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18

Plexopathies

KURT A. JAECKLE

Tumors may invade the cervical, brachial, and lum-bosacral plexus by direct extension from primarytumors in regional organs or by secondary invasion following metastases to regional lymph nodes. Oc-casionally, tumor tracks along the epineurium sur-rounding the trunks of the nerve plexuses. In thepreviously treated cancer patient, the major differ-ential diagnostic consideration is radiation-inducedplexopathy. Less frequently, the plexopathy resultsas a complication of regional (usually intra-arter-ial) chemotherapy or is due to fibrosis followingsurgical resection of primary tumor within the re-gion.

Tumor plexopathy is a symptomatic complicationin approximately 1 of 100 patients with cancer. Intwo retrospective reviews from cancer hospitals,based on 12,000 patient visits per year, the preva-lence of brachial plexopathy resulting from tumor in-vasion was 0.43%, and the prevalence of lumbosacralplexopathy was 0.71% (Kori et al., 1981; Jaeckle etal., 1985). The actual prevalence may be higher, asnot all patients with plexopathy accompanying termi-nal malignancy are reported. The best estimates havebeen obtained from breast cancer patients treatedwith conventional radiotherapy in whom the preva-lence of brachial plexopathy at 5 years was 1.8% to4.9%; however, this study likely included some pa-tients with radiation-induced plexopathy (discussedbelow) (Pierce et al., 1992; Powell et al., 1990; Shel-don et al., 1987).

Familiarity with plexus neuroanatomy is neces-sary to correctly interpret the clinical findings andto distinguish between plexopathies and neurologic

dysfunction due to epidural compression by tumor,neoplastic meningitis, and other disorders of pe-ripheral nerves. In clinical practice, physiciansusually encounter patients with brachial or lum-bosacral plexopathy. Cervical plexopathy is alsodiscussed as its clinical presentation, tumor his-tologies, and therapeutic implications differ some-what, although there is considerable overlap withbrachial plexopathy. Finally, one must be able todistinguish between those patients with plex-opathies due to radiation or other causes, which isdiscussed separately.

CERVICAL PLEXOPATHY

Anatomy

The cervical plexus is formed from the ventral ramiof the four upper cervical nerve roots (C1–C4). Af-ferent sensory fibers from the skin and soft tissues ofthe neck travel via the greater and lesser occipitalnerves (posterior occiput and postauricular area);the great auricular and transverse cervical nerves(preauricular area, mandibular angle, anterosupe-rior neck, and submandibular area); and the medialand lateral supraclavicular nerves (inferior antero-lateral neck) through the cervical plexus. The cervi-cal plexus supplies motor innervation to the di-aphragm and, deep cervical and hyoid muscles andvia the spinal accessory nerve to the sternocleido-mastoid and trapezius muscles (Truex and Carpen-ter, 1969).

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Pathophysiology

The cervical plexus is usually invaded by tumor fromneighboring soft tissue or bony structures (Fig.18–1). The neoplasm may invade the plexus directlyor indirectly by metastatic spread to regional lymphnodes, ribs, or vertebral bodies. The most commonlyassociated tumors of the cervical plexus include squa-mous cell carcinoma of the head and neck, lym-phoma, and adenocarcinomas of the lung and breast.

Clinical Presentation

Patients with cervical plexopathy usually present withpain located in the neck, shoulder, or throat, whichis often exacerbated by neck movement, swallowing,and coughing. The pain is often deep, boring, andconstant, but may have intermittent sharp compo-nents or caulsalgic features. On examination, the cer-vical musculature may be tender to palpation. Oneshould suspect tumor plexopathy from tumor inva-sion if large palpable tumors or firm anterior or pos-

terior cervical chain or supraclavicular nodes arepresent. Local sensory loss may be demonstrable, butis often incomplete due to overlap of root zones. Of-ten, one must distinguish postsurgical sensory lossfrom that due to tumor recurrence. The timing andlocation of sensory loss are useful points of distinc-tion. Most commonly, surgical dissection transectssuperficial branches of the greater auricular nerveover the preauricular area and mandibular angle, orthe transverse cervical branches, producing numb-ness in the skin of the upper anterior neck and sub-mandibular area.

