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BACKGROUND: Little is known about the course of Complex Regional Pain Syndrome 1 and potential factors influencing the course of this disorder over time. The goal of this study is a) to set up a database with patients suffering from suspected CRPS 1 in an initial stadium, b) to perform investigations on epidemiology, diagnosis, prognosis, and socioeconomics within the database and c) to develop a prognostic risk assessment tool for patients with CRPS 1 taking into account symptomatology and specific therapies.
METHODS: Prospective cohort study. Patients suffering from a painful swelling of the hand or foot which appeared within 8 weeks after a trauma or a surgery and which cannot be explained by conditions that would otherwise account for the degree of pain and dysfunction will be included. In accordance with the recommendations of International Classification of Functioning, Disability and Health (ICF model), standardised and validated questionnaires will be used. Patients will be monitored over a period of 2 years at 6 scheduled visits (0 and 6 weeks, 3, 6, 12, and 24 months). Each visit involves a physical examination, registration of therapeutic interventions, and completion of the various study questionnaires. Outcomes involve changes in health status, quality of life and costs/utility.
DISCUSSION: This paper describes the rationale and design of patients with CRPS 1. Ideally, potential
OBJECTIVE: Complex regional pain syndrome (CRPS) type I, also known as reflex sympathetic dystrophy, usually develops after trauma or immobilization, is characterized by focal pain and autonomic dysregulation, and sometimes focal trophic changes such as osteoporosis. The pathophysiology is unknown and there have been few controlled treatment trials. The purpose of this study was to obtain pilot data on the safety and efficacy of a highly potent bisphosphonate, ibandronate, for the treatment of CRPS, which might be responsive to bisphosphonates' inhibition of osteoclast and anti-inflammatory activity.
METHODS: An open-label trial (n=10) of 6 mg ibandronate infusions was administered on each of 3 days. The infusions were preceded by a 2-week baseline period, and followed by a 4-week follow-up period.
RESULTS: One participant dropped out after the first infusion because of a decreased glomerular filtration rate. Otherwise, aside from transitory flu-like symptoms characteristic of bisphosphonate treatments, the drug was well tolerated. Significant postintervention improvements were observed in average and worst pain ratings; the neuropathic pain qualities of "unpleasant," "sensitive," "deep," "intense," "surface," "hot," "cold," "sharp," and "dull"; and hyperalgesia and allodynia. Participants with hand CRPS improved significantly more than those with foot CRPS in average and worst pain, as well as in the following neuropathic pain qualities: "dull," "intense," "deep," and "time."
DISCUSSION: These data justify a randomized, double-blind, placebo-controlled trial of ibandronate that should perhaps be limited to patients with hand CRPS.
We report a case of complex regional pain syndrome developing in a 57-year-old woman after minor skin surgery in the sole of her right foot. This was diagnosed and treated in its early phase with sympathetic blockade using guanethedine with complete recovery of symptoms
Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery.
Besse JL, Gadeyne S, Galand-Desmé S, Lerat JL, Moyen B. Foot Ankle Surg. 2009;15(4):179-82.
BACKGROUND: The public health cost impact of complex regional pain syndrome type I (CRPS I) is considerable in both emergency and scheduled orthopaedic surgery. We proposed to assess the effectiveness of vitamin C in prevention of CRPS I in foot and ankle surgery.
METHODS: We carried out a "before-after" quasi-experimental study comparing two chronologically successive groups without (Group I: July 2002-June 2003) and with (Group II: July 2003-June 2004) preventive 1g daily vitamin C treatment. All patients having surgery on the foot or ankle were enrolled, with the exception of diabetic foot cases. Several factors were analysed: sex, age, type of pathology, history of CRPS I, psychological context, tourniquet time, and cast immobilisation time.
RESULTS: 420 feet (392 patients) were included in the study: 185 in Group I, 235 in Group II. CRPS I occurred in 18 cases in Group I (9.6%) and 4 cases in Group II (1.7%) (p<10(-4)), with history of CRPS I as a significantly correlated factor (relative risk=10.4). The psychological context (anxio-depressive state) showed a (sub-significant) tendency to increase the risk of CRPS I (relative risk=2.6).
