Complex regional pain syndrome

Complex regional pain syndrome
Reflex sympathetic dystrophy
Classification and external resources
Specialty	Neurology
ICD-10	M89.0, G56.4
ICD-9-CM	337.21, 337.22, 354.4, 355.71
DiseasesDB	12635 16345
MedlinePlus	007184
eMedicine	pmr/123
Patient UK	Complex regional pain syndrome
MeSH	D020918

Complex regional pain syndrome (CRPS) formerly reflex sympathetic dystrophy (RSD), "causalgia", or reflex neurovascular dystrophy (RND) is an amplified musculoskeletal pain syndrome (AMPS). It is a chronic systemic disease characterized by severe pain, swelling, and changes in the skin. CRPS often worsens over time. It may initially affect an arm or leg and spread throughout the body; 35% of people report symptoms throughout their whole body.^[1] Other potential effects include: systemic autonomic dysregulation; neurogenic edema; musculoskeletal, endocrine, or dermatological manifestations; and changes in urological or gastrointestinal function.^[2]

The cause of CRPS is unknown though CRPS is associated with dysregulation of the central nervous system^[3] and autonomic nervous system resulting in multiple functional loss, impairment, and disability. Precipitating factors include injury and surgery, although there are documented cases where no injury had occurred at the original site. CRPS is not caused by psychological factors, yet the constant pain and reduced quality of life has been known to cause psychological problems (such as increased depression and anxiety). Although "research does not reveal support for specific personality or psychopathology predictors of the condition," CRPS is associated with psychosocial effects, including impaired social and occupational function.^[4] Treatment is complicated, involving medications, physical therapy, psychological treatments, and neuromodulation and is often unsatisfactory, especially if delayed.^[5]

Classification

• Type I, formerly known as reflex sympathetic dystrophy (RSD), Sudeck's atrophy, or algoneurodystrophy, does not exhibit demonstrable nerve lesions. As the vast majority of patients diagnosed with CRPS have this type, it is most commonly referred to in medical literature as Type I.
• Type II, formerly known as causalgia, has evidence of obvious nerve damage. Type II CRPS tends to feature the more painful and difficult-to-control symptomes of CRPS; The Type II disease scores 47 out of 50 on the McGill pain scale^[6] (however there are seemingly little or no data pertaining to Type I specifically here). In Type II the "cause" of the syndrome is a known or obvious nerve injury, although the cause of the mechanisms of CRPS Type II are as unknown as the mechanisms of Type I.

Signs and symptoms

Clinical features of CRPS have been found to be neurogenic inflammation, nociceptive sensitisation, vasomotor dysfunction, and maladaptive neuroplasticity.^[7] The symptoms of CRPS usually initially manifest near the site of a, typically minor, injury. The most common symptoms are pain sensations, including burning, stabbing, grinding, and throbbing. Moving or touching the limb is often intolerable. The patient may also experience muscle spasms, local swelling, sensitivity to things such as water, touch, and vibrations, abnormally increased sweating, changes in skin temperature (usually hot but sometimes cold) and color (bright red or a reddish violet), softening and thinning of bones, joint tenderness or stiffness, and/or restricted or painful movement. Falls, pre-syncope, and syncope (fainting) are infrequently reported, as are visual problems. Regional Osteoporosis is possible. The symptoms of CRPS vary in severity and duration. Since CRPS is a systemic problem, potentially any organ can be affected.

The pain of CRPS is continuous, and it is widely recognised that it can be heightened by emotional or physical stress.^[8]

Complex regional pain syndrome's cause is unknown. Nerve damage is considered to be the cause in many cases. Evidence of nerve damage as the trigger for CRPS is supported by observations that the disruption of certain nerve relationships to pain signaling result in improvements for patients.

