Introduction
Thoracic outlet syndrome (TOS) constitutes a group of diverse disorders that result in compression of the neurovascular bundle exiting the thoracic outlet. The thoracic outlet is an anatomical area in the lower neck defined as a group of three spaces between the clavicle and the first rib through which several important neurovascular structures pass; more detailed anatomical descriptions will correspond with discussions of the relevant pathology [
1]. These structures include the brachial plexus, subclavian artery, and subclavian vein. Compression of this area causes a constellation of distinct symptoms, which can include upper extremity pallor, paresthesia, weakness, muscle atrophy, and pain [
2].
TOS classifications are based on the pathophysiology of symptoms with subgroups consisting of neurogenic (nTOS), venous (vTOS), and arterial (aTOS) etiologies [
3]. Furthermore, each one of these subgroups can be related to either congenital, traumatic, or functionally acquired causes [
4]. Examples of congenital etiologies include the presence of a cervical rib or an anomalous first rib. Traumatic causes most commonly include whip-lash injuries and falls. Functional acquired causes can be related to vigorous, repetitive activity associated with sports or work. Diagnosis of TOS is generally dependent on clinician familiarity of TOS coupled with an evaluation of symptoms and patient-specific risk factors. Clinical suspicion can then be confirmed with provocative physical exam maneuvers, radiographic, and/or vascular studies. Because of the wide range of etiologies and lack of expert consensus for diagnostic testing, the true incidence of TOS is difficult to discern. Several articles report an incidence of 3–80/1000 [
4]. Neurogenic TOS accounts for over 90% of the cases, followed by venous and arterial etiologies [
3]. Historically, TOS presents with symptom onset between the ages of 20–50 years old and is more prevalent in women [
5].
With the wide range of multifactorial etiologies, it also makes sense that best-practice treatments for TOS involve a comprehensive and multi-disciplinary approach. Management options can include surgery, lifestyle modification, pain management, anticoagulation, physical therapy, and rehabilitation [
6]. This article therefore intends to review the most relevant, noteworthy, and up-to-date literature, and to provide clinicians with a concise summary of both diagnosis and management for TOS. A comprehensive electronic literature search (1970–2018) process was conducted that included PubMed, EMBASE, and MEDLINE databases, and Google Scholar. Previous materials published in peer-reviewed journals and grey literature were reviewed in a systematic manner. References cited in relevant articles were also reviewed. Search terms used included “thoracic outlet syndrome” AND “imaging” OR “angiography” OR “diagnosis” OR “neurogenic” OR “venous” OR “arterial” OR “NSAIDs” OR “physical therapy” OR “surgery” OR “antidepressants” OR “Raynaud’s” OR “neuropathy.”
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Clinical Implications
Prompt recognition of the presenting signs of TOS is crucial to prevent long-term sequelae, specifically chronic upper extremity pain and severe disability. In each subtype of TOS, an understanding of the causative anatomic aberrancy can guide diagnosis.
