INTRODUCTION TO THORACIC OUTLET SYNDROME

What is thoracic outlet syndrome?

The thoracic outlet syndrome, or simply TOS, is a collective term describing several conditions associated with compression of nerves and/or blood vessels in the thoracic outlet area, which represents the upper exit (outlet) of the chest cavity.

What is thoracic outlet area?

The thoracic outlet is an area located at the top of the chest cavity arbitrarily representing its exit. The term thoracic inlet area was used in the past to refer to this region but had been abandoned. This area has heart-shaped contour bounded by the first thoracic vertebra, the left and right first ribs, and the upper edge of the sternum. The area is tightly packed with vital anatomical strucutes and has therefore great clinical significance.

What structures are affected by TOS?

The neurovascular bundle comprising brachial plexus, subclavian artery and vein is the main anatomical structure compromised during thoracic outlet syndrome. Five nerve roots emanating from the spinal cord (C5, C6, C7, C8, and T1) intermingle with each other to form a complex network called the brachial plexus. The brachial plexus itself branches to several nerves that eventually innervate the neck, upper chest area and the arm. These nerves carry electric neural impulses between the spinal cord and upper extremity. They control every aspect of arm function: skin sensation, muscle contraction, sweating, blood vessel tone, etc. Additionally, the brachial plexus innervates skin and muscles of the neck, upper chest, and the shoulder girdle.

The subclavian artery and subclavian vein are main vessels providing blood flow to and from the arm. They pass with the brachial plexus over the first rib at the thoracic outlet. Similar configurations can be found in many body areas and nerves frequently travel along with blood vessels, forming various neuro-vascular bundles.

Artistic drawing demonstrating the course of the brachial plexus, subclavian artery, and vein in the thoracic outlet area. Note that all structures pass above the first rib.

The neurovascular bundle travels directly above the first rib and components of neurovascular bundle are in contact with the first rib. In fact the first rib has two specific grooves to accomodate passing subclavian artery and vein. Additionally C8, T1 nerve roots and inferior trunk of the brachial plexus also are in direct contact with the first rib. The brachal plexus and subclavian artery pass through a narrow anatomical window called the scalene triangle. This triangle is located in between two scalene muscles (anterior and middle) and the first rib. The scalene triangle or space is densely packed and, thus, is prone to compression. The subclavian vein doesn't pass through this triangle and cannot be compressed in it. It passes through a separate triangle named costoclavicular or venous triangle. Subclavius muscle, anterior scalene musce and the first rib form this venous triangle which is just anterior and medial to scalene triangle. Thus, the vein can be compressed between the first rib and subclavius muslce. The other potential compression site is subpectoral area (the space underneath the pectoralis muscle).

Types of TOS

There are three different clinical TOS variants:

• Neurogenic TOS – nTOS. The most common form (approximately 90-95%). Brachial plexus is involved, and symptoms develop due to neural compression. 
• Venous TOS – vTOS. Far less common (3-4%). The subclavian vein is affected, and the symptoms are due to insufficient blood return from the affected arm.
• Arterial TOS – aTOS. The least common form (1-2%). The subclavian artery is compressed, and the symptoms are due to insufficient flow to the affected arm. Arterial and venous cases are sometimes collectively called vascular TOS.

Causes of TOS

The thoracic outlet syndrome is a collective term describing the site (location) of disease rather than the cause. This term is similar to other entrapment neuropathies like carpal tunnel syndrome. It is customary in peripheral nerve surgery to classify the conditions according to pathology site. However, the term itself doesn't pinpoint the cause of the problem. Rarely, the compressing factor can be identified (like cervical accessory rib or a tumor) on imaging studies. Unfortunately, this is not the case for the majority of patients even with advanced imaging modalities. 