Patients are frequently classified into two groups based upon temperature: "warm" or "hot" CRPS in one group and "cold" CRPS in the other group. The majority of patients (approximately 70%) have the "hot" type, which is said to be an acute form of CRPS.^[9] Cold CRPS is said to be indicative of a more chronic CRPS and is associated with poorer McGill Pain Questionnaire (MPQ) scores, increased central nervous system involvement, and a higher prevalence of dystonia.^[9] Prognosis is not favourable for cold CRPS patients; longitudinal studies suggest these patients have "poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression".^[10]

Previously it was considered that CRPS had three stages; it is now believed that patients with CRPS do not progress through these stages sequentially. These stages may not be time-constrained and could possibly be event-related, such as ground-level falls or re-injuries of previously damaged areas. thus, rather than a progression of CRPS from bad to worse, it is now thought, instead, that patients are likely to have one of the three following types of disease progression:

1. "Stage" one is characterized by severe, burning pain at the site of the injury, muscle spasms, joint stiffness, restricted mobility, rapid hair and nail growth, and vasospasm. The vasospasm is that which causes the changes in the color and temperature of the skin. Some may experience hyperhydrosis (increased sweating). In mild cases this stage lasts a few weeks, in which it can subside spontaneously or respond rapidly to treatment (physical therapy, pain specialist).
2. "Stage" two is characterized by more intense pain. Swelling spreads, hair growth diminishes, nails become cracked, brittle, grooved, and spotty, osteoporosis becomes severe and diffuse, joints thicken, and muscles atrophy.
3. "Stage" three is characterized by irreversible changes in the skin and bones, while the pain becomes unyielding and may involve the entire limb. There is marked muscle atrophy, severely limited mobility of the affected area, and flexor tendon contractions (contractions of the muscles and tendons that flex the joints). Occasionally the limb is displaced from its normal position, and marked bone softening and thinning is more dispersed.

Cause

Investigators estimate that 2-5% of those with peripheral nerve injury,^[11] and 13-70 percent of those with hemiplegia (paralysis of one side of the body),^[12] will develop CRPS. In addition, some studies have indicated that cigarette smoking was strikingly present in patients and is statistically linked to RSD. In one study, 68% of patients versus 37% of hospitalized controls were found. This may be involved in its pathology by enhancing sympathetic activity, vasoconstriction, or by some other unknown neurotransmitter-related mechanism.^[13] 7% of people who have CRPS in one limb later develop it in another limb.

Pathophysiology

Complex regional pain syndrome is a multifactorial disorder with clinical features of neurogenic inflammation (swelling in the central nervous system), nociceptive sensitisation (which causes extreme sensitivity or allodynia), vasomotor dysfunction (blood flow problems which cause swelling and discolouration) and maladaptive neuroplasticity (where the brain changes and adapts with constant pain signals); CRPS is the result of an "aberrant [inappropriate] response to tissue injury".^[7] The "underlying neuronal matrix" of CRPS is seen to involve cognitive and motor as well as nociceptive processing; pinprick stimulation of a CRPS affected limb was painful (mechanical hyperalgesia) and showed a "significantly increased activation" of not just the S1 cortex (contralateral), S2 (bilateral) areas, and insula (bilateral) but also the associative-somatosensory cortices (contralateral), frontal cortices, and parts of the anterior cingulate cortex.^[14] In contrast to previous thoughts reflected in the name RSD, it appears that there is reduced Sympathetic Nervous System outflow, at least in the affected region (although there may be sympatho-afferent coupling).^[15] Wind-up (the increased sensation of pain with time)^[16] and central nervous system (CNS) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of CRPS.^[17]

There is compelling evidence that the N-methyl-D-aspartate (NMDA) receptor has significant involvement in the CNS sensitization process.^[18] It is also hypothesized that elevated CNS glutamate levels promote wind-up and CNS sensitization.^[17] In addition, there is experimental evidence that demonstrates NMDA receptors in peripheral nerves.^[19] Because immunological functions can modulate CNS physiology, it has also been hypothesized that a variety of immune processes may contribute to the initial development and maintenance of peripheral and central sensitization.^[20][21] Furthermore, trauma related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation,^[22] and oxidative damage (e.g., by free radicals) are all concepts that have been implicated in the pathophysiology of CRPS.^[23]

The pathophysiology of complex regional pain syndrome has not yet been defined; there is conjecture that CRPS, with its variable manifestations, could be the result of multiple pathophysiologies.^[15]

Diagnosis

CRPS types I and II share the common diagnostic criteria shown below. Spontaneous pain or allodynia (pain resulting from a stimulus which would not normally provoke pain, such as a light touch of the skin) is not limited to the territory of a single peripheral nerve and is disproportionate to the inciting event.

1. There is a history of edema, skin blood flow abnormality, or abnormal sweating in the region of the pain since the inciting event.
2. No other conditions can account for the degree of pain and dysfunction.

