Neoplastic Brachial Plexopathy 

Updated: Jan 04, 2016
Author: Mark A Wren, MD, MPH; Chief Editor: Robert H Meier, III, MD 

Overview

Background

Neoplastic brachial plexopathy (NBP) is an uncommon diagnosis in most physiatrists' offices, but the condition bears review as it can mimic symptoms of many common upper limb neuropathies. Approximately 10% of all peripheral nerve lesions involve some type of brachial plexus lesion. Neoplastic invasion of the brachial plexus is an uncommon, though not rare, cause of plexopathy. This article reviews the more common issues associated with physiatric treatment of patients with NBP.[1]

Pathophysiology

Lesions of the brachial plexus occur most often secondary to neoplasms that reach the plexus by direct extension (Pancoast syndrome) or, more commonly, by metastasis through lymphatics from the axilla. Pain in the shoulder, radiating down the limb, may be observed, as well as pain in the medial forearm and hand with lower trunk innervation (C8-T1 roots) in some series. The most common pathophysiology revealed on electrodiagnostic tests is axonal loss. Peripheral pain mechanisms may include lowering of the nociceptor threshold by prostaglandins and other noxious chemical substances and persistent nociceptor stimulation. Compression or infiltration of the nerves of the plexus by a tumor may produce neuralgia and inflammation.

Epidemiology

Frequency

United States

Approximately 14% of all upper limb neurologic lesions are due to brachial plexopathy of all types. Neoplastic plexopathies were responsible for 1.4 and 14.5% of symptoms in 2 series of patients who had undergone surgery. Insufficient data have been published to determine the frequency of NBP, but symptomatic NBP has been estimated to occur in 4% of patients with lung cancer and 2% of patients with breast cancer.

International

The international incidence of NBP is unknown.

In a single institution in Ireland, a 5-year retrospective study of 20 MRIs performed in patients with neoplasms, 6 (30%) confirmed a diagnosis of NBP.[2]

Mortality/Morbidity

Primary neoplasms of the brachial plexus generally are benign, while secondary neoplasms are malignant. Most secondary tumors are metastatic, contributing to higher mortality.[3]

Sex

Solitary neoplastic lesions of the brachial plexus are more common in females. Neurofibromas demonstrate a male-to-female ratio of 1:1.

Age

Incidence of metastatic neoplasm of the brachial plexus increases with age; thus, the condition is more common in elderly patients.

 

Presentation

History

Pain is the most common presenting symptom of NBP (seen in 89% of the Kori series).[4] In one series, 17 of 55 patients presented with brachial plexopathy as the initial manifestation of cancer. Patients with NBP may present with shoulder pain and paresthesias with radiation of pain into the medial forearm and/or hand. Symptoms often are related to breast or lung metastases or lymphoma in a generalized plexus involvement, sometimes with a lower trunk predominance. Symptoms may be diffuse but more often involve the C8-T1 dermatomes and myotomes (mimicking ulnar neuropathy or C8 or T1 radiculopathy).

A Korean case study described thoracic outlet syndrome caused by schwannoma of the brachial plexus, initially suspicious for C8-T1 radiculopathy by electromyography (in the absence of contralateral limb studies to show low amplitudes); however, MRI of the brachial plexus later revealed a mass confirmed to be schwannoma.[5]

The Pancoast syndrome (superior pulmonary sulcus tumor) usually is caused by carcinoma at the lung apex, encroaching on the lower trunk of the brachial plexus. Patients with this condition frequently are males with a history of cigarette smoking. For primary brachial plexus tumors, usually from the nerve sheath (neurofibromas and schwannomas), slightly higher incidence is noted in the upper brachial plexus; thus, symptoms appear in the C5-C6 dermatomes and myotomes (mimicking C5 or C6 radiculopathy or possibly carpal tunnel syndrome).

Radiation-induced brachial plexopathy (RBP) is another relevant topic since it can be confused with NBP. As treatment may be different for the two conditions, differentiation between RBP and NBP is important, although it may be difficult. As many as 73% of patients who have undergone radiotherapy at more than 60 Gy develop plexopathy. Overall incidence of brachial plexopathy is approximately 1.8% of treated patients; however, several factors play a role in development of the condition, including dose (incidence is higher with doses more than 50 Gy), volume irradiated, and treatment technique, as well as whether chemotherapy is administered concurrently. Emami reports 5% incidence of NBP at 5 years when the patient has been treated at doses of 60 Gy to the entire plexus; however, up to one third of patients with RBP find that the deterioration may stop after several years.

