Acute inflammatory demyelinating polyradiculoneuropathy
Mar. 22, 2023
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US Number: +1-619-640-4660
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Brachial plexopathy is the most common complication of therapeutic irradiation affecting the peripheral nervous system. Patients treated for breast carcinoma are most often affected; radiation brachial plexopathy is a significant source of morbidity. Lumbosacral plexopathy is also an increasingly recognized complication of radiation therapy for a number of neoplasms. Radiation techniques such as stereotactic body irradiation and intensity-modulated radiotherapy also carry a risk of plexus injury. It is important for neurologists to diagnose radiation-induced plexopathies early and to differentiate them from plexus metastases or other causes of plexopathy. The authors discuss the clinical presentations, diagnostic issues, and management of patients with radiation plexopathies.
• Radiation injury to the brachial plexus most often occurs after treatment for breast cancer, whereas lumbosacral plexopathy occurs after treatment of a number of primary or metastatic pelvic tumors.
• Radiation plexopathy generally presents with painless numbness and sensory symptoms in the affected limb, with variable weakness. Pain may occur, but is usually not early or prominent.
• The most frequent differential diagnosis is distinguishing radiation plexopathy from metastases to the brachial or lumbosacral plexus.
• The clinical course of radiation plexopathy is variable, though most patients suffer from progressive sensory and motor deficits. Therapy options are very limited.
The first reports of radiation-induced brachial plexopathy appeared in the early 1960s shortly after the widespread introduction of modern megavoltage radiotherapy for treatment of breast carcinoma. Radiation brachial plexopathy is currently the most frequent complication of radiotherapy affecting the peripheral nervous system. Lumbosacral plexopathy is less common and has been clearly recognized only during the past 20 years.
Radiation-induced brachial plexopathy can be divided into two categories: (1) relatively rare instances occurring during or shortly after completion of radiotherapy and (2) the more common "delayed progressive" cases. Acute brachial plexopathy may occur during the course of axillary and supraclavicular irradiation for Hodgkin disease (86; 75). Severe unilateral or bilateral shoulder pain is followed by weakness involving mainly the deltoid and supraspinatus muscles, with partial recovery. The acute onset of symptoms and the distribution of weakness in these patients closely resemble "cryptogenic" brachial plexopathy or "neuralgic amyotrophy."
A syndrome of "early delayed" radiation, brachial plexopathy occurs in approximately 1% of women treated for breast carcinoma (94; 87). Onset of neurologic symptoms occurs within the first six months after completion of radiotherapy. Paresthesias of the hand and forearm are the presenting symptoms in 90% of patients, with shoulder and axillary pain in some patients; the pain and sensory symptoms improve over several months. During this time some patients develop mild weakness, which resolves almost completely.
The latent interval for delayed radiation brachial plexopathy is generally at least 12 months, with a broad peak of onset of neurologic symptoms from 1.5 years to four years after radiotherapy (08; 64; 37; 20; 15). Patients may continue to develop brachial plexopathy 10 years or more after radiation therapy (59). There is no obvious relationship between the latent period and the radiation dose, except for shorter latencies in patients who receive a second course of irradiation to the plexus.
The most common presenting symptoms of radiation brachial plexus injury are numbness and paresthesias of the hand and fingers, with weakness tending to develop later in the course (108; 64; 68; 53; 37; 15). Most patients do not have pain at the outset, and approximately one third of patients have minimal or no pain throughout their entire course (108; 64).
