Complex Regional Pain Syndrome (CRPS): Difference between revisions

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== Characteristics/Clinical Presentation<br>  ==
== Characteristics/Clinical Presentation<br>  ==


We can subdivide CRPS in type I and type II. The difference between type I and II is based on a consensus between clinicians and scientists. The definition of type II (see below) can be largely interpreted. For example post-traumatic neuralgia has different syndromes with different underlying mechanisms but it can be included in type II. This means that the definition of both types need to be improved in specificity and sensitivity in the future. In both cases we assume that long-term central changes have occurred. Somatosensory changes, changes in the sympathetic nervous system, changes in the peripheral, changes in the somatomotor system and changes in the neuroendocrine systems cause changes in the central nervous system. All symptoms of CRPS II show many similarities to those of CRPS I. [1, 3, 6, 17]
<br>
 
CRPS is clinically characterized by sensory, autonomic and motor disturbances. The table below shows an overview of the different characteristics of CRPS I and II: [3, 4,6, 16, 17, 18]<br>Type Type I Type II<br> = formerly reflex sympathetic dystrophy = formerly causalgia<br>Definition After an injury with minor or without nerve damage, after a trauma remote from the affected extremity After injury to a major peripheral nerve<br>Etiology minor, soft tissue trauma (sprains, bruises and skin lesions);<br>bone fracture or surgery;<br>frostbite or burns;<br>stroke, myocardial infarction or lesion of the central nervous system;<br>immobilisation <br>Sensory disturbances ● Allodynia and hyperalgesia<br>● Hypoesthesia and hypoalgesia ● Allodynia and hyperalgesia<br>● Hypersensitivity of the skin to light mechanical stimulation.<br>Autonomic disorders + inflammatory symptoms ● Swelling and edema<br>● Changes of sweating (especially hyperhidrosis)<br>● Abnormal skin blood flow<br>● Color changes (redness or pale)<br>● Temperature changes ● Limb is cold and sweaty<br>● Distal extremity swelling<br>● Changes of sweating<br>● Abnormal skin blood flow<br>● Temperature changes<br>Trophic changes ● Abnormal nail growth<br>● Increased or decreased hair growth<br>● Fibrosis<br>● Thin glossy skin<br>● Osteoporosis (chronic stage) ● Smoothness and mottling of the skin<br>● Acute arthritis<br>Motor dysfunction ● Weakness of all muscles<br>● inability to move the extremity<br>● Stiffness<br>● Tremor<br>● Reduced range of motion<br>● Severe impairment of complex movements<br>● Atrophy ● Weakness of all muscles<br>● Inability to move the extremity<br>● Stiffness<br>● Tremor <br>● Dystonia<br>● Reduced range of motion<br>● Severe impairment of complex movements<br>Pain (sympathetic nervous system) ● Burning and spontaneous<br>● Disproportionable in intensity to the inciting event<br>● Increase when the extremity is in a dependent position<br>● Elicited by movement and pressure at the joints<br>● Not in all cases<br>● Deep, unpleasant, sensitive, surface, dull ● Ongoing<br>● Neuropathic<br>● Spontaneous<br>● Triggered by movement, loud noises or strong emotions<br>● Deep, unpleasant, sensitive, surface, dull
 
<br>Symptoms can spread beyond the territory of the lesioned nerve in type II. Ongoing neurogenic inflammation, vasomotor dysfunction, central sensitization and maladaptive neuroplasticity contribute to the clinical phenotype of CRPS. Genetic and psychological factors can influence the vulnerability to CRPS and also affect the mechanisms that maintain CRPS. Peripheral and central changes can be irreversible. The sympathetic nervous system plays a key role in maintaining pain and autonomic dysfunction in the affected extremity. [3, 13]<br>


== Differential Diagnosis  ==
== Differential Diagnosis  ==

Revision as of 14:11, 4 October 2015

Welcome to PPA Pain Project. This page is being reviewed and updated by participants of a project to populate the Pain section of Physiopedia.  The project is supervised and co-ordinated by the The Physiotherapy Pain Association.
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Search Strategy[edit | edit source]

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Definition/Description[edit | edit source]

Complex regional pain syndrome (CRPS) is a term for a variety of clinical conditions characterized by chronic persistent pain. It is a disease that may develop after a limb trauma. [1] This appears mostly in 1 or more limbs, usually in the arms or legs. We can say a CRPS is a regional posttraumatic neuropathic pain problem. [2] Neuropathic pain disorders are a disproportionate consequence of painful trauma or nerve lesion. [3]


CRPS is subdivided into type I and type II CRPS.