There are several conditions predisposing to thoracic outlet syndrome. Women are affected 3-4 more often than men. People working with repetitive arm and hand movements tend to develop TOS more frequently. Bad upper body posture, particularly shoulder slouching can contribute to compression. Various congenital and acquired conditions responsible for TOS development are summarized below:

1. Cervical accessory rib. There are 12 pairs of ribs in normal human body. They are attached to thoracic vertebrae and form chest cavity. Some people possess accessory or supernumerary cervical rib(s). Normally, human fetus develops tinu cervical ribs during intrauterine period. However, they disappear later and should not be present after the birth. The remnants of embryological cervical ribs remain in normal humans as transverse processes of cervical vertebra. These small bone protrusions serve as attachment points for various neck muscles. In some people, accessory ribs fail to vanish and are present after the birth. Recent large scale meta-analysis study has found that approximately 1.1% of population has cervical ribs [1]. Furthermore, the incidence of accessory cervical ribs in TOS patients is 29% – approximately 25 times more than in general population [1]. These ribs extend from the seventh cervical vertebra (which is the last cervical vertebra). Therefore, the accessory cervical rib is just above the first rib. The shape and size of the rib may vary dramatically - from a slightly elongated C7 transverse process to a well-formed, almost normally looking rib. If supernumerary accessory rib is big, its tip usually touches the first rib via bone or cartilaginous junction. The exact mechanism responsible for supernumerary cervical rib formation in unknown but there is evidence that it might be due to glitch in HOX genes. HOX genes or homeobox genes are responsible for sequence of events responsible for correct body segmentation. Disturbances and mutations affecting these genes lead to number of vertebral anomalies and abnormal cervical ribs. It was shown experimentally that mice with mutant HOX genes develop supernumerary ribs at seventh cervical vertebra [2]. Interestingly, HOX genes also play certain role in cancer development and there is evidence that the incidence of accessory cervical ribs is higher in cancer patients [3] further supporting HOX hypothesis. Cervical accessory ribs are easily visible on plain X-ray images and thus have been long known to cause TOS. Yet even nowadays untrained eye may fail to recognize them, thus leading to misdiagnosis.  
2. First rib diseases. Like in case of cervical ribs plain X-rays can diagnose first rib abnormalities fairly accurately. However, complex anatomy of the first rib, overlapping bones and variety of first rib pathologies may obscure the underlying cause. Therefore, in the vast majority of cases only experts with significant expertise in the field can identify first rib abnormalities. First rib is a curved flat bone spanning from the first thoracic vertebra to sternum. It has three joints. The head of the rib has a joint with first thoracic vertebral body. Tubercle makes a joint with transverse process of the first thoracic vertebra. And the sternal end blends in cartilage connecting the rib to the sternum. Anomalous, fractured or subluxated first ribs can cause TOS by stretching or compressing the neuro-vascular package. Unlike cervical supernumerary ribs these abnormalities are less evident on imaging and therefore easily missed. Congenital abnormalities such as fused cervical and first ribs, fused second and first ribs, bifid first ribs are well-known causes of TOS. Trauma is also a significant contributor to TOS. Fractured first ribs with either excessive callus formation or pseudoarthrosis (lack of bone healing) can also cause thoracic outlet syndrome. Tumors of the first rib including benign lesions like hemangiomas expand the bone and compress nearby neurovascular bundle. One study found that widening of the vertebral and sternal ends of the first rib is strongly associated with TOS [4]. Another study has found that abnormal bone tubercle on the sternal end of the first rib is responsible for venous TOS development [5]. 
3. Fibromuscular soft tissue bands constitute significant portion of TOS cases. The cause of compression may be an abnormal muscle, a fibrous band, or a combination of them. Scalenus anticus, scalenus minimus and subclavius posticus are examples of such muscles although their incidence is relatively rare. These sturdy bands of fibro-muscular tissue run from various portions of the spine (usually C7 transverse process) to the first rib stretching and compressing the neurovascular bundle [6]. 
4. Hypertrophic muscles also may cause compression. People extensively using their arms and hands for work and sports are especially prone to this type of TOS. This condition is frequently seen in athletes. Scalene muscle hypertrophy usually results in n- and a-TOS (since both the artery and brachial plexus run inside the scalene triangle) [7]. Sublclavius muscle hypertrophy may cause compression and even thrombosis of the subclavian vein (Paget–Schroetter disease).
5. Costo-clavicular compression. Both clavicle and first rib make joint with upper part of sternum. First rib has little mobility whereas clavicle is a very mobile bone. Clavicle is also attached to scapula at the lateral end. Its main function is work as a lever between the immobile sternum medially and mobile scapula laterally. Normally the gap between the clavicle bone and the first rib – costo-clavicular space is quite wide. Neurovascular bundle passes through this space just above the first rib and below clavicle. However, with arm abduction clavicula's lateral (scapular) end moves close to midline while medial (sternal) end remains stable. Such a "nutcracker mechanism" between clavicle and first rib significantly narrows costo-clavicular space. Anterior part of this space comprising venous triangle is particularly affected leading to compression and occlusion of the subclavian vein [8]. 
6. Blood vessels branching from subclavian vessels may loop around or through the brachial plexus and cause compression. These vascular causes have been identified as the source of TOS relatively recently and the research in this area is still ongoing [9]. 
7. Chronic kidney disease and dialysis. Therapeutic arterio-venous fistula is a commonly used method for easy vascular access in hemodialysis patients. However, one of the major shortcomings is increased blood flow and turbulence in the subclavian vein. This leads to central venous stenosis and the thoracic outlet area is a particularly vulnerable region. Like in most vTOS cases, such stenosis usually develops in the costo-clavicular (or venous) triangle due to "nutcracker effect" between the clavicle and first rib [10]. 

