Neurogenic Thoracic Outlet Syndrome

Presentation, diagnosis, and treatment

Background: Thoracic outlet syndrome (TOS) refers to a group of disorders in which there is compression of and/or damage to the neurovascular structures at the thoracic outlet, i.e., at the transition from chest to neck. The incidence of neurogenic thoracic outlet syndrome (nTOS) is estimated to be 2–3 / 100 000 / year, with an estimated prevalence of 10 / 100 000. Patients present with upper extremity sensorimotor symptoms that are often related to movement. The aim of the present article is to highlight the clinical presentation patterns of nTOS and to provide an overview of its diagnosis and treatment.

Methods: Selective literature search for prospective observational studies and RCTs, including systematic reviews and meta-analyses.

Results: There is no multicenter randomized controlled trial available on the treatment of nTOS. Prospective observational studies with a hierarchical study design report a positive effect of physiotherapy in 27–59% of cases. After unsuccessful conservative treatment, up to 56–90% benefit from surgical management. Patients with nTOS are more severely affected compared with those with other forms of TOS and benefit less from transaxillary first rib resection. nTOS patients who underwent supraclavicular decompression without rib resection had excellent surgical outcomes in 27%, good outcomes in 36%, acceptable outcomes in 26%, and poor surgical outcomes in 11% of cases. There is no systematic comparison available of the types of surgical management involved. Also, there is currently no uniform classification available for all medical sub-disciplines. Therefore, interpretation, and comparability of the study results are limited.

Conclusion: Although nTOS is the most common form of TOS, studies on its treatment are currently limited in terms of numbers and quality. The type of surgical management varies according to the experience and preference of the surgeon, treating specialty, special anatomic features, and clinical symptoms.

Cite this as:
Dengler NF, Pedro MT, Kretschmer T, Heinen C, Rosahl SK, Antoniadis G: Neurogenic thoracic outlet syndrome—presentation, diagnosis, and treatment. Dtsch Arztebl Int 2022; 119: 735–42. DOI: 10.3238/arztebl.m2022.0296

Thoracic outlet syndrome (TOS) is a heterogeneous group of disorders characterized by compression of, and/or damage to, the neurovascular structures at the thoracic outlet, i.e., the passage from the chest into the neck. One or more anatomic structures of the upper thoracic outlet may be affected (the brachial plexus, the subclavian artery [a.], and/or the subclavian vein [v.]). There are a variety of causes for compression of, and damage to, these structures (1). The classic distinction is between arterial (aTOS), venous (vTOS), and neurogenic thoracic outlet syndrome (nTOS) (2). In German-speaking countries, the literature in current journals and textbooks focuses on aTOS, as does the S2 guideline of the German Society for Vascular Surgery and Vascular Medicine (Deutsche Gesellschaft für Gefäßchirurgie und Gefäßmedizin e. V., DGG) (an update was due in 2010, but did not appear; no update is now planned, according to a reply from the DGG to an inquiry on May 23, 2022) (3, 4). Yet the more recent international literature, based on the uniform classification of the Society for Vascular Surgery (in the USA), reveals a trend toward recognition of primary nTOS as the most common type of TOS (2). In large case series from the USA, for example, in a prospective analysis of outpatient cases at the University of South Florida, the percentage of nTOS was 82%. (5) 82–85% of patients who underwent TOS surgery and whose TOS was classified by the uniform standards of the Society for Vascular Surgery had nTOS (6,7). The percentage of women among nTOS patients ranged from 59% to 95% (6, 8, 9). The accurate determination of the incidence and prevalence of nTOS presents a methodological challenge. An analysis in the United States in 2021 yielded an estimated incidence of 2–3 cases and an estimated prevalence of approximately 10 cases per 100 000 persons per year (5, 10). The numbers are thought to be much higher in athletes, particularly in sports involving intense use of the upper limbs, such as swimming, rowing, or volleyball (11, 12). Some authors also describe a further type called “disputed” thoracic outlet syndrome (dTOS), which is characterized by inconsistent symptoms (1). The Society for Vascular Surgery, when it proposed the adoption of the uniform classifying standard in 2016, explicitly advised against the use of the term dTOS (2). In everyday clinical practice, there is much uncertainty about the presentation, proper diagnostic evaluation, characterization, and treatment of nTOS. The road to correct diagnosis and appropriate treatment is often long. Rochkind et al. described a group of patients with pronounced motor deficits for whom there were delays of 1.3 to 15 years before diagnosis and surgical treatment (13, 14). As described vividly by Dubuisson et al., patients with TOS are often misdiagnosed and subjected to unnecessary operations and therapies. In the cited study, three of seven patients were initially treated incorrectly. One of them underwent two unhelpful surgical procedures—cervical discectomy and ulnar nerve decompression at the elbow—before the correct diagnosis of nTOS was made (15).

