Neural substrates for poststroke complex regional pain syndrome type I: a retrospective case-control study using voxel-based lesion symptom mapping analysis.

Poststroke complex regional pain syndrome (CRPS) is characterized by swelling, pain, and changes in the skin that appear on the affected wrist and hand. In this retrospective study, we analyzed the relationship between poststroke CRPS and the location of stroke lesion. From all patients admitted to our hospital from 2009 to 2019, we recruited 80 patients affected by their first unilateral stroke who met the inclusion/exclusion criteria. Thirty-eight patients diagnosed with CRPS after stroke were assigned to the experimental group according to the "Budapest criteria" adopted by the International Association for the Study of Pain, and 42 patients without CRPS were included as controls. Regions of interest were manually drawn on T1-weighted magnetic resonance images, and data were normalized to a standard brain template. In the poststroke CRPS group, the relationship between the location of brain lesion and pain severity was analyzed using Freedman-Lane multivariable regression adjusting for Medication Quantification Scale rating, which was the only parameter to show a statistically significant correlation with pain intensity. A threshold of P < 0.01 was considered statistically significant for all voxel-based lesion symptom mapping tests, corrected for multiple comparisons with 5000 permutations. Analyses using voxel-wise subtraction and Liebermeister statistics indicated that the corticospinal tract (CST) was associated with the development of poststroke CRPS. Statistically significant correlations were found between pain intensity and the CST and the adjacent lentiform nucleus. Our results suggest that the CST may be a relevant neural structure for development of poststroke CRPS and the intensity of pain caused by the syndrome.

Evaluation Through Transcutaneous Tissue Oximetry (Near Infrared Spectroscopy) of Spinal Cord Stimulation in Patients With Complex Regional Pain Syndrome Type I.

OBJECTIVE: One of the physiopathological hypothesis behind complex regional pain syndrome (CRPS) type I involves the deep-tissue hypoxia of the affected areas. Spinal cord stimulation (SCS) appears to be effective in the treatment of these patients. We evaluated whether ESCS modifies tissue oxygen saturation (StO2 ) measured with near-infrared spectroscopy (NIRS) in the affected limbs in patients diagnosed with CRPS type I. MATERIALS AND METHODS: Nonrandomized, cross-sectional study that evaluated 16 patients with CRPS type I who were receiving SCS applied to the posterior cords. NIRS was used to evaluate baseline StO2 (primary outcome) and variations in StO2 (secondary outcome) during an ischemia-reperfusion test performed using a vascular occlusion test, comparing the hands of limbs unilaterally affected by CRPS type I with the unaffected contralateral hands. We also determined whether the variations in StO2 were related to a modification in the percentage of subjective pain improvement and in the visual analog scale score. RESULTS: The baseline StO2 of the affected hands was significantly higher than that of the unaffected hands (mean 4.7%; 95% confidence interval: 1.41, 6.7; p = 0.005). Variations in StO2 during the ischemia-reperfusion test revealed no differences between affected and unaffected hands. No significant correlations were detected between baseline StO2 values or variations in StO2 during the vascular occlusion test and the pain measurements. CONCLUSIONS: Baseline StO2 evaluated by NIRS was greater in the affected hands of patients with CRPS type I treated with SCS than in the unaffected, contralateral hands.

Clinical applications of nuclear medicine in the diagnosis and assessment of musculoskeletal sports injuries. / Aplicaciones clínicas de la medicina nuclear en el diagnóstico y evaluación de las lesiones deportivas musculoesqueléticas.

Increased participation in sports and physical exercise are widely promoted as an approach to a physically active lifestyle which has a positive effect on healthy aging, in patients and athletes of all ages, beginners and experts, including amateur athletes and professional athletes. Unfortunately, this has caused a higher incidence of sports-related injuries. In the sports context, the early and accurate diagnosis of injuries is of the utmost importance in order to enable early treatment to achieve a full recovery. Imaging techniques are increasingly important for the successful diagnosis and management of the patient. The nuclear medicine techniques with bone tracers provide physiological and metabolic information in the early phases of musculoskeletal injuries, which often precede anatomical changes and they reflect changes in bone turnover. This allows early diagnosis, along with evaluation of the activity and phase of the injury. In this article, the applications of nuclear medicine techniques, focusing on bone scintigraphy, alongside the important contribution of hybrid studies (SPECT/CT), in the diagnosis of bone and soft tissue sports injuries, will be described. In addition, we explain their usefulness in the expression of the pathophysiology of these lesions and their scintigraphic patterns. The article will also describe biomechanical and physiopathological aspects, injury mechanisms and clinical presentations of bone and joint sports injuries, knowledge of this is essential for the correct diagnostic assessment of imaging studies.

