A Review of Musculoskeletal Embolization to Treat Pain Outside of the Knee

Abstract

Chronic inflammation leading to musculoskeletal pain has garnered interest in the past decade with the success of genicular artery embolization for knee pain secondary to osteoarthritis. Outside the knee joint, musculoskeletal embolization has been applied to other anatomical locations, mainly shoulder pain secondary to adhesive capsulitis and elbow pain secondary to lateral epicondylitis. The success of these early trials and other case reports highlights the efficacy of musculoskeletal embolization and its future potential.

Many musculoskeletal conditions that cause pain and disability can be characterized by the presence of chronic inflammation. ^{1 2} In this milieu, mediators such as C-reactive protein, prostaglandins (PGE2), cytokines (TNF, IL-1B, IL-6, IL-15, IL-17, IL-18, and IL-21), leukotrienes (LKB4), growth factors (transforming growth factor-beta and vascular endothelial growth factor), complement proteins, and nitric oxide upregulate angiogenesis leading to abnormal hypervascularity. ³ Studies suggest that these abnormal vessels could activate neuropeptides resulting in subsequent nerve growth and chronic pain. ^{4 5} The purpose of embolization is to disrupt this inflammatory cycle and prevent the development of sensory nerves by targeting the hypervascularity. ^{6 7}

This principle has been successfully applied to knee pain secondary to osteoarthritis (OA), as genicular artery embolization (GAE) was found to significantly reduce pain and increase function in patients with mild to moderate OA. ^{8 9 10 11 12 13 14 15 16} The success of GAE for OA has led to the application of musculoskeletal embolization to other inflammatory conditions like adhesive capsulitis (AC), lateral epicondylitis (LE), and other isolated cases of tendinitis.

Adhesive Capsulitis

AC, also known as frozen shoulder, refers to the pathological formation of adhesions and scar tissue around the glenohumeral joint leading to pain and stiffness. It has an incidence of around 5% in the general population that rises to around 20% in patients with diabetes. ^{17 18} Although it is often described as self-limiting in 1 to 3 years, 20 to 50% of patients can develop long-lasting symptoms. ^{19 20}

Okuno et al were the first to describe adhesive capsulitis embolization (ACE) to relieve symptoms in patients with AC. ²¹ In this study, seven patients underwent ACE with impinem/cilastatin, an antibiotic that crystallizes in solution to form temporary embolic particles. The six arteries of interest targeted were (1) suprascapular artery, (2) thoracoacromial artery, (3) coracoid branch, (4) circumflex scapular artery, (5) anterior circumflex humeral artery, and (6) posterior circumflex humeral artery. Selective angiography of these vessels was performed to evaluate for “tumor blush” ( Fig. 1 ). If present, embolization was performed very slowly with a dilute embolic solution until the “tumor blush” was no longer evident. At 6-month follow-up, there were significant improvements in mean visual analog score (VAS) and American Shoulder and Elbow Surgeons (ASES) score. Patients also reported no major adverse events.

Fig. 1.

Angiography in the anterior humeral circumflex artery that displays classic hypervascularity ( a ) with a postembolization angiography and return to normal anatomy ( b ).

The success of the initial study was confirmed by Okuno et al and Hwang et al who performed ACE in 8 and 25 patients, respectively. ^{22 23} Okuno et al had a 36-month follow-up with consistently significant VAS and ASES improvements compared to baseline at the short- and long-term follow-up end points. Reductions in analgesic use were also noted along with the absence of any major adverse events throughout the study period. Hwang et al presented similar data with improvements in shoulder pain and mobility after ACE. Fernández-Martinez et al reported on a larger cohort of 40 patients. ²⁴ Like previous studies, significant improvements were noted in pain scores at 6-month follow-up. Small differences included femoral artery access for almost all patients and the use of detailed range of motion analysis. Bagla et al were the first to perform ACE in the Unites States and used a permanent embolic agent instead of the temporary antibiotic solution that had been used in the previous studies. ^{16 25} No major differences in AEs and outcomes were noted between the two agents.

The early data on ACE are encouraging and suggest that glenohumeral joint embolization is a safe and effective option for patients with AC resistant to conservative treatment. Future randomized control trials comparing ACE to sham embolization or orthopaedic intervention is necessary to establish ACE in the AC treatment algorithm.

Lateral Epicondylitis

LE or “tennis elbow” is a painful degenerative process involving the extensor carpi radialis brevis with an incidence of 1 to 3%. ^{26 27} While conservative management resolves the pain in most patients, 5 to 10% of patients can develop chronic symptoms. ²⁸

Iwamoto et al were the first to perform embolization for pain secondary to LE refractory to conservative management . ²⁹ Digital subtraction angiography of the brachial artery was performed to evaluate the radial recurrent artery, interosseous recurrent artery, and the radial collateral artery. Each vessel was checked for hypervascularity and embolized as necessary to decrease the “tumor blush.” Twenty-four patients underwent embolization with a 2-year follow-up. Significant improvements at 2 years were noted with VAS; Patient-Rated Tennis Elbow Evaluation (PRTEE); and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaires. Although a two-stage procedure intervention was part of the original study design, only eight patients required repeat embolization, as the others had complete resolution with no further symptoms.

Hwang et al confirmed the success of transcatheter arterial embolization (TAE) for LE in seven patients and noted significant improvements in pain and elbow function. ²³ Unlike the initial trial, Hwang et al were the first to use permanent embolic agents with successful results. There is an ongoing study by Okuno and Shibuya with a sample size of 52 patients that is pending for publication with initial results that are encouraging with significant improvements in outcomes that last almost 4 years after TAE. ³⁰ No major AEs were noted and magnetic resonance imaging analysis 2 years after TAE confirmed lack of side effects. Overall, embolization is a promising minimally invasive option for patients with LE that is refractory to conservative management.

Tendonitis

There have been case reports of embolization for chronic pain secondary to tendonitis in various anatomic locations. Okuno et al described cases of embolization for patellar tendinopathy ( n  = 1), plantar fasciitis ( n  = 1), iliotibial band syndrome ( n  = 1), and Achilles tendinopathy ( n  = 1). ³¹ Like other musculoskeletal embolization, the procedures involved angiography of the local anatomy with identification of hypervascularity followed by embolization to treat the “tumor blush.” Okuno et al had 4-month follow-up for these patients who reported significant improvements in pain with limited AEs. Correa et al similarly used embolization to safely improve pain secondary to hip synovitis in one patient. ³²

Although these individual cases are encouraging, they are limited to case reports. Further clinical and basic science investigation is needed to better understand how embolization affects the chronic inflammatory state that is the common tie to all of the described conditions.

Conclusion

With the recent publication of data supporting embolization for the treatment of knee pain secondary to OA, many investigators have attempted to obtain similar results in different anatomical locations that are affected by musculoskeletal inflammation. Although ACE and embolization for LE have the most data supporting their efficacy, the smattering of additional case reports suggests that we are just crossing the threshold of potential applications.