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 . 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 . 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 . 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.  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 . 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 .
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 . 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 . 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 . 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 . 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 . 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 .
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 . 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 . 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 . Likewise, in a study of cyclists with ulnar nerve neuropathy, proximal neural lesions contributing to a double crush syndrome were symptomatically contributory . 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 . 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% [30,31,32,33]. 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 . Persistent entrapment neuropathy following surgical treatment for TOS should raise suspicion for distal nerve entrapment syndrome . 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.