Author(s): Michael Dean Stubblefield, MD, Noble Jones, MD
Originally published: July 25, 2012 Last updated: October 30, 2025
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Disease/Disorder

Definition

Radiation-induced plexopathy (RIP) is a potentially severe, debilitating iatrogenic neurologic impairment of the peripheral nervous system at the level of the cervical, brachial or lumbosacral plexus. Injury to these plexuses commonly presents with nonspecific neurologic changes that can include a combination of numbness, paresthesias, neuropathic pain, vasomotor changes and weakness that can progress to complete loss of function of the affected limb.1 Additionally, RIP can affect other plexuses such as the plexuses of the cardiovascular system, notably the cardiac plexuses, conduction pathways and plexuses of the great vessels. This often results in cardiac conduction abnormalities, arrhythmias, autonomic dysfunction, heart rate variability and baroreflex dysfunction.2 Neurologic impairment may also occur in the submucosal and myenteric plexus within the enteric nervous system with patients commonly presenting with pain, motility and absorption dysfunction, impaired sphincter control, bloating and tenesmus.3

Etiology and pathophysiology

The pathophysiology of RIP can be attributed to direct and indirect injury to the nerve plexus after exposure to ionizing radiation energy via external beam radiation or internal emitters such as radiopharmaceuticals delivered intravenously (i.e., radioactive iodine) or by insertion of radioactive “seeds” or plaques directly at the site of the tumor (i.e., brachytherapy). RT can achieve this by either direct cellular damage or indirectly through the production of free radicals. All cells are affected but rapidly dividing cancer cells are more susceptible.4

Radiation therapy causes immediate and long-term damage to healthy tissue near treated cancer. Because neurons are fully differentiated cells, they have poor repair capacity and dose-dependent susceptibility to radiation injury. Radiation directly damages the cellular DNA of the nerve resulting in axonal injury and demyelination. Acutely, nerves may have reversible demyelination and intraneural edema. Chronic effects may be the result of indirect radiation injury such as radiation induced fibrosis due to abnormal fibroblast proliferation which leads to excess collagen and extracellular matrix deposition. Inflammation, oxidative stress and vascular damage leads to tissue ischemia, setting the stage for late, irreversible radiation effects. Nerve plexuses are especially vulnerable because they are close to regions frequently targeted by radiation, increasing their risk of vascular damage.5

Epidemiology including risk factors and primary prevention

Depending on cancer type up to 50% of cancer patients will receive radiation therapy at some point during their cancer care, with up to 30% of patient receiving radiation therapy in the initial phase of treatment.6 Furthermore, patients at the highest risk or developing a radiation induced plexopathy include patients treated for head and neck cancer, breast cancer, apical tumors of the lungs, and lymphomas treated in the supraclavicular and axillary regions. The incidence of RIP affecting the cervical, brachial and lumbosacral plexus increases sharply with total radiation doses higher than 60 Gy, even with fractionation as low as 2 Gy.7 The enteric nerve plexus is also susceptible to radiation therapy, resulting in both acute and chronic functional changes in the gastrointestinal system. This results in dysmotility and disruption in secretion and absorption due to reduced cholinergic function and disorganized nitric oxide mediated activity due to neurotransmitter imbalance.3,8 Radiation therapy causes DNA damage, inflammation and neuroimmune dysregulation between enteric neurons and immune cells, later resulting in fibrotic changes.9

Acute onset of plexopathy related symptoms

Acute onset of symptoms varies from days to several weeks11 following radiation administration. For nerve plexuses that innervate voluntary muscle, paresthesias are the most common presenting symptom in RIP. Disorders of sensation such as tingling, burning, numbness and/or pain are common findings in the upper and lower extremities and pelvis as a result of radiation-induced cervical, brachial and lumbosacral plexopathies.10 Patients treated for gastrointestinal (GI) and pelvic cancers may show early signs of radiation-induced myenteric plexopathy resulting in dysregulation of the migrating motor complex (MMC) within the gastrointestinal system. These patients commonly present with symptoms of bloating, fecal incontinence, nausea, vomiting.11 In one rat study delayed gastric emptying of solids was experienced acutely after irradiation of the stomach.12

Subacute plexopathy related symptoms

In the weeks following the acute onset of RIP, patients’ symptoms may progress to include limb edema and worsening motor and sensory deficits.10 Within the GI system, decreased absorptive and secretory function may be associated with radiation-induced submucosal plexopathy and increased transit time may be associated with alterations to the MMC.11