Neurogenic TOS is caused by compression of the C5 through T1 brachial plexus nerve roots and comprises up to 90% of total TOS cases [
15]. Compression of the nerve roots most often occurs within the scalene triangle but can also occur in the subarachnoid space as the nerve roots traverse beneath the pectoralis minor tendon. In this scenario, congenitally anomalous anatomy such as aberrant scalene musculature, cervical ribs, and connective tissue may compress and entrap nerve roots [
16]. Additionally, acquired anatomical variation, e.g., scarring from injury, can affect these nerve roots. Accordingly, nTOS is often seen in young, active individuals who participate in athletic activities that involve repetitive overhead upper extremity motion and heavy lifting [
11]. Diagnosis of nTOS is thereby based on the history of symptom presentation and clinical exam findings. Patients with nTOS often report consistently reproducible symptoms when performing the responsible activities and demonstrate positional exacerbation when mimicking these specific upper extremity motions. Symptoms generally correspond secondary to the level of nerve compression, with the most common being upper extremity heaviness with above-the-shoulder activities. A systematic review by Sanders et al. [
11] described symptom distribution in neurogenic TOS to include upper extremity paresthesia (98%), neck pain (88%), trapezius pain (92%), shoulder and/or arm pain (88%), supraclavicular pain (76%), chest pain (72%), occipital headache (76%), and paresthesias in all five fingers (58%), the fourth and fifth fingers only (26%), or the first, second, and third fingers. In upper plexus TOS, involving compression of the C5, C6, and C7 nerves, pain is most often described in the lateral neck, with radiation superior to the ear and occiput. Pain may also radiate posteriorly to the rhomboid area, anteriorly across the clavicle into the upper pectoral region, laterally through the deltoid and trapezius muscle areas, and down the outer aspect of the arm [
17]. In general, patients present with lower plexus TOS rather than upper, which corresponds to compression of the C8 and T1 nerves. Pain is typically distributed along the posterior of anterior shoulder with radiculopathy down the arm in a medio-brachial distribution along the inner aspect of the arm. Paresthesia tends to affect an ulnar nerve distribution along the ring and little fingers. Despite this etiological understanding of pathoanatomy, differentiation from other cervicobrachial symptoms may still prove challenging difficult [
18].
Venous TOS, also referred to as Paget–von Schroetter syndrome, comprises 10–15% of cases, and is caused by subclavian compression within the costoclavicular space [
19]. Mechanical compression and repetitive injury of the subclavian vein between the clavicle and first rib can lead to abrupt blood flow stagnation and subsequent effort thrombosis. This causes the pathognomonic presentation of acute upper extremity swelling, cyanosis, heaviness, and ultimately pain. Raynaud’s-like symptoms may be appreciated with vTOS but are typically unilateral, unlike the former disease [
20]. It is important to remember, however, that Raynaud’s itself may present as unilateral in ~ 7% of cases, thus the clinician need maintain awareness of other causes of vascular compromise in their approach [
21]. Like nTOS, venous TOS occurs frequently in physically active individuals, aged 15–45, many of whom participate in work or recreational activities that involve heavy lifting and repetitive upper extremity overhead motion. Pulmonary embolism is an important complication of venous and occurs in 10–20% of patients. In comparison to lower extremity DVT, however, clot burden is typically minimal and infrequently life-threatening, as extrinsic mechanical obstruction of blood flow theoretically prevents proximal embolization of venous blood clot. Though patients with effort thrombosis may initially present with an abnormal coagulation profile, genetic hypercoagulable parameters are typically negative, thusly distinguishing vTOS as a mechanical problem rather than a pro-coagulative hematologic disorder [
22,
23]. As subclavian vein thrombosis may arise from alternative etiologies, imaging such as venous duplex, MRI, and CT can assess the proximal subclavian vein status to confirm the mechanical diagnosis [
19]. Differentiation from nTOS is clinical; in contrast to pain exacerbated by overhead upper arm positioning, the symptomatology of venous thrombosis is stable.
Arterial TOS is by far the most rarely observed, occurring in 2–5% of TOS cases. Subclavian artery compression within the scalene triangle may be caused by an anomalous first rib, which ultimately developing an aneurysm distally. Acquired types may also be seen in physically active patients and athletes in whom arterial entrapment may occur at the level of the pectoralis minor tendon and the humeral head [
24]. Arterial compression incites intimal damage, turbulent blood flow, and vessel dilation. Eventual arterial thrombosis and distal embolization may result in acute distal upper extremity ischemia. Clinical features are primarily vascular, as discussed, with secondary neurologic abnormalities as sequelae.
Clinicians should recall TOS on their differential diagnosis when confronted with a patient suffering from upper extremity pain and supporting physical exam findings. Adult patients who present with features of TOS necessitate a low threshold for imaging, as delay in treatment can lead to irreversible changes and chronic pain. While nTOS is the most frequent subtype, its diagnosis may be the most challenging by the lack of readily apparent clinical findings, such as vascular abnormalities on radiography [
18].