In the literature, there are a lot of names used to describe this syndrome such as ‘‘Reflex Sympathetic Dystrophy’’, ‘‘causalgia’’, ‘‘algodystrophy’’, ‘‘Sudeck’s atrophy’’, ‘‘neurodystrophy’’, and ‘‘post-traumatic dystrophy’’. To standardize the nomenclature, the name ‘complex regional pain syndrome’ was adopted in 1995 by the ‘International Association for the Study of Pain’ (IASP).[4]


Clinically Relevant Anatomy[edit | edit source]

CRPS can take place in any body part, but often in the extremities. The wrist is most frequently affected after distal radial fractures.[5] It is a disorder with assorted clinical appearances and gravity of disease. Central and peripheral nervous system are connected through neural and chemical pathways, there is a direct control over the autonomic system. It is for this reason that there can be changes in the vasomotor and sudomotor without any impairment in the peripheral nervous system. Pain, heath and swelling are usually not located at the site of inciting injury and there may be no clear damage. Central sensitisation is seen as a main cause for developing CRPS. [6, 7]

Epidemiology /Etiology[edit | edit source]

Complex regional pain syndrome can develop after different types of inciting injuries.
A few examples are:
● sprains and strains,
● post-surgical,
● fractures,
● contusions,
● crush injuries,
● nerve lesions,
● stroke.
Sometimes the inciting injury can occur spontaneously or can not be determined. [5][6][7][8][9][10]
Fifty-six percent of patients reported CRPS was due to an ‘on-the-job’ injury. The most common type of work-related injury occurred in service employments, such as in restaurants, bakeries and police offices.[11]

The location of the CPRS varies from person to person. It often occurs in the extremities, a little bit more in the lower extremities (+/- 60%) than in the upper extremities (+/- 40%). It can also appear on the left and the right side and in both extremities.[12][13][14]

Complex regional pain syndrome occurs regularly in young adults. It is more frequent in females than males.[15][16]

The onset is mostly associated with a trauma in history, immobilization, injections or surgery. But there is no relation between the grade of severity of the initial injury and the following syndrome. A stressful life and other psychological factors may be potential risk factors that impact the severity of symptoms in CPRS.[17]



Characteristics/Clinical Presentation
[edit | edit source]


Differential Diagnosis[edit | edit source]

The differential diagnosis includes the direct effects of [18][19]


● Bony or soft tissue injury
● Peripheral neuropathy, nerve lesions
● Arthritis
● Infection
● Compartment syndrome
● Arterial insufficiency
● Raynaud’s Disease
● Lymphatic or venous obstruction
● Thoracic outlet syndrome
● Gardner-Diamond Syndrome
● Erythromelalgia
● Self-harm or malingering
● Cellulitis
● Undiagnostic fracture


Diagnostic Procedures

The diagnosis of CRPS requires a complicated process due to the absence of a golden standard test for diagnosis.[20][21][22][23] There are some criteria for diagnosis of CRPS, known as the Budapest criteria, and until there is a golden standard these criteria must suffice.[24] The Budapest criteria, also called the IASP clinical diagnostic criteria for complex regional pain syndrome are[25][26][27][28][29][30]:
● Constant pain, higher than the normally perceived pain
● Minimum one symptom in three of the following four symptom categories must be reported:
○ Vasomotor: temperature asymmetry and/or skin color changes/asymmetry
○ Sensory: hyperalgesia and/or allodynia
○ Sudomotor/edema: changes in sweating
○ Motor/trophic: smaller range of motion,motor dysfunction and/or changes in hair, nails and skin
● In addition to these symptoms the patient must also show signs that he will develop symptoms in at least two symptom categories
● No other illness could explain the set of symptoms the patient is showing.
CRPS diagnosis is mainly based on history, clinical examination, and some supportive investigations, just like:

1. Infrared thermography
Infrared thermography (IRT) is an effective mechanism to find significant asymmetry in temperature between both limbs by determining if the affected side of the body shows vasomotor differences in comparison to the other side. It is reported having a sensitivity of 93% and a specificity of 89%.[31] This test is hard to obtain so it is not often used for diagnosis of CRPS.[32][33][34]

2. Sweat Testing
To determine if the patient sweats abnormally the amount of sweat that he produces can be measured. Q-sweat is an adequate instrument to measure sweat production. The sweat samples should be taken from both sides of the body at the same time.[35][36][37]

3. Radiographic Testing
Irregularities in the bone structure of the affected side of the body can become visible with the use of X-rays. If the X-ray shows no sign of osteoporosis, CRPS can be excluded if the patient is an adult.[38][39][40] 4. Three-phase bone scan
With the use of technetium Tc 99m-labeled bisophosphonates increase in bone metabolism can be shown. Higher uptake of the substance means increased bone metabolism which means the body part could be affected.[41][42]

