Brachial plexus syndromes

INTRODUCTION — The brachial plexus is a network of nerve fusions and divisions that originate from cervical and upper thoracic nerve roots and terminate as named nerves that innervate muscles and skin of the shoulder and arm. Although detailed knowledge of the elements of the network is important for distinguishing between radiculopathy and mononeuropathy, a syndromic approach is more useful for diagnosing lesions involving the plexus itself.

This topic will briefly review the underlying anatomy, pathogenesis, and general clinical features of brachial plexopathies, and discuss specific brachial plexopathies, classified by clinical setting into traumatic, nontraumatic, iatrogenic, and neonatal types.

ANATOMY — Nerve roots from C5 through T1 contribute to the brachial plexus (figure 1 and figure 2). The plexus can be divided into regions that include (from proximal to distal) trunks, divisions, cords, branches, and nerves. Trunks and divisions are further subdivided with a nomenclature based on overall relationships with other upper extremity anatomic structures and include upper, lower, and middle trunks, and posterior, lateral, and medial cords.

●C5 and C6 roots merge to form the upper trunk. The C7 root forms the middle trunk. C8 and T1 roots merge to form the lower trunk.

●The upper trunk divides and gives branches to the lateral and posterior cords. The middle trunk divides and gives branches to the lateral and posterior cords. The lower trunk divides and gives branches to the posterior and medial cord.

●The lateral cord branches and gives rise to the musculocutaneous nerve and contributes to the median nerve. The posterior cord branches and gives rise to the axillary nerve and then becomes the radial nerve. The medial cord branches and contributes to the median nerve and then becomes the ulnar nerve.

●Other nerves arise from various elements of the plexus. The dorsal scapular nerve arises from the C5 root. The long thoracic nerve arises from C5, C6, and C7 roots. The suprascapular nerve arises from the upper trunk.

●Contributions to motor and sensory function vary within the brachial plexus. The largest percentages of motor fibers are from C5 and C6 roots, and the least from C7 and T1 roots. The greatest number of sensory fibers is from the C7 root, with lesser amounts from C5, C6, C8, and T1 roots [1]. Postganglionic sympathetic nerve fibers from vertebral ganglia course through the brachial plexus.

PATHOGENESIS — The pathologic basis and histologic changes seen with brachial plexus lesions vary with the underlying causes, which include compression, transection, ischemia, inflammation, metabolic abnormalities, neoplasia, and radiation therapy. Because the brachial plexus is relatively inaccessible to direct investigation, most pathologic processes are deduced.

●Nerve compression is relatively uncommon because the brachial plexus is protected by bony structures. Contact sports are the most frequent cause of nerve compression injury to the brachial plexus; focal forces to the shoulder region result in brief compression of underlying plexus elements.

●Overt nerve transection occurs with major trauma to the neck and shoulder, causing downward traction on the shoulder and movement of the neck to the contralateral side, or with trauma to the arm, causing upward traction on the arm and shoulder. High-force traction to the plexus may also be associated with avulsion of nerve roots.

●Ischemia due to occlusion of small intraneural (vasa nervorum) vessels is more common than ischemia due to occlusion of large vessels. Small vessel ischemia may be a common pathologic basis for inflammatory, metabolic, and radiation-induced plexopathies [2-4]. Ischemia causes localized axonal damage, resulting in denervation of muscle and skin receptors.

●Inflammation, perhaps leading to small vessel occlusion, is hypothesized to cause brachial plexopathies of acute onset (excluding those associated with mechanical causes). However, precipitating events for such an inflammatory response and its consequences are poorly understood.

●Metabolic abnormalities are the most likely initiating factors underlying plexopathies related to diabetes mellitus. That said, the specific factors are not known and the pathophysiology may include inflammation and focal ischemia [3].

●Neoplastic plexopathies can result from direct pressure by a local cancer mass, but invasion by cancer cells along nerves or tracking along connective tissue is more common [2].

●Radiation treatment for cancer is a common cause of damage to brachial plexus nerves [2]. The toxic effects of radiation may injure axons directly or injure the vasa nervorum causing ischemic changes to axons with multifocal denervation.

EPIDEMIOLOGY — Brachial plexus syndromes are rare, as illustrated by the prevalence of plexopathies associated with cancer (approximately 0.4 percent of patients with cancer) and those associated with radiation treatment (approximately 2 to 5 percent of those treated) [2]. Idiopathic brachial plexopathy, or brachial amyotrophy, has an estimated annual incidence of 2 to 3 per 100,000 [5,6]. In one large series, the male-to-female ratio was 2:1 [7].

CLINICAL FEATURES AND DIAGNOSIS

Symptoms and signs — The onset of symptoms from brachial plexopathies may vary from acute to insidious. Acute onset is usually characterized by pain in the shoulder or upper arm, while insidious onset can manifest as progressive pain, evolving numbness, weakness of selected muscles, or any combination. Early on, distinguishing between symptoms arising from bones and ligaments about the shoulder and those from nerves in the plexus may be difficult. Acute onset, in the absence of trauma, favors a metabolic or inflammatory process. Chronic progression of symptoms in patients with a history of cancer and radiation treatment suggests either as a cause.

