Evaluation of upper extremity rehabilitation in hemiplegic patients with and without complex regional pain syndrome type 1

We investigated the effects of the complex regional pain syndrome (CRPS) type 1 on upper extremity rehabilitation in hemiplegic patients. Eighty patients were enrolled and were randomly assigned to either study (40 hemiplegic patients with CRPS) or control (40 hemiplegic patients without CRPS) groups. All patients participated in a hemiplegia rehabilitation program consisting of neurodevelopmental techniques, stretching and strengthening exercises, and conventional methods. Additionally, participants in the study group received analgesic and calcitonin therapy, elevation, range of movement therapy for the affected joints, and contrast baths. Clinical findings were assessed before and after rehabilitation using the upper-limb function (ULF), hand movements (HM), and advanced hand activities (AHA) subscales of the Motor Assessment Scale (MAS) and the Ashworth scale for upper extremities. A statistically significant difference in MAS ULF was apparent at admission and upon discharge in both groups. In the control group, a significant difference was found between MAS HM and MAS AHA on admission and at discharge, no difference was found in the study group for these parameters. No difference was found for either group with regard to the Ashworth scale. No between-group differences were found regarding MAS ULF, MAS HM, and MAS AHA at admission and at discharge. Our data showed no influence of CRPS on MAS ULF, MAS HM, and MAS AHA and the Ashworth scale for upper extremities.     

Hemisensory impairment in patients with complex regional pain syndrome

The purpose of the present study was to investigate the extent and quality of sensory impairment and their relation to pain characteristics and movement disorders in patients suffering from complex regional pain syndrome (CRPS) type I. Neurological testing was performed independently by two examiners in 24 patients with CRPS type I. In eight patients (33%), a hemisensory impairment with decreased temperature and pinprick sensation ipsilateral to the limb affected by CRPS could be observed. In four patients (17%), a sensory deficit in the upper quadrant of the body could be demonstrated and in eight patients (33%), sensory impairment was limited to the limb affected by CRPS. Mechanical allodynia and mechanical hyperalgesia could be observed in a higher percentage of patients with hemisensory deficit or sensory impairment in the upper quadrant (92%), than in those patients with sensory impairment limited to the affected limb (17%) (P < 0.005). In patients with left-sided CRPS, sensory abnormalities in the upper quadrant or hemisensory impairment were more frequently demonstrated (77%) than in patients with right-sided CRPS (18%) (P < 0.005). There was a high correlation (92%) for the sensory findings between the two examiners, and hemisensory abnormalities were stable over a period of 3-6 months in all six patients with repeated examinations. Motor impairment (contractures, weakness, tremor or difficulties in initiating movement) could be observed in a higher percentage in patients with sensory abnormalities in the upper quadrant or hemisensory impairment (83%) than in patients with sensory impairment limited to the affected limb (42%) (P < 0.05) and was significantly correlated with allodynia/hyperalgesia (P < 0.005). The results demonstrated that sensory deficits in patients with CRPS, frequently extend past the painful area of the affected limb. The increased frequency of mechanical allodynia and movement disorders in patients with hemisensory impairment or sensory deficits in the upper quadrant, might indicate that central mechanisms are involved in the pathogenesis of CRPS in these patients.     

Proximal myofascial pain in patients with distal complex regional pain syndrome of the upper limb

BackgroundPatients suffering from complex regional pain syndrome (CRPS) endure myofascial-related pain in at least 50% of cases.AimsTo evaluate the association of upper limb CRPS with myofascial pain in muscles that might influence arm or hand pain, and to evaluate whether the paraspinal skin and subcutaneous layers’ tenderness and allodynia are associated with CRPS.MethodsA case-control study comprising 20 patients presenting with upper limb CRPS, and 20 healthy controls matched for sex and age, were evaluated in the thoracic paraspinal area and myofascial trigger points (MTrPs) (infraspinatus, rhomboids, subclavius, serratus posterior superior and pectoralis minor) via a skin rolling test.ResultsThe prevalence of MTrPs in the affected extremity of the subjects was significantly higher than in the right limb of the controls: 45% exhibited active and latent MTrPs in the infraspinatus muscle (χ² = 11.613, p = 0.001); 60% in active and latent MTrPs in the subclavius muscle (χ² = 17.143, p < 0.001); and in the pectoralis minor muscle (χ2 = 13.786, p < 0.001). In addition, 55% of the cases exhibited active and latent MTrPs in the serratus posterior superior muscle (χ² = 15.172, p < 0.001). Significant differences between the groups in skin texture and pain levels (p = 0.01, p < 0.001, respectively) demonstrated that CRPS patients felt more pain, and their skin and subcutaneous layers were much tighter than in the healthy controls.ConclusionThere is a high prevalence of MTrPs in the shoulder and upper thoracic area muscles in subjects who suffer from CRPS. We recommend adding an MTrPs evaluation to the standardized examination of these patients.     