5. Bone densitometry
An affected limb often shows less bone mineral density and a change in the content of the bone mineral. During treatment of the CPRS the state of the bone mineral will improve. So this test can also be used to determine if the patient’s treatment is effective.[43]

6. Magnetic resonance imaging (MRI)
MRIs are useful to detect periarticular marrow edema, soft tissue swelling and joint effusions. And in a later stage atrophy and fibrosis of periarticular structures can be detected. But these symptoms are not exclusively signs of CRPS.[44][45][46]

7. Sympathetic Blocks
If the patient shows vasomotor or sudomotor dysfunction and severe pain, blocking the sympathetic nerves proves to be an effective technique to evaluate if the sympathetic nervous system is causing the pain to remain. This technique requires local anesthetic or ablation and is successful if at least 50% of the pain is reduced.[47]

Outcome Measures[edit | edit source]

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Examination[edit | edit source]

The original International Association for the Study of Pain criteria required only history and subjective symptoms for a diagnosis of CRPS. But recent consensus guidelines developed by experts have argued for the inclusion of objective findings. [48]

The examination of the affected limb should be done from the neck downwards. The examination should be carried out at rest, during activity, and during ambulation. [49]

During the physical examination, it is very important to investigate the sensory, motor and autonomic dysfunctions. [50][51][52]

1. Autonomic dysfunction
The majority of patients with CRPS have side-to-side differences in temperature of the limbs. The skin temperature depends of the chronicity of the disease. The temperature will increase in acute stages, this is most of the time in combination with a white or reddish skin with more swelling. The temperature will decrease in chronic stages. This is associated with bluish skin and more atrophy. [53]

2. Motor dysfunction
Studies have shown that approximately 70% of the patients with CRPS show muscle weakness in the affected limb, exaggerated tendon reflexes or tremor, irregular myoclonic jerks, and dystonic muscle contractions. Muscle dysfunction often coincides with a loss of range of motion in the distal joints. [54]

3. Sensory dysfunction
The distal ends of the extremities require more attention when examining a patient with CRPS. However, common findings of regional neuropathic and motor dysfunction have shown us that it is important to broaden the examination both proximally and contra laterally.[55]

Light touch, pinprick, temperature and vibration sensation should be assessed to have a correct examination of CRPS.[56] Most assessments are linked with each other. This means that when for example vibration sensation is very positive, light touch should be positive too.[57]

To help distinguish the findings of a sensory dysfunction, you have to compare the affected area with an unaffected area. The findings should be clear and reliable.[58][59]


Medical Management
[edit | edit source]

Treatment of complex regional pain syndrome should be immediate, and most importantly directed toward restoration of full function of the extremity. There are several options to treat CRPS. [60]


Bone demineralization is not unusual in CRPS patients, so treatment with calcitonin and biphosphonates is suitable. Calcitonin has received considerable interest in the management of CRPS because of its analgesic properties through release of ß-endorphin as well as its inhibition of bone resorption.[61] Biphosphonates are potent inhibitors of bone resorption;
- Alendronate: less pain and swelling, more range of motion.[62][63][64]
- Clodronate: less pain, improved global assessment (evaluated by investigator), and higher perceived efficacy (evaluated by patients).[65][66][67]
- Palmidronate: less pain, higher overall improvement (patient’s assessment), and higher functional assessment scores.[68][69]
Generally biphosphonates have been shown to decrease pain and swelling as well as to increase range of motion for patients with CRPS[70]

An excessive inflammatory reaction can lead to the overproduction of free radicals, resulting in the destruction of healthy tissue and possibly leading to CRPS. Thus, free radical scavengers have been proposed to curtail the disease process. To date, three free radical scavengers, like dimethyl sulfoxide (DMSO), have been investigated for the treatment of CRPS.[71]
A scorelist (based on pain, daily activities, edema, color, and ROM) showed greater improvement by dimethyl sulfoxide treatment. DMSO seems to provide a mild improvement in range of motion and vasomotor instability in patients with CRPS.[72]

Biopsy studies showing tissue inflammation in CRPS caused many researchers to use steroids.These steroids showed great improvement in pain and edema. They showed a better post treatment score.[73][74][75]

Intravenous immunoglobulin can reduce pain in refractory CRPS.The average pain intensity was 1.55 units lower after IVIG treatment.[76]

Hyperbaric oxygen therapy is an effective and well tolerated method for decreasing pain, allodynia, oedema and increasing the range of motion in CRPS. Also, the skin colour returns to normal.[77][78]

