The first symptoms attributed to thoracic outlet syndrome (TOS) date back to 1818, even though the definition of TOS was definitively coined in 1956 [1] . The thoracic outlet is delimited: anteriorly, from the sternum manubrium, the sternoclavicular joint (SCC), the clavicle and by the acromioclavicular joint (AC); posteriorly, from the first costovertebral joint and the scapulothoracic joint (ST). Anatomists define this area as thoracic inlet, since it represents a passage for air and food; doctors define it as thoracic outlet, focusing the attention on vessels pathways [1] . The debate is purely academic. The neurovascular brachial plexus can be affected by pathologic processes which take in place in this region. The lowest roots of the brachial plexus pass through the triangular gap between the anterior and the middle scalene muscles (whose base is formed by the first rib), along with the subclavian artery (rarely penetrating the anterior scalene); this space is defined as the interscalene triangle [2] . The subclavian vein lies on the anterior scalene [3] . Then, the nerves and the subclavian vessels pass through an area delimited from the clavicle and the subclavian muscle superiorly and from the first rib inferiorly, named as costoclavicular space [2] [3] . Another potential site of neurovascular compression is the sub-coracoid tunnel, below the tendon of the pectoralis minor muscle [2] [3] .

Symptoms resulting from TOS are various and complex, exacerbated by movements of the shoulder and neck; the syndrome affects about 8% of the population, with higher prevalence in females, and rarely in children [2] . According to recent definitions we can differentiate nervous and vascular compression, even according to the involved anatomic space: neurological TOS (nTOs) and vascular TOS (VTOS), when the first spaces are affected; neurological minor pectoralis muscle―PMM (nPMM) and vascular PMM (vPMM), when pathology is found at the level of sub-coracoid tunnel [3] . The nTOs sub-definitions have been abandoned: true (tnTOS), disputed (dnTOS), traumatic.

The tnTOS dealt with a neurological problem usually assessed with imaging studies and in presence of muscle atrophy; the dnTOS represents a similar condition, not assessed through clinical examination; according to another classification (traumatic), the cause could be represented by previous fractures to bone components of the thoracic outlet [3] . The first sub-classification is not true, as a neurological disorder is usually associated to vascular pathology [4] . The second one could cause confusion in diagnosis [3] . The last one was discarded, since the presence of previous fractures not necessarily lead to the syndrome [3] . The prevalence of nTOS ranges between 90% and 95%, compared to VTOS; only 1% of the cases result from arterial compressions; however, neurological problems resulting from nPMM are not included in the mentioned data [3] [5] [6] . Compression or irritation of the brachial plexus always present with a triad of symptoms: pain; paresthesia; weakness [3] (see Table 1).

Symptoms of nTOS and nPMM overlap, involving pain or tenderness in the cervical spine and the trapezius muscle; all the upper limb or part of it may be interested. Paresthesia or numbness can affect one or more fingers; the weakness appears only after several months as the difficulty to grab [3] . To differentiate between the two components, in the presence of nTOS the pain to the cervical

and occipital area is more frequent, while in patients with nPMM pain involves the anterior aspect of the chest and the armpit; both conditions are present in frequent cases [3] . The pain can occur during the day, with daily activities, or at night, or in both situations [2] . Other symptoms are cold sensation and Raynaud phenomenon, probably due to irritation of the sympathetic nervous system causing vasoconstriction [5] . Less common symptoms are the vertigo and dizziness, tinnitus, tachycardia and pseudoangina [2] .

Venous obstructions present similar symptoms in VTOS and vPMM (see Table 2).

The axillo-subclavian vein obstruction can occur with or without thrombotic changes; in case of thrombus, symptoms such as swelling of the extremities, feelings of pressure and cyanosis are constant and intense, without relation with the movements, persisting for days or weeks [3] . The presence of thrombus is also classified as thrombosis stress syndrome or Paget-Schroetter, while the absence of thrombotic changes is defined as McCleery syndrome [1] . In the absence of a venous thrombus, symptoms may decrease when the arm is at rest [3] . Pain and paresthesias are not always present; if paresthesia is present, it is usually caused by pressure in the region of the hand level and not from in the thoracic outlet [3] [5] . The arterial obstructions, less common but more dangerous (they can lead to gangrene), in the presence of VTOS/vPMM can cause similar symptoms (see Table 3).

