A brief review of complex regional pain syndrome and current management.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Complex regional pain syndrome (CRPS) is a debilitating and complex condition that places a significant physical, psychological and emotional burden upon afflicted patients necessitating multi-modal approaches to treatment.The development of the Budapest criteria provided a robust and well-tested set of diagnostic criteria to aid clinicians in the diagnosis of CRPS.The pathophysiology of CRPS has been challenging to elucidate with numerous proposed mechanisms, altogether suggesting a multi-factorial process is involved in the development of this condition.Non-invasive treatments for CRPS are essential in addressing the physical limitations this disease can cause as well as addressing the significant psychological burden that involves increased incidence of depression and suicidal ideation.Invasive treatments offer promising results, especially when considering dorsal root ganglion stimulation; however, the need for more robust clinical trials remains, especially when considering a small portion of patients who have refractory CRPS resort to amputation to control their pain symptoms.

Evidence of a genetic background predisposing to complex regional pain syndrome type 1.

BACKGROUND: Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition. METHODS: Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n=34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n=50). Gene expression of peripheral blood macrophages was assessed. RESULTS: In the discovery cohort, the rare allele frequencies of four non-synonymous SNPs were statistically increased. The replication cohort confirmed this finding. In a chronic pain cohort, these alleles were not overexpressed. In total, 25 out of 84 (29.8%) patients with CRPS-1 expressed a rare allele. The SNPs were rs41289586 in ANO10, rs28360457 in P2RX7, rs1126930 in PRKAG1 and rs80308281 in SLC12A9. Males were more likely than females to have a rare SNP allele, 8 out of 14 (57.1%) vs 17 out of 70 (24.3%) (Fisher's p=0.023). ANO10, P2RX7, PRKAG1 and SLC12A9 were all expressed in macrophages from healthy human controls. CONCLUSION: A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 was associated with developing chronic CRPS-1, with more males than females expressing these rare alleles. Our work suggests the possibility that a permissive genetic background is an important factor in the development of CRPS-1.

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: Evidence-Based Advances in Concepts and Treatments.

PURPOSE OF REVIEW: This review presents the most current information about the epidemiology of complex regional pain syndrome (CRPS), classification and diagnostic criteria, childhood CRPS, subtypes, pathophysiology, conventional and less conventional treatments, and preventive strategies. RECENT FINDINGS: CRPS is a painful disorder with multifactorial pathophysiology. The data describe sensitization of the central and peripheral nervous systems, inflammation, possible genetic factors, sympatho-afferent coupling, autoimmunity, and mental health factors as contributors to the syndrome. In addition to conventional subtypes (type I and type II), cluster analyses have uncovered other proposed subtypes. Prevalence of CRPS is approximately 1.2%, female gender is consistently associated with a higher risk of development, and substantial physical, emotional, and financial costs can result from the syndrome. Children with CRPS seem to benefit from multifaceted physical therapy leading to a high percentage of symptom-free patients. The best available evidence along with standard clinical practice supports pharmacological agents, physical and occupational therapy, sympathetic blocks for engaging physical restoration, steroids for acute CRPS, neuromodulation, ketamine, and intrathecal baclofen as therapeutic approaches. There are many emerging treatments that can be considered as a part of individualized, patient-centered care. Vitamin C may be preventive. CRPS can lead to progressively painful sensory and vascular changes, edema, limb weakness, and trophic disturbances, all of which substantially erode healthy living. Despite some progress in research, more comprehensive basic science investigation is needed to clarify the molecular mechanisms of the disease so that targeted treatments can be developed for better outcomes. Incorporating a variety of standard therapies with different modes of action may offer the most effective analgesia. Introducing less conventional approaches may also be helpful when traditional treatments fail to provide sufficient improvement.

Anxiety, Disability, and Pain Predict Outcomes of Complex Regional Pain Syndrome: An 8-year Follow-up of a Prospective Cohort.