Tumor may involve the phrenic nerve producing aparalyzed hemidiaphragm, which can be confirmedby chest radiograph or fluoroscopy. Patients may havedyspnea and paradoxical diaphragmatic excursions.Motor dysfunction of branches to the deep cervicaland hyoid muscles are usually asymptomatic. In-volvement of the spinal accessory XIth cranial nervemay produce shoulder weakness and instability. Ster-nocleidomastoid weakness may produce head devia-tion or tilt. Head and neck tumors and lymphomas

414 SYMPTOMS SECONDARY TO CANCER AND ITS TREATMENT

Figure 18–1. Cervical plexopathy. Magnetic resonance imaging scan of metastatic adenocarcinoma from submandibular primarytumor to lower left cervical plexus (arrows), producing C4–C5 pain, tingling, hoarseness, and Horner’s syndrome.

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involving the anterior cervical lymphatic chain maygrow inferiorly, producing additional involvement ofthe upper brachial plexus.

By definition, involvement of the cervical plexusimplies a close proximity of the tumor to the cervi-cal spine. If sharp and severe pain occurs with neckmovements, or pain is elicited with percussion overthe spine, there may be associated involvement of thecervical spine or impending epidural extension.

BRACHIAL PLEXOPATHY

Anatomy

The brachial plexus originates from ventral rami ofthe lower four cervical (C5–C8) and the first tho-racic roots and forms three trunks: a superior trunk(C5–C6); a medial trunk (C7); and an inferior trunk(C8–T1). These trunks each divide into dorsal andventral divisions. The three dorsal divisions jointogether to form the posterior cord, which thensplits into (1) the thoracodorsal nerve, to the latis-simus dorsi; (2) the subscapular nerve, which in-nervates the subscapularis; (3) the axillary nerve,which supplies the deltoid; and (4) the radial nerve,which innervates the triceps, brachioradialis, wrist,and finger extensors and provides sensory supply tothe posterior arm and forearm. The ventral divisionforms two cords: the lateral cord, which receivescontributions from the superior and medial trunks,and the medial cord, which is a direct continuationof the inferior trunk. The lateral cord then dividesinto two branches: one becomes the musculocuta-neous nerve (C5–C7, motor to biceps, brachialis,coracobrachialis and sensory innervation of the ra-dial forearm); and the other joins a similar branchfrom the medial cord to form the median nerve(C8–T1, forearm flexors and pronators, medialhand flexor, and lumbrical muscles; and sensationto medial palm, first three fingers, and radial one-half of the fourth finger). The remaining portion ofthe medial cord forms (1) the medial brachial cu-taneous nerve (T1, sensory to medial arm); (2) themedial antebrachial cutaneous nerve (C8–T1,sensory to medial forearm) and; (3) the ulnarnerve (C8–T1, ulnar forearm flexor muscles, in-terossei, and lumbricals; and sensation to the ulnaraspect of hand the hand and fifth finger) (Truex andCarpenter, 1969).

Pathophysiology

More than two-thirds of tumors involving the bra-chial plexus originate from the lung or breast andgenerally spread to the plexus directly from the lungor from regional metastases to the axillary lymphnodes or lung apex (Kori et al., 1981) (Fig. 18–2).Early in the disease process, the tumor often invadesthe lower plexus, particularly the inferior trunk andmedial cord, a pattern that was part of the originaldescription of the superior sulcus syndrome (Pan-coast, 1932). Conversely, tumors of the head andneck usually invade the superior trunk or posteriorcord from above. Often, the clinical pattern ofplexus involvement is patchy, due to irregular in-volvement of the plexus by growth from the rela-tively random arrangement of lymph node metas-tases. Patchy involvement is most commonlyidentified when formal electrophysiologic investiga-tions are performed.

Clinical Presentation

In a large series of patients with cancer and brachialplexopathy, pain was the most common presentingsymptom (75%), followed by dysesthesias (25%)(Kori et al., 1981). The pain was typically located inthe shoulder and axilla and often radiated along themedial aspect of the arm and forearm into the fourthand fifth fingers. Initially, pain was often incorrectlyattributed to other potential causes, such as arthritisand fibromyalgia. Pain, reflex changes, and atrophywere concentrated in the lower plexus (C8–T1) dis-tribution in 75% of patients, whereas the remaining25% of patients had global signs of involvement of theentire (C5–T1) plexus.

When brachial plexopathy is due to tumor, lymph-edema is relatively infrequent (15%). It is most oftenseen in the setting of prior radiotherapy or axillarylymph node dissection. Involvement of the sympa-thetic trunk or ganglia near the upper thoracic (par-ticularly T1) vertebrae may produce unilateralHorner’s syndrome, which has been identified in ap-proximately 23% of patients. When Horner’s syn-drome is present, concomitant epidural disease canbe identified in 32% of patients. In general, the pres-ence of Horner’s syndrome, serratus anterior orrhomboid muscle weakness, or pain consistent withvertebral involvement should raise the clinical suspi-cion of epidural extension.