The treatment of complex regional pain syndrome (CRPS) involving upper extremity with continuous sensory analgesia.

Continuous sensory analgesia of brachial plexus (CSA BP) was only occasionally reported to have been used in the treatment of CRPS. In the past four years, we have treated 21 patients with a working diagnosis of CRPS. The treatment was instituted one to six months after inciting injury. All patients were admitted to hospital. In the first two days, the therapy consisted of elevation, cryotherapy, and active exercises. Five patients responded well to this initial physiotherapy (5/21). In 16 cases, no evident improvement was observed and CSA BP was introduced. At follow-up (3-36 months), the results were: 13/16 (81%) had at least good results (excellent 2, good without any sequelae 5, good with sequelae of initial injury 6, and poor 3). The results were judged as follows: excellent (completely normal hand); good (only temporary pain up to 2 on a 0-10 numeric rating scale; no signs of dysfunction of sympathetic nervous system; ROM of wrist over 50% of normal hand; ROM of fingers excellent or good; and the strength of hand grasp and key pinch over 50% of normal hand measured with dynamometer) and if any of the former criteria was missing, the result was defined as poor.     

Management of pediatric patients with complex regional pain syndrome

This review summarizes current information about diagnosis and treatment of complex regional pain syndrome (CRPS) in children. Although it has been widely held that CRPS in children is intrinsically different from adults, there appear to be relatively few differences. However, there is a marked preponderance of lower extremity cases in children. Historically, psychological factors have been invoked to explain the genesis and persistence of CRPS in children, but the evidence is not compelling. Treatment outcome studies are limited but indicate that children generally respond to a primary focus on physical therapy. Multidisciplinary treatment reports are particularly encouraging. The general perception that children have a milder course may relate to the potentially greater willingness of children to actively participate in appropriately targeted treatment rather than to innate differences in the disease process itself. Recurrence rates appear higher than in adults, but response to reinitiation of treatment seems to proceed efficiently. Clinical judgment dictates the extent of medication or interventional therapy added to the treatment to facilitate rehabilitation. In many ways, the approach to the treatment of children mirrors that of adults, with perhaps greater restraint in the use of medications and invasive procedures. The rehabilitation of children with CRPS, like that of adults with CRPS, needs further rigorous investigation.     

Mitochondrial dysfunction in muscle tissue of complex regional pain syndrome type I patients

Reactive oxygen species (ROS) are known to be involved in the pathophysiology of complex regional pain syndrome type I (CRPS I). Since the mitochondrial respiratory chain is a major source of ROS, we hypothesized that mitochondria play a role in the pathophysiology of CRPS I. The hypothesis was tested by studying mitochondrial energy metabolism in muscle tissue from amputated limbs of CRPS I patients. We observed that mitochondria obtained from CRPS I muscle tissue displayed reduced mitochondrial ATP production and substrate oxidation rates in comparison to control muscle tissue. Moreover, we observed reactive oxygen species evoked damage to mitochondrial proteins and reduced MnSOD levels. It remains to be established if the mitochondrial dysfunction that is apparent at the end‐stage of CRPS I is also present in earlier stages of the disease, or are secondary to CRPS I. The observation of a reduced mitochondrial energy production combined with reactive oxygen species induced damage in muscle tissue from CRPS I patients warrants further studies into the involvement of mitochondrial dysfunctioning in the pathophysiology of CRPS I.     

Treatment of complex regional pain syndrome type I.

