RT Journal Article
SR Electronic
T1 Clinical phenotypes and classification algorithm for complex regional pain syndrome
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e357
OP e367
DO 10.1212/WNL.0000000000008736
VO 94
IS 4
A1 Dimova, Violeta
A1 Herrnberger, Myriam Selma
A1 Escolano-Lozano, Fabiola
A1 Rittner, Heike Lydia
A1 Vlckova, Eva
A1 Sommer, Claudia
A1 Maihöfner, Christian
A1 Birklein, Frank
YR 2020
UL http://n.neurology.org/content/94/4/e357.abstract
AB 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.ANOVA=analysis of variance; BDI=Beck Depression Inventory; CDT=cold detection threshold; CPT=cold pain threshold; CRPS=complex regional pain syndrome; CSS=complex regional pain syndrome severity score; DFNS=German Research Network on Neuropathic Pain; HPT=heat pain threshold; MDT=mechanical detection threshold; MPT=mechanical pain threshold; PCS=Pain Catastrophizing Scale; PPT=pressure pain threshold; QNS=Questionnaire of Neglect-like Symptoms in CRPS; QST=quantitative sensory testing; STAI-T=trait anxiety subscale of the State-Trait Anxiety Inventory; WDT=warm detection threshold; WSS=within-cluster sum of squares