A decision tree algorithm to identify predictors of post-stroke complex regional pain syndrome.

This prospective cohort study aimed to identify the risk factors for post-stroke complex regional pain syndrome (CRPS) using a decision tree algorithm while comprehensively assessing upper limb and lower limb disuse and physical inactivity. Upper limb disuse (Fugl-Meyer assessment of upper extremity [FMA-UE], Action Research Arm Test, Motor Activity Log), lower limb disuse (Fugl-Meyer Assessment of lower extremity [FMA-LE]), balance performance (Berg balance scale), and physical inactivity time (International Physical Activity Questionnaire-Short Form [IPAQ-SF]) of 195 stroke patients who visited the Kishiwada Rehabilitation Hospital were assessed at admission. The incidence of post-stroke CRPS was 15.4% in all stroke patients 3 months after admission. The IPAQ, FMA-UE, and FMA-LE were extracted as risk factors for post-stroke CRPS. According to the decision tree algorithm, the incidence of post-stroke CRPS was 1.5% in patients with a short physical inactivity time (IPAQ-SF < 635), while it increased to 84.6% in patients with a long inactivity time (IPAQ-SF ≥ 635) and severe disuse of upper and lower limbs (FMA-UE score < 19.5; FMA-LE score < 16.5). The incidence of post-stroke CRPS may increase with lower-limb disuse and physical inactivity, in addition to upper-limb disuse. Increasing physical activity and addressing lower- and upper-limb motor paralysis may reduce post-stroke CRPS.

Case report: Dorsal root ganglion stimulator lead fracture.

BACKGROUND: One of the unique advances in neuromodulation for chronic pain has been spinal cord stimulators (SCS) and dorsal root ganglion stimulators (DRG-S). These devices have aided in conditions such as neuropathic pain, complex regional pain syndromes, failed back surgery, and peripheral neuropathies. With these benefits, however, complications from implantable stimulators have included lead fractures and migration. The authors reviewed a lead migration, kinking, and subsequent fracture event involving a patient with complex regional pain syndrome (CRPS) II, who was treated with a DRG-S. CASE PRESENTATION: The case report follows this patient, from their past medical history to assessment of appropriate qualifications for neuromodulation, to successful surgical placement, to follow-up care. The authors further monitored assessment of inefficacy of pain relief, and identification of lead migration and kinking through imaging. In the process of removal, due to lead stress, lead fracturing occurred. After lead removal, the leads were fully replaced, and the patient was followed up and experienced improved pain relief. CONCLUSION: The case report assesses probable mechanisms of lead fracture and considerations for physicians for future assessment and triage of neuromodulation efficacy.

Prevalence and predisposing factors of post-stroke complex regional pain syndrome: Retrospective case-control study.

INTRODUCTION: Poststroke complex regional pain syndrome (CRPS) is an important complication in stroke survivors. The identification of factors associated with post-stroke CRPS is important for preventive measures and early diagnosis. METHODS: A total of 141 first-ever stroke survivors in the subacute stage were retrospectively analyzed. Demographic data, diagnosis time, duration of hospitalization, location of brain lesion, etiology, comorbidities, and blood test findings were investigated. Clinical data included Medical Research Council (MRC) grade, Fugl-Meyer assessment (FMA), National Institute for Health Stroke Scale (NIHSS), Berg Balance Scale (BBS). RESULTS: Among 141 patients with subacute stroke, 22 were diagnosed with CRPS, with a prevalence of 15.6 %. The mean time to diagnosis was 38.6 (±16.5) days. The prevalence according to the degree of paralysis was 33.3 % in MRC grades 0 and 1, 8.6 % in grade 2, and 0 % in grade 3 or higher. The incidence rates within 1 month after stroke were 1.42 % and 22.47 % between 1 and 3 months after stroke, respectively. The independent risk factors for CRPS were hospitalization duration and FMA, NIHSS, and BBS scores. The sensitivity and specificity of the NIHSS score for predicting post-stroke CRPS were 86.4 % and 59.7 %, respectively, with an optimal cutoff value of 7.5. CONCLUSIONS: CRPS of the affected upper limb in stroke patients is associated with stroke severity, including paralysis, and the incidence increases over time during the subacute phase. Additionally, having sufficient strength to move through a full range of motion against gravity had a protective effect against CRPS.

Patients With Preexisting Anxiety and Mood Disorders Are More Likely to Develop Complex Regional Pain Syndrome After Fractures.