Clinical signs of brachial plexopathy include muscle weakness, atrophy, and sensory loss. With a painful plexopathy of acute onset, it may be difficult to distinguish true weakness from reduced effort due to pain. Muscle atrophy may not be appreciated for several weeks. Tendon reflexes may be reduced in weak muscles. Sensory loss commonly involves the axillary nerve distribution, but may be diffuse or reflect the distributions of other involved nerves (figure 3).

Nerve conduction studies and needle electromyography — The primary pathologic lesion in most plexopathies is axonal loss, with demyelination and conduction block as secondary processes. Nerve conduction studies primarily assess terminal segments of nerves, and the distribution of abnormalities can be helpful in localizing lesion sites lying more proximally in the plexus. They can also determine if there are alternative diagnoses, such as nerve entrapment syndromes. Sensory nerve conduction studies are more sensitive to axonal loss than motor nerve studies, and application of a battery of sensory nerve tests can be diagnostically helpful [1].

Needle electromyography (EMG) is the most sensitive test of axonal damage in motor nerves and can further localize the lesion [8]. In addition, essentially any muscle can be studied with needle EMG, and thus any element of the plexus can be assessed. However, abnormal spontaneous activity in the form of positive waves and fibrillation potentials may not be apparent for three weeks after the acute onset of plexopathies.

Imaging — Routine chest and spine films may reveal osseous injuries or altered posture due to muscle weakness. Plain computed tomography (CT) is useful for detecting bony abnormalities, and CT myelography is useful for detecting root avulsions. Magnetic resonance imaging (MRI) is more sensitive for structural abnormalities than CT.

Magnetic resonance neurography is a specialized procedure that can visualize individual roots, segments of the plexus, and peripheral nerves [9-11]. It has low specificity but is more sensitive than conventional MRI for plexus lesions, and can identify local factors relevant to possible demyelination and/or compression, including nerve edema, thickening, and T2 hyperintensities.

Ultrasound has been used to image the brachial plexus [12] and may be able to distinguish preganglionic from postganglionic traumatic lesions noninvasively [13].

TRAUMATIC PLEXOPATHIES — Traumatic injuries are the most common cause of brachial plexus lesions in children and adults [14]. Motor vehicle accidents (particularly involving motorcycle riders), industrial accidents, falls, objects falling on a shoulder, sports injuries, and prolonged pressure on the plexus during deep sleep are among the many causes of closed brachial plexus trauma [14-16]. Open traumatic brachial plexus injuries result from gunshot wounds, lacerations, and animal bites [14]. Open injuries are frequently associated with trauma to nearby blood vessels, with the result that the plexus suffers secondary injury from expanding hematomas, pseudoaneurysms, and arteriovenous fistulas.

In the setting of closed or open traumatic brachial plexus injuries caused by acute trauma, it is important to evaluate the patient for concomitant head injuries, bone fractures, dislocations, rotator cuff tears, and vascular disruptions [17-19]. (See "Initial management of trauma in adults" and "Trauma management: Overview of unique pediatric considerations" and "Management of acute moderate and severe traumatic brain injury" and "Acute mild traumatic brain injury (concussion) in adults" and "Severe traumatic brain injury (TBI) in children: Initial evaluation and management" and "Minor head trauma in infants and children: Management" and "Traumatic causes of acute shoulder pain and injury in children and adolescents" and "Presentation and diagnosis of rotator cuff tears".)

Root avulsions, the burner syndrome, and backpack palsy are types of traumatic plexopathies discussed in further detail below.

Root avulsions — Root avulsions are caused by high-energy traction (stretch) and occur in parallel with brachial plexus injuries [8,14]. Thus, traumatic injuries may include a combination of plexopathy and root avulsions. The torn nerve roots and axons are incapable of regeneration and are not amenable to surgical repair. Thus, the resulting motor and sensory deficits are permanent. Multiple root avulsions are frequent with traumatic injury, resulting in extensive deficits. In addition, most patients develop severe avulsion pain, often involving the hand.

The lowest two brachial plexus roots (C8 and T1) are the most susceptible to root avulsion, while the upper two (C5 and C6) are more susceptible to extraforaminal rupture [8]. Unlike root avulsions, extraforaminal nerve ruptures may be accessible to surgical repair.

Burner syndrome — The burner syndrome (also called the stinger syndrome) is a term that describes the transient burning and stinging sensations experienced during contact sports due to forceful contact by a helmet to the neck or anterior shoulder region. This type of athletic injury causes transient dysfunction of the brachial plexus and occasionally the spinal cord. The upper trunk is most commonly involved, due to downward traction of the shoulder. (See "Burners (stingers): Acute brachial plexus injury in the athlete", section on 'Pathophysiology'.)

Symptoms are usually transient with no nerve damage. However, some cases are associated with denervation, with or without weakness. Some clinicians use the term "burner" to indicate more severe episodes of numbness in limbs that implicate damage to the spinal cord. (See "Burners (stingers): Acute brachial plexus injury in the athlete", section on 'Clinical features'.)

The diagnosis of burner syndrome is straightforward in the context of American football or other contact sports. There may be a degree of weakness that raises the question of a more substantial injury. Needle electromyography (EMG) is usually normal, but can detect mild degrees of denervation when there is no weakness, and more marked changes when there is weakness. However, EMG is only indicated if symptoms persist for more than three weeks, since the effects of acute injury are not evident prior to this time. The physical examination should include assessment for a myelopathy if symptoms suggest spinal cord damage, and when there is a concern, an imaging study of the cervical spine is appropriate. (See "Burners (stingers): Acute brachial plexus injury in the athlete", section on 'Diagnosis and evaluation'.)