CONCLUSION: Vitamin C has been shown to be effective in preventing CRPS I secondary to wrist fracture, but few data are available with respect to foot and ankle cases. The present study demonstrates the effectiveness of vitamin C in preventing CRPS I of the foot and ankle-a frequent complication in our control group (9.6%). The authors recommend preventive management by vitamin
Efficacy and Safety of High-dose Vitamin C on Complex Regional Pain Syndrome in Extremity Trauma and Surgery—Systematic Review and Meta-Analysis
Naohiro Shibuya, Jon M. Humphers, Monica R. Agarwal, Daniel C. Jupiter Journal of Foot and Ankle Surgery (in press)
Complex regional pain syndrome (CRPS) is a devastating condition often seen after foot and ankle injury and surgery. Prevention of this pathology is attractive not only to patients but also to surgeons, because the treatment of this condition can be difficult. We evaluated the effectiveness of vitamin C in preventing occurrence of CRPS in extremity trauma and surgery by systematically reviewing relevant studies. The databases used for this review included: Ovid EMBASE, Ovid MEDLINE, CINAHL, and the Cochrane Database. We searched for comparative studies that evaluated the efficacy of more than 500 mg of daily vitamin C. After screening for inclusion and exclusion criteria, we identified 4 studies that were relevant to our study question. Only 1 of these 4 studies was on foot and ankle surgery; the rest concerned the upper extremities. All 4 studies were in favor of this intervention with minimal heterogeneity (Tau2 = 0.00). Our quantitative synthesis showed a relative risk of 0.22 (95% confidence interval = 0.12, 0.39) when daily vitamin C of at least 500 mg was initiated immediately after the extremity surgery or injury and continued for 45 to 50 days. A routine, daily administration of vitamin C may be beneficial in foot and ankle surgery or injury to avoid CRPS. Further foot and ankle specific and dose-response studies are warranted.
Complex Regional Pain Syndrome (CRPS) is a neuropathic pain disorder that is characterized by: 1) Severe pain beyond the area of injury; 2) Autonomic dysregulation; 3) Neuropathic edema; 4) A movement disorder, atrophy and dystrophy. It is most often caused by a fracture, soft-tissue injury or surgical procedure and is divided into Type I, in which no nerve lesion is identified (classic reflex sympathetic dystrophy), and Type II where a specific nerve has been damaged (causalgia). In addition to the peripheral manifestations, there are many internal medical complications whose etiology is often not appreciated. This article will examine how CRPS affects the systems of: cognition; constitutional, cardiac, and respiratory complications; systemic autonomic dysregulation; neurogenic edema; musculoskeletal, endocrine and dermatological manifestations; as well as urological and gastrointestinal function.
Treatment of complex regional pain syndrome in adults: A systematic review of randomized controlled trials published from June 2000 to April 2010
L. Cossins et al European Journal of Pain (in press)
Complex regional pain syndrome (CRPS) is a disabling pain condition with sensory, motor and autonomic manifestations. Uncertainty remains about how CRPS can be effectively managed. We conducted a systematic review of randomized controlled trials (RCTs) for treatment and prophylactic interventions for CRPS published during the period 2000–2012, building on previous work by another group reviewing the period 1966–2000. Bibliographic database searches identified 173 papers which were filtered by three reviewers. This process generated 29 trials suitable for further analysis, each of which was reviewed and scored by two independent reviewers for methodological quality using a 15-item checklist. A number of novel and potentially effective treatments were investigated. Analysing the results from both review periods in combination, there was a steep rise in the number of published RCTs per review decade. There is evidence for the efficacy of 10 treatments (3× strong – bisphosphonates, repetitive transcranial magnetic stimulation and graded motor imagery, 1× moderate and 6× limited evidence), and against the efficacy of 15 treatments (1× strong, 1× moderate and ×13 limited). The heterogeneity of trialled interventions and the pilot nature of many trials militate against drawing clear conclusions about the clinical usefulness of most interventions. This and the observed phenomenon of excellent responses in CRPS subgroups would support the case for a network- and multi-centre approach in the conduct of future clinical trials. Most published trials in CRPS are small with a short follow-up period, although several novel interventions investigated from 2000 to 2012 appear promising.
Complex Regional Pain Syndrome Acceptance and the Alternative Denominations in the Medical Literature
Jasmina Todorova, Nikolaj Dantchev, Guenka Petrova Med Princ Pract (in press)
Objective: To analyze the use of the term ‘complex regional pain syndrome’ in the medical literature and evaluate whether or not the traditional names ‘reflex sympathetic dystrophy’ and ‘causalgia’ have already been replaced with the new terms ‘complex regional pain syndrome type I’ and ‘complex regional pain syndrome type II’, respectively.