  • Some historical findings suggestive of NBP include the following:

    • Onset of limb pain less than 6 months following radiation

    • Rapid progression

    • Horner syndrome (in two thirds of patients with Pancoast syndrome)

    • Severe pain predominant

    • Other metastases

    • Focal mass or neoplasm on biopsy

  • The most reliable feature of NBP (in 80% of patients) is early severe unrelenting pain. Fewer than 20% of RBP patients present with pain, and approximately 33% have minimal or no pain throughout the course of the disease. Two thirds of patients with RBP show severe neurologic deficit progression over several years, while in one third of patients, progression spontaneously ceases after 1-3 years.[6] More common findings in RBP include the following:

    • Slowly progressive course, duration greater than 4 years

    • Predominant paresthesias

    • Median sensory amplitude decreased early

    • Involvement of the upper trunk or C5-C6 portions of the plexus

    • Conduction block on supraclavicular stimulation

    • Myokymia on needle examination

Physical

Examination findings depend on the specific parts of the plexus involved. As can be inferred from the information above, weakness in the hand intrinsics and sensory loss in the C8 and/or T1 dermatomes may be present with the most common lower trunk involvement. For more widespread involvement, motor and sensory loss may be present throughout the limb.

Less common primary neoplasms may occur and present as limb pain and/or a tender mass, causing radiating paresthesias upon palpation. Sensory and motor deficits may be found corresponding to the tumor's location in the plexus; however, weakness and sensory changes in the lower trunk distribution of patients with Pancoast syndrome are reported in approximately one third of cases.

Causes

The most common causes of NBP are metastatic lesions from breast or lung cancer, and the clinician also should be aware of possible concurrent cervical spine metastases.

Kamenova et al examined the cause of BP in 28 breast cancer patients suffering from homolateral arm pain and neurologic deficits.[7] In 26 patients, BP arose at the same time that supraclavicular, axillary, or chest wall metastases developed. The metastases resulted either from recurrent cancer (21 patients; found a median of 34 months after primary breast cancer treatment) or from progressing, inoperable primary tumors and nodes (5 patients). Nineteen patients developed arm edema at the same time that locoregional metastases appeared.

Primary NBP is less common than secondary metastatic lesions and usually is benign. Neural sheath tumors comprise 67-85% of primary NBP, and benign neurofibromas represent 66% of primary NBP tumors. Most neurofibromas are solitary, fusiform, and supraclavicular, and they are more common in females than males (3:1 in one series). A smaller number of plexus neurofibromas (37-42%) are associated with Von Recklinghausen disease. They can arise or extend intraspinally, and their nerve fibers often are nonfunctional.

Benign schwannomas (eg, neurinomas, neurilemomas) are the second most common type of sheath tumors, comprising about 20%. Approximately 15% of neural sheath tumors are malignant (eg, neurogenic sarcomas, fibrosarcomas). Many of these malignant tumors occur in tumors that initially are benign and undergo malignant transformation, as occurs often in Von Recklinghausen disease. They may develop many years after radiation for Hodgkin disease or breast cancer. Among other types of primary neoplasms, only lymphomas metastasize to the brachial plexus with any appreciable frequency. Rarely, NBP may occur as a paraneoplastic syndrome in patients with Hodgkin lymphoma, encephalomyelitis, and small cell carcinoma of the lung.

 

DDx

Diagnostic Considerations

These include the following:

  • Neuralgic amyotrophy

  • Subacromial bursitis

  • Supraspinatus tendonitis

  • Paraneoplastic syndrome

Differential Diagnoses

 

Workup

Laboratory Studies

See the list below:

  • A general lab survey, such as a complete metabolic panel, complete blood count, and urinalysis, usually has been obtained by the primary physician and can be used to screen for signs of neoplasm. (More involved studies exist, but they are beyond the scope of this text/specialty.) If a patient is referred for what might be thought of as simple shoulder pain and turns out to have constitutional symptoms (eg, fevers, weight loss, malaise) and signs of brachial plexopathy, other lab tests certainly may be of value. Examples include a carcinoembryonic antigen (CEA) in a patient with prior colon cancer, a prostate specific antigen (PSA) in a patient with prior prostate cancer, or serum protein electrophoresis (SPEP) in a patient with back pain and pain at rest.

