|
INTRODUCTION:
Some of these studies are abstracts and others are review articles of research studies on RSD/CRPS. Studies are listed alphabetically according to author. Prominent researchers in the field are listed also. International Dutch RSD/CRPS Conference 2003 studies by European doctors and researchers are featured. Studies of note are listed with *** at beginning.
STUDIES 2005:
To see abstracts presented at the August 2005 International Association for the Study of Pain (IASP) Conference in Sydney, Australia, or studies in 2005, click here.
STUDIES 2004:
Studies A-M
Studies N-Z
STUDIES 2003:
Charles Berde MD PhD
Robert Schwartzman MD
Studies A-M
Studies N-Z
International Dutch RSD Conference: Nov. 14-15, 2003.
HOT OFF THE PRESS! STUDIES 2004
STUDIES A-M
For a copy of this or any CRPS article, visit McMaster Health Sciences Library. Search Pub Med using the PMID number listed.
Backonja MM, Serra
Pharmacologic management part 2: lesser-studied neuropathic pain diseases.
J.Pain Med. 2004 Mar;5 Suppl 1:S48-59.
University of Wisconsin Hospital and Clinics, Madison, Wisconsin; Neuropathic Pain Unit, Hospital General de Catalunya, Barcelona, Spain.
This second part of a review of the pharmacologic management of neuropathic pain diseases describes the current treatment options for three lesser-studied neuropathic syndromes: Central post-stroke pain, spinal cord injury, and complex regional pain syndrome II. Diagnosis can be difficult in patients with these syndromes, because the pain experienced is much greater and of a different type than would normally be expected following a stroke or injury to the spinal cord or a peripheral nerve. Even when an accurate and timely diagnosis is made, treatment options are limited and frequently suboptimal. However, the results of published trials do support the use of anticonvulsants and/or tricyclic antidepressants as first-line pharmacotherapy in these three neuropathic pain syndromes. To maximize treatment outcomes, future research must: Continue to more fully elucidate the relationship between the signs and symptoms of pain and the underlying pathophysiology; Delineate the natural history of central post-stroke pain, spinal cord injury, and complex regional pain syndrome; Identify patient-related factors that may indicate an increased risk of developing neuropathic pain following stroke or nerve injury; Investigate emerging treatments that target underlying pain mechanisms.
PMID: 14996229
***Carter ML.
Spinal cord stimulation in chronic pain: a review of the evidence.
Anesth Intensive Care. 2004 Feb;32(1):11-21.
Department of Anaesthesia, Bundaberg Base Hospital, PO Box 34, Bundaberg, Qld 4670.
This review looks at the evidence for the effectiveness of spinal cord stimulation in various chronic pain states. Spinal cord stimulation can only be effective when appropriate dorsal column fibres in the spinal cord are preserved and able to be stimulated. Spinal cord stimulation has been shown to have little to offer for patients with some diagnoses. Although 50 to 60% of patients with failed back surgery syndrome obtain significant pain relief with this technique, the strength of the evidence available is insufficient to clearly advocate its use in all patients with this condition. Though limited in quantity and quality, better evidence exists for its use in neuropathic pain, complex regional pain syndrome, angina pectoris and critical limb ischaemia. There is a lack of high quality evidence relating to spinal cord stimulation due to difficulties in conducting randomized controlled trials in this area. Serious methodological problems are encountered in blinding, recruitment and assessment in nearly all published trials of spinal cord stimulation. Suggestions regarding appropriate methodologies for trials which would produce better quality evidence are summarized.
PMID: 15058115
Cordivari C, Misra VP, Catania S, Lees AJ.
New therapeutic indications for botulinum toxins.
Mov Disord. 2004 Mar;19 Suppl 8:S157-61.
Department of Clinical Neurophysiology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
The efficacy of botulinum toxin (BTX) without systemic effects has led to the rapid development of applications in neuromuscular disorders, hyperactivity of sudomotor cholinergic-mediated glandular function, and pain syndromes. The successful use of BTX in conditions with muscle overactivity, such as dystonia and spasticity, has been established and new areas in the field of movement disorders such as tics, tremor, myoclonic jerks, and stuttering has been explored with satisfactory results. Strategies to temporarily inactivate muscle function after orthopaedic or neurosurgery have also been developed. BTX treatment of hyperhidrosis was followed by its application in other hypersecretory conditions (hyperlacrimation and nasal hypersecretion) and in excessive drooling. Studies are in progress, aimed at optimising the technique and protocol of administration. Other applications for BTX have been proposed in gastroenterological and urogenital practice; it appears to be effective in replacing standard surgical procedures. Trials of BTX in painful conditions are ongoing mainly on refractory tension headache, migraine, and backache as well as dystonia-complex regional pain syndrome and myofascial pain with promising results. Recently, the fastest growing use for BTX toxin has been in the cosmetic applications. Clearly, the indications for the use of BTX are expanding, but further clinical trials will be needed in many different areas. Copyright 2004 Movement Disorder Society
PMID: 15027069
Drummond PD, Finch PM.
Persistence of pain induced by startle and forehead cooling after sympathetic blockade in patients with complex regional pain syndrome.
J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):98-102
School of Psychology, Murdoch University, Perth, Western Australia, Australia.
BACKGROUND: Stimuli arousing sympathetic activity can increase ratings of clinical pain in patients with complex regional pain syndrome (CRPS). OBJECTIVE: To determine whether the increase in pain is mediated by peripheral sympathetic activity. METHODS: The effect of sympathetic ganglion blockade on pain evoked by a startle stimulus and cooling the forehead was investigated in 36 CRPS patients. RESULTS: Loss of vasoconstrictor reflexes and warming of the limb indicated that sympathetic blockade was effective in 26 cases. Before sympathetic blockade, pain increased in 12 of these 26 patients when they were startled. Pain increased in seven of the 12 patients and in another five cases when their forehead was cooled. As expected, pain that increased during sympathetic arousal generally subsided in patients with signs of sympathetic blockade. However, pain still increased in three of 12 of patients after the startle stimulus and in six of 12 of patients during forehead cooling, despite indisputable sympathetic blockade. CONCLUSIONS: These findings suggest that stimuli arousing sympathetic activity act by a central process to exacerbate pain in some patients, independent of the peripheral sympathetic nervous system. This may account for the lack of effect of peripheral sympathetic blockade on pain in some CRPS patients.
PMID: 14707316
Forouzanfar T, Kemler MA, Weber WE, Kessels AG, van Kleef M.
Spinal cord stimulation in complex regional pain syndrome: cervical and lumbar devices are comparably effective.
Br J Anesth 2004 Mar;92(3):348-53. Epub 2004 Jan 22.
Department of Anaesthesiology, University Hospital Maastricht, Maastricht, The Netherlands.
BACKGROUND: Spinal cord stimulation (SCS) has been used since 1967 for the treatment of patients with chronic pain. However, long-term effects of this treatment have not been reported. The present study investigated the long-term effects of cervical and lumbar SCS in patients with complex regional pain syndrome type I. METHODS: Thirty-six patients with a definitive implant were included in this study. A pain diary was obtained from all patients before treatment and 6 months and 1 and 2 years after implantation. All patients were asked to complete a seven-point Global Perceived Effect (GPE) scale and the Euroqol-5D (EQ-5D) at each post-implant assessment point. RESULTS: The pain intensity was reduced at 6 months, 1 and 2 years after implantation (P<0.05). However, the repeated measures ANOVA showed a statistically significant, linear increase in the visual analogue scale score (P=0.03). According to the GPE, at least 42% of the cervical SCS patients and 47% of the lumbar SCS patients reported at least 'much improvement'. The health status of the patients, as measured on the EQ-5D, was improved after treatment (P<0.05). This improvement was noted both from the social and from the patients' perspective. Complications and adverse effects occurred in 64% of the patients and consisted mainly of technical defects. There were no differences between cervical and lumbar groups with regard to outcome measures. CONCLUSION: SCS reduced the pain intensity and improves health status in the majority of the CRPS I patients in this study. There was no difference in pain relief and complications between cervical and lumbar SCS.
PMID: 14742334
Gorodkin R, Moore T, Herrick A.
Assessment of endothelial function in complex regional pain syndrome type I using iontophoresis and laser Doppler imaging.
Rheumatology (Oxford). 2004 Mar 16
University of Manchester Rheumatic Disease Centre, Hope Hospital, Salford, UK.
OBJECTIVES: To assess microvascular endothelial function in patients with complex regional pain syndrome type I (CRPS) compared with healthy controls, as measured by iontophoresis of vasoactive chemicals and laser Doppler imaging. METHODS: Microvascular blood flow was stimulated locally in affected and contralateral limbs of patients with CRPS (n = 17) and in control subjects (n = 16) using iontophoresis of the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial-independent vasodilator sodium nitroprusside (NaNP). Changes in blood flow were measured using laser Doppler imaging. Comparisons were made between right and left limbs and between patients and controls. RESULTS: No significant differences in blood flow [expressed as a median percentage increase from baseline (interquartile range)] were detected between affected and contralateral limbs in patients with CRPS for ACh [affected 237 (95-344); unaffected 251 (152-273)] or for NaNP [affected 102 (49-300); unaffected 190 (53-218)]. In addition, there were no significant differences between patients and healthy controls [controls, ACh 216 (119-316); controls, NaNP: 122 (48-249)]. CONCLUSIONS: In this pilot study, CRPS was not associated with impairment of microvascular endothelial function. This may be a true result or may reflect the diversity of the CRPS disease process.
PMID: 15026582
Clark, Triesman GJ Pain and Depression An Interdisciplinary Patient-Centered Approach Adv Psychosom Basel Karger 2004 Vol. 25 pp 89-101
Grabow T, MD Raja, MD S Christo, P.
CRPS: Diagnostic Controversies, Psychological Dysfunction and Emerging Concepts
Division of Pain Medicine, Dept. of Anesthesia and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore MD USA
ABSTRACT: Complex regional pain syndrome types I and II are neuropathic pain disorders that involve dysfunction of the peripheral and central nervous system. CRPS type I and II are formerly known as reflex sympathetic dystrophy and causalgia, respectively. Most experts believe that a multidisciplinary approach including pharmacotherapy, physiotherapy, and psychotherapy is warranted. Historically, there has been considerable controversy regarding this disease entity. In particular, the precise mechanism of the sympathetic dysfunction as well as the nature of the psychological dysfunction commonly observed in patients with CRPS has been the subject of considerable debate. Current strides in our understanding of the pathophysiology of this disease have improved treatment options.
Introduction
Complex regional pain syndrome (CRPS) types I and II formerly known as reflex sympathetic dystrophy and causalgia, are neuropathic pain disorders likely involving dysfunction of the both the peripheral and central nervous system. The pathophysiology is poorly understood and treatments often are directed at managing signs and symptoms of the disease. A significant number of patients exhibit comorbid psychological dysfunction which has led some clinicians to believe incorrectly that it is entirely a psychiatric disease. Animal research has improved our mechanistic understanding of neuropathic pain and this awareness hay facilitate our understanding of CRPS (particularly type II). Recent clinical investigation has resulted in an improved understanding of the biological dysfunction observed in patients with CRPS. This review will (1) summarize the historical arguments and controversy surrounding the disease, (2) describe the psychological dysfunction often observed in patients with CRPS and (3) discuss recent trends in the neurobiological understanding of CRPS.
