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

Radiation is used in the treatment of various neoplasms. When directed toward management of abdominal and pelvic malignancies, such treatment can result in lumbosacral plexopathy.

Anatomically, lumbosacral plexus consists of lumbar (L1-L4) and sacral (L5-S5) portions, which are connected by the lumbosacral trunk (L4-L5). The L1-L4 nerve roots transverse through psoas muscle and then coalesce into lumbar plexus, which then divides into anterior and posterior divisions. The first 3 nerves (iliohypogastric, ilioinguinal, and femoral) of the 7 major branches of lumbar plexus provide motor and sensory innervation to the abdominal wall. The next 3 nerves (lateral femoral cutaneous, femoral, and obturator) innervate the anteromedial thigh. The femoral nerve terminates in the saphenous nerve providing sensation along the medial aspect of the leg.

The sacral plexus also divides into anterior and posterior divisions, which further divide into various peripheral nerves providing sensory motor innervation to posterior hip girdle, thigh, and anterior and posterior leg. The 5 main nerves are superior gluteal, inferior gluteal, posterior femoral cutaneous, sciatic, and pudendal. The sciatic nerve divides into the common peroneal and tibial nerves in the thigh.

Pathophysiology

The effects of radiation are correlated to the dose, technique, and concomitant use of chemotherapy. Also, risk particularly increases with intracavitary radiation. The mechanism may be related to a combination of localized ischemia and subsequent soft tissue fibrosis due to microvascular insufficiency. With doses above 1000 cGy, pathologic changes can be seen in Schwann cells, endoneurial fibroblasts, vascular cells, and perineural cells. Injury to anterior and posterior nerve roots in rodents has been shown with doses of 3500 Gy.

Such plexopathy is noted particularly with uterine, cervical, ovarian, and testicular cancers, as well as lymphomas.

Frequency

United States

The condition is rare (0.3-1.3% of patients treated with radiation). It was noted in 1.3% of patients after abdominal irradiation and in 0.32% of patients after pelvic irradiation.

International

International incidence is unknown.

Mortality/Morbidity

Generally, symptoms progress gradually and with variable rapidity. Clinical manifestations of lumbosacral plexopathy have appeared 3 months to 22 years after the completion of radiation therapy. Jaeckle et al found that 20% of patients developed moderate or even severe weakness over 6 months. Others were found to have mild weakness at 4-5 years following the onset of neurologic symptoms.

Race

No predilection toward any racial group is reported.

Sex

The male-to-female ratio is 1:1.2.

Age

Age at the time of presentation ranges from 34-68 years, with median age of 47.5 years.

CLINICAL

Section 3 of 10  

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

History

With prior radiation treatment and initial symptoms, a recurrent tumor may need to be distinguished from postradiation plexopathy. The median symptom-free interval from treatment to the initial neurologic symptom is 5 years, with a range of 1-31 years.

• Patients most commonly present with painless weakness in one or both legs. Pain is present initially in only 10% of patients, although ultimately it is noted in as many as 50% of patients. Incidence of initial pain is lower compared with brachial plexopathy. This pain is described in varying terms, such as aching, burning, pulling, cramping, and lancinating; however, pain rarely is a major problem.
• Weakness is asymmetric. At the height of illness, the ratio of bilateral to unilateral illness is 5:1. Acute lower extremity paralysis has been noted in a patient with cervical cancer 10 weeks after completion of radiation treatment.
• Sensory loss occurs in 50-75% of patients and is more severe with greater motor impairment, which can add significantly to disability.
• Bladder or bowel incontinence may occur.

Physical

• Motor deficits in the lower extremities commonly are bilateral (80%) and asymmetric. Diffuse limb weakness with distal predominance in L5-S1 distribution is more common (55%). Exclusive proximal paresis, in the distribution of L2-L4 and femoral neuropathy are less common, occurring in 10% and 5% of patients respectively. Moderate weakness is present in 50% of patients, with equal distribution of mild and severe weakness.
• Deep tendon reflexes (DTRs) almost always are abnormal at the knees, ankles, or both, and usually present bilaterally.
• Sensory impairments are present in most patients (75%) and more often are bilateral. No specific sensory modality is favored. The distal lower extremities are affected more commonly than the proximal lower extremities. Impaired deep sensation occurs with severe superficial sensory loss.
• Skin changes may be present in areas of radiation portals.