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LUMBOSACRAL PLEXOPATHY

Anatomy

The lumbosacral plexus forms from the ventral ramiof the L1–S2 nerve roots and is anatomically dividedinto lumbar and sacral portions. The lumbar plexusforms within the iliacus muscle lateral to the L1–L4vertebrae and then courses posterolaterally, just an-terior to the iliac wing.

The lumbar plexus consists of anterior and pos-terior divisions. The anterior division gives rise tothe iliohypogastric, ilioinguinal, and genitofemoralnerves (L1–L2), which carry sensory fibers from theskin of the lower abdomen, upper thigh, and lateralgenitalia, and the obturator nerve (L2–L4), whichprovides motor supply to the adductors and gracilismuscles. The posterior division of the lumbar plexusdivides into the iliohypogastric and lateral femoralcutaneous nerves (L2–L3), which provide sensationto the lateral hip and thigh, and to the femoral nerve(L2–L3), which carries motor fibers to the psoas, il-iacus, sartorius, and quadriceps muscles and pro-vides sensory fibers to the skin of the anterior thighand medial upper leg.

The sacral plexus arises from the ventral rami ofS1–S4 and runs lateral to the border of the sacrum,penetrating the sciatic notch. A portion of the lowerlumbar plexus (L4–L5) connects to the sacral plexusvia the lumbosacral trunk, which runs over the sacralala to join the upper sacral plexus within the truepelvis. The anterior division of the sacral plexus pro-vides motor supply to the gemelli, quadratus femoris,obturator internus, and hamstrings; the remainingcomponents continue as the tibial nerve (L4–S3),which provides motor supply to the foot plantar flex-ors and intrinsic muscles and sensation to the heeland sole. The posterior division continues as thecommon peroneal nerve (L4–S2) to the peronealmuscles, the tibialis anterior, extensor digitorum, andextensor hallucis muscles and carries sensory fingersfrom the lateral leg and dorsal foot and toes. The pos-terior division also gives rise to the superior (L4–S1)and inferior (L5–S2) gluteal nerves, which supplythe gluteus muscles. The sciatic nerve, which con-tains components of the common peroneal and tib-ial nerves, is part of the posterior division; the pos-terior femoral cutaneous nerve (S1–S3), whichfollows the course of the sciatic nerve as a separatebundle, carries sensory fibers from skin of the pos-

416 SYMPTOMS SECONDARY TO CANCER AND ITS TREATMENT

Figure 18–2. Brachial plexopathy. Computed tomography scan of patient with non-Hodgkin’s lymphoma showing a huge shoul-der and chest wall mass displacing mediastinal structures and invading the left brachial plexus (arrows).

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terior thigh from the buttock to the knee. The puden-dal nerve (S2–S4), along with many smaller nervebundles, supplies the pelvic floor and genital muscu-lature, as well as the external anal and urethral sphinc-ters. This nerve also carries afferent sensory fibersfrom the perineum (Truex and Carpenter, 1969).

Pathophysiology

Tumors commonly invade the lumbosacral plexus bydirect extension from pelvic primary neoplasms andless frequently by secondary extension from metas-tases to regional pelvic lymph nodes, the sacrum oriliac wings, or lumbar vertebrae (Fig. 18–3). Themost commonly reported tumors producing lum-bosacral plexopathy include carcinomas of the colonand rectosigmoid, gynecologic malignancies, retro-peritoneal sarcomas, and lymphomas (Jaeckle et al.,1985; Pettigrew et al., 1984). Plexopathy is part ofthe original tumor presentation in approximately 15%of patients. In general, bulky tumors within the pelviscompress and invade the plexus directly. On occa-sion, tumor tracks along the connective tissue andepineurium of the nerve trunks (Ebner et al., 1990).This tendency to infiltrate along the nerve may explainwhy some patients with findings of diffuse plexopathydo not have radiographically demonstrable mass le-

sions and why in some circumstances the location ofthe pelvic tumor seems unrelated to the principal siteof neurologic involvement.