Diagnosis of TOS is further complicated by alternative disorders with similar presentation. Nerve compression at the cervical spine or elbow and wrist, involving the median and ulnar nerve, may occur in conjunction with TOS. A presentation as such is referred to as double crush syndrome and may mask the presentation of TOS [
25]. In these patients, careful consideration of multiple imaging modalities, electromyographic studies, and detailed physical examination are crucial to discern the foci of neurovascular compromise. Despite this, in as many as 29% of patients who present with symptoms consistent with distal peripheral nerve entrapment syndromes (e.g., carpal tunnel syndrome), there is no evidence of clinical or physical exam findings supporting a distal nerve lesion [
26]. Furthermore, in patients with electrophysiologically proven distal entrapment syndrome, proximal neurological lesions at the level of the cervical spine may contribute to symptoms; in a review of 1000 cases of carpal tunnel syndrome, 89% of patients exhibited concomitant cervical arthritis, which is capable of eliciting similar symptoms [
27]. Likewise, in a study of cyclists with ulnar nerve neuropathy, proximal neural lesions contributing to a double crush syndrome were symptomatically contributory [
28]. The prevalence and diagnosis of nTOS is controversial, and much debate surrounds the role of nTOS to upper limb entrapment neuropathies. Careful consideration should, therefore, be given to compressive neuropathies at distinct, alternative sites which can lead to similarly disabling upper extremity pain and weakness.
Owing to the high prevalence of carpal tunnel syndrome (CTS), the concurrence of TOS with CTS has been extensively examined. However, controversy remains in terms of double crush phenomenon pathology, diagnosis, and treatment of these two syndromes. TOS is rare, and diagnosis often lacks specificity. Moreover, carpal tunnel syndrome is often inaccurately diagnosed. Compounded, the occurrence of simultaneous TOS and CTS becomes exceedingly rare. As such, it is unlikely that the combination would precipitate double crush syndrome [
29]. In patients with persistent symptoms following decompression of distal nerve entrapment, though TOS may not be entirely excluded, proximal nerve compression stemming from cervical radiculopathy may be the more likely etiology. While reports have demonstrated TOS as a contributing factor to double crush phenomena with distal entrapment neuropathies, the prevalence of TOS in CTS is around 1% [
30‐
33]. Furthermore, although the presence of double crush syndrome is difficult to confidently diagnose, the fact that CTS is a highly accepted diagnosis may explain the elevated incidence of reported coincident CTS with TOS. The association of TOS with CTS is both plausible and previously documented, but the unpredictability of both syndromes warrants surgical treatment of the distal compressive neuropathy first [
32]. Persistent entrapment neuropathy following surgical treatment for TOS should raise suspicion for distal nerve entrapment syndrome [
34]. Complete resolution of symptoms is achievable only by addressing all points of suspected neural compression [
35,
36].
Though inherently distinct etiologically, the three forms of TOS share a fundamental mechanism of extrinsic neurovascular compression that ultimately produces severe pain and disability. In all cases, early recognition and diagnosis is crucial to initiation of the proper treatment. TOS remains a challenging and highly controversial diagnosis, and alternative, and possibly coincidental, proximal or distal compressive neuropathies must be excluded.
Surgical Management Strategy in Failed Conservative Management and Treatment Outcomes
Surgery for TOS is reserved for patients who have failed conservative management. The threshold for decompression varies widely for mild to moderate symptoms, but certain symptoms require surgery.
As previously discussed, physical therapy and conservative management of nTOS should persist for at least 4–6 months prior to consideration of surgical intervention [
46]. However, for patients with arterial or venous TOS, the initial intervention is most often surgical. A trial of anticoagulation via catheter-directed thrombolysis and systemic heparin therapy may be first attempted for patients with arterial or vascular TOS [
47]. In cases of mild upper extremity ischemia, catheter-directed thrombolysis may restore perfusion. Symptoms refractory to these measures require surgery.