Acute lumbosacral plexopathy may occur during or shortly after radiation therapy for pelvic tumors (44); in some of these patients, pain is intractable and out of proportion to motor or sensory symptoms. A subacute lumbosacral plexopathy has been reported in 3% of young men treated with radiation for testicular seminoma (13). Patients develop some combination of pain, weakness, and sensory symptoms after a postradiation latency of two to six months; the symptoms generally resolve over several weeks to months. The latent interval between irradiation and the onset of neurologic symptoms in patients with "delayed" lumbosacral plexopathy varies from three months to 30 years, with a median interval of approximately five years (85; 107). There is not a clear correlation between the radiation dose and the duration of the latent interval. Radiation-induced lumbosacral plexopathy usually presents as bilateral but asymmetric leg weakness (107). The weakness may involve any muscles innervated by L2 through S1, but it often has an L5-S1 predominance. Atrophy, fasciculations, and loss of tendon reflexes accompany the weakness. Pain eventually occurs in approximately one half of patients, but it is usually not early or severe. Approximately one third of patients have early and prominent numbness and paresthesias (05). Bladder or bowel symptoms are unusual, and, if present, they are often attributable to radiation-induced proctitis or bladder fibrosis (107).
Radiation brachial plexopathy generally takes one of two courses (108; 08; 64; 37). In at least two thirds of patients, the motor and sensory deficits gradually worsen over several years to a level of severe neurologic disability. The remaining patients have a spontaneous cessation of progression after one year to three years (108; 53; 61). Spontaneous recovery of neurologic function is highly unusual. In some patients, the dysesthesias and pain diminish concurrently with worsening weakness, whereas other patients suffer from persistent or even increasing pain with progressive motor and sensory loss.
Patients with a syndrome suggestive of lumbosacral plexopathy occurring shortly after radiation often show neurologic improvement (13). The most frequent course of “delayed” radiation lumbosacral plexopathy is a slow progression over months to years (107). A few patients have a more rapid progression or alternatively show stabilization of neurologic deficits after a period of progression (48). Exceptional patients eventually have significant resolution of weakness and sensory symptoms (34; 24).
A 56-year-old woman underwent right modified radical mastectomy and axillary lymph node dissection for breast carcinoma followed by radiotherapy (55 Gy) encompassing the supraclavicular and axillary areas. She remained well until 50 months after completion of radiation, when she developed painless numbness and paresthesias of the first three digits of the right hand, extending along the dorsum of the hand and forearm. Over the subsequent three months she noted decreased grip strength and dexterity of the right hand. Examination revealed postradiation skin changes and lymphedema of the right arm. There was no Horner syndrome. Motor exam showed 4+/5 weakness of the right triceps, wrist dorsiflexors, wrist pronation, and supination. Muscle stretch reflexes were 2+ and symmetric except for decreased right triceps jerk. There was patchy decrease in pinprick sensation over the dorsum of the hand and first two digits. Chest x-ray and MR scans of the cervical spine and brachial plexus were all unremarkable. Electrophysiologic studies showed normal nerve conduction velocities but low amplitude median and ulnar sensory nerve action potentials. Needle EMG showed large amplitude motor units, fibrillations and positive sharp waves in the triceps and first dorsal interosseous, and myokymic discharges in the first dorsal interosseous. A 2-week tapering course of dexamethasone had no effect on her symptoms. Over the next four months, she noted further decrease in grip strength. A three-month trial of warfarin did not produce any improvement in symptoms, neurologic exam, or electrophysiologic findings. Eighteen months after the onset of neurologic symptoms, she remained without evidence for recurrent tumor.
The restricted occurrence of acute brachial plexopathy during radiotherapy for Hodgkin disease, but not for other tumors (86; 75), argues against direct radiation damage to the plexus and in favor of an inflammatory or immune process specifically related to the Hodgkin disease. Early delayed reversible brachial plexopathy reported within several months of treatment for breast carcinoma is most likely due to reversible damage to axons or myelin (94).
The exact pathogenesis of delayed radiation injury to the brachial or lumbosacral plexus remains unclear. The bulk of experimental animal data support vascular injury as the key event (56); however, peripheral axons and myelin sheaths are also clearly susceptible to direct damage by irradiation (109).