Clinical Presentation

Tumors invading the lumbosacral plexus typicallyproduce clinical syndromes based on their level ofinvolvement. Clinical patterns of plexus involvementinclude the upper plexus (L1–L4), the lumbosacraltrunk (L4–L5), and the lower plexus (S1–S4). Plex-opathy is usually unilateral, although bilateral find-ings are present in 25% of patients. Patients typicallypresent with leg pain, which is often followed weeksto months later by progressive leg numbness andweakness. The pain is typically severe, constant, dull,and aching and may have sharp or cramping super-imposed local, referred, or radicular components.Pain is often worse when the patient becomes supine;usually the patient has difficulty finding a comfortableposition. Additional pain that worsens with movementor weight bearing generally implies nearby bony in-vasion. Involvement of the iliopsoas muscle may forcethe patient to assume a position in bed with the hipsand knees flexed, similar to that seen with meningealinflammation. The pain may worsen following a bowelmovement or be exacerbated by a rigorous neuro-

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Figure 18–3. Lumbosacral plexopathy. Computed tomography scan showing large left pelvic node metastases from melanomathat caused severe pain and weakness in L4–L5 distribution.

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logic examination. Pain is so common (98%) that itsabsence should raise a red flag regarding this diag-nosis.

Symptomatic weakness and sensory complaintseventually develop in 60% of patients. In a series of85 cancer patients with lumbosacral plexopathy andradiographic or surgical evidence of tumor in the re-gion of the plexus (Jaeckle et al., 1985), objective legweakness was identified in 86%, sensory loss in 73%,focal reflex loss in 64%, and ipsilateral leg edema in47% of patients. Patients typically had tenderness overthe sciatic notch, and straight leg raising tests oftenreproduced their pain. Clinical dysfunction of thelower plexus is most common and is most commonlyseen with colorectal tumors. A dysesthetic syndrome(“hot dry foot”) has been described in as many asone-third of patients (Dalmau et al., 1989) due tosympathetic plexus involvement within the pelvis. In-continence and impotence are typically absent unlessbilateral plexopathy is present.

Tumors deep in the pelvis, in particular those ac-companying cervical carcinomas and tumors of therectosigmoid region, present with numbness anddysesthesias in the perianal area and perineum. Thesepatients may have a palpable rectal mass, decreasedanal sphincter tone, and sensory loss of the perineumfrom involvement of the lower sacral plexus, locatedanterior to the piriformis muscle. The sensory symp-toms often occur early and are followed later by lowerextremity pain and weakness.

DIFFERENTIAL DIAGNOSIS:PLEXOPATHY IN THE CANCER PATIENT

Radiation Plexopathy

Because the timing of onset of tumor plexopathy fol-lowing the original cancer diagnosis overlaps with thetypical time frame for radiation plexopathy, the clin-ician is often confronted with the difficult task of dis-tinguishing these two entities in previously treated pa-tients. Complicating this issue, these conditions maycoexist simultaneously in a given patient, which may in part explain why patients whose tumor re-sponds to treatment may not have clinical improve-ment. The single most valuable diagnostic clinical pa-rameter suggestive of tumor plexopathy is thedemonstration of persistent or recurrent tumor in thegeneral region of the plexus (e.g., in the axilla or lung

apex), as determined by clinical examination, mag-netic resonance imaging (MRI), and/or computed to-mography imaging (CT) (Thyagarajan et al., 1995).Radiation plexopathy is implicated if there is evidenceof radiation-induced changes in skin, bone or soft tis-sues and if myokymic discharges are found on elec-tromyography (EMG), which are unusual findings intumor plexopathy.

The syndromes of brachial and lumbosacral plex-opathy due to irradiation have been reasonably welldescribed (Kori et al., 1981; Pierce et al., 1992; Pow-ell et al., 1990; Sheldon et al., 1987; Basso-Ricci etal., 1980; Bagley et al., 1978; Harper et al., 1989;Killer and Hess, 1990; Mondrup et al., 1990; Thomaset al., 1985; Olsen et al., 1990; Ashenhurst et al.,1977). The incidence was probably higher in patientstreated in the 1960s with telecobalt therapy. Recently,a long-term (34 years) follow-up study of 71 breastcancer patients who received a calculated dose of 57Gy in 16 to 17 fractions over 3 to 4 weeks to the ax-illa, supraclavicular area, and parasternal lymphnodes, reported that late-stage progressive plexopa-thy was common. Eleven of the 12 patients alive atthe time of follow-up had paralysis of the limb (Jo-hansson et al., 2000).

The frequency of radiation plexopathy in treatedpatients is approximately 1.8% to 4.9% (Pierce et al.,1992; Powell et al., 1990; Sheldon et al., 1987). Shel-don et al. (1987) reported this complication in 2%of patients with stage III breast cancer treated with4.5 to 5 Gy to the breast and regional lymphatics ata median follow-up period of 65 months (5 years).In other series, the interval between administrationof radiotherapy and the development of plexopathyranged from 3 months to 14 years, with a median of1.5 years, and was most frequent at tissue dosesgreater than 50 Gy (Kori et al., 1981; Killer and Hess,1990).

