Clinical manifestations

Presentation and course

	• Typical symptoms and signs of true neurogenic thoracic outlet syndrome include sensory symptoms over the medial hand or forearm and intrinsic hand muscle weakness and atrophy, disproportionately involving the thenar eminence; motor signs predominate.
	• Disputed thoracic outlet syndrome is best considered a cervicoscapular pain syndrome.
	• Arterial thoracic outlet syndrome often coexists with neurogenic thoracic outlet syndrome, and symptoms relate to limb ischemia.
	• Venous thoracic outlet syndrome results from thrombosis of the axillosubclavian vein; at-risk individuals include athletes and persons with hypercoagulable states.
	• The medial cord of the brachial plexus passes behind the midshaft of the clavicle and is highly susceptible to injury.

True neurogenic thoracic outlet syndrome. True neurogenic thoracic outlet syndrome will usually present with unilateral symptoms and signs, often initiated with pain. True neurogenic thoracic outlet syndrome has clear and well-accepted clinical and electrophysiologic features, reflecting involvement of T1>C8 sensory and motor fibers. The motor abnormalities are usually more pronounced and may be quite advanced at presentation because of the indolent progression of this disorder. Patients present with intrinsic hand muscle weakness, loss of dexterity, and wasting, primarily of the median-innervated thenar muscles, which are innervated primarily by T1>C8 axons (30). Weakness is present but less pronounced in ulnar-innervated hand and forearm muscles and least in radial-innervated forearm muscles. Sensory features in the form of pain, paresthesias, or numbness are usually present and involve the medial forearm or hand (30); they can, however, be subtle and require a careful sensory exam to demonstrate a deficit. This clinical phenotype has also been referred to as the Gilliatt-Sumner hand (07).

Disputed thoracic outlet syndrome. Best considered as a cervicoscapular pain syndrome, as suggested by Ferrante and Ferrante, this is the most common form of thoracic outlet syndrome and also the most nonspecific (04; 05). This is a highly controversial disorder that frequently frustrates clinicians and leads to disputes in the literature. The most prominent symptom is pain but it may also present with weakness, fatigue, or sensory loss. A lower plexus and an upper plexus pain pattern is described. The neurologic exam is typically unremarkable. Bilateral features are common compared to the other subtypes of thoracic outlet syndrome. Proponents of disputed thoracic outlet syndrome espouse the utility of provocative maneuvers such as the Adson, Wright, costoclavicular, and elevated arm stress test maneuvers, but these suffer from high false positive rates; an exhaustive discussion of this topic is presented by Ferrante and Ferrante (04; 05).

Arterial thoracic outlet syndrome. Arterial thoracic outlet syndrome is a rare condition, but the most devastating of all the thoracic outlet syndromes, and is caused by intermittent or prolonged arterial compression of the subclavian artery, typically by a cervical rib (12). Other etiologies include bony anomalies of the first thoracic rib, scalene muscle hypertrophy, or intramuscular fibrous bands (04; 05). It affects both males and females and is often found in young adults. Symptoms relate to limb ischemia and may include claudication, hypersensitivity to cold in the hands, and numbness or pain in the fingers. Uncommonly, arterial thrombosis may occur abruptly and distal emboli can result in finger ulcers or embolic ischemic strokes (20). Association between embolic stroke and arterial thoracic outlet syndrome was first described by Symonds in 1927 (29). Arterial thoracic outlet syndrome often coexists with neurogenic thoracic outlet syndrome (12).

Venous thoracic outlet syndrome. Venous thoracic outlet syndrome refers to the compression and thrombosis of the axillosubclavian vein and is frequently referred to as Paget-Schroetter syndrome or “effort thrombosis”. At risk individuals include athletes, especially weight lifters, baseball pitchers, and swimmers, which forms the basis of the term “effort thrombosis” (17). Persons with hypercoagulable states are also predisposed to develop this condition (13). An occlusive thrombosis may result in limb edema, cyanosis, congested veins, and pain. This disorder affects men more often than women, often unilaterally, involving the dominant limb.

Traumatic neurovascular thoracic outlet syndrome. This syndrome follows clavicular fracture and its presentation depends on the specific neurovascular elements involved in the injury, either directly through compression or laceration or indirectly through an expanding hematoma or aneurysm. Pain at the site of trauma often radiates down the arm. The medial cord of the brachial plexus passes behind midshaft of the clavicle and is highly susceptible to injury. Accordingly, sensory deficits may involve the distributions of the medial brachial, medial antebrachial, and ulnar nerves. Motor axons for the C8 and T1 roots are affected without clear predilection for T1>C8 involvement as seen in true neurogenic thoracic outlet syndrome. Furthermore, C8 radial motor axons are spared as they cross over to the posterior cord proximal to the lesion site.

