Complex regional pain syndrome.

ABSTRACT: Complex regional pain syndrome (CRPS), formerly called reflex sympathetic dystrophy (RSD), is a chronic pain phenomenon associated with an alteration in peripheral and central pain perception in a localized body region. Because of the many risk factors associated with this phenomenon, the true nature of the disease risk and clinical course are a challenge to predict. After the diagnosis is confirmed and treatment is provided promptly, clinicians must consider patient health and function holistically to foster improvement in overall quality of life.

Morphological and electrophysiological evaluation of median and ulnar nerve in complex regional pain syndrome type 1.

OBJECTIVE: Complex regional pain syndrome (CRPS) can be distinguished as type I without and type II with electrophysiological evidence of major nerve lesion. The pathophysiology of both subgroups is still under investigation. The aim of this research is to demonstrate the nerve morphology and electrophysiology in CRPS type I patients. MATERIALS AND METHODS: Bilateral median and ulnar nerve cross-sectional areas were evaluated with ultrasound and also median and ulnar nerve conduction studies of both hands were performed. Cross-sectional areas of median and ulnar nerves and nerve conduction studies in healthy controls were also obtained and compared with the patients. RESULTS: Twenty-five male patients and 11 healthy male controls were enrolled in the study. The mean age of the patients was 24.08 ± 5.50 years and controls was 23.18 ± 5.09 (p > 0.05). Compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes of the diseased side were found significantly lower than the healthy side (p < 0.05). Both median and ulnar nerve distal motor latency values were significantly higher in the patient group (p < 0.05). There was no significant difference in the median and ulnar nerve cross-sectional area when compared with the opposite extremity and healthy volunteers. CONCLUSION: The lower SNAP and CMAP amplitudes of the median and ulnar nerves compared to the healthy side and the prolongation of the affected side median and ulnar nerve distal motor latencies of the affected individuals may indicate axonal involvement in patients with CRPS type 1. Decreased CMAP amplitudes may also indicate muscle atrophy due to a decrease in the number of functional motor units.

Complex regional pain syndrome following vascular access creation for hemodialysis.

Pain and swelling of a limb following creation of arterio-venous fistula (AVF) are often attributable to vascular disorders like venous hypertension or limb ischaemia. Here we report the case of a 70-years old man who developed pain and swelling of upper limb distal to the AVF during second post-operative week due to a complex regional pain syndrome (CRPS). CRPS is characterized by pain that is disproportionate to the invoking injury, autonomic dysfunction, trophic changes and functional impairment of affected limb. Hyperalgesia and allodynia are pain patterns characteristic of CRPS. CRPS has been reported rarely following AVF creation surgery. Prompt diagnosis of CRPS is important to avoid misdiagnosis of vascular disorders and for implementation of right therapeutic strategy.

Sympathetic Blocks as a Predictor for Response to Ketamine Infusion in Patients with Complex Regional Pain Syndrome: A Multicenter Study.

BACKGROUND: Ketamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions. OBJECTIVES: We sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion. METHODS: In this multi-center retrospective study, 71 patients who underwent sympathetic blocks followed by ketamine infusions at 4 hospitals were evaluated. Sympathetically maintained pain (SMP) was defined as ≥ 50% immediate pain relief after sympathetic block and a positive response to ketamine was defined as ≥ 30% pain relief lasting over 3 weeks. RESULTS: Factors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome. CONCLUSIONS: The response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.

Combining Stellate ganglion block and intravenous regional anesthesia to treat complex regional pain syndrome: A 19-years' experience in a tertiary center.

OBJECTIVES: To study reduction in pain score after treatment with intravenous regional anesthesia (IVRA) and Stellate ganglion block (SGB) combination on complex regional pain syndrome (CPRS) patients and to quantify patients' satisfaction with treatment and occurrence of complications. METHODS: This is a record-based retrospective review carried out in 2020, targeting patients treated in the University of Jordan Hospital, Amman, Jordan, over the years 2002-2020. RESULTS: Among 99 patients, a significant drop in pain scores occurred in 88% of the patients' sample. Gender, age, type of CRPS, and duration of symptoms didn't affect statistical results. An average of 8.6 sessions needed to achieve 50% drop in pain score, and 2-3 sessions for first clinical improvement. Patients with previous application of plaster of Paris had increased success rates. CONCLUSION: We find it practical, inexpensive, safe, and straightforward to combine SGB with IVRA for CRPS patients.