Radiation plexopathy is characterized by extensive fibrosis within and surrounding nerve trunks of the brachial or lumbosacral plexus with demyelination and loss of axons (108; 107). It is difficult, however, to reconstruct the pathophysiology based on this end-stage appearance. The occasional finding of hyalinized and obliterated vessels supports the hypothesis that vascular damage is an important, if not the primary, cause of plexopathy.
There is a correlation between the risk of radiation brachial plexopathy and the total dose of radiation administered to the plexus. The risk of brachial plexopathy is generally considered to be 5% or less within five years after 60 to 62 Gy given in daily fractions of 2 Gy or less (33). At doses above 70 Gy the risk of brachial plexopathy rises sharply, to as high as 50% after 75 to 77 Gy (20; 32). There is some evidence for increased risk of plexopathy when patients receive daily dose fractions of more than 2 Gy (“hypofractionation”) (45; 43). However, newer data may suggest that hypofractionated radiation results are similar compared to conventional fractionated courses (98; 09; 74; 112) and possibly have decreased rates of plexopathy (22). Plexopathy occurs more frequently when a larger volume of the plexus is irradiated (32; 21), which may be more pronounced in thin and younger patients as they typically receive a higher dose of radiation during breast treatment (117). It also occurs when patients receive two separate courses of "subthreshold" irradiation, and some evidence suggests a higher risk of plexopathy if patients receive concurrent radiation and chemotherapy, though this remains unclear (87; 83).
Changes in clinical practice and the development of new radiotherapy technologies have increased concern for radiation brachial plexopathy. The recommended radiation dose for non-small-cell lung carcinoma has increased, leading to an increased incidence of brachial plexopathy after treatment of apical tumors (04; 32). Stereotactic body radiation therapy (SBRT), which delivers an extremely conformal treatment course in less than five fractions, for apical lung carcinoma results in conflicting amounts of plexopathy (41; 99), with the risk from stereotactic body radiation therapy being low when the maximum dose to the brachial plexus is less than 30 Gy in three fractions (71). Moreover, stereotactic body radiation therapy to the cervical/thoracic spine is being used to provide durable control of painful metastases but also poses a risk for brachial plexopathy (125). Other forms of radiation, specifically for patients with head and neck cancer, can exceed 70 Gy (21). In one modern series, 20% of five-year survivors had symptoms of brachial plexopathy (20). Intensity-modulated radiation therapy (IMRT) for head and neck cancer may increase exposure of the plexus compared to historical conventional radiation therapy (19). However, intensity-modulated radiation therapy may also allow a higher dose of radiation delivered to the adjacent tumors while avoiding the brachial plexus (110; 80), and may still be safe when delivered at high doses to the brachial plexus (89). So, these modern treatments allow improved dose delivery to tumors near adjacent critical structures but they may place patients at increased risk for plexopathy.
There are several formulas for computing a dose equivalent to allow comparison of the radiobiological effect (and risk of delayed tissue injury) for different radiation fractionation schedules. As of 2021, the most frequently used formula is the linear-quadratic model (42; 118), and most recently a log-linear model demonstrating a low rate of plexopathy when the conventionally fractionated dose is less than 60-66 Gy (119). Although these models are reassuring, there is no absolute safety threshold for radiation brachial plexopathy, as there are reports of a higher than expected incidence after relatively low radiation doses (81; 83). Whereas other series report a low incidence of brachial plexopathy despite radiation schedules delivering a high dose equivalent (07).
The relationship between radiation dose and the occurrence of lumbosacral plexopathy is more complicated than for brachial plexopathy. With standard once-daily external beam radiotherapy, lumbosacral plexopathy has occurred after doses ranging from 30 Gy to 67.5 Gy (05; 107). Many patients with radiation lumbosacral plexopathy received two courses of external beam irradiation (05), a combination of external beam treatment plus intracavitary radiation implants (85; 48), or combined photon and proton beam radiation (88). The radiation exposure to the lumbosacral plexus and cauda equina in these patients may be 80 “Gy equivalents" or more. Another factor is that irradiation of the para-aortic region or pelvis exposes the nerves over long distances. Irradiation injury to peripheral nerves becomes more likely as the radiation field size increases, but this factor is difficult to quantify (109). Intensity-modulated radiation therapy (IMRT) is increasingly used to treat several pelvic neoplasms, including carcinomas of the cervix, rectum and prostate. Pre-treatment delineation of the lumbosacral plexus is important to avoid inadvertent over-exposure to the plexus (121), with dose constraints being proposed for cervical cancer treatments (114). Lumbosacral plexopathy has been reported following re-irradiation of spinal and pelvic metastases with stereotactic body radiation (47; 12; 125).