Clinical vignette

A 42-year-old right-handed woman presented for another opinion regarding a diagnosis of “monomelic amyotrophy” of the right arm made 8 years previously. There was a long indolent history of at least 10 years of progressive right-hand weakness, atrophy, and loss of dexterity, though she managed to compensate and function well at work. She did not recall ever having significant pain or numbness but did have a vague discomfort in the medial forearm. Examination revealed severe right thenar atrophy and abductor pollicis brevis weakness, mild ulnar intrinsic atrophy and weakness, and mild weakness of finger extension. Reflexes were normal. There was reduced pinprick and touch sensation over the medial forearm. The left arm and legs were normal.

Nerve conduction studies in the right arm revealed an absent medial antebrachial cutaneous sensory nerve action potential, reduced ulnar sensory amplitude, normal median sensory potential, severely reduced median compound muscle action potential amplitude, and mildly reduced ulnar motor amplitude. Comparable studies on the left arm were normal. EMG showed reduced recruitment of polyphasic, large-amplitude, long duration, rapidly firing motor unit potentials in the abductor pollicis brevis, first dorsal interosseous, abductor digiti minimi, and extensor indicis muscles; the abductor pollicis brevis muscle also had few fibrillations. The study was consistent with a lower trunk brachial plexopathy and the clinical syndrome consistent with true neurogenic thoracic outlet syndrome. Plain films and cervical CT showed a right cervical rib at C7. Routine MRI failed to reveal a fibrous band or other anomaly. Surgical exploration with resection of the cervical rib and likely fibrous band was offered but the patient declined due to concern about possible complications and given her high level of function without pain.

Biological basis

• True neurogenic thoracic outlet syndrome is typically caused by a fibrous band extending from the first thoracic rib to a C7 rib or elongated C7 transverse process.

Etiology and pathogenesis

True neurogenic thoracic outlet syndrome. True neurogenic thoracic outlet syndrome is typically caused by a fibrous band extending from the first thoracic rib to a C7 rib or elongated C7 transverse process, which compressed the lower trunk of the brachial plexus or the T1 spinal root. The fibrous band abuts the brachial plexus from below, resulting in T1>C8 involvement. The predominant pathology is axon loss.

In a cohort of 32 patients, a fibrous band was confirmed surgically in all 32 patients whereas a C7 bony anomaly was detected on the symptomatic side in only 79% (30). The same study also found a higher incidence of true neurogenic thoracic outlet syndrome in women (94%) and with involvement of the dominant arm (81%). Although women are more likely to develop true neurogenic thoracic outlet syndrome, they are not more likely to have a cervical rib, as a study of stillborn fetuses showed an even distribution in men and women (16). Again, this emphasizes the point that the presence of a fibrous band rather than a C7 bony anomaly is what typically causes true neurogenic thoracic outlet syndrome. Because the prevalence of cervical ribs is far greater than the prevalence of true neurogenic thoracic outlet syndrome, most cervical ribs are incidental findings (04; 05).

Disputed thoracic outlet syndrome. Unlike the other thoracic outlet syndrome subtypes, disputed thoracic outlet syndrome does not have an agreed upon anatomic basis or pathophysiology. Mild trauma without clavicular fracture has been proposed to cause brachial plexus traction scars, scalene muscle fibrosis, and other nonspecific muscle imbalances. Postural factors and congenital anomalies are also proposed as contributory mechanisms to brachial plexus irritation in the thoracic outlet (04; 05). The so-called “droopy shoulder syndrome” in women with low-set droopy shoulders and long swan neck probably falls under this umbrella (03; 28).

Arterial thoracic outlet syndrome. Arterial thoracic outlet syndrome is caused by intermittent or prolonged arterial compression of the subclavian artery, typically by a cervical rib (12). Other etiologies include bony anomalies of the first thoracic rib, scalene muscle hypertrophy, or intramuscular fibrous bands (04; 05). Arterial thrombosis may also occur and result in embolic strokes.

Venous thoracic outlet syndrome. Compression and thrombosis of the axillosubclavian vein may occur in otherwise healthy individuals, especially athletes and manual laborers, perhaps related to repetitive activities that constrict the thoracic outlet. Thrombosis is thought to occur after muscle stretch and strain. Anatomic abnormalities such as scalene muscle hypertrophy or even a fibrous band and cervical rib may also contribute to venous compression. Disorders associated with venous stasis or hypercoagulability may also play a role.

Traumatic neurovascular thoracic outlet syndrome. This syndrome follows clavicular fracture and its presentation depends on the specific neurovascular elements involved in the injury either directly through compression or laceration or indirectly through an expanding hematoma or aneurysm. The medial cord of the brachial plexus passes behind midshaft of the clavicle and is highly susceptible to injury with clavicular fracture. Delayed neurovascular injury can be related to excessive callus formation with compression.