Radiation plexopathy probably has a multifactor-ial etiology. Cavanaugh (1968) studied the effects ofradiation and crush injury of rat sciatic nerve at dosesbetween 200 and 2000 R. At doses above 1000 R,there was failure of cellular proliferation and devel-opment of pathologic changes in Schwann cells, en-doneurial fibroblasts, and vascular and perineuralcells. In another physiologic study, severe delayeddamage of the anterior and posterior nerve roots wasobserved following 35 Gy administered to the lumbarregion in rodents (Bradley et al., 1977). In humans,radiation plexopathy is presumably caused by tissue

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fibrosis with retraction of nerve trunks, direct toxiceffects on axons, and radiologic effects involving thevasa nervorum, producing microinfarction of nerveaxons (Greenfield and Stark, 1948).

In the clinical setting, several points can help todistinguish radiation-induced from tumor-inducedplexopathy (Table 18–1). Radiation plexopathy usu-ally presents with causalgic dysesthesias in the arm,often accompanied by lymphedema. In contrast, onlya small percentage of patients with tumor plexopathywill present with dysesthesias, and lymphedema is lessfrequent. In tumor plexopathy, the presenting featureis often severe unrelenting pain; in contrast, pain usu-ally develops late in the course of radiation plexopa-thy and is less often the major symptom. These twoentities can sometimes be distinguished by the levelof plexus involvement: Radiation plexopathy usuallyaffects the upper (77%) or entire (23%) plexus; intumor plexopathy, the lower plexus (75%) or the en-tire plexus (25%) appears to be more frequently af-fected (Kori et al., 1981; Mondrup et al., 1990). How-ever, recent studies have shown that the neurologiclevel of plexus involvement can be more variable thannoticed in these earlier reports (Boyaciyan et al.,1996). Sparing of the lower plexus from radiationdamage afforded by intervening bony and soft tissueshas been postulated as a reason for the more frequentoccurrence of upper plexus involvement with radia-tion, but seems questionable based on studies of tis-sue dosimetry and observations of associated ra-dionecrosis of the clavicle or ribs in these patients

(Pierce et al., 1992). Many patients with radiation-induced plexopathy also have skin changes, includ-ing telangiectasia, atrophy, and diffuse induration; ra-diographs may show other associated radiationchanges, including typical changes in the apex of thelung, radionecrosis of regional bony structures, andpericardial fibrosis.

The lumbosacral plexus is also subject to radia-tion-induced injury. The median onset of this com-plication is approximately 5 years (range, 1 month to31 years) (Thomas et al., 1985). Another series foundan earlier onset of 12 months (range, 1 month to 156months) (Ashenhurst et al., 1977). The incidence ap-pears to be higher with larger doses of radiation, buthas been reported at doses as low as 17 Gy.

The clinical features of radiation plexopathy overlapwith tumor plexopathy. Patients with radiation plex-opathy usually present with weakness (60%), numb-ness, or paresthesias (50%) (Thomas et al., 1985). Asin radiation brachial plexopathy, pain at presentation isalso uncommon (10%) in patients with radiation lum-bosacral plexopathy and frequent (98%) in patients withrecurrent tumor. Later in the course of lumbosacralplexopathy due to radiation, pain develops in 50% ofpatients. Weakness is often bilateral in radiation plex-opathy in contrast to tumor plexopathy, in which morethan 75% of patients primarily have unilateral involve-ment. The distribution of plexopathy is not as useful adistinguishing point as it is in brachial plexopathy; bothconditions most commonly affect the lower (L5–S1)portion. The presence of a rectal mass supports tumor

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Table 18–1. Differential Diagnosis of Radiation Plexopathy Versus Recurrent Tumor Plexopathy

Tumor Radiation

Presentation Pain Paresthesias, weakness

Pain Common, severe Occasional

Edema Occasional Common

Plexus involvement

Brachial Usually lower plexus Upper or whole plexus

Lumbrosacral Lower plexus, unilateral Commonly bilateral

Horner’s syndrome Common Infrequent

Local tissue necrosis Infrequent Common

Rectal mass lumbosacral Common Unusualplexopathy (LSP)

Myokymia (EMG) Unusual Common

Nerve enhancement (MRI) Common Unusual

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recurrence; sphincteric dysfunction is slightly morecommon with radiation-induced plexopathy. Leg edemaoccurs with approximately equal frequency in the twoconditions. The progression of neurologic dysfunctionis generally slower in radiation plexopathy than with tu-mor recurrence.