Factors contributing to the varied outcomes of complex regional pain syndrome (CRPS) are not well known. This study aimed to determine whether baseline psychological factors, pain, and disability influence long-term CRPS outcomes. We conducted an 8-year follow-up from a previous prospective study of CRPS outcomes. Sixty-six people diagnosed with acute CRPS were previously assessed at baseline, 6 months, and 12 months and in the current study, 45 were followed up after 8 years. At each timepoint, we measured signs and symptoms of CRPS, pain, disability, and psychological factors. Mixed-model repeated measures were used to identify baseline predictors of CRPS severity, pain, and disability at 8 years. Predictors of greater CRPS severity at 8 years were female sex, greater baseline disability, and greater baseline pain. Predictors of greater pain at 8 years were greater baseline anxiety and disability. The only predictor of greater disability at 8 years was greater baseline pain. Findings suggest CRPS is best understood from a biopsychosocial perspective, and baseline anxiety, pain, and disability may influence the trajectory of CRPS outcomes as far as 8 years later. These variables could be used to identify those at risk of poor outcomes or form targets for early interventions. PERSPECTIVE: This paper presents the findings of the first study to prospectively investigate predictors of CRPS outcomes over 8 years. Baseline anxiety, pain, and disability predicted greater CRPS severity, pain, and disability over 8 years. These factors could identify those at risk of poor outcomes or form targets for early interventions.

Epidemiology of Upper Limb Complex Regional Pain Syndrome in a Retrospective Cohort of Persons Aged 9-30 Years, 2002-2017.

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.

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.

Post-fracture serum cytokine levels are not associated with a later diagnosis of complex regional pain syndrome: a case-control study nested in a prospective cohort study.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is a disabling pain disorder that is most common after a distal limb fracture. While the acute systemic immune response to the injury is thought to play a role in the development of CRPS, this hypothesis has never been tested directly. Thus, we evaluated whether elevated levels of circulating pro-inflammatory cytokines early after a fracture were associated with the development of CRPS. METHODS: We conducted a case-control study nested within a prospective cohort study. Individuals with wrist and/or hand fractures were recruited from specialist hand units. Baseline clinical data were obtained from participants within 28 days of fracture. CRPS status was determined 16 weeks after the fracture using a two-stage diagnostic process. Cytokine assays were obtained from all cases (defined using the Budapest criteria) and a random sample of those who did not have CRPS at 16 weeks. We calculated odds ratios with 95% confidence intervals to determine the risk of CRPS associated with the expression of each of 25 cytokines. RESULTS: Baseline data were collected for 702 consenting participants, of whom 535 provided blood samples. Follow-up at 16 weeks was 97.2%. 15 (2.2% of the cohort) met the Budapest CRPS criteria and 69 (including those who met the Budapest criteria; 9.8%) met the International Association for the Study of Pain (IASP) CRPS criteria. In all of the primary analyses (using Budapest criteria) and 49/50 secondary analyses (using IASP criteria), 95% confidence intervals for the association between cytokine levels and the risk of subsequently developing CRPS included the null value (OR = 1). However, the confidence intervals were wide. CONCLUSION: There was no evidence that early post-injury expression of systemic cytokines was associated with a CRPS diagnosis 16 weeks after injury. This study does not provide support for the hypothesis that innate immune activation has a determinative role in the development of CRPS.

Determinants of Complex Regional Pain Syndrome Type I among Radial Head Fracture Patients with Unilateral Arthroplasty.

OBJECTIVE: This study aims to assess the proportions of complex regional pain syndrome type I (CRPS I) in radial head fracture patients undergoing unilateral arthroplasty and to explore associated factors. METHODS: This is a prospective observational study. From March 2016 to May 2019, a total of 221 adult patients with radial head fracture patients were included in consecutive studies and completed the 1-year follow-up. All patients were treated by unilateral arthroplasty. At each follow-up visit, the visual analogue scale was used to measure patients' pain level. Occurrence of CRPS I, which was diagnosed by Budapest criteria, was the main outcome collected at baseline and the 1-, 3-, 6-, and 9-month follow-ups. The baseline data were collected before surgery and included demographic and clinical data. Independent t-tests and χ2 tests were used as univariate analyses to compare the baseline data of patients with and without CRPS I. Multivariate analysis (Backword-Wald) was used to identify factors independently associated with CRPS I. RESULTS: The proportion of CRPS I cases among radial head fracture patients undergoing unilateral arthroplasty was 11% (n = 24). A total of 19 (79%) patients were diagnosed with CRPS I within 1 month after surgery. Multivariable logistic regression analysis revealed that female gender (odds ratios [OR]: 1.537; 95% confidence interval [CI]: 1.138-2.072), age younger than 60 years (OR: 1.682; 95% CI: 1.246-2.267), moderate and severe Mayo Elbow Performance Score (MEPS) pain (OR: 3.229; 95% CI: 2.392-4.351) and anxiety (OR: 83.346; 95% CI: 61.752-112.320) were independently associated with CRPS I. CONCLUSIONS: This exploratory study reported that the incidence of CRPS I developing after radial head arthroplasty was 11%. Female sex, younger age, moderate and severe MEPS pain and anxiety patients seems more likely to develop CRPS I.