The two types differ only in the nature of the inciting event. Type I CRPS develops following an initiating noxious event that may or may not have been traumatic, while type II CRPS develops after a nerve injury.

No specific test is available for CRPS, which is diagnosed primarily through observation of the symptoms. However, thermography, sweat testing, x-rays, electrodiagnostics, and sympathetic blocks can be used to build up a picture of the disorder. Diagnosis is complicated by the fact that some patients improve without treatment. A delay in diagnosis and/or treatment for this syndrome can result in severe physical and psychological problems. Early recognition and prompt treatment provide the greatest opportunity for recovery.

The International Association for the Study of Pain (IASP) lists the diagnostic criteria for complex regional pain syndrome I (CRPS I) (RSDS) as follows:

1. The presence of an initiating noxious event or a cause of immobilization
2. Continuing pain, allodynia (perception of pain from a nonpainful stimulus), or hyperalgesia (an exaggerated sense of pain) disproportionate to the inciting event
3. Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the area of pain
4. The diagnosis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction.

According to the IASP, CRPS II (causalgia) is diagnosed as follows:

1. The presence of continuing pain, allodynia, or hyperalgesia after a nerve injury, not necessarily limited to the distribution of the injured nerve
2. Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain
3. The diagnosis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction.

The IASP criteria for CRPS I diagnosis has shown a sensitivity ranging from 98–100% and a specificity ranging from 36–55%. Per the IASP guidelines, interobserver reliability for CRPS I diagnosis is poor. Two other criteria used for CRPS I diagnosis are Bruehl's criteria and Veldman's criteria, which have moderate to good interobserver reliability. In the absence of clear evidence supporting one set of criteria over the other, clinicians may use IASP, Bruehl’s, or Veldman’s clinical criteria for diagnosis. While the IASP criteria are nonspecific and possibly not as reproducible as Bruehl’s or Veldman’s criteria, they are cited more widely in literature, including treatment trials.^[24]

Thermography

Presently, established empirical evidence suggests against thermography's efficacy as a reliable tool for diagnosing CRPS. Although CRPS may, in some cases, lead to measurably altered blood flow throughout an affected region, many other factors can also contribute to an altered thermographic reading, including the patient's smoking habits, use of certain skin lotions, recent physical activity, and prior history of trauma to the region. Also, not all patients diagnosed with CRPS demonstrate such "vasomotor instability" — less often, still, those in the later stages of the disease.^[25] Thus, thermography alone cannot be used as conclusive evidence for - or against - a diagnosis of CRPS and must be interpreted in light of the patient's larger medical history and prior diagnostic studies.^[26]

In order to minimise the confounding influence of external factors, patients undergoing infrared thermographic testing must conform to special restrictions regarding the use of certain vasoconstrictors (namely, nicotine and caffeine), skin lotions, physical therapy, and other diagnostic procedures in the days prior to testing. Patients may also be required to discontinue certain pain medications and sympathetic blockers. After a patient arrives at a thermographic laboratory, he or she is allowed to reach thermal equilibrium in a 16–20 °C, draft-free, steady-state room wearing a loose fitting cotton hospital gown for approximately twenty minutes. A technician then takes infrared images of both the patient's affected and unaffected limbs, as well as reference images of other parts of the patient's body, including his or her face, upper back, and lower back. After capturing a set of baseline images, some labs further require the patient to undergo cold-water autonomic-functional-stress-testing to evaluate the function of his or her autonomic nervous system's peripheral vasoconstrictor reflex. This is performed by placing a patient's unaffected limb in a cold water bath (approximately 20 °C) for five minutes while collecting images. In a normal, intact, functioning autonomic nervous system, a patient's affected extremity will become colder. Conversely, warming of an affected extremity may indicate a disruption of the body's normal thermoregulatory vasoconstrictor function, which may sometimes indicate underlying CRPS.^[27]

Radiography

Scintigraphy, plain radiographs, and magnetic resonance imaging (MRI) may all be useful diagnostically. Patchy osteoporosis (post-traumatic osteoporosis), which may be due to disuse of the affected extremity, can be detected through X-ray imagery as early as two weeks after the onset of CRPS. A bone scan of the affected limb may detect these changes even sooner. Bone densitometry can also be used to detect changes in bone mineral density. It can also be used to monitor the results of treatment since bone densitometry parameters improve with treatment.