Since most burners and stingers are transient, lasting minutes to hours, no work-up or treatment is usually required. Those associated with weakness typically improve without treatment, but refraining from football and other contact sports is appropriate until strength is regained. (See "Burners (stingers): Acute brachial plexus injury in the athlete", section on 'Management'.)

Backpack palsy — Backpack palsy (also known as rucksack paralysis and cadet palsy) is an upper plexus disorder. Patients with this condition present with painless arm and/or shoulder weakness, usually unilateral, after wearing a backpack or similar apparatus (eg, child carrying harness) for a prolonged period of time, resulting most often in an upper trunk lesion [8]. Some sensory loss is also present in the same distribution.

The pathogenesis of backpack palsy is thought to be direct compression from the weight of the backpack. The lesions are predominantly demyelinating conduction block, and full recovery usually ensues over a few months. In a minority, axon loss predominates, and recovery may be incomplete or slow.

Prognosis and treatment — The natural history of traumatic brachial plexopathies, whether from forceful trauma or iatrogenic trauma, is difficult to document but is generally poor, with most natural improvements occurring within six months [20]. However, there are few published data regarding the outcome of unoperated traumatic plexopathies.

Most surgical interventions are performed after documenting no improvement over three to four months, although there are situations when emergent intervention is appropriate. The type of surgical intervention is dependent upon the nature and degree of the lesion, and includes neurolysis, nerve grafts, nerve transfers, and tendon and muscle transfers [21-24]. There are data suggesting that delaying surgical treatment for longer than two to six months diminishes the chance for an improved level of function [25-27]. Injuries that have a degree of axonal continuity may have a more favorable outcome, and nerve grafts are most successful for injuries of C5, C6, and C7 roots; upper and middle trunks; and lateral and posterior cords [28].

Outcome may be partially dependent upon surgical experience with brachial plexus injuries, and data from experienced centers support improved function in approximately 60 percent after surgical interventions. However, many patients remain disabled, with one survey finding that one-half of those previously employed did not return to work [29]. In a case report, three patients with a traumatic global brachial plexus injury regained some useful hand function 2 to 17 years after the injury with a novel bionic reconstruction technique [30]. This technique involves a combination of selective nerve and muscle transfers, elective amputation of the nonfunctional hand, reconstruction with a prosthetic hand, and cognitive rehabilitation to activate muscles attached to the prosthetic hand. More data are needed to determine whether there is sufficient benefit to warrant this heroic procedure.

NONTRAUMATIC PLEXOPATHIES — Nontraumatic brachial plexopathies include neuralgic amyotrophy, hereditary brachial plexopathy, neoplastic and radiation-induced plexopathy, thoracic outlet syndrome (TOS), and brachial plexopathy related to diabetes.

Neuralgic amyotrophy — Neuralgic amyotrophy is considered to be an inflammatory disorder of the brachial plexus. It is known by a number of terms, including Parsonage-Turner syndrome, paralytic brachial neuritis, idiopathic brachial plexopathy, brachial plexus neuropathy, and acute brachial radiculitis. It has been described in children and adults [31].

The pathology for all forms of idiopathic brachial plexopathy is speculative, as most cases are neither biopsied nor come to autopsy. However, careful clinical and electrophysiologic assessment suggests that neuralgic amyotrophy is a multifocal rather than a global process, with motor nerves seeming more vulnerable than sensory [32,33]. Hypothesized underlying causes focus on immune-mediated processes [34]. In this regard, approximately 50 percent of patients describe some type of antecedent event or possible predisposing condition, such as infection, exercise, surgery, pregnancy and puerperium, or vaccination [4,7].

Classic form — In its classic form, neuralgic amyotrophy is characterized clinically by the onset of severe pain followed by patchy weakness in the distribution of the upper and/or middle brachial plexus, usually involving winging of the scapula. There is rapid or subacute onset of unilateral shoulder girdle and lateral arm pain, often awakening the individual in the night. The pain can be excruciating and may last up to four weeks before subsiding [7]. Bilateral onset of pain has been reported in up to 29 percent of patients, almost always with asymmetric involvement [7]. Sensory symptoms occur in a majority of patients, most commonly manifesting as hypesthesia and/or paresthesia, and usually involving the lateral shoulder and arm and/or the hand.

The time to onset of weakness is highly variable, as illustrated by the finding that weakness occurs within the first 24 hours after onset of pain in one-third of patients, and more than two weeks after onset of pain in approximately one-quarter [7]. The distribution of muscle atrophy and weakness may be limited to muscles supplied by one nerve, or in extreme cases may involve all muscles of the shoulder or arm. There is a predilection for muscles innervated by the suprascapular, long thoracic, musculocutaneous, radial, anterior interosseous, and axillary nerves [7,33]. Variable weakness may also be present in the contralateral limb. Recovery of strength begins within several months, and the maximal degree of recovery may not be achieved for several years [4].