Breast carcinoma is the tumor most often associated with radiation brachial plexopathy, accounting for 40% to 75% of patients in the literature, followed by lung carcinoma, head and neck cancer, and then by lymphoma (64; 53).
Radiation-induced lumbosacral plexopathy most often follows irradiation for pelvic tumors such as carcinomas of the bladder, rectum, uterus, or cervix; testicular tumors; or lymphoma involving para-aortic lymph nodes (05; 02; 85; 107; 48). Patients may have received external beam photon therapy or interstitial or intracavitary radiation implants (104; 48). With the use of 3D imaging for target delineation and improvements in radiation delivery, the incidence of plexopathy is 1.2% to 1.6% for brachial plexopathy in women radiated for breast cancer (76; 92) and 0.4% with the use of intensity-modulated radiation therapy (92).
The main preventive measures are to deliver radiation within the broad guidelines for total dose and daily dose fractions. Radiographic "contouring atlases" are available to aid in the accurate delineation of the brachial plexus for treatment planning (120). In a small number of patients with apical lung carcinoma, stereotactic proton radiation was able to reduce exposure to the brachial plexus relative to conventional photon radiation (91).
The major issue in differential diagnosis is distinguishing brachial or lumbosacral radiation plexopathy from tumor metastasis to the plexus. Carcinomas of the breast and lung together account for an overwhelming majority of brachial plexus metastases. Symptomatic brachial plexus metastases have been estimated to occur in approximately 4% of patients with lung cancer and 2% of patients with breast cancer. Among other primary tumors only lymphomas metastasize to the brachial plexus with any appreciable frequency (70). There are scattered reports of brachial plexus metastases from a variety of other tumors (64; 16). In most cases, metastatic tumors reach the plexus by extension from axillary or supraclavicular lymph nodes, whereas superior sulcus (Pancoast) bronchogenic carcinomas spread directly to the adjacent plexus. Rarely, tumors may spread hematogenously into the nerve trunks in the absence of tumor in the adjacent soft tissues or lymph nodes (79).
The diagnosis of radiation brachial plexopathy in the literature is often made inferentially because of the limitations of imaging studies (especially in the pre-MR era) and the fact that few patients undergo surgical exploration. Patients were, therefore, presumed to have radiation brachial plexopathy if they had not concurrently developed systemic metastases; if there was no evident tumor in bone, lymph nodes, or soft tissue adjacent to the plexus; and if follow-up over a certain period of time did not reveal evidence for brachial plexus metastases. These criteria clearly have exceptions because brachial plexus metastases may occur as an isolated site of tumor spread, and some patients have no other evidence for metastatic tumor for several years or more after the onset of metastatic plexopathy (108; 64; 77).
The latent period between the completion of irradiation and the onset of neurologic symptoms for patients with metastatic versus radiation brachial plexopathy can be as short as several months or longer than five years following irradiation. Median latent intervals were shorter for metastatic than for radiation plexopathy patients in some series (64; 68), but the two groups overlap considerably, and a shorter interval for metastatic disease has not been observed universally (108; 06).
Radiation-induced skin changes, lymphedema, and soft-tissue induration of the axilla and supraclavicular fossa are each present in 30% to 75% of patients with radiation brachial plexopathy (108; 06; 64; 68). These changes are also present in a lower, but still sizable, proportion of patients with brachial plexus metastases. Horner syndrome is present in up to one half of patients with metastatic plexopathy and is virtually never seen in patients with radiation brachial plexopathy (64; 68; 81).