Outcomes of Carpal Tunnel Release in Complex Regional Pain Syndrome/Reflex Sympathetic Dystrophy/Sudeck Disease Patients.

BACKGROUND: The clinical features of classic carpal tunnel syndrome are well known. However, some patients who display atypical symptoms and signs of pain and dysesthesias in the hand, worsening of symptoms at night, and above all, inability to make a full fist, respond equally well to carpal tunnel release. This same clinical picture was shared by some patients labeled as having complex regional pain syndrome. Because of the poor outcome of complex regional pain syndrome patients with current regimens, the authors tested the hypothesis that carpal tunnel release could be effective on them. The purpose of this article is to report the outcome of carpal tunnel release in complex regional pain syndrome patients who presented the above signs and symptoms. METHODS: Fifty-three patients with an average age of 55 years presenting the above cluster of symptoms were operated on. All were unilateral cases, had sustained trauma, and were treated for complex regional pain syndrome before referral for an average of 16 months. All patients underwent carpal tunnel release. RESULTS: At a minimum of 6 months' follow-up, pain dropped 7.5 points on a numerical rating scale of 0 to 10 ( p < 0.001). Disabilities of the Arm, Shoulder and Hand scoring fell from 82 to 17 ( p < 0.001). Six patients had an unsatisfactory result. CONCLUSIONS: Some patients with complex regional pain syndrome may respond successfully to a carpal tunnel release operation. Recognition of this possibility is crucial, as the symptoms and signs might lead the clinician away from the proper diagnosis and treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Two years follow-up of continuous erector spinae plane block in a patient with upper extremity complex regional pain syndrome type I.

BACKGROUND: Recalcitrant complex regional pain syndrome (CRPS) type 1 is a devastating condition. CASE PRESENTATION: We report a case of a patient in their twenties with left hand and forearm CRPS type I, transiently responsive to spinal cord stimulation, thoracic sympathectomy, and multimodal analgesia. The investigators initiated a trial of a single-shot erector spinae plane block at the T2 level, resulting in a clinically significant improvement in pain, function, vasomotor and sudomotor symptoms transiently for a 36-hour interval. As a result, a permanent e-port catheter implantation under combined ultrasound and fluoroscopic guidance was trialed. Two-year follow-up of the continuous erector spinae plane block (CESPB) indicated an 80% reduction in pain scores from baseline, and a 50% reduction in opiate consumption, with a clinically significant reduction in swelling, color changes, allodynia, and temperature asymmetry. CONCLUSION: Recalcitrant CRPS type 1 is a challenging life-altering condition that results in a cyclical triad of chronic pain, disability, and impaired psychosocial health. The profound and prolonged analgesic response to CESPB, highlights the clinical utility of this technique, and warrants more clinical investigation.

Successful treatment of complex regional pain syndrome type 1 of upper limb with cryoneurolysis of the stellate ganglion: A rare case report.

Complex regional pain syndrome type I (CRPS I) is a multifactorial condition that is related to neural damage, and leads to chronic neuropathic pain. Due to its multifactorial nature, there are many methods that have been recruited for its management. Most of them limit the symptoms to some degree, but the most effective of them so far seems to be blockade of the sympathetic innervation of the region. We present the case of a 71-year-old woman, with an upper limb fracture which was treated conservatively, and later on developed CRPS type I. Analgesic medications and pregabalin were ineffective in controlling her symptoms. Blockade of the stellate ganglion was performed with local anesthetic and dexamethasone. After the stellate ganglion blockade was marked as successful in relieving her symptoms, cryoneurolysis was performed which was very effective. There are not many cases that have been treated with cryoneurolysis, and this is what makes this case interesting.