Relative Prevalence and Associated Factors of Complex Regional Pain Syndrome Type I in Patients with Radial Head Fractures Treated with Open Reduction and Internal Fixation: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to examine the incidence and associated factors of complex regional pain syndrome type I (CRPS I) in patients who underwent open reduction and internal fixation (ORIF) for radial head fractures. Methods: The study enrolled 601 radial head fracture patients treated with ORIF, 523 of which completed the 1-year follow-up. The incidence of CRPS I in those patients was assessed using the Budapest criteria. Patients were then divided into 2 groups: patients with CRPS I (n = 28) and patients without CRPS I (n = 495). The patients' demographic and clinical data before the operation were prospectively collected by our team. Independent t-tests and χ 2 tests were used as univariate analyses to compare the demographic and clinical data between the two groups. Meanwhile, multivariate regression analysis was conducted to identify the associated risk factors for CRPS I. Results: The incidence of CRPS I in patients with radial head fractures treated with ORIF was 5.5% during the first year following surgery. Significant differences were observed in age, gender, type of trauma, modified Mason Classification, and depressive personality disorders. The logistic regression analysis revealed that the female gender, modified Mason type III fractures, and depressive patients were significantly more likely to develop CRPS I (p=0.021, 0.023, and 0.025, respectively). Conclusions: The incidence of CRPS I among radial head fracture patients undergoing ORIF was 5.5%. In addition, early detection of CRPS I and providing adequate intervention will likely result in greater benefits for those patients.

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a "warm CRPS" phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P's < .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P's < .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P's < .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P's < .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

Treatment of Distal Radius Fracture: Does Early Activity Postinjury Lead to a Lower Incidence of Complex Regional Pain Syndrome?

Background: The optimal treatment for a distal radius fracture (DRF) remains an ongoing discussion. This study observed whether early activity postinjury can lead to the prevention of type 1 complex regional pain syndrome (CRPS-1). Method: Patients who underwent nonoperative treatment for a DRF were invited to participate in this study. Patients followed an exercise program with progressive loading exercises at home immediately after cast removal. After a minimum of 3 months, patients were interviewed by telephone to determine the presence of disproportionate pain. If present, the patients were seen during a clinical consultation to determine whether they had CRPS-1, using the Budapest Diagnostic Criteria. Results: Of the 129 patients included in this study, 12 reported disproportionate pain, and none were diagnosed with CRPS-1. The incidence of CRPS-1 was zero in this study. Conclusion: A more active treatment approach seems to lower the incidence of CRPS-1. A larger randomized study is necessary to strengthen the evidence.

Separating Fact From Fiction: A Nationwide Longitudinal Examination of Complex Regional Pain Syndrome Following Treatment of Dupuytren Contracture.

BACKGROUND: One of the most feared complications following treatment of Dupuytren contracture is complex regional pain syndrome (CRPS). This study aims to provide a national perspective on the incidence of CRPS following treatment of Dupuytren contracture and identify patient factors to target for risk reduction. METHODS: Using the Truven MarketScan databases from 2007 to 2016, individuals aged ≥18 years who developed CRPS within 1 year of treatment of Dupuytren contracture were identified using the International Classification of Disease diagnosis code for CRPS. Predictor variables included: age, sex, employment status, region, type of procedure, and concurrent carpal tunnel surgery. Multivariable logistic regression was used to analyze outcomes. RESULTS: In all, 48 327 patients received treatment for Dupuytren contracture, including collagenase injection (13.6%); percutaneous palmar fasciotomy (10.3%); open palmar fasciotomy (3.9%); palmar fasciectomy with 0 (10.8%), 1 (29.2%), or multiple (19.6%) digit releases; or a combination of these procedures (12.8%). One hundred forty-five patients (0.31%) were diagnosed with CRPS at a mean of 3.4 months (standard deviation, 2.3) following treatment. Significant predictors of CRPS included female sex (odds ratio [OR], 2.02; P < .001), Southern region (OR, 1.80; P = .022), long-term disability status (OR, 4.73; P = .035), palmar fasciectomy with release of 1 (OR, 5.91; P = .003) or >1 digit (OR, 13.32; P < .001), or multiple concurrent procedures for Dupuytren contracture (OR, 8.23; P = .001). CONCLUSIONS: Based on national commercial claims data, there is a lower incidence of CRPS following treatment of Dupuytren contracture than previously reported. Risk factors identified should help with preoperative counseling and assist clinicians in targeting risk reduction measures.

