The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Frank Birklein - One of the best experts on this subject based on the ideXlab platform.
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Complex Regional Pain Syndrome: a focus on the autonomic nervous system
Clinical Autonomic Research, 2019Co-Authors: Lone F. Knudsen, Astrid J. Terkelsen, Peter D. Drummond, Frank BirkleinAbstract:Purpose Although autonomic features are part of the diagnostic criteria for complex Regional Pain Syndrome (CRPS), the role of the autonomic nervous system in CRPS pathophysiology has been downplayed in recent years. The purpose of this review is to redress this imbalance. Methods We focus in this review on the contribution of the autonomic nervous system to CRPS pathophysiology. In particular, we discuss Regional sympathetic and systemic autonomic disturbances in CRPS and the mechanisms which may underlie them, and consider links between these mechanisms, immune disturbances and Pain. Results The focused literature research revealed that immune reactions, alterations in receptor populations (e.g., upregulation of adrenoceptors and reduced cutaneous nerve fiber density) and central changes in autonomic drive seem to contribute to Regional and systemic disturbances in sympathetic activity and to sympathetically maintained Pain in CRPS. Conclusions We conclude that alterations in the sympathetic nervous system contribute to CRPS pathology. Understanding these alterations may be an important step towards providing appropriate treatments for CRPS.
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complex Regional Pain Syndrome phenotypic characteristics and potential biomarkers
Nature Reviews Neurology, 2018Co-Authors: Frank Birklein, Seena K Ajit, Andreas Goebel, Roberto S G M Perez, Claudia SommerAbstract:Complex Regional Pain Syndrome (CRPS) is a Pain condition that usually affects a single limb, often following an injury. The underlying pathophysiology seems to be complex and probably varies between patients. Clinical diagnosis is based on internationally agreed-upon criteria, which consider the reported symptoms, presence of signs and exclusion of alternative causes. Research into CRPS biomarkers to support patient stratification and improve diagnostic certainty is an important scientific focus, and recent progress in this area provides an opportunity for an up-to-date topical review of measurable disease-predictive, diagnostic and prognostic parameters. Clinical and biochemical attributes of CRPS that may aid diagnosis and determination of appropriate treatment are delineated. Findings that predict the development of CRPS and support the diagnosis include trauma-related factors, neurocognitive peculiarities, psychological markers, and local and systemic changes that indicate activation of the immune system. Analysis of signatures of non-coding microRNAs that could predict the treatment response represents a new line of research. Results from the past 5 years of CRPS research indicate that a single marker for CRPS will probably never be found; however, a range of biomarkers might assist in clinical diagnosis and guide prognosis and treatment.
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complex Regional Pain Syndrome up to date
Pattern Recognition, 2017Co-Authors: Frank Birklein, Violeta DimovaAbstract:Complex Regional Pain Syndrome (CRPS) was described for the first time in the 19th century by Silas Weir Mitchell. After the exclusion of other causes, CRPS is characterised by a typical clinical constellation of Pain, sensory, autonomic, motor, or trophic symptoms which can no longer be explained by the initial trauma. These symptoms spread distally and are not limited to innervation territories. If CRPS is not improved in the acute phase and becomes chronic, the visible symptoms change throughout because of the changing pathophysiology; the Pain, however, remains. The diagnosis is primarily clinical, although in complex cases further technical examination mainly for exclusion of alternative diagnoses is warranted. In the initial phase, the pathophysiology is dominated by a posttraumatic inflammatory reaction by the activation of the innate and adaptive immune system. In particular, without adequate treatment, central nociceptive sensitization, reorganisation, and implicit learning processes develop, whereas the inflammation moderates. The main symptoms then include movement disorders, alternating skin temperature, sensory loss, hyperalgesia, and body perception disturbances. Psychological factors such as posttraumatic stress or Pain-related fear may impact the course and the treatability of CRPS. The treatment should be ideally adjusted to the pathophysiology. Pharmacological treatment maybe particularly effective in acute stages and includes steroids, bisphosphonates, and dimethylsulfoxide cream. Common anti-neuropathic Pain drugs can be recommended empirically. Intravenous long-term ketamine administration has shown efficacy in randomised controlled trials, but its repeated application is demanding and has side effects. Important components of the treatment include physio- and occupational therapy including behavioural therapy (eg, graded exposure in vivo and graded motor imaging). If psychosocial comorbidities exist, patients should be appropriately treated and supported. Invasive methods should only be used in specialised centres and in carefully evaluated cases. Considering these fundamentals, CRPS often remains a chronic Pain disorder but the devastating cases should become rare.
