1 Introduction

Adhesive capsulitis(AC)is characterized by shoulder joint capsular thickening, fibrosis, and adherence of the capsule to itself and to the anatomic neck of the humerus causing a mechanical restraint to motion.^1–4 The prevalence rate of AC is 2%–5%, and it's etiology can be divided into intrinsic, extrinsic and systemic ones.^5,6 A wide range of treatment modalities have been described, such as supervised neglect, physiotherapy, intra-articular corticosteroid injections, capsular distension injections, manipulation under anesthesia (MUA), arthroscopic capsular release and trans catheter arterial embolisation.^7,8 Recent literature suggested that there is hypervascularity at the rotator interval with increased expression of vascular endothelial growth factor which might be the causative factor of adhesive capsulitis. Abnormal neo-vessels and substance-P positive nerves in their vicinity have been identified as a possible source of pain. Transcatheter arterial embolisation (TAE) has been used to occlude the target neovessels by infusing an embolic agent in a few studies.^9–12

This is first systemic review on Transcatheter arterial embolisation as treatment modality for adhesive capsulitis, after conservative management fails to produce satisfactory result. There is no clear guideline regarding the routine use of TAE in conservatively managed resistant cases of adhesive capsulitis. Although few researchers advocates the use of TAE,but unfortunately there is no consensus which treatment modality is superior. The aim of the current review is to determine whether TAE is a superior modality than the conventional mode of management, pain relief from TAE is permanent or temporary and whether this method can be advocated as a routine procedure at current understanding of literature.

2 Methods

The systematic review was performed following PRISMA(Preferred Reporting Items for Systemic Reviews and Meta-analysis) guidelines.

3 Eligibility criteria

Scientific articles describing the procedure and results of transcatheter arterial embolisation were selected for analysis based on our inclusion criteria. Results must have included pre and post intervention clinical outcome in terms of shoulder range of motion and pain. Studies must have recruited patients after conservative management trial of at least 3 months.

Inclusion criteria-1.Patients with adhesive capsulitis-severe shoulder pain, night shoulder pain; painful restriction of both active and passive elevation2.Trial of conservative therapies comprising rest, anti-inflammatory drugs, cortico-steroid injections, and physical therapy and post treatment persistent moderate to severe pain (visual analog scale)

Exclusion criteria-1.Secondary adhesive capsulitis like arthritis, rotator cuff tears, calcific tendinitis etc.2.Local infection,3.Malignancy4.Prior shoulder surgery5.Inflammatory arthritis

4 Searches

The search algorithm used for PubMed, Google Scholar, Scopus was Transcatheter arterial embolisation and or resistant adhesive capsulitis or refractory adhesive capsulitis or vascular adhesive capsulitis. For the CDSR, term used was “Transcatheter arterial embolisation and or resistant adhesive capsulitis or refractory adhesive capsulitis or vascular adhesive capsulitis.” These online databases were searched in March 2021.

5 Study selection

The study selections were performed independently by 2 investigators(SK and VK). These same authors extracted relevant data from the studies. Discrepancies between selected studies were none. Fig. 1 demonstrates the step by step process of section of the articles included in the study.

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Fig. 1 Literature selection algorithm as per PRISMA guidelines.

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6 Results

The databases mentioned above showed a total of 12,026 scientific articles. The non relevant articles were excluded and a total of 113 abstracts were selected for review. Duplicate articles were removed and finally three publications were included in the review. All of these articles were level IV studies. Search for references was performed but no additional articles were found relevant. Table 1 summarizes studies which were included in this review.

7 Technique

Interventional radiologist with more than 5 years of experience performed the procedure in all the included studies under local anaesthesia. Radial artery (25 patients out of 71) or femoral artery(46 patients out of 71) of ipsilateral side was used to gain access for selective catheterization of subclavian artery.¹⁰ After that, digital subtraction angiography (DSA) was performed to determine the “abnormal neovessels”.¹¹ Targetted embolisation of the neovessels were performed with embolic agent IMP/CS (imipenem/cilastatin sodium) in all the cases. Repeat angiogram was performed to determine the success of the procedure. The average amount of the embolic substance used in each procedure was 1.6 ml (0.2–3.1 ml) and mean duration of the procedure was 48 ± 17.2 min.¹⁰ Patients were discharged from hospital after 8 h of the procedure and no shoulder movement was allowed at the day of surgery. Shoulder ROM was started the next day of the procedure. Patients were encouraged to continue the conservative therapy they were undergoing before surgery. But the patients were not allowed to start on any new therapy for 6 months after the procedure.