The challenge of recognizing severe pain and autonomic abnormalities for early diagnosis of CRPS.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a disabling usually post-traumatic pain condition. International guidelines emphasize early diagnosis for treatment and improved outcome. Early intense and persistent pain along with features of autonomic dysfunction in the first week's post-injury are early warning signs for development of CRPS. We have previously reported a delayed diagnosis of CRPS. The main purpose of the present study was to investigate possible causes of a delayed diagnosis, with a special focus of recognition of risk factors. METHODS: A total of 52 CRPS 1 (without detectable nerve damage) and CRPS 2 (with evidence of nerve lesion) patients were included in the study. When examined at OUS-Rikshospitalet, we retrospectively asked the patients on the development of pain and autonomic abnormalities from the time of the eliciting injury, performed a thorough clinical investigation with an emphasis on signs of autonomic failure and compared symptoms and clinical findings with such information in previous medical records. We also evaluated symptoms and signs according to the type of injury they had suffered. RESULTS: Of a total of 52 patients (30 women and 22 men, mean age 39.0 years at the time of injury), 34 patients had CRPS type 1 (65.4%) and 18 CRPS type 2 (34.6%), 25 patients with pain in the upper and 27 in the lower extremity. A total of 35 patients (67.3%) were diagnosed with CRPS (following mean 2.1 years) prior to the investigation at OUS-Rikshospitalet (mean 4.86 years following injury). Mean time from injury to diagnosis was 33.5 months (SD 30.6) (2.8 years) for all patients. In retrospect, all 17 patients first diagnosed at OUS met the CRPS diagnosis at an earlier stage. All patients retrospectively reported intense pain (numeric rating scale > 7) from the time of injury with a large discrepancy to previous medical records which only stated intense pain in 29.4% of patients with CRPS type 1 and 44.4% of patients with CRPS type 2 within the first four months. While the patients reported an early onset of autonomic dysfunction, present in 67.3 and 94.2% of the patients within one week and one month, respectively, reports of autonomic abnormalities within the first four months was far less (maximum in 51.7% of patients with CRPS type 1 and in 60% in CRPS 2). In 10 patients with CRPS type 1, no symptom nor sign of autonomic abnormalities was reported. CONCLUSIONS: We still find a significant delay in the diagnosis of CRPS. There is a large discrepancy between both self-reporting of intense, disproportionate pain, as well as symptoms of autonomic abnormalities from the time of injury, and documentation in previous medical records. Our findings suggest a lack of awareness of risk factors for the development of CRPS, such as early intense pain and autonomic abnormalities without recovery, contributing to delayed diagnosis. The present results suggest causes of delayed CRPS-diagnosis. An increased attention to early warning signs/risk factors may improve diagnosis of CRPS.

Determinants of Diagnostic Delay in Complex Regional Pain Syndrome Type 1: An Observational Study of 180 Consecutive New Cases.

BACKGROUND/OBJECTIVE: Complex regional pain syndrome type 1 (CRPS-1) is a disabling painful disease, with variable outcomes in terms of chronic pain and disability. A long time between onset and diagnosis seems predictive for late recovery and progression toward a chronic disease. This study aims to investigate demographic and clinical variables associated with delayed CRPS-1 diagnosis. METHODS: From March 2013 to January 2018, consecutive patients newly diagnosed according to International Association for the Study of Pain diagnostic criteria for CRPS-1 were recruited. Demographic and clinical variables were collected at diagnosis. Student t test and Mann-Whitney U test were used for comparisons; Cox proportional hazards model was applied to evaluate the variables associated with delayed CRPS-1 diagnosis. RESULTS: One hundred eighty patients entered the study. At diagnosis, women were older, and foot was more often involved than hand. The triggering event was more commonly a trauma without fracture for foot disease and a fracture for hand localization. No differences between hand and foot disease were found by the International Association for the Study of Pain diagnostic categories (clinical vs research) or pain measures. Variables significantly associated with a longer time between disease onset and diagnosis were foot localization, general practitioner referral, higher number of visits before CRPS diagnosis, and prior physiotherapy prescribed for symptoms later diagnosed as CRPS. An overt clinical manifestation (research CRPS-1) predicted a shorter delay. CONCLUSIONS: Foot localization, prior physiotherapy prescribed for symptoms later diagnosed as CRPS, and a disease without overt clinical manifestations were independent predictive factors for a delayed diagnosis. Clinicians should pay attention to these issues to ensure a timely diagnosis and possibly avoid progression toward a chronic disease.