BACKGROUND: Complex regional pain syndrome (CRPS) is a multifactorial condition that may affect patients who sustain a fracture in the upper and lower extremities. Prior investigations have formed a foundation for exploring a possible association between psychiatric disorders and the development of CRPS; however, current studies are conflicted regarding the existence and temporality of a relationship between psychiatric disorders and the potential development of CRPS. QUESTIONS/PURPOSES: (1) Are patients with preexisting anxiety and mood disorders (AMDs) at increased risk of receiving a diagnosis of CRPS after upper or lower extremity fractures? (2) Are patients with preexisting AMDs at increased risk of being diagnosed with CRPS after surgical fixation of their fracture? METHODS: A large, retrospective cohort study was conducted using the TriNetX electronic medical record platform, which contains data from more than 100 million patients. This platform gathers data from healthcare organizations in the United States and Europe and collects comprehensive data over time that includes temporality rather than simply the binary presence or absence of conditions. The cohort included 760,595 patients older than 18 years with upper or lower extremity fractures between 2003 and 2022. Included patients had a minimum 1-year follow-up. We defined AMDs as any diagnosis of anxiety, depressive episode or disorder, a manic episode, or bipolar disorder. Patients with polytrauma or concurrent upper and lower extremity fractures were excluded to reduce confounders. CRPS I diagnosis was identified via International Classification of Diseases, Tenth Edition codes. Propensity score matching was performed to balance cohorts based on age, gender, and race. Hazard ratios and Aalen-Johansen cumulative incidence curves for the diagnosis of CRPS were calculated for patients with and without AMD diagnoses before sustaining a fracture. A subanalysis was performed in which we examined individuals in the upper and lower extremity fracture cohorts who underwent surgical treatment. RESULTS: Patients with preexisting AMDs were at a higher risk of experiencing CRPS I than patients without AMDs were (upper extremity: HR 1.8 [95% CI 1.7 to 1.9]; p < 0.01, lower extremity: HR 2.2 [95% CI 2.0 to 2.3]; p < 0.01). Similarly, patients with preexisting AMDs were at higher risk of experiencing CRPS I after fracture fixation than patients without AMDs were (upper extremity: HR 1.3 [95% CI 1.2 to 1.5]; p < 0.01, lower extremity: HR 2.3 [95% CI 2.1 to 2.5]; p < 0.01). CONCLUSION: Awareness of the relationship between AMDs and CRPS I will direct future research about the development of this condition and associated neurologic changes. Additionally, surgeons can address AMDs perioperatively and arrange for the treatment of these AMDs with psychiatrists, neurologists, or social work, as appropriate. Accordingly, patients with AMDs should also be made aware of the inherent risk of CRPS I after an upper or lower extremity fracture to comprehensively educate and care for this at-risk patient population. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

Animal models of complex regional pain syndrome: A scoping review.

BACKGROUND: complex regional pain syndrome (CRPS) leads to a debilitating chronic pain condition. The lack of cause, etiology, and treatment for CRPS has been widely explored in animal models. OBJECTIVE: Provide a comprehensive framework of the animal models used for investigating CRPS. ELIGIBILITY CRITERIA: Preclinical studies to induce the characteristics of CRPS, with a control group, in any language or publication date. SOURCES OF EVIDENCE: The search was performed in the Medline (PubMed) and ScienceDirect databases. RESULTS: 93 studies are included. The main objective of the included studies was to understand the CRPS model. Rats, males and adults, exposed to ischemia/reperfusion of the paw or fracture of the tibia were the most common characteristics. Nociceptive evaluation using von Frey monofilaments was the most widely adopted in the studies. CONCLUSIONS: For the best translational science between the animal models and individuals with CRPS, future studies should include more heterogeneous animals, and multiple assessment tools, in addition to improving the description and performance of measures that reduce the risk of bias.

[Complex regional pain syndrome]. / Syndrome douloureux régional complexe.

Complex regional pain syndrome is a clinical entity that usually occurs following trauma, surgery, or other triggering event. Patients complain of pain described as burning, associated with sensory, vasomotor, sudomotor, motor and/or trophic disorders. The pain appears disproportionate to the initial lesion. The diagnosis is purely clinical and based on the Budapest criteria. It is a diagnosis of exclusion. The pathophysiology is still poorly understood and is thought to be multifactorial. Several mechanisms have been described: an inflammatory state, an overactivation of the sympathetic autonomic nervous system and a poor perception of pain at the central level. The management of signs and symptoms is therefore global. It involves physiotherapy and occupational therapy, often combined with analgesic medications. Psychological treatment may be proposed in certain circumstances. The natural evolution is rather favourable.