CRPS Controversy and Misunderstanding
CRPS History
Several authors have questioned the validity of CRPS type I as an actual organically based neurological disease and have doubted the involvement of the sympathetic nervous system in the maintenance of the pain. Many aspects of the disease, including nomenclature, etiopathogenesis, diagnosis and treatment have generated considerable controversy. As a result, CRPS type I (RSD), has been considered by some experts an expression of somatoform disease and therefore has been designated as pseudoneuropathy of psychogenic origin. A brief discussion of several of these arguments is warranted.
Nomenclature
Causalgia was first described in 1864 as a distinct disease entity by Silas Weir Mitchell who noted extreme pain, autonomic abnormalities, trophic changes and involuntary movements in Civil War soldiers who suffered from traumatic injury to peripheral nerves.
Renee Leriche later postulated in 1916 that the sympathetic nervous system was involved in pain states involving major tissue or nerve injury, the term RSD was coined nearly half a century later in 1946 by JA Evans to describe patients who exhibited causalgia-like symptoms but without evidence of major tissue or nerve injury. Several other terms have been used to describe this disease such as minor causalgia, algodystrophy, shoulder-hand syndrome, posttraumatic dystrophy, and Sudeck’s atrophy. In general, the disease was given different names based on the personal assumptions, frame of reference, institutional background, or country of origin of the investigators who were describing the disease process.
In 1994, a task force commissioned by the IASP introduced the present day descriptive terminology to standardize the nomenclature, remove obsolete mechanistic understandings, and improve disease recognition, Until this time, scholars had argued that the term RSD erroneously implied an underlying “reflexive” mechanism presumably related to aberrant function (ex. hyperactivity) of the sympathetic nervous system that if left untreated, would inevitably lead to permanent dystrophic change. Today, most authorities recognize that sympathetic (overactivity) is not observed and that sympathetic dysfunction and dystrophic changes occur only in a subset of patients with CRSP. Furthermore, certain therapies specifically aimed at the sympathetic nervous system may be unwarranted. (1,2). Despite the efforts of the IASP, many clinicians are unfamiliar with the modern taxonomy and the majority of contemporary investigations fail to utilize the diagnostic criteria proposed by the IASP.
Diagnosis
According to the IASP, the diagnosis of CRPS requires (1) an initiating noxious event or cause of immobilization (2) continuing pain, allodynia or hyperaglesia disproportionate to any inciting event (3) evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity and (4) the exclusion of a medical condition that would otherwise account for the degree of pain and dysfunction. the presence on an initiating noxious event or cause of immobilization was not required according to the original publication by the IASP in 1994; however, this statement was omitted from the more widely available and Meddling-indexed summary statement from the consensus meeting published in 1995.. Importantly, a precipitating inciting event may not be detected in approximately 10% of patients with CRPS(6). This definition is entirely descriptive and does not imply etiology or specific pathophysiology. This lack of mechanism based specificity in the proposed diagnostic criteria has detracted somewhat from its universal acceptance by the scientific community.
Etiopathogenesis
Patients with CRPS exhibit signs of emotional duress and psychological dysfunction. Consequently, it was tempting for early investigators to conclude that much of the pain and symptomatology was the results of untreated psychiatric disease or caused by exaggerated sympathoarousal secondary to underlying stress. The term RSD helped to maintain this cause and effect link between the sympathetic nervous system, and the pain. As a result, many patients underwent therapies designed to mitigate sympathetic nervous system dysfunction. Today there is convincing evidence in animals and humans that nerve injury and tissue inflammation may be associated with aberrant functioning of the sympathetic nervous system. (7) (Table 1) Despite this link, the pathophysiology of CRPS is incompletely understood and several mechanisms may be operating simultaneously. Furthermore, it is commonly recognized that only a subset of patients with CRPS have sympathetically maintained pain ((SMP) which is defined as pain that is modulated by sympathetic block or pharmacological antagonism of alpha adrenoreceptor function.
Psychological Dysfunction
Psychiatric Comorbid Conditions in Chronic Pain
Chronic pain patients frequently have associated comorbid psychiatric disease.(8). When ranked form most frequent to least frequent, the following comorbid conditions likely are associated more with chronic pain patients than with the general population: affective disorders (depression), psychoactive substance, use-related disorders, somatoform disorders, and anxiety disorders. Moreover, a significant number of chronic pain patients may have more than one axis I psychiatric comorbidity. Psychiatric comorbidities can have a negative impact on chronic pain and functional status. In addition, there are a group of conditions commonly observed in chronic pain patients that are not necessarily psychiatric in nature which in addition, do not satisfy formal Diagnostic and Statistical Manual (DSM) criteria. These observations include such things as pain behaviours, sleep disturbance, somatization, nonorganic physical findings, and impaired functional status out of proportion to physician expectations based on objective findings(8). The prognostic implication of these conditions is unknown.
Psychiatric Disease in CRPS
Patients with CRPS commonly suffer from psychological dysfunction. In fact, patients with CRPS experience a significant amount of depression, anxiety and phobia. However, attempts to establish a unique “CRPS personality” have been unsuccessful. In general, early studies lacked validity due to various flaws in methodological design. For example, studies failed to examine premorbid personality data, investigators used heterogenous definitions of psychiatric terminology and psychometric instruments had nor been normed on pain populations(9). Nevertheless, reported prevalence of psychiatric disorders in patient with CRPS ranges from 18-64%(10). Psychological examination using the Structured Clinical Interview (SCID) of the DSM-IV demonstrates a high frequency of affective disorder (46%), anxiety disorder (27%), and substance abuse disorder (14%) in patients with CRPS.(11). However, the prevalence of psychiatric disorders in patients with CRPS may not be much different from chronic pain patients in general. For example, the prevalence of major depression (1.5-54.5%), anxiety disorders (7-62.5%) and substance abuse disorders (3.2-18.9%).in chronic pain patients is reported in similar rates as CRPS patients (8) Finally Breuhl and Carlson (10) reviewed data strictly from studies which used the MMPI and concluded that patients with CRPS like patients with chronic pain in general, are somatically preoccupied, depressed and use repression as a psychological defense mechanism.
There has been historical debate whether chronic pain or psychiatric illness is the primary process. The reciprocal relationship between pain and psychological dysfunction in patient with CRPS is evident from a recent study of daily diaries which demonstrated that yesterday’s depressed pain also contributed to today’s depression, anxiety and anger.(12)> Several literature reviews have examined whether psychological dysfunction was the cause or effect of CRPS. (9,10,13). In general, the majority of historical studies suffered from flaws in methodology such as lack of consistent and homogenous diagnostic groups, lack of control groups and significant statistical tests, lack of objective measures of psychological disease, poorly defended behavioural criteria, and incorrect use of psychiatric or psychological terminology(13). As a result, Lynch (13) concluded there is no valid evidence that certain personality traits or psychological factors predispose one to the development of CRPS. Similarly, due to the methodological weakness of the literature, Breuhl and Carlson (10) concluded that there is insufficient data to draw meaningful conclusions whether or not pre-existing psychological factors predispose to the development of CRPS.
In summary, most authors have concluded that cormorbid psychological disease in patients with CRPS is a consequence of the chronic pain rather than its cause. (9, 13). Further more, there is no evidence that individuals with certain personality types are predisposed to developing CRPS. Finally there are no consistent psychological differences between CRPS and non-CRPS pain patients (14-22).
Table 2)
Factitious Disorder
The overall prevalence of factitious disorder in chronic pain patients is between 0,14 and 2% (8). Patients with conversion disorder and factitious illness my have similar clinical presentation to patients with CRPS. In Fact, certain sensory sign (ex. Non-anatomical and expansive areas of hypoesthesia or hyperalgesia with normal peripheral sensory nerve conduction of somatosensory evoked potentials) or features (e.g. normalization of hypoesthesia by nerve blocks) identified in patients with CRPS type 1 likely are psychogenic in origin. Moreover, neurophysiological investigation suggest that certain positive motor signs (dystonia, tremors, spasms, irregular jerks) identified in patients with CRPS type I are in fact psychogenic in origin and represent psuedoneurological illness(23).
Strain and Distress in Caregivers
Caregivers of patients with CRPS experience significant levels of strain and susceptibility to depression measured by the Caregiver Strain Index (CSI) and General Health Questionnaore012 (GHQ 12), respectively(24). Caregiver health can have a significant impact on recipient care. Thus, physicians should not only implement psychosocial interventions directed at patients but also caregivers of patient with CRPS.
Other Issues (Legal, Disability)
Allen et al (25) recently performed a retrospective chart review of the epidemiology of CRPS. They reported that 54% of patients had a worker compensation claim and that 17% had a lawsuit related to the CRPS. The effect of litigation on pain severity and clinical outcomes for patients with CRPS is unknown.
Neglect-like Symptoms
Patients with CRPS often display signs of motor dysfunction that appear to be related to voluntary guarding in order to avoid exacerbation of pain. However, recent evidence suggest that motor dysfunction may be related to neglect-like symptoms ( e.g. cognitive neglect, motor neglect)in a subset of patients with CRPS(26.) Of note, self-reported motor dysfunction is the second most commonly reported groups of symptoms after sensory dysfunction in patient with CRPS. (27).
Quality of Life
A pilot study demonstrated substantial interference with quality of like measured by modified Brief Pain Inventory (mBPI) as well as significant sleep disturbance in patient with CRPS(27).
Stressful Life Events
Stressful life events were more common in patients with CRPS than in a control group of patients with hand pathology measured by the Social Readjustment Rating Scale (SRRS) (20). However, these authors concluded that there was no direct casual relationship between these stressful life events or any underlying psychological dysfunction measured by SCL-90 and the onset of CRPS. In a retrospective study, Geertzen et al (28) concluded that stressful life events and psychological dysfunction measured by the SRRS and RAND-36 item health Survey (RAND-36), respectively, already existed at the time of diagnosis of CRPS and did not results from CRPS.
RECENT TRENDS
Sympathetic Nervous System
In animals, there is overwhelming evidence that nerve injury and inflammation can result in functional coupling between the sympathetic efferents and primary sensory afferent neurons within the peripheral nervous system (7).The site of this aberrant sympathetic-sensory coupling involves the dorsal root ganglia (DRG) the area of injury itself (e.g. neuroma site) or within the tissue innervated by the injured nerve.
Several of these correlates exist in humans and these findings have been summarized in recent reviews (7). For example, peripheral nerve injury results in sympathetic sprouting and functional coupling between sympathetic efferents and primary sensory afferent neurons in the DRG (29). An increase of alpha-adrenoreceptors have been observed in the hyperalgesic skin of patients with CRPS type 1 (30). Patients with CRPS I have decreased sympathetic outflow but increased ?-adrenergic responsiveness in the affected limbs suggesting adrenergic supersensitivity. This supersensitivity is reversed with CRPS symptoms resolve. Pharmacological or surgical sympathectomy can decrease pain in patient with CRPS and patients with neuropathic pain report increased pain during stress or after intradermal injection of a physiological dose of norepinephrine(NE)(31). In addition, injections of NE can rekindle pain and mechanical hyperalgesia in patient who have had a previous sympathetic block. Finally, inflammatory pain and hyperalgesia produced by topical capsaicin is decreased by a-adrenoceptor antagonists and increased by NE(32).
Despite this evidence, systematic reviews have failed to demonstrate the efficacy of therapies designed to inhibit sympathetic function and question their unity (1,2).In fact, some investigators have challenged the validity of pharmacological tests to establish the diagnosis of SMP. The pain can be challenging even for clinicians with considerable expertise. (33).