Clinical variability — It is worth emphasizing that the pattern of nerve involvement observed in neuralgic amyotrophy can be more diverse than the classic syndrome [34]. Any part of the brachial plexus or muscles it innervates may be involved [7]. In very severe cases, there may be bilateral arm paralysis. Other patients may have involvement of single or multiple nerves in the limb, more akin to a mononeuritis or mononeuritis multiplex. Individual limb nerves that may be affected include long thoracic, anterior interosseous, radial, median, and a variety of cutaneous nerves [32]. As an example, isolated anterior interosseous nerve involvement may be the only motor manifestation in some patients [7].

In a minority of patients, attacks may involve nerves outside of the brachial plexus, including the lumbosacral plexus, phrenic nerve, and recurrent laryngeal nerve [5,7]. Symptomatic diaphragm dysfunction due to unilateral or bilateral phrenic neuropathy is often unrecognized but has been identified in approximately 7 percent of cases of neuralgic amyotrophy [7,35]. The most common symptoms are exertional dyspnea, sleep disturbance, and orthopnea. Chest radiograph has suboptimal sensitivity for detecting diaphragm dysfunction, particularly when involvement is bilateral [35]. Spirometry in the supine and sitting positions is more sensitive and typically shows a decrease in forced vital capacity (FVC) that is more pronounced in the supine position. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Diagnostic evaluation'.)

A similar clinical disorder to neuralgic amyotrophy occurs in association with a variety of surgical procedures [36]. Onset is heralded by shoulder girdle pain 1 to 14 days after surgery, so that direct nerve traction and compression are not likely causative factors. Weakness ensues within several days and has similar distributions to that seen in idiopathic brachial plexopathy. Electrodiagnostic studies support axonal loss. Recovery is good.

Diagnosis — Neuralgic amyotrophy is primarily a clinical diagnosis supported by electrodiagnostic testing. Clinical suspicion is based upon the pattern of initial sudden and severe pain followed by atrophic weakness with slow recovery. Nerve conduction studies are supportive and can exclude more common mononeuropathies, while needle electromyography (EMG) is important to document denervation. The pattern of denervation supports either specific nerve involvement or a more patchy distribution.

The primary role of laboratories and imaging is to exclude alternative causes of an acute plexopathy such as infection (eg, Lyme disease, human immunodeficiency virus [HIV]), diabetes, or malignancy [37-40]. We typically obtain a complete blood count, serum glucose and HbA1C, erythrocyte sedimentation rate (ESR), and serologic testing for rarely implicated but treatable infections including Borrelia burgdorferi, syphilis, and HIV. In most patients with a suspected idiopathic brachial plexopathy, one-time imaging is indicated to exclude the possibility of a mass lesion, especially in those with atypical clinical symptoms or a history suggestive of malignancy. If EMG localizes to the plexus, magnetic resonance imaging (MRI) of the brachial plexus without and with contrast is the best study, provided there are no contraindications to MRI; if EMG or clinical features suggest possible cervical root involvement, MRI of the cervical spine should also be obtained in most cases. Lumbar puncture is not indicated unless there is suspicion for an alternative infectious, inflammatory, or neoplastic etiology involving the cerebrospinal fluid.

Laboratory studies in patients with neuralgic amyotrophy are normal, and imaging studies are often unrevealing. MRI and magnetic resonance neurography of the brachial plexus and affected nerves may show abnormalities including focal thickening, increased T2 signal, and gadolinium enhancement, but sensitivity appears to be low, particularly in the acute phase of neuralgic amyotrophy [7,41-43]. Neuromuscular ultrasound at centers with appropriate technical expertise in this method may reveal focal or diffuse nerve enlargement, focal constriction, torsion, or fascicular entwinement, though data are limited [43,44]. Multifocal nerve involvement often obviates the need for imaging. (See "Diagnostic ultrasound in neuromuscular disease".)

Patients with symptoms of diaphragm dysfunction (eg, orthopnea, exertional dyspnea) should undergo chest radiograph and spirometry. Ultrasound of the diaphragm may be the most accurate test for neuromuscular diaphragmatic dysfunction [45,46]. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Diagnostic evaluation' and "Diagnostic ultrasound in neuromuscular disease", section on 'Physics of neuromuscular sonography'.)

Management and prognosis — There is no specific treatment for neuralgic amyotrophy. Management is conservative. Physical and occupational therapy may be helpful to preserve shoulder, arm, and hand functional capacity but will not hasten recovery [47]. Glucocorticoids have been advocated by some [34], but no clinical studies have demonstrated efficacy. In the first weeks, analgesic drugs, including narcotics, may be required to manage patients with severe pain.

Recovery occurs slowly over one to three years, and some patients have persistent disability, as illustrated by the following observations:

●An early series of 99 patients with neuralgic amyotrophy suggested that most had good recovery, essentially to normal strength [4].

●Another series included 199 patients with idiopathic neuralgic amyotrophy [7]. Among 39 with three or more years of follow-up, mild, moderate, or severe paralysis was still present in 69, 14, and 3 percent, respectively. Overall, recurrence of idiopathic neuralgic amyotrophy was observed in 26 percent of patients, with a median time to recurrence of just over two years. This recurrence rate is higher than the estimated rate of 5 percent previously reported [4].

●A third series surveyed 248 patients with either idiopathic or hereditary neuralgic amyotrophy; approximately 90 percent had the idiopathic form [48]. After 6 to 36 months of follow-up, residual pain or severe fatigue was present in approximately 60 percent.