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complex Regional Pain Syndrome significant progress in understanding
Pain, 2015Co-Authors: Frank Birklein, Tanja SchlerethAbstract:Research into complex Regional Pain Syndrome (CRPS) has made significant progress. First, there was the implementation of the official IASP "Budapest" diagnostic criteria. It would be desirable to also define exclusion and outcome criteria that should be reported in studies. The next step was to recognize the complex pathophysiology. After trauma, some inflammation is physiological; in acute CRPS, this inflammation persists for months. There is an abundance of inflammatory and a lack of anti-inflammatory mediators. This proinflammatory network (cytokines and probably also other mediators) sensitizes the peripheral and spinal nociceptive system, it facilitates the release of neuropeptides from nociceptors inducing the visible signs of inflammation, and it stimulates bone cell or fibroblast proliferation, and endothelial dysfunction leading to vascular changes. Trauma may also expose nervous system structures to the immune system and triggers autoantibodies binding to adreno- and acetylcholine receptors. In an individual time frame, the Pain in this inflammatory phase pushes the transition into "centralized" CRPS, which is dominated by neuronal plasticity and reorganization. Sensory-motor integration becomes disturbed, leading to a loss of motor function; the body representation is distorted leading to numbness and autonomic disturbances. In an attempt to avoid Pain, patients neglect their limb and learn maladaptive nonuse. The final step will be to assess large cohorts and to analyze these data together with data from public resources using a bioinformatics approach. We could then develop diagnostic toolboxes for individual pathophysiology and select focused treatments or develop new ones.
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complex Regional Pain Syndrome an optimistic perspective
Neurology, 2015Co-Authors: Frank Birklein, Darragh P Oneill, Tanja SchlerethAbstract:Complex Regional Pain Syndrome (CRPS) presents with clinical symptoms that can no longer be explained by the initial trauma, including Pain, sensory, motor, and trophic symptoms, and impairment of autonomic control of the limb. These symptoms spread distally and go beyond single nerve innervation territories. Typically, the symptoms change through the course of CRPS as a result of the varying pathophysiology. Diagnosis is made clinically after the rigorous elimination of other possible causes, and 3-phase bone scintigraphy can be a useful tool for confirming CRPS. In acute stages, inflammatory symptoms prevail and should be treated with anti-inflammatory agents (steroids), bisphosphonates, or topical application of dimethyl sulfoxide. In chronic stages, many symptoms are related to so-called central neuroplasticity; these include hyperalgesia, sensory loss, motor symptoms, body perception disturbance, autonomic symptoms, and learned incorrect behavior such as nonuse. At this stage, the only medical treatment that is effective against Pain without improving the function is ketamine infusions, but this has side effects. Physical therapy, graded motor imagery, and Pain exposure/graded exposure in vivo therapy can help to overcome central reorganization. If a relevant mental comorbidity is present, the patient should be referred for psychotherapeutic treatment. Invasive treatment should be restricted to special cases and only offered after psychosomatic assessment. If these recommendations are followed, CRPS prognosis is not as poor as commonly assumed. Whether the patients can return to their previous life depends on particular individual factors.
Stephen Butler - One of the best experts on this subject based on the ideXlab platform.
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cortical reorganization of the healthy hand in upper limb complex Regional Pain Syndrome crps is reorganizations of common beliefs about crps necessary
Scandinavian Journal of Pain, 2016Co-Authors: Stephen ButlerAbstract:Cortical reorganization of the healthy hand in upper-limb complex Regional Pain Syndrome (CRPS) : Is reorganizations of common beliefs about CRPS necessary?
Christian Maihofner - One of the best experts on this subject based on the ideXlab platform.
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clinical features and pathophysiology of complex Regional Pain Syndrome
Lancet Neurology, 2011Co-Authors: Johan Marinus, Wade S Kingery, Christian Maihofner, Lorimer G Moseley, Frank Birklein, Ralf Baron, J J Van HiltenAbstract:A complex Regional Pain Syndrome (CRPS)—multiple system dysfunction, severe and often chronic Pain, and disability—can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant infl ammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.