Recent studies have examined the effect of the natural stimulation of the subject’s own sympathetic nervous system on spontaneous pain and hyperalgesia rather than the effect of pharmacological treatment such as sympathetic blocks or injections of NE. Sympathetic arousal increased pain and vasoconstriction in the affected extremity of patients with CRPS I and II. (34). Also sympathetic activation increased spontaneous pain and spatial distribution of mechanical hyperalgesia in patients with CRPS I who have SMP. (34). These two investigations were the first to demonstrate that physiological activation of the sympathetic nervous system can modulate the pain experience in humans through endogenous release of NE from sympathetic nerve endings. These findings provide evidence in support of the concept of SMP or pain as the result of sympathetic efferent activity.
SYMPATHETIC NERVOUS SYSTEM (SNS) DYSFUNCTION
In the acute stage of CRPS I there is complete functional loss of cutaneous sympathetic vasoconstrictor activity as well as decreased venous plasma levels of NE (presumably secondary to decreased postganglionic release from sympathetic terminals) confined to the affected extremity (36). This autonomic impairment may recover within weeks and likely reflects dysfunction within the CNS. During chronic CPRS sympathetic vasoconstrictor neurons are still inhibited but adrenoreceptor supersensitive in vascular tissue results in ongoing vasoconstriction and subsequent cold skin. These vascular abnormalities are dynamic and more pronounced when examined over the entire range of the thermoregulatory cycle (37).
Patients with acute CRPS I also demonstrate a-adrenergic super sensitivity of sudomotor nerves that is reversible with disease progression (38). Unilateral disturbances in sudomotor function determined by quantitative sudomotor axon reflex test (QSART) and thermoregulatory sweat test (TST) also have been reported in patients with chronic CRPS (39).
Sensory Dysfunction
Sensory disturbances are common in patients with CRPS I and II and predominately consist of hyperalgesia, allodynia, and spontaneous pain (6). Quantitative sensory testing (QSART) demonstrates an increase in warm perception thresholds and a decrease of cold pain thresholds in patient with CRPS I and II. Sensory impairments frequently extend beyond the affected area and may involve quadratic or hemilateral regions of the body (41).
Motor Dysfunction
Motor disturbances are prevalent in patients with CRPS I and II.(6) and are independent of sensory and autonomic complaints (40). The most frequently described motor disturbance is loss of function of the affected extremity. Detailed neurological examination may detect objective evidence of isolated motor weakness, muscle atrophy, tremor, dystonia, or ataxia. Furthermore, electrodiagnostic and nerve conduction velocity can be used to document muscle and large fiber abnormalities, respectively. Decrease in active range of motion can be assessed by goniometer. Similarly, muscle power can be assessed by measuring grip force strength or by manual muscle testing. More complex motor tasks can be measured by kinematic analysis. A recent study has demonstrated neurophysiological evidence of impairment of central sensor motor integration in patients with CRPS I (42). These motor deficits may be secondary to abnormal integration of visual and sensory inputs to the parietal cortex (43).
CNS Dysfunction
Evidence suggests that certain autonomic, motor and sensory disturbances in patients with CRPS are caused by dysfunction within the CNS whereas certain aspects of the pain itself may be related to aberrant peripheral mechanisms. Potential peripheral and central mechanisms are described elsewhere (7,44). Occasionally, dysfunction of the sensory, motor, or autonomic nervous system, may involve bilateral structures after unilateral nerve or tissue injury (45). In addition, several investigators have described CNS abnormalities by fMRI, MRS, or SPECT. Recent investigation suggests that patients with CRPS may develop function or structural reorganization and change in central representation of sensory maps. However it is unclear whether these abnormalities are as a result of the chronic pain or whether they represent specific regions of primary dysfunction within the CNS.
Treatment Algorithm for CRPS
The therapeutic strategy for patients with CRPS involves the concurrent utilization of pharmaoco-,physio- and psychotherapy. However, randomized controlled trials (RCT) investigating the impact of psychological intervention on homogenous groups of patient with neuropathic pain, including patients with CRPS have not been undertaken (46) Nevertheless, principles derived from operant and cognitive behaviour theory are useful to treat chronic pain patient in general and these strategies should be used for patients with CRPS. The goal of pharmacological therapy is to reduce pain in order to facilitate functional restoration. In general medications that are effective for the treatment of neuropathic pain are used for patients with CRPS. The goal of physiotherapy is to improve functional status. In general desensitization and physical rehabilitation cannot proceed without adequate pain control. Most authorities believe that active participation in physical therapy is instrumental for improvement in patient with CRPS. To date, only the short term efficacy of physical therapy has been demonstrated by a RCT specifically for CRPS patients (47). The use of these interventional techniques should be considered in the treatment algorithm when other therapies have failed. A summary of current therapeutic strategies has been published. (48).
Low doses of a common intravenous anesthetic may relieve debilitating pain syndrome
Harbut R MD
23 Sep 2004
Limited, low-dose infusions of a widely used anesthetic drug may relieve the often intolerable and debilitating pain of Complex Regional Pain Syndrome (CRPS), a Penn State Milton S. Hershey Medical Center researcher found.
"This pain disorder is very difficult to treat. Currently-available therapies, at best, oftentimes only make the pain bearable for many CRPS sufferers," said Ronald E. Harbut, M.D., Ph.D., assistant professor of anesthesiology, Penn State Hershey Medical Center. "In our retrospective study, some patients who underwent a low-dose infusion of ketamine experienced complete relief from their pain, suggesting that this therapy may be an option for some patients with intolerable CRPS."
The study, titled "Subanesthetic Ketamine Infusion Therapy: A Retrospective Analysis of a Novel Therapeutic Approach to Complex Regional Pain Syndrome," was published in the September 2004 issue of Pain Medicine, the official journal of the American Academy of Pain Medicine.
CRPS (type I), also known as Reflex Sympathetic Dystrophy Syndrome (RSD), affects between 1.5 million and 7 million people in the United States and is oftentimes marked by a severe, burning pain that can be very resistant to conventional therapies. The pain frequently begins after a fall or sprain, a fracture, infections, surgery, or trauma. Often present in the limbs with possible later spreading to other parts of the body, patients also may experience skin color changes, sweating abnormalities, tissue swelling, and an extreme sensitivity to light touch or vibrations. The McGill Pain Index rates CRPS as 42 on the scale of 50, with 50 being most severe.
Although much is unknown about CRPS, the pain experienced by patients appears to be caused by over-stimulation of a nerve receptor complex involved in the process of feeling pain. Therefore, efforts have been made to treat CRPS by blocking these receptors. Whereas most pain medications do not effectively block these receptor complexes (often referred to as NMDA-receptors), ketamine does.
The study was initiated by Graeme E. Correll, B.E., M.B.B.S., and involved reviewing the medical records of 33 patients with CRPS treated by Correll. The patients, some of whom had failed to obtain pain relief from conventional therapies, were treated with low-dose inpatient intravenous infusions of ketamine between 1996 and 2002 in Mackay, Queensland, Australia. Ketamine infusions were started at very low rates and were slowly increased in small increments as tolerated by selected patients. The therapy was then continued as long as the patient tolerated the drug and continued to benefit from it. Treatment cycles generally continued until the patient experienced complete pain relief; until initially-obtained relief would not improve any further; or for no more than 48 hours if there was no improvement in pain severity.
Pain was completely relieved for 25 (76 percent) patients, partially relieved for six (18 percent) patients, and not relieved for two (6 percent) patients. Although the relief obtained did not last indefinitely, 54 percent remained completely pain-free for three months or more and 31 percent for six months or more. For 12 patients who received a second treatment, 58 percent experienced relief for one year or more with 33 percent remaining pain-free for more than three years.
The most frequent side effect reported was a feeling of inebriation. Hallucinations occurred in six patients with less frequent side effects including complaints of light-headedness, dizziness and nausea. Liver enzymes were altered in four patients but resolved after therapy.
The exact mechanism of sustained pain relief is unknown, but is currently under study at Penn State Hershey Medical Center. Harbut likened the ketamine treatment to the healing of a broken bone. "If someone breaks a bone and you simply put the two pieces back together, they won't immediately heal. However, if you add a splint and hold the bones steady for a period of time, and then later take away the splint the bone is healed. I believe that the ketamine treatment does something similar that lends support and allows the nerve cells to heal themselves, so that when you take away the ketamine, the pain is reduced or gone."
Harbut began studying CRPS with Correll during a work assignment Harbut volunteered to take in far northern Queensland, Australia, in the late 1990s. Correll was developing a therapy for CRPS but wanted a collaborator to formally research the effectiveness of the therapy. Harbut brought Correll's method back to the U.S. where he developed an FDA-approved study protocol (used at the Mayo Clinic Scottsdale) using this method to attempt to treat post herpetic neuralgia, another pain disorder with symptoms somewhat similar to CRPS. At the same time, Harbut met a patient who had suffered with intolerable CRPS for nine years who wanted to try this new therapy. That patient became the first successful treatment of intractable CRPS in the U.S. (A Case Report of this treatment appeared in the June 2002 issue of Pain Medicine.)
"Ultimately, we want to find a way to improve the quality of life for those who suffer with intolerable CRPS, some of whom at times contemplate suicide because of their endless pain," Harbut said. "Although optimistic about these early findings, certainly more study is needed to further establish the safety and efficacy of this novel approach." (A large clinical study is currently planned and under development at Penn State Hershey Medical Center.)
In addition to Harbut and Correll, the team involved in this study included: Jahangir Maleki, M.D., Ph.D., and Edward J. Gracely, Ph.D., Drexel University College of Medicine; and Jesse J. Muir, M.D., Mayo Clinic Scottsdale.
***Huygen FJ, Ramdhani N, Van Toorenenbergen A, Klein J, Zijlstra FJ.
Mast cells are involved in inflammatory reactions during Complex Regional Pain Syndrome type 1.
Immunol Lett. 2004 Feb 15;91(2-3):147-154.
Pain Treatment Center, Department of Anesthesiology, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Background: The Complex Regional Pain Syndrome type 1 (CRPS1) is a complication of surgery or trauma but spontaneous development is also described. Although the pathogenesis remains debatable, afferent, efferent and central nervous system mechanisms are proposed. Recently we showed involvement of the proinflammatory cytokines IL-6 and TNFalpha which is direct evidence for an inflammatory process. Many types of cells, such as activated T lymphocytes, monocytes,macrophages and skin resident cells like mast cells, could contribute to the production of cytokines. Involvement of mast cells is relatively easy to detect by measurement of tryptase. Aim: To establish whether mast cells are involved in the inflammatory reactions during CRPS1. Methods: Twenty patients fulfilling the Bruehl criteria with CRPS1 in one extremity were studied. Impairment was assessed by registration of pain and measurement of differences in temperature, volume and mobility between the involved and uninvolved extremity. Blisters were made with a suction method in order to determine cytokines and mast cell derived tryptase in the involved and uninvolved extremity. Results: In the blister fluid a significant difference ( [Formula: see text] range, Wilcoxon signed-ranks test [Formula: see text] ) was found between the involved and uninvolved extremity in IL-6 {53.5 (17.3-225) versus 6.2 (2-20.3) pg/ml}, TNFalpha {31 (15.5-131.5) versus 8 (4-39) pg/ml}, and tryptase {37 (20.5-62.3) versus 12.5 (6.7-23.5)ng/ml}. There was a significant correlation (0.455) between the intensity of pain and tryptase levels in the involved extremity (Spearman's test, [Formula: see text] ). Conclusion: Mast cells are involved in inflammatory reactions during the CRPS1. Mast cells could play a role in the production of cytokines such as TNFalpha.