Reflex sympathetic dystrophy (RSD), also known as complex regional pain syndrome type I (CRPS I), is a disabling neuropathic pain syndrome. Controversy exists about the effectiveness of therapeutic interventions for the management of RSD/CRPS I. In order to ascertain appropriate therapies we conducted a review of existing randomized controlled trials of therapies for this disabling disease. Eligible trials were identified from the Cochrane, Pubmed, Embase and MEDLINE databases from 1966 through June 2000, from references in retrieved reports and from references in review articles. Twenty-six studies concerning treatment modalities were identified. Eighteen studies were randomized placebo-controlled trials and eight studies were randomized active-controlled trials. Three independent investigators reviewed articles for inclusion criteria using a 15-item checklist. Seventeen of the trials were of high quality according to the 15-item criteria. There was limited evidence for the effectiveness of these interventions because of the heterogeneity of treatment modalities. The search for trials concerning prevention of RSD/CRPS I resulted in two eligible studies. Both were of high quality and dealt with different interventions. There is limited evidence for their preventive effect.     

Risk perception of developing complex regional pain syndrome I

This study investigated how members of a hand team perceive clinical signs after a fracture of the distal radius. The risk of developing complex regional pain syndrome I (CRPS-I) was assessed on a 100-mm straight line based on clinical signs 5 weeks, 7 weeks and 10 weeks after the accident. Members of the hand team perceived clinical signs significantly differently.     

Muscle hyperalgesia is widespread in patients with complex regional pain syndrome

Patients with complex regional pain syndrome (CRPS) frequently show prominent sensory abnormalities in their affected limb, which may extend proximally and even to unaffected body regions. This study examines whether sensory dysfunction is observed in unaffected body parts of CRPS patients, and investigates whether the extent of dysfunction is similar for the various sensory modalities. Quantitative sensory testing was performed in the unaffected extremities and cheeks of 48 patients with CRPS of the arm (31 with dystonia), and the results were compared with values obtained among healthy controls. The most prominent abnormality was the pressure pain threshold, which showed a consistent pattern of higher sensitivity in unaffected contralateral arms and unaffected legs, as well as the cheek, and demonstrated the largest effect sizes. The cheeks of CRPS patients showed thermal hypoesthesia and hyperalgesia as well as a loss of vibration detection. Except for a lower vibration threshold in the contralateral leg of CRPS patients with dystonia, no differences in sensory modalities were found between CRPS patients with and without dystonia. These results point to a general disturbance in central pain processing in patients with CRPS, which may be attributed to impaired endogenous pain control. Since pressure pain is the most deviant sensory abnormality in both unaffected and affected body regions of CRPS patients, this test may serve as an important outcome parameter in future studies and may be used as a tool to monitor the course of the disease.     

Altered central sensorimotor processing in patients with complex regional pain syndrome

Alterations in tactile sensitivity are common in patients with chronic pain. Recent brain imaging studies have indicated that brain areas activated by acute experimental pain partly overlap with areas processing innocuous tactile stimuli. However, the possible effect of chronic pain on central tactile processing has remained unclear. We have examined, both clinically and with whole-head magnetoencephalography, six patients suffering from complex regional pain syndrome (CRPS) of the upper limb. The cortical somatosensory responses were elicited by tactile stimuli applied to the fingertips and the reactivity of spontaneous brain oscillations was monitored as well. Tactile stimulation of the index finger elicited an initial activation at 65 ms in the contralateral SI cortex, followed by activation of the ipsi- and contralateral SII cortices at about 130 ms. The SI responses were 25-55% stronger to stimulation of the painful than the healthy side. The distance between SI representations of thumb and little finger was significantly shorter in the hemisphere contralateral than ipsilateral to the painful upper limb. In addition, reactivity of the 20-Hz motor cortex rhythm to tactile stimuli was altered in the CRPS patients, suggesting modified inhibition of the motor cortex. These results imply that chronic pain may alter central tactile and motor processing.     