Causes

Radiation dosage, treatment technique, and concomitant use of chemotherapy are associated with development of radiation-induced lumbosacral plexopathy.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Meningeal carcinomatosis, also known as leptomeningeal disease, may cause subacute motor or sensory deficits that are present with low back or leg pain. In addition, patients with meningeal carcinomatosis often also have mental status changes, headaches, cranial nerve palsies, and/or nuchal rigidity. In cancer patients with thrombocytopenia, retroperitoneal bleeding can cause plexopathy with rapid onset of pain and neurologic signs that usually are developed fully in 24 hours. Other associated findings also include flank, thigh, or low back ecchymoses.

Causes of lumbosacral plexopathy not related to cancer include aortic aneurysms, diabetes mellitus (DM), obstetric procedures, trauma, and intragluteal injections. With aortic aneurysms, acute pain commonly is seen, and the resultant weakness typically worsens over 1-2 weeks and then stabilizes. A pulsatile rectal or abdominal mass also can be seen in many patients. Acute thigh pain with acute or insidious onset weakness can result from diabetic amyotrophy and can be difficult to differentiate from the aortic aneurysms. Weakness with diabetic amyotrophy usually is noted proximally, with relative sparing of distal lower extremity muscles.

WORKUP

Section 5 of 10  

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

Imaging Studies

• Routine spine and pelvis radiographs and myelograms are unremarkable.
• The diagnosis of radiation plexopathy can be supported by diagnostic studies such as CT scans and MRI of the pelvis. MRI is more sensitive than CT in detecting tumor recurrence. Enhancement of nerve roots and T2-weighted hyperintensity usually suggests tumor. Generally, radiation plexopathy does not produce nerve enhancement. PET scan with 2-fluorodeoxyglucose may be helpful in diagnosing recurrent tumor.

Other Tests

• Electromyography (EMG) reveals myokymic discharges in most patients (57%). Such changes occur over years; however, absence of myokymia does not exclude radiation injury. EMG in clinically weak muscles also may reveal fibrillation potentials (ie, chronic neurogenic motor unit changes with decreased recruitment). Paraspinal involvement occurs in 50% of cases. Compound muscle action potential (CMAP) of motor nerves may be low.

TREATMENT

Section 6 of 10  

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

Rehabilitation Program

Physical Therapy

Strengthening of lower extremity muscles, use of assistive devices for ambulation (eg, cane, walker), and gait training should be prescribed for patients with weakness and proprioceptive feedback loss. Use of orthotics also may be beneficial in certain individuals with lumbosacral plexopathy.

Occupational Therapy

The patient's ability to perform activities of daily living (ADL) should be assessed and appropriate assistive device(s) prescribed as needed. In particular, safety with standing transfers may be impaired with more distal involvement. With more proximal involvement, sit-to-stand transfers also may be affected. Strengthening exercises, along with sensory re-education techniques, may be employed.

Medical Issues/Complications

Treatment of postradiation plexopathy is symptomatic. For issues of pain, consider use of nonopiate pharmacologic medications, such as tricyclic antidepressants or antiepileptic agents (eg, gabapentin, carbamazepine). Use of steroids and opiates, including methadone, can also be considered.

Other Treatment

Nonpharmacologic measures, such as transcutaneous electrical nerve stimulation (TENS), may be used for pain.

While not studied in patients with radiation-induced lumbosacral plexopathy, hyperbaric oxygen therapy has not led to slowing or reversal of radiation-induced brachial plexopathy symptoms, although improvement was noted in warm sensory threshold.

In a small population, partial recovery of motor function was noted in few patients treated with anticoagulant therapy for a period of 3-6 months.

MEDICATION

Section 7 of 10  

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

TCAs, such as amitriptyline, may be used in lower doses. Use of antiepileptics may be helpful.

Drug Category: Tricyclic antidepressants

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. The efficacy of these drugs can be potentiated with concomitant use of opiates and nonsteroidal anti-inflammatory drugs (NSAIDs). Rarely should these drugs be used in treatment of acute pain, since a few weeks may be required for them to become effective.

Drug Category: Antiepileptic drugs

These drugs stabilize neuronal membranes and reduce neuronal hyperexcitability. The analgesic effect may be due to such stabilization and control of hyperexcitability since aberrant electrical activity has been recorded with neuropathic pain.