PMID: 15019283
______________________
***Huygen FJ, Niehof S, Klein J, Zijlstra FJ.
Computer-assisted skin videothermography is a highly sensitive quality tool in the diagnosis and monitoring of complex regional pain syndrome type I.
Eur J Appl Physiol. 2004 Jan 21
Department of Anesthesiology, Pain Treatment Centre, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
The use of thermography in the diagnosis and evaluation of complex regional pain syndrome type 1 (CRPS1) is based on the presence of temperature asymmetries between the involved area of the extremity and the corresponding area of the uninvolved extremity. The interpretation of thermographic images is, however, subjective and not validated for routine use. The objective of the present study was to develop a sensitive, specific and reproducible arithmetical model as the result of computer-assisted infrared thermography in patients with early stage CRPS1 in one hand. Eighteen patients with CRPS1 on one hand and 13 healthy volunteers were included in the study. The severity of the disease was determined by means of pain questionnaires [visual analogue scale (VAS) pain and McGill Pain Questionnaire], measurements of mobility (active range of motion) and oedema volume. Asymmetry between the involved and the uninvolved extremities was calculated by means of the asymmetry factor, the ratio and the average temperature differences. The discrimination power of the three methods was determined by the receiver-operating curve (ROC). The regression between the determined temperature distributions of both extremities was plotted. Subsequently the correlation of the data was calculated. In normal healthy individuals the asymmetry factor was 0.91 (0.01) (SD), whereas in CRPS1 patients this factor was 0.45 (0.07) (SD). The performance of the arithmetic model based on the ROC curve was excellent. The area under the curve was 0.97, the P value was <0.001, the sensitivity 92% and specificity 94%. Furthermore, the temperature asymmetry factor was correlated with the duration of the disease and VAS pain. In conclusion, in resting condition, videothermography is a reliable additive diagnostic tool of early stage CRPS1. This objective tool could be used for monitoring purposes during experimental therapeutic intervention.
PMID: 14735366
Karacan I, Aydin T, Ozaras N.
Bone loss in the contralateral asymptomatic hand in patients with complex regional pain syndrome type 1.
Metab. 20 J Bone Miner 04;22(1):44-7.
SSK Vakif Gureba Hospital Physical Medicine and Rehabilitation Clinic, Istanbul, Turkey.
Regional osteoporosis was seen radiographically in clinically affected areas in patients with complex regional pain syndrome type 1 (CRPS1). The aim of the this study was to investigate whether bone loss developed in the contralateral hand in patients with unilateral CRPS1 of the hand. Thirty-two patients with CRPS1 of the hand were included in this study. Bone mineral density was measured in the left proximal femur and both ultradistal radiuses, using dual-energy X-ray absorptiometry. The subjects were classified as grades 1 to 3 according to the T-score of both ultradistal radiuses (densitometric grades): grade 1, both radiuses were normal; grade 2, bone loss was determined only in the affected radius; and grade 3, there was bone loss in both radiuses. Twenty (62.5%) patients had bone loss in the affected hand; 11 patients (34.4%) had bone loss only on the affected side and 9 patients (28.1%) had bone loss on both sides. The mean duration of the period between the diagnosis of the injury and the measurement of bone density was 1.9 +/- 0.6 months in patients with grade 1, 3.1 +/- 1.0 months in patients with grade 2, and 5.5 +/- 2.2 months in patients with grade 3. The Spearman test showed a significant correlation between the period of injury and the densitometric grade ( R = 0.774; P = 0.0001). In conclusion, the current study of patients with CRPS1, showed that the bone loss in the asymptomatic contralateral hand developed at a later stage than that in the affected hand. This bone loss was less frequent and of a lower degree in the asymptomatic contralateral hand than in the affected hand. The bone loss in the asymptomatic contralateral hand could be explained by the loss of sympathetic tone in CRPS1 and contralateral sympathetic innervation.
PMID: 14691686
Lake AP.
Intravenous regional sympathetic block: past, present and future?
Pain Res Manag. 2004 Spring;9(1):35-7.
Glan Clwyd Hospital, Bodelwyddan, Denbighshire, United Kingdom.
Intravenous regional sympathetic block is a valued component of the pain clinician's armamentarium for the management of the complex regional pain syndrome type 1. Treatment of this multifaceted condition is multimodal, and despite a lack of convincing supporting evidence from clinical trials, the author makes the case for retaining the technique while recommending both appropriate guidance and further study.
PMID: 15007401
Mense S.
Neurobiological basis for the use of botulinum toxin in pain therapy.
J Neurol. 2004 Feb;251 Suppl 1:1-7.
Institut fur Anatomie und Zellbiologie III, Universitat Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
The various serotypes of botulinum toxin (BoNT) exert their action by inhibiting the exocytosis of acetylcholine (ACh) on cholinergic nerve endings. BoNT cleaves proteins (e.g. SNAP-25 or VAMP) that are necessary for the docking of the ACh vesicle to the presynaptic membrane. Without docking, no ACh can be released into the synaptic cleft and the innervated structure is paralyzed. This article focuses on the neuromuscular endplate. The main targets of BoNT therapy are states of muscle hyperactivity such as contractures (in the physiological sense), or spasm and focal dystonias. CONTRACTURES: The "integrated hypothesis" of the formation of myofascial trigger points suggests that a lesion of a muscle damages the endplate so that excessive ACh is released. This causes a local contracture (partial contraction of a muscle fiber) underneath the endplate. The contracture compresses small blood vessels, and the tissue becomes ischemic. Ischemia leads to the release of bradykinin (BKN) and sensitization or excitation of nociceptors. BoNT is a causal therapy in these cases, because it stops the excessive ACh release. SPASM: Reflex spasm in a given muscle can be induced by nociceptive input from neighboring joints or muscles. If the force generated by a spasm is relatively high, it will compress the large blood vessels supplying the muscle. The final effect again is ischemia. In this case a drop in pH may accompany the ischemia and BKN are known to be effective stimulants for muscle nociceptors. DYSTONIA: In cases of weak dystonias, a compression of blood vessels is unlikely. However, the tonic contraction will cause a lowering of pH and a release of ATP. Muscle cells contain ATP at concentrations sufficient to excite muscle nociceptors. In cases of spasm and dystonia, BoNT can abolish the pain by relaxing the muscle. Since many patients report alleviation of their pain before the muscle relaxing effect of BoNT has set in, a direct analgesic action of BoNT is being discussed. Most hypotheses rest on the assumption that BoNT inhibits not only the exocytosis of ACh but also of their neurotransmitters. Such an action could be analgesic if the release of neuropeptides from nociceptive nerve endings is prevented. This way, BoNT could alleviate the pain of neuropathies and various types of headache where neurogenic inflammation plays a role. Another site of an analgesic action could be the postganglionic sympathetic nerve ending that uses norepinephrine and ATP as transmitters. Norepinephrine is known to increase cases of chronic pain, and ATP is a stimulant of muscle nociceptors. If BoNT inhibits the release of these transmitters, it could be analgesic in cases of sympathetically maintained pain including the complex regional pain syndrome.
PMID: 14991335
STUDIES N-Z
For a copy of this or any CRPS article, visit McMaster Health Sciences Library. Search Pub Med using the PMID number listed.
Pleger B, Tegenthoff M, Schwenkreis P, Janssen F, Ragert P, Dinse HR, Volker B, Zenz M, Maier C.
Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I.
Exp Brain Res. 2004 Mar;155(1):115-9. Epub 2004 Jan 27.
Department of Neurology, BG-Kliniken Bergmannsheil, Ruhr University Bochum, Buerkle-de-la-Camp Platz 1, 44789, Bochum, Germany.
Chronic back pain as well as phantom-limb pain is characterized by a close relationship between the amount of cortical reorganization and the magnitude of pain. In patients with positively assessed complex regional pain syndrome type I (CRPS I), we found a positive correlation between representational changes of primary somatosensory cortex (SI) and mean sustained pain levels. We investigated seven right-handed patients with CRPS I of one upper limb by means of somatosensory evoked potential (SSEP) mapping. Cortical representation of the CRPS-affected hand was significantly smaller than that of the contralateral healthy hand, giving rise to a substantial side difference. Subjective pain levels experienced over the last 4 weeks were estimated according to the visual analogue scale (VAS). Individual expansion of hand representation contralateral to the CRPS-affected limb was significantly correlated with mean pain intensity. Accordingly, low pain levels were linked to small representational side-to-side differences, while subjects with a distinctive hemispherical asymmetry reported the highest pain levels. Follow-up studies using functional imaging methods might be instrumental in providing a better understanding of this issue.
PMID: 15064892
Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff M.
Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I.
Neurosci Lett. 2004 Feb 12;356(2):87-90.
Department of Neurology, Ruhr-University Bochum, BG-Kliniken Bergmannsheil, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany.
In complex regional pain syndrome (CRPS) many clinical symptoms suggest involvement of the central nervous system. Neuropathic pain as the leading symptom is often resistant to therapy. In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation (rTMS) applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later. Pain re-intensified increasingly 45 min after rTMS. In contrast, sham rTMS did not alter pain perception. These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation.
Rizzo M, Balderson SS, Harpole DH, Levin LS.
Thoracoscopic sympathectomy in the management of vasomotor disturbances and complex regional pain syndrome of the hand.
Orthopedics. 2004 Jan;27(1):49-52.
Division of Orthopedic, Duke University Medical Center, Box 3945, Durham, NC 27710, USA.
Complex regional pain syndrome, vasospastic disorders, and hyperhidrosis are chronic and debilitating upper extremity problems. Twenty-nine consecutive patients treated with thoracoscopic sympathectomy are presented. Diagnoses included complex regional pain syndrome, hyperhidrosis, Buerger's disease, Raynaud's disease, and peripheral vascular disease. All patients with hyperhidrosis had complete symptom resolution. Patients with Buerger's and Raynaud's disease had excellent/good results. Six patients with complex regional pain syndrome had excellent or good relief; the remaining six patients had varying degrees of recurrence. A statistically significant association was noted between duration of complex regional pain syndrome prior to sympathectomy and outcome. Thoracoscopic sympathectomy is an effective treatment for hyperhidrosis and vasospastic disorders. Although the results for complex regional pain syndrome are not uniformly excellent, this technique offers promise in the treatment of this difficult problem.
PMID: 14763530
CHARLES BERDE, MD PhD, presenter at the Tampa conference, is a well known expert in the treatment of CRPS in children and teens. The Pain Treatment Service has treated over 600 children since 1986 and continues to do so.There is also ongoing research at the Boston Hospital where he works.
PHYSICAL THERAPY AND COGNITIVE BEHAVIOURAL TREATMENT FOR CRPS
Berde CB,Lee BH, Scharff L, Sethna NF, McCarthy CF, Scott-Sutherland J, Shea AM, Sullivan P, Meier P, Zurakowski D,Masek BJ. J Pediatr 2002 Jul;141(1):135-40
Pain Treatment Service and the Departments of Physical Therapy, Orthopaedic Surgery, and Psychiatry,Children's Hospital, Boston, Massachusetts.
