Radiation-induced brachial plexus neuropathy: A review
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.250704
Source of Support: None, Conflict of Interest: None
Keywords: Brachial plexopathy, carcinoma, radiation
Radiation-induced brachial plexus neuropathy (RIBPN) is a delayed nontraumatic injury to the brachial plexus, which occurs following radiation therapy to the chest wall, neck, and/or axilla in previously treated patients with cancer. It is defined as the neurologic impairment of transient or permanent nature involving the brachial plexus as a sequel to radiation treatment. Stoll and Andrew were the first to report it in 1966, in patients treated with radiation therapy after surgery for breast carcinoma. An extensive literature is available on radiation-induced brachial plexopathy, and more emphasis has been given to clinical findings and magnetic resonance imaging (MRI) characteristics. With day-to-day advancement in surgical and radiation therapy techniques, the longevity of patients with primary cancer has improved tremendously, and as a result, more and more delayed effects of radiation therapy are gaining greater attention among treating physicians. The occurrence of RIBPN is dependent on the radiation dosage, treatment technique, and concomitant use of chemotherapy. Often, tumor-related brachial plexus involvement is difficult to differentiate from radiation-induced brachial plexopathy.,
The incidence of RIBPN is more common in patients treated for carcinoma of the breast and Hodgkin's lymphoma. With improvement in radiation techniques, the incidence of acute injury to the brachial plexus following radiotherapy has dramatically reduced. However, with the rising philosophy of conservative surgery and radiotherapy in the treatment of early-stage breast cancer, the incidence of radiation-induced brachial plexopathy has also risen, and the reported incidence is 1.2% in women irradiated for breast cancer.,,
It has been suggested that there may be two phases of neuropathy following irradiation. The first phase involves direct effect in the form of changes in electrophysiology and histochemistry. A later phase may be due to fibrosis surrounding the nerve and injury to vessels supplying the nerves. Pathologically, post radiation plexopathy seems to be partly due to the fibrous tissue severely constricting the nerve bundles. In addition, the endoneurium is often thickened, and there may be extensive loss of myelin, disappearance of axis cylinders, hyalinization, and obliteration of the blood vessels. In short, it is a combination of failure of cellular proliferation and localized ischemia which results in fibrosis of the neural and perineural soft tissues secondary to microvascular insufficiency, leading to entrapment of nerve fibers. In addition, nerve ischemia may lead to ischemic demyelination, thereby resulting in conduction block that is commonly observed in brachial plexus neuropathy following radiation treatment. The occurrence of brachial plexus neuropathy is directly related to radiation dosage (>50 Gy), radiation fraction (>2 Gy per fraction), use of three-field radiation technique, concomitant use of adjuvant cytotoxic chemotherapy, surgical lymph node dissection, and associated vascular disease and diabetes. All these factors contribute to the development of fibrosis within and around the neural elements.,,,,,,
The symptomatology of radiation-induced brachial plexopathy is variable and can occur from 6 months to 20 years after radiation therapy. The common presenting symptoms are numbness, paresthesia, dysesthesia, lymphedema [Figure 1], and motor weakness. Neurogenic pain can vary from mild to severe type. In severe cases, there can be associated fibrosis of the scapulothoracic and glenohumeral joints leading to restriction of range of movements at the shoulder joint. The progression of symptoms is gradual in about two-third of cases and the patients may initially present with paresthesia and pain, and later progress to have motor weakness in the affected upper limb. Often, the pain subsides once the motor weakness becomes more profound and severe. However, the pain may persist even in the presence of complete paralysis of the upper limb. About one-third of patients deteriorate rapidly and exhibit sensorimotor deficits. Rarely, the disorder is mild and the progression may get arrested or become reversible.,,,,,,,,,
A detailed clinical assessment of the patients helps in differentiating radiation-induced brachial plexopathy from tumor infiltrating the brachial plexus. The pain in radiation-induced brachial plexopathy is mild-to-moderate and tolerable in a majority of cases, and that associated with tumor involving the brachial plexus is severe and more pronounced. However, this may not be true in all cases and often severe distressing pain is noted in patients with brachial plexus involvement following radiation treatment. Motor weakness in the affected upper limb is present in both the disorders, but is more rapid in tumor infiltrating the brachial plexus.
The magnetic resonance imaging (MRI) scan is an ideal investigation to diagnose RIBPN from other pathologies affecting the brachial plexus. It exhibits inherent contrast differences between the brachial plexus, blood vessels, surrounding fat, and the multiplanar imaging has significant possibilities in further delineating the pathology. The fibrosis due to radiation is iso- to hypointense relative to muscle on T2-weighted (T2W) images. In contrast, tumor infiltration of the brachial plexus appears as a mass lesion that is hyperintense on T2W sequences. However, the vascularized fibrous scar tissues appear hyperintense on T2W images [Figure 2]a,[Figure 2]b,[Figure 2]c and thereby make the diagnosis extremely difficult. It can only be confirmed intraoperatively during exploration or by ultrasonography-guided biopsy. The enhancement is more marked in tumor infiltration in comparison to fibrosis that is generally non-enhancing. Thus, MRI is a noninvasive modality for distinguishing radiation induced fibrosis from a recurrent tumor.,,,,,,
Fluorodeoxyglucose-positron emission tomography computed tomographic (FDG-PET CT) scan is diagnostic in tumor involvement in the brachial plexus. It shows an increase in metabolism locally, and the presence of metastatic depositis in other parts of the body.
The electromyography-nerve conduction (EMG-NC) study can be very useful in making a diagnosis of brachial plexopathy. NC velocities help in detecting the block across the damaged nerve. In severe cases, EMG demonstrates fibrillation and absence of motor unit potential in the affected group of muscles supplied by the brachial plexus. The electrophysiologic study helps in assessing the severity of brachial plexopathy and, to some extent, in prognosticating the problem.,,,,,,
There is no definitive treatment of RIBPN. The options are mainly directed toward treatment of the presenting symptoms, such as pain, paresthesias, and psychological disturbances. The therapeutic modalities should focus on pain reduction, strengthening of the muscles, preservation of the range of motion of the joints of the upper limb, and limiting lymphedema. The motor weakness, once it is established, is very unlikely to recover irrespective of any treatment because of severe axonal damage secondary to fibrosis and local ischemia.
The neuropathic pain is relatively insensitive to conventional analgesics, including nonsteroidal anti-inflammatory drugs and opioids. B-isobutyl-G-aminobutyric acid (commonly known as pregabalin), tricyclic antidepressant, amitriptyline, and anticonvulsant such as carbamazepine and sodium valproate, can be used for alleviation of pain and paresthesia. The role of steroids is debatable especially for chronic pain in the upper limb.
Noninvasive techniques, such as transcutaneous electrical nerve stimulation, are often used in the treatment of neuropathic pain. These can be given along with medical therapy. Physiotherapy helps in raising the pain threshold, strengthening the muscles, preventing joint stiffness and contractures, and limiting lymphedema. Invasive options for treatment of chronic and severe neurogenic pain include epidural injection of steroids and local anesthetic