Chronic plexopathy related symptoms

Signs and symptoms of plexopathy can develop and progress months, years, or decades following treatment. This phenomenon can be seen in patients in remission of any cancer treated by radiation. Hodgkin’s lymphoma (HL) patients13 treated with now obsolete techniques (e.g., mantle field radiation), head and neck cancer patients, and even those treated with advanced techniques (i.e., involved site radiation therapy), in which the radiation beam is more focused to affected lymph nodes in an attempt to reduce the size of the treatment area, are commonly affected. These patients often develop cervical and/or brachial plexopathy leading to severe atrophy, weakness and pain in their neck and upper extremities.14 In addition to severe lower extremity atrophy, weakness and pain, patients treated for GI cancers, pelvic cancers or malignancy of the thoracic or lumbar spine, often experience chronic gastrointestinal and genitourinary dysfunction such as sexual dysfunction, and bowel and/or bladder incontinence.15

Specific secondary or associated conditions and complications

Radiation fibrosis syndrome is a common side effect of external beam radiation therapy. It is associated with RIP and has a similar pathophysiology in that it is the result of radiation injury that triggers inflammatory pathways, resulting in the proliferation of myofibroblasts and excess production collagen and extracellular matrix. For reasons unclear at this time, neuronal tissue in the plexuses in these affected regions may be spared or minimally effected. However, symptoms associated with radiation fibrosis syndrome may overlap RIP and include dropped head syndrome, cervicalgia, cervical dystonia, trismus, dysphagia, dysarthria, paralysis of the affected limb(s), contracture, lymphedema, bowel or bladder incontinence, impotence, and chronic radiation enteritis.13,16,17

Essentials of Assessment

History

Patients with cervical, brachial, and/or lumbosacral radiation-induced plexopathy may report paresthesias, numbness, weakness, heaviness and swelling of the upper and lower distal limb(s).Pain (e.g. dysesthesias, allodynia, and hyperpathia) is generally seen later in the course of the disease and is more frequent in brachial than in lumbosacral plexopathy.Metastasis or local tumor recurrence should be considered in all patients presenting with signs and symptoms of RIP.18 The clinician should document a complete oncologic treatment history including specifics of radiation, systemic therapy and surgery. Understanding the total dose, fractionation and which tissues are encompassed by the radiation field is key to elucidating the potential clinical manifestations of RIP. Multiple neural structures including the spinal cord, nerve roots, plexus, peripheral nerve, and muscles may be damaged in head and neck cancer and HL patients. HL patients treated with mantle field radiation, for instance, can have a myelo-radiculo-plexo-neuro-myopathy underlying cervical dystonia, dropped head syndrome, and a variety of other clinical manifestations.19 Patients with radiation-induced myenteric plexus and or submucosal plexus may report frequent loose stools, nausea, vomiting, loss of appetited, abdominal cramps and pain, mucus discharge from the rectum and hematochezia or melena.18

Physical examination

A comprehensive history will inform and guide the physical exam. It is important to perform a detailed visual inspection of the patient’s anatomy to look for asymmetry, muscle atrophy, skin changes and lymphedema. Enlarged and/or indurated and non-mobile lymph nodes may indicate cancer recurrence. A detailed and comprehensive neurological exam including strength, sensation, and reflexes is critical to diagnosing plexopathy, clarifying which components of the plexus are affected and confirming if other neural structures are involved.20 Because nerve injury occurs distal to the anterior horn cell in isolated RIP, diminished reflexes and flaccid paralysis are generally expected. An abdominal exam and rectal exam may be necessary for patients who have received abdominal or pelvic irradiation, assessing for hyperactive or hypoactive bowel sounds, guarding, and abnormal masses. These findings along with correlation to patient history can be used to guide further management.

Functional assessment

Functional assessment tools help objectively document the patient’s functional status and monitor their progress or deterioration in response to various interventions.