8 Adverse events

No major adverse reactions were noted during or after the procedure in the included studies. Few minor side effects were noted that resolved without any major interventions. Pain, spasm of radial artery, discomfort of groin due to haematoma formation are few minor reactions. Fever at the night of the procedure was noted in few cases but subsided without intervention.^9,11 Theoretically, there might be occurrence of avascular necrosis(AVN) of humeral head if non target arteries are embolised. We did not note any case of this devastating complication in studies incorporated in this review. The possible explanation is generation of micron sized particles due to IMP/CS (imipenem/cilastatin sodium) that acts as short acting embolic agent and resorb within 48 h of administration. At present, there is no evidence that TAE increases the risk of AVN of humealhead, although large database is lacking on this event.

9 Outcome measures

Three different outcome measures were visual analog scale (VAS) score, shoulder range of motion and American shoulder and elbow surgeon score. Overall outcome scores are summarized in Table 2.

10 Results

Three studies meeting criteria for the systematic review included 72 shoulders from 72 patients. There were 16 men and 56 women with mean age of 51.3 years (range 39–69 years). Follow-up was done at one week,4 week, 12 week, 24 week and 36 months with a mean reported follow-up of 24.5 months (range 6–36 months). Pre and post operative data was compared and analyzed for 71 shoulders from 71 patients. One patient was lost to follow up. There were gradual improvement of VAS score from week 1 to final follow up which was statistically significant (p < 0.001). Most significant improvement was noted in night time pain. Statistically significant improvement of shoulder motion and American shoulder and elbow score was also noted(Fig. 2 and 3).

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Fig. 2 Depicting improvement in range of motion at different follow up intervals.

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Fig. 3 Showing improvement in ASES score at different follow up intervals.

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11 Discussion

Abnormal neovascularization around the shoulder joint capsule causing pain is the most crucial finding described in the recent literature.^9–11 The inciting event of the neovascularization is still under consideration of research and has not been mentioned precisely in any study. But, one study mentioned that tenderness at the coracoid process tip is almost a constant finding among the patients of adhesive capsulitis.¹ The arthroscopic findings also indicates extensive involvement of rotator interval with neovascularization.^9–11,14,15 The magnetic resonance imaging suggests that the most characteristic finding was thickening of coracohumeral ligament and fat in the triangle beneath the coracoid process.¹³ Even the open exploration has indicated that most of the abnormal and thickened part of the shoulder joint capsule is a part of coracohumeral ligament.^16,17 Histopathological examination of the excised tissue also indicated an ongoing inflammation leading to extensive myofibroblastic proliferation suggesting firmly that inflammation around the shoulder capsule that incites neovascularization and subsequent fibrosis is the central part of pathogenesis of the adhesive capsulitis. The neovascular area generates inflammatory cytokines that causes pain in adhesive capsulitis.²² ‘The abnormal neovascularization’ was characterized by poor formation of arteriovenous shunt that resulted in early venous drainage.⁹

Most significant improvement in outcome was decrease in pain score. All the studies mentioned VAS score to denote the degree of pain. The VAS score decreased significantly one week after the procedure and that continued up to 6 months. Major improvement was also noted in nighttime pain.^9–11 Recurrence of the pain score was not noted at follow up at 16 months.^9,11 This signifies the irreversibility of the procedure performed.

There was serial improvement of the shoulder range of motion as described in all studies. Although there was no mechanical manipulation of shoulder that releases soft tissues there was gain of motion. The most anticipated mechanism of the same can be explained by the neurovascular theory that has been postulated. In an immunohistochemical study, the nerve fibres were found to be located in the vicinity of the small blood vessels of the rotator interval tissues as well as along the capsule.¹⁸ The occlusion of the neovessels lead to destruction of the nocciceptors leading to relief of pain in immediate post operative period. In one study, few patients relieved pain during the procedure of performing the angioembolisation procedure.¹¹ The improvement of the pain lead to higher motivation in part of patient as well as ease of therapist performing physical therapy. Most of the patients maintained their improved global range of motion at final follow up.

The natural history of adhesive capsulitis historically describes this as aself-limiting disease.²¹ But the recent literature disapproves this classic description.^19,20 The patients gradually suffers for a prolonged period that diminish the quality of life. This can be mitigated by this procedure that relives pain earlier and thus physical therapy can be started early. To summarize, trascatheterembolisation leads to earlier recovery from pain and greater patient satisfaction in midterm follow up.

The favorable outcome of transcatheterembolisation must be critically analyzed from a different angle to recommend the treatment modality in all the patients of adhesive capsulitis. All the patients were advised to perform range of motion exercises in post operative period.^9–11 In one study, the previous conservative therapy(like injection of steroid) was continued even after the operative embolisation.¹⁰ The range of motion exercises(ROM) break the adhesive fibrous bands that limit the range of motion. As ROM exercises were prescribed in all the patients before and after the procedure it is difficult to measure the efficacy of the individual procedure that modify the final outcome. Only two patients in this review did not receive any physical therapy but improved in terms of pain and motion.¹⁰ We think that this is the most important confounding factor to approve (or disprove) the efficacy of the angioembolisation therapy.