The distribution of neurologic signs and symptoms varies somewhat between patients with metastatic versus radiation brachial plexopathy, but the degree of overlap does not permit an absolute distinction to be made on these grounds alone. In some series, patients with plexus metastases had predominant involvement of C8-T1 roots or of the lower trunk (64; 68). Of the patients with signs and symptoms of "diffuse" metastatic brachial plexopathy, many were found to have epidural tumor extension to account for the "upper trunk" deficits (64). In contrast, patients with radiation brachial plexopathy reported paresthesias of the first two digits as the earliest symptom, and the majority of patients had weakness restricted to muscles innervated by the C5 to C6 roots (64). The differential localization of radiation versus metastatic plexopathy was thought to be due to the close proximity of the lower trunk of the plexus to the lateral group of axillary lymph nodes (which drains the breast) and to the upper lobe of the lung, enabling breast and lung tumors to reach the plexus by direct extension. The relative sparing of the lower plexus in radiation injury was believed to be due to partial shielding of these elements by the clavicle.
In several other series, however, there was a much less clear-cut clinical distinction between radiation and metastatic brachial plexopathy. Many patients with radiation brachial plexopathy in these series had weakness involving mainly the muscles innervated by the C8-T1 roots or lower trunk (68; 53). Conversely, "diffuse" involvement of the plexus was equally common among patients with metastases and patients with radiation damage (108; 111; 37).
The most reliable clinical feature to distinguish radiation brachial plexopathy from plexus metastases is pain. Metastatic brachial plexopathy is characterized by early, severe, and unrelenting pain in more than 80% of patients (108; 64; 68; 53). Pain often precedes numbness or weakness by up to several months (64). Pain is generally, but not always, most severe in a C8-T1 dermatomal distribution (64). In contrast, fewer than 20% of patients with radiation brachial plexopathy report pain at the outset, and approximately one third of patients have minimal or no pain throughout their entire course (108; 64). Exceptional patients with radiation plexopathy do have early and severe pain.
Metastases to the lumbosacral plexus most often arise from colorectal carcinomas, breast carcinoma, gynecologic carcinomas, retroperitoneal or pelvic sarcomas, or lymphoma (58; 107). In most patients, tumors invade the plexus by direct extension from pelvic tumor or from metastases to nearby lymph nodes. At least 75% of patients with lumbosacral plexus metastases present with pain, usually unilateral and affecting the low back, hip, and thigh (85; 58; 107). Nearly all patients eventually develop local or radicular pain that is characteristically worse at night and is usually unrelenting despite narcotics. Most patients subsequently develop weakness and sensory symptoms after a lag period of weeks to months. Bladder dysfunction is uncommon. The tempo of progression of symptoms is usually faster in patients with metastases than with radiation plexopathy. Some patients with lumbosacral plexus metastases show clinical improvement with dexamethasone; this does not occur with radiation plexopathy (85).
The brachial plexus may rarely be the site of primary benign or malignant nerve sheath tumors. Schwannomas and neurofibromas are the most common benign tumors arising in the brachial plexus (62; 26). Approximately one third of reported patients have type 1 neurofibromatosis. Nearly all patients with brachial plexus schwannomas have a palpable mass. Slightly fewer than half the patients have local or radiating pain at the time of diagnosis; pain is more frequent with neurofibromas than with schwannomas. Paresthesias or sensory loss are less common, and fewer than 20% of patients have weakness at presentation. There is no particular predilection for involvement of specific segments of the plexus. Some neurofibromas are "dumbbell tumors," which extend into the spinal epidural space.
Malignant nerve sheath tumors (including malignant schwannomas and neurofibrosarcomas) arising in the brachial plexus are much less common than benign tumors. Malignant nerve sheath tumors of the plexus occasionally arise from malignant degeneration of preexisting benign tumors, particularly in the setting of neurofibromatosis. Malignant nerve sheath tumors of the brachial plexus typically present as a painful mass with a relatively short duration of symptoms (30; 62).