The Tourniquet Ischemia Test in the Diagnosis of Complex Regional Pain Syndrome.

BACKGROUND: The tourniquet ischemia test (IT) is a hitherto rarely used tool for the diagnostic work-up of patients with suspected complex regional pain syndrome (CRPS). This analysis aims to determine the sensitivity and specificity of this test, and elucidate factors that can influence the test result. METHODS: Consecutive data on clinical presentation, results of the IT and other diagnostic tests, and clinical characteristics were analyzed from patients presenting at our autonomic laboratory between 2000 and 2011. IT results were compared with the final clinical diagnosis at discharge, and statistical analysis was performed to determine specificity, sensitivity, and positive and negative predictive values of the IT. RESULTS: A total of 78 patients were assessed. IT results were positive (≥50% reduction in pain during ischemia) in 26 cases and negative in 52 cases. CRPS was the final diagnosis in 45 cases, and in 33 cases, a different diagnosis was made. This results in a test sensitivity of 49% and a specificity of 88%, with a positive predictive value of 85% and a negative predictive value of 56%. Age, sex, the type and stage of CRPS, and the affected extremity did not influence the test result in a statistically significant manner. Specificity worsened to 76% if any pain reduction was rated as a positive test result. CONCLUSIONS: A positive tourniquet IT has a high positive predictive value for the diagnosis of CRPS. It is thus useful as a confirmatory assay in patients with suspected CRPS. Low sensitivity rules out its use as a screening test. SIGNIFICANCE: This study retrospectively analyzed the clinical significance of the tourniquet IT that was routinely used in patients with suspected CRPS. It showed that a positive IT result is useful as a confirmatory assay in patients fulfilling the clinical criteria.

Complex regional pain syndrome following a centipede bite: a case report.

Context: Complex Regional Pain Syndrome (CRPS) is a chronic neuropathic pain condition associated with autonomic features. To date, the development of CRPS following centipede bite has not been reported. We report a case of CRPS likely secondary to a centipede bite.Case details: A 31-year-old female was bitten by a centipede on the right 2nd toe. She was initially treated with analgesics, and two weeks later developed severe pain, allodynia, pruritus, and edema of the right foot, with hyperpigmentation over the affected toe. The X-ray, ultrasound, electromyography, nerve conduction velocity studies of the foot, blood chemistries, and erythrocyte sedimentation rate showed no abnormalities. The patient was diagnosed with CRPS type 1 by fulfilling the Budapest criteria. She was treated with gabapentin, amitriptyline, desloratadine, and fluoxetine, along with physical rehabilitation. Clinical symptoms gradually improved, and resolved at approximately 9 months with persistent hyperpigmentation.Discussion: Centipede bite may be an eliciting event for CRPS. It is unknown whether direct bite trauma or envenomation was the primary etiology in this case. Awareness of this condition is important for early diagnosis and appropriate management.

Prognostic Factors in Complex Regional Pain Syndrome Type 1 Occurring in the Korean Army.

OBJECTIVES: In Korea, patients diagnosed with complex regional pain syndrome (CRPS) in the army are typically discharged from the army; however, the course of the disease after discharge is not known. The purpose of this study was to investigate the course of CRPS that occurred in the army and to identify the influences of various clinical and psychosocial factors immediately before discharge on the disease course. METHODS: Clinical profiles and psychosocial status were collected from the medical records of 16 patients with CRPS type 1 who were discharged during the period between March 2017 and April 2018. The degree of improvement after discharge was assessed by follow-up evaluation through telephone contact. Cox proportional hazards regression was performed to identify clinical and psychosocial predictors for the rate of recovery. RESULTS: The median time to recovery after discharge was 39 weeks (95% confidence interval [CI] = 8.8-69.2 weeks). The sole predictor for time to recovery after discharge was the time period from the onset of pain to discharge. Each one-week increase in the duration of pain experienced in the military was associated with a 18.2% (95% CI = 5.3%-29.5%) reduction in the rate of recovery after discharge (P = 0.007). CONCLUSIONS: Patients who experienced a short period of pain in the military demonstrated a relatively good prognosis after discharge. This may show how prolonged pain in the army could affect the experience of pain from a social point of view, in that it shows the disease course after a change in the social environment.