Complex regional pain syndromes (CRPS; type 1, reflex sympathetic dystrophy, and type 2, causalgia) involve persistent pain, allodynia, and vasomotor signs. We conducted a prospective, randomized, single-blind trial of physical therapy (PT) and cognitive-behavioral treatment for children and adolescents with CRPS. Children 8 to 17 years of age (n = 28) were randomly assigned to either group A (PT once per week for 6 weeks) or group B (PT 3 times per week for 6 weeks). Both groups received 6 sessions of cognitive-behavioral treatment. Assessments of pain and function were repeated at two follow-up time periods. Outcomes were compared at the three time points through the use of parametric or nonparametric analysis of variance and post hoc tests. All five measures of pain and function improved significantly in both groups after treatment, with sustained benefit evident in the majority of patients at long-term follow-up. Recurrent episodes were reported in 50% of patients, and 10 patients eventually received sympathetic blockade. Most children with CRPS showed reduced pain and improved function with a noninvasive rehabilitative treatment approach. Long-term functional outcomes were also very good.
PMID: 12091866
For a copy of this or any CRPS article, visit McMaster Health Sciences Library. Search Pub Med using the PMID number listed.
GENDER DIFFERENCES IN CRPS I/ RSD IN CHILDREN AND ADOLESCENTS
Charles Berde, M.D., Ph.D., Harvard Medical School, Director, Pain Treatment Service, Boston Children's Hospital, Boston, Massachusetts
Complex regional pain syndrome, type 1 (CRPS1) or reflex sympathetic dystrophy (RSD) is being diagnosed more frequently in children and adolescents. Over the last 12 years, our pain center has examined the demographics, associated medical and lifestyle factors, and responses to treatment in over 450 patients. Some demographic features in children appear different from those described for adults:
(1) Children and adolescents have lower extremity involvement 6 times more often than upper extremity involvement.
(2) Girls are affected roughly 5 times as often as boys.
(3) RSD/CRPS1 is rare below age 8; the incidence increases markedly just before puberty.
(4) Female dancers, gymnasts and competitive athletes comprise a high percentage of the patients.
A high percentage of patients present either confined to crutches or in a wheelchair. School absenteeism is more common in these patients than in a matched population of rheumatology patients. Coexisting psychiatric diagnoses commonly include depression, anxiety disorders, post-traumatic stress disorders, distorted body image and eating disorders, and stressful family dynamics.
Treatments advocated for RSD have varied largely according to subspecialty and training of health providers. A program for prospective evaluation of these patients was established recently with funding from NICHD. Preliminary studies by Dr. Sethna and others on quantitative sensory and autonomic evaluation will be summarized. Treatments under prospective controlled evaluation include physical therapy, cognitive-behavioral interventions, tricyclics and anticonvulsants, and continuous infusion sympathetic blocks.
RSDS IN CHILDREN AND ADOLESCENTS
(summary of Dr. Berde’s presentation at RSDSA's Tampa conference)
Treatment varies according to the individual child. It is essential to maintain a close rapport with the patient and family so that they can understand and cope with the treatment.
Active PT and CBT (cogntive behaviour therapy) are at the top of the list for treatment and a large percentage of kids improve with these two methods. It is a stepwise return to weight bearing and understanding the role of pain. Desensitization and aqua therapy are also used. CBT includes relaxation training, biofeedback and other coping pain skills. Many children recount that CBT helps with daily stress and solving problems. If the pain and limb problem becomes chronic, then treatment for depression or anxiety is considered. Tricyclic antidepressants help with sleep and sometimes anticonvulsants (Neurontin) are used. Finding the right dose of the right drug and assessing side effects are all very important.Those who do not improve with PT and CBT, can receive sympathetic blockade.
Various methods can be used from lumbar paravertebral, lumbar epidural or IV regional with single shot or continuous methods. It depends on the individual case. Invasive procedures are saved for those who have tried all other therapies and did not respond well. These treatments include spinal cord or peripheral stimulation, implantable pumps and sympathectomy. No form of neurodestructive sympathectomy is done due to possible long term complications.
Note: This review article appears in the Winter Issue of the PARC PEARL.
FURTHER READING
Berde, C.B., & Sethna, N.F. (in press).
Sethna, N.F. (1999). Pharmacotherapy in long-term pain: Current experience and future direction. In P. McGrath, & G.A. Finley (Eds.), Chronic and recurrent pain in children and adolescents. Progress in pain research and management (pp. 243-266). Seattle: IASP Press.
Sherry DD et al Short and long term outcomes of children with CRPS 1 treated with exercise therapy. Clinical Journal of Pain 1999; 15:218-33
Stanton, R.P., Malcolm, J.R., Wesdock, K.A., & Singsen, B.H(1993). Reflex sympathetic dystrophy in children: An orthopedic perspective. Orthopedics, 16, 773-779.
Wilder, R.T., Berde, C.B., Wolohan, M., Vieyra, M.A., Masek, B.J., & Micheli, L.J. (1992). Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients. Journal of Bone & Joint Surgery American Volume, 74, 910-919.
INTRODUCTION
Dr Robert Jay Schwartzman, presenter at the Tampa conference, is a well known expert in the treatment of CRPS in children and adults.He has been treating and researching CRPS for many years and continues to break new ground. He was the first to document the spread of CRPS (see Studies file) and discover the movement disorder component of CRPS. What follows are some of his most recent studies.
KETAMINE-MIDAZOLAM ANAESTHESIA FOR INTRACTABLE CRPS-1
INTRODUCTION
CRPS-1 is a very hard to treat syndrome characterized by neuropathic pain. CRPS can spread and become resistant to therapy. More treatments are urgently needed. NMDA receptors are thought play an active role in central pain and NMDA agonists as therapy for CRPS (and neuropathic pain) are being studied.
METHODS
Ten patients with intractable CRPS-1 were given anesthesia which consisted of ketamine and midazolam for 5 days. Some patients were intubated and some had spontaneous breathing. On day 6 they were slowly tapered from infusions.
OBSERVATIONS
INITIAL
All TEN responded by having no pain, no hyperalgesia, no allodynia and an absence of CRPS-1 signs.
LONG TERM
Five out of ten had full pain relief for 2 months up to 3.5 years. In 8/10 patients, after 6-8 weeks the original nociceptive pain returned. In 7/8 the pain was at the original injury site. Hyperalgesia and allodynia recurred in 4/10 who then received another ketamine treatment. Success happened in 2/3. Patients were all able to use less pain medication.
CONCLUSIONS
The authors are quick to say that this treatment shows potential and could be an effective treatment option for severe CRPS-1. They do raise the following issues: which patients would benefit most, what selection criteria would be used to select patients, when to treat the CRPS, and maintenance schedules for re-treatment.
This is the first attempt at using ketamine anesthesia for intractable CRPS-1 and it does not come without its risks. Patients need to be asleep and monitored carefully during the five day treatment. Perhaps in future trials, a less risky form of treatment can be found.
Source: Schwartzman, RJ et al "Ketamine-Midazolam Anesthesia for Intractable CRPS-1" 2002 presented to IASP 2002 Conference
SKIN BLOOD FLOW CHANGES DURING KETAMINE/MIDAZOLAM ANESTHESIA FOR INTRACTABLE CRPS-1
REVIEW
Skin temperature and color changes are an integral part of CRPS. The skin can turn blue, reddish, mottled, or purple. Temperatures vary from hot to warm or cold. Monitoring skin blood flow changes help clinicians decide on the effectiveness of CRPS treatments e.g. when using sympathetic blocks. One such new promising treatment is ketamine/midazolam anesthesia for chronic CRPS-1. This study is the first of its kind to investigate this treatment.
AIMS
Data on skin blood flow (SBF) at rest and during vasomotor ic challenge (with heating probe) was collected. Patient's status and responses before, during and after ketamine anesthesia were observed. Could this method be used to asses the ability of the blood vessels to regulate themselves or determine vasomotor impairment in CRPS? Could this be used as a tool to assess treatment success ?
PATIENTS
Eight patients with intractable CRPS-1 were analyzed for blood flow with laser doppler flowmetry (PF 4001) and a heating probe was used to raise skin temperature. Patients were measured at rest and during the vasomotor challenge.
RESULTS
Under ketamine anesthesia, a significant increase in SBF was observed in the first 72 hours. Interestingly, the areas of the most pain showed the strongest increase, up to 10 fold. Then SBF normalized and vasomotor reagibility occurred e.g. decreased, edema, hyperemia and temperature changes. When the limb was locally heated, the highest increase of SBF was found on day 2 and 3 of therapy.
CONCLUSIONS
The authors are the first to admit that more studies must be done before LDF can be recommended as a diagnostic tool or for therapy. Suggestions include monitoring SBF changes in CRPS, possibly predicting therapeutic success, to quantify vasomotor reactive capacity (rest/vasomotor challenge), to help assess sympathetic activity and to contribute to a piece of the diagnostic puzzle of CRPS. Using LDF as a diagnostic tool would be another first since there is none available at this time.
Source: Schwartzman, RJ et al "Skin Blood Flow Changes During Ketamine/Midazolam Anesthesia for Intractable CRPS-1 2002
Note: Low dose ketamine treatments are now being developed in Canada. Contact us for the name of Canadian doctors offering ketamine treatments. These review articles can be found in the PARC PEARL March issue.
STUDIES A-M
***Argoff CE. A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain. 2002 Nov-Dec;18(6 Suppl):S177-81.
Cohn Pain Management Center, North Shore University Hospital, New York University School of Medicine, Bethpage, New York 11714, USA. pargoff@optonline.net
Understanding the pathophysiology of a pain syndrome is helpful in selecting appropriate treatment strategies. Nociceptive pain is related to damage to tissues due to thermal, chemical, mechanical, or other types of irritants. Neuropathic pain results from injury to the peripheral or central nervous system. Common examples of neuropathic pain include postherpetic neuralgia, diabetic neuropathy, complex regional pain syndrome, and pain associated with spinal cord injuries. Nociceptive pain may have similar clinical characteristics to neuropathic pain. It is also possible for acute nociceptive pain to become neuropathic in nature, as with myofascial pain syndrome. A clear benefit of botulinum toxin therapy for treatment of neuropathic pain disorders is that it often relieves pain symptoms. Although the precise mechanism of pain relief is not completely understood, the injection of botulinum toxin may reduce various substances that sensitize nociceptors. As a result, botulinum toxin types A and B are now being actively studied in nociceptive and neuropathic pain disorders to better define their roles as analgesics.
PMID: 12569966
---------------
Basford JR, Sandroni P, Low PA, Hines SM, Gehrking JA, Gehrking TL.Effects of linearly polarized 0.6-1.6 &mgr;M irradiation on stellate ganglion function in normal subjects and people with complex regional pain (CRPS I). Lasers Surg Med. 2003 Jun;32(5):417-423.
Department of Physical Medicine and Rehabilitation, Autonomic Disorder Center, Mayo Clinic and Foundation, 200 Southwest Second Street, Rochester, Minnesota 55905.
BACKGROUND AND OBJECTIVES: Stellate ganglion blocks are an effective but invasive treatment of upper extremity pain. Linearly polarized red and near-infrared (IR) light is promoted as a safe alternative to this procedure, but its effects are poorly established. This study was designed to assess the physiological effects of this latter approach and to quantitate its benefits in people with upper extremity pain due to Complex Regional Pain Syndrome I (CRPS I, RSD). STUDY DESIGN/MATERIALS AND METHODS: This was a two-part study. In the first phase, six adults (ages 18-60) with normal neurological examinations underwent transcutaneous irradiation of their right stellate ganglion with linearly polarized 0.6-1.6 &mgr;m light (0.92 W, 88.3 J). Phase two consisted of a double-blinded evaluation of active and placebo radiation in 12 subjects (ages 18-72) of which 6 had upper extremity CRPS I and 6 served as "normal" controls. Skin temperature, heart rate (HR), sudomotor function, and vasomotor tone were monitored before, during, and for 30 minutes following irradiation. Analgesic and sensory effects were assessed over the same period as well as 1 and 2 weeks later. RESULTS: Three of six subjects with CRPS I and no control subjects experienced a sensation of warmth following active irradiation (P = 0.025). Two of the CRPS I subjects reported a >50% pain reduction. However, four noted minimal or no change and improvement did not reach statistical significance for the group as a whole. No statistically significant changes in autonomic function were noted. There were no adverse consequences. CONCLUSIONS: Irradiation is well tolerated. There is a suggestion in this small study that treatment is beneficial and that its benefits are not dependent on changes in sympathetic tone. Further evaluation is warranted. Lasers Surg. Med. 32:417-423, 2003. Copyright 2003 Wiley-Liss, Inc.