Neurofibroma, schwannoma, or malignant nerve sheath tumors may arise in the brachial plexus as a sequel to prior irradiation. These nerve sheath tumors may occur from two years to more than 30 years following irradiation to the region for Hodgkin lymphoma, breast cancer, or other tumors (40; 113; 29; 123). Postirradiation malignant fibrous histiocytoma or other sarcomas in the brachial or lumbosacral plexus have also been reported (85; 51; 111).
There are anecdotal reports of plexopathy occurring as a complication of cancer treatment other than radiation, including acute brachial plexopathy occurring after high-dose cytarabine (95) or after infusion of cisplatin into the axillary artery (60). Reversible unilateral or bilateral brachial plexopathy has occurred within one week of interleukin-2 treatment for renal carcinoma or melanoma (73).
Bilateral "demyelinating" brachial plexopathy has been reported in a patient with syngeneic graft-versus-host disease (122). Lumbosacral plexopathy with acute onset and permanent neurologic deficit may occur after infusion of cisplatin, doxorubicin, 5-fluorouracil, or other chemotherapy agents into the internal iliac artery (85; 17). Lumbosacral polyradiculopathy can occur acutely after intrathecal methotrexate administration (84).
Brachial plexopathy may rarely occur as a paraneoplastic syndrome in patients with Hodgkin lymphoma (66), manifesting as painless, bilateral asymmetric weakness and sensory symptoms that may improve with prednisone. Involvement of the anterior horns of the cervical spinal cord in patients with paraneoplastic encephalomyelitis and small cell lung carcinoma may produce bilateral upper extremity weakness mimicking brachial plexopathy (78).
Delayed injury to the cauda equina after radiation can mimic lumbosacral radiation plexopathy. Patients develop asymmetric bilateral leg weakness and less often pain or sensory loss more than 10 years after radiation for lymphoma, seminoma, or other abdominal or pelvic tumors (57; 88; 31). MRI scans show patchy or multinodular enhancement along the conus medullaris and cauda equina. CSF protein is elevated but cytology is negative. The neurologic deficits eventually stabilize or may continue to worsen slowly over years.
Radiation injury to the cauda equina may overlap with what was previously described as a selective lower motor neuron syndrome following periaortic lymph node radiotherapy for testicular tumors or lymphoma or following spinal axis radiation for medulloblastoma (65; 46; 67; 11). Patients develop subacute, unilateral, or asymmetric bilateral leg weakness beginning six to 24 months after completion of irradiation with no pain or sensory symptoms. Examination shows muscle atrophy, fasciculations, normal or decreased muscle stretch reflexes, flexor plantar responses, and no sensory or sphincter involvement. Nerve conduction over sensory pathways is usually normal, but some patients have prolonged somatosensory evoked potentials (38). Needle EMG shows denervation changes. MR scanning was unremarkable in the few cases published. In most patients, the syndrome progresses slowly over several months and then stabilizes but does not improve. In one autopsied patient, microvascular changes were present in the cauda equina, whereas the spinal cord was normal (11). It is believed that nerve roots are the primary site of injury in these patients; the selective involvement of motor fibers is unexplained.
A syndrome termed "subacute motor neuronopathy" occurs as a paraneoplastic syndrome in patients with lymphomas or thymoma (96). Patients develop subacute, progressive weakness, often asymmetric or patchy and predominantly involving the legs, without pain or significant sensory loss. Examination reveals a pure lower motor neuron picture with moderate to severe weakness, fasciculations, atrophy, and diminished deep tendon reflexes. The syndrome has occurred prior to the discovery of a neoplasm as well as after complete remission. The neurologic deficits eventually stabilize spontaneously or partially improve in most patients after a period of months to years.