Surgical candidates should have failed conservative management [
40]. Most surgical candidates exhibit nTOS with uncontrolled pain or progressively worsening upper extremity weakness. The surgery of choice is a first rib resection aimed at brachial plexus decompression, typically performed by vascular surgeons. The operation can also be performed by thoracic surgeons, neurosurgeons, orthopedic surgeons, and plastic surgeons [
46]. In nTOS, the first rib is removed in addition to a scalenectomy or scalenotomy.
The three approaches to brachial plexus decompression by first rib removal include transaxillary, supraclavicular, and infraclavicular techniques. Each approach has achieved good outcomes, with no definitively superior technique [
48]. While the transaxillary and supraclavicular approaches are utilized more frequently, technique is often chosen based on the individual patient and unique anatomical considerations. The supraclavicular approach requires a scalenectomy of the middle and anterior scalene muscles to expose a small portion of the first rib. The compression is thereby easily exposed, allowing for access to the brachial plexus if neurolysis is indicated. The transaxillary approach is performed by accessing the first rib between the pectoralis major and latissimus dorsi in the axilla. With the patient in the lateral position, careful dissection of the axillary vasculature and nerves may expose the first rib. In this approach, exposure is limited and potential brachial plexopathy may occur through over-manipulation and retraction. Less common, the infraclavicular approach allows for vascular reconstruction in patients with venous or arterial TOS and should be pursued if central venous exposure is required.
Brachial plexus injury after first rib resection does occur, but reporting varies widely [
49]. In a multi-institution database study, brachial plexus injuries were reported in 0.6% patients with nTOS following transaxillary first rib resection [
50]. However, another study of transaxillary first rib resections in patients with nTOS reported a brachial plexus injury incidence of 9%, with an incidence of 4% after supraclavicular first rib resection [
51].
More recently, the introduction of minimally invasive techniques has achieved superior outcomes in first rib removal, as both robotic and thoracoscopically assisted approaches minimize brachial plexus manipulation [
46]. Additional training, equipment, and expertise is required but may limit the overall surgical risk.
Overall outcomes from surgical decompression are very positive. Following surgical intervention, 95% of patients with nTOS reported “excellent” results [
52]. In a 5-year follow-up study of patients with vTOS, patency rates were better than 95% [
53]. Impediments to successful outcomes include major depression or comorbid conditions that skew the initial diagnosis [
53].
Recent Developments
As more patients receive diagnosis and treatment for TOS, the referral pattern has changed. Instead of evaluation and treatment by multiple disciplines before consideration of TOS, patients are now referred sooner despite a shorter duration of symptoms, which improves the predicted response to surgical treatment [
3]. Additionally, a rise in the number of adolescent cases has been described, owing to repetitive or vigorous activity such as musical instrument or athletic endeavors. More common in adolescents than adults, first rib resection has been successfully and safely performed for vTOS and aTOS with good outcomes and fast recovery [
54].
Since TOS is a rare and complex group of disorders with potentially severe and disabling symptoms, care can be challenging for health care providers. Therefore, a systematic, organized approach to the diagnosis and treatment of TOS provides an opportunity for specialists to deliver patient-centered care and achieve optimal results. This specialized type of care is best delivered through the efforts of a multi-disciplinary team that consists of various specialists, including vascular surgery, thoracic surgery, neurology/neurosurgery, orthopedics, radiology, anesthesiology, pain management, physical therapy, and occupational therapy [
55]. For this reason, centers of excellence for TOS have been established around the country with demonstrable improvements in outcomes [
3].