Electrodiagnostic testing

Electromyography (EMG) and Nerve Conduction Studies (NCS) are important ancillary tests in CRPS because they are among the most reliable methods of detecting nerve injury. They can be used as one of the primary methods to distinguish between CRPS I & II, which differ based on whether there is evidence of actual nerve damage. EMG & NCS are also among the best tests for ruling in or out alternative diagnoses. CRPS is a "diagnosis of exclusion", which requires that there be no other diagnosis that can explain the patient's symptoms. This is very important to emphasise because otherwise patients can be given a wrong diagnosis of CRPS when they actually have a treatable condition that better accounts for their symptoms. An example is severe Carpal Tunnel Syndrome, which can often present in a very similar way to CRPS. Unlike CRPS, Carpal Tunnel Syndrome can often be corrected with surgery in order to alleviate the pain and avoid permanent nerve damage and malformation.^[28]

Both EMG and NCS involve some measure of discomfort. EMG involves the use of a tiny needle that is inserted into specific muscles to test the associated muscle and nerve function. Both EMG & NCS involve very mild shocks that in normal patients are comparable to a rubber band snapping on the skin. Although these tests can be very useful in CRPS, thorough informed consent needs to be obtained prior to the procedure, particularly in patients experiencing severe allodynia. In spite of the utility of the test, these patients may wish to decline the procedure in order to avoid discomfort.

Prevention

Vitamin C may be useful in prevention of the syndrome following fracture of the forearm.^[29]

Treatment

The general strategy in CRPS treatment is often multi-disciplinary, with the use of different types of medications combined with distinct physical therapies.

Physical therapy

Physical and occupational therapy are important components of the management of CRPS primarily by desensitising the affected body part, restoring motion, and improving function. Physical therapy interventions for CRPS can include specific modalities such as transcutaneous electrical nerve stimulation, progressive weight bearing, tactile desensitization, massage, and contrast bath therapy. These interventions tailored specifically to each individual person can be used to improve pain and function to help people return to normal activities of daily living.^[30] Some people at certain stages of the disease are incapable of participating in physical therapy due to touch intolerance. This may be where Graded Motor Imagery and Mirror Therapy (see below) are particularly helpful. People with CRPS often develop guarding behaviors where they avoid using or touching the affected limb. This inactivity exacerbates the disease and perpetuates the pain cycle. Therefore, optimizing the multimodal treatment is paramount to allow for use of the involved body part. Physical therapy works best for most patients, especially goal-directed therapy, where the patient begins from an initial point, regardless of how minimal, and then endeavors to increase activity each week. Therapy is directed at facilitating the patient to engage in physical therapy, movement, and stimulation of the affected areas. One difficulty with the idea of physical therapy, however, is that it means different things to different people. There is one systematic review of the use of physical and occupational therapy for the treatment of CRPS.^[31] That review concluded, "Narrative synthesis of the results, based on effect size, found there was good to very good quality level II evidence that graded motor imagery is effective in reducing pain in adults with CRPS-1, irrespective of the outcome measure used. No evidence was found to support treatments frequently recommended in clinical guidelines, such as stress loading. CONCLUSIONS: Graded motor imagery should be used to reduce pain in adult CRPS-1 patients."^[31]

Physical therapy has been used under light general anesthesia in an attempt to remobilize the extremity. Such remobilization is used cautiously to avoid damage to atrophied tissue and bones that have become osteodystrophic.

Although there is no denying the importance of a multidisciplinary approach in the management of CRPS,^[32] recent research suggests that physical therapy intervention may be successful in decreasing symptoms of CRPS without the use of medications. “Pain exposure” physical therapy (PEPT) is based on the premise that pain may be exacerbated and maintained by psychosocial and behavioural factors, and therefore, these factors must be addressed as a component of CRPS management. PEPT combines a progressive loading exercise program with pain-avoidance behaviour management. Progressive loading (i.e., loading extremities beyond limit of pain) includes passive and active exercises to mobilize joints and muscle stretching and is believed to reduce sensitization (both central and peripheral) and may also restore autonomic deregulation and cortical representation in CRPS. As the name suggests, pain avoidance behaviour management attempts to reduce behaviours that maintain disuse and pain avoidance (e.g., kinesiophobia, pain avoidance and learned non-use, and pain catastrophizing), with the goal of increasing self-confidence in the individual’s physical capabilities.^[33]

A recent multiple single-case design study by Van de Meent et al. (2011)^[33] found PEPT to be a safe and effective method of treatment for individuals with CRPS. Results showed improvements on a variety of outcomes measures, including pain intensity, kinesiophobia, muscle strength, arm/shoulder/hand disability, walking speed, and perceived health. However, although these results are promising, this is a relatively new topic of study and more research needs to be done in the area.