  • Cervical Plexus Assessment Tools
    • The Toronto Bedside Swallowing Screening Test (TOR-BSST)
    • Gothenburg Trismus Questionnaire (GTQ)
    • Eating Assessment Tool-10 (EAT-10)
  • Brachial Plexus Assessment Tools
    • Brachial Assessment Tool (BrAT)
    • Upper Extremity Functional Index (UEFI)
  • Lumbosacral Plexus Assessment Tools
    • The Lower Extremity Functional Scale (LEFS)
    • Get Up and Go Test
    • Cleveland Clinic Florida (CCF)/Wexner Fecal Incontinence Score
    • The Michigan Incontinence Symptom Index (M-ISI)
  • Myenteric and Submucosal Plexus Assessment Tools
    • Cleveland Clinic Florida (CCF)/Wexner Fecal Incontinence Score

Laboratory studies

There are no lab abnormalities that would suggest a cervical, brachial, or lumbosacral radiation-induced plexopathy. However, electrolyte abnormalities may be present in patients with chronic enteritis, secondary myenteric and submucosal plexopathy. Additionally, these patients may also have a positive fecal occult blood stool. Depending on the region of the GI system irradiated, patients may also present with labs consistent with pancreatic or hepatic dysfunction.

Imaging

The only way to ensure that plexopathy is due to radiation and not cancer recurrence is with imaging and ultimately biopsy if a mass or infiltration is identified. Magnetic resonance imaging (MRI) with and without gadolinium, preferably comparing side-to-side, is usually the initial imaging study ordered to make this determination. Cancer mediated plexopathy typically shows contrast enhancement of a non-uniform asymmetric mass. With tumor involvement of the plexus (primary or metastatic), there is usually enhancement of nerve roots and T2-weighted hyper intensity, though different tumor types will have different, characteristic enhancement patterns, whereas radiation induced fibrosis will show low-signal intensity on T1-T2-weighted images in the tissue surrounding the nerve plexus.11,16 If MRI is negative and suspicion is high for tumor, then positron emission tomography should be ordered.If suspicion for tumor remains high, then repeating MRI and PET in 3-4 months may be indicated. If present, post-radiation plexopathy will typically reveal symmetric uniform swelling that may be enhanced with contrast up to several years after the last radiation treatment.

Supplemental assessment tools

Nerve conduction studies and electromyography (NCS/EMG) may be used to assess cervical, brachial plexus or lumbosacral plexus involvement. Gastric motility studies such as gastric emptying scintigraphy, wireless pH and motility capsules, stable isotope breath tests, single photon emission computed tomography (SPECT) and functional ultrasonography are some of the tests that can be used to assess the function of the migratory motor complex, but do not directly assess the enteric nervous system.7,11,16 Additionally, urodynamic studies and anorectal manometry can be used to assess the effects of the lumbosacral plexopathy on the genitourinary (GU) and gastrointestinal (GI) system, respectively. Video fluoroscopic swallow studies are used to evaluate swallow function.

Early predictions of outcomes

RIP is almost always chronically progressive, but the rate and pattern of deterioration is highly variable. The anatomical structures experiencing fibrosis are dependent on the radiation field of view as there may be a sharp demarcation of affected plexus structures with conformal radiation techniques. If the entire plexus is involved, complete loss if limb function is possible. The severity of radiation effects is also dependent on the type of radiation used, radiation total dose received as well as the fractional dose of each treatment. The effects on the myenteric and submucosa plexuses have a similar prognosis, but is poorly understood due to the lack of sophistication of current diagnostic technology in isolating and testing the enteric nervous system.

Social role and social support system

The effect of cancer on a patient’s social role largely depends on the extent and type of physical or functional impairments experienced. These may include challenges such as bowel or bladder dysfunction, occupational and physical limitations, chronic or hard-to-manage pain, and increased risk of social isolation. Participation in cancer support groups can provide significant social support by offering education about various illness-related syndromes, available treatment options, and opportunities to express the emotional and psychological impact of living with cancer, whether as a patient, survivor, or caregiver.

Rehabilitation Management and Treatments

Available or current treatment guidelines

There is no definitive treatment to arrest RIP progression or improve neurologic function. Treatment with a combination of tocopherol and pentoxifylline has been touted as helpful in reducing radiation-induced fibrosis and possibly stabilizing neurologic symptoms, but larger randomized trials are lacking and the available data is uncompelling.16 Hyperbaric oxygen has not been shown convincingly to have benefit for RIP. Potential aggravating factors, such as diabetes, hypertension, alcohol abuse, and acute edema, should be managed aggressively to prevent synergistic neurologic damage.10

An interdisciplinary team approach will improve the efficacy of both the intervention and communication with the patient. Physical therapy and occupational therapy are necessary to address weakness, myofascial restrictions, functional impairment, activities of daily living, return to work (including workplace modifications), adaptive equipment and orthotic restoration, tissue desensitization, and lymphedema management.Speech and language pathologists help to address dysphagia and apraxia. Cardiology gastroenterology, urology and nutrition specialists are necessary to support patients with severe cardiac, bowel or bladder dysfunction.