Drug Name	Carbamazepine (Tegretol)
Description	Used typically for generalized tonic-clonic seizures and partial seizures, as well as trigeminal neuralgia. Plasma levels are between 4-12 mcg/mL for analgesic and antiseizure response.
Adult Dose	100-200 mg PO bid initial dose; titrate up by 100-200 mg q3-7d; usual dosage for pain control is 400-800 mg/d; increase to tid/qid with larger dose; not to exceed 1200 mg; in rare instances, up to 1600 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; history of bone marrow depression; administration of MAOIs within last 14 d
Interactions	Serum levels may increase significantly within 30 days of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; carbamazepine may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels)
Pregnancy	D - Unsafe in pregnancy
Precautions	Serious reactions include leukopenia and agranulocytosis; risk is 5-8 times higher than in control population; overall risk per 1,000,000 population per year is 2 patients for aplastic anemia and 6 patients for agranulocytosis; prior to treatment, obtain CBC counts and differentials, along with LFTs; repeat blood count in 2-3 wk and then monthly for 3 mo; if no evidence of bone marrow suppression, then biannual counts should follow; WBC counts below 4000 is contraindication to treatment; discontinue if WBC falls <3000 after treatment, significant thrombocytopenia, abnormality in other blood elements, or significant abnormality in LFTs; other rare drug adverse effects include cardiovascular effects, such as congestive heart failure, arrhythmias, and orthostatic hypotension; hepatotoxicity; inappropriate secretion of antidiuretic hormone (IASDH); severe dermatologic reactions, including Stevens-Johnson syndrome (extremely rare); caution with other TCAs

Drug Name	Valproic acid (Depakene)
Description	Generally indicated for absence seizures and generalized tonic-clonic seizures. Some relief may be noted with neuropathic pain, especially lancinating type.
Adult Dose	15 mg/kg/d PO initial dose in 2 or more divided doses; titrate by 5-10 mg/kg/d until pain relief is achieved or adverse effects occur; pain relief at levels less than required for antiepileptic activity (50-150 mcg/mL)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; hepatic disease/dysfunction
Interactions	Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce valproate levels significantly; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients
Pregnancy	D - Unsafe in pregnancy
Precautions	Idiosyncratic reactions include hepatotoxicity (fatalities have been reported), dermatitis, alopecia, encephalopathy, and rare hyperammonemia syndrome; obtain baseline LFTs followed at frequent intervals for first 6 months; monitor serum ammonia, since it can be elevated without corresponding elevation in LFTs

Drug Category: Corticosteroids

Glucocorticoids have anti-inflammatory, hormonal, and metabolic effects. Inflammation is suppressed with blockage of phospholipase A2, which inhibits formation of arachidonic acid and, thus, the prostaglandins. The analgesic effect may be due to the anti-inflammatory activity, with decrease in edema.

Drug Category: Analgesics

These drugs are generally used for short-term acute pain, moderate to severe in nature, as well as in chronic pain (eg, cancer). They provide analgesia without antipyretic or anti-inflammatory action. Mechanism of action is inhibition of nociceptive impulses at the dorsal horn of the spinal cord and at supraspinal sites due to interaction with opiate receptors. Structural derivatives of GABA are also used in the management of neuropathic pain.

Drug Name	Methadone (Dolophine)
Description	Used in the management of severe pain. Inhibits ascending pain pathways, diminishing the perception of and response to pain.
Adult Dose	2.5-10 mg PO/IM/SC q3-8h prn; increase to a maintenance dose of 5-20 mg q6-8h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; bronchial asthma or increased intracranial pressure
Interactions	Phenytoin, rifampin, and pentazocine may decrease blood levels of methadone; phenothiazines, tricyclic antidepressants, MAOIs, and CNS depressants may increase the toxicity of methadone
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in severe liver disease; due to its relatively long half-life, titrate dose slowly

Drug Name	Morphine sulfate (Duramorph, MS Contin, Astramorph)
Description	Available in immediate (3-4 h duration) and extended release preparation (12 h). Switch over to long-acting preparations (MS Contin) once pain is controlled with short-acting preparation (MS IR). Morphine can produce drug dependence and has potential for being abused. Tolerance may develop with repeated exposure. Abrupt cessation or sudden reduction in dose with prolonged use may result in withdrawal symptoms. Physical dependence is not of paramount importance in terminally ill patients.
Adult Dose	30 mg PO q3-4h initial dose in opiate-naive patients (no exposure to opiates) or with limited opiate exposure; may be titrated upward by 50% if pain control is inadequate after first 24 h; balance between analgesia and adverse effects
Pediatric Dose	0.3 mg/kg PO q3-4h initial dose
Contraindications	Documented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult
Interactions	Phenothiazines may antagonize analgesic effects of opiate agonists; TCAs, MAOIs, and other CNS depressants may potentiate adverse effects of morphine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Elderly patients; hepatic or renal dysfunction; respiratory disease, both obstructive and restrictive (eg, COPD, asthma, kyphoscoliosis); patients with severe obesity or cor pulmonale; head injury and increased intracranial pressure; history of drug abuse; circulatory shock; adverse effect profile includes nausea/vomiting, constipation, sedation, respiratory depression (which occurs more so with opiate-naive patients and with significant pulmonary disease), cardiovascular abnormalities (eg, bradycardia, hypotension), and urinary retention