Pathologic conditions may involve the subclavian and axillary arteries, due to compression, stenosis and aneurysms; blood flow to the arm is reduced, producing symptoms which do not clarify the origin of the occlusion (subclavian or axillary artery) [3] . The typical symptoms are fatigue in moving the arm, unilateral Raynaud phenomenon, pallor, cyanosis and hyper-sensitivity to cold; there is a discoloration and ischemia of fingers [3] . Arm claudication is also present. The subclavian artery can completely occlude, with potential onset of gangrene [1] . Symptoms related to vPMM are similar but less intense; pain and paraesthesia can appear, because the axillary nerve can be compressed in the quadrangle

of Velpeau, together with the humeral posterior circumflex artery, branch of the axillary artery [3] . Rarely the involvement of the subclavian artery can cause symptoms in neck and shoulders, since emboli or thrombi may have retrograde pathways [5] .

Surgeons diagnose nTOS about 100 times more frequently than neurologists [7] . Frequent causes are bone or tissue abnormalities or traumatic changes.

A cervical rib is present in about 1% of the population, where 70% are women; the presence of this bone anomaly is often asymptomatic, while in case of cervical trauma it can become a cause of compression of the brachial plexus, in particular in hypertension [3] [5] . An elongated transverse process of C7 is another congenital variation potentially leading to nTOS. It is virtually always associated with the presence of a ligament or fascial tissue, which connects the transverse process with the body of the first or second rib, crossing the middle scalene muscle [3] . It is asymptomatic in most cases but it can be symptomatic after cervical trauma [3] . Other causes are related to anatomical abnormalities could of other components of the thoracic outlet, such as muscle groups with abnormal insertions or dimensions (scalene, pectoralis minor, subclavian), ligaments too lose or too fibrotic, bony insertions with abnormal position or size, supernumerary muscles [5] [7] - [12] . Even the brachial plexus could present abnormalities causing nTOS, such as direct crossing of muscles [13] .

Work or sports habits inducing the complete abduction of the shoulder may, in the presence or absence of anatomical abnormalities, cause the syndrome, continuously reducing the anatomic space for the brachial nerve passage; or, the in case of raising a weight repeatedly (condition in which the scapula is pushed against the rib cage), an excessive tension is caused on the pectoralis minor [3] . All the articular structures of the thoracic outlet are potentially at risk of causing nTOS, which appears when one or more causes limit their range of motion, such as trauma or other pathologies [7] .

Other causes of nTOS are related to the pleural dome, since anatomic or functional abnormalities of the pulmonary apex at the level of the first rib could lead to brachial nerves compressions [14] . In the presence of chronic obstructive pulmonary disease (COPD), the diaphragm assumes a position of inspiration, increasing lung pressures; we can hypothesize that such pressures and the position of the diaphragm can lead to nTOS, for example for elevation of the first rib and hypertrophy of the scalene muscles [15] [16] [17] .

Vascular compression of the subclavian vein can happen in the space between the clavicle (top), the first rib (bottom), the subclavian muscle/ligament costoclavicular (lateral-upper) and the scalene muscle (lateral); less common is a compression of the axillary vein under the pectoralis minor [3] . Repeated venous compression, trauma or repetitive motion, hypertrophy of the anterior scalene and subclavian muscle, skeletal abnormalities lead to inflammation of the vessel intima, breaking the delicate balance between formation and destruction of clots; thickening and fibrosis of the vessel lumen can lead to scars and vascular stenosis [3] [18] . Significant alteration of blood flow in the presence of inflammation may lead to trombotic change [3] . A stenosis may also occur in presence of foreign bodies, such as catheters or wires in the vein (pacemaker) [3] [18] . The presence of coagulopathy (genetic abnormality of factor 5, deficiency of protein C or S, and other types) can cause defects in coagulation, in particular if presence of predisposing factors (abnormalities of the structures of the thoracic outlet), acute or repetitive trauma, or movements described to be associated with the onset of nTOS [3] .

Pathologic conditions related to the axillary and subclavian arteries represent about 1% of the TOS, although they can lead to dangerous situations, such as gangrene of the fingers or arm [3] . Compressions can cause stenosis, occlusions and aneurysms; for the subclavian artery common causes are found in bone abnormalities (cervical rib, post-traumatic callus of the clavicle as result of previous fractures, and anatomical anomalies between the coast and the clavicle); other causes are represented by muscle abnormalities, also found for nTOS [19] [20] . Subclavian artery compression is common in sports where athletic movement requires the complete abduction of the arm, with potential arterial embolism; embolism is usually distal to the site of compression, but retrograde thrombosis can happen [19] . The reasons are the same that lead to the formation of clots in veins [19] [20] . Aneurysms and post-stenotic ectasia can be observed [20] . Compression of the axillary artery is often caused by abnormal traction of the posterior circumflex humeral artery, often for repeated movements or trauma of the humeral head [3] [19] [21] . These abnormal tensions in the artery can damage the intima, with potential aneurysmatic or trombotic changes [3] [19] [21] (see Table 4).