Plasma endothelin-1 levels in patients with complex regional pain syndrome

The clinical characteristics of complex regional pain syndrome (CRPS)--spontaneous and stimulus-evoked pain, autonomic abnormalities, motor dysfunction, and trophic changes in the affected limb--are well known. However, its pathogenesis is unclear, and the diagnosis is often delayed, in part due to lack of objective laboratory tests. Endothelin-1 (ET-1) is a potent vasoconstrictor that has recently been shown to produce pain, allodynia, edema, and muscle weakness, as well as to exert a direct excitatory effect on nociceptive afferents. Furthermore, new evidence indicates that ET-1 is involved in various cancer- and non-cancer-related painful conditions. The aim of the present explorative study was to determine the ET-1 plasma levels in patients with CRPS in an attempt to identify a 'laboratory marker' for CRPS and to search for evidence suggesting that ET-1 may be involved in the pathogenesis of CRPS. ET-1 plasma levels were determined in 20 severely affected CRPS patients, in eight patients with non-CRPS chronic painful conditions, and in 10 healthy volunteers. The results showed that there were no significant differences in ET-1 plasma levels between the three groups. We conclude that the plasma level of ET-1 cannot be regarded as a 'marker' for CRPS. Yet, the possibility that ET-1 is involved in the pathophysiology of CRPS has not been excluded and deserves further investigation.     

Comparison of muscle and joint pressure-pain thresholds in patients with complex regional pain syndrome and upper limb pain of other origin

Pain localized in the deep tissues occurs frequently in complex regional pain syndrome (CRPS). In addition, hyperalgesia to blunt pressure over muscles is common in CRPS, but it often appears in limb pain of other origin as well. Considering that 3-phase bone scintigraphy (TPBS) reveals periarticular enhanced bone metabolism in CRPS, joint-associated hyperalgesia to blunt pressure might be a more specific finding than hyperalgesia over muscles. In 34 patients with upper limb pain (18 CRPS, 16 non-CRPS; diagnosed in accordance to the Budapest criteria) and in 18 healthy controls, pressure-pain thresholds (PPT) were assessed bilaterally over the thenar (PPT_Thenar), the metacarpophalangeal (PPT_MCP), and the proximal interphalangeal (PPT_PIP) joints using a pressure algometer (Somedic, Sweden). Beforehand, all patients had received TPBS for diagnostic purposes independently of the study. Region-of-interest (ROI) ratios (mineralization phase) for the MCP and PIP, excluding fracture sites, were correlated with the PPT. In CRPS, all ROI ratios were significantly increased and all PPT of the affected hand were decreased compared to non-CRPS (PPT_Thenar: 243 ± 150 kPa vs 358 ± 197 kPa, PPT_MCP: 80 ± 67 kPa vs 159 ± 93 kPa, PPT_PIP: 80 ± 56 kPa vs 184 ± 110 kPa; P < .01) and controls (PPT_Thenar: 478 ± 106 kPa, PPT_MCP: 254 ± 50 kPa, PPT_PIP: 275 ± 76 kPa; P < .01). A PPT_Thenar below 293 kPa revealed 77% sensitivity but only 63% specificity, whereas a PPT_PIP below 102 kPa had 82% sensitivity and 94% specificity to identify CRPS. Only in CRPS were PPT_MCP and PPT_PIP correlated significantly inversely with the ROI ratio (MCP: r = −0.439, PIP: r = −0.447). PPT_PIP shows higher specificity for CRPS type I than PPT_Thenar without loss of sensitivity. Therefore, measurement of joint PPT could be a noninvasive diagnostic tool reflecting increased bone metabolism assessed by TPBS as a sign of bone pathophysiology.     

Mirror box therapy added to cognitive behavioural therapy in three chronic complex regional pain syndrome type I patients: a pilot study

Complex regional pain syndrome type I is a disorder of the extremities with disability and pain as the most prominent features. This paper describes the results of cognitive behavioural therapy combined with mirror box therapy in three patients with chronic complex regional pain syndrome type I. Before, during and at follow-up the following measurements were assessed: pain (visual analogue scale, 0-100), range of motion, muscle strength, and the areas of allodynia and of hyperalgesia. Furthermore, patients were asked for their feelings and thoughts about mirror box therapy and about the affected limb. Pain at rest, pain after measuring allodynia/hyperalgesia and pain after measuring strength decreased. Range of motion improved in two patients. Strength improved in one patient. The area of hyperalgesia increased for all three patients, whereas the area of allodynia remained stable in two patients and decreased in one patient. Two patients felt that their affected limb still belonged to them, one did not. Cognitive behavioural therapy combined with mirror box therapy for patients with chronic complex regional pain syndrome type I may facilitate rehabilitation. Measuring whether the affected limb still belongs in the patient's body scheme could be of prognostic value in the treatment of chronic complex regional pain syndrome type I patients.     

