AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Although radiation therapy is used in the treatment of a myriad of neoplastic diseases, it has potentially adverse effects on several organs and systems that are exposed during treatment. Radiation-induced neurotoxicity can involve the central and peripheral nervous systems. Radiation-induced brachial plexopathy can occur when radiotherapy is directed at the chest, axillary region, thoracic outlet, or neck.

Pathophysiology

The radiation dose, treatment technique, and concomitant use of chemotherapy all demonstrate significant association with the development of radiation injury to the brachial plexus. The mechanism is believed to be a combination of localized ischemia and failure of cellular proliferation. The net result is fibrosis of the neural and perineural soft tissues secondary to microvascular insufficiency.

Frequency

United States

The frequency of radiation-induced brachial plexopathy is estimated at 1.8-4.9% and is most common in patients with underlying breast or lung carcinoma.

International

No satisfactory data have been reported.

Mortality/Morbidity

The natural course of radiation injury to the brachial plexus varies. Two thirds of the patients diagnosed with radiation-induced brachial plexopathy appear to have a stable course over months to years with a gradual worsening of paresthesias and pain. One third of patients deteriorate rapidly and exhibit significant weakness, lymphedema, and pain. No extant studies quantify the degree of disability experienced by patients with this disorder.

Race

No sources in the literature have examined the racial or ethnic distribution of patients with radiation-induced brachial plexopathy.

Sex

Given that breast cancer often is treated with radiation therapy, women experience a greater incidence and prevalence of radiation-induced brachial plexopathy than men.

Age

No studies have suggested that any given age group is more likely to develop radiation-induced brachial plexopathy. Otherwise, the age range closely parallels that of patients with breast cancer.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The interval from the last dose of radiation to the first symptom of plexus disorder varies widely. The average interval range reported is 7.5 months to 6 years.
• Sensory symptoms, such as numbness, paresthesia, and dysesthesia, along with swelling and weakness of the arm, are the predominant presenting symptoms. One series reported that 55% of patients presented with paresthesia, and the remainder had arm swelling and weakness. These neurologic symptoms can be progressive and may lead to a weak and edematous arm.
• Only 18% of patients presented with any significant pain, and pain was a major symptom in only 35% of patients. The pain symptoms usually are limited to the shoulder and proximal arm. Such pain usually is rated as mild to moderate in intensity.
• The physician, therefore, must ask both temporal and neurologically focused questions.
• • Address the existence, onset, and pattern of weakness, as well as the presence, quality, and distribution of any altered sensation.
  • Explore the history if the patient also is experiencing pain in the involved extremity.
  • The characteristics of the pain need to be investigated and documented. Also document details of any swelling in the involved extremity.

Physical

Physical examination findings fall into two categories.

• Neurologic findings are most prominent in the C5-C6 myotomes and dermatomes, as well as diminished deep tendon reflexes supplied by C5-C6. However, Schierle and Winograd reported frequent involvement in the C7 distribution. Myokymia is difficult to visualize by inspection or palpation. In the series by Monidrup, 78% of patients with radiation-induced plexopathy presented with upper trunk involvement. The lymphatic-vascular system may reveal prominent lymphedema of the involved extremity without cyanotic or dusky features. There should be no disturbance of arterial or venous circulation in the involved extremity and no changes in the limb to suggest venous insufficiency (varicosities, stasis ulcers, or dermatitis). The Allen test should be negative. Horner syndrome is not present in patients with radiation-induced brachial plexopathy.
• The musculoskeletal examination may reveal decreased scapulothoracic and glenohumeral joint range of motion. This development is not secondary to the plexopathy; rather, it may be experienced if (1) previous surgery was performed in the chest wall or axillary region or (2) the finding is secondary to fibrosis of the musculoskeletal tissues from the radiotherapy. No specific joint tenderness or effusions should be encountered during the examination of the involved extremity.