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Inpatient care is not required.

Further Outpatient Care

• Follow up with patients on functional issues after diagnosis. Address issues of pain in a timely fashion.

Complications

• Pain and decreased functional status may result.

Prognosis

• Gradual, rather than stepwise, progression of the disease is the rule. Eventually, patients may have significant or severe disability. Spontaneous recovery is less common.

Patient Education

• Educate patients about the effects of radiation and the reason for altered function, pain, and sensory deficits.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Failure to diagnose and treat may result in medicolegal liability.

REFERENCES

Section 10 of 10

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

• Abu-Rustum NR, Rajbhandari D, Glusman S, Massad LS. Acute lower extremity paralysis following radiation therapy for cervical cancer. Gynecol Oncol. Oct 1999;75(1):152-4. [Medline].
• Ashenhurst EM, Quartey GR, Starreveld A. Lumbo-sacral radiculopathy induced by radiation. Can J Neurol Sci. Nov 1977;4(4):259-63.
• Bradley WG, Fewings JD, Cumming WJ. Delayed myeloradiculopathy produced by spinal X-irradiation in the rat. J Neurol Sci. Jan-Feb 1977;31(1):63-82.
• Cavanagh JB. Prior x-irradiation and the cellular response to nerve crush: duration of effect. Exp Neurol. Oct 1968;22(2):253-8.
• Enevoldson TP, Scadding JW, Rustin GJ, Senanayake LF. Spontaneous resolution of a postirradiation lumbosacral plexopathy. Neurology. Nov 1992;42(11):2224-5. [Medline].
• Glantz MJ, Burger PC, Friedman AH. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology. Nov 1994;44(11):2020-7. [Medline].
• Iglicki F, Coffin B, Ille O, et al. Fecal incontinence after pelvic radiotherapy: evidences for a lumbosacral plexopathy. Report of a case. Dis Colon Rectum. Apr 1996;39(4):465-7. [Medline].
• Jaeckle KA, Young DF, Foley KM. The natural history of lumbosacral plexopathy in cancer. Neurology. Jan 1985;35(1):8-15. [Medline].
• Jaeckle KA. Neurological manifestations of neoplastic and radiation-induced plexopathies. Semin Neurol. Dec 2004;24(4):385-93.
• Moskovic E, Curtis S, A''Hern RP. The role of diagnostic CT scanning of the brachial plexus and axilla in the follow-up of patients with breast cancer. Clin Oncol (R Coll Radiol). Mar 1992;4(2):74-7.
• Pettigrew LC, Glass JP, Maor M, Zornoza J. Diagnosis and treatment of lumbosacral plexopathies in patients with cancer. Arch Neurol. Dec 1984;41(12):1282-5. [Medline].
• Pritchard J, Anand P, Broome J, et al. Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy. Radiother Oncol. Mar 2001;58(3):279-86. [Medline].
• Stryker JA, Sommerville K, Perez R, Velkley DE. Sacral plexus injury after radiotherapy for carcinoma of cervix. Cancer. Oct 1 1990;66(7):1488-92. [Medline].
• Stubgen JP. Neuromuscular disorders in systemic malignancy and its treatment. Muscle Nerve. Jun 1995;18(6):636-48. [Medline].
• Taylor BV, Kimmel DW, Krecke KN. Magnetic resonance imaging in cancer-related lumbosacral plexopathy. Mayo Clin Proc. Sep 1997;72(9):823-9. [Medline].
• Thomas JE, Cascino TL, Earle JD. Differential diagnosis between radiation and tumor plexopathy of the pelvis. Neurology. Jan 1985;35(1):1-7. [Medline].
• Wilbourn AJ. Electrodiagnosis of plexopathies. Neurol Clin. Aug 1985;3(3):511-29. [Medline].

Article Last Updated: Feb 6, 2007