References

1. Henry BM, Vikse J, Sanna B, et al. Cervical Rib Prevalence and its Association with Thoracic Outlet Syndrome: A Meta-Analysis of 141 Studies with Surgical Considerations. World Neurosurg. 2018;110:e965-e978. https://doi.org/10.1016/j.wneu.2017.11.148

2. Horan GS, Wu K, Wolgemuth DJ, Behringer RR. Homeotic transformation of cervical vertebrae in Hoxa-4 mutant mice. Proc Natl Acad Sci U S A. 1994;91(26):12644-12648. https://doi.org/10.1073/pnas.91.26.12644

3. Merks JH, Smets AM, Van Rijn RR, et al. Prevalence of rib anomalies in normal Caucasian children and childhood cancer patients. Eur J Med Genet. 2005;48(2):113-129. https://doi.org/10.1016/j.ejmg.2005.01.029

4. Chang CS, Chuang DC, Chin SC, Chang CJ. An investigation of the relationship between thoracic outlet syndrome and the dimensions of the first rib and clavicle. J Plast Reconstr Aesthet Surg. 2011;64(8):1000-1006 https://doi.org/10.1016/j.bjps.2011.03.017

5. Gharagozloo F, Meyer M, Tempesta B, Strother E, Margolis M, Neville R. Proposed pathogenesis of Paget-Schroetter disease: impingement of the subclavian vein by a congenitally malformed bony tubercle on the first rib. J Clin Pathol. 2012;65(3):262-266 http://dx.doi.org/10.1136/jclinpath-2011-200479

6. Roos DB. Congenital anomalies associated with thoracic outlet syndrome. Anatomy, symptoms, diagnosis, and treatment. Am J Surg. 1976;132(6):771-778. https://doi.org/10.1016/0002-9610(76)90456-6

7. Qaja E, Honari S, Rhee R. Arterial thoracic outlet syndrome secondary to hypertrophy of the anterior scalene muscle. J Surg Case Rep. 2017;2017(8):rjx158. https://doi.org/10.1093/jscr/rjx158

8. Illig KA, Doyle AJ. A comprehensive review of Paget-Schroetter syndrome. J Vasc Surg. 2010;51(6):1538-1547. https://doi.org/10.1016/j.jvs.2009.12.022

9. Hanna A, Bodden LO, Siebiger GRL. Neurogenic Thoracic Outlet Syndrome Caused by Vascular Compression of the Brachial Plexus: A Report of Two Cases. J Brachial Plex Peripher Nerve Inj. 2018;13(1):e1-e3. https://doi.org/10.1055/s-0037-1607977

10. Davies MG, Hart JP. Venous thoracic outlet syndrome and hemodialysis. Front Surg. 2023;10:1149644. https://doi.org/10.3389/fsurg.2023.1149644