In children, CRPS is often treated with an intense physical and occupational therapy program for amplified musculoskeletal pain syndromes. These programs also employ counseling, art therapy, and music therapy. These evidence-based programs report long-term pain resolution success rates as high as 88%.^[34] In one study of 103 children with CRPS, 92% finished such a program pain-free and 88% were pain-free five years later at the time of follow-up.^[35] The efficacy of such a program has not been studied in adults.

Mirror box therapy

Mirror box therapy uses a mirror box, or a stand-alone mirror, to create a reflection of the normal limb such that the patient thinks they are looking at the affected limb. Movement of this reflected normal limb is then performed so that it looks to the patient as though they are performing movement with the affected limb (although it will be pain free due to the fact it is a normal limb being reflected).

Mirror box therapy appears to be beneficial in early CRPS (McCabe et al., 2003b);.^[36] However, Lorimer Moseley (University of South Australia) has cautioned that the beneficial effects of mirror therapy for CRPS are still unproven.^[37] Importantly, the precise neural mechanisms of action are unknown and need to be studied using a combination of behavioural and neuroimaging approaches.^[38]

Graded motor imagery

Because studies have shown that problems in the primary motor cortex are found in patients who suffer from CRPS, treatments have been developed that focus on normalizing motor representations in that part of the brain. Graded motor imagery^[39][40] has now been tested in three^[41][42][43] randomised controlled trials and has shown to be effective at reducing pain and disability in people with chronic CRPS or phantom limb pain after amputation or avulsion injury of the brachial plexus.

Graded motor imagery is a sequential process that consists of (a) laterality reconstruction, (b) motor imagery, and (c) mirror therapy.^[32][44]

Tactile discrimination training

Another approach to CRPS is based on a treatment called sensory discrimination training, which was used for phantom limb pain. A randomised controlled trial ^[45] demonstrated a significant drop in pain after ten days training. For CRPS, a replicated case series ^[37] and a randomised repeated measures experiment ^[46] both demonstrated an effect of tactile discrimination training on pain, disability, and sensory function in people with CRPS of various durations. This treatment has not been tested in a randomised controlled trial.

Medications

Physicians use a variety of drugs to treat CRPS, including antidepressants, anti-inflammatories such as corticosteroids, COX-inhibitors such as piroxicam, bisphosphonates, vasodilators, GABA analogs such as gabapentin and pregabalin, alpha- or beta-adrenergic-blocking compounds, and the entire pharmacy of opioids. Occasional uses of Butorphanol also can be helpful during moments of heightened pain. In a limited study, Low-dose naltrexone has been found to be effective in the remittance of many prominent symptoms, including dystonic spasms and fixed dystonia (respectively).^[47]

Ketamine

Ketamine, a dissociative anesthetic, appears promising as a treatment for complex regional pain syndrome.^[48] It may be used in low doses if other treatments have not worked.^[49][50] No benefit on either function or depression; however, has been seen.^[50]

Bisphosphonate treatment

Bisphosphonates were described in 2009 as "among the only class of medications that has survived placebo-controlled studies showing statistically significant improvement (in CRPS) with therapy."^[51] Researchers in the 2000s used steadily increased dosages and experimented with other bisphosphonates to improve results, increase response, and put higher percentages of patients treated into long-term remission.^[52][53]

In Varenna et al.'s 2000 study, patients who had CRPS for up to a year were dosed with 300 mg infusions of clodronate on ten consecutive days (3000 mg total). The group receiving clodronate reported pain falling significantly in the first 40 days and average pain in the group was reported as being close to zero 180 days following treatment. For Varenna et al.'s 2013 study,^[54] patients were given four infusions of 100 mg of intravenous neridronate within 4 to 10 days (400 mg total). The group receiving the neridronate infusions reported rapid reduction in pain levels.