●Patients with phrenic neuropathy usually have spontaneous improvement within two years, but persistent complaints are common [35]. Treatment of diaphragm dysfunction consists primarily of supportive measures; overnight polysomnography and noninvasive positive pressure ventilation is typically indicated in more symptomatic patients. (See "Treatment of bilateral diaphragmatic paralysis in adults".)

There is a pathologically distinct, yet clinically similar, hereditary recurrent brachial plexopathy that should be considered when there are multiple episodes in an individual or among related family members. (See 'Hereditary brachial plexopathy' below.)

Hereditary brachial plexopathy — Hereditary brachial plexopathy (MIM 162100), also known as hereditary neuralgic amyotrophy, is a rare autosomal dominant disorder characterized by recurrent, painful brachial plexopathies. Genetic studies in families with this condition identified variants in the septin 9 gene (SEPT9) on chromosome 17q25 [49-51]. Hereditary brachial plexopathy is distinct from hereditary neuropathy with predisposition to pressure palsies (HNPP), a recurrent demyelinating neuropathy that can involve the brachial plexus. (See "Charcot-Marie-Tooth disease: Genetics, clinical features, and diagnosis", section on 'Hereditary neuropathy with liability to pressure palsy'.)

Childhood onset of hereditary brachial plexopathy is not unusual [52]. In one series of 47 patients, the age at onset ranged from 3 to 54 years, with a mean of 28 years [7]. Many patients exhibit a relapsing-remitting course characterized by attacks that resolve spontaneously, either completely or incompletely, leaving additive residual weakness. Reported triggering events include physical exertion, anesthesia, surgery, pregnancy, and childbirth [53].

The disorder can also follow a progressive pattern. In one study that analyzed 101 attacks in 24 patients from nine different families, both a classic relapsing-remitting type and a chronic undulating type with exacerbations were observed [54]. Only one type occurred per family.

Attacks are heralded by pain and paresthesias, followed by paresis of the shoulder and arm. While any nerve in the brachial plexus can be involved, injury to the upper part of the brachial plexus is most frequent. Winging of the scapula caused by long thoracic nerve involvement is common, and facial weakness and autonomic nervous system dysfunction may occur [52]. Sympathetic activity with flushing can be observed. Sensory involvement (mainly involving hypesthesia and paresthesias of the shoulder, arm, or hand) is present in most patients [7]. Nerves outside the brachial plexus can also be involved, including the lumbosacral plexus, the phrenic nerve (causing weakness of the diaphragm), and the recurrent laryngeal nerve [7].

Characteristic somatic features of hereditary brachial plexopathy include short stature, hypotelorism, a small face, unusual skin folds, and creases on the neck [55].

Although electrophysiologic studies are limited, sensory nerve conduction velocity is typically normal, while motor conduction latencies are prolonged. These findings suggest an axonal neuropathy, but are also compatible with focal demyelination, conduction block, or a chronic process with remyelination [56].

The histopathology of hereditary brachial plexopathy is nonspecific. Muscle demonstrates pathologic changes consistent with neurogenic atrophy. Both motor and sensory nerves show widely dispersed pathologic involvement throughout the brachial plexus; the changes involve very focal damage to individual nerves with lesions restricted to isolated fascicles within the nerve [57]. The changes are predominantly demyelinating, but axonal changes are also present.

Diagnosis — A pattern of recurrent brachial plexopathies and a similar history in related family members should raise consideration for the diagnosis of hereditary neuralgic amyotrophy. Finding of dysmorphic features is strongly supportive.

Management and prognosis — Most patients with hereditary brachial plexopathy have some degree of disability. In a series that followed 10 patients for three or more years, mild, moderate, or severe weakness was present in four, three, and two patients, respectively [7]. Management is supportive, although glucocorticoids have been given in uncontrolled studies [53].

Neoplastic and radiation-induced brachial plexopathy — These conditions are briefly reviewed here, and discussed elsewhere in greater detail. (See "Overview of cancer pain syndromes", section on 'Tumor-related neuropathic pain' and "Overview of cancer pain syndromes", section on 'Postradiation pain syndromes'.)

Neoplastic — Breast and lung cancers are the most frequent neoplasms leading to brachial plexopathy. Pain in the shoulder and axilla is the most common presenting symptom of neoplastic brachial plexopathy. Invasion of the lower plexus (inferior trunk and medial cord) occurs more frequently than invasion of the upper trunk. (See "Overview of cancer pain syndromes", section on 'Plexopathies'.)

The Pancoast syndrome is most commonly due to non-small cell lung cancer in the superior sulcus, and is associated with a Horner syndrome in three-quarters of patients. Weakness usually occurs in a lower plexus distribution, but may also be more widespread and patchy in distribution. (See "Superior pulmonary sulcus (Pancoast) tumors" and "Horner syndrome".)

In the setting of a known neoplasm and radiation therapy, distinguishing between cancer recurrence and radiation-induced plexopathy can be challenging. In general, compared with radiation-induced brachial plexopathies, neoplastic plexopathies are more likely to produce pain at symptom onset, more often involve the lower plexus, and are more frequently associated with a Horner syndrome.

Primary brachial plexus tumors, such as schwannomas or neurofibromas, are uncommon, and most occur as solitary tumors. These rarely cause symptomatic plexopathies. However, multiple tumors occur in patients with neurofibromatosis type 1, and these are more likely than solitary tumors to present with pain or clinical deficits.