The assessment begins with the medical history interview and a clinical examination, in order to compare the arm with the contralateral one [2] [7] . Active limb movements are globally observed (shoulder, elbow and wrist), with special attention to the onset of any symptoms [7] [19] . Patient’s posture has to be observed, since an altered body alignment may cause stress to the thoracic outlet, such as an abnormal position of the shoulders or scapula (projecting or falling shoulder, or winged scapula) [2] [19] . Then, the palpation of the limb and painful area needs to be performed, even without a precise procedure, as well as the passive mobilization of the different components [2] . The strength of the various muscles of the limb and thoracic outlet has to be tested; then a neurological examination must be performed [2] . Classical orthopedic and neurological tests must be performed in order to rule out any other underlying cause of the symptoms, such a disc hernia, rupture of the rotator cuff, multiple sclerosis, chronic pain syndrome, peripheral nerve entrapment [6] . Anyway, a reliable evaluation process for the assessment of the syndrome is currently missing; few tests can be used, but they show low diagnostic accuracy [1] [18] .

Before instrumental tests are performed, other tests have to be performed, the so-called provocative tests. The rotation of the head actively performed by the patient, in the presence of TOS, may trigger the symptoms on the opposite side, such as pain and paresthesia; the same event may occur if the patient tilts his head toward the shoulder (head tilting) [3] [5] . Such tests are performed to activate the contralateral brachial plexus. The upper limb tension test of Elvey (ULTT) is performed; in the first phase the patients abducts the limb to 90 degrees in neutral position (palm down) and elbow straight, with head straight; then, in the second phase of the test, the patient dorsiflects the wrists. In the last phase of the test the patient tilts the head towards the shoulder [5] . In each phase the brachial plexus stretching is increased; the first and second positions stimulate the appearance of ipsilateral symptoms, while the third position cause symptoms on the opposite side [5] .

An immediate onset of symptoms is suspicious for a highly compromised situation, while a late appearance of the symptoms is considered less serious [5] .

Another test is the elevated arm stress test of Roos (EAST). In this test, the patient has to abduct the shoulder at 90 degrees with the elbows bent at right angles, with the hand palms face forward; then the patient is asked to close and open his hands alternatively for 3 minutes [2] [3] . The examiner observes the changes that may occur, such as a falling arm, an alteration of skin color and asks if other symptoms appear [2] [3] . During this test the space for the passage of the brachial neurovascular bundle is reduced [2] [3] .

Another test is the 90˚ AER (ninety degree abduction in external rotation stress); in this test the patient is asked to abduct the arm in external rotation to 90 degrees (the palms are faced up) [3] [5] . The active movement reduced the space for the brachial plexus [3] [5] . These tests can be performed consecutively [3] .

A test considered obsolete, with too many false positives, is the Adson’s test. The patient rotates and tilts his head to one side, remaining in inspiratory apnea for 30 seconds or in normal breathing for a minute, while the examiner evaluates the radial pulse of the ipsilateral side; if the radial pulse disappears, there is a vascular compression in the thoracic outlet [2] . The test is now considered unreliable [3] [7] . The measurement of the blood pressure is a fast way to assess the presence of any vascular problems. In patients with a compressed arterial lumen, a difference of more than 20 mmHg in systolic blood pressure between the two arms is considered as a significative value [19] . The diagnosis of TOS can be complicated by the presence of the so-called “double crush syndrome”, in which peripheral neurological symptoms (ulnar or carpal compression), probably depending on tensions at the level of the brachial plexus at the thoracic outlet, can interfere with the diagnosis [1] [2] [22] . If the tests for the TOS are all positive (false negatives are rare), instrumental tests are performed [3] . To differentiate nTOS and vTOS, the first examinations are a radiograph and/or a CT scan, in particular for bone abnormalities [1] [5] . An electrophysiological assessment of nerve conduction can be obtained through electromyography (EMG) and the evaluation of nerve conduction velocity (NCV); slow electrical conduction (less than 85 m/s) and a decreased action potential indicate nerve compression [1] [5] . These electrophysiological evaluations, in combination with ultrasound, may be employed after an anesthetic block on scalene muscles or the pectoralis minor, to verify if the nerve response improves, or if the symptomatic area remain silent at palpation; a good response is strongly suspicious for the presence of nTOS [3] . The neurography can show abnormalities of the brachial plexus position, but it is less used for its costs.3 MRI can give false positive results [3] . To verify a VTOS venous type, a duplex ultrasound scan can be used, with a high sensitivity (78% - 100%) and high specificity (82% - 100%); if the interpretation remains uncertain, venography can lead to the correct diagnosis [1] [3] [18] . For a problem of arterial origin, duplex ultrasound scan can be used; then, other tests such as MRI, CT and arteriography may be performed [3] [19] [20] .