Use of calcitonin to prevent complex regional pain syndrome type I in severe hemiplegic patients after stroke

Purpose. To evaluate the effects of calcitonin in preventing complex regional pain syndrome type I (CRPS) in patients with severe hemiplegia following stroke.

Methods. In this observer-blinded, controlled study comparison with historical controls between April 2003 and May 2004, subjects comprised consecutive patients with post-stroke hemiplegia admitted between June 2004 and September 2005, with any upper limb or finger graded as Brunnstrom stage (BrST) III or below. One group was administered intramuscular injection of 20 units of elcatonin (EL) (Asu^1–7 eel calcitonin) weekly from immediately after admission to discharge, together with rehabilitation therapy. The control group received rehabilitation therapy alone. Patients were observed during the in-hospital rehabilitation period. The main outcome measure was onset of CRPS.

Results. Incidence of CRPS in all patients with post-stroke hemiplegia during the control period was about 8.2%, similar to recent studies. Limited to serious hemiplegic patients graded as BrST III or below, incidence of CRPS was significantly lower in the EL group (12.5%) than in controls (57.1%). No significant differences in patient background were seen between groups. CRPS was completely prevented when EL injection was started ≤4 weeks after stroke, but prophylactic effects were weak when EL was started >6 weeks after stroke.

Conclusion. Intramuscular calcitonin appears to suppress onset of CRPS after stroke, particularly when started early after stroke.     

Status of immune mediators in complex regional pain syndrome type I

Complex regional pain syndrome type I (CRPS-I) can affect an extremity after minor trauma or operation. The pathogenesis of this syndrome is unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response, but neurogenic dysregulation is also a contributor. Several studies investigated the role of inflammatory mediators and cytokines thus far; however, the results are heterogeneous and vary between different settings. This review summarizes recent study results that show a clear underlying inflammatory response at the local site, where systemic responses seem to be inconsistent. An induction of CRPS-like symptoms by application of neuroinflammatory mediators was shown recently. Local inflammation is involved in the pathophysiology of CRPS-I. We must expand our knowledge of pathophysiologic mechanisms, and we are still far away from using inflammatory markers in diagnosis and follow-up of CRPS-I.     

Interobserver reliability of diagnosis in patients with complex regional pain syndrome.

Complex regional pain syndrome type I (CRPS-I), formerly reflex sympathetic dystrophy (RSD), is a chronic pain syndrome of unknown aetiology. Its diagnosis is a clinical one, for which several criteria systems have been defined. Despite their widespread use, the reliability of these criteria has never been studied. In this interobserver study 25 chronic CRPS patients were interviewed and examined by six physicians. Through structured questionnaires signs, symptoms, and diagnosis were recorded, after which observer agreement for these was calculated with kappa statistics. Physicians' agreement in assessment of signs and symptoms in CRPS patients varied greatly. More importantly, final diagnosis of CRPS showed poor observer agreement (kappa: 0.20). The kappa values were higher, had physicians applied IASP criteria, but still insufficient. The application of Bruehl's criteria results in a fair kappa of 0.38, but then frequency of CRPS diagnosis in our study population decreased from 73% to 43% in comparison with physicians' own diagnosis. We conclude that, using current criteria systems, the diagnosis of CRPS is not reliable.     

Sensory changes in the forehead of patients with complex regional pain syndrome

The aim of this study was to investigate involvement of central mechanisms in complex regional pain syndrome (CRPS). In particular, we wished to determine whether hyperalgesia extends ipsilaterally from the affected limb to the forehead. The heat-pain threshold, pressure-pain threshold, and ratings of cold and sharpness were investigated on each side of the forehead and in the affected and unaffected limbs of 38 patients with features of CRPS. In addition, touch thresholds were investigated in the limbs. The pressure-pain threshold was lower on the ipsilateral forehead than contralaterally, consistent with the presence of static mechanical hyperalgesia. Although the heat-pain threshold and ratings of sharpness and cold did not differ between the two sides of the forehead in the group as a whole, the sharpness of pinprick sensations in the affected limb was mirrored by similar sensations in the ipsilateral forehead. Conversely, diminished sensitivity to light touch in the affected limb was associated with diminished sensitivity to sharpness, cold and heat-pain in the ipsilateral forehead. These findings suggest that central nociceptive processing is disrupted in CRPS, possibly due to disturbances in the thalamus or higher cortical centres.