Causes

Treatment technique (2 vs 3 fields of radiation therapy) and concomitant use of chemotherapy are associated with development of radiation injury to the brachial plexus. No other risk factors or causes have yet been identified.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No laboratory studies help differentiate radiation-induced brachial plexopathy from other disorders involving the brachial plexus.

Imaging Studies

• Plain radiography does not have diagnostic value for detecting radiation-induced brachial plexopathy.
• CT scanning of the involved brachial plexus may reveal a diffuse infiltration of the tissue planes.
• MRI often reveals a low signal intensity on T2-weighted images; minimal changes are found with gadolinium.
• All of these characteristics are in contrast to neoplastic processes, which would be identified by the presence of a focal mass. In addition, if traditional modalities demonstrate normal findings, positron emission tomography imaging may provide an additional tool for excluding suspected malignant plexopathy. Malignant etiologies of brachial plexopathy are associated with significantly increased uptake of 18-fluoro-2-deoxy-D-glucose, reflecting the increased metabolism associated with neoplastic processes.

Other Tests

• Electrodiagnostic testing can be used to distinguish between radiation-induced and neoplastic disorders of the brachial plexus. No significant differences between the 2 conditions are noted between results of sensory and motor conduction studies or late responses.
• Electromyography in radiation-induced brachial plexopathy reveals myokymia more often than in neoplastic-induced brachial plexopathy. Myokymia represents spontaneous discharges accompanied by wavelike muscle quivering. The frequency may be paroxysmal motor unit action potentials or a slow continuous discharge at 1-5 Hz in motor unit action potentials.
• Evoked potential studies do not have any particular value for this diagnosis.

Procedures

• In some cases, surgical exploration and biopsy are required to distinguish between radiation-induced and tumor-induced brachial plexopathy. Nerve grafting has been attempted in animals with fair results, but data from human trials are lacking.
• Surgical treatment options are aimed at breaking up fibrotic tissue to eliminate mechanical constriction of the plexus and its blood supply. Attempts have been made at exoneurolysis/endoneurolysis, with or without placement of an omental or latissimus dorsi flap as a source of well-perfused tissue. Unfortunately, these approaches have proven ineffective and even harmful. Indeed, dissection alone can lead to a significant worsening of symptoms. Some relief of pain may be achieved in a minority of patients, with little or no impact on other sensory or motor deficits.

Histologic Findings

• Fibrosis of the neural elements and surrounding soft tissues
• Chronic perineurial microvascular ischemia

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Rehabilitation Program

Physical Therapy

The role of physical therapy does not differ much in cases of radiation-induced brachial plexopathy compared with tumor-related plexopathy. The interventions and modalities should address the following underlying impairments:

• Weakness: Assign therapeutic exercise to enhance flexibility and strength of the shoulder girdle paracervical and parathoracic muscles. The glenohumeral joint may require a sling for sitting or standing activities to reduce the degree of glenohumeral joint subluxation and discomfort.
• Pain: Use caution when considering the application of heat and cold if the sensation in the extremity is impaired. Transcutaneous electrical nerve stimulation therapy may be considered for pain control.
• Lymphedema: Educate the patient. Perform manual lymphatic therapy and motorized intermittent pneumatic compression therapy; use graded pressure upper extremity garments.

Occupational Therapy

• Assess basic and instrumental activities of daily living and provide appropriate adaptive equipment.
• Provide fine motor skills training, if the lower plexus is involved.
• Employ sensory and motor re-education techniques.
• Consider using a flexor hinge tenodesis orthosis with or without long opponens orthosis if it allows the patient to be functionally prehensile.

Medical Issues/Complications

• As with other conditions that produce lymphedema of the upper extremity, hygiene plays an important role in radiation-induced brachial plexopathy, and venipuncture should be avoided to obviate the risk of cellulitis/lymphangitis.
• If the affected extremity is involved in trauma with skin laceration, exercise vigilance in monitoring for cellulitis or lymphangitis. Prophylactic antibiotic treatment, although controversial, can be initiated.

Surgical Intervention

• Glenohumeral joint arthrodesis rarely is indicated.
• Lymphatic bypass surgery interventions to divert or to redirect lymphatic flow rarely are required.

