are often used to document peripheral nerve damage. However, surface electrode nerve conduction studies only measure large (fast-conducting) myelinated A alpha beta fiber activity in mixed peripheral nerves, not the small A delta and C fibers primarily affected in CRPS. Abnormal nerve conduction studies can reveal a generalized or focal, eg, entrapment, neuropathy, thereby determining large-nerve-fiber damage, but coincident small-fiber dysfunction is inferred. Normal nerve conduction studies do not rule out the presence of nerve damage and cannot be used to differentiate between CRPS I and II, as has occurred in some studies (Bruehl et al 1999; 2002; Harden et al 1999; Harden and Bruehl 2005; Rommel et al 2005). The same points also apply to electromyography, in which abnormal “neurogenic” patterns only identify axonal injuries to large myelinated motor axons.

Quantitative sensory testing. Quantitative sensory testing is a more formal and sensitive method of testing various sensory thresholds (most commonly thermal, mechanical, and vibratory) than the clinical examination. Similarly, the findings are subjective and dependent on patient motivation and alertness (Freeman et al 2003), and are not specific to CRPS. Maier and colleagues studied 1236 patients with a variety of neuropathic pain syndromes with qualitative sensory testing and characterized the findings: thermal and mechanical hyperalgesias were most frequent in CRPS (Maier et al 2010). The method is not recommended as a routine laboratory test for CRPS (Rommel et al 2005); it is mainly a research tool at present.

Radiological studies. Useful studies include bone scintigraphy (Wuppenhorst et al 2010) and to a lesser extent x-ray and bone densitometry, as these can reveal focal subchondral or subperiosteal osteoporosis. These are underutilized for identifying patients whose bone remodeling is a source of pain that can be treated with nasal calcitonin or bisphosphonates (Hamamci et al 1996; Cortet et al 1997). Computerized axial tomography and MRI are less often useful but can identify neurogenic edema of affected bones, joints, and deep tissues. MR neurography and ultrasound are emerging techniques for visualizing nerves (Aagaard et al 1998; Walker et al 2010). They can help identify entrapment neuropathies amenable to surgery (Thimineur and Saberski 1996; Grant et al 2004).

Punch skin biopsy. This increasingly popular method involves removing a small piece of skin under local anesthesia. This is sectioned and immunolabeled with a pan-axonal marker that permits evaluation and quantitation of the unmyelinated sensory axons, A delta and C fibers. Neurodiagnostic skin biopsy, currently the best diagnostic test for small-fiber polyneuropathy (England et al 2009), has provided critical research evidence of small-fiber nerve injury in CRPS I, obviating its distinction from CRPS II (Oaklander et al 2006). As normative densities differ at different body locations and with high inter-individual variability, skin biopsy is not useful clinically except for rare situations in which comparison of biopsies from patients’ CRPS-affected and matching unaffected areas confirm focal small-fiber losses.

Sympathetic nerve blocks. Sympathetic nerve blocks are a controversial subject with a complicated history. For an affected upper limb, the stellate ganglion is blocked with local anesthetic with or without corticosteroids, and for a lower limb the lumbar sympathetic chain is blocked. Following Evans’ enthusiasm, for decades these were used not only for treatment, but a positive response was required for diagnosis of reflex sympathetic dystrophy (Evans 1946; 1947). Few, if any, early studies of sympathetic nerve blocks are considered adequate today. They were unblinded and generally uncontrolled; the importance of the placebo response, which is particularly strong for therapeutic interventions, was unrecognized. Later, patients with temporary post-block pain reduction were diagnosed with sympathetically maintained pain; those not responding had sympathetically independent pain. Given the technical and interpretational limitations of this method, and evidence that somatic axons co-innervate most structures traditionally thought only autonomically innervated, use of sympatholytic procedures has waned.