The diagnosis of neoplastic brachial plexopathy is suggested by the clinical setting, including symptoms, past medical history (eg, smoking), and physical examination, particularly the breast examination. Imaging of the chest by computed tomography (CT) is the most sensitive way to detect a pulmonary tumor. A Horner syndrome in the setting of shoulder pain and weakness is strongly supportive of a pulmonary tumor. Electrodiagnostic studies and MRI of the brachial plexus are useful to more precisely define the relationship between the tumor and the brachial plexus (image 1 and image 2).

There are limited data on the benefit of treating neoplastic brachial plexopathy with radiation therapy to the plexus; the goal is mostly directed at reducing pain. Medical management of pain is appropriate if radiation therapy is not beneficial. These options are discussed in greater detail separately. (See "Cancer pain management: General principles and risk management for patients receiving opioids" and "Cancer pain management with opioids: Optimizing analgesia" and "Cancer pain management: Role of adjuvant analgesics (coanalgesics)".)

Radiation-induced — Radiation-induced brachial plexopathy is a consideration in patients with cancer who develop plexopathy after radiation therapy in the vicinity of the brachial plexus. As mentioned above, either cancer recurrence or radiation therapy can cause a brachial plexopathy in this setting.

Lung and breast cancers are the most common neoplasms that are treated with radiation therapy in the vicinity of the brachial plexus, but any patient with radiation therapy to the region is at risk for subsequent plexopathy. Nevertheless, brachial plexopathy is most frequently seen in females with early stage breast cancer, who have been treated with conservative surgery and radiation therapy [58-60]. (See "Breast-conserving therapy" and "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

The features of brachial plexopathy in this setting are illustrated by an analysis of 1624 females, in which the following findings were noted [58]:

●The incidence of brachial plexopathy was 1.3 percent among females who received less than 50 Gy to the axilla, and 1.8 percent in those receiving radiation to the supraclavicular fossa.

●The incidence was higher in females who also received chemotherapy (4.5 percent) and in those treated with axillary doses greater than 50 Gy (5.6 percent).

●The median time to development of symptoms after therapy was approximately 10 months.

The use of larger radiation fractions may increase the risk of developing radiation-induced brachial plexus damage. In a series of 449 females, the incidence of plexopathy was 6 percent in patients receiving 45 Gy in 15 fractions versus 1 percent for those receiving 54 Gy in 30 fractions [59].

There are few clinical features that distinguish radiation-induced damage from that due to cancer, but radiation-induced plexopathy frequently has less pain than neoplastic brachial plexopathy, and what pain there is typically occurs later in the course of symptoms. In addition, the degrees of paresthesia and weakness typically are more severe with radiation-induced plexopathy than with neoplastic brachial plexopathy. Survival in the setting of radiation-induced plexopathy is related to the underlying cancer and is good with respect to the side effects of radiation.

The diagnosis of a radiation-induced rather than neoplastic plexopathy is supported by the presence of fasciculations on electrodiagnostic testing. Myokymic discharges add further support to the diagnosis, since these are rarely found in other conditions. However, myokymic discharges are not a universal feature of radiation-induced plexopathy, and their absence does not exclude the diagnosis.

Symptomatic management of patients with radiation-induced plexopathy includes medications used for other types of chronic or neuropathic pain such as gabapentinoids, glucocorticoids, and tricyclic antidepressants [61,62]. Individual reports have described benefit for refractory cases with hyperbaric oxygen therapy, neurolysis, or pulsed radiofrequency ablation [63-65]. Medications for symptomatic management are discussed in greater detail separately. (See "Cancer pain management: Role of adjuvant analgesics (coanalgesics)".)

Thoracic outlet syndrome — Thoracic outlet syndrome (TOS) is a term used to denote a variety of upper extremity syndromes, with only a small number having a neurologic basis [66]. TOS is generally divided into five subtypes, which are [67,68]:

●Arterial TOS

●Venous TOS

●Traumatic neurovascular TOS

●True neurogenic TOS

●Disputed TOS

The vascular forms of TOS are reviewed in detail separately. (See "Overview of thoracic outlet syndromes".)

True neurogenic TOS is rare, with an estimated incidence of 1:1,000,000, and occurs most commonly in females, with a female-to-male ratio of 9:1 [69]. Symptoms of true TOS include slowly progressive unilateral atrophic weakness of intrinsic hand muscles and numbness in the distribution of the ulnar nerve, with occasional numbness of the ulnar aspect of the forearm. The motor involvement is much greater than the sensory involvement [66]. Weakness and atrophy involve the thenar eminence (median-innervated hand intrinsic muscles) more than the ulnar-innervated hand intrinsic muscles, while medial forearm muscles are less involved. The syndrome may be caused by a taut congenital fibrous band from the first rib to the tip of an elongated C7 transverse process or to a rudimentary cervical rib. The lower portion of the plexus is stretched over this band, and chronic traction injury results (figure 4). This explains why true TOS has the clinical features of a lower trunk plexopathy [69]. Other potential causes of TOS include hypertrophy of the scalene, subclavius, or pectoralis minor muscles, as might be seen in weight lifters or other kinds of athletes. (See "Overview of thoracic outlet syndromes", section on 'Pathogenesis'.)