Imaging Studies

See the list below:

  • Plain radiographs of the chest, shoulder, and cervical spine should be obtained to look for neoplastic changes.

  • MRI of the plexus has a high sensitivity (some studies have reported 100%) in detecting neoplastic involvement of the brachial plexus; however, both CT scan and MRI can present difficulty detecting infiltrating neoplasms and distinguishing them from radiation fibrosis. A well-defined mass lesion on CT scans or MRIs is more suggestive of NBP than RBP.[8]

  • Bone scan may be helpful in finding evidence of metastases.

  • Myelography may be more successful at finding epidural metastasis extruding through neural foramina (so-called dumbbell tumor).

  • Positron emission tomography may be useful in identifying metastasis in or near the brachial plexus; FDG-PET identifies tumors not clearly imaged by CT or MR scanning in some patients.

Other Tests

See the list below:

  • The conventional diagnostic procedures for differentiating brachial plexopathy are nerve conduction and electromyography studies. Advances in MRI techniques have shown promise as well.

  • In general, electrodiagnostic examination is used to localize a lesion, characterize its pathology, and establish prognosis and facilitate a treatment plan. The key question is whether the limb weakness is due to axonotmetic (dead) or neurapraxic (functionally blocked) axons.

  • Nerve conduction studies (NCS) may reveal axon loss that often is so severe that lower trunk-mediated sensory potentials (eg, ulnar, medial antebrachial) are absent, and motor responses (median and ulnar) are of low amplitude or absent. Needle examination often reveals motor unit potential loss and spontaneous activity. For axonotmetic lesions, the longer regrowth distance (especially for the lower plexus, where reinnervation must reach the hand) indicates a less favorable prognosis. Neurapraxic lesions are observed less commonly in NBP than RBP, but, barring progression of the lesion/mass, function resumes relatively rapidly, and the prognosis is excellent.

  • Comparison of the amplitude of a peripheral evoked response after 7 days with that of the contralateral side can provide an estimate of the degree of injury/recovery. The number of voluntary motor units on needle examination is also a guide to outcome. Peak muscle strength can be regained even with 50% axon loss, although this gain is at the expense of muscle endurance. Remarkably, in muscles where high force or sustained use is not needed, a 90% axon loss might be tolerated, but a year's recovery time might be required. Myokymia is common is RBP, occurring in 50-70% of patients, but it is rare in NBP (4%). Despite the potential utility of electrodiagnostic studies, limitations exist. When pain is the only initial symptom, EMG results may be within the reference range, although the results almost always reveal abnormalities by the time permanent motor and/or sensory deficits are present.

  • Somatosensory evoked potentials (SSEP) are noninvasive tests that may be used to assess sensory impairments associated with NBP.

Histologic Findings

The histopathology for secondary neoplasms most often involves adenocarcinoma, squamous cell carcinoma, or, less often, large cell carcinoma. Of the primary neoplasms, schwannomas are encapsulated tumors, and neurofibromas are unencapsulated tumors believed to arise from the near fascicles.

 

Treatment

Rehabilitation Program

Physical Therapy

Early passive range of motion (PROM) of the upper limb is appropriate to prevent contracture. If there is preserved volitional motor function, active-assistive range of motion (AAROM) and active range of motion (AROM) exercises may be instituted. Progressive resistance exercises, when tolerated, can help to maintain as much strength as possible. The physical therapist should instruct the patient in a home exercise program to incorporate self-directed range of motion (ROM) and strengthening activities whenever possible.

Physical therapy modalities also may be warranted for assisting in pain reduction in patients with NBP. Electrical modalities for pain control, such as transcutaneous electrical nerve stimulation (TENS) or interferential current, are reasonable but are considered to be a relative contraindication when applied directly over a malignant neoplasm. Edema control measures (eg, retrograde massage, elevation, compressive garments) may be considered. A sling or splint can help the patient maintain a comfortable position and protect the affected limb. A sling also can reduce edema, retard shoulder subluxation, and reduce additional traction on the brachial plexus.

Occupational Therapy

See the Physical Therapy section above. Completing a home safety evaluation for patients with NBP and their families is important. The home evaluation should include use of compensatory strategies and adaptive equipment to improve the patient's functional abilities. For example, a patient who can no longer perform bimanual skills may benefit from a device to help manipulate buttons in order to dress independently. The occupational therapist can work with the patient and maximize his/her capabilities in performing activities of daily living (ADL). The occupational therapist also can engage the patient in a sensory and motor re-education program if there is impaired function in the hand.