In the majority of patients with chronic reflex sympathetic dystrophy, electrical stimulation of the spinal cord can reduce pain intensity and improve health-related quality of life.[79][80]


Physical Therapy Management
[edit | edit source]

It is difficult to manage CRPS because there is lack of understanding of the pathophysiologic abnormalities and lack of specific diagnostic criteria. In literature there is very low quality evidence to treat CRPS. [81]
The main goals of treating the patient are reduction of pain, preservation of limb function and return to work. Don’t forget to check the comorbidities such as depression, sleep disturbance and anxiety. Those have to be treated concurrently.
The basic rule is treating the patient in a multidisciplinary approach. This multidisciplinary team should include neurologists, anesthesiologists, orthopedics, physiotherapists and psychologists.


The treatment should be based on basic principles of pain management (pain and symptom relief, supportive care, rehabilitation). Due to the lack of evidence in treatment of CRPS we have to rely on treatments of other neuropathic pain syndromes.[82][83]


Acute phase
Immobilization and contralateral therapy should be the treatment in the acute phase. Intensive active therapy in the acute phase can lead to deterioration.[84]


Chronic phase
1. Passive physical therapy including manipulation, manual therapy[85], massage[86][87] and mobilizations. Lymphatic drainage can be used to facilitate regression of edema.[88] You can also threat tender points by the following rules: more severe tender points as identified by tenderness to palpation are treated before less severe tender points; more proximal or more medial tender points are addressed before more distally and laterally located points; the area of greatest accumulation of tender points is treated first; when tender points are located in a row, the one in the middle of the row is treated first.[89] (level of evidence 4)


2. Therapeutic exercise including isometric strengthening therapy followed by active isotonic training in combination with sensory desensitization programs.[90] 70[91] (level of evidence 3A) The strengthening training includes exercises for all four extremities and trunk. The exercises can be done with Theraband.[92] Desensitization programs contains giving stimuli of different fabrics, different pressure (light or deep), vibration, tapping, heat or cold. The exercises can be stress-loading (f.e. scrubbing, walking, carrying weights), endurance training, written instructions and functional training.[93] When CRPS occurs in the lower extremities, in that case including gait training in the therapy is recommended.[94] (level of evidence 4). It is also useful to give the patient an home exercise program.[95]


3. Mirror therapy or mirror visual feedback[96] (level of evidence 3A)
Mirror therapy contains placing both hands into a box with a mirror separating the two compartments and, while moving both hands, watching the reflection of the unaffected hand in the mirror[97]
Evidence:
-reducing pain intensity and improve function in post-stroke CRPS[98] (level of evidence 2A)[99][100]
-a significant improvement in pain with mirror therapy in a study where they compare a group with mirror therapy doing the same exercises as a group without mirror[101] (level of evidence 2C)
-improve function (low quality evidence)[102]
-no conclusions could be drawn regarding the efficacy of mirror therapy (Rothgangel)[103]

4. Graded motor imagery/learning[104][105][106][107] (level of evidence 1B)
Graded motor imagery consists of recognition of hand laterality (= pictures were presented of right and left hands and then you have to identify the correct size) and imagined hand movement (= pictures of a hand in different positions are presented and then the patient has to move his hand in that position).[108]
Evidence:
-Further trials are required[109][110] (level of evidence 1B)
-GMI plus medical management more effective than medical management plus physiotherapy[111] (level of evidence 3A)
-GMI may reduce pain and improve function[112] (level of evidence 1B)

5. Relaxation[113][114] (level of evidence 1C)
Cognitive-behavioral therapy[115] (level of evidence 2B) contains relaxation training, deep breathing exercises, biofeedback. 4 Relaxation therapy falls under the responsibility of the psychologist.

6. Neuromodulation or invasive stimulation techniques
Neuromodulation contains peripheral nerve stimulation with implanted electrodes, epidural spinal cord stimulation, deep brain stimulation and electrotherapy.[116]
Electrotherapy includes transcutaneous electric nerve stimulation TENS[117][118] (level of evidence 3A), Spinal cord stimulation SCS[119][120][121] (level of evidence 1B),non-invasive brain stimulation (repetitive transcranial magnetic stimulation).[122]
Evidence:
-to reduce pain[123]
-further trials are required[124]

Examples of spinal cord stimulation in the treatment of CRPS in the lower extremities.[125] (level of evidence 4)