In their 2004 paper "Efficacy of Pamidronate in Complex Regional Pain Syndrome Type I", Robinson et al. report that with single 60 mg infusions, "several patients with established disease of several years duration responded to pamidronate, perhaps reflecting the heterogeneity of this condition".^[55]

The 2009 European Journal of Pain article "Bisphosphonates for the therapy of complex regional pain syndrome I - Systematic Review" by Florian Brunner et al. concluded that the "very limited data reviewed showed that bisphosphonates have the potential to reduce pain associated with bone loss in patients with CRPS I, however, at present there is not sufficient evidence to recommend their use in practice".^[56] Varenna et al. report in their 2013 double blind placebo-controlled study of 80 patients that all 78 patients who participated in a lengthy follow-up were dramatically improved and continued to improve. The authors conclude that "These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice for CRPS-I".^[54]

At the University of Verona, which participated in the 2013 Varenna et al. study, 7500 I.U. of Vitamin D per week are often given after treatment to help the bones heal. Varenna et al. states that the results are "conjectural, mainly because the exact pathophysiology of the disease is still unknown."^[54]

Topical treatment

CRPS can also be treated with DMSO 50% cream.^[57] A novel approach to treat CRPS is with the multimodal stepped care approach.^[58] Step by step a topical analgesic will be tried to examine its effectiveness in reducing pain. When a topical analgesic has some pain reducing effects, though not completely, another topical analgesic from a different class can be added to enhance the pain reducing effects.^[58] Usually one to four topical agents can be used simultaneously to get an optimal pain reducing effect. Combination therapy between ketamine cream and the anti-inflammatory palmitoylethanolamide seems worth mentioning.^[59]

Local anaesthetic injections

Injection of a local anesthetic, such as lidocaine, is often the first step in treatment. Injections are repeated as needed. The results of local anesthetic injections are short lasting, and the procedure is risky. However, early intervention with non-invasive management may be preferred to repeated nerve blockade. The use of topical lidocaine patches has not been shown to be of use in the treatment of CRPS-1 and 2.

Botox injections

Intramuscular botulinum injections have been shown recently to benefit patients with CRPS symptoms localized to one extremity.^[60] These injections may reduce the muscle spasm associated with CRPS and likely also decrease the inflammation associated with CRPS. The main advantages of this treatment are that it is relatively cheap, safe, and easy to administer. The major disadvantage is that it may need to be repeated after a few months.

Surgery

Spinal cord stimulators

Neurostimulation (spinal cord stimulator) may also be surgically implanted to reduce the pain by directly stimulating the spinal cord. These devices are surgically placed by trained physicians. An electrode is placed in the epidural space in the region of the spinal cord associated with the body part to be treated. Once placed, programming by a knowledgeable clinician will personalize the device to each patient's pain complaints for the optimal outcome. High frequencies are normally utilized for CRPS patients. A systematic review concluded that spinal cord stimulation appears to be an effective therapy in the management of patients with CRPS type I (Level A evidence) and type II (Level D evidence).^[61] Moreover, there is evidence to demonstrate that SCS is a cost-effective treatment for CRPS type I.

A randomised controlled trial performed by Kemler et al. (2000) on spinal cord stimulation (SCS) in patients with refractory RSD demonstrated that the group receiving SCS + physical therapy (n=36) had a mean reduction of 2.4 cm (using Visual analogue scale) in the intensity of pain at six months compared to a mean increase of 0.2 cm in the group assigned to receive physical therapy alone (n=18). The intensity of pain was found to be statistically significantly different between the two groups (P < 0.001). In addition, a greater proportion of patients in the SCS + physical therapy reported a 6 (“much improved” outcome) based on a global perceived effect scale compared to physical therapy alone (39% vs. 6%, P = 0.01). However, the study did not find clinically significant improvement in functional status.^[62]

Sympathectomy

Surgical, chemical, or radiofrequency sympathectomy — interruption of the affected portion of the sympathetic nervous system — can be used as a last resort in patients with impending tissue loss, edema, recurrent infection, or ischemic necrosis.^[63] However, there is little evidence that these permanent interventions alter the pain symptoms of the affected patients, and in addition to the normal risks of surgery, such as bleeding and infection, sympathectomy has several specific risks, such as adverse changes in how nerves function.