Speech Therapy

Though not directly related to plexopathies, metastatic neoplasm also may alter communication, swallowing, or cognitive function, requiring a speech therapy consultation.

Recreational Therapy

Recreational therapy can help to maintain the patient's interest and skills by incorporating leisure time activities into the rehabilitation program.

Medical Issues/Complications

For more severe lesions, an interdisciplinary approach may be most effective, including prescription of physical, occupational, and recreational therapies. Coordination of therapies, consultants, complications, and medications is needed.

Treatment often is difficult and may be palliative; chemotherapy and radiation therapy (up to 50% of patients obtain significant pain relief) are used if the tumor is sensitive to them. In the aforementioned investigation by Kamenova and colleagues (see Causes), 22 of the study's patients received BP treatment, aimed specifically at the locoregional metastases, with radiation therapy (8 patients) or endocrine treatment or chemotherapy (14 patients) initially being employed.[7] In 19 of these patients, partial or complete remission of pain and neurologic deficits, lasting a median period of 8 months, occurred.

As the disease progresses, adequate pain control is the most important goal as most patients succumb to neoplastic involvement of vital organs within a few years.

Medical and Surgical Intervention

Several authorities advise referral of patients with NBP to surgeons with special expertise in treatment of NBP. Accurate diagnosis may prevent unnecessary surgery for carpal tunnel syndrome or thoracic outlet syndrome. Surgery usually is performed only for definite tissue diagnosis in secondary neoplasms. Primary tumors, like benign schwannomas, are encapsulated, permitting surgical excision without sacrificing adjacent nerves.

Most solitary neurofibromas can be resected without producing or increasing deficit, but this procedure is more difficult than excision of encapsulated tumors and usually requires magnification, intraoperative nerve action potential recording, and sometimes cable grafts. Some neurofibromas are "dumbbell tumors" that extend into the epidural space. Many benign tumors (including neurofibromas) can be removed without significant loss using surgical loupes or microscope and repetitive NAP recording. Plexiform neuromas are more difficult to remove because of extensive segments of nerve fiber involvement. Some elements may have to be sacrificed for pain control and to save the remainder of the plexus. In patients with severe intractable pain, dorsal rhizotomy, dorsal root entry zone surgery, or high contralateral percutaneous cordotomies can be considered. Amputation and other destructive procedures often are ineffective.

A study by Zinboonyahgoon et al indicated that a single-shot brachial plexus block made up of local anesthetic and corticosteroid can produce a sustained reduction in NBP pain. Patients in the study suffered from refractory, cancer-related pain in the brachial plexus region, primarily as a result of NBP. Those who responded to the treatment experienced a decrease in pain lasting between 2 weeks and 10 months.[9]

Consultations

Most patients have a consulting oncologist, as well as an internist or family practitioner. Some patients may need an anesthesiologist or interventional physiatrist for injections, and some may have seen a neurologist, or less commonly, a neurosurgeon (for more drastic measures mentioned above). Consultation with a psychologist may be helpful in terms of emotional adjustment, pain control, and supportive counseling.

Other Treatment

Paravertebral nerve blocks or other injection procedures may be indicated, depending on the location of the tumor(s). NBP often is widespread and is not amenable to application of selective blocks.

 

Medication

Medication Summary

No medications are specific for this diagnostic entity. Typical analgesic and adjunct analgesic agents may be worthwhile in managing neoplastic plexopathy.

Opioid analgesics (eg, long-acting oxycodone or fentanyl) are associated with fewer concerns about tolerance and dependency than many other opiates. A ceiling effect is also absent with these agents, while use of combination agents like hydrocodone/acetaminophen may be limited by maximum dose of acetaminophen allowable (4 g/d). Opiates may be effective at acceptable doses and often are tried first. For more mild symptoms, topical analgesics should be tried.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can be helpful and usually are tried in conjunction with other agents.

Adjunct agents such as tricyclic antidepressants (eg, nortriptyline, amitriptyline) or other antidepressants (eg, sertraline, venlafaxine), anticonvulsants (pregabalin, gabapentin, carbamazepine), and, less commonly, antiarrhythmics (eg, mexiletine) may be used for control of neuropathic pain.

Opioid analgesic agents

Class Summary

Should be used early in the disease. As in most painful conditions, begin with low potency medications at low doses and taper to desired response. For information on converting between opioid analgesics, see Opioid Equivalents.

