Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modeling Approach

Background: Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. Involvement of dysfunctional GABAergic interneurons has been suggested, however the mechanisms that underpin fixed dystonia are still unknown. We hypothesized that dystonia could be the result of aberrant proprioceptive reflex strengths of position, velocity or force feedback. Methods: We systematically characterized the pattern of dystonia in 85 CRPS-patients with dystonia according to the posture held at each joint of the affected limb. We compared the patterns with a neuromuscular computer model simulating aberrations of proprioceptive reflexes. The computer model consists of an antagonistic muscle pair with explicit contributions of the musculotendinous system and reflex pathways originating from muscle spindles and Golgi tendon organs, with time delays reflective of neural latencies. Three scenarios were simulated with the model: (i) increased reflex sensitivity (increased sensitivity of the agonistic and antagonistic reflex loops); (ii) imbalanced reflex sensitivity (increased sensitivity of the agonistic reflex loop); (iii) imbalanced reflex offset (an offset to the reflex output of the agonistic proprioceptors). Results: For the arm, fixed postures were present in 123 arms of 77 patients. The dominant pattern involved flexion of the fingers (116/123), the wrists (41/123) and elbows (38/123). For the leg, fixed postures were present in 114 legs of 77 patients. The dominant pattern was plantar flexion of the toes (55/114 legs), plantar flexion and inversion of the ankle (73/114) and flexion of the knee (55/114). Only the computer simulations of imbalanced reflex sensitivity to muscle force from Golgi tendon organs caused patterns that closely resembled the observed patient characteristics. In parallel experiments using robot manipulators we have shown that patients with dystonia were less able to adapt their force feedback strength. Conclusions: Findings derived from a neuromuscular model suggest that aberrant force feedback regulation from Golgi tendon organs involving an inhibitory interneuron may underpin the typical fixed flexion postures in CRPS patients with dystonia.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

Integration of Sensory Force Feedback Is Disturbed in CRPS-Related Dystonia

Complex regional pain syndrome (CRPS) is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. The origin of this movement disorder is poorly understood, although recent insights suggest involvement of disturbed force feedback. Assessment of sensorimotor integration may provide insight into the pathophysiology of fixed dystonia. Sensory weighting is the process of integrating and weighting sensory feedback channels in the central nervous system to improve the state estimate. It was hypothesized that patients with CRPS-related dystonia bias sensory weighting of force and position toward position due to the unreliability of force feedback. The current study provides experimental evidence for dysfunctional sensory integration in fixed dystonia, showing that CRPS-patients with fixed dystonia weight force and position feedback differently than controls do. The study shows reduced force feedback weights in CRPS-patients with fixed dystonia, making it the first to demonstrate disturbed integration of force feedback in fixed dystonia, an important step towards understanding the pathophysiology of fixed dystonia.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin