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|Year : 2022 | Volume
| Issue : 2 | Page : 491-503
Complex Regional Pain Syndrome after Carpal Tunnel Syndrome Surgery: A Systematic Review
Luis Henrique A. Sousa1, Caroline de O. Costa2, Eduardo M Novak2, Giana S Giostri2
1 Division of Neurosurgery, Cajuru University Hospital, Curitiba, Brazil Cajuru University Hospital, Curitiba, Brazil
2 Division of Hand Surgery, Cajuru University Hospital, Curitiba, Brazil Cajuru University Hospital, Curitiba, Brazil
|Date of Submission||22-Aug-2020|
|Date of Decision||21-Sep-2020|
|Date of Acceptance||20-Dec-2020|
|Date of Web Publication||3-May-2022|
Dr. Luis Henrique A. Sousa
Albuquerque Sousa, Adress: Rua Capote Valente, 1300, zip code: 05409003
Source of Support: None, Conflict of Interest: None
Background: Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment. One of the most devastating complications is complex regional pain syndrome.
Objectivities: The aim of this study was to systematically analyze available evidence about complex regional pain syndrome after carpal tunnel syndrome surgery (CTSS), its risks, associated factors, and treatments.
Material and Methods: Research conducted from 1962 through December 31, 2018, in the following databases: PubMed, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. The quality assessment of the methodology followed the definitions by the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. The GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation) was applied to evaluate the efficacy of the stellate ganglion block, one of the most cited and recurrent treatments.
Results: Of the 246 studies retrieved, 44 articles were included. Concerning patients' gender, we identified a ratio of 5 females: 3 males. The mean age for women was 57.79, a standard deviation of 14.96, and for men 60.75, a standard deviation of 9.4. Considering the total of primary publications of CTSS outcomes, the accumulated incidence reached the maximum of 0.15 CRPS after CTSS patients/CTSS patients. The known risk factors for CRPS after CTSS: female gender, from the fifth decade of life, tourniquet time, immobilization and surgery on dominant hand.
Conclusion: CRPS affects 2-5% of people undergoing CTSS. Its diagnosis is still a challenge and its risk factors are unclear, although it seems more likely to affect women, in the dominant hand. The most used treatments include physiotherapy and stellate ganglion block. Most patients show improvement of symptoms within one year. Further clinical trials comparing treatment modalities are required.
Keywords: Carpal tunnel syndrome, carpal tunnel syndrome surgery, complex regional pain syndrome, complications
Key message: CRPS after CTSS is more likely to affect women, older than 40 years of age, in the dominant hand. The most used treatments include physiotherapy and stellate ganglion block. Most patients improve the symptoms within one year.
|How to cite this article:|
A. Sousa LH, O. Costa Cd, Novak EM, Giostri GS. Complex Regional Pain Syndrome after Carpal Tunnel Syndrome Surgery: A Systematic Review. Neurol India 2022;70:491-503
|How to cite this URL:|
A. Sousa LH, O. Costa Cd, Novak EM, Giostri GS. Complex Regional Pain Syndrome after Carpal Tunnel Syndrome Surgery: A Systematic Review. Neurol India [serial online] 2022 [cited 2022 Jul 3];70:491-503. Available from: https://www.neurologyindia.com/text.asp?2022/70/2/491/344616
Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment at global level,, with a prevalence among the general population ranging from 4 to 7%., Surgical treatment presents complication rates lower than 3%, including complex regional pain syndrome (CRPS),, a devastating chronic pain syndrome with difficult and not well-known prevention and management. Despite low complication rates, the high incidence of CTS makes CRPS common in clinical practice.
This paper aims to analyze available evidence about the complex regional pain syndrome after carpal tunnel syndrome surgery (CTSS), its risks, associated factors, and treatments.
| » Material and Methods|| |
A systematic literature review was performed and registered at Prospero (International prospective register of systematic reviews), under number CRD42019122840.
The two main authors searched the articles in PubMed, Web of Science, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, by applying the following MeSH terms and subheadings in all fields: “Carpal Tunnel Syndrome” OR “Carpal Tunnel Syndrome Surgery” associated with “Complex Regional Pain Syndromes” OR “Causalgia” OR “Reflex Sympathetic Dystrophy”. The covered search period was from 1962 to December 31st, 2018.
Authors followed the PICOT approach, specifying Population as patients that developed CRPS after CTSS; Intervention as any form of CRPS treatment; Primary outcome as the improvement of CRPS symptoms, measured in any scale. Secondary outcomes included any scale of measured quality of life and complications related to CRPS treatment. Publications with missing or incomplete description of outcomes were also accepted. The study designs accepted included literature reviews, clinical trials, case-control studies, cohort studies, case reports, and specialist reports. Regarding Time, any length of follow-up was accepted. Additionally, only articles published in English, Portuguese, and Spanish, with available abstracts were included. A secondary review was performed using the reference list of the eligible articles. Some other articles were included aiming to improve the discussion.
All titles and abstracts were evaluated by main authors and excluded by consensus if CRPS symptoms reported were caused by other comorbidities. Articles that reported CRPS cases in which patients developed CTS after trauma or those that received conservative treatment were also excluded. Additionally, articles that did not meet the main purpose of this manuscript were excluded.
The quality assessment of the methodology, performed by the two main authors, followed the definitions by Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (OCEBM L).,, Other authors were consulted when consensus regarding the inclusion of articles was not reached. It has been recurrently described that stellate ganglion block, used in the treatment for CRPS after CTSS, represents an important outcome, whose quality was assessed by applying the GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation). Meta-analysis was not performed due to paucity of complete data and quantitative analysis was used to summarize previous results.
| » Results|| |
According to previous search strategy, a total of 246 citations, published from 1962 to 2018, were collected. After removal of duplicates (43), articles in other languages (28) and without abstract (22), 153 articles remained. Some articles were excluded for their out-of-date nature and for not being available in the online journal repository,,, (4), for being categorized as conference papers (2) and for not presenting published data of trial results (1). Seventy-four additional articles were excluded after title and abstract evaluation, and 28 after full-text reading. The remaining 44 articles were considered suitable to be used in this review [Figure 1], namely 11 literature reviews,,,,,,,,,, (6 systematic), 10 randomized controlled trials (RCT),,,,,,,,,, 9 cohort studies,,,,,,,, and 14 case reports/case series.,,,,,,,,,,,,,
The quality of evidence of the selected articles, provided by GRADE, ranged from level 1 to 5 (almost 30% with OCBM level of 4-5). Although several articles describe CTSS techniques and surgical procedures, few describe CRPS after CTSS condition [Table 1], [Table 2], [Table 3], [Table 4]. In fact, the lack of specific information limits the analysis of patient characterization and CRPS treatment in the present review. It has been identified that epidemiological information, such as age and gender, is missing in 50% of the articles (22 studies: 9 CR/CS, 4 Cohort, 9 RCT). Similarly, clinical information, such as comorbidities, symptoms and physical examination, is not reported in 20 studies (9CR/CS, 2 Cohort, 9RCT); specification and description of CRPS treatment are not provided in 13 studies (7 CR/CS, 4 Cohort, 6 RCT); and follow up information related to its length and related outcomes is not listed in 22 studies (9 CS/CR, 6 Cohort, 7 RCT). Considering the information available, only 61 patients were identified according to their gender, a ratio of 5 females: 3 males. Regarding the patients' age, the mean for women was 57.79, a standard deviation of 14.96. For men, the mean age was 60.75, a standard deviation of 9.4.
|Table 1: Case series and case reports studies included in the review criteria and Author analysis of their limitations and level of evidence|
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|Table 2: Cohort studies included in the review criteria and Author analysis of their limitations and level of evidence|
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|Table 3: Randomized clinical trials studies included in the review criteria and author analysis of their limitations and level of evidence|
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|Table 4: Literature Reviews included in the review criteria and Author analysis of their limitations and level of evidence|
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Considering the total number of primary publications on CTSS outcomes (24 studies: 8CS, 6 cohort, 10 RCT), the accumulated incidence reached the maximum of 0.15 CRPS after CTSS patients/CTSS patients [Figure 2].
|Figure 2: CRPS accumulative incidence described in follow up studies of CTSS outcomes per publication study year|
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Seventeen articles reported treatments used for CRPS after CTSS; the most prevailing were stellate ganglion block (5 papers – 2 CS/CR, 2 Cohort, 1 RCT) and physiotherapy (6 papers – 1 CS/CR, 3 Cohort, 2 RCT). The overall efficacy grade for the CRPS treatment, measured in any scale for pain control and quality of life, is very low (1 RCT, 4 observational studies, limited due to indirectness and use of spare data).
Only 7 papers (2 LR, 3 Cohort, 1 CS/CR, 1 RCT) addressed risk factors for developing CRPS, and only 3 articles detailed risk factors for CRPS after CTSS, namely, tourniquet time (RCT), immobilization (CS/CR), female gender, surgery on dominant hand and age older than 42 years (Cohort). One cohort study suggested that Laser Doppler Image may identify patients with higher risk for developing CRPS again, even after being successfully treated. Fewer than one third of publications documented CRPS after CTSS as one of the major topics (7CR/CS, 4 Cohort, 1 RCT, 1 SR, 1 NR).
| » Discussion|| |
This is the first systematic review, to the best of our knowledge, addressing complex regional pain syndrome after CTSS. Although it is a well-described complication, publications on the syndrome are relatively new. The first case series was published in 1978, while the first systematic review included cases 20 years later,. There has been an increasing interest over the years addressing this complication, reflecting the number of publications and the quality of primary study design [Figure 3], while the total number of publications for year about CTS have decreased.
|Figure 3: CRPS after CTSS patients described along years of medical publication of primary studies. Logarithmic scale (base 5)|
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CRPS definition and diagnosis
CRPS is a clinical debilitating condition characterized by chronic pain, sensorial changes and vasomotor symptoms in the affected limb., The typical signs are burning and severe pain, edema, allodynia, differences in temperature and skin color and motor dysfunction, usually with joint stiffness.,,,,,, The first symptoms of CRPS after CTSS may appear early in the recovery room, although most patients present symptoms 1 to 3 weeks after surgery.
Full identification of CRPS has been challenging. For a long time, other names, such as reflex sympathetic dystrophy and causalgia, have described the syndrome. This inconsistency has caused a delay in identifying its risk factors, diagnostic criteria and treatment options. Only in 1994, were diagnostic criteria defined at the Orlando conference, being adopted by the Committee for Classification of Chronic Pain of the International Association for the Study of Pain (IASP)., These criteria were modified into a higher specificity version, the Budapest criteria, which included the motor features. [Figure 4].
|Figure 4: Schematic representative overview of the original and updated IASP criteria for CRPS. For a complete review of criteria, the authors suggest further reading of the references provided in the text|
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Even though CRPS diagnosis is performed by clinical criteria, mechanical testing, autonomic function evaluation and 3-phase bone scans can help confirm it. However, none of these exams has been determined as a prerequisite for diagnosis.,
CRPS is divided into 2 types: type I (CRPS I), which occurs in the absence of a known or confirmed nerve injury, and type II (CRPS II), which occurs in the presence of an identifiable nerve lesion.,,, Although these subtypes are well defined, there are some difficulties in categorizing CRPS after CTSS. Some authors define CRPS after CTSS as CRPS I, considering that it is difficult to determine that an injury was caused intraoperatively, whereas others determine that it is actually CRPS II,, accepting the fact that an iatrogenic lesion occurred intraoperatively. Although some progress in diagnosis has been reached, there still remain some issues about the authenticity of CRPS I, mainly because it presents many non-specific symptoms inconsistent with the causative event.,
CRPS after CTSS: epidemiology, risks, and associated factors
The reported incidence of CRPS is 5-25 per 100.000 people/year, Type I being the most common.,, The exact epidemiology of CRPS after hand surgery is uncertain; however, literature reports it as a complication of CTSS in 2-5% of patients.,, There is a tendency to decrease the incidence over the first 3 postoperative months with stabilization of the prevalence after 6 months.
Many authors describe that women are more affected than men, probably due to the higher prevalence of CTS in females.,, Diabetes Mellitus and hypertension are risk factors for CTS, but not for CRPS post CTS; migraine also has no association.,
Some authors claim that there is no difference between genders, age and body mass index (BMI), while others suggest that age higher than 42 years and surgery of the dominant hand represent risk factors. Also, there is the possibility of misleading diagnosis of CTS as CRPS in earlier stage. Regarding the anesthetic techniques commonly used at the surgery for carpal tunnel release, there are no differences in the development of CRPS, although the duration of tourniquet can be a factor for the development of this complication in patients undergoing general anesthesia and brachial plexus block.
Although the type of CTSS procedure (endoscopic x open) do not influence the rate of CRPS, early surgery for moderate to severe cases have better outcome; and the control of postoperative acute pain is extremely important to prevent the development of chronic pain. Some papers recommend the use of perioperative gabapentin to reduce its incidence. However, these data have not been supported in RCTs. Some surgeons still apply some kind of splint after CTSS, although there are no evidences that orthoses following routine release of carpal tunnel can prevent CRPS.
CRPS after CTSS management
Several treatment modalities were described for CRPS post CTSS. Management includes physiotherapy with or without associated medications and interventions,,,,,,,, botulinum toxin, stellate ganglion blockage, peripheral nerve stimulation in median nerve, axillary brachial plexus block with patient-controlled analgesia, neurolysis and flap coverage of median nerve, even amputation was disclosed in a report to treat CRPS complications [Table 1 and 4]. Calcitonin, for a long time used as a treatment for CRPS, is no longer recommended. Other modalities as intrathecal delivery of medications and spinal cord stimulation are options to CRPS treatment, but not specifically to treat CRPS after CTSS, and could be appraised in an earlier phase.
Early diagnostic and treatment are extremely important in the management of CRPS., There are no evidences to determine how long conservative measures should be applied before the adoption of more invasive procedures. Most patients improve within one year, while others remain with symptoms up to nine years.
Patients treated for CRPS with good results are at risk of developing it again if required to undergo a surgery in the same region. This suggest the syndrome, regardless of treatment, can be recurrent or migratory, but this information is controversial and reported in few case on literature. The reasons why this complication affects only some patients are not clear. However, an evaluation of the function of the sympathetic nervous system preoperatively can help to identify them. This evaluation can be performed with Laser Doppler Image. Once identified, the patient can have a preemptive stellate ganglion block to lessen the regress of CRPS. An alternative treatment for recurrent CTS associated with CRPS is a new release of the transverse carpal ligament combined with neurolysis of the median nerve, although this may be insufficient to ease the symptoms. Preoperative gabapentin was used for many years to decrease pain intensity and the development of CRPS after CTSS. However, there are no evidences confirming its efficacy. Myofascial pain syndrome (MFPS) is described in association with CRPS affecting proximal muscles, and evidences suggest that treatment of this condition may improve CRPS.
For patients that show no improvement with any form of treatment and persist with severe symptoms, functional disability and incapacitant pain, amputation may represent the only option.
CRPS after CTSS: other considerations
Some RCTs stress the importance of advising patients about CTSS risks, expressing their concern that many of the patients, despite receiving written information about complications following CTSS, did not remember that CRPS is a possible complication.
The strength of this publication lies in the summary of the epidemiology and associate factors and risks. The main limitation is the impossibility to provide a high degree of treatment recommendation, considering the lack of systematic treatment procedures, biased publications and the overall low-quality assessment of the included papers.
| » Conclusion|| |
CRPS affects 2-5% of patients undergoing CTSS, configuring a dreaded complication involving functional and psychological disabilities. Its diagnosis still represents a challenge in clinical practice. Risk factors are unclear, although it seems to affect more women, from the fifty decades of life, in dominant hand. The most used treatments are physiotherapy and stellate ganglion blockage. Most patients show improvement of symptoms within one year. Further clinical trials, comparing treatment modalities, are required.
The Authors would like to thank Areta Ulhana Galat (Master of Arts in Teaching of English as a Second Language of Ilinois – Urbana – Champaign) for language editing.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]