Electromyography appears to be helpful in distin-guishing between these two entities. Approximately60% of patients with radiation-induced plexopathywill exhibit myokymia, which is rarely seen in meta-static plexopathy (Roth et al., 1988). Neuroimagingwith CT (Moskovic et al., 1992) or with MRI can beof help in distinguishing tumor recurrence from ra-diation injury. Magnetic resonance imaging appearsto be more sensitive than CT in detecting tumor re-currence (Taylor et al., 1997).

The treatment of radiation-induced plexopathy issymptomatic. Most patients have a slow but steadyprogressive loss of motor function and require sup-portive therapy.

Additional Causes of Plexopathy inCancer Patients

Plexopathy following chemotherapy appears to be as-sociated primarily with regional intra-arterial ad-ministration (Kahn et al., 1989). Although rare, plex-opathy has been reported as a paraneoplastic disorderand on occasion may be steroid responsive (Lachanceet al., 1991). When making a diagnosis, the physicianmust also consider conditions affecting the plexus that occur in noncancer patients, including aorticaneurysms (Chapman et al., 1964); diabetic amyotro-phy (Chokroverty et al., 1977), vasculitis, and otherrare conditions (Chad and Bradley, 1987). Idiopathicor postinfectious brachial neuritis can produce symp-toms very similar to those of metastatic plexopathy, al-though the onset is usually more acute and often fol-lows a history of viral infection or immunization.Because patients with metastatic systemic cancer oftenhave more than one site of nervous system involvement,the possibility of concomitant leptomeningeal orepidural metastases must be considered, which canhave a similar clinical appearance.

DIAGNOSIS

The clinical diagnosis of metastatic plexopathy is bestconfirmed by MRI or CT scanning of the appropriateareas. Magnetic resonance imaging provides the best

anatomic detail and is usually a preferred procedure,when available. MRI has been shown to be more sen-sitive than CT in the identification of tumor plexopa-thy (Taylor et al., 1997; Qayyum et al., 2000; Thya-garajan et al., 1995). Diagnosis can be difficult if thescan does not show a mass lesion. In these instances,one must maintain a high clinical suspicion of tumorrecurrence and consider repeating the imaging pro-cedures at further neurologic progression. AlthoughCT or MRI scans may identify tumor recurrence, theradiographic appearance can be difficult to interpret.Increased T2 intensity within nerve trunks with orwithout enhancement has been identified in patientsmeeting clinical criteria for radiation plexopathy,findings considered more typical for tumor plexopa-thy; and fibrotic masses may also mimic local tumorrecurrence (Wouter van Es et al., 1997). A carefulevaluation by an experienced radiologist may be help-ful, as detection of a pattern of T2 abnormalities andenhancement and an associated mass effect may pro-vide provisional bias toward one of these diagnoses.

The presence of a local or regional tumor recur-rence, by clinical examination or imaging, supports thediagnosis of tumor plexopathy. In one study, the ab-sence of a palpable axillary mass was inversely diag-nostic as 95% of patients with CT evidence of brachialplexus tumor have a palpable axillary mass (Moskovicet al., 1992). In a recent study, positron emission to-mography (PET) was utilized to evaluate the brachialplexopathy in 19 breast carcinoma patients with plex-opathy; 14 had abnormal 18-fluorodeoxyglucose uptakewithin the involved plexus. However, the specificity andsensitivity of PET for tumor plexopathy have not beenelucidated (Ahmad et al., 1999).

Electromyography can be useful in delineating thedistribution and extent of denervation. It occasionallyreveals more extensive findings than would have beenpredicted clinically. The main clinical usefulness ap-pears to be in distinguishing radiation plexopathy fromneoplastic involvement, as stated above, and occasion-ally in supplementing the radiographic findings whenplanning treatment fields. Electromyography in experi-enced hands can be used to differentiate plexopathyfrom other entities, such as neoplastic meningitis,radiculopathy from epidural tumor, and neuropathy.