Amputation

There is no randomized study in medical literature that has studied the response with amputation of patients who have failed the above-mentioned therapies and who continue to be miserable. Nonetheless, there are reports that on average cite about half of the patients will have resolution of their pain, while half will develop phantom limb pain and/or pain at the amputation site. It is likely that as in any other chronic pain syndrome, the brain becomes chronically stimulated with pain, and late amputation may not work as well as it might be expected. In a survey of fifteen patients with CRPS Type 1, eleven responded that their life was better after amputation.^[64] Since this is the ultimate treatment of a painful extremity, it should be left as a last resort.

Adjunctive treatment

EEG Biofeedback,^[65] various forms of psychotherapy,^[66] relaxation techniques, and hypnosis ^[67] are adjunctive treatments that assist coping.

Prognosis

Good progress can be made in treating CRPS if treatment is begun early, ideally within three months of the first symptoms. If treatment is delayed, however, the disorder can quickly spread to the entire limb, and changes in bone, nerve, and muscle may become irreversible. The prognosis is not always good. Johns Hopkins Hospital reports that 77% of sufferers have spreads from the original site or flares in other parts of the body. The limb, or limbs, can experience muscle atrophy, loss of use, and functionally useless parameters that require amputation. RSD/CRPS will not "burn itself out", but if treated early, it is likely to go into remission. Once you are diagnosed with Complex Regional Pain Syndrome the likelihood of it resurfacing after going into remission is significant. It is important that you take precautions and seek immediate treatment upon any injury. Notify the treating physicians of your prior history of Complex Regional Pain Syndrome.

Epidemiology

CRPS can occur at any age with the average age at diagnosis being 42.^[11] It affects both men and women; however, CRPS is three times more frequent in females than males.^[11] It affects adults and children. The number of reported CRPS cases among adolescents and young adults is increasing.^[68]

History

The condition currently known as CRPS was originally described during the American Civil War by Silas Weir Mitchell, who is sometimes also credited with inventing the name "causalgia."^[69] However, this term was actually coined by Mitchell's friend Robley Dunglison from the Greek words for heat and for pain.^[70] Contrary to what is commonly accepted, it emerges that these causalgias were certainly major by the importance of the vasomotor and sudomotor symptoms but stemmed from minor neurological lesions. Mitchell even thought that the CRPS etiology came from the cohabitation of the altered and unaltered cutaneous fibres on the same nerve distribution territory.^[71] In the 1940s, the term reflex sympathetic dystrophy came into use to describe this condition, based on the theory that sympathetic hyperactivity was involved in the pathophysiology.^[72] In 1959, Noordenbos observed in caulsalgia patients that "the damage of the nerve is always partial."^[73] Misuse of the terms, as well as doubts about the underlying pathophysiology, led to calls for better nomenclature. In 1993, a special consensus workshop held in Orlando, Florida, provided the umbrella term "complex regional pain syndrome", with causalgia and RSD as subtypes.^[74]

Society and culture

• Paula Abdul, Singer, Actor, TV Personality.^[75]
• Jill Kinmont Boothe, US ski slalom champion.^[76]
• Gemma Collis, British paralympic fencer.^[77]
• Shin Dong-wook, South Korean actor and model.^[78]
• Howard Hughes, American business tycoon, aviator, inventor, filmmaker and philanthropist.^[79]
• Barby Ingle, Author, radio and television personality.^[80]
• Rachel Morris, British paralympic cyclist.^[81]
• Cynthia Toussaint, Author and media personality.^[82]
• Danielle Brown, British paralympic archer.^[83]

Research

The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), supports and conducts research on the brain and central nervous system, including research relevant to RSDS, through grants to major medical institutions across the country. NINDS-supported scientists are working to develop effective treatments for neurological conditions and ultimately, to find ways of preventing them. Investigators are studying new approaches to treat CRPS and intervene more aggressively after traumatic injury to lower the patient's chances of developing the disorder. In addition, NINDS-supported scientists are studying how signals of the sympathetic nervous system cause pain in CRPS patients. Using a technique called microneurography, these investigators are able to record and measure neural activity in single nerve fibers of affected patients. By testing various hypotheses, these researchers hope to discover the unique mechanism that causes the spontaneous pain of CRPS, and that discovery may lead to new ways of blocking pain. Other studies to overcome chronic pain syndromes are discussed in the pamphlet "Chronic Pain: Hope Through Research", published by the NINDS.