PMID: 12766967
-------------------
Bennett GJ. Are the complex regional pain syndromes due to neurogenic inflammation?
Neurology. 2001 Dec 26;57(12):2161-2.
Comment on:
Neurology. 2001 Dec 26;57(12):2179-84.
Letter
PMID: 11756591
***Cordivari, MD 1 2, V. Peter Misra, MD, FRCP 1, Santiago Catania, MRCP 1, Andrew J. Lees, MD, FRCP 2 *
Treatment of dystonic clenched fist with botulinum toxin.
Mov Disord. 2001 Sep;16(5):907-13.
Department of Clinical Neurophysiology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom
2Reta Lila Weston Institute of Neurological Studies, University College of London, United Kingdom
email: Andrew J. Lees (alees@ion.ucl.ac.uk)
* Correspondence to Andrew J. Lees, Reta Lila Weston Institute of Neurological Studies, Windeyer Building, 46 Cleveland Street, University College of London W1T 4JF, UK
A videotape accompanies this article.
Abstract
Fourteen patients with dystonic clenched fist (three with Corticobasal Ganglionic Degeneration, seven with Parkinson's disease, and four with Dystonic-Complex Regional Pain Syndrome) were treated with botulinum toxin A (BTXA, Dysport®). The muscles involved were identified by the hand posture and EMG activity recorded at rest and during active and passive flexion/extension movements of the finger and wrist. EMG was useful in distinguishing between muscle contraction and underlying contractures and to determine the dosage of BTX. All patients had some degree of flexion at the proximal metacarpophalangeal joints and required injections into the lumbricals. The response in patients depended on the severity of the deformity and the degree of contracture. All patients had significant benefit to pain, with accompanying muscle relaxation, and palmar infection, when present, was eradicated. Four patients with Parkinson's disease and one patient with Dystonia-Complex Regional Pain Syndrome obtained functional benefit. © 2001 Movement Disorder Society.
Received: 18 December 2000; Revised: 4 April 2001; Accepted: 19 April 2001
__________
***Kobana,M. S. Leisa, S. Schultze-Mosgaub and F. Birklein
Tissue hypoxia in complex regional pain syndrome
c/a Neurologische Klinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, D-91054, Erlangen, Germany
b Klinik für Mund-, Kiefer- und Gesichtschirurgie Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, D-91054, Erlangen, Germany c Neurologische Klinik, Johannes Gutenberg-Universität Mainz, Langenbeckstraße 1, D-51101, Mainz, Germany
Received 26 February 2002; accepted 6 December 2002. ; Available online 14 May 2003.
Untreated complex regional pain syndrome (CRPS) may progress from acute stages with increased hair and nail growth in the affected limb to chronic stages with atrophy of the skin, muscles and bones. The aim of this study was to investigate whether tissue hypoxia could be one mechanism responsible for this late CRPS symptoms.
Nineteen patients with CRPS and two control groups (healthy control subjects, surgery patients with edema) participated in this study. Skin capillary hemoglobin oxygenation (HbO2 ) was measured non-invasively employing micro-lightguide spectrophotometry (EMPHO). The EMPHO probe was mounted force-controlled onto the skin of the affected and unaffected hand. HbO2 was measured at rest and during postischemic reactive hyperemia.
HbO2 did not differ between the right (58.20%±1.12) and left (57.79%±1.31, ns) hand in control subjects. However, in patients, HbO2 of the affected side (36.63%±2.16) was significantly decreased as compared to the clinically unaffected side (46.35%±2.97, P<0.01). As compared to controls, HbO2 in CRPS was reduced on both sides (P <0.001). Postischemic hyperoxygenation was impaired on the affected side in CRPS (60.81%±2.90) – as compared to the unaffected side (67.73%±1.50, P<0.04) and to controls (68.63%±0.87, P<0.005). The unaffected limb in CRPS did not differ from controls. Despite skin edema, pre- (49.06%±2.02) and postsurgery HbO2 (53.15%±4.44, ns) were not different in the second control group.
Our results indicate skin hypoxia in CRPS. Impairment of nutritive blood flow in the affected limb may be one factor contributing to atrophy and ulceration in chronic CRPS. The investigation of patients after surgery revealed that edema could not be the only reason for hypoxia.
[Corresponding Author Contact Information] Corresponding author. Tel.: +49-6131-173270; fax: +49-6131-175625
--------------
Kuczkowski, KM. Bretylium in the treatment of complex regional pain syndrome: uncommon side-effect of a common drug. Anaesthesia 2003 Feb;58(2):201-2 Letter.
PMID: 12562438
---------------------------------------------
STUDIES N-Z
McCabe CS, Haigh RC, Ring EF, Halligan PW, Wall PD, Blake DR. A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1).
Rheumatology (Oxford) 2003 Jan;42(1):97-101
The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. candy.mccabe@rnhrd-tr.swest.nhs.uk
BACKGROUND: We assessed mirror visual feedback (MVF) to test the hypothesis that incongruence between motor output and sensory input produces complex regional pain syndrome (CRPS) (type 1) pain. METHODS: Eight subjects (disease duration > or =3 weeks to < or =3 yr) were studied over 6 weeks with assessments including two controls (no device and viewing a non-reflective surface) and the intervention (MVF). Pain severity and vasomotor changes were recorded. RESULTS: The control stages had no analgesic effect. MVF in early CRPS (< or =8 weeks) had an immediate analgesic effect and in intermediate disease (< or =1 yr) led to a reduction in stiffness. At 6 weeks, normalization of function and thermal differences had occurred (early and intermediate disease). No change was found in chronic CRPS. CONCLUSIONS: In early CRPS (type 1), visual input from a moving, unaffected limb re-establishes the pain-free relationship between sensory feedback and motor execution. Trophic changes and a less plastic neural pathway preclude this in chronic disease.
PMID: 12509620
--------------------------------
Parisod E, Murray RF, Cousins MJ.
Conversion disorder after implant of a spinal cord stimulator in a patient with a complex regional pain syndrome. Anesth Analg 2003 Jan;96(1):201-6, University of Sydney, Pain Management & Research Centre, Royal North Shore Hospital, St. Leonards, Australia.
IMPLICATIONS: This case history describes the treatment of a patient suffering with persistent pain. He was treated surgically with implantation of a spinal cord stimulator. After surgery, a partial paralysis that could not be explained medically and that was probably related to emotional factors occurred, and cognitive behavioral treatment was begun. This paper discusses the importance of considering social and psychological factors when medical treatment options are considered.
PMID: 12505953
------------------
***Sandroni,P., Lisa M. Benrud-Larson, Robyn L. McClelland and Phillip A. Low Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study
Mayo Clinic, 200 First Stret SW, Rochester, MN 55905, USA
Received 5 September 2002; accepted 9 December 2002. ; Available online 8 May 2003.
Abstract
The objective of this study is to undertake a population based study on the incidence, prevalence, natural history, and response to treatment of complex regional pain syndrome (CRPS). All Mayo Clinic and Olmsted Medical Group medical records with codes for reflex sympathetic dystrophy (RSD), CRPS, and compatible diagnoses in the period 1989–1999 were reviewed as part of the Rochester Epidemiology Project. We used IASP criteria for CRPS. The study population was in the Olmsted County, Minnesota (1990 population, 106,470). The main outcome measures were CRPS I incidence, prevalence, and outcome. Seventy-four cases of CRPS I were identified, resulting in an incidence rate of 5.46 per 100,000 person years at risk, and a period prevalence of 20.57 per 100,000. Female:male ratio was 4:1, with a median age of 46 years at onset. Upper limb was affected twice as commonly as lower limb. All cases reported an antecedent event and fracture was the most common trigger (46%). Excellent concordance was found between symptoms and signs and vasomotor symptoms were the most commonly present. Three phase bone scan and autonomic testing diagnosed the condition in >80% of cases. Seventy-four percent of patients underwent resolution, often spontaneously. CRPS I is of low prevalence, more commonly affects women than men, the upper more than the lower extremity, and three out of four cases undergo resolution. These results suggest that invasive treatment of CRPS may not be warranted in the majority of cases.
[Corresponding Author Contact Information] Corresponding author. Tel.: +1-507-284-2090; fax: +1-507-266-6754
--------------------
Schasfoort FC, Bussmann JB, Zandbergen AM, Stam HJ.
Impact of upper limb complex regional pain syndrome type 1 on everyday life measured with a novel upper limb-activity monitor.
Pain 2003 Jan;101(1-2):79-88
Department of Rehabilitation Medicine, Erasmus MC, University Medical Center Rotterdam, PO Box 1738, 300 DR Rotterdam, Rotterdam, The Netherlands. schasfoort@rev.fgg.eur.nl
Complex regional pain syndrome type 1 (CRPS1) often leads to serious activity limitations in everyday life. To date, however, limitations in patients with CRPS1 of an upper limb have not been objectively measured .Therefore, the aim of this study was to determine the long-term impact of upper limb CRPS1 on general mobility and upper limb usage during everyday life, as measured with a novel upper limb-activity monitor (ULAM). In ten female chronic CRPS1 patients and ten healthy control subjects, 24-h activity patterns were measured with the ULAM. This ULAM consists of body-fixed acceleration sensors, connected to a recorder worn around the waist. The ULAM automatically detects upper limb activity during mobility-related activities. Several outcome measures related to general mobility and upper limb usage were compared between patients and controls. The results showed that CRPSI in the dominant upper limb had modest impact on general mobility; i.e. on the percentages spent in body positions and body motions and on mean intensity of body activity. For upper limb usage outcome measures during sitting, there was a marked difference between CRPS1 patients and controls. Especially patients with dominant side involvement clearly showed less activity of their involved limb during sitting, indicated by significant differences for the mean intensity (P=0.014), percentage (P=0.004), and proportion (P=0.032) of upper limb activity. It is concluded that these ten chronic CRPS1 patients still had limitations in upper limb usage during everyday life, 3.7 years (average) after the causative event.
PMID: 12507702
-----------------------
Schouten AC, Van De Beek WJ, Van Hilten JJ, Van Der Helm FC.
Proprioceptive reflexes in patients with reflex sympathetic dystrophy.
Delft University of Technology, Department of Mechanical Engineering, Man Machine Systems and Control, Mekelweg 2, 2628 CD Delft, Leiden, The Netherlands.