Materials and Methods: The Scopus and PubMed databases were searched for reports written between 2001 and 2012 for the following descriptors in the titles: ‘complex regional pain syndrome’, ‘complex regional pain syndrome type I’, ‘complex regional pain syndrome type 1’, ‘complex regional pain syndrome type II’, ‘complex regional pain syndrome type 2’, ‘CRPS’, ‘CRPS type I’, ‘CRPS type 1’, ‘CRPS type II’, ‘CRPS type 2’, ‘reflex sympathetic dystrophy’, ‘algodystrophy’, ‘algoneurodystrophy’, ‘causalgia’, ‘transient osteoporosis’, ‘Sudeck’, and ‘shoulder-hand syndrome’.
Results: Systematization of the 1,318 articles found yielded the following: 953 (72.31%) articles for the descriptor ‘complex regional pain syndrome’ and a further 94 (7.13%) for its abbreviation ‘CRPS’; 180 (13.66%) for ‘reflex sympathetic dystrophy’; 33 (2.50%) for ‘shoulder-hand syndrome’; 29 (2.20%) for ‘algodystrophy’; 13 (0.99%) for ‘causalgia’; 13 (0.99%) for ‘Sudeck’; 2 (0.15%) for ‘algoneurodystrophy’, and 1 (0.08%) for ‘transient osteoporosis’. The total number of articles using new terminology represents 1,047 (79.44%) of all articles.
Conclusion: The new neutral term ‘complex regional pain syndrome’ was most commonly used and will likely replace the traditional names ‘reflex sympathetic dystrophy’ and ‘causalgia’. The new terminology is now widely accepted by the medical professionals who are mostly engaged in the treatment of CRPS patient
Objectives: We conducted a systematic review of the literature with meta-analysis to determine whether complex regional pain syndrome (CRPS) is associated with a specific inflammatory profile and whether this is dependent on the duration of the condition.
Methods: Comprehensive searches of the literature using MEDLINE, Embase, Scopus, Web of Science, and reference lists from published reviews identified articles that measured inflammatory factors in CRPS. Two independent investigators screened titles and abstracts, and performed data extraction and risk of bias assessments. Studies were subgrouped by medium (blood, blister fluid, and CSF) and duration (acute and chronic CRPS). Where possible, meta-analyses of inflammatory factor concentrations were performed and pooled effect sizes were calculated using random-effects models.
Results: Twenty-two studies were included in the systematic review and 15 in the meta-analysis. In acute CRPS, the concentrations of interleukin (IL)-8 and soluble tumor necrosis factor receptors I (sTNF-RI) and II (sTNF-RII) were significantly increased in blood. In chronic CRPS, significant increases were found in 1) TNFα, bradykinin, sIL-1RI, IL-1Ra, IL-2, sIL-2Ra, IL-4, IL-7, interferon-γ, monocyte chemoattractant protein-1 (MCP-1), and sRAGE (soluble receptor for advanced glycation end products) in blood; 2) IL-1Ra, MCP-1, MIP-1β, and IL-6 in blister fluid; and 3) IL-1β and IL-6 in CSF. Chronic CRPS was also associated with significantly decreased 1) substance P, sE-selectin, sL-selectin, sP-selectin, and sGP130 in blood; and 2) soluble intercellular adhesion molecule-1 (sICAM-1) in CSF. Most studies failed to meet 3 or more of our quality criteria.
Conclusion: CRPS is associated with the presence of a proinflammatory state in the blood, blister fluid, and CSF. Different inflammatory profiles were found for acute and chronic cases.
Complex Regional Pain Syndrome (CRPS) is a serious and painful condition involving the peripheral and central nervous systems. Full comprehension of the disorder’s pathophysiology remains incomplete, but research implicates the immune system as a contributor to chronic pain. Because of the impact gastrointestinal bacteria have in the development and behavior of the immune system, this study compares the GI microbial communities of 16 participants with CRPS (5 of whom have intestinal discomforts) and 16 healthy controls using 454 sequencing technology. CRPS subjects were found to have significantly less diversity than their healthy counterparts. Statistical analysis of the phylogenetic classifications revealed significantly increased levels of Proteobacteria and decreased levels of Firmicutes in CRPS subjects. Clustering analysis showed significant separation between healthy controls and CRPS subjects. These results support the hypothesis that the GI microbial communities of CRPS participants differ from those of their healthy counterparts. These variations may hold the key to understanding how CRPS develops and provide information that could yield a potential treatment.
