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.
ABSTRACT
This topical update reports recent progress in the international effort to develop a more accurate and valid diagnostic criteria for complex regional pain syndrome (CRPS). The diagnostic ...entity of CRPS (published in the International Association for the Study of Pain’s Taxonomy monograph in 1994; International Association for the Study of Pain IASP) was intended to be descriptive, general, and not imply etiopathology, and had the potential to lead to improved clinical communication and greater generalizability across research samples. Unfortunately, realization of this potential has been limited by the fact that these criteria were based solely on consensus and utilization of the criteria in the literature has been sporadic at best. As a consequence, the full potential benefits of the IASP criteria have not been realized. Consensus‐derived criteria that are not subsequently validated may lead to over‐ or underdiagnosis, and will reduce the ability to provide timely and optimal treatment. Results of validation studies to date suggest that the IASP/CRPS diagnostic criteria are adequately sensitive; however, both internal and external validation research suggests that utilization of these criteria causes problems of overdiagnosis due to poor specificity. This update summarizes the latest international consensus group’s action in Budapest, Hungary to approve and codify empirically validated, statistically derived revisions of the IASP criteria for CRPS.
Complex regional pain syndrome (CRPS) develops after-limb injury, with persistent pain and deficits in movement frequently co-occurring. The striatum is critical for mediating multiple mechanisms ...that are often aberrant in CRPS, which includes sensory and pain processing, motor function, and goal-directed behaviors associated with movement. Yet, much remains unknown with regards to the morphological and functional properties of the striatum and its subregions in this disease. Thus, we investigated 20 patients (15 female, age 58 ± 9 years, right-handed) diagnosed with chronic (6+ months of pain duration) CRPS in the right hand and 20 matched, healthy controls with anatomical and resting-state, functional magnetic resonance imaging. In addition, a comprehensive clinical and behavioral evaluation was performed, where each participant's pain, motor function, and medical history were assessed. Complex regional pain syndrome patients harbored significant abnormalities in hand coordination, dexterity, and strength. These clinical pain- and movement-related findings in CRPS patients were concomitant with bilateral decreases in gray matter density in the putamen as well as functional connectivity increases and decreases among the putamen and pre-/postcentral gyri and cerebellum, respectively. Importantly, higher levels of clinical pain and motor impairment were associated with increased putamen-pre-/postcentral gyri functional connectivity strengths. Collectively, these findings suggest that putaminal alterations, specifically the functional interactions with sensorimotor structures, may underpin clinical pain and motor impairment in chronic CRPS patients.
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.
Here we describe a case of latent infection at the implantable generator pocket site 9 years after SCS implantation in a patient with CRPS.
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.
The patient underwent SCS removal surgery.
All SCS devices were removed successfully. The patient was discharged without any complications.
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.
Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three ...stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels.
We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts.
In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4 weeks but not 16 weeks. However, spinal levels of NK1 receptor, TNFα, IL-1β, and NGF were elevated at 4 and 16 weeks, and intrathecal injection of an NK1-receptor antagonist (LY303870), anakinra, or anti-NGF each reduced nociceptive behaviors at both 4 and 16 weeks.
These results demonstrate that tibia fracture and immobilization cause peripheral changes in neuropeptide signaling and inflammatory mediator production acutely, but central spinal changes may be more important for the persistent nociceptive changes in this CRPS model.
Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison with healthy or pain ...controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patient-reported outcomes, and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FCs) not fulfilling the CRPS diagnostic criteria. We included upper-extremity FCs, acute CRPS I patients within 1 year after trauma, a second disease control group (painful diabetic polyneuropathy), and healthy controls. Fracture controls were not symptoms-free, but reported some pain, disability, anxiety, and cold pain hyperalgesia in quantitative sensory testing. Patients with CRPS had higher scores for pain, disability, and all patient-reported outcomes. In quantitative sensory testing, ipsilateral and contralateral sides differed significantly. However, on the affected side, patients with CRPS were more sensitive in only 3 parameters (pinprick pain and blunt pressure) when compared to FCs. Two principal components were identified in the cohort: pain and psychological parameters distinguishing FC and CPRS. Furthermore, the immunobarrier-protective hsa-miR-223-5p was increased in plasma exosomes in FCs with normal healing, but not in CRPS and healthy controls. Low hsa-miR-223-5p was particularly observed in subjects with edema pointing towards barrier breakdown. In summary, normal trauma healing includes some CRPS signs and symptoms. It is the combination of different factors that distinguish CRPS and FC. Fracture control as a control group can assist to discover resolution factors after trauma.