Venous and arterial TOS are diagnosed by a combination of clinical presentation and imaging. Ongoing developments in the diagnosis of TOS include dynamic CT angiography, MR neurography, and Diffusion Tensor Imaging (DTI). These imaging modalities can be used to identify brachial plexus branching variants in which susceptibility to compression by the scalene muscle is increased. Neurogenic TOS is generally more difficult to diagnose as nerve and tissue inflammation lack consistent radiographic evidence. However, as imaging studies evolve, newer modalities with higher quality allow for improved diagnostic objectivity [
56]. MRI can evaluate the anatomy of the thoracic outlet, the soft tissue structures causing compression, and allow direct visualization of brachial plexus compression [
40]. Magnetic resonance neurography (MRN) is an imaging modality that allows non-invasive visualization of nerve morphology and signal. In this technique, signals from surrounding soft tissue such as adipose are suppressed, and pulsation artifact from pulsating blood is removed. Continued improvements in high-resolution MRN may, therefore, augment current diagnostic modalities by facilitating prompt identification of brachial plexus compression across the thoracic outlet in patients with nTOS [
57].
While MRN denotes a class of techniques intended for assessment of peripheral nerves, diffusion tension imaging (DTI) or tractography is reserved for the CNS [
58]. Short tau inversion recovery (STIR) sequences and the spectral adiabatic inversion recovery (SPAIR) preparatory module are variations of MRN and deliver a more complete anatomical description of the nerves comprising the brachial plexus. DTI sequences to visualize nerve fascicles are employed in the modeling technique of tractography, allowing for a more comprehensive assessment of peripheral nerve injury [
57]. One study regarding MRN demonstrated a 100% positive predictive value in all 30 patients involved; however, ultrasound also identified compression all patients with nerve lesions visualized on MRN [
59].
Current mainstays of diagnosis include duplex ultrasound, arteriography, hemodynamic testing (finger plethysmography) at rest and with symptom-producing maneuvers, as well as CT and MR angiography [
60]. Invasive arteriography and angiography are useful in the detection of complications from aTOS such as thrombosis, embolization, and aneurysm. The invasive nature of these techniques limits their use to surgical planning rather than pure diagnostics. Other non-invasive tests such as MR and CT angiography are more readily employed for their diagnostic utility outside of surgical planning. Dynamic testing allows the clinician to evaluate arterial compression with provocative maneuvers, while imaging helps to define the anatomic source of compression and confirm the diagnosis of arterial, venous, or nTOS [
40].
Surgical Advancements
As noted above, first rib resection with scalenectomy remains the operation of choice for decompression, but as surgical advancements continue to emphasize minimally invasive approaches, some institutions now employ VATS in order to achieve a clearer visualization of the operative field and potentially minimize injury to the neurovascular bundle [
61]. Two additional strategies, the robotic-assisted and endoscopic-assisted trans-axillary approaches, are novel techniques with potential benefit, the latter aiming to decrease risk of pneumothorax [
56].
Conclusions
Since the first use of the term TOS by Peet et al., there have been significant advancements in the understanding and treatment of the syndrome. The upper extremity pain and numbness typical of the condition have been subcategorized into distinct disorders based on the structures involved. A history of trauma or repetitive motions combined with supportive physical exam findings suggests the correct diagnosis. Other diagnostic modalities such as MRI, ultrasound, and nerve conduction studies can further support the diagnosis, and ongoing developments in this sphere are currently underway.
Despite advances, substantial controversy regarding the diagnosis remains. This is evidenced by the lack of objective findings surrounding nTOS, the most common and widely disputed form of TOS. The challenges associated with diagnosis complicate the selection of the appropriate treatment option. In some cases, e.g., acute vascular insufficiency or progressive neurologic dysfunction, surgical decompression is clearly indicated. Prompt recognition and treatment of TOS provide the greatest opportunity for optimal recovery. Unfortunately, the multitude of nonspecific symptoms and challenges in diagnosis can delay treatment and increase the risk of complications.
Surgical intervention for TOS syndrome is reserved for patients who have failed conservative management. Conservative treatment including physical therapy need be trialed for at least 4–6 months prior to consideration of surgical intervention [
46]. Definitive therapy for patients with refractory aTOS or vTOS, however, remains surgical intervention.