Prevalence and Related Factors for Poststroke Complex Regional Pain Syndrome: A Retrospective Cross-Sectional Cohort Study.

OBJECTIVE: The objective of this study was to evaluate the prevalence of poststroke complex regional pain syndrome (CRPS) to estimate related factors for poststroke CRPS in patients with first-ever stroke. DESIGN: This was a retrospective cross-sectional cohort study of adult patients (age >18y) with stroke who were admitted to rehabilitation unit from December 2014 to May 2018 in Korea. SETTING: Single acute rehabilitation unit of university hospital. PARTICIPANTS: Participants (N=313) diagnosed with first-ever stroke were identified from the stroke rehabilitation registry of our institute. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of poststroke CRPS based on clinical features and 3-phase bone scintigraphy and the related factors of poststroke CRPS. RESULTS: A total of 313 records were analyzed, including demographic, clinical characteristics, and functional variables. Poststroke CRPS was found in 8.94% (28 of 313) patients with first-ever stroke. Logistic regression analysis showed that Fugl Meyer Assessment of Upper Extremity (FMA-UE) score was a significant associated factor for the presence of CRPS (odds ratio, 0.96; 95% confidence interval, 0.94-0.98; P=.003). The cutoff value of 76 points for FMA-UE score yielded moderate accuracy in identifying of poststroke CRPS (92.6% sensitivity, 65.8% specificity, and 0.85 area under the curve). CONCLUSIONS: The prevalence of poststroke CRPS was 8.94% in patients with first-ever stroke. The FMA-UE score was associated with the poststroke CRPS. Therefore, in patients with low FMA-UE score, prevention and high suspicion of post-stroke CRPS is necessary.

Co-morbidity between trigeminal autonomic cephalalgias and complex regional pain syndrome: Two case reports.

BACKGROUND: Trigeminal autonomic cephalalgias and complex regional pain syndrome are rare conditions, and their co-occurrence has not been reported previously.Clinical findings: In two patients, ipsilateral trigeminal autonomic cephalalgias developed after the onset of upper limb complex regional pain syndrome. Hyperalgesia to thermal and mechanical stimuli extended beyond the affected limb to encompass the ipsilateral forehead, and was accompanied by ipsilateral hyperacusis and photophobia. In addition, examination of the painful limb and bright light appeared to aggravate symptoms of trigeminal autonomic cephalalgias. Detailed examination of the association between facial and upper limb pain indicated that both sources of pain cycled together. Furthermore, in one case, stellate ganglion blockade inhibited pain for an extended period not only in the affected limb but also the face. CONCLUSIONS: These findings suggest some overlap in the pathophysiology of complex regional pain syndrome and trigeminal autonomic cephalalgias. Specifically, central sensitization and/or disruption of inhibitory pain modulation on the affected side of the body in complex regional pain syndrome might trigger ipsilateral cranial symptoms and increase vulnerability to trigeminal autonomic cephalalgias.

Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

Complex regional pain syndrome type 1 (CRPS-I) is a complex complication that occurs after limb extremity surgeries. Controversy exists regarding the effectiveness of vitamin C in reducing that condition. Therefore, we conducted this systematic review and meta-analysis to assess the role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries. We searched Medline (via PubMed), Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar for relevant studies comparing perioperative vitamin C versus placebo after distal radius, wrist, foot, and ankle surgeries from infinity to May 2021. Continuous data such as functional outcomes and pain scores were pooled as mean differences, while dichotomous variables such as the incidence of complex regional pain syndrome and complications were pooled as odds ratios, with 95% confidence interval, using R software (meta package, version 4.9-0) for Windows. Eight studies were included. The timeframe for vitamin C administration in each study ranged from 42 to 50 days postinjury and/or surgical fixation. The effect size showed that vitamin C was associated with a decreased rate of CRPS-1 than placebo (odds ratio 0.33, 95% confidence interval [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (odds ratio 1.90, 95% confidence interval [0.99, 3.65]), functional outcomes (mean difference 6.37, 95% confidence interval [-1.40, 14.15]), and pain scores (mean difference -0.14, 95% confidence interval [-1.07, 0.79]). Overall, vitamin C was associated with a decreased rate of CRPS-I than placebo, while no significant difference was found regarding complications, functional outcomes, and pain scores. These results hold true when stratifying fracture type (distal radius, ankle, and foot surgeries) and vitamin C dose (500 mg or 1 g).

Canadian surveillance study of complex regional pain syndrome in children.

ABSTRACT: This study describes the minimum incidence of pediatric complex regional pain syndrome (CRPS), clinical features, and treatments recommended by pediatricians and pain clinics in Canada. Participants in the Canadian Paediatric Surveillance Program reported new cases of CRPS aged 2 to 18 years monthly and completed a detailed case reporting questionnaire from September 2017 to August 2019. Descriptive analysis was completed, and the annual incidence of CRPS by sex and age groupings was estimated. A total of 198 cases were reported to the Canadian Paediatric Surveillance Program, and 168 (84.8%) met the case definition. The minimum Canadian incidence of CRPS is estimated at 1.14/100,000 (95% confidence interval 0.93-1.35/100,000) children per year. Incidence was highest among girls 12 years and older (3.10, 95% confidence interval 2.76-3.44/100,000). The mean age of CRPS diagnosis was 12.2 years (SD = 2.4), with the mean time from symptom onset to diagnosis of 5.6 months (SD = 9.9) and no known inciting event for 19.6% of cases. Most cases had lower limb involvement (79.8%). Nonsteroidal anti-inflammatory drugs (82.7%) and acetaminophen (66.0%) were prescribed more commonly than antiepileptic drugs (52.3%) and antidepressants (32.0%). Referrals most commonly included physical therapy (83.3%) and multidisciplinary pain clinics (72.6%); a small number of patients withdrew from treatment because of pain exacerbation (5.3%). Pain education was recommended for only 65.6% of cases. Treatment variability highlights the need for empiric data to support treatment of pediatric CRPS and development of treatment consensus guidelines.

A Meta-Analysis and Meta-Regression of Frequency and Risk Factors for Poststroke Complex Regional Pain Syndrome.

Background and Objectives: This article aimed to investigate the risk factors for poststroke complex regional pain syndrome (CRPS). Materials and Methods: We searched electronic databases including PubMed, Medline, Web of Science, Cochrane Library, and Embase up to 27 October 2021. We enrolled analytical epidemiological studies comprising cohort, case-control, and cross-sectional studies. A quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies and the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Binary outcomes were reported as odds ratios (ORs), and continuous outcomes were described as standardized mean differences (SMDs) with 95% confidence intervals. For the meta-regression, beta coefficient and p value were adopted. Results: We included 21 articles comprising 2225 participants. Individuals with shoulder subluxation and spasticity were found to have higher risks for poststroke CRPS. Spasticity with higher modified Ashworth scale score, lower Brunnstrom hand stage, and inferior Barthel index scores were observed in patients with poststroke CRPS. The pooled incidence proportion in nine articles was 31.7%, and a correlation was found between effect sizes and the ratio of women and the proportion of left hemiparesis. The summarized prevalence in nine cross-sectional studies was 33.1%, and a correlation was observed between prevalence and the subluxation ratio and Brunnstrom stage. Conclusions: Based on our meta-analysis, being female, left hemiparesis, shoulder subluxation, spasticity, a lower Brunnstrom stage of distal upper limb, and an inferior Barthel index are all features for poststroke CRPS. Larger studies with greater statistical power may confirm our findings and clarify some other unknown risk factors for poststroke CRPS.