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hypertrichosis in alopecia universalis and complex Regional Pain Syndrome
Neurology, 2010Co-Authors: Florian T Nickel, Christian MaihofnerAbstract:This 46-year-old woman developed complex Regional Pain Syndrome (CRPS) I in the right hand after distortion of the wrist. Ten …
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central opioidergic neurotransmission in complex Regional Pain Syndrome
Neurology, 2010Co-Authors: Andre Klega, Christian Maihofner, T Eberle, Hansgeorg Buchholz, S Maus, M Schreckenberger, Frank BirkleinAbstract:Objective: Complex Regional Pain Syndrome (CRPS) is a chronic Pain condition characterized by sensory, motor, and autonomic symptoms. It develops after limb trauma and may be associated with relevant psychiatric comorbidity. As there is evidence for central pathophysiology which might be related to an altered opioidergic neurotransmission, we investigated the cerebral opioid receptor status under resting conditions in this patient population. Methods: In this case-control study, 10 patients with CRPS and 10 age- and gender-matched healthy subjects underwent a PET scan using the subtype-nonselective opioidergic radioligand [ 18 F]fluoroethyl-diprenorphine. As a surrogate for Regional cerebral opioid receptor availability, the opioid receptor binding potential (OR-BP) was assessed by means of the modified Logan plot with reference region input for categorical group comparison and correlation with clinical data in the patient group. Results: Patients with CRPS showed reduced OR-BP in contralateral amygdala and parahippocampal gyri and increased OR-BP in contralateral prefrontal cortical areas. When OR-BP in the midcingulate cortex and the ipsilateral temporal cortex was low, the McGill Pain rating index was high. In general, when anxiety and depression scales were high, contralateral temporal OR-BP was high as well. In addition, the anxiety scale decreased with increasing OR-BP in the contralateral parahippocampal cortex. Conclusions: These results demonstrate altered central opioidergic neurotransmission in CRPS. The correlation of Regional opioid receptor availability to measures of Pain, anxiety, and depression underlines the clinical importance of these findings.
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cortical reorganization during recovery from complex Regional Pain Syndrome
Neurology, 2004Co-Authors: Christian Maihofner, B Neundorfer, Hermann O Handwerker, Frank BirkleinAbstract:Objective: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex Regional Pain Syndrome (CRPS). Background: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS Pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy. Methods: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up. Results: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS Pain correlated with recovery from cortical reorganization. Conclusions: Changes of the somatotopic map within the S1 cortex may depend on CRPS Pain and its recovery.
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patterns of cortical reorganization in complex Regional Pain Syndrome
Neurology, 2003Co-Authors: Christian Maihofner, B Neundorfer, Hermann O Handwerker, Frank BirkleinAbstract:Objective To use magnetoencephalography to assess possible cortical reorganization in the primary somatosensory cortex (S1) of patients with complex Regional Pain Syndrome (CRPS). Background Patterns of Pain and sensory symptoms in CRPS may indicate plastic changes of the CNS. Methods Magnetic source imaging was used to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 12 patients. Results The authors found a significant shrinkage of the extension of the cortical hand representation for the CRPS affected side. The center of the hand was shifted toward the cortical representation of the lip. The cortical reorganization correlated with the amount of CRPS Pain (r = 0.792), as measured by the McGill questionnaire, and the extent of mechanical hyperalgesia (r = 0.860). Using multiple regression analysis, the best predictor for the plastic changes was found to be mechanical hyperalgesia. Additionally, S1 sources following tactile stimulation were significantly increased on the CRPS side compared to the unaffected limb. Conclusions This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic Pain.
B Neundorfer - One of the best experts on this subject based on the ideXlab platform.
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cortical reorganization during recovery from complex Regional Pain Syndrome
Neurology, 2004Co-Authors: Christian Maihofner, B Neundorfer, Hermann O Handwerker, Frank BirkleinAbstract:Objective: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex Regional Pain Syndrome (CRPS). Background: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS Pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy. Methods: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up. Results: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS Pain correlated with recovery from cortical reorganization. Conclusions: Changes of the somatotopic map within the S1 cortex may depend on CRPS Pain and its recovery.