The incidence of the nonneurogenic forms of TOS is less clear. Arterial and venous forms of TOS are caused by compression of the subclavian artery or vein. Patients may present with arm ischemia (claudication and/or acute embolic events) or venous thrombosis. (See "Overview of thoracic outlet syndromes", section on 'Arterial TOS' and "Overview of thoracic outlet syndromes", section on 'Venous TOS'.)

Disputed TOS (also called nonspecific TOS) is the most controversial form [67,68,70,71]. Proponents of this entity believe that pathologic processes in the thoracic outlet, such as soft tissue anomalies that can only be appreciated at time of surgery, are the cause of a myriad of symptoms affecting the neck, shoulder, and arm, including involvement of upper trunk nerves [70]. Other experts consider disputed TOS to be a cervicoscapular pain syndrome because it lacks a clear anatomic abnormality, an established pathogenesis, consistent clinical manifestations, and a reliable method of diagnostic testing [67,68].

Diagnosis — The diagnosis of true neurogenic TOS is based on a highly characteristic pattern of nerve conduction abnormalities involving the C8 and T1 fibers, and disproportionally involving the T1 sensory and motor fibers more than the C8 fibers [66,72,73]:

●Reduced or absent ulnar and medial antebrachial cutaneous sensory responses and normal median sensory response

●Reduced or absent ulnar and median motor responses, with the median response often more affected than the ulnar

Needle EMG shows denervation in ulnar and median innervated muscles [72].

Imaging studies in true neurogenic TOS are of limited diagnostic utility. Cervical ribs can be visualized on plain films, but the fibrous band compressing the brachial plexus is radiolucent and therefore cannot be demonstrated reliably by plain films or CT [66,74]. There are sparse and inconsistent data regarding the ability of MRI to identify a fibrous band or distortion of the brachial plexus (image 3) in patients with true neurogenic TOS [66,75-78].

The diagnosis of true vascular TOS is supported by abnormal arteriography or venography, while electrodiagnostic tests are normal. The diagnosis of axillosubclavian vein thrombosis is discussed separately. (See "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Diagnosis'.)

Most advocates of disputed TOS maintain that testing will be normal and the diagnosis is purely clinical with confirmation at surgery.

Management — With true neurogenic TOS, treatment options include physical therapy, botulinum toxin injections, or surgical release of the fibrous band or resection of the rudimentary cervical rib [79-81]. Symptoms of pain typically respond, but strength is unlikely to return in the setting of axonal damage [66,72].

Decompressive surgery for vascular TOS may also be helpful. The treatment of venous and arterial TOS is reviewed in detail elsewhere. (See "Overview of thoracic outlet syndromes", section on 'Approach to management' and "Overview of thoracic outlet syndromes", section on 'Thoracic outlet decompression'.)

Surgery for disputed TOS is not to be undertaken lightly because of high postoperative complication rates, which include postoperative iatrogenic brachial plexopathy [69,82]. Conservative measures include passage of time, weight reduction, and a strengthening program to improve sloping shoulders and posture [83].

Diabetic-related brachial plexopathy — Plexopathies related to diabetes mellitus usually involve the lumbosacral plexus, but upper extremity involvement has also been observed as part of the syndrome. In contemporary series, upper extremity involvement occurs in up to one-third of patients and may be in the form of mononeuropathies of the ulnar and median nerves, or at more proximal sites in the brachial plexus [84]. Most upper extremity symptoms are in association with lumbosacral plexus involvement, and thus, clinical features in the arm, such as presence of pain, are not fully reported.

Since most cases of brachial plexus involvement occur in the setting of lumbosacral plexus symptoms, the diagnosis of brachial symptoms is linked. Needle EMG studies show denervation in the distribution of a nerve or more diffusely in the plexus.

Lumbar polyradiculopathy and diabetic amyotrophy are discussed in greater detail elsewhere. (See "Lumbosacral plexus syndromes" and "Diabetic amyotrophy and idiopathic lumbosacral radiculoplexus neuropathy".)

IATROGENIC PLEXOPATHIES — Iatrogenic brachial plexopathies related to surgery and other medical procedures account for approximately 7 to 10 percent of all brachial plexopathies [8,85]. Classic postoperative paralysis, postmedian sternotomy plexopathy, medial fascial compartment syndrome, and nerve injury associated with regional anesthetic blocks are briefly reviewed in the following sections. An iatrogenic plexopathy has also been reported following surgery for the disputed form of thoracic outlet syndrome (TOS). (See 'Thoracic outlet syndrome' above.)

Classic postoperative paresis — Classic postoperative paresis is caused by traction or pressure during surgery [8,14]. The presentation is painless weakness in the distribution of the upper brachial plexus. Some cases are accompanied by paresthesias, and occasional cases are bilateral. The lesions are predominantly demyelinating conduction block, and most patients have rapid and complete recovery unless there is significant axonal loss. Thus, conservative management is employed.

Postmedian sternotomy plexopathy — As the name suggests, postmedian sternotomy plexopathy occurs in the setting of open heart surgery and other operations requiring median sternotomy [8,14]. The typical presentation is that of hand weakness accompanied by paresthesias, and sometimes pain, involving the fourth and fifth fingers. Weakness of muscles supplied by C8 via the median nerve (eg, flexor pollicis longus) and radial nerve (eg, extensor indicis proprius, extensor pollicis brevis) clinically distinguishes this from an ulnar neuropathy. Localization is aided by electrodiagnostic studies.