Shifting brain circuits in pain chronicity.

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

Risk Factor Analysis of Change in Intraoperative Neurophysiologic Monitoring During Cervical Open Door Laminoplasty.

OBJECTIVE: The aim of this study is to determine the risk factors affecting intraoperative neurophysiologic monitoring (IONM) changes, when such changes take place, and clinical outcomes associated with IONM change during cervical open door laminoplasty (COL) for cervical compressive myelopathy. METHODS: Between 2010 and 2015, 79 patients who underwent COL with IONM recording were studied. Changes in motor evoked potentials or somatosensory evoked potentials over an alarm criterion were defined as IONM change. Patients with IONM change were assigned to the alarm group, and the others were classified as the control group. Baseline data and radiographic measurements were compared between the 2 groups. Radiologic parameters including maximal compression level (MCL), area and diameter of the spinal canal and ventral compressive lesion, stenosis grade, and occupying ratio of area (ORA) and length at the MCL were measured with magnetic resonance imaging. RESULTS: Thirteen patients were assigned to the alarm group and 66 patients were assigned to the control group. Multivariate analysis identified ORA at the MCL (odds ratio, 1.520; 95% confidence interval, 1.192-1.37; P = 0.001) as an independent risk factor for IONM change. Immediately after decompression, the IONM change occurred. One of 4 patients who did not fully recover from the IONM change had postoperative motor deficits. CONCLUSIONS: IONM change during COL occurred immediately after decompression, and a risk factor of IONM change was ORA at the MCL. If the IONM change was not fully recovered, a new motor deficit occurred after COL.

Bone SPECT/CT Localizes Increased Bone Metabolism and Subsequent Bone Resorption in Reflex Sympathetic Dystrophy.

A 64-year-old man with lung cancer with a history of revascularization of the occluded right femoral artery underwent bone scintigraphy, which showed intense uptake in the distal side of the right leg. The additional SPECT/CT clarified that the uptake was predominantly increased in the epiphyses of the right ankle and foot with possible osteopenia. One month later, follow-up SPECT/CT showed the manifestation of periosteal resorption in the hypermetabolic sites with slight decrease in bone metabolism. Radiological correlation between bone metabolism and subsequent bone resorption in addition to clinical symptoms in this patient suggested the diagnosis of reflex sympathetic dystrophy.

Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a neurological disorder producing peripheral neurogenic inflammatory process in hands and feet distal to injury, which may lead to severe disability. Symptoms are often out of proportion to the initiating event and not limited to a single peripheral nerve. There is no gold standard in diagnosis of this entity, and a multidisciplinary approach is necessary for proper diagnosis. Magnetic resonance imaging (MRI) is one of the most useful diagnostic modalities in early stages of CRPS (when clinical diagnosis is most difficult), the most desirable time to diagnose this disorder to expedite treatment and improve function. This article discusses MRI findings of CRPS, particularly in the early phase, and differential considerations.

Putative Physiopathological Explanation for the "Sock Sign" in Bone Scans.

Four patients were referred to our department to undergo a bone scan for suspected reflex sympathetic dystrophy in the upper limbs. After TC-HMDP injection in the foot, they developed a "sock sign," defined by highly increased uptake in the injected lower limb. The sock sign has been previously described in only 1 case in the literature and attributed to intra-arterial injection. Our images suggest that the sock sign might instead be the consequence of tracer extravasation at the injection site.

Musculoskeletal Ultrasonography to Distinguish Muscle Changes in Complex Regional Pain Syndrome Type 1 from Those of Neuropathic Pain: An Observational Study.