Le syndrome douloureux régional complexe constitue une entité clinique survenant habituellement suite à un traumatisme, une chirurgie ou un autre événement déclencheur. Les patients se plaignent d'une douleur décrite comme une brûlure, associée à des troubles sensoriels, vasomoteurs, sudomoteurs, moteurs et/ou trophiques. La douleur apparaît disproportionnée par rapport à la lésion initiale. Le diagnostic est purement clinique et repose sur les critères de Budapest. Il s'agit d'un diagnostic d'exclusion. La physiopathologie est encore peu connue, et serait multifactorielle. Plusieurs mécanismes sont décrits : un état inflammatoire, une suractivation du système nerveux autonome sympathique et une mauvaise perception de la douleur au niveau central. La prise en charge des signes et symptômes est donc globale. Elle fait intervenir une rééducation en kinésithérapie et ergothérapie, souvent associée à un traitement antalgique médicamenteux. Une prise en charge en psychologie peut être proposée dans certaines circonstances. L'évolution naturelle est plutôt favorable.

Latent infection after spinal cord stimulation device implantation for complex regional pain syndrome: A case report.

RATIONALE: Spinal cord stimulation (SCS) is one of the invasive treatments of complex regional pain syndrome (CRPS). The positive effect has been observed for several years after implantation. However, infection is a common cause of SCS failure and device removal. PATIENT CONCERNS: Here we describe a case of latent infection at the implantable generator pocket site 9 years after SCS implantation in a patient with CRPS. DIAGNOSES: A 52-year-old patient was diagnosed with type 1 CRPS. The right foot pain was intractable with standard treatments. SCS implantation was performed and SCS worked well without complication. Nine years later, the patient revisited due to pain, tenderness, and redness at the abdominal wall for 2 weeks. The right foot pain was maintained with NRS 4 for 8 years, and the stimulation stopped 1 year back. SCS infection was diagnosed. INTERVENTIONS: The patient underwent SCS removal surgery. OUTCOMES: All SCS devices were removed successfully. The patient was discharged without any complications. CONCLUSIONS: While uncommon, infection after SCS implantation can occur even 9 years later. Immediate diagnosis, proper antibiotics, and surgical removal could be needed to prevent further spread of infection and better prognosis.

Management of complex regional pain syndrome in trauma and orthopaedic surgery-a systematic review.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a neurological pain disorder that is challenging to diagnose and manage, resulting in increased morbidity and costs. It most commonly occurs following traumatic injury, such as a fracture, crush injury or surgery. Recent research has evaluated the efficacy of treatments which have contradicted previous hypotheses. This systematic review summarizes these findings to improve clinician's decision-making. SOURCES OF DATA: A comprehensive search of PubMed, MEDLINE and Embase databases from inception through January 2021 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened relevant articles discussing the management of CRPS in adult trauma patients. All prospective and retrospective studies, non-randomized comparison studies and case series were considered for inclusion. Data extraction was performed by populating a predefined data abstraction sheet. AREAS OF AGREEMENT: There is strong evidence to suggest the efficacy of prompt physiotherapy, lidocaine, ketamine, bisphosphonates, sympathectomy and brachial plexus blocks in the management of CRPS. AREAS OF CONTROVERSY: The latest evidence suggests that vitamin C has no significant role to play in the treatment or prevention of CRPS. GROWING POINTS: A multidisciplinary team approach and early diagnosis are imperative for successful treatment of CRPS. The Budapest criteria and the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines should be used when diagnosing CRPS. There is currently no clear evidence of superiority in any treatment. AREAS TIMELY FOR DEVELOPING RESEARCH: There are few high-quality studies that inform the best treatment modalities for CRPS. Though emerging treatments show promise, further research is needed.