TREATMENT

Treatment of cancer-related plexopathy is largely pal-liative and symptom directed. Treatment generally in-

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volves radiation to the involved field and pain controlmeasures. Consultation with pain management spe-cialists is recommended. Studies have shown that painis often poorly controlled in patients with plexopathy.Proper pain control often requires multimodality ap-proaches, including a clear understanding of theproper use of opiate analgesics, continuous infusionpumps, local and regional blocks, sympathectomy,rhizotomy, or other specialized procedures that aregenerally outside the normal experience of radiationand medical oncologists. In appropriate settings, spe-cific chemotherapy for the underlying neoplasm iswarranted, and tumor response may be associatedwith improvement of pain and other symptoms (par-ticularly in responsive tumors such as lymphomas).Occasional relief of chronic pain has been achievedwith plexus dissection and neurolysis (Sundaresanand DiGiacinto, 1987). Dysesthesias and causalgiaare resistant to therapy, but may respond to transcu-taneous nerve stimulation, tricyclic antidepressants,anticonvulsants such as gabapentin, carbamazepineor phenytoin, or regional nerve or sympathetic gan-glion blocks. Often, opiate analgesics are required.Lymphedema may be treated with compressive de-vices and elevation.

Unfortunately, the reported results of treatment arelargely disappointing. In brachial plexopathy, radia-tion therapy to the involved plexus relieved pain inonly 46% of cases (Kori et al., 1981). Treatment oftumor in the lumbosacral plexus produced improve-ment in pain in only 15% of patients reassessed at 1month from treatment; objective improvement instrength occurred in only 17% and objective reduc-tion in tumor size in only 28% (Jaeckle et al., 1985).In another study of 28 patients with carcinomatouslumbosacral plexus neuropathy, radiation producedimprovement in 85% but only a 29% objective re-sponse rate (Ampil, 1986). The best subjective/ob-jective treatment result was observed with a total doseof at least 30 Gy. In most cases, the duration of re-sponse has been brief, and the relatively short sur-vival of patients with tumor plexopathy suggests thatits occurrence represents a late-stage complication ofmalignancy.

Plexopathy patients are particularly prone to painful contractures, compressive neuropathies,pressure ulcerations, respiratory and urinary tract in-fections, joint subluxations, and deep venous throm-boses. Preventative measures, including adequatepain management, initiation of physical rehabilitation,and assessment of home equipment needs may have

a significant impact on preservation of quality of lifein these patients.

REFERENCES

Ahmad A, Barrington S, Maisey M, Rubens RD. 1999. Use ofpositron emission tomography in evaluation of brachial plex-opathy in breast cancer patients. Br J Cancer 79:478–482.

Ampil FL. 1986. Palliative irradiation of carcinomatous lum-bosacral plexus neuropathy. Int J Radiation Oncol Biol Phys12:1681–1686.

Ashenhurst EM, Quartey GR, Starreveld A. 1977. Lumbo-sacralradiculopathy induced by radiation. Can J Neurol Sci4:259–263.

Basso-Ricci S, della Costa C, Viganotti G, Ventafridda V, ZanollaR. 1980. Report on 42 cases of postirradiation lesions of thebrachial plexus and their treatment. Tumori 66:117–122.

Bagley FH, Walsh JW, Cady B, Salzman FA, Oberfield RA,Pazianos AG. 1978. Carcinomatous versus radiation-in-duced brachial plexus neuropathy in breast cancer. Cancer41:2154–2157.

Boyaciyan A, Oge AE, Yazici J, Aslay I, Baslo A. 1996. Elec-trophysiological findings in patients who received radia-tion therapy over the brachial plexus: a magnetic stimu-lation study. Electroencephalogr Clin Neurophysiol101:483–490.

Bradley WG, Fewings JD, Cumming WJ, Harrison RM. 1977.Delayed myeloradiculopathy produced by spinal X-irradia-tion in the rat. J Neurol Sci 31:63–82.

Cavanaugh JB. 1968. Prior X-irradiation and the cellular re-sponse to nerve crush: duration of effect. Exp Neurol22:253–258.

Chad DA, Bradley WG. 1987. Lumbosacral plexopathy. SeminNeurol 7:97–107.

Chapman EM, Shaw RS, Kubik CS. 1964. Sciatic pain from ar-terioscleriotic aneurysm of pelvic arteries. N Engl J Med271:1410–1411.

Chokroverty S, Reyes MG, Rubino FA, Tonaki H. 1977. Thesyndrome of diabetic amyotrophy. Ann Neurol 2:181–194.

Dalmau J, Graus F, Marco M. 1989. “Hot and dry foot” as ini-tial manifestation of neoplastic lumbosacral plexopathy.Neurology 39:871–872.

Ebner I, Anderl H, Mikuz G, Frommhold H. 1990. [Plexus neu-ropathy: tumor infiltration or radiation damage]. ROFOFortschr Geb Rontgenstr Neuen Bildgreb Verfahr 152:662–666.

Greenfield MM, Stark FM. 1948. Post-irradiation neuropathy.Am J Roentgen 60:617–619.