Electrodiagnostic studies are useful in assessing the topography and severity of radiation brachial plexopathy. Characteristic changes include diminished amplitude of sensory nerve action potentials (often the earliest finding), prolongation of F wave latencies, and EMG evidence for chronic partial denervation (116; 81). A motor nerve conduction block across the plexus is present in the majority of patients (53; 35). In many patients, the electromyographic abnormalities are more extensive than would have been predicted by the clinical examination. In agreement with the clinical signs and symptoms, EMG evidence of denervation in many patients with radiation plexopathy is diffuse or is present predominantly in muscles supplied by the upper trunk (116). In some patients, however, the EMG abnormalities are mainly in the distribution of C8 and T1 (36).
The electrophysiologic abnormality that most reliably differentiates radiation from metastatic brachial plexopathy is myokymia, defined as spontaneous, semirhythmic bursts of potentials. Myokymia is present in one or more muscles in 50% to 70% of patients with radiation brachial plexopathy (03; 102; 68; 53). Other abnormal discharges less frequently seen include low-frequency bizarre discharges, "grouped discharges," and "myoclonic" discharges (102). The number of myokymic discharges may vary considerably among muscles innervated by the same trunks and cords of the plexus. Myokymia is rarely if ever present in patients with brachial plexus metastases (03; 68; 53; 111).
Electrophysiologic testing in patients with radiation lumbosacral plexopathy shows reduced amplitude of compound muscle action potentials, abnormal or absent sural nerve potentials, fibrillations, and chronic motor unit changes (107). One half of patients have fibrillations in paraspinal muscles, indicating additional injury to nerve roots. Myokymic discharges are present in approximately 60% of patients, especially in proximal muscles (102; 107). The discharges may be widely scattered and are often present in muscles not overly weak. Low-frequency periodic discharges have also been reported (02).
CT or MR scanning is often, but not always, useful in distinguishing between radiation brachial plexopathy and plexus metastases.
MR scanning with and without contrast provides simultaneous multiplanar images and better resolution of soft tissue structures than CT scanning. The sensitivity of MR scanning in detecting metastases in or near the brachial plexus is more than 80% (111). MR appears to be somewhat more sensitive than CT in detecting metastases (111). The presence of a mass in the plexus is the most reliable feature distinguishing metastases from radiation injury. Patients with radiation plexopathy may have low or high signal intensities in the plexus on T2-weighted images, and some patients show gadolinium enhancement (10; 115; 93). Some patients have no obvious tumor mass on MR scans and have changes consistent with "fibrosis" or radiation injury, but they later turn out to have plexus metastases. MR scanning may identify myositis or unsuspected bone metastases, which may contribute to patients' symptoms (72).
High-quality contrast-enhanced CT scans show a circumscribed soft tissue mass or diffuse soft tissue infiltration in up to 90% of patients with brachial plexus metastases (16). CT scans in patients with radiation plexopathy are either normal or show an ill-defined loss of normal tissue planes without any identifiable mass (16; 07; 53). CT scanning with multiplanar reconstruction probably increases the sensitivity in detecting metastases (39). In patients unable to undergo MRI, CT scanning provides the next best anatomic evaluation of the plexopathy (14).
Positron emission tomography using fluoro-deoxyglucose may be useful in identifying metastatic breast cancer in or near the brachial plexus (01; 55; 101). In some patients, fluoro-deoxyglucose-PET identify tumor not clearly imaged by CT or MR scanning. Conversely, fluoro-deoxyglucose-PET scans are negative in a few patients believed to have radiation plexopathy. A negative fluoro-deoxyglucose-PET scan may prove useful in diagnosing radiation plexopathy in select cases with positive MR findings (18). However, to date, there is little solid information regarding the reliability with which fluoro-deoxyglucose-PET can differentiate brachial plexus metastases from radiation plexopathy.