Incidence and risk factors for complex regional pain syndrome in radius fractures: meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the incidence and risk factors for complex regional pain syndrome (CRPS) in radius fractures. METHODS: The meta-analysis was performed using the PubMed, Embase, Scopus, and Cochrane Collaboration Library databases. Studies focusing on patients with conservative or surgically treated radius fractures leading to CRPS were included. A control group consisting of patients with radius fractures and no CRPS (-) was included. The outcome measures were incidence and risk factors. Comparative studies were also included. Data were combined using Review Manager 5.4. RESULTS: Out of 610 studies, nine studies were included. The incidence of CRPS after radius fractures ranged from 0.19 to 13.63% (95% CI: 11.12-16.15%). Open fractures, high-energy mechanisms in radial head fractures, and associations with ulnar fractures were risk factors for CRPS [(RR: 0.98; 95% CI: 0.97-1.00), (RR: 0.18; 95% CI: 0.07-0.47), and (RR: 1.25; 95% CI: 1.17-1.35), respectively]. Other risk factors were female sex and high body mass index [(RR: 1.20; 95% CI: 1.05-1.37) and (MD: 1.17; 95% CI: 0.45-1.88)]. Psychiatric factors also increased the incidence of CRPS (RR: 2.04; 95% CI: 1.83-2.28). On the other hand, the type of surgery (external fixation or open reduction and internal fixation) and manipulations; associated comorbidities (diabetes and hypertension) together with tobacco and alcohol abuse; marital status, educational level, employment status, and socioeconomic status were not risk factors (p > 0.05). CONCLUSION: The incidence of CRPS in radius fractures was 13.63%. Fractures with greater complexity or greater associated tissue damage, female sex, high BMI, and psychiatric disorders were risk factors for the development of CRPS. LEVEL OF EVIDENCE: Meta-analysis of cohort and case series studies; II.

Diagnosis and Outcomes of 225 Consecutive Cases of Complex Regional Pain Syndrome of the Hand.

BACKGROUND: The lack of specific tests and potential diagnostic inaccuracy may be behind the stunning figures of complex regional pain syndrome (CRPS) cases. The author tested the hypothesis that patients diagnosed with CRPS at referral could be assigned to recognized conditions and treated accordingly. METHODS: From January of 2018 to April of 2021, 225 consecutive patients attended the author's office having been diagnosed with and treated for CRPS for an average of 16 ± 26 months. There were 180 women and 45 men; no patient was excluded. RESULTS: All patients could be allocated in named conditions: 79 had a wrong diagnosis; seven had a true causalgia; 16 were dystonic-psychogenic hands; 20 presented a flare reaction; and 90 had an "irritative" carpal tunnel syndrome. The remaining 13 patients had a miscellany of symptoms within a substandard management setting. Surgery was offered to 175 with a correctable cause; 50 (20 of whom had a tangible cause responsible for their pain) declined, and their outcome is unknown. The remaining 125 were operated on and tracked for an average of 20 ± 9 months. In the operated group, pain dropped 7.5 ± 2.2 points ( P < 0.0001) on a numerical rating scale of 0 to 10. Disabilities of the Arm, Shoulder, and Hand questionnaire scores fell from 80 to 16 ( P < 0.0001). Patients who were operated on rated their satisfaction on a scale of 0 to 10 as 8.9 ± 1.9. CONCLUSIONS: Unlike with CRPS, all patients in this series had a true, diagnosable condition explaining their clinical picture. Most patients who agreed to be operated on had a favorable outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Usefulness of the perfusion index for monitoring the response to intravenous ketamine infusion therapy in patients with complex regional pain syndrome.

BACKGROUND: This study was performed to compare the perfusion index (PI) between affected and unaffected limbs in patients with complex regional pain syndrome (CRPS); it also evaluated the usefulness of the PI for monitoring the response to intravenous ketamine infusion therapy in such patients. METHODS: In total, 46 patients with CRPS in one arm or leg were enrolled in this study. The PIs of the unaffected (PIControl ) and affected (PICRPS ) limbs were simultaneously evaluated before and after treatment. RESULTS: PICRPS was significantly lower than PIControl at all time points. The change in PI from immediately before to 30 min after intravenous ketamine infusion therapy (TBefore and T30 min , respectively) in the affected limb was significantly correlated with the change in visual analog pain scale (VAS) between the two time points (r = 0.646, p < 0.001). The area under the curve for the changes in VAS and PICRPS between TBefore and T30 min was 0.928. The optimal threshold value for the change in PICRPS between TBefore and T30 min , to distinguish responders with a ≥ 50-point reduction in VAS score from nonresponders, was 22.60% with a sensitivity of 0.811 (95% CI: 0.774-0.848) and a specificity of 0.889 (95% CI: 0.848-0.930). Thirty-one patients showed a ≥ 50-point reduction in VAS score [67% (95% CI: 54%-80%)] and 15 patients showed a < 50-point reduction in VAS score [33% (95% CI: 20%-46%)]. Thirty patients showed an increased PI ≥ 22.60% [65% (95% CI: 50%-78%)] and 16 patients showed an increased PI < 22.60% [35% (95% CI: 22%-50%)]. Twenty-seven patients had a ≥ 50-point reduction in VAS score and an increased PI ≥ 22.60% [59% (95% CI: 44%-74%)]. Eleven patients had shown a < 50-point pain reduction in VAS score and increased PI < 22.60% [24% (95% CI: 13%-37%)]. CONCLUSION: The PI significantly differed between affected and unaffected limbs in patients with CRPS. The PI may be useful for monitoring the response to intravenous ketamine therapy in patients with CRPS.