Pain relief may be one of the reasons to advocate the angioembolisation who does not respond to conservative management. But various studies have demonstrated good to excellent outcome in terms of pain relief with corticosteroid injection or suprascapular nerve block^23–29]. In the studies included in this review, we noted that patients who were not improving after 3 months of conservative management underwent angioembolisation. This time period is not absolute one that denotes non improvement of adhesive capsulitis. The patients with known trigger factors of adhesive capsulitis like diabetes, hypothyroidism, trauma, cancer breast or smoking^30–33 may need more time to recover with physiotherapy. Although there was no mention regarding these risk factors among patient who underwent thromboembolisation, the course of follow up was not precisely mentioned among these subset of cases.^10,11 These patients may suffer a microvascularangiopathy which may manifest as pain generating triggers as a spectrum of small vessel vasculitis. The evidence is also not clear regarding the use of the angioembolisation procedure among patients not improving after a pronged period of conservative management. The fate of the neovessels in long term is yet to be clarified (whether these gets self embolisedor remain patent throughout the course of disease)with serial angiography in different time period of a specific treatment option. Another crucial fact is that no study had control group. All the patients were recruited, operated and followed up by same group of surgeons that can be easily biased.^9–11

The simplified pathogenesis of adhesive capsulitis is-pain generators limit the motion of shoulder joint and inflammation causes fibrosis leading to painful range of motion. Fibrosis can be considered as a terminal event (coraco humeral ligament thickening is a universal finding as well as rotator interval narrowing) of the pathogenesis. When fibrosis is progressed, adhesive bands should be dissected out with arthroscopy or by physiotherapy. However, the time frame in which irreversible fibrosis is formed is not studied in details hence arbitrary time frame of 3 months of conservative treatment may not be acceptable in all the cases before proceeding for transcatheter angioembolisation.

Transcatheter embolisation has been experimentally applied to treat various orthopedic ailments but their application is still not wide due to limitation of resources and cost of the treatment. TAE is most successfully applied to treat highly vascular bone metastatic tumor like renal cell carninoma or thyroid cancer,ostersarcoma and giant cell tumor.³⁴ TAE, in these cases, reduce the tumor bulk as well as significantly reduce bleeding during surgical excision. TAE has also been used experimentally to treat spontaneous haematoma after total hip and knee arthroplasty,³⁵ chronic musculoskeletal pain36, resistant lateral epicondylitis³⁷ osteroarthritis,³⁸ trapezius myalgia³⁹ and shoulder and elbow tendinopathy.^40,41 We believe that with advancement of interventional radiology, we will be able to understand the pathogenesis and pathology of the abnormal neovessels that generate pain and successful treatment of adhesive capsulitis and above mentioned chronic painful conditions is possible with this modality.

12 Limitations

Limitations of this review:as inherent to all reviews, shortcoming of this study is number and quality of studies included. Only three studies included in our review in view of paucity of research available in the literature. All the three studies included in the review are of level four evidence in from of case series and treatment studies, that too with a small number of patients. Studies comprising of multicentric trial with properly matched control group and adequate sample size makes a review comprehensive and solid conclusions can be drawn from such review, that's lacking in this review. Using similar technique for transcatheter embolisation, similar follow up intervals and minimal loss of patients to follow up constitutes strengths of the studies included in our review.

Limitation of TAE as a procedure:TAE is still in infancy for general use in orthopaedics. There are several reasons for the same. Firstly, there is lack of uniform training among interventional radiologists on musculoskletal ailments and learning curve is steep. Secondly, only experienced interventional radiologists can perform these procedure who may not be available in most centers. In our review, five years experienced interventional radiologists performed all these procedure. Thirdly, cost of this treatment (including the availability of the set up like digital subtraction angiography) is higher in comparison to other modalities of treatment.

13 Conclusion

The existing literature does not provide ample evidence regarding the usefulness of the transcatheterangioembolisation as a sole treatment modality among adhesive capsulitis patients resistant to other conservative management. But resistant cases may undergo the same if intractable pain does not respond to conservative management. Multicentric trials with properly matched control group to be undertaken before advocating this procedure in general population.

Level of clinical evidence

Level III, systematic review.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author contribution

Dr. Vijay Kumar Digge and Dr. Santanu Kar were involved in the conception of the idea for the study. Dr. Sai Krishna and Dr. Vijay Kumar were involved in the literature search based on the Prisma guidelines and identifying the final studies to be included in the review. Dr. Sai Krishna, Dr. vijay kumar Jain, Dr. Jagannath Desai and Dr. santanu were involved in interpreting the involved studies, data extraction and analysis. Dr. Santanu and Dr. vijay kumar were involved in writing the initial proof. Dr. Sai Krishna and Dr. Vijay Kumar Digge were involved in writing the manuscript post analysis. Dr. Buddhadev chaudhury and Dr. vijay Jain were involved in overseeing and proof reading the manuscript. All the authors read the final manuscript and gave consent for publication.