People with Complex Regional Pain Syndrome (CRPS) following limb injury can show neuropsychological symptoms in the absence of observable brain pathologies. These can include sensory changes, ...distorted body representation, and inattention to their affected limb and its surrounding space, resembling post-stroke hemispatial neglect. The precise nature and mechanisms of these neuropsychological symptoms are unclear, however insights could be gained by testing for dissociations and associations that have been observed in stroke patients. Drawing from clinical and experimental methods for investigating spatial attention bias and related symptoms in stroke patients, we conducted a detailed investigation of neuropsychological symptoms in a woman with CRPS of her left arm who initially presented to us with pronounced inattention to her affected side. The patient showed visual and tactile neglect and extinction on her affected side on confrontation tests, but no attention deficits on “bedside” tests of neglect. On sensitive computer-based measures, attention biases were found in the patient's body and near space (in Temporal Order Judgements), but not far or imagined space (on the Greyscales task and Mental Number Line Bisection). Unique to the current literature, the patient showed a reversal in her Temporal Order Judgement bias across time, from inattention (first and second session) to hyperattention (third session) to her affected side. In contrast, pain and self-reported body representation distortion were similar across the three sessions. The patient had reduced central and peripheral visual acuity, however these deficits were near symmetrical and therefore could not explain her performance on the visual attention tasks. Given that spatial attention bias has been linked to imbalance in relative activation of the two cerebral hemispheres, we administered a Global-Local processing task to test for hemispheric asymmetry. This revealed no difference in global compared to local interference refuting any hemispheric imbalance. Instead, the patient showed impaired performance (compared to controls) on incongruent trials regardless of trial type, consistent with executive impairment. We conclude that spatial attention bias in CRPS can generalize across different sensory modalities and extend beyond the affected limb to the external space around it, independent of any low-level sensory disturbances. This bias is not necessarily directed away from the affected side or stable over time. People with CRPS can also demonstrate more generalized neuropsychological changes in sensory and executive functions. Our observations refute several existing theories about the mechanisms of attention bias in CRPS, and their relationship to pain, and have potential implications for treatment.
•A woman with Complex Regional Pain Syndrome (CRPS) showed altered spatial attention.•Attention shifted over time: from less, to more attention to her affected side.•This shift was independent of pain intensity and cognitive body representation.•Attention bias in CRPS can vary over time, and may be unrelated to pain.•This calls into question the role of spatial attention bias in the CRPS.
OBJECTIVESTo develop and test a new immersive digital technology for complex regional pain syndrome (CRPS) that combines principles from mirror therapy and immersive virtual reality and the latest ...research from multisensory body processing.
METHODSIn this crossover double-blind study, 24 patients with CRPS and 24 age- and sex-matched healthy controls were immersed in a virtual environment and shown a virtual depiction of their affected limb that was flashing in synchrony (or in asynchrony in the control condition) with their own online detected heartbeat (heartbeat-enhanced virtual reality HEVR). The primary outcome measures for pain reduction were subjective pain ratings, force strength, and heart rate variability (HRV).
RESULTSHEVR reduced pain ratings, improved motor limb function, and modulated a physiologic pain marker (HRV). These significant improvements were reliable and highly selective, absent in control HEVR conditions, not observed in healthy controls, and obtained without the application of tactile stimulation (or movement) of the painful limb, using a readily available biological signal (the heartbeat) that is most often not consciously perceived (thus preventing placebo effects).
CONCLUSIONSNext to these specific and well-controlled analgesic effects, immersive HEVR allows the application of prolonged and repeated doses of digital therapy, enables the automatized integration with existing pain treatments, and avoids application of painful bodily cues while minimizing the active involvement of the patient and therapist.
CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that HEVR reduces pain and increases force strength in patients with CRPS.
Abstract
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.
Complex regional pain syndrome type I (CRPS-I) highly affects patients' ability to perform daily life activities. Pain-related fear might be a key target to reduce disability in chronic pain. Current ...treatments aiming at reducing pain show little improvements on pain and disability, whereas novel exposure-based treatments targeting pain-related fears have shown to be promising. We conducted a randomized controlled trial (N = 46) comparing exposure in vivo (EXP) with pain-contingent treatment as usual (TAU), for CRPS-I patients with at least moderate levels of pain-related fear. Primary outcome is self-reported disability, for upper and lower extremity, respectively. Secondary outcomes are self-reported pain-intensity, pain-catastrophizing, perceived harmfulness of physical activity, and health-related quality of life. Pretreatment to posttreatment and pretreatment to 6-month follow-up change scores were tested using randomization-based inference. EXP was superior to TAU in reducing upper extremity disability from pretreatment to posttreatment (between-group difference, 1.082; 95% confidence interval CI, 0.563-1.601; P < 0.001) and from pretreatment to 6-month follow-up (1.303; 95% CI, 0.917-1.690; P < 0.001). EXP was superior in reducing lower extremity disability from pretreatment to 6-month follow-up (3.624; 95% CI, 0.467-6.781; P = 0.02), but not from pretreatment to posttreatment (3.055; 95% CI, -0.018 to 6.128; P = 0.054). All secondary outcomes significantly favored EXP pretreatment to posttreatment, as well as pretreatment to 6-month follow-up. Exposure to daily activities shows to be more effective than a protective pain-contingent TAU in reducing self-reported disability in daily life of CRPS-I patients with at least moderate levels of pain-related fear.
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