Pharmacologic treatment should be tailored to its efficacy and the patient’s side effect tolerance. Treatment options for neuropathic pain include tricyclic antidepressants (e.g., amitriptyline), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine), nerve stabilizers (e.g., gabapentin, pregabalin, carbamazepine), tramadol, antiarrhythmics (e.g., mexiletine), narcotics, and anesthetic interventions (e.g., nerve block).2,5,7

Microsurgical techniques such as nerve decompression, nerve transfers using healthy donor nerves, neurolysis and free function muscle transfer have been used to restore functionality in patients with RIP with varying success rates. Studies have shown that patients with RIP tend to have less favorable outcomes than patients who experience traumatic plexopathies. Surgical exploration has been attempted for restoration of vascular supply with mixed results and should be undertaken with caution only when conservative measures fail and symptoms are severe.

Coordination of care

In cancer rehabilitation, coordination of care is recognized as valuable in improving the patient’s experience during and after cancer treatments, improving outcomes, and lessening caregiver burden. Integrated treatment is provided by physiatrists, oncologists, pain specialists, gastroenterologists, urologists, speech and language pathologists, occupational and physical therapists, lymphedema specialists, and psychologic services.

Patient & family education

Patients and their family should be made aware of potential clinical progression in RIP. They should understand that there is no definite cure and that there is no evidence that available treatment options will delay or halt the progression of the disease. Family members should know and understand that their supportive role for the patient may include assistance with activities of daily living.

Translation into practice

Cancer patients who receive radiation as part of cancer treatment should be educated about potential long-term complications associated with both the disease and treatment. Providers must ensure that the patient understands why radiation is used as part of the treatment. It is important to remember that RIP can present and progress decades following radiation treatment and should be considered in patients who developed appropriate symptoms. If neurologic symptoms develop following radiation treatment, differentiation between radiation-induced and neoplastic plexopathy is critical to preserve function and life. Primary management for RIP is supportive and directed at lessening symptoms.

Cutting Edge/Emerging and Unique Concepts and Practice

Upper and lower limb exoskeletal systems and hybrid assistive limb devices may help to bridge the gap until new medical therapies, such as tissue engineering, can prove effective at repairing peripheral nerve injury. Transcutaneous nerve stimulation has shown to be an effective method of managing neuropathic pain in radiation-induced plexopathy.

Gaps in the Evidence-Based Knowledge

It is known that effective postoperative radiotherapy can diminish cancer relapse and RIP is a potential complication of high dose radiation. Even though there is no cure for RIP, the consequences for not optimally treating it can be severe. Although RIP occurrence has diminished with new treatment approaches, the evidence-based therapeutic options to prevent progression of RIP and manage its symptoms are limited.