Anatomic particularities in the individual can be a risk factor, especially an accessory rib, a prominent C7 transverse process, additional ligaments and muscles such as the costotransverse ligament, Sibson‘s fascia or muscle between the C7 transverse process and the first rib, or a short costoclavicular distance (13, 14, 16, 17). There can also be acquired factors such as trauma, high-performance sports, a job demanding intense use of the upper limb(s), and the normal descent of the shoulder muscles between age 30 and 50. Musicians, for example, suffer disproportionately from nTOS, as do persons whose jobs demand a great deal of work on a computer or overhead (18, 19, 20, 21).

In this article, we discuss the current state of the evidence on nTOS in order to help physicians identify patients with this condition more easily in clinical practice, while providing an overview of the diagnostic evaluation and of the options for treatment.

Methods

Two independent reviewers (MTP, NFD) carried out a selective literature search in Medline via PubMed, employing the search terms „thoracic outlet syndrome“ and „neurogenic thoracic outlet syndrome“ for the period 1982–2022. This yielded 2979 and 392 hits, respectively (date of search, 28 February 2022). Only articles in German or English were considered.

Results

Clinical features

Patients with nTOS typically present with movement-dependent pain, especially upon abduction and retroversion of the arm, with or without a neurologic deficit (motor: paresis; sensory: hypesthesia) and/or a tingling paresthesia in the dermatomes and muscles supplied by the inferior trunk (C8/Th1), along with local tenderness at the thoracic outlet (eTable 1) (1, 22, 23, 24, 25, 26). In rarer cases, structures innervated by the superior and middle trunks may also be affected. Pronounced damage is indicated by the presence of a Gilliatt-Sumner hand, i.e., combined atrophy of the thenar, hypothenar, and intrinsic hand muscles, which are supplied by the median and ulnar nerves (27). There may be simultaneous compression of the vascular structures of the thoracic outlet, with corresponding symptoms (22). The criteria for the presence of nTOS proposed by the Society for Vascular Surgery and the nTOS classification proposed by the European Society of Neurosurgical Specialists are reproduced in eTable 2 (2, 28).

eTable 1

Clinical manifestations of neurogenic thoracic outlet syndrome and their frequency of appearance (1, 23, 24, 25, 26)

eTable 2

The state of the evidence on neurogenic thoracic outlet syndrome

Diagnostic evaluation: history, clinical examination, provocative tests, imaging, and neurophysiology

When the history is taken, particular attention should be paid to previous trauma to the clavicle and thoracic outlet. The intensity, severity, duration, and motion dependence of the current symptoms should be documented. At this point, the distinction between nTOS, aTOS, and vTOS can already be made. If there is swelling of the arm associated with pain, vTOS (also called Paget-von-Schroetter syndrome) can be tentatively diagnosed. Typical features of aTOS include cold fingers, livid or pale coloration of the hand, individual fingers, or fingertips, a faint or absent pulse at the wrist, arm weakness during use, and/or throbbing pain in the arm (1, 2). If a diagnosis of vTOS or aTOS is suspected, further vascular tests are indicated (Doppler ultrasonography, CT angiography, digital subtraction angiography [DSA], MR angiography).

If nTOS is suspected, the clinical neurological examination is very important, with special attention to motor, sensory, and autonomic function, particularly the identification of signs of muscle weakness (1,27). Studies have shown that provocative maneuvers such as the Adson test, elevated arm stress test (EAST), supraclavicular pressure test, and costoclavicular maneuver are generally of moderate sensitivity (72%) and low specificity (53%). The low specificity (corresponding to a high false positive rate) is shown in detail in Table 1 and needs to be borne in mind when these tests are used (29, 30, 31). The most informative finding in the experience of many clinicians is a positive Hoffmann-Tinel sign on deep supraclavicular palpation, with a comparison of the two sides (18).