Reflex sympathetic dystrophy (RSD) is a syndrome that frequently follows an injury and is characterized by sensory, autonomic and motor features of the affected extremities. One of the more common motor features of RSD is tonic dystonia, which is caused by impairment of inhibitory interneuronal spinal circuits. In this study the circuits that modulate the gain of proprioceptive reflexes of the shoulder musculature are quantitatively assessed in 19 RSD patients, 9 of whom presented with dystonia. The proprioceptive reflexes are quantified by applying two types of force disturbances: (1) disturbances with a fixed low frequency and a variable bandwidth and (2) disturbances with a small bandwidth around a prescribed centre frequency. Compared to controls, patients have lower reflex gains for velocity feedback in response to the disturbances around a prescribed centre frequency. Additionally, patients with dystonia lack the ability to generate negative reflex gains for position feedback, for these same disturbances. Proprioceptive reflexes to the disturbances with a fixed low frequency and variable bandwidth present no difference between patients and controls. Although dystonia in the RSD patients was limited to the distal musculature, the results suggest involvement of interneuronal circuits that mediate post synaptic inhibition of the motoneurons of the proximal musculature.
PMID: 12743675
------------------------
Singh B, Moodley J, Shaik AS, Robbs JV.
Sympathectomy for complex regional pain syndrome.
J Vasc Surg 2003 Mar;37(3):508-11
Department of Surgery, Nelson R. Mandela School of Medicine, Faculty of Health Sciences, University of Natal, 4013 Congella, South Africa.
BACKGROUND: With the easier and earlier recognition of complex regional pain syndrome (CRPS), a reappraisal of its therapy, particularly the role and timing of sympathectomy, is warranted. PATIENTS AND METHODS: Over a 9-year period, 42 patients with CRPS type II of the upper extremity were referred for sympathectomy. Patients were categorized according to the duration of the symptoms (group I, <3 months; group II, >3 months). All patients underwent initial medical treatment; stellate ganglion blocks were performed when symptoms persisted beyond 6 weeks. Patients were referred for thoracoscopic sympathectomy on persistence of the pain syndrome. A visual linear analogue scale was used to evaluate outcome of sympathectomy. RESULTS: Thoracoscopic dorsal sympathectomy was successfully undertaken in 32 patients. In the remaining 10 patients, thoracoscopy was not technically feasible and open sympathectomy was performed. There was an overall improvement in all 42 patients undergoing sympathectomy (P <.001, Wilcoxon signed rank test). The outcome in group I was significantly better than in group II (P <.003, Mann-Whitney U test). The diagnosis of sympathetically mediated pain with stellate blockade did not correlate with clinical outcome. Patients undergoing thoracoscopic sympathectomy had a better outcome than those undergoing open sympathectomy. There were no complications, and the hospital stay was shorter in the thoracoscopic group. CONCLUSION: Early recognition of CRPS and prompt recourse to surgical sympathectomy is a useful option in the management of CRPS.
PMID: 12618683
-------------------------------------
Son UC, Kim MC, Moon DE, Kang JK.
Motor cortex stimulation in a patient with intractable complex regional pain syndrome type II with hemibody involvement. Case report.
J Neurosurg 2003 Jan;98(1):175-9
Department of Neurosurgery, Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. sbc@cmc.cuk.ac.kr
The authors describe the effectiveness of motor cortex stimulation (MCS) in a patient with complex regional pain syndrome (CRPS) Type II, formerly known as causalgia, with hemibody allodynia. During MCS, a subjective sensation of warm paresthesia developed in the painful hand and forearm and spread toward the trunk. Pain and allodynia in the areas associated with this sensation were alleviated significantly. The analgesic effect of stimulation proved to be long lasting and was still present at the 12-month follow up. The authors speculate that MCS might exert its effect through the modulation of thalamic activity in this particular case of CRPS with hemisensory deficit. A central mechanism associated with functional disturbance in noxious-event processing in the thalamus might have an important role in the pathogenesis of the condition.
PMID: 12546368
---------------
van de Beek WJ, Schwartzman RJ, van Nes SI, Delhaas EM, van Hilten JJ. Diagnostic criteria used in studies of reflex sympathetic dystrophy.
Neurology. 2002 Feb 26;58(4):522-6.
Department of Neurology, Leiden University Medical Center, the Netherlands.
OBJECTIVE: Assessment of the diagnostic criteria of reflex sympathetic dystrophy (RSD) and evaluation of the impact of the introduction of the diagnostic criteria of complex regional pain syndrome (CRPS) on the international application of diagnostic criteria of RSD. METHODS: Randomized controlled trials and clinical investigations, published between January 1980 and June 2000, were evaluated with regard to the applied diagnostic criteria of RSD. RESULTS: One hundred seven studies were identified. Thirty-four of these studies were excluded because of inadequate reporting of diagnostic criteria. The 73 included studies were not homogeneous with regard to the diagnostic criteria because they applied many different aspects of sensory and autonomic features. Only 12% of the studies considered the presence of motor features, mostly vaguely described, as mandatory for the diagnosis RSD. Although 10 of the 23 studies published since the introduction of CRPS have applied this term, only 3 used the exact criteria without additions or other modifications. CONCLUSION: Diagnostic criteria sets of RSD focus on many different aspects of sensory and autonomic features that generally are described vaguely. This has not changed since the introduction of the CPRS criteria. These findings question whether the current criteria adequately define RSD.
PMID: 11865127
--------------
***van de Beek WJ, Vein A, Hilgevoord AA, van Dijk JG, van Hilten BJ.
Neurophysiologic aspects of patients with generalized or multifocal tonic dystonia of reflex sympathetic dystrophy.
J Clin Neurophysiol. 2002 Jan;19(1):77-83.
Department of Neurology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Reflex sympathetic dystrophy (RSD) is a syndrome dominated by sensory, autonomic, and motor features of the extremities. In this study, 10 severely affected RSD patients who progressed to multifocal or generalized tonic dystonia underwent H-reflex evaluation, needle electromyography (EMG), polysomnography, somatosensory evoked potentials, and transcranial magnetic stimulation. H-reflex evaluation revealed an impaired vibratory inhibition of the H-reflex and a higher facilitation peak in the recovery curve between 200 to 350 msec. Needle EMG revealed an impaired reciprocal inhibition, and many patients were unable to alter the amount of muscle activity voluntarily. Evaluations of the stretch reflex showed a markedly decreased threshold and abnormal responses to tonic and phasic changes. Polysomnography performed in five patients revealed no abnormal EMG activity during nonrapid eye movement and rapid eye movement sleep, but EEG arousal phenomena provoked abnormally high and brief bursts of surface EMG activity in all registered muscle groups. Somatosensory evoked potentials and transcranial magnetic stimulation were normal. Taken together, the findings in these patients with tonic dystonia of RSD are in accordance with an impairment of inhibitory interneuronal circuits at the level of the brainstem or spinal cord.
PMID: 11896357
--------------
***van de Beeka, Willem-Johan T., Bart O. Roepb, Arno R. van der Slikb, Marius J. Giphartb and Bob J. van Hilten,
Susceptibility loci for complex regional pain syndrome
a) Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands b) Department Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Received 11 April 2002; accepted 22 October 2002. ; Available online 27 March 2003.
An association between HLA-DR13 and patients with complex regional pain syndrome (CRPS) who progressed towards multifocal or generalized tonic dystonia was recently reported. We now report on a new locus, centromeric in HLA-class I, which was significantly associated with a spontaneous development of CRPS, suggesting an interaction between trauma severity and genetic factors conferring CRPS susceptibility. Additionally, an association with the D6S1014 locus was found, supporting the previous finding of an association with HLA-DR13.
[Corresponding Author Contact Information] Corresponding author. Tel.: +31-71-526-2895; fax: +31-71-524-8253
DUTCH RSD CONFERENCE
NOVEMBER 14-15 , 2003.
RSD AND THE SYMPATHETIC NERVOUS SYSTEM
R. Baron, Klink fur Neurologie, Christian-Alrechts-Universitat, Kiel, Germany,
The striking response of neuropathic pain syndromes such as CRPS (CRPS, causalgia) and RSD to
sympatholytic procedures together with signs of autonomic nervous system abnormalities suggest that the
sympathetic efferent system can generate or enhance pain (SMP) and may be involved in the dysregulation of skin blood flow and sweating. Evidence from animal experiments: There is convincing evidence from animal studies that after complete and partial nerve injury both damage and undamaged nociceptive C-fibers acquire a chemical sensitivity to noradrenergic agents and can be activated by sympathetic - trunk stimulation. This sympatho-afferent transmission is mediated by alpha 2 adrenoreceptors Accordingly, mRNA for alpha 2-Aadrenoreceptors is up-regulated in DRG neurons after nerve transection.
Pathophysiology of SMP in patients: The adrenergic influence on afferents in humans was analyzed in
patients with CRPS type 2. In a subgroup of patients with SMP, intracutaneous application of
alpha-adrenergic agents enhances pain and hyperalgesia. Accordingly, autoradiographic studies indicate
that the number of alpha-1-adrenorecptrs in hyperalgesic skin of patients with SMP is significantly greater
than in the skin of normal subjects. Further more, it could be demonstrated in CRPS1 that spontaneous
pain and mechanical hyperalgesia was augmented when sympathetic cutaneous vasoconstrictor neurons
were activated physiologically by thermoregulatory cold stress. There was a high correlation between pain relief during sympathetic blocks and augmentation of pain during sympathetic chain activation. The latter results show that also sympathetic activity modulated in physiological ranges and endogenous
noradrenaline release is able to enhance pain in CRPS.
Autonomic abnormalities in patients: Controlled thermoregulatory reflexes (Whole body warming, cooling) were used to experimental regulation patterns were identified related to the duration of the disorder: in the warm regulation type (acute stage) the affected limb was warmer and skim perfusion values were higher than contralaterally during the entire spectrum of sympathetic activity, Even massive body cooling failed to activate sympathetic vasoconstrictor neurons. In the intermediate type temperature and perfusion were either warmer or colder depending on the degree of sympathetic activity. In the cold type (Chronic stages) temperature and perfusion were lower on the affected side during the entire thermoregulatory cycle.
In conclusion, a central unilateral inhibition of cutaneous sympathetic vasoconstrictor neurons leads to a
warmer affected limb in the acute stage. Secondary changes in the neurovascular transmission induce
vasoconstriction and cold skin in chronic CPRS. The maximal skin temperature difference between the
affected and unaffected extremity that occurs during the theromregulatory cycle can be sued as a
diagnostic tool. With high sensitivity and specificity it distinguishes CRPS from other extremity pain
syndromes.
INFLAMMATION AND RSD
RJA Goris, MD University Hospital Nijmegen, Dept. of Surgery, Nijmegen.
The majority of scientific publications on RSD/CRPS I address late problems relating to pain, tissue
dystrophy, and atrophy and neurological changes. However, in the early phase, signs and symptoms of
inflammation are prominent. Acute inflammation in RSD could be documented by studying the
extravasation of immunoglobulin in the affected extremity. Also, morphologically, signs of tissue damage
could be demonstrated in skeletal muscle, related to tissue damage caused by toxic oxygen radicals. Such
alterations could be reproduced in an experimental model of oxygen radical-induced skeletal muscle
damage in the rat. The therapeutic effect of oxygen radical scavengers and corticosteroids in acute RSD
also indicates the role of these compounds in generating pathological changes.
The problem of performing “normal” skeletal muscle work with an RSD-affected extremity was objectified by NMR-spectroscopy studies indicating that at tissue level, the supply and or utilization of oxygen in impaired. which also is a characteristic encountered in severe inflammation. As a consequence oxygen extraction in the affected limb is impaired, as shown by elevated venous oxygen saturation levels. In a recent study, the inflammatory response to a Colles fracture was prospectively studied in 115 patients. A wide variety was found in the severity of the inflammatory reaction, After one year. follow-up, the incidence of RSD in these will be documented and the early response related to late RSD.
