Clinical phenotypes and classification algorithm for complex regional pain syndrome

Abstract

ObjectiveWe 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.MethodsClinical 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.ResultsA 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.ConclusionsStatistically determined CRPS phenotypes may reflect major pathophysiologic mechanisms of peripheral inflammation and central reorganization.

Prism adaptation treatment for upper-limb Complex Regional Pain Syndrome: a double-blind randomized controlled trial

“…Overall, there were no apparent clusters of participants or relationships between these factors. Subgroup analyses of whether response to treatment depended on clinical phenotypes of CRPS [16] or baseline neuropsychological differences are also reported in Supplemental Text 3, showing results consistent with the primary analyses.…”

“…We address three potential reasons why we did not find the hypothesised effects of PA on clinical outcomes: (1) non-central pathophysiology of CRPS, (2) absence of neuropsychological symptoms, and (3) trial limitations. First, because PA targets neuropsychological deficits, it would possibly be most appropriate for a subset of individuals who predominately show signs of central neuroplasticity (compared to peripheral inflammation) [5,16]. However, post-hoc classification of participants into central or peripheral phenotypes and follow-up exploratory subgroup analysis did not reveal different responses to PA versus sham treatment (Supplemental Table S1 and Text S3).…”

Microvascular Barrier Protection by microRNA-183 via FoxO1 Repression: A Pathway Disturbed in Neuropathy and Complex Regional Pain Syndrome

“…Clinical features are based on observed signs according to the CRPS Severity Score 8 . Details on the cohort have been published before 18,19 ; controls comprised healthy subjects and subjects after trauma who did not develop CRPS. Pain symptoms in controls included prolonged healing pain after trauma and back pain.…”

Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome

“…112 Furthermore, it has been shown that signs and symptoms of CRPS are dynamic, ie, can change at different time points dependent, for example, on surrounding temperature, 113 and that different clinical phenotypes of CRPS exist. 114 Other prospective work suggests that elevations in inflammatory mediators (cytokines and peptides), which can contribute to edema as well as skin redness, are present in acute CRPS patients but generally normalize within the first 18 months post-onset. 81 Evidence that the presentation and mechanisms of CRPS can change over time within individuals argues for a single syndrome that evolves in character over time rather than these differing CRPS presentations reflecting two different, unrelated syndromes.…”