Comparison of Epidemiological Data of Complex Regional Pain Syndrome (CRPS) Patients in Relation to Disease Severity-A Retrospective Single-Center Study.

A retrospective data analysis of 159 complex regional pain syndrome (CRPS) patients (n = 116 women, 73.0%, mean age 60.9 ± 14.4 years; n = 43 men, 27.0%, mean age 52.3 ± 16.7 years) was performed from 2009 to 2020. The right side was affected in 74 patients (46.5%), the left in 84 patients (52.8%), and 1 patient (0.7%) developed a bilateral CRPS. Data were analyzed for the frequency and distribution of symptoms. The number of reduction maneuvers and the number of Budapest criteria were compared in relation to the severity of CRPS. Hand and wrist (n = 107, 67.3%), followed by foot and ankle (n = 36, 22.6%) and other locations (n = 16, 10.1%) were mainly affected by CRPS. The main causes included direct trauma (n = 120, 75.5%), surgery without previous trauma (n = 25, 15.7%), other causes (n = 9, 5.7%), and spontaneous development (n = 3, 1.9%); there was also missing documentation (n = 2, 1.3%). The most common symptoms were difference in temperature (n = 156, 98.1%), limitation of movement (n = 149, 93.7%), and swelling (n = 146, 91.8%). There was no correlation between the number of reduction maneuvers and the number of Budapest criteria. In summary, patients with the following constellation are at increased risk of CRPS: a female, over 60 years old, who has fallen and has sustained a fracture in the hand or wrist with persistent pain and has been immobilized with a cast for approx. 4 weeks.

Complex regional pain syndrome after mRNA-based COVID-19 vaccination.

We describe the case of a 17-year-old woman diagnosed with complex regional pain syndrome (CRPS) at a pain clinic after the second dose of the COVID-19 vaccine. She was referred to our department for surgical treatment of movement disorder seven months after the second inoculation. Baclofen (50 µg), administered intrathecally, improved the involuntary movements of her right hand. After administration of zolpidem (5 mg), involuntary movements of the right index finger almost disappeared. However, neither zolpidem nor intrathecal baclofen improved the limited range of motion of the first joint of the left-hand finger. Despite various reports on CRPS development after vaccination, only one case post COVID-19 vaccination has been reported. Therefore, healthcare providers should keep in mind that CRPS can appear after the COVID-19 vaccination.

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.

Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. MATERIALS AND METHODS: This study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. RESULTS: In total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. CONCLUSIONS: Standard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research. ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Glomus Tumor of the Lower Extremity Previously Misdiagnosed as Complex Regional Pain Syndrome in Close Proximity to a Myxofibrosarcoma: A Case Report.

Complex regional pain syndrome (CRPS) is a potentially devastating condition that can result in severe psychological and social morbidity. It is a diagnosis of exclusion, and other pathologic entities must be ruled out first. Glomus tumors are exquisitely painful benign vascular tumors that are most common in the hand and are rarely found in the lower extremity. Here, we present a case of a patient who developed a focus of severe anterior knee pain and tenderness a few months after a car accident that had been misdiagnosed as CRPS for 15 years. She coincidentally developed a sarcoma of her ipsilateral leg distal to this site. Magnetic resonance imaging of the sarcoma included the area of knee pain where, interestingly, it identified a separate small soft-tissue mass. A glomus tumor was diagnosed histologically in a needle biopsy specimen from this mass, which was resected along with the sarcoma. For the first time in 15 years, despite the additional sarcoma surgery, she reported relief of her pain and complete resolution of her "CRPS."