The Effectiveness of Fluidotherapy in Poststroke Complex Regional Pain Syndrome: A Randomized Controlled Study.

OBJECTIVE: To evaluate whether combining fluidotherapy to conventional rehabilitation program provides additional improvements on pain severity, upper extremity functions, and edema volume in patients with poststroke complex regional pain syndrome (CRPS). DESIGN: Randomized controlled trial. SETTING: Training and research hospital. PARTICIPANTS: Thirty hemiplegic patients with subacute stage CRPS type-1 of the upper extremity. INTERVENTIONS: The patients randomly divided into 2 groups. Both groups received a 3 week conventional rehabilitation program (5 days/week, 2-4 hours/day). Experimental group received 15 sessions additional fluidotherapy application to the affected upper extremity (40 °C, 20 minutes in continuous mode, 5 sessions/week). MAIN OUTCOME MEASURES: We evaluated the distal upper arm edema with a volumeter. Other used clinical assessment scales were Brunnstrom recovery stages of the arm and hand for motor recovery, motor items of the functional independence measure for functional status, visual analog scale for pain severity, and the painDETECT questionnaire for presence and the severity of neuropathic pain. RESULTS: The mean age of the participants was 64.3 ± 11.66 (28-84). At the post-treatment evaluation, significant improvements were revealed regarding to the edema volume, pain visual analog scale, painDETECT and functional independence measure scores, and the Brunnstrom stages of upper extremity and hand in both groups (P < .05). But among the parameters mentioned above, only the decrease in edema volume and the painDETECT scores were greater in fluidotherapy group than the control group (P < .05). CONCLUSIONS: Addition of the fluidotherapy to the conventional rehabilitation program provides better improvements on neuropathic pain and edema volume in subacute stage poststroke CRPS.

Electroacupuncture for Reflex Sympathetic Dystrophy after Stroke: A Meta-Analysis.

BACKGROUND: Reflex sympathetic dystrophy (RSD) is the common complication among stroke and cerebral injury patients, which is lack of safe and effective treatment. Electroacupuncture (EA) may potentially be a reliably therapy, but the evidence is insufficiency. METHODS: Cochrane Library, MEDLINE, Embase, Chinese National Knowledge Infrastructure, Wan Fang Data, the Chinese Biology Medicine disc, etc., were searched, until July 20, 2018. We included random control trials that contrast EA with conventional rehabilitation therapy for the treatment of RSD. Main outcomes were visual analog scale score and Fugl-Meyer upper limb motor function scoring scale, other outcomes such as Barthel index, and hand swelling score were also collected. Data in included studies were extracted into an excel and pooled by Stata/MP 14.1. RESULTS: We incorporated 13 studies involving 1040 RSD patients and outcomes were from 2 to 6 weeks' follow-up. The analgesic effect between 2 groups had statistically significant difference (weighted mean difference [WMD] = -1.122, 95% confidence interval [CI] [-1.682 to -.562], P = .000], a statistical difference existed in improving dysfunction between 2 groups: (WMD = 6.039, 95% CI [2.231-.916], P = .000). EA groups had a better effect on improving activities of daily life abilities (WMD = 12.170, 95% CI [6.657-17.682], P < .00011] and better detumescence effect (WMD = -.800, 95% CI [-1.972 to -.212], P = .000] contrast to conventional rehabilitation therapy. CONCLUSIONS: This meta-analysis supports that EA has a positive effect on alleviating pain, improving limb dysfunction, and promoting activities of daily living. On account of moderate-quality random control trials and high heterogeneity, further high-quality studies are imperative to optimize the EA treatment program.