Incidence of Complex Regional Pain Syndrome after Foot and Ankle Surgery
Matthew J. Rewhorn, MBCHB, Andraay H. Leung, MBCHB, MRCS, Alan Gillespie, MBCHB, J. Stuart Moir, MBCHB, FRCS, Orth, Roslyn Miller, MBCHB, FRCS, Orth Journal of Foot and Ankle Surgery; Article in Press
Complex regional pain syndrome (CRPS) is an uncommon complication of orthopedic surgery, and few investigators have considered the incidence in foot and ankle surgery. In the present retrospective cohort study of 390 patients who had undergone elective foot and/or ankle surgery in our department from January to December 2009, the incidence of postoperative CRPS was calculated and explanatory variables were analyzed. A total of 17 patients (4.36%) were identified as meeting the International Association for the Study of Pain criteria for the diagnosis of CRPS. Of the 17 patients with CRPS, the mean age was 47.2 ± 9.7 years, and 14 (82.35%) were female. All the operations were elective, and 9 (52.94%) involved the forefoot, 3 (17.65%) the hindfoot, 3 (17.65%) the ankle, and 2 (11.76%) the midfoot. Twelve patients (70.59%) had new-onset CRPS after a primary procedure, and 5 (29.41%) had developed CRPS after multiple surgeries. Three patients (17.65%) had documented nerve damage intraoperatively and thus developed new-onset CRPS type 2. Blood test results were available for 14 patients (82.35%) at a minimum of 3 months postoperatively, and none had elevated inflammatory markers. Five of the patients (29.41%) were smokers, and 8 (47.06%) had had a pre-existing diagnosis of anxiety and/or depression. From our findings, we recommend that middle-age females and those with a history of anxiety or depression, who will undergo elective foot surgery, should be counseled regarding the risk of developing CRPS during the consent process. We recommend similar studies be undertaken in other orthopedic units, and we currently are collecting data from other orthopedic departments within Scotland.
Complex regional pain syndrome is a severe complication following trauma that is associated with vasomotor, sudomotor and sensory disturbances in an affected limb or region of the body. The exact physiopathology is not fully understood yet. Recently, autoantibody findings suggested an immune-mediated physiopathology of the disease. We here describe two otherwise treatment-resistant patients with complex regional pain syndrome and high-titre beta2 adrenergic receptor autoantibodies, who did respond to plasmapheresis. Both patients showed strong improvement of pain and autonomic symptoms measured by impairment level sum score.
A Systematic Review of Ketamine for Complex Regional Pain Syndrome
Sara B. Connolly, Joshua P. Prager, and Harden R. Norman Pain Medicine; Early View
This systematic review aims to examine the available literature and to synthesize published data concerning the treatment of Complex Regional Pain Syndrome (CRPS) with ketamine.
The search was conducted utilizing the databases Medline, Embase and the Cochrane Central Registry of Controlled Trials. All relevant articles were systematically reviewed.
The search yielded 262 articles, 45 of which met the inclusion/exclusion criteria. Of those included, 6 were reviews, 5 were randomized placebo-controlled trials, 13 were observational studies, and 21 were case reports.
There is no high quality evidence available evaluating the efficacy of ketamine for CRPS and all manuscripts examined in this review were of moderate to low quality. Therefore, we conclude there is currently only weak evidence supporting the efficacy of ketamine for CRPS, yet there is clearly a rationale for definitive study.
Research into complex regional pain syndrome (CRPS) has made significant progress. First, there was the implementation of the official IASP "Budapest" diagnostic criteria. It would be desirable to also define exclusion and outcome criteria that should be reported in studies. The next step was to recognize the complex pathophysiology. After trauma, some inflammation is physiological; in acute CRPS, this inflammation persists for months. There is an abundance of inflammatory and a lack of anti-inflammatory mediators. This proinflammatory network (cytokines and probably also other mediators) sensitizes the peripheral and spinal nociceptive system, it facilitates the release of neuropeptides from nociceptors inducing the visible signs of inflammation, and it stimulates bone cell or fibroblast proliferation, and endothelial dysfunction leading to vascular changes. Trauma may also expose nervous system structures to the immune system and triggers autoantibodies binding to adreno- and acetylcholine receptors. In an individual time frame, the pain in this inflammatory phase pushes the transition into "centralized" CRPS, which is dominated by neuronal plasticity and reorganization. Sensory-motor integration becomes disturbed, leading to a loss of motor function; the body representation is distorted leading to numbness and autonomic disturbances. In an attempt to avoid pain, patients neglect their limb and learn maladaptive nonuse. The final step will be to assess large cohorts and to analyze these data together with data from public resources using a bioinformatics approach. We could then develop diagnostic toolboxes for individual pathophysiology and select focused treatments or develop new ones.