Many problems still have to be elucidated in RSD such as why patient develops RSD and most others do
not. Studying the genetic characteristics in respect to generating an exaggerated inflammatory response,
may be one of the pathways to explore further.
1. Veldman PHJM et al Signs and symptoms of RSD Lancet 1993
2. Goris RJA RSD World Jour Surg 1998
3. van der Laan L Goris RJA Sudeck Syndrome Unfallchir 1997
4. van der Laan, Goris RJA RSD Hand Cline 1997
5. Oyen WJG et al RSD of the hand Pain 1993
6. van der Laan et al CRPS 1 RSD Neurology 1998
7. van der Laan L et al A novel animal model Free Rad Res. 1997
8. Goris RJA et al Are toxic oxygen radical... Free Rad RES Comms 1987
9. Heereschap A et al; Metabolic changes in RSD Muscle Nerve 1993
10. Goris RJA Conditions associated with impaired O2 extraction Springer Verlag 1991
11. Vaneker M et al Genetic factors associated with CRPS Disability Med 2002
NEUROGENIC INFLAMMATION IN RSD
F Birklein, Dept. of Neurology, University Clinic, Mainz, Germany.
Many clinical symptoms of acute CRPS resemble inflammation--pain,edema, increased skin temperature
and blood flow. However, inflammation in the classical sense has not been unequivocally proven. Rather
the coincidence, of inflammatory signs with trophic changes (hair, growth, high-turnover osteoporosis) and mechanical hyperalgesia without hyperalgesia to heat strongly suggests “neurogenic” inflammation.
Trauma related activation of primary afferents cause neuropeptide release in the affected body region
(mainly substance P (SP) and calcitonin-gene related peptide (CRGP) and chronic release of neuropeptides might be responsible for the above mentioned peripheral CRSP symptoms. In addition, central neuropeptide release facilitates nociceptitve sensitization and may cause motor disturbances.
After experimental nerve lesions experiments in rats have shown that neuropeptides, in particular SP,
contribute to pain behaviour and many clinical symptoms resembling CRPS. In analogy to migraine studies, we therefore measure CGRP (RIA) in serum samples from patients with acute CRPS. CGRP was significantly increase, in particular when clinical inflammatory signs were pronounced and if there was
evidence for trauma related nerve lesion. In order to verify that increased CGRP indeed comes from
primary nociceptive afferents, neurogenic inflammation was elicited directly in the skin by transcutaneous
electrical stimulation via intraderrmal microdialysis capillaries, We first investigated the flare by
Laser-Doppler scanning on the affected and on the unaffected side in our CRPS patients. Neurogenic
flare was significantly more intense in patients, surprisingly on both side, the affected and the
clinically unaffected one.
Another characteristic of neurogenic inflammation in rodents is SP mediated plasma protein extravasation
(PPE). IN health humans, however, there are regularly too few SP containing C fibers for PPE. In CRPS, however, significant PPE could be shown in almost all patients investigated. In contrast to the flare response this increased PPE was limited to the affected side. These results so far suggested two possible pathomechanisms leading to facilitated neurogenic inflammation in CRPS--either increased release or hampered inactivation of neuropeptides. In order to further unravel this mechanisms we perfused SP in ascending concentrations through dermal microdialysis fibers, We found SP significantly more effective to induce PPE in CRPS patients than controls. Alike increased flare, this increase responsiveness to SP was present on both the affected and unaffected limbs.
To summarize, our investigations: we found evidence that neurogenic inflammation may be essential
to explain many symptoms of CRPS. There must be a trauma-related upregulation of neuropeptide
release from primary afferents on the affected side. However, in addition, there must be constitutionally
impaired inactivation of neuropeptides which predisposes some subjects to develop CRPS in response to
limb trauma.
SPINAL CORD STIMULATION IN PATIENTS WITH CRPS TYPE 1:
LONG TERM RESULTS(translation)
M van Kleef, AZ Maastricht, Dept. of Anesthesiology and Pain Management, Maastricht.
Spinal cord stimulation (SCS) has been used since 1967 for treating chronic pain patients. Since the
beginning of the 90’s it has been used to treat CRPS type 1. In 1997, AZM, compared research of the
effects of SCS with chronic pain patients and those with CRPS. From this study you can see that after one half year significant reduction in pain perception and quality of life with patients treated with SCS.
During his speech he will discuss possible mechanisms of neuropathic pain. He will also announce clinical
long term effects after 6 months, in 36 patients with subcutaneous implants they were followed. Pain scores were examined 6 months, 1 and 2 years after implantation. With all the patients there was a pain diary and quality of life was measured by scientific testing EQ5D.
The result was that the pain was clearly reduced in 1 year and 2 years after implantation. There was still
significant reduction of VAS score. 42% of CRPS type 1 in UE and 47% of CRPS I LE reported that since the beginning of treatment they were much improved. Also the quality of life scale was clearly improved after treatment. In conclusion SCS pain intensity with majority of patients with CRPS-I reduced pain and quality of life improved. No significant difference in outcome between patients with cervical or lumbar SCS.
PSYCHOLOGICAL ASPECTS OF CRPS
EC Covington, Cleveland Clinic Foundation, Pain Rehabilitation Program, Cleveland Ohio USA
Historically, CRPS has been strongly associated with psychological disorder and several relationships have been proposed: 1) CRPS is a psychiatric (somatoform/conversion) disorder; 2) psychiatric
illness/personality disorder create a predisposition to the development of CRPS; 3) CRPS causes
psychiatric illness; 4) psychological factors modify the course of CRPS and 5) adjustment and function in
CRPS are determined by psychological factors. These ideas derived from the obscure nature of the disease and the marked discordance between the often trivial injury and the severity of complaints and spread of symptoms. It is also likely that failures of coping and adaptation are disproportionately represented among intractable cases, and that patients in pain centers (where CRPS has been studied) have more psychopathology than those in the community.
The myth of CRPS as a psychogenic condition has faded in the face of substantial evidence that the
psychopathology in these patients does not differ appreciably from that in others with chronic pain. It has
been further weakened by studies showing genetic determinants of that illness and evidence of central
reorganization with thalamic and cortical changes.
One origin of the myth of psychogenicity in CRPS may be that the condition is relatively easy to simulate.
Several patients with “typical RSD” had clear evidence of a ligature on the arm or leg. Less obvious cases of self-inflicted disease or exacerbation have involved prolonged dependency and forced abnormal
posturing. These conditions constitute “faux CRPS” and the patients are profoundly psychiatrically
impaired.
The major sequela of CRPS is depression. Axis II disorders are reportedly common as well; however,
severe pain and disability produce such profound changes in “personality” that these disorders are
probably not true personality disorders, but maladaptive attitudinal and behavioural responses
induced by the disease. A psychophysiologic component to CRPS is suggested by the studies of
stress at onset and by the fact that autonomic arousal increase its symptoms.
The influence of behavioral factors on the course of CRPS is suggested by the fact that disuse produces a
clinical picture similar to that of CRPS. and exercise and mobilization have been shown to reverse edema,
trophic changes and vasomotor signs.
Cognitive factors are likely to play a role in the person’s ability to cope with the pain of CRPS and issues
of gain/reinforcement/reward influence coping behaviour as well.
While psychological issues do not explain CRPS, they do play a major role in its treatment and in the
response to such invasive treatments as spinal cord stimulation. Cognitive therapies and interventions
focused on improved physiologic self regulation (biofeedback training, autogenic training, self hypnosis)
are most important. Formal behaviour modification may be required to assist the difficult patient to initiate
a recovery program and family members must be partners in this endeavor.
Multidisciplinary pain rehabilitation, with simultaneous focus on symptom control, physical rehabilitation,
psychotherapy and behavioral management is probably the best option for patients who fail less extensive
approaches.
-----------------
Lecture notes:
There is no such thing as an RSD personality. There is no personality for asthma or migraine either.
Extreme behaviour after a minor injury is questioned by doctors. They take the attitude: “If I can’t see it, it does not exist”. Since there is no single test for CRPS, “if I can’t explain it with evidence, then it does not exist”. This is an inaccurate conclusion from tertiary care doctors.
There is no difference between CRPS and lower back pain patients. CRPS patients were less depressed and scored lower on hysteria in a recent study.
The mind plays a role in suffering: we either cope or do not adapt. What is a personality? We think, feel
and behave. An irritable bladder or bowel or chest pain is not perceived as psychogenic, why should
CRPS?
With visceral CPRS in the organs ie. bladder, bowel etc. those with high anxiety develop visceral
hyperalgesia easily. ( Gunter 2000.)
“Limbically augmented pain syndrome” is a sensitization process in some chronic pain patients where loud
noises result in seizures. Also “polymodial allodynia” is where the noise causes pain or trauma and
psychological stress. (Rome Pain Med 2000)
Suffering is the emotional part of pain. In pain centers the most common is anxiety. In 104 CRPS patients, 96% suffer from chronic depression. (Rudy,TE Pain 1988) there is a definite link between pain and depression. It needs interference to break the link e.g. a control factor like therapy.
In lower extremity CRPS 79.2% experienced major stress at the onset of CRPS. Therefore, we can
conclude that high stress predisposes someone to CRPS.
In behaviour, the stigma of CRPS is that patients are “poorly motivated to get well and they do not make
the effort”. Active exercise can reverse edema and disuse is detrimental. Cognition and pain lead to
misinformation e.g. that pain means body damage and that they are helpless and fragile. This leads to
inactivity which results in deconditioning and it becomes a cycle of pain and disability.
Learned helplessness is found in many chronic pain patients. You are not fragile or powerless. We need to empower them and give them a sense of control. Good behaviour should be rewarded. Immediate
consequences: if it feels good now it may be bad for you later. ie. resting too much and not exercising
enough.
Many chronic pain patients do not do well in treatment if they continue to look for who is at fault. They
will have a poor response to treatment and blame is toxic.
There is no data on “psuedo-CRPS” like ligatures, forced dependency or posture. Doctors need to make
the correct diagnosis.
“Chronic pain changes who you are”. Stress can make CRPS worse. It is rare that it is self-induced. There is cross talk between nerves: emotional allodynia cause organic allodynia.
IS THERE A GENETIC EXPLANATION FOR CRPS? (translation)
Prof WAA Zuurmond, University of Amsterdam, Amsterdam.
Introduction
CRPS is a complication that can occur after a trauma or operation to an extremity. Patients can become
quite disabled, to losing total function in an affected extremity. Not everyone develops CRPS after a
trauma or operation. Why is this complication in one patient and not in another?
Hypothesis
The symptoms of CRPS resemble an exaggerated inflammatory reaction. Could CRPS be the result of an
exaggerated inflammatory response from an anti stress or anti-immune reaction?
Lecture notes:
CRPS is neurogenic inflammation. Is it an auto-immune response? Many diseases have HLA factors e.g.
MS. Is HLA the initiator in CRPS? Is the modulator TNF? The HLA molecule has various parts A and B.
Method: A control group of 1,000 and 161 CRPS patients were typed for HLA A and B. then TNF-a using PCR-SSP-SSO-ELISA typing. Results were:
| Type |
CRPS-1 patients |
Control Group |
| HLA-DR 6(cold RSD) |
50% |
31% |
| HLA-DQ 1(warmRSD) |
99% |
83% |
| TNF-a |
40% |
19% |
| Subgroup(more than one extremity) |
50% |
31% |
Patients in subgroup have HLA-TNF-a2 association. This result needs research on treatments that will
have an effect on TNF-a.
*from Dutch Conference handouts and lecture notes from attendees. Special thanks to Marijn Birnie for translations.
File last updated April 2004.
|