Table 1

Descriptions and false-positive rates of clinical functional tests for thoracic outlet syndrome (29, 31)

In a review paper, the American College of Radiology recommends that patients with nTOS should have a chest x-ray to rule out a bony anomaly. Magnetic resonance imaging (MRI) of the cervicobrachial plexus and the chest can be used to rule out a local neoplasm or infectious/inflammatory process (2). Advances in magnetic MR neurography now enable high-resolution imaging of neural structures and the visualization of compression sites (32, 33). MRI of the cervical spine is recommended to rule out common differential diagnoses including cervical disc herniation, cervical spinal canal stenosis, and cervical neuroforaminal stenosis (28, 34). Other potential differential diagnoses and their characteristics, and differential-diagnostic techniques, are listed in the Box (35, 36, 37, 38, 39, 40, e1).

Box

The major differential diagnoses of thoracic outlet syndrome with their individual features and differential-diagnostic modalities (35, 36, 37, 38, 39, 40, e1)

High-resolution nerve ultrasound (HNUS) is increasingly used in clinical practice. HNUS enables simultaneous visualization of the arterial, venous, and neural elements of the thoracic outlet in dynamic positions, with direct visualization of any compressing structures. Its disadvantages are that it is examiner-dependent and has a shallow penetration (e2, e3). A typical neurosonographic finding is the wedge-sickle sign, i.e., crescentic elongation of the inferior trunk because of compressing structures.

Neurophysiological diagnostic testing in nTOS serves to exclude common differential diagnoses such as carpal tunnel syndrome, cubital tunnel syndrome, Loge-de-Guyon syndrome, and cervical radiculopathy (e4). The utility of sensory nerve action potentials (SNAP) of the medial cutaneous antebrachial nerve for the diagnosis of nTOS has been shown in multiple studies (eBox) (e4, e5).

eBox

Ancillary diagnostic testing

Local anesthetic infiltration may be helpful; botulinum toxin and steroids, too, can be injected as trial therapy. These interventions are used as diagnostic aids, but sometimes also as treatment (2, e6).

Treatment: conservative treatment and the timing and type of surgery

In a prospective observational study, the conservative treatment of nTOS with physical therapy satisfactorily improved symptoms in 27% of cases (e7). Other studies of conservative therapy were not conducted or evaluated specifically for nTOS. The injection of botulinum toxin into the anterior and middle scalene muscles reduced pain but had no effect on functional scores (SF-36, Disability of the Arm, Shoulder, and Hand [DASH] questionnaire, paresthesia). Kinesiology tapes lessened pain and improved DASH scores compared to placebo tapes. In the DASH, a commonly used questionnaire for assessing the severity of TOS symptoms, functional restrictions of the upper limb with respect to 30 different activities are rated on a scale (e8). A randomized trial with a cross-over design demonstrated that steroid injections alleviated pain (as measured by the VAS) to a greater extent than scalene muscle stretching exercises (e6, e9, e10).

Primary conservative therapy is indicated in the absence of motor manifestations (28, e11). Appropriate surgical treatment should be performed promptly (within a few weeks at most) if there is weakness, hypotrophy, or atrophy of the upper limb muscles (nTOS 1).

There is no consensus on when surgery is indicated in patients without motor weakness. Proper patient selection and surgical timing are essential to lessen the suffering of those who can benefit from surgery while avoiding needless operations in those who cannot. In the authors’ view, surgery should be offered to patients with typical motion-dependent symptoms, severe distress, and an anatomical abnormality (nTOS 2). It may also be proposed to patients who have no anatomic abnormality, yet display typical radicular symptoms, after differential diagnoses have been excluded (nTOS 3a), if they have not benefited from 8–12 weeks of conservative treatment and their quality of life and everyday activities are markedly impaired (28).

For patients with diffuse symptoms or purely cervicoscapular symptoms and without an anatomical anomaly (nTOS 3b and nTOS 3c), the authors consider that surgery is only rarely indicated. Other differential diagnoses should be meticulously excluded. In such cases, intensified conservative treatment, interdisciplinary pain therapy, and a psychosomatic evaluation (where indicated) are advisable, so that needless operations and their complications can be avoided (e12).

A variety of surgical treatments are carried out by specialists in different surgical disciplines. A transaxillary approach with removal of the first rib or an accessory cervical rib may be complicated by injury to the brachial plexus (in 1–3% of cases), the subclavian vein or the thoracic duct, by pneumothorax (3% to 26% of cases), or by an injury of the sympathetic chain resulting in Horner syndrome (6,25,e13,e14). Neurosurgeons often prefer a microsurgical approach from above the clavicle, with the aid of intraoperative neuromonitoring to protect the brachial plexus (see Figure, modified from [e15]). This approach is considered less traumatic and thus less likely to cause scarring. It enables good circumferential exposure of the compressed (nerve, artery, vein) and compressing structures (scalene muscles, ligaments, C7 transverse process, an accessory rib if present, and the first rib if necessary). In recent years, some plastic surgeons and vascular surgeons have also turned to the supraclavicular approach, with or without standard resection of the first rib (e16, e17). The posterior subscapular approach is now rarely used, generally only for recurrences.