Consultations

A radiation oncologist, neurooncologist, neuroradiologist, and physical medicine/rehabilitation specialist can assist in diagnosis and management.

Other Treatment

One clinical investigation suggested that vasoactive pharmacotherapy with pentoxifylline in conjunction with alpha-tocopherol substantially reversed the course of radiation induced plexopathy. However, drug administration needs to be in temporal proximity to the course of radiation therapy.

• Dorsal root entry zone lesion can be considered for intractable cases of chronic severe pain.
• Neurolysis/decompression of the first rib or clavicle and neural grafting generally are not indicated.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goal of pharmacotherapy is to reduce morbidity and prevent complications.

Drug Category: Anticonvulsants

Used to manage severe muscle spasms and provide sedation in neuralgia.

Drug Category: Tricyclic antidepressants

Have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Continue to monitor the neurologic examination findings. If changes occur, consider repeating electromyelography or MRI.
• Reinforce patient education regarding protection and care of the extremity with lymphedema. If lymphedema worsens, consider the aforementioned therapeutic interventions and perform an MRI to rule out metastatic disease.

In/Out Patient Meds

• For pain control - Tricyclic antidepressants or anticonvulsants for lancinating pain

Transfer

• If there is evidence of neoplastic disease, the patient needs to be enrolled in an appropriate facility for radiation or chemotherapy.

Deterrence

• Use radiotherapy doses below 60 cGy.

Complications

• Lymphangitis
• Cellulitis
• Complex regional pain syndrome, type 2
• Glenohumeral joint subluxation
• Contractures in the involved upper extremity

Prognosis

• One third of patients experience significant progression of their radiation-induced plexopathy, whereas the remainder of patients demonstrate gradual progression.

Patient Education

• Educate patients about lowering the risks of infection secondary to the incident associated with upper extremity trauma.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to make an accurate diagnosis

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Delanian S, Balla-Mekias S, Lefaix JL. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol. Oct 1999;17(10):3283-90. [Medline].
• Fathers E, Thrush D, Huson SM, Norman A. Radiation-induced brachial plexopathy in women treated for carcinoma of the breast. Clin Rehabil. Mar 2002;16(2):160-5. [Medline].
• Galecki J, Hicer-Grzenkowicz J, Grudzien-Kowalska M, et al. Radiation-induced brachial plexopathy and hypofractionated regimens in adjuvant irradiation of patients with breast cancer--a review. Acta Oncol. 2006;45(3):280-4.
• Garden FH. Radiation injury to the spinal cord and peripheral nerves. State of the art reviews PM&R. 1994;8:405-411.
• Hoeller U, Rolofs K, Bajrovic A, et al. A patient questionnaire for radiation-induced brachial plexopathy. Am J Clin Oncol. Feb 2004;27(1):1-7.
• Jaeckle KA. Plexopathies in cancer patients. Cancer in the nervous system. 1996;347-360.
• Kori SH. Diagnosis and management of brachial plexus lesions in cancer patients. Oncology (Huntingt). Aug 1995;9(8):756-60; discussion 765. [Medline].
• Mondrup K, Olsen NK, Pfeiffer P, Rose C. Clinical and electrodiagnostic findings in breast cancer patients with radiation-induced brachial plexus neuropathy. Acta Neurol Scand. Feb 1990;81(2):153-8. [Medline].
• Pierce SM, Recht A, Lingos TI, et al. Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys. 1992;23(5):915-23. [Medline].
• Posner J. Side effects of radiation therapy. In: Neurologic Complications of Cancer. 1995;45:311-337.
• Schierle C, Winograd JM. Radiation-induced brachial plexopathy: review. Complication without a cure. J Reconstr Microsurg. Feb 2004;20(2):149-52.
• Stubgen JP. Neuromuscular disorders in systemic malignancy and its treatment. Muscle Nerve. Jun 1995;18(6):636-48. [Medline].

Article Last Updated: Dec 7, 2006