References

  1. Stubblefield MD, Ibanez K, Riedel ER, et al. Peripheral nervous system injury after high-dose single-fraction image-guided stereotactic radiosurgery for spine tumors. Neurosurg Focus. 2017;42(3):E12. doi:10.3171/2016.11.FOCUS16348
  2. Wei T, Cheng Y. The cardiac toxicity of radiotherapy – a review of characteristics, mechanisms, diagnosis, and prevention. Int J Radiat Biol. 2021;97(10):1333-1340. doi:10.1080/09553002.2021.1956007
  3. Kung VWS, Broad J, Makwana R, et al. The impact of long‐course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum. United Eur Gastroenterol J. 2024;12(10):1417-1428. doi:10.1002/ueg2.12653
  4. Baskar R, Dai J, Wenlong N, Yeo R, Yeoh KW. Biological response of cancer cells to radiation treatment. Front Mol Biosci. 2014;1:24. doi:10.3389/fmolb.2014.00024
  5. Attard KA, Vella JC, Chircop C. Late-onset radiation-induced brachial plexopathy. BMJ Case Rep. 2021;14(9):e243354. doi:10.1136/bcr-2021-243354
  6. Assessment of Patient Attribution to Care From Medical Oncologists, Surgeons, or Radiation Oncologists After Newly Diagnosed Cancer | Oncology | JAMA Network Open | JAMA Network. Accessed October 8, 2025. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779755?utm_source=openevidence&utm_medium=referral
  7. Colevas AD, Cmelak AJ, Pfister DG, et al. NCCN Guidelines® Insights: Head and Neck Cancers, Version 2.2025. J Natl Compr Cancer Netw JNCCN. 2025;23(2):2-11. doi:10.6004/jnccn.2025.0007
  8. François A, Dublineau I, Lebrun F, Ksas B, Griffiths NM. Modified absorptive and secretory processes in the rat distal colon after neutron irradiation: in vivo and in vitro studies. Radiat Res. 1999;151(4):468-478.
  9. Wang J, Hauer-Jensen M. Neuroimmune interactions: potential target for mitigating or treating intestinal radiation injury. Br J Radiol. 2007;80 Spec No 1:S41-48. doi:10.1259/bjr/33057885
  10. Mosa A, Brogan DM, Dy CJ. Radiation Plexopathy. J Hand Surg. 2025;50(2):216-221. doi:10.1016/j.jhsa.2024.09.026
  11. Afifi ANAM, Powerski M, Jechorek D, Brunner TB, Weigt J, Venerito M. Radiation-induced damage in the upper gastrointestinal tract: clinical presentation, diagnostic tests and treatment options. Best Pract Res Clin Gastroenterol. 2020;48-49:101711. doi:10.1016/j.bpg.2020.101711
  12. Breiter N, Sassy T, Trott KR. [Acute and chronic disorders in gastric emptying after the x-ray irradiation of the rat stomach and their therapeutic modification]. Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al. 1992;168(7):412-418.
  13. Enam N, Chou K, Stubblefield MD. Prevalence of function-limiting late effects in Hodgkin lymphoma survivors. PM R. 2022;14(7):811-817. doi:10.1002/pmrj.12662
  14. Ando J, Ueno Y, Yasuda H, et al. Radiation-Induced Myopathy Developing in a Hodgkin Lymphoma Patient: An Autopsy Case with Systemic Muscle Sampling. Case Rep Oncol. 2021;14(1):338-342. doi:10.1159/000512070
  15. Herwig R, Bruns F, Strasser H, et al. Late urologic effects after adjuvant irradiation in stage I endometrial carcinoma. Urology. 2004;63(2):354-358. doi:10.1016/j.urology.2003.09.040
  16. Stubblefield MD. Clinical Evaluation and Management of Radiation Fibrosis Syndrome. Phys Med Rehabil Clin N Am. 2017;28(1):89-100. doi:10.1016/j.pmr.2016.08.003
  17. Fijardo M, Kwan JYY, Bissey PA, Citrin DE, Yip KW, Liu FF. The clinical manifestations and molecular pathogenesis of radiation fibrosis. eBioMedicine. 2024;103:105089. doi:10.1016/j.ebiom.2024.105089
  18. Unger JM, Till C, Tangen CM, et al. Long-Term Adverse Effects and Complications After Prostate Cancer Treatment. JAMA Oncol. 2024;10(12):1654-1662. doi:10.1001/jamaoncol.2024.4397
  19. Di Stefano V, Attanasi C, Ferrante C, Di Muzio A. Late onset of dropped head syndrome following mantle radiation therapy for Hodgkin lymphoma. BMJ Case Rep. 2018;11(1):e226822. doi:10.1136/bcr-2018-226822
  20. Jaeckle KA. Neurologic manifestations of neoplastic and radiation-induced plexopathies. Semin Neurol. 2010;30(3):254-262. doi:10.1055/s-0030-1255219

    Original Version of the Topic

    Maricarmen Cruz, MD, Jesuel Padro-Guzman MD. Radiation Plexopathy. 7/25/2012.

    Previous Revision(s) of the Topic

    Christian Custodio, MD, Cody Christopher Andrews, MD. Radiation Plexopathy. 8/1/2017.

    Noble Jones, MD, Michael Dean Stubblefield, MD. Radiation Plexopathy. 11/30/2022.

    Author Disclosure

    Noble Jones, MD
    Nothing to Disclose

    Michael Dean Stubblefield, MD
    Nothing to Disclose