eMedicine Specialties > Physical Medicine and Rehabilitation > Plexopathy

Radiation-Induced Brachial Plexopathy

Robert J Kaplan, MD, James E Van Zandt VA Medical Center, Staff Physician, Department of Rehabilitation Medicine

Updated: Jun 11, 2009

Introduction

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.^1,2

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.²

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

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 temporally 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 for radiation-induced brachial plexopathy fall into the following 2 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.³ Myokymia is difficult to visualize by inspection or palpation.⁴ In the series by Mondrup and colleagues, 68% of patients with radiation-induced plexopathy presented with upper trunk involvement.¹⁴ 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.

A 2009 report examined the incidence of brachial plexopathy resulting from the use of stereotactic body radiotherapy to treat apical lesions in early-stage, non – small cell lung cancer.⁵ The study found that grade 2, 3, or 4 plexopathy developed in 7 out of 37 apical lesions exposed to radiotherapy. The report's authors advised that the risk of brachial plexopathy be reduced by keeping the maximum radiation dose to a brachial plexus below 26 Gy in 3 or 4 fractions.

Differential Diagnoses

Brachial Neuritis
Cervical Disc Disease
Cervical Myofascial Pain
Neoplastic Brachial Plexopathy
Traumatic Brachial Plexopathy

Other Problems to Be Considered

Workup

Laboratory 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.
• Computed tomography (CT) scanning of the involved brachial plexus may reveal a diffuse infiltration of the tissue planes.
• Magnetic resonance imaging (MRI) often reveals low signal intensity on T2-weighted images; minimal changes are found with gadolinium.^4,6
• 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.⁴
• 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.^1,7
• 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

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, neuro-oncologist, 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

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

Anticonvulsants

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

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.
Titration to effect can take place over several days (300 mg on day 1, 300 mg bid on day 2, and 300 mg tid on day 3).

Dosing

Adult

300-3600 mg/d PO divided tid/qid

Pediatric

Not established

Interactions

Antacids may reduce bioavailability of gabapentin significantly (administer at least 2 h following antacids); may increase norethindrone levels significantly

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in severe renal disease

Tricyclic antidepressants

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

Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain.

Dosing

Adult

10-100 mg PO qhs

Pediatric

Not established

Interactions

Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Contraindications

Documented hypersensitivity; patient has taken MAOIs in past 14 d; has history of seizures, cardiac arrhythmias, glaucoma, and urinary retention

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances, history of hyperthyroidism, and renal or hepatic impairment; avoid using in elderly patients

Nortriptyline (Aventyl, Pamelor)

Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, increases synaptic concentration of these neurotransmitters in CNS.

Dosing

Adult

25 mg tid/qid PO; not to exceed 150 mg/d

Pediatric

Not established

Interactions

Cimetidine may increase levels when used concurrently; may increase PT in patients stabilized with warfarin

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; MAOIs in past 14 d

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances, history of hyperthyroidism, and renal or hepatic impairment; due to pronounced effects in cardiovascular system, best to avoid in elderly patients

Follow-up

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.

Inpatient & Outpatient Medications

• 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

Medicolegal Pitfalls

• Failure to make an accurate diagnosis of radiation-induced brachial plexopathy

References

1. Wong M, Tang AL, Umapathi T. Partial ulnar nerve transfer to the nerve to the biceps for the treatment of brachial plexopathy in metastatic breast carcinoma: case report. J Hand Surg Am. Jan 2009;34(1):79-82. [Medline].

2. 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. [Medline]. [Full Text].

3. Schierle C, Winograd JM. Radiation-induced brachial plexopathy: review. Complication without a cure. J Reconstr Microsurg. Feb 2004;20(2):149-52. [Medline].

4. Shimazaki H, Nakano I. [Radiation myelopathy and plexopathy]. Brain Nerve. Feb 2008;60(2):115-21. [Medline].

5. Forquer JA, Fakiris AJ, Timmerman RD, et al. Brachial plexopathy from stereotactic body radiotherapy in early-stage NSCLC: Dose-limiting toxicity in apical tumor sites. Radiother Oncol. May 17 2009;[Medline].

6. Sureka J, Cherian RA, Alexander M, et al. MRI of brachial plexopathies. Clin Radiol. Feb 2009;64(2):208-18. [Medline].

7. Tung TH, Liu DZ, Mackinnon SE. Nerve transfer for elbow flexion in radiation-induced brachial plexopathy: a case report. Hand (N Y). Jun 2009;4(2):123-8. [Medline].

8. 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].

9. 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].

10. Garden FH. Radiation injury to the spinal cord and peripheral nerves. State of the art reviews PM&R. 1994;8:405-411.

11. 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. [Medline].

12. Jaeckle KA. Plexopathies in cancer patients. In: Levin, Victor A, ed. Cancer in the Nervous System. New York, NY: Churchill Livingstone; 1996:347-60.

13. Kori SH. Diagnosis and management of brachial plexus lesions in cancer patients. Oncology (Huntingt). Aug 1995;9(8):756-60; discussion 765. [Medline].

14. 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].

15. 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].

16. Posner JB. Side effects of radiation therapy. In: Neurologic Complications of Cancer. Philadelphia, Pa: FA Davis; 1995:311-37.

17. Stubgen JP. Neuromuscular disorders in systemic malignancy and its treatment. Muscle Nerve. Jun 1995;18(6):636-48. [Medline].

Keywords

radiation-induced brachial plexopathy, brachial plexus, plexopathy, brachial plexopathy, radiation therapy, radiation treatment, breast cancer radiation therapy, breast radiation therapy, cancer radiation therapy, irradiation brachial plexopathy,

Contributor Information and Disclosures

Author

Robert J Kaplan, MD, James E Van Zandt VA Medical Center, Staff Physician, Department of Rehabilitation Medicine
Robert J Kaplan, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists, and Physiatric Association of Spine, Sports and Occupational Rehabilitation
Disclosure: Nothing to disclose.

Medical Editor

Rajesh R Yadav, MD, Assistant Professor, Section of Physical Medicine and Rehabilitation, MD Anderson Cancer Center, University of Texas at Houston
Rajesh R Yadav, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Patrick M Foye, MD, FAAPMR, FAAEM, Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Patrick M Foye, MD, FAAPMR, FAAEM is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, Association of Academic Physiatrists, and International Spine Intervention Society
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Regional Medical Director, IMX-Medical Management Services
Disclosure: Nothing to disclose.

Chief Editor

Robert H Meier III, MD, Director, Amputee Services of America; Active Medical Staff, Presbyterian/St Luke's Hospital, Spalding Rehabilitation Hospital, Select Specialty Hospital; Consulting Staff, Kindred Hospital
Robert H Meier III, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation and Association of Academic Physiatrists
Disclosure: Nothing to disclose.

Related eMedicine topics:
Brachial Neuritis
Diabetic Lumbosacral Plexopathy
Neoplastic Brachial Plexopathy
Neoplastic Lumbosacral Plexopathy
Radiation-Induced Lumbosacral Plexopathy
Traumatic Brachial Plexopathy

Clinical guidelines:
ACR Appropriateness Criteria® plexopathy. American College of Radiology - Medical Specialty Society.  2006.  13 pages.  NGC:005539

Clinical trials:
Stem Cell Therapy to Improve the Muscle Function of Patients With Partly Denervated Muscles of the Arm

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