Figure

The supraclavicular approach to the neurovascular bundle of the thoracic outlet

Summary of the state of the evidence

There has been only one single-center randomized controlled trial (RCT) of surgery for a form of TOS that should probably be classified as dTOS or nTOS 3b or nTOS 3c. In this study, transaxillary rib resection was compared with supraclavicular “neuroplasty” without rib resection. In the group with rib resection, good to excellent results were obtained in 75% of cases, after a median follow-up interval of 37 months; the corresponding figure in the group without rib resection was only 48% (p = 0.05) (e18). This study has also been included in the current Cochrane analyses despite weaknesses in study design with respect to randomization and inclusion criteria (e19, e20). The second RCT in the updated 2014 Cochrane analysis concerned the effect of botulinum toxin injections in TOS patients, but without any specific evaluation in patients with nTOS; we have, therefore, not included this RCT in our tabular review (e6). No other RCTs on nTOS can be found in the literature. Three prospective observational studies, in which patients first underwent standardized physiotherapy and were operated on only if they did not benefit from it, showed a benefit from physiotherapy in 27–59% of cases. Two of these studies were designed specifically for nTOS, while the third contained an nTOS-specific analysis. Moreover, it was found that many (ca. 90%) of the patients who underwent surgery after unsuccessful physiotherapy benefited from it, with 75% returning to work within five months after surgery (e7, e13, e21). Patients with nTOS are more severely affected than those with other types of TOS, benefit less from transaxillary rib resection, and need secondary treatment more often than vTOS patients (e13). In nTOS patients who underwent supraclavicular decompression without rib resection, the surgical outcome was excellent in 27% of cases, good in 36%, acceptable in 26%, and poor in 11% (Table 2, eTable 3) (25, e7, e13, e19-e28). In a systematic review of ten single-center trials with heterogeneous inclusion criteria and treatment methods, there was an nTOS-specific pooled analysis of four trials, but no conclusions could be drawn regarding the efficacy of surgical therapies because variations in trial design did not enable a valid comparison (e23). The published case series of robot-assisted first rib resection are single-center studies with low case numbers and do not yet enable a systematic, nTOS-specific evaluation (e29, e30).

Table 2

The state of the evidence on neurogenic thoracic outlet syndrome (short version)

eTable 3

The definition of neurogenic thoracic outlet syndrome (nTOS) according to the Society for Vascular Surgery (USA) and the nTOS subclassification according to the Peripheral Nerve Section of the European Association of Neurosurgical Societies (EANS) (2, 28)

Overview

The available evidence on the treatment of nTOS is limited in both quality and quantity. The available nTOS-specific evidence does, however, permit the conclusion that conservative treatment should be tried first in patients who have no motor deficit. If surgery is needed, there is a strong case for supraclavicular decompression without rib resection. The single available RCT on rib resection versus supraclavicular neuroplasty must be viewed critically from the methodological point of view; its results cannot be generalized to patients with motor deficits (nTOS 1) or anatomical anomalies (nTOS 2). The choice of treatment depends, at present, on the experience and expertise of the treating physicians. A consensus document recently issued by experienced European neurosurgeons contains a recommendation for the anterior and supraclavicular microsurgical approach, with the aid of intraoperative neuromonitoring.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 1 April 2022, revised version accepted on 21 July 2022.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
PD Dr. med. Nora Franziska Dengler
Charité – Universitätsmedizin Berlin Campus Benjamin Franklin
Klinik für Neurochirurgie
Hindenburgdamm 30, D-12203 Berlin, Germany

Cite this as:
Dengler NF, Pedro MT, Kretschmer T, Heinen C, Rosahl SK,
Antoniadis G: Neurogenic thoracic outlet syndrome—presentation, diagnosis, and treatment. Dtsch Arztebl Int 2022; 119: 735–42. DOI: 10.3238/arztebl.m2022.0296

►Supplementary material

eReferences, eTables, eBox:
www.aerzteblatt-international.de/m2022.0296

cme plus

This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet: cme.aerzteblatt.de. The deadline for submission is 27 October 2023.

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