Epidemiology

	• True neurogenic thoracic outlet syndrome is extremely rare and more commonly found in women.
	• Venous thoracic outlet syndrome is the most common.
	• The prevalence of a cervical rib in the general population is 0.5% to 2%.

Data on the epidemiology of thoracic outlet syndromes are constrained by nosology. The lumping of true neurogenic thoracic outlet syndrome and disputed thoracic outlet syndrome into neurogenic thoracic outlet syndrome often occurs in the literature (33; 34). True neurogenic thoracic outlet syndrome is extremely rare, occurring in 0.1 per 100,000 individuals whereas venous thoracic outlet syndrome is the most common (06). True neurogenic thoracic outlet syndrome is more commonly found in women and more often in the dominant limb. In one cohort of surgically verified true neurogenic thoracic outlet syndrome, 30 of 32 patients were women. The majority of patients with thoracic outlet syndromes of all subtypes are 25 to 40 years of age; thoracic outlet syndromes are extremely rare in children (23), but they may be seen in adolescents (19). It is important to know that the prevalence of a cervical rib in the general population is 0.5% to 2%, so that its presence in a patient with nonspecific upper extremity symptoms is most likely incidental (04; 05). Disputed thoracic outlet syndrome is more common among women and is frequently bilateral.

Differential diagnosis

Confusing conditions

A number of diseases can mimic the presentation of the thoracic outlet syndromes. A careful clinical assessment, combined with electrodiagnostic and imaging studies will sort these out.

True neurogenic thoracic outlet syndrome:
	• Advanced carpal tunnel syndrome
	• Combined median and ulnar entrapments
	• C8-T1 radiculopathies
	• Other structural lower trunk/medial cord plexopathies (Pancoast tumor, nerve sheath tumors, lipomas)
	• Intrinsic spinal cord lesions (syringomyelia, tumors)
True neurogenic thoracic outlet syndrome without clear-cut or only subtle sensory involvement:
	• Motor neuron disease
	• Hirayama disease
	• Multifocal motor neuropathy
Disputed thoracic outlet syndrome, traumatic neurovascular thoracic outlet syndrome:
	• Cervical radiculopathies
	• Rotator cuff syndrome
	• Parsonage Turner syndrome
	• Complex regional pain syndrome

Diagnostic workup

	• An absent or reduced medial antebrachial cutaneous response is regarded as the most sensitive sensory abnormality in true neurogenic thoracic outlet syndrome.
	• A T1>C8 pattern of motor and sensory axonal loss is essentially pathognomonic for true neurogenic thoracic outlet syndrome, though some variability may be encountered.
	• Disputed thoracic outlet syndrome is a diagnosis of exclusion.

True neurogenic thoracic outlet syndrome.

Electrodiagnostic studies. Nerve conduction studies and electromyography are helpful in the diagnostic evaluation of patients with suspected thoracic outlet syndrome (31; 25). Demonstrating a T1>C8 pattern of motor and sensory axonal loss is essentially pathognomonic for true neurogenic thoracic outlet syndrome.

(1) Ulnar and medial antebrachial cutaneous sensory nerve action potentials are absent or decreased in amplitude. The medial antebrachial cutaneous nerve is predominantly T1-innervated and may be affected more than the ulnar digit5 sensory nerve action potential, which is predominantly C8-innervated. In one series of 32 patients, the medial antebrachial cutaneous sensory potential was absent in 68% whereas the ulnar-digit5 response was absent in just 6% (30). The medial antebrachial cutaneous response was more sensitive (95%) than other sensory studies.

(2) The median compound muscle action potential recorded over the abductor pollicis brevis muscle is decreased in amplitude. Thenar muscles receive T1>C8 innervation and are affected disproportionately.

(3) The ulnar compound muscle action potential amplitude is normal or slightly decreased. Ulnar innervated muscles receive equal T1 and C8 innervation.

(4) The median sensory nerve action potential is normal. This assesses sensory axons from the C6 to C7 roots, which should be spared.

(5) Although the classic electrodiagnostic findings described above are characteristic, some variability may be encountered in bona fide cases. These include equally severe involvement of C8 and T1 axons, more severe C8 involvement, pure motor abnormalities, needle EMG abnormalities in non-C8/T1 muscles (flexor carpi radialis, biceps), and abnormal median sensory potential from digit 3 (18). Occasional patients with suggestive symptomatology will have normal clinical exams and electrodiagnostic studies, but clearly supportive neuroimaging abnormalities (11).

Imaging studies. In addition to electrodiagnostic studies, imaging studies are also indicated in the evaluation of true neurogenic thoracic outlet syndrome (04; 05). Plain films, CT, and MRI can be utilized to detect structural abnormalities such as a C7 bony anomaly. Fibrous bands are radiolucent on plain films and CT and routine MRI also does not reliably identify these bands. MR neurography is able to detect fibrous bands and individual peripheral nerves, as can high-resolution ultrasound in some cases (26; 15; 22; 10).