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patterns of cortical reorganization in complex Regional Pain Syndrome
Neurology, 2003Co-Authors: Christian Maihofner, B Neundorfer, Hermann O Handwerker, Frank BirkleinAbstract:Objective To use magnetoencephalography to assess possible cortical reorganization in the primary somatosensory cortex (S1) of patients with complex Regional Pain Syndrome (CRPS). Background Patterns of Pain and sensory symptoms in CRPS may indicate plastic changes of the CNS. Methods Magnetic source imaging was used to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 12 patients. Results The authors found a significant shrinkage of the extension of the cortical hand representation for the CRPS affected side. The center of the hand was shifted toward the cortical representation of the lip. The cortical reorganization correlated with the amount of CRPS Pain (r = 0.792), as measured by the McGill questionnaire, and the extent of mechanical hyperalgesia (r = 0.860). Using multiple regression analysis, the best predictor for the plastic changes was found to be mechanical hyperalgesia. Additionally, S1 sources following tactile stimulation were significantly increased on the CRPS side compared to the unaffected limb. Conclusions This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic Pain.
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facilitated neurogenic inflammation in complex Regional Pain Syndrome
Pain, 2001Co-Authors: Margarete Weber, Frank Birklein, B Neundorfer, Martin SchmelzAbstract:Abstract Complex Regional Pain Syndrome (CRPS) is characterized by a variety of clinical features including spontaneous Pain and hyperalgesia. Increased neuropeptide release from peripheral nociceptors has been suggested as a possible pathophysiologic mechanism triggering the combination of trophic changes, edema, vasodilatation and Pain. In order to verify the increased neuropeptide release in CRPS, electrically induced neurogenic vasodilatation and protein extravasation were evaluated in patients and controls. We performed a prospective study on 10 patients with acute and untreated CRPS and 10 matched healthy controls. Neurogenic inflammation was elicited by strong transcutaneous electrical stimulation via intradermal microdialysis capillaries which simultaneously enabled measurement of protein extravasation. Laser-Doppler scanning was used to assess axon reflex vasodilatation. Axon reflex vasodilatation was significantly increased in CRPS patients (438±68% of baseline vs. 306±52%; P
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facilitated neurogenic inflammation in complex Regional Pain Syndrome
Pain, 2001Co-Authors: Margarete Weber, Frank Birklein, B Neundorfer, Martin SchmelzAbstract:Complex Regional Pain Syndrome (CRPS) is characterized by a variety of clinical features including spontaneous Pain and hyperalgesia. Increased neuropeptide release from peripheral nociceptors has been suggested as a possible pathophysiologic mechanism triggering the combination of trophic changes, edema, vasodilatation and Pain. In order to verify the increased neuropeptide release in CRPS, electrically induced neurogenic vasodilatation and protein extravasation were evaluated in patients and controls. We performed a prospective study on 10 patients with acute and untreated CRPS and 10 matched healthy controls. Neurogenic inflammation was elicited by strong transcutaneous electrical stimulation via intradermal microdialysis capillaries which simultaneously enabled measurement of protein extravasation. Laser-Doppler scanning was used to assess axon reflex vasodilatation. Axon reflex vasodilatation was significantly increased in CRPS patients (438 +/- 68% of baseline vs. 306 +/- 52%; P < 0.05) and transcutaneous electrical stimulation provoked protein extravasation only in the patients (before, 0.28 +/- 0.03 mg/ml; during stimulation, 0.34 +/- 0.04 mg/ml), whereas protein concentration steadily declined during stimulation in the healthy controls (before, 0.23 +/- 0.04 mg/ml; during stimulation, 0.18 +/- 0.04; P < 0.001). The time course of electrically induced protein extravasation in the patients resembled the one observed following application of exogenous substance P (SP). We conclude that neurogenic inflammation is facilitated in CRPS. Our results suggest an increased releasability of neuropeptides in CRPS.
Angelo Cacchio - One of the best experts on this subject based on the ideXlab platform.
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mirror therapy for chronic complex Regional Pain Syndrome type 1 and stroke
The New England Journal of Medicine, 2009Co-Authors: Angelo Cacchio, Elisabetta De Blasis, Stefano Necozione, Ferdinando Di Orio, Valter SantilliAbstract:The results indicate that mirror therapy effectively reduces Pain and enhances motor function in the arm of patients with stroke and chronic complex Regional Pain Syndrome type 1 in the arm.
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mirror therapy in complex Regional Pain Syndrome type 1 of the upper limb in stroke patients
Neurorehabilitation and Neural Repair, 2009Co-Authors: Angelo Cacchio, Elisabetta De Blasis, Valter Santilli, Vincenzo De Blasis, Giorgio SpaccaAbstract:Background. Complex Regional Pain Syndrome type 1 (CRPSt1) of the upper limb is a Painful and debilitating condition, frequent after stroke, and interferes with the rehabilitative process and outco...