Hydrocodone and acetaminophen (Vicodin, Lortab, Norcet)

Drug combination indicated for moderate to severe pain.

Oxycodone (OxyContin)

Indicated for the relief of moderate to severe pain.

Fentanyl transdermal (Duragesic)

Potent opioid analgesic. Indicated for severe chronic pain requiring continuous, around-the-clock opioid analgesia for an extended period in opioid-tolerant patients. Not for acute pain or breakthrough pain. After patch removal, continued systemic absorption occurs from residual fentanyl in skin, so that serum concentrations fall by average of 50% in ~20-27 h.

Buprenorphine transdermal (Butrans)

Semisynthetic narcotic mixed agonist-antagonist analgesic. Buprenorphine elicits agonistic effects at the mu and delta opioid receptors in the CNS, and antagonistic effects at the kappa opioid receptor. It is indicated for severe chronic pain requiring continuous, around-the-clock opioid analgesic for an extended period. The patch may be started with a low dose (ie, 5 mcg/h) in opioid-naïve patients, or converted from other opioid analgesics in opioid-tolerant patients.

Corticosteroids

Class Summary

Can be helpful since inflammation may be part of the pathophysiology of the pain of NBP, as previously mentioned.

Prednisone (Deltasone, Orasone, Meticorten)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Cyclooxygenase-2 (COX-2) inhibitors

Class Summary

Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is clearly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.

Celecoxib (Celebrex)

Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose for each patient.

Nonsteroidal anti-inflammatory drugs

Class Summary

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions. Inexpensive older NSAIDs like ibuprofen or naproxen may be considered; however, COX-2 inhibitors with their lower GI toxicity are often first-line agents.

Ibuprofen (Motrin, Ibuprin)

DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Naprosyn, Naprelan, Anaprox)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis.

Tricyclic antidepressants

Class Summary

A complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission and block the active reuptake of norepinephrine and serotonin.

Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain. Used as adjunct therapy.

Nortriptyline (Pamelor, Aventyl HCl)

Used as adjunct therapy. Has demonstrated effectiveness in the treatment of chronic pain. Used as adjunct agent.

By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS.

Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.

Anticonvulsants

Class Summary

Use of certain antiepileptic drugs, such as the GABA analogue Neurontin (gabapentin), has proven helpful in some cases of neuropathic pain. Have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin. The multifactorial mechanism of analgesia could include improved sleep, altered perception of pain, and increase in pain threshold. Rarely should these drugs be used in treatment of acute pain, since a few weeks may be required for them to become effective.

Carbamazepine (Tegretol)

May reduce polysynaptic responses and block post-tetanic potentiation. Used as adjunct therapy.

Gabapentin (Neurontin)

Has anticonvulsant properties and antineuralgic effects; however, exact mechanism of action is unknown. Structurally related to GABA but does not interact with GABA receptors. There are no firm rules, but, in elderly patients, less potentially anticholinergic medications like gabapentin may be a good first choice. Used as adjunct therapy.

Pregabalin (Lyrica)

It is a structural derivative of GABA but does not bind directly to GABA or benzodiazepine receptors. Mechanism of action is unknown. It binds with high affinity to alpha2 -delta site (a calcium channel subunit) in the CNS. In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, or spinal cord injury. It is also FDA approved as adjunctive therapy in partial-onset seizures and for pain associated with fibromyalgia.

 

Follow-up

Further Outpatient Care

See the list below:

  • Routine follow-up care is necessary for monitoring the patient's condition and titrating medications.

Further Inpatient Care

See the list below:

  • Further inpatient care is needed if more invasive procedures are performed or if medical complications need to be monitored during radiation or chemotherapy.

Complications

See the list below:

  • Potential complications of NBP include rapid progression of symptoms with disabling pain, edema, muscle contractures, or bony deformities. Most patients with secondary neoplasms succumb to metastatic involvement of vital organs within a few years.

Prognosis

See the list below:

  • Most patients with benign primary neoplasms have a good prognosis, while patients with malignant primary neoplasms have a less favorable prognosis, regardless of therapy performed. For secondary neoplasms, most patients succumb to death within a few years from metastases to vital organs. On the other hand, preservation of some function and provision of adequate analgesia may be realistic goals for many patients.

Patient Education

See the list below:

  • See the Rehabilitation Program section above.