The serum protease network-one key to understand complex regional pain syndrome pathophysiology.

Complex regional pain syndrome (CRPS) develops after fracture. The acute CRPS phenotype resembles exaggerated inflammation, which is explained by local and systemic activation of a proinflammatory network including peptides and cytokines. Epidemiologic data suggest that inactivation of the peptidase angiotensin-converting enzyme in patients treated for hypertension increases the odds to develop CRPS. This hint leads us to investigate the serum protease network activity in patients with CRPS vs respective controls. For this purpose, we developed a dabsyl-bradykinin (DBK)-based assay and used it to investigate patients with CRPS, as well as healthy and pain (painful diabetic neuropathy [dPNP]) controls. The major result is that the degradation of DBK to fragments 1-8 and 1-5 in healthy control and dPNP is shifted to higher values for DBK1-8 and lower values for DBK1-5 at 1 hour of incubation in patients with CRPS. Using this novel reporter peptide assay, we have been able to show that the resolving protease network for mediators such as BK might be different in patients with CRPS; having a look at the clinical signs, which resemble inflammation, this resolving protease network is probably less effective in CRPS.

Investigate the Effect of Psychological Factors in Development of Complex Regional Pain Syndrome Type I in Patients with Fracture of the Distal Radius: A Prospective Study.

BACKGROUND: To investigate the role of psychological factors (anxiety and depression) and pain measured on a visual analogue scale (VAS) in the development of complex regional pain syndrome type I (CRPS I) following the distal radius fracture (DRF). METHODS: A consecutive sample of patients (N=60) with a distal radius fracture was measured for signs of CRPS by Budapest criteria weekly till 8 weeks and then another follow-up one year after injury to determine the incidence and predictors of developing CRPS I in a prospective cohort study and also to discover whether there is difference between pain, depression, and anxiety level in the patients with and without CRPS I. The most of the patients were treated by Pin stabilization. The Beck depression inventoryshort form (BDI), State-Trait Anxiety Inventory, and Numerical pain rating scale were used to determine the patients' psychological features and pain intensity at the base line and 8 weeks after the fracture. RESULTS: CRPS I developed in 15 (25%) patients after eight weeks and just last in 10 (16.67%) patients after one year. No difference was found between the two groups (CRPS and non-CRPS group) in terms of state (STAI-I) and trait (STAI-II) anxiety, and BDI score. Pain at the base line was the most important risk factor in developing CRPS (odds ratio [OR] =1.52; 95% CI). CONCLUSIONS: After fracturing the distal radius, patients who have high pain intensity have a higher risk of developing CRPS I. To following these patients closely for the development of CRPS I may be advantageous for early preventative and therapeutic interventions.

Bisphosphonates in the treatment of complex regional pain syndrome: is bone the main player at early stage of the disease?

Complex Regional Pain Syndrome type 1 (CRPS-1) is a disabling painful disease whose hallmark is pain disproportionate to inciting event. CRPS is also characterized by symptoms and signs, such as vasomotor, sudomotor, trophic and motor changes. Therapeutic approach of CRPS-1 still remains a challenge for clinicians treating a disease with potential heavy consequences on patient prognosis. In the past years, the treatment with bisphosphonates (BPs) has gained some success as confirmed by the results of a number of meta-analyses. The aim of this paper is to point out the pivotal role of bone in CRPS pathogenesis. The efficacy of BPs is likely to be related to bone tissue involvement in the early pathophysiological steps of the disease, as demonstrated by evidences highlighting the central role of bone in the initial phases. Bone can become a source of inflammatory cytokines when triggered by a direct injury. Moreover, peptidergic fibers that innervate both mineralized bone and bone marrow can play a role in triggering or maintaining the microvascular disturbance at bone level. Indeed, bone involvement is consistent with the mineralization disturbance as well as the results of instrumental investigations (e.g., MRI, bone scan). In this regard, an intriguing issue relies on the excellent therapeutic response to BPs treatment of other diseases (e.g., Transient Osteoporosis of the Hip and Regional Migratory Osteoporosis) that share with CRPS-1 some clinical and instrumental features.