CT scans of the abdomen and pelvis are generally normal in patients with radiation lumbosacral plexopathy (85; 107). CT scans of the pelvis or abdomen show lymphadenopathy, tumor masses, or bone erosion in 75% of patients with lumbosacral plexus metastases (58; 107). Tumor cells that spread in a linear fashion along nerve roots may not be apparent on scans; in these patients the initial scan is normal, but repeat scans usually show a tumor within six months (58). MR scanning is somewhat more sensitive than CT in detecting thickening of the lumbosacral plexus or tumor masses that involve the plexus (105). MR "neurography" using high-resolution T1-weighted sequences and fat-suppression T2-weighted sequences probably increases the sensitivity for detecting diffuse tumor infiltration of the lumbosacral plexus (82). Although imaging of plexopathy can be challenging, knowledge of anatomy, pathology, and imaging findings can significantly aid in noninvasive diagnosis (49).
Surgical exploration of the brachial plexus or CT-guided needle biopsy is rarely needed given the advances in diagnostic imaging but may be done as a "last resort" effort in attempting to differentiate metastases from radiation damage, but surgery carries morbidity and may miss metastatic tumor (06; 64; 23).
There are numerous anecdotal reports or uncontrolled studies of surgical attempts to improve neurologic function and relieve pain in patients with radiation-induced brachial plexopathy. The most common procedure is neurolysis (opening the epineural sheath) and removal of scar tissue, with or without placement of an omental flap to "revascularize" the plexus (69). Some patients with severe pain obtained significant pain relief following surgery (63; 61; 28; 52). However, the likelihood of improvement is difficult to glean from the literature, and there are few reports that include long-term follow-ups of patients. Neurolysis rarely relieves motor or sensory deficits, and it is not clear whether surgery can halt the progression of deficits (108; 61). In 20% to 50% of patients, surgery causes a significant deterioration in sensory or motor function (63; 28). Some patients who undergo neurolysis are found to have previously unsuspected plexus metastases (28). Additional surgical options include omentoplasty (76) and adipofascial deltopectoral flap (27), in which 82% of patients reported improved pain symptoms. Both techniques are thought to improve symptoms by promoting revascularization.
There are anecdotal reports of long-lasting pain relief in patients with radiation brachial plexopathy following dorsal root entry zone lesions (124; 106) or chemical sympathectomy (37). There is a single case report using pulsed radio frequency ablation showing decrease in total opiate use; however, this patient passed away in hospice 2 weeks after ablation, and therefore, long-term data are limited (97).
Anticoagulation with intravenous heparin followed by chronic warfarin has been reported to bring about neurologic improvement in a few patients with radiation-induced brachial or lumbosacral plexopathy (50; 100). Based on only a few anecdotal reports, the actual likelihood of neurologic improvement in patients treated with anticoagulants is not known.
Several regimens including hyperbaric oxygen and vitamin E have been tried with limited success. In a double-blind randomized trial, hyperbaric oxygen did not produce clear beneficial effects in patients with radiation brachial plexopathy (90). A triplet regimen of pentoxifylline-tocopherol and clodronate was used in a randomized comparison to placebo and failed to show a benefit regarding pain, paresthesia, or motor disability (25). However limited these experiences are, providers still recommend vitamin E and hyperbaric oxygen (103).
Although there are conflicting results with the aforementioned methods, conservative measures with occupational and physical therapy may provide some improvement (54). Medical management options include opiates, anticonvulsants, tricyclic antidepressants, and selective serotonin-norepinephrine reuptake inhibitors (97).
The lack of clearly effective treatments for radiation plexopathy underscores the importance of delivering radiation therapy, which is effective and yet minimizes the risk of occurrence of plexopathy.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Muzamil Arshad MD
Dr. Arshad of the University of Chicago has no relevant financial relationships to disclose.See Profile
Steven J Chmura MD
Dr. Chmura of the University of Chicago has no relevant financial relationships to disclose.See Profile
Deric M Park MD
Dr. Park of the University of Chicago has no relevant financial relationships to disclose.See Profile
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