Musculoskeletal ultrasonography (MSK USG) can identify myofascial structural lesions. We describe in this retrospective report the observational findings of USG data of muscles from limbs affected with neuropathic pain in 7 patients and compare them with muscles affected with complex regional pain syndrome type 1 (CRPS-1) in 7 patients. We highlight findings that distinguish between the 2 conditions. Musculoskeletal ultrasonography of muscles in CRPS was characterized by a variable or/and global intramuscular structural disruption with loss of muscle bulk. Adjacent muscles coalesced with one another to present an uniform hyperechogenic mass of tissue. Muscle edema was found in some patients. In comparison, MSK USG in muscles affected by neuropathic pain exhibited structural normalcy, but also showed considerable reduction in muscle bulk. Musculoskeletal ultrasonography shows promise as a diagnostic modality to distinguish between these 2 conditions which presently have only clinical diagnostic criteria to aid diagnosis.

Three-Phase 99mTc-MDP Bone Scintigraphy and SPECT/CT in Pediatric Pseudodystrophy.

Pseudodystrophy is a rare condition clinically resembling reflex sympathetic dystrophy. Distinction between both disorders is based on clinical features and bone scintigraphy. We report a case of 12-year-old girl presented with pain, swelling, and functional impairment of left foot after minor trauma. Clinical assessment revealed atrophy of left calf, cyanosis and coldness of left foot. Laboratory investigations were normal. X-ray and MRI of the foot were unremarkable. Bone scintigraphy showed hypoperfusion and diffusely reduced tracer uptake in the left lower leg and left foot. Diagnosis of pseudodystrophy was made on the basis of history, clinical examination, and bone scintigraphy findings.

Complex regional pain syndrome in a competitive athlete and regional osteoporosis assessed by dual-energy X-ray absorptiometry: a case report.

INTRODUCTION: Dual-energy X-ray absorptiometry is rarely utilized in the clinical care of patients with complex regional pain syndrome, but may be useful for the non-invasive determination of regional bone fragility and fracture risk, as well as muscular atrophy and regional body composition. This is the first report in the literature of complex regional pain syndrome and musculoskeletal co-morbidities in an athlete, and is the first to focus on dual-energy X-ray absorptiometry for the clinical assessment of complex regional pain syndrome. CASE PRESENTATION: In this report, we describe the case of a 29-year-old Caucasian man with type 1 complex regional pain syndrome. His body mass index was 29.4kg/m2 at the time of presentation. Despite severe complex regional pain syndrome in the left limb and long term use of a wheelchair, the patient participated in high-performance powerlifting. Dual-energy X-ray absorptiometry revealed marked unilateral differences in bone strength and lean mass between the affected regions and the contralateral regions. Low bone mineral density for age was found in the left hip, with Z-scores ranging from -2.2 to -3.0, and the patient had previously suffered two fractures. Bone density Z-scores in the right hip and legs were normal. CONCLUSIONS: Dual-energy X-ray absorptiometry is a valuable tool for the clinical investigation of musculoskeletal health in patients with complex regional pain syndrome. Regional osteoporosis in complex regional pain syndrome patients is complicated and should be investigated and monitored. Physical activity is possible for some complex regional pain syndrome patients, depending on the type of exercise and the region affected, and it may protect bone density and strength at non affected skeletal sites.

Evaluation of the structural quality of bone in a case of progressive osteoporosis complicating a Complex Regional Pain Syndrome (CRPS) of the upper limb.

Densitometry is considered to be the gold standard in bone quality assessment. However, since its introduction, the medical community has been aware that mineral density is only one of the factors that influence the bone risk of fracture, which also depends on the bone's trabecular arrangement and, in particular, on the trabecular architecture's load bearing capabilities. At the University of Trieste, in recent years, a test has been developed that simulates the application of compressive loads on trabecular architecture's reconstructions extracted from digital radiographs. In this work, the test is described, and the results obtained by applying the appraisal in a particular case of severe osteoporosis of the hand, complicating a Complex Regional Pain Syndrome (CRPS) type II, are presented. The test was able to quantify the pathological alterations of bone micro-architecture by means of a Structural Index (SI), which was absolutely significant and relevant to the clinical situation. Important research and clinical opportunities of application of the test include accurate evaluation of osteoporotic bone diseases, careful clinical follow-up and monitoring of responses to therapeutic approaches, and, prospectively, reliable quantification of biological damage (forensic field).

