Dimova V, Herrnberger MS, Escolano-Lozano F, et al. Clinical phenotypes and classification algorithm for complex regional pain syndrome. Neurology. 2019 Dec 24. pii: WNL.0000000000008736. doi: 10.1212/WNL.0000000000008736. (Original study)

OBJECTIVE: We pursued the hypothesis that complex regional pain syndrome (CRPS) signs observed by neurologic examination display a structure allowing for alignment of patients to particular phenotype clusters.

METHODS: Clinical examination data were obtained from 3 independent samples of 444, 391, and 202 patients with CRPS. The structure among CRPS signs was analyzed in sample 1 and validated with sample 2 using hierarchical clustering. For patients with CRPS in sample 3, an individual phenotype score was submitted to k-means clustering. Pain characteristics, quantitative sensory testing, and psychological data were tested in this sample as descriptors for phenotypes.

RESULTS: A 2-cluster structure emerged in sample 1 and was replicated in sample 2. Cluster 1 comprised minor injury eliciting CRPS, motor signs, allodynia, and glove/stocking-like sensory deficits, resembling a CRPS phenotype most likely reflecting a CNS pathophysiology (the central phenotype). Cluster 2, which consisted of edema, skin color changes, skin temperature changes, sweating, and trophic changes, probably represents peripheral inflammation, the peripheral phenotype. In sample 3, individual phenotype scores were calculated as the sum of the mean values of signs from each cluster, where signs from cluster 1 were coded with 1 and from cluster 2 with -1. A k-means algorithm separated groups with 78, 36, and 88 members resembling the peripheral, central, and mixed phenotypes, respectively. The central phenotype was characterized by cold hyperalgesia at the affected limb.

CONCLUSIONS: Statistically determined CRPS phenotypes may reflect major pathophysiologic mechanisms of peripheral inflammation and central reorganization.

Discipline Area Score
Physician 5 / 7
Comments from MORE raters

Physician rater

This is an excellent attempt at categorizing CRPS into three distinct phenotypes - central, peripheral and mixed - depending on clinical features. This is a must read article for all those who manage patients with this complex disorder.

Physician rater

This is an interesting cross sectional study of three independent cohorts of patients with chronic regional pain syndrome affecting either upper or lower limbs and occurring after either major trauma or minor injury. The premise was to use a statistical method to analyse signs and separate patients into either a central or peripheral diagnostic group. The statistical method was tested in one cohort, validated in the second patient cohort and then applied to the third patient cohort. The statistical method utilised is quite complicated and more suited to research studies than to a diagnostic tool in the clinic for individual patients. What is not clear from this study is whether the CRPS group (central or peripheral) is stable over time for an individual patient or varies depending on disease duration, type of injury and treatment received. It is also unclear whether the grouping of CRPS patients into peripheral or central groups has any value in prognostication or treatment selection.

Physician rater

With this elegant design, this document helps clinicians to improve the skills they need to assess a very difficult and relevant issue. The results need to be validated in different settings.

Physician rater

These results seem promising to me since they can generate more research questions. However, I don't think they currently have a real and direct impact on our clinical practice. More studies are needed to determine if these subtypes have different prognosis or could respond to different therapeutic modalities.
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