Nicholas Shenker

Establishing the characteristics for patients with chronic Complex Regional Pain Syndrome: the value of the CRPS-UK Registry

Objective: The long-term prognosis of patients with Complex Regional Pain Syndrome (CRPS) is unknown with no reported prospective studies from the United Kingdom longer than 18 months. The CRPS-UK Network aims to study this by use of a Registry. The aims of this article are, to outline the CRPS-UK Registry, assess the validity of the data and to describe the characteristics of a sample of the UK CRPS population. Methods: A web-based CRPS-UK Registry was developed and made accessible to centres experienced in diagnosing and managing patients with CRPS. Pragmatic annual follow-up questions were agreed. Results: Up until July 2013, the Registry has recruited 240 patients. A blinded, validation study of 20 consecutive patients from two centres (10 each) demonstrated 95.6% completion and 99.4% accuracy of a random sample of the recorded data. These patients had chronic disease (median duration: 29 months); 72.5% were female (2.6:1), with a mean age at symptoms onset of 43 years, and were left-handed more than expected (21.8% versus 10% in the general population). Patients reported a delayed diagnosis, with the median time between symptom onset and diagnosis of 6 months. In all, 30 patients (12.5%) had multiple limb involvement and (83.3%) had a contiguous spread of CRPS. Conclusion: CRPS-UK Registry is a validated method for actively recruiting well-characterised patients with CRPS to provide further information on the long-term outcome.

Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aortic Stiffness in Patients With Rheumatoid Arthritis

Background Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH 4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness. Methods and Results We conducted 2 randomized, double‐blinded, placebo‐controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH 4 400 mg versus placebo (n=18), and a short‐term regimen, composed of a 1‐week treatment with BH 4 400 mg once daily versus placebo (n=15). Flow‐mediated dilatation and aortic pulse wave velocity were studied 4 times, before and after each treatment phase. Acute BH 4 supplementation led to an improvement of flow‐mediated dilatation, whereas placebo had no effect (mean±SD of effect difference 2.56±4.79%; P=0.03). Similarly, 1‐week treatment with BH 4 improved endothelial function, but there was no change with placebo (mean±SD of effect difference 3.50±5.05%; P=0.02). There was no change in aortic pulse wave velocity following acute or short‐term BH 4 supplementation or placebo (mean±SD of effect difference: acute 0.09±0.67 m/s, P=0.6; short‐term 0.03±1.46 m/s, P=0.9). Conclusion Both acute and short‐term supplementation with oral BH 4 improved endothelial function but not aortic stiffness. This result suggests that BH 4 supplementation may be beneficial for patients with rheumatoid arthritis by improving endothelial dysfunction and potentially reducing risk of cardiovascular disease. There appears to be no causal relationship between endothelial function and aortic stiffness, suggesting that they occur in parallel, although they may share common risk factors such as inflammation.

Novel Signs and Their Clinical Utility in Diagnosing Complex Regional Pain Syndrome (crps): A Prospective Observational Cohort Study

Objectives: Delays in diagnosis occur with complex regional pain syndrome (CRPS). We define and prospectively demonstrate that novel bedside tests measuring body perception disruption can identify patients with CRPS postfracture. Methods: The objectives of our study were to define and validate 4 bedside tests, to identify the prevalence of positive tests in patients with CRPS and other chronic pain conditions, and to assess the clinical utility (sensitivity, specificity, positive predictive value, negative predictive value) for identifying CRPS within a Fracture cohort. This was a single UK teaching hospital prospective cohort study with 313 recruits from pain-free volunteers and patients with chronic pain conditions. Four novel tests were Finger Perception (FP), Hand Laterality identification (HL), Astereognosis (AS), and Body Scheme (BS) report. Five questionnaires (Brief Pain Inventory, Upper Extremity Functional Index, Lower Extremity Functional Index, Neglect-like Symptom Questionnaire, Hospital Anxiety and Depression Score) assessed the multidimensional pain experience. Results: FP and BS were the best performing tests. Prospective monitoring of fracture patients showed that out of 7 fracture patients (total n=47) who had both finger misperception and abnormal BS report at initial testing, 3 developed persistent pain with 1 having a formal diagnosis of CRPS. Discussion: Novel signs are reliable, easy to perform, and present in chronic pain patients. FP and BS have significant clinical utility in predicting persistent pain in a fracture group thereby allowing targeted early intervention.