7. Other treatments:
-Whirlpool bath/ contrast baths[126] (level of evidence 3B)
-Vocational and recreational rehabilitation[127]
-Psychological therapies: cognitive-behavioral therapy (CBT), operant conditioning (OC), counselling, pain education and relaxation techniques[128][129][130]
-Acupuncture, electroacupuncture[131] (level of evidence 3A)
-Tactile sensory discrimination training[132][133]
-Weight bearing[134]
-Ultrasound therapy
-Kinesiotaping[135] (level of evidence 3B)

The conclusion we can make is that a few clinical studies could demonstrate a significant improvement of CRPS after physical therapy.[136][137][138][139][140] (level of evidence 1B) But further trials are required for an optimal treatment.[141]

Key Research[edit | edit source]

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Resources
[edit | edit source]

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Clinical Bottom Line[edit | edit source]

Complex regional pain syndrome (CRPS) is a term for a variety of clinical conditions characterized by chronic persistent pain. There are two types of CRPS: The difference between type I and type II is based on a consensus between clinicians and scientists. All symptoms of CRPS II show many similarities to those of CRPS I.[142][143][144][145] It is difficult to manage CRPS because there is lack of understanding of the pathophysiologic abnormalities and lack of specific diagnostic criteria. In literature there is very low quality evidence to treat CRPS.[146] The little amount of clinical studies that could demonstrate a significant improvement after physical therapy needs to become more complete by further trials. This is required for an optimal physical management.

Recent Related Research (from Pubmed)[edit | edit source]

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References[edit | edit source]

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  1. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  2. ↑ RHO, R. e.a., Concise Review for Clinicians: Complex Regional Pain Syndrome. Mayo Foundation for Medical Education and Research, 2002. (level of evidence 3A)
  3. ↑ WASNER, G., e.a., Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnostic value. Oxford University Press, 2001. (level of evidence 3A)
  4. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  5. ↑ ROSS A.H. et al., The Theoretical Basis for and Treatment of Complex Regional Pain Syndrome with Prolotherapy. Journal of Prolotherapy, 2010. (level of evidence 2C)
  6. ↑ BARON, et al., Complex regional pain syndrome: mystery explained? The Lancet Neurology, 2003. (level of evidence 3B)
  7. ↑ ALLEN, G., et al., Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain,1999. (level of evidence 2B)
  8. ↑ SUMITANI M., et al., Complex regional pain syndrome. Rheumatology, 2014. (level of evidence 2C)
  9. ↑ JUOTTONEN, K., et al., Altered central sensorimotor processing in patients with complex regional pain syndrome. Pain, 2002. (level of evidence 5)
  10. ↑ ATALA, N.S., et al., Prednisolone in Complex Regional Pain Syndrome. Pain Physician, 2014. (level of evidence 2B)
  11. ↑ ALLEN, G., et al., Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain,1999. (level of evidence 2B)
  12. ↑ ROSS A.H. et al., The Theoretical Basis for and Treatment of Complex Regional Pain Syndrome with Prolotherapy. Journal of Prolotherapy, 2010. (level of evidence 2C)
  13. ↑ ALLEN, G., et al., Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain,1999. (level of evidence 2B)
  14. ↑ SUMITANI M., et al., Complex regional pain syndrome. Rheumatology, 2014. (level of evidence 2C)
  15. ↑ SRINIVASA N. et al., Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy). American Society of Anesthesiologists, 2002. (level of evidence 3B)
  16. ↑ SANDRONI, P., et al., Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study. Pain, 2003. (level of evidence 2B)
  17. ↑ SRINIVASA N. et al., Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy). American Society of Anesthesiologists, 2002. (level of evidence 3B)
  18. ↑ TURNER-STOKES, L., e.a., Complex regional pain syndrome in adults: concise guidance. Clinical Med, 2011. (level of evidence 5)
  19. ↑ MCBRIDE, A., e.a., Complex Regional Pain Syndrome, Current Orthopaedics, 2005. (level of evidence 3A)
  20. ↑ PEREZ, R., et al., Diagnostic criteria for CRPS I: Differences between patient profiles using three different diagnostic sets. European Journal of Pain, 2007. (level of evidence 2A)
  21. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  22. ↑ HARDEN, R. N., et al., Validation of proposed diagnostic criteria (the ‘‘Budapest Criteria”) for Complex Regional Pain Syndrome. International Association for the Study of Pain, 2010. (level of evidence 1C)
  23. ↑ CHOI, E., et al., Interexaminer reliability of infrared thermography for the diagnosis of complex regional pain syndrome. Skin Research and Technology, 2013. (level of evidence 2B)
  24. ↑ HARDEN, R. N., Commentary: The Diagnosis of CRPS: Are we there yet?. International Association for the Study of Pain, 2012. (level of evidence 1B)
  25. ↑ PEREZ, R., et al., Diagnostic criteria for CRPS I: Differences between patient profiles using three different diagnostic sets. European Journal of Pain, 2007. (level of evidence 2A)
  26. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  27. ↑ HARDEN, R. N., et al., Validation of proposed diagnostic criteria (the ‘‘Budapest Criteria”) for Complex Regional Pain Syndrome. International Association for the Study of Pain, 2010. (level of evidence 1C)
  28. ↑ HARDEN, R. N., Commentary: The Diagnosis of CRPS: Are we there yet?. International Association for the Study of Pain, 2012. (level of evidence 1B)
  29. ↑ WASNER, G., et al., Complex regional pain syndrome - diagnostic, mechanisms, CNS involvement and therapy. International Spinal Cord Society, 2003. (level of evidence 2A)
  30. ↑ HODGE, S., et al., Complex Regional Pain Syndrome: The Anatomy Of A Controversy. Anatomy For Litigators: complex regional pain syndrome, p. 163-167. (level of evidence 2A)
  31. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  32. ↑ PEREZ, R., et al., Diagnostic criteria for CRPS I: Differences between patient profiles using three different diagnostic sets. European Journal of Pain, 2007. (level of evidence 2A)
  33. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  34. ↑ CHOI, E., et al., Interexaminer reliability of infrared thermography for the diagnosis of complex regional pain syndrome. Skin Research and Technology, 2013. (level of evidence 2B)
  35. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  36. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  37. ↑ CHEMALI, K., et al., α-adrenergic supersensitivity of the sudomotor nerve in complex regional pain syndrome. Annals of Neurology, 2001. (level of evidence 2B)
  38. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  39. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  40. ↑ HODGE, S., et al., Complex Regional Pain Syndrome: The Anatomy Of A Controversy. Anatomy For Litigators: complex regional pain syndrome, p. 163-167. (level of evidence 2A)
  41. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  42. ↑ HODGE, S., et al., Complex Regional Pain Syndrome: The Anatomy Of A Controversy. Anatomy For Litigators: complex regional pain syndrome, p. 163-167. (level of evidence 2A)
  43. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  44. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  45. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  46. ↑ HODGE, S., et al., Complex Regional Pain Syndrome: The Anatomy Of A Controversy. Anatomy For Litigators: complex regional pain syndrome, p. 163-167. (level of evidence 2A)
  47. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  48. ↑ PENTLAND, B., e.a., Parkinsonism and dystonia. Neurological Rehabilitation, 1997. (level of evidence 2C)
  49. ↑ SANDEEP, J., Complex Regional Pain Syndrome. Indian Journal of Plastic Surgery, 2011. (level of evidence 2A )
  50. ↑ PENTLAND, B., e.a., Parkinsonism and dystonia. Neurological Rehabilitation, 1997. (level of evidence 2C)
  51. ↑ ROMMEL, e.a., Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits. Ruhr-University, 2000. (level of evidence 1B)
  52. ↑ SANDEEP, J., Complex Regional Pain Syndrome. Indian Journal of Plastic Surgery, 2011. (level of evidence 2A )
  53. ↑ FRONTERA, W, e.a., Essentials of Physical Medicine and Rehabilitation - Musculoskeletal disorders, pain and rehabilitation. Saunders Elsevier, 2002. (level of evidence 5)
  54. ↑ SANDEEP, J., Complex Regional Pain Syndrome. Indian Journal of Plastic Surgery, 2011. (level of evidence 2A )
  55. ↑ FRONTERA, W, e.a., Essentials of Physical Medicine and Rehabilitation - Musculoskeletal disorders, pain and rehabilitation. Saunders Elsevier, 2002. (level of evidence 5)
  56. ↑ FRONTERA, W, e.a., Essentials of Physical Medicine and Rehabilitation - Musculoskeletal disorders, pain and rehabilitation. Saunders Elsevier, 2002. (level of evidence 5)
  57. ↑ FRONTERA, W, e.a., Essentials of Physical Medicine and Rehabilitation - Musculoskeletal disorders, pain and rehabilitation. Saunders Elsevier, 2002. (level of evidence 5)
  58. ↑ FRONTERA, W, e.a., Essentials of Physical Medicine and Rehabilitation - Musculoskeletal disorders, pain and rehabilitation. Saunders Elsevier, 2002. (level of evidence 5)
  59. ↑ SANDEEP, J., Complex Regional Pain Syndrome. Indian Journal of Plastic Surgery, 2011. (level of evidence 2A )
  60. ↑ WASNER, G., et al., Complex regional pain syndrome - diagnostic, mechanisms, CNS involvement and therapy. International Spinal Cord Society, 2003. (level of evidence 2A)
  61. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  62. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  63. ↑ WASNER, G., et al., Complex regional pain syndrome - diagnostic, mechanisms, CNS involvement and therapy. International Spinal Cord Society, 2003. (level of evidence 2A)
  64. ↑ ADAMI, S., et al., Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis,1997. (level of evidence 2B)
  65. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  66. ↑ WASNER, G., et al., Complex regional pain syndrome - diagnostic, mechanisms, CNS involvement and therapy. International Spinal Cord Society, 2003. (level of evidence 2A)
  67. ↑ VARENNA, M., et al., Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. Journal of Rheumatology, 2000. (level of evidence 2B)
  68. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  69. ↑ ROBINSON, J.N., et al., Efficacy of pamidronate in complex regional pain syndrome type I. Pain Medicine, 2004. (level of evidence 2B)
  70. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  71. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  72. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  73. ↑ WASNER, G., et al., Complex regional pain syndrome - diagnostic, mechanisms, CNS involvement and therapy. International Spinal Cord Society, 2003. (level of evidence 2A)
  74. ↑ CHRISTENSEN, K., et al., The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1982. (level of evidence 2B)
  75. ↑ BRAUS, D.F., et al., The shoulder-hand syndrome after stroke: a prospective clinical trial. Annals of Neurology, 1994. (level of evidence 1B)
  76. ↑ GOEBEL, A. et al., Intravenous Immunoglobulin Treatment of the Complex Regional Pain Syndrome: A Randomized Trial, Annals of internal medicine, 2010. (level of evidence 1B)
  77. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  78. ↑ KIRALP, M.Z. et al., Effectiveness of Hyperbaric Oxygen Therapy in the Treatment of Complex Regional Pain Syndrome, The Journal of International Medical Research, 2004. (level of evidence 1B)
  79. ↑ KEMLER M. et al., Spinal Cord Stimulation in Patients with Chronic Reflex Sympathetic Dystrophy. The New England Journal of Medicine, 2000. (level of evidence 2B)
  80. ↑ FOROUZANFAR T. et al., Spinal cord stimulation in complex regional pain syndrome: cervical and lumbar devices are comparably effective. British Journal of Anaesthesia, 2004. (level of evidence 2B)
  81. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  82. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  83. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  84. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  85. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  86. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  87. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  88. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  89. ↑ COLLIN, C., Physical Therapy Management of Complex Regional Pain Syndrome I in a 14-Year-Old Patient Using Strain Counterstrain: A Case Report. J Man Manip Ther., 2007. level of evidence 4)
  90. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  91. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  92. ↑ STANTON-HICKS, M., et al., Complex Regional Pain Syndromes: Guidelines for Therapy. The Clinical Journal of Pain, 1998. (level of evidence 5)
  93. ↑ STANTON-HICKS, M., et al., Complex Regional Pain Syndromes: Guidelines for Therapy. The Clinical Journal of Pain, 1998. (level of evidence 5)
  94. ↑ COLLIN, C., Physical Therapy Management of Complex Regional Pain Syndrome I in a 14-Year-Old Patient Using Strain Counterstrain: A Case Report. J Man Manip Ther., 2007. level of evidence 4)
  95. ↑ STANTON-HICKS, M., et al., Complex Regional Pain Syndromes: Guidelines for Therapy. The Clinical Journal of Pain, 1998. (level of evidence 5)
  96. ↑ SMITH, T., How effective is physiotherapy in the treatment of complex regional pain syndrome type I? A review of the literature. Musculoskeletal care, 2005. (level of evidence 3A)
  97. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  98. ↑ MCGABE, C.S., et al., Mirror visual feedback for the treatment of complex regional pain syndrome (Type 1). Current Pain and Headache Reports, 2008. (level of evidence 2A)