Morphological macrovascular alterations in complex regional pain syndrome type I demonstrated by increased intima-media thickness.

BACKGROUND: Although intima-media thickness (IMT) was increased in several inflammatory diseases, studies investigating whether the inflammatory processes lead to macrovascular alteration with increased IMT in complex regional pain syndrome (CRPS) lack. METHODS: Using ultrasound (high-resolution B-mode), we compared bilaterally the IMT of the common carotid artery (CCA-IMT), the radial artery (RA-IMT), the brachial artery (BRA-IMT) and the quotient QRA/CCA, in CRPS type I (n=17), peripheral nerve injury (PNI, n=17) and pain-free controls (PFC, n=22, matched to CRPS by gender, age and traditional cardiovascular risk factors). STATISTICS: Spearman's correlation, paired t-test, ANOVA (p<0.05). RESULTS: Compared to PFC, RA-IMT were significantly increased in both patient groups bilaterally (mean±standard deviation, CRPS affected side vs. PFC dominant side: 0.32±0.08 mm vs. 0.19±0.08 mm, p<0.001; PNI affected side vs. PFC dominant side: 0.27±0.09 mm vs. 0.19±0.08 mm, p< 0.05; CRPS non-affected side vs. PFC non-dominant side: 0.30±0.10 mm vs. 0.19±0.09 mm, p<0.001; PNI non-affected side vs. PFC non-dominant side: 0.25±0.10 mm vs. 0.19±0.09 mm, p<0.05) and QRA/CCA (CRPS affected-side vs. PFC dominant side: 0.49±0.12 vs. 0.30±0.11, p<0.001; PNI affected side vs. PFC dominant side: 0.41±0.10 vs. 0.30±0.11, p<0.05; CRPS non-affected side vs. PFC non-dominant side: 0.43±0.19 vs. 0.30±0.13, p<0.001; PNI non-affected side vs. PFC non-dominant side: 0.39±0.14 vs. 0.30±0.13, p<0.05), and BRA-IMT - only on the affected side in CRPS (CRPS: 0.42±0.06 mm vs. PFC: 0.35±0.08 mm; p<0.05). In CRPS, QRA/CCA was significantly higher on the affected side compared to PNI (p<0.05). However, only CRPS displayed within-group side-to-side differences with a significantly increased RA-IMT and QRA/CCA on the affected side (p<0.05). The CCA-IMT was comparable between all groups and sides. CONCLUSIONS: The increased IMT of peripheral arteries in CRPS suggests ongoing inflammatory process. Until now, only endothelial dysfunction has been reported. The presented morphological macrovascular alterations might explain the treatment resistance of some CRPS patients.

Concordance of qualitative bone scintigraphy results with presence of clinical complex regional pain syndrome 1: meta-analysis of test accuracy studies.

BACKGROUND: To date, no attempt has been made to investigate the agreement between qualitative bone scintigraphy (BS) and the presence of complex regional pain syndrome 1 (CRPS 1) and the agreement between a negative BS in the absence of CRPS 1. AIMS: To summarize the existing evidence quantifying the concordance of qualitative BS in the presence or absence of clinical CRPS 1. DATA SOURCES: We searched Medline, Embase, Dare and the Cochrane Library and screened bibliographies of all included studies. STUDY ELIGIBILITY CRITERIA: We selected diagnostic studies investigating the association between qualitative BS results and the clinical diagnosis of CRPS 1. The minimum requirement for inclusion was enough information to fill the two-by-two tables. RESULTS: Twelve studies met our inclusion criteria and were included in the meta-analysis. The pooled mean sensitivity of 12 two-by-two tables was 0.87 (95% CI, 0.68-0.97) and specificity was 0.69 (95% CI, 0.47-0.85). The pooled mean sensitivity for the subgroup with clearly defined diagnostic criteria (seven two-by-two tables) was 0.80 (95% CI, 0.44-0.95) and specificity was 0.73 (95% CI, 0.40-0.91). CONCLUSIONS: Based on this study, clinicians must be advised that a positive BS is not necessarily concordant with presence of absence or CRPS 1. Given the moderate level of concordance between a positive BS in the absence of clinical CRPS 1, discordant results potentially impede the diagnosis of CRPS 1.