Harper CM Jr, Thomas JE, Cascino TL, Litchy WJ. 1989. Dis-tinction between neoplastic and radiation-induced brachialplexopathy, with emphasis on the role of EMG. Neurology39:502–506.

Jaeckle KA, Young DF, Foley KM. 1985. The natural history oflumbosacral plexopathy in cancer. Neurology 35:8–15.

Johansson S, Svensson H, Larsson LG, Denekamp J. 2000. Bra-chial plexopathy after postoperative radiotherapy of breastcancer patients—a long-term follow-up. Acta Oncol39:373–382.

Kahn CE Jr, Messersmith RN, Samuels BL. 1989. Brachial plex-

Plexopathies 421

3601_e18_p413-422 2/19/02 8:58 AM Page 421

opathy as a complication of intraarterial cisplatin chemo-therapy. Cardiovasc Intervent Radiol 12:47–49.

Killer HE, Hess K. 1990. Natural history of radiation-inducedbrachial plexopathy compared with surgically treated pa-tients. J Neurol 237:247–250.

Kori SH, Foley KM, Posner JB. 1981. Brachial plexus lesionsin patients with cancer: 100 cases. Neurology 31:45–50.

Lachance DH, O’Neill BP, Harper CM Jr, Banks PM, CascinoTL. 1991. Paraneoplastic brachial plexopathy in a patientwith Hodgkin’s disease. Mayo Clin Proc 66:97–101.

Mondrup K, Olsen NK, Pfeiffer P, Rose C. 1990. Clinical andelectrodiagnostic findings in breast cancer patients with ra-diation-induced brachial plexus neuropathy. Acta NeurolScand 81:153–158.

Moskovic E, Curtis S, A’Hern RP, Harmer CL, Parsons C. 1992.The role of diagnostic CT scanning of the brachial plexusand axilla in the follow-up of patients with breast cancer.Clin Oncol (R Coll Radiol) 4:74–77.

Olsen NK, Pfeiffer P, Mondrup K, Rose C. 1990. Radiation-in-duced brachial plexus neuropathy in breast cancer patients.Acta Oncol 29:885–890.

Pancoast HK. 1932. Superior pulmonary sulcus tumor. J AmMed Assoc 99:1391–1393.

Pettigrew LC, Glass JP, Maor M, Zornoza J. 1984. Diagnosisand treatment of lumbosacral plexopathies in patients withcancer. Arch Neurol 41:1282–1285.

Pierce SM, Recht A, Lingos TI, et al. 1992. Long-term radia-tion complications following conservative surgery (CS) andradiation therapy (RT) in patients with early stage breastcancer. Int J Radiat Oncol Biol Phys 23:915–923.

Powell S, Cooke J, Parsons C. 1990. Radiation-induced bra-

chial plexus injury: follow-up of two different fractionationschedules. Radiother Oncol 18:213–220.

Qayyum A, MacVicar AD, Padhani AR, Revell P, Husband JE.2000. Symptomatic brachial plexopathy following treatmentfor breast cancer: utility of MR imaging with surface-coiltechniques. Radiology 214:837–842.

Roth G, Magistris MR, Le Fort D, Desjacques P, Della Santa D.1988. [Postradiation brachial plexopathy. Persistent con-duction block. Myokymic discharges and cramps]. RevNeurol (Paris) 144:173–180.

Sheldon T, Hayes DF, Cady B, et al. 1987. Primary radiationtherapy for locally advanced breast cancer. Cancer60:1219–1225.

Sundaresan N, DiGiacinto GV. 1987. Antitumor and antinoci-ceptive approaches to control cancer pain. Med Clin NorthAm 71:329–348.

Taylor BV, Kimmel DW, Krecke KN, Cascino TL. 1997. Mag-netic resonance imaging in cancer-related lumbosacralplexopathy. Mayo Clin Proc 72:823–829.

Thomas JE, Cascino TL, Earle JD. 1985. Differential diagnosisbetween radiation and tumor plexopathy of the pelvis. Neu-rology 35:1–7.

Thyagarajan D, Cascino T, Harms G. 1995. Magnetic resonanceimaging in brachial plexopathy of cancer. Neurology45:421–427.

Truex RC, Carpenter MB. 1969. Segmental and peripheral in-nervation. In: Human Neuroanatomy, 6th ed. Baltimore:Williams & Wilkins, 194 pp.

Wouter van Es H, Engelen AM, Witkamp TD, Ramos LM, Feld-berg MA. 1997. Radiation induced brachial plexopathy: MRimaging. Skeletal Radiol 26:284–288.

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