  99. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  100. ↑ BOWERING, K. J., The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis. The American Pain Society, 2013. (level of evidence 1A)
  101. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  102. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  103. ↑ ROTHGANGEL, A.S., et al., The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature. International Journal of Rehabilitation Research, 2011. (level of evidence 3A)
  104. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  105. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  106. ↑ MOSELEY, G.L., Graded motor imagery is effective for long standing complex regional pain syndrome: a randomised controlled trial. Pain, 2004. (level of evidence 1B)
  107. ↑ SMITH, T., How effective is physiotherapy in the treatment of complex regional pain syndrome type I? A review of the literature. Musculoskeletal care, 2005. (level of evidence 3A)
  108. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  109. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  110. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  111. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  112. ↑ MOSELEY, G.L., Graded motor imagery is effective for long standing complex regional pain syndrome: a randomised controlled trial. Pain, 2004. (level of evidence 1B)
  113. ↑ BRUEHL, S., Psychological interventions. In: Harden RN editor(s). Complex regional pain syndrome: treatment guidelines. Reflex Sympathetic Dystrophy Syndrome Association, 2006 (level of evidence 1C)
  114. ↑ SMITH, T., How effective is physiotherapy in the treatment of complex regional pain syndrome type I? A review of the literature. Musculoskeletal care, 2005. (level of evidence 3A)
  115. ↑ LEE, B., et al., Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. Pain Treatment Service, 2002. (level of evidence 2B)
  116. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  117. ↑ OAKLANDER, A., et al., Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy). Pain, 2006. (level of evidence 1B)
  118. ↑ SMITH, T., How effective is physiotherapy in the treatment of complex regional pain syndrome type I? A review of the literature. Musculoskeletal care, 2005. (level of evidence 3A)
  119. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  120. ↑ ALBAZAZ, R. N., et al., Complex Regional Pain Syndrome: A review. Annals of Vascular Surgery Inc., 2008. (level of evidence 2A)
  121. ↑ KENLER, M., et al., The effect of Spinal Cord Stimulation in Patients with Chronic Reflex Sympathetic Dystrophy: Two Years’ Follow-up of the Randomized Controlled Trial. Annals of Neurology, 2004. (level of evidence 1B)
  122. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  123. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  124. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  125. ↑ COLLIN, C., Physical Therapy Management of Complex Regional Pain Syndrome I in a 14-Year-Old Patient Using Strain Counterstrain: A Case Report. J Man Manip Ther., 2007. level of evidence 4)
  126. ↑ DEVRIMSEL, G., et al., The effects of whirlpool bath and neuromuscular electrical stimulation on complex regional pain syndrome. J. Phys. Ther. Sci., 2015. (level of evidence 3B)
  127. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  128. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  129. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  130. ↑ BRUEHL, S., Psychological interventions. In: Harden RN editor(s). Complex regional pain syndrome: treatment guidelines. Reflex Sympathetic Dystrophy Syndrome Association, 2006 (level of evidence 1C)
  131. ↑ SMITH, T., How effective is physiotherapy in the treatment of complex regional pain syndrome type I? A review of the literature. Musculoskeletal care, 2005. (level of evidence 3A)
  132. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  133. ↑ BOWERING, K. J., The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis. The American Pain Society, 2013. (level of evidence 1A)
  134. ↑ TRAN, Q., e.a., Treatment of complex regional pain syndrome: a review of the evidence. Canadian Anesthesiologists’ Society, 2010. (level of evidence 1A)
  135. ↑ ANANDKUMAR, S.; MANIVASAGAM, M., Multimodal physical therapy management of a 48-year-old female with post-stroke complex regional pain syndrome. Physiother Theory Pract, 2014. (level of evidence 3B)
  136. ↑ BIRKLEIN, F., et al., Neurological findings in complex regional pain syndromes—analysis of 145 cases. Acta Neurol Scand, 2000. (level of evidence 2A)
  137. ↑ SHERRY, D., et al., Short- and long-term outcomes of children with complex regional pain syndrome type I treated with exercise therapy. Clin J Pain, 1999. (Level of evidence 1B)
  138. ↑ OERLEMANS, H., et al., Adjuvant Physical Therapy Versus Occupational Therapy in patients With Reflex Sympathetic Dystrophy/Complex Regional Pain Syndrome type I. Arch Phys Med Rehabil, 2000. (level of evidence 1B)
  139. ↑ LEE, B., et al., Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. Pain Treatment Service, 2002. (level of evidence 2B)
  140. ↑ OERLEMANS, H., et al., Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomised controlled clinical trial of adjuvant physical therapy versus occupational therapy. Pain, 1999. (level of evidence 1B)
  141. ↑ PEREZ, R., Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurology, 2010. (level of evidence 2C)
  142. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
  143. ↑ WASNER, G., e.a., Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnostic value. Oxford University Press, 2001. (level of evidence 3A)
  144. ↑ BARON, R., Complex regional pain syndromes. Curr Pain Headache Rep., 2001. (level of evidence 2A)
  145. ↑ JANIG, W., et al., Complex regional pain syndrome is a disease of the central nervous system. Clinical Autonomic Research, 2002. (level of evidence 5)
  146. ↑ O’CONNEL, N.E., e.a., Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews (Review). The Cochrane Collaboration, 2013. (level of evidence 3A)
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