Although the mechanism is not entirely clear, the leading hypothesis is that this type of plexopathy results from traction injuries to the C8 anterior primary ramus [14]. The lesions are mainly demyelinating conduction block, and the prognosis for full recovery is generally good unless there is significant axon loss.

Anesthetic block plexopathy — Plexopathy after regional infraclavicular brachial plexus blockade has been described with a frequency of 1 to 4 percent [86]. Mechanisms include trauma from the infusion needle, hematoma formation, and neurotoxicity from local anesthetic. Evaluation includes imaging and electromyography (EMG).

Medial brachial fascial compartment syndrome — The medial brachial fascial compartment extends from the clavicle to the elbow and is formed by the medial intramuscular septum, which divides into two fascial extensions that enclose the neurovascular bundle, including the five terminal nerves of the brachial plexus [87]. Puncture of the axillary or brachial artery during procedures such as arteriography or axillary regional anesthetic blocks can produce an expanding hematoma that causes a compartment syndrome and compresses one or more of the terminal nerves [8,14,87-89]. The median and ulnar nerves are most frequently affected.

Initial symptoms of the medial brachial fascial compartment syndrome may be delayed for two weeks or longer after the procedure [14]. Unilateral pain and paresthesia are followed by progressive weakness. Distal pulses typically remain normal. Urgent surgical decompression may improve recovery, which is otherwise poor [8,90].

NEONATAL BRACHIAL PLEXUS PALSY — Neonatal brachial plexus palsy (NBPP) is an uncommon disorder identified by arm weakness at birth. It may involve any of the nerve roots from C5 to T1. NBPP is discussed in detail elsewhere. (See "Neonatal brachial plexus palsy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neuropathy".)

SUMMARY

●Anatomy – Nerve roots from C5 through T1 contribute to the brachial plexus (figure 1). The plexus can be divided into regions that include (from proximal to distal) trunks, divisions, cords, branches, and nerves. Trunks and divisions are further subdivided into upper, lower, and middle trunks and posterior, lateral, and medial cords. (See 'Anatomy' above.)

●Clinical features – The onset of symptoms from brachial plexopathies may be acute or insidious. Acute onset is usually characterized by pain in the shoulder or upper arm, while insidious onset can manifest as progressive pain, evolving numbness, and/or weakness of selected muscles. Clinical signs include muscle weakness, atrophy, and sensory loss. (See 'Symptoms and signs' above.)

●Traumatic plexopathies – Traumatic injuries are the most common cause of brachial plexus lesions. Motor vehicle accidents, industrial accidents, falls, objects falling on a shoulder, and sports injuries are among the many causes of closed brachial plexus trauma. Open traumatic brachial plexus injuries may result from gunshot wounds, lacerations, and animal bites. (See 'Traumatic plexopathies' above.)

●Neuralgic amyotrophy – Neuralgic amyotrophy is characterized clinically by the onset of severe pain followed by patchy weakness in the distribution of the upper and/or middle brachial plexus, usually involving winging of the scapula. Sensory symptoms typically involve the lateral shoulder and arm and/or the hand. (See 'Neuralgic amyotrophy' above.)

●Hereditary brachial plexopathy – Hereditary brachial plexopathy is a rare autosomal dominant disorder characterized by recurrent, painful brachial plexopathies. In some families the cause has been identified as variants in the SEPT9 gene. (See 'Hereditary brachial plexopathy' above.)

●Neoplastic and radiation-induced brachial plexopathy – Neoplastic brachial plexopathy is most frequently related to breast and lung cancer. Pain in the shoulder and axilla is the most common presenting symptom of neoplastic brachial plexopathy. Invasion of the lower plexus (inferior trunk and medial cord) occurs more frequently than invasion of the upper trunk. (See 'Neoplastic and radiation-induced brachial plexopathy' above and "Overview of cancer pain syndromes", section on 'Plexopathies'.)

Radiation-induced brachial plexopathy is a consideration in patients with cancer who develop plexopathy after radiation therapy in the vicinity of the brachial plexus. Either cancer recurrence or radiation therapy can cause a brachial plexopathy in this setting. (See 'Neoplastic and radiation-induced brachial plexopathy' above and "Overview of cancer pain syndromes", section on 'Plexopathies'.)

●Thoracic outlet syndrome – Thoracic outlet syndrome (TOS) is a term used to denote a variety of upper extremity syndromes, with a minority having a neurologic cause. Symptoms of neurogenic TOS include slowly progressive unilateral atrophic weakness of intrinsic hand muscles and numbness in the distribution of the median and ulnar nerve. (See 'Thoracic outlet syndrome' above.)

●Diabetic-related brachial plexopathy – Plexopathies related to diabetes mellitus usually involve the lumbosacral plexus, but additional upper extremity involvement may also occur. Upper extremity diabetic plexopathy may be at proximal sites in the brachial plexus. (See 'Diabetic-related brachial plexopathy' above.)

●Iatrogenic brachial plexopathy – Iatrogenic brachial plexopathies related to surgery and other medical procedures include classic postoperative paralysis, postmedian sternotomy plexopathy, and medial fascial compartment syndrome. (See 'Iatrogenic plexopathies' above.)