Disputed thoracic outlet syndrome. There is no agreed upon “gold standard” diagnostic test for disputed thoracic outlet syndrome. Testing revolves around excluding other thoracic outlet syndrome subtypes and other disorders with a similar presentation. Electrodiagnostic testing is indicated mainly to rule out true neurogenic thoracic outlet syndrome, cervical radiculopathy, median and ulnar entrapments, or other brachial plexopathies. Imaging, including vascular imaging, may be indicated to rule out arterial thoracic outlet syndrome, venous thoracic outlet syndrome, and traumatic neurovascular thoracic outlet syndrome. In one series, 65% of patients with a presumed diagnosis of disputed thoracic outlet syndrome were found to have an alternative diagnosis (27).

Arterial thoracic outlet syndrome. The subclavian artery may be imaged with ultrasonography, CT angiography, MR angiography, or conventional angiography. Positioning of the arm is critical to detect cases of dynamic subclavian artery compression. An associated bony abnormality is identified with plain films or CT scanning. A blood pressure difference of 20 mm Hg between the upper extremities is a rare finding of vascular thoracic outlet syndrome (01).

Venous thoracic outlet syndrome. Venous duplex ultrasonography is utilized to detect thrombosis in the subclavian-axillary veins. Lack of venous compressibility on ultrasonography is a sign of an acute thrombosis when the clot is echolucent (02). Dynamic subclavian vein compression may also occur when the arm is in certain positions and it may be necessary to replicate these positions during imaging. Contrast-enhanced MRI and MR venography are useful when ultrasonography is unrevealing. Patients should also be screened for prothrombotic disorders, particularly those without an identifiable structural abnormality.

Traumatic neurovascular thoracic outlet syndrome. Plain film is utilized to detect clavicular fracture or callus and CT or MRI defines thrombosed pseudoanuerysms. Arteriography and venography can be used to detect vascular abnormalities. Electrodiagnostic testing can characterize concomitant nerve injury, including localization and severity (04; 05).

Management

• Management of true neurogenic thoracic outlet syndrome and arterial thoracic outlet syndromes is surgical.

True neurogenic thoracic outlet syndrome. The slow progression of true neurogenic thoracic outlet syndrome allows reinnervation to keep pace with denervation and most patients may not recognize motor involvement in the earlier stages and often only present when motor features are advanced (04; 05).

The treatment of true neurogenic thoracic outlet syndrome is surgical and involves sectioning of the fibrous band and sometimes the distal aspect of the C7 bony anomaly. A supraclavicular approach is preferred. After removal of the fibrous band, pain and paresthesias often improve. Weakness and atrophy stop progressing but improvement is unlikely as reinnervation is already maximal (04; 05). One randomized controlled trial comparing surgery (transaxillary thoracic outlet decompression) to conservative treatment in patients with neurogenic thoracic outlet syndrome found significant short-term benefit from surgery (08).

Disputed thoracic outlet syndrome. The mainstay of treatment for disputed thoracic outlet syndrome is nonsurgical. Conservative treatments involve correcting postural abnormalities and muscle imbalances and stretching programs (34). Surgical intervention, often first rib resection or scalenectomy, has unclear benefits, and historical cure rates of more than 90% were gross overestimates (04; 05). Brachial plexus and nerve injuries can be serious complications of surgical intervention (32; 04; 05).

Arterial thoracic outlet syndrome. Timely surgical decompression of the subclavian artery by resection of a cervical rib or first thoracic rib or other compressive structure is critical. Additional vascular surgery may be necessary if an aneurysm or thrombosed artery or aneurysm are detected. Prognosis is dependent on prompt diagnosis and treatment.

Venous thoracic outlet syndrome. Anticoagulation is started once venous thoracic outlet syndrome is suspected. Anticoagulation alone results in poor outcomes, with symptoms persisting in over 90% of patients (14). Pulmonary embolism also occurs in up to 15% of patients on anticoagulation alone. When thrombosis of the subclavian-axillary vein is detected, emergent intravascular thrombolysis within the first 10 to 14 days is optimal for recanalization, followed by long-term anticoagulation. Thrombosis also recurs in up to a third of patients if an underlying structural problem is not corrected. Transaxillary first fib resection is the most common method of decompression (09). Prognosis depends on prompt recognition and the severity of vascular damage.

Traumatic neurovascular thoracic outlet syndrome. Treatment of traumatic neurovascular thoracic outlet syndrome often requires surgery to repair the underlying vasculature including pseudoaneurysms or blood vessel tears with hematoma formation (33; 34). Internal fixation of the clavicle may be necessary. Injury to neural structures may require conservative management for incomplete/partial lesions and surgery for neural disruption. Prognosis will depend on severity of axon loss and vascular damage.