The decision on the type of treatment (conservative or surgical treatment) has to be taken based on the symptoms and on instrumental and clinical information. Conservative treatment for nTOS and nPMM includes several approaches: physiotherapy (massage, stretching, muscle strengthening or relaxation, postural and breathing exercise), with or without associated drugs and physical therapies (ultrasound, laser, magnetotherapy); osteopathy (articular and muscular techniques); chiropractic (articular technique); acupuncture [1] [3] [23] [24] [25] .

There is no specific conservative treatment protocol [25] . Despite the lack of a homogenous protocol, 60% - 70% of patients with brachial nerve compression reported an improvement of the symptoms [6] . This improvement would be even more evident in comparison with surgery [26] . The main purpose of surgical treatment in the presence of nTOS and nPMM is to remove the cause of compression, for example through full or partial resection of the first rib, scalenectomy (anterior or medial muscle); tenotomy of the pectoralis minor; partial resection of the pectoralis minor [2] [3] [23] . Symptoms recurrence is observed in about 10% - 20% of patients who underwent surgery for neurological compression [3] . In patients with VTOS and/or vPMM venous type, the conservative treatment is represented only by anticoagulation and compression therapy [27] . This approach is not completely accepted, with drug therapy alone we risk a recurrence of the clot formation; the indication of compression is deduced especially for lower limbs [18] . Surgical treatment for venous compressions of VTOS and/or vPMM consists in: thrombolysis with direct access via venous catheter (in case of thrombosis); mechanical aspiration of thrombus from the vein (if the occlusion does not allow thrombolysis); angioplasty (if the patient still shows venous symptoms); resection of the first rib; anterior scalenectomy; reconstructive surgery [2] [3] [6] [18] [23] . The venous surgical treatment shows good results (85% - 100% of resolution), especially if surgery is performed shortly after the onset of symptoms [3] [6] [18] .

There is no conservative treatment for arterial occlusion [19] . In the presence of VTOS and/or vPMM with arterial compression surgery is the best option: resection of the first rib and hypertrophic muscles; embolectomy; artery surgical repair (with synthetic prostheses); venous or arterial bypass (saphenous vein, carotid artery) [2] [3] [20] [21] [23] .

The results of surgical treatment on symptoms resolution are good (about 80%) [3] . The surgical approach to be used depends on the patient’s needs.

There is not a conservative protocol universally considered as the best one; existing ones are not specific, or do not fully involve all the components of the thoracic outlet. Specific conservative therapeutic procedures are not available, and a proper evaluation of the results is not possible, since a complete manual evaluation of the musculoskeletal components is currently missing. We propose a hypothesis of manual evaluation.

This hypothesis of assessment should be carried out after than the clinician has ruled out the necessity of surgery with instrumental examinations. The same doctor may use this manual evaluation to get the first summary information on the area less mobile and sore. The physiotherapist, osteopath or chiropractor should know what the precise area that needs conservative intervention is; the operator will be able to know in detail where to work, only with a comprehensive assessment of thoracic outlet.

Palpation is an important tool to evaluate, classify and make diagnosis; the fingertip has a tactile sensitivity and is able to evaluate objects measured in micron [28] [29] [30] [31] . Palpation is able to report the position of the joints and to recognize abnormal joint movements, tissue abnormalities (temperature, tone, hardness) from the surface to the depth of the various layers, and to identify the painful area [30] [32] [33] .

The evaluation protocol consists of three phases, lasting about 15 minutes, with the patient standing, sitting and being supine.

The thoracic outlet syndrome (TOS) is caused by compression in certain anatomical areas of the vascular-nervous brachial plexus, between the scalene triangle, the clavicle, the first rib and the pectoralis minor. It is an insidious syndrome, not always easy to be managed, whose curative approach can be conservative and/or surgical. A comprehensive osteopathic manual evaluation of this musculoskeletal anatomical area is currently missing; in this scenario, a specific conservative therapeutic procedure cannot be properly assessed, and therapeutic results are not easily evaluated. The present article suggests a potential manual evaluation, which could highlight the anatomical area or areas that need more therapeutic attention. This kind of approach may potentially lead to higher results of non-surgical approach therapeutic techniques. The authors auspicate that this article could represent a starting point and a stimulus for further research in the field of manual evaluations.

The authors report no conflicts of interest in this work.

Bruno Bordoni, article writing, figures insertion; Fabiola Marelli, Bruno Morabito, text correction; Beatrice Sacconi, article translation.

Bruno, B., Fabiola, M., Bruno, M. and Beatrice, S. (2018) New Proposal of Evaluation of the Thoracic Outlet. Open Journal of Therapy and Rehabilitation, 6, 17-42. https://doi.org/10.4236/ojtr.2018.62003