Research into treating the condition with Mirror Visual Feedback is being undertaken at the Royal National Hospital for Rheumatic Disease in Bath. Patients are taught how to desensitize in the most effective way, then progress to using mirrors to rewrite the faulty signals in the brain that appear responsible for this condition.

The Netherlands currently has the most comprehensive program of research into CRPS, as part of a multi-million Euro initiative called TREND.^[84] German and Australian research teams are also pursuing better understanding and treatments for CRPS.

Other animals

CRPS has also been described in animals.^[85]

References

External links

• Complex regional pain syndrome at DMOZ
• Reflex sympathetic dystrophy at DMOZ

Nervous system pathology, PNS, somatic (G50–G64, 350–357)   Nerve, nerve root, plexus Cranial nerve disease V Trigeminal neuralgia Anesthesia dolorosa VII Facial nerve paralysis Bell's palsy Melkersson–Rosenthal syndrome Parry–Romberg syndrome Central seven XI Accessory nerve disorder Radiculopathy, plexopathy brachial plexus Brachial plexus lesion Thoracic outlet syndrome Phantom limb Mono- neuropathy Upper limb median nerve: Carpal tunnel syndrome Ape hand deformity ulnar nerve: Ulnar nerve entrapment Froment's sign Guyon's canal syndrome Ulnar claw radial nerve: Radial neuropathy Wrist drop Cheiralgia paresthetica long thoracic nerve: Winged scapula Backpack palsy Lower limb lateral cutaneous nerve of thigh: Meralgia paraesthetica tibial nerve: Tarsal tunnel syndrome plantar nerve: Morton's neuroma superior gluteal nerve: Trendelenburg's sign sciatic nerve: Piriformis syndrome General Causalgia Mononeuritis multiplex Neuropathy Neuralgia/Neuritis Nerve compression syndrome   Polyneuropathies/Polyradiculoneuropathy HMSN Charcot–Marie–Tooth disease Dejerine–Sottas disease Refsum's disease Hereditary spastic paraplegia Hereditary neuropathy with liability to pressure palsy Familial amyloid neuropathy Autoimmune/demyelinating Guillain–Barré syndrome Chronic inflammatory demyelinating polyneuropathy Other Alcoholic polyneuropathy

Bone and joint disease (M80–M94, 730–733) Bone Inflammation endocrine: Osteitis fibrosa cystica Brown tumor infection: Osteomyelitis Sequestrum Involucrum Sesamoiditis Brodie abscess Periostitis Vertebral osteomyelitis Metabolic Bone density Osteoporosis Juvenile Osteopenia Osteomalacia Paget's disease of bone Bone resorption Osteolysis Hajdu-Cheney syndrome Ainhum Other Ischaemia Avascular necrosis Osteonecrosis of the jaw Algoneurodystrophy Hypertrophic pulmonary osteoarthropathy Nonossifying fibroma Pseudarthrosis Stress fracture Fibrous dysplasia Monostotic Polyostotic Skeletal fluorosis bone cyst Aneurysmal bone cyst Hyperostosis Infantile cortical hyperostosis Osteosclerosis Melorheostosis Pycnodysostosis Joint Chondritis Relapsing polychondritis Other Tietze's syndrome Combined Osteochondritis Osteochondritis dissecans Child leg: hip Legg–Calvé–Perthes syndrome tibia Osgood-Schlatter disease Blount's disease foot Köhler disease Sever's disease spine Scheuermann’s disease arm: wrist Kienbock's disease elbow Panner disease

Arthritis in children Inflammatory Idiopathic Juvenile idiopathic arthritis Inflammatory disease Inflammatory bowel disease Sarcoidosis Cystic fibrosis Autoimmune hepatitis Hematological malignancy Acute lymphoblastic leukemia Lymphoma Malignancy Neuroblastoma Reactive post-streptococcal Rheumatic fever postenteric, post-viral Infection Septic arthritis Osteomyelitis Tuberculosis Lyme arthritis Mechanical Osgood–Schlatter disease Tumours of cartilage bone or muscle Benign Osteoid osteoma Pigmented villonodular synovitis Hemangioma Malignant Synovial sarcoma Rhabdomyosarcoma Ewing's sarcoma Central Nervous System Idiopathic pain syndromes Local Complex regional pain syndrome/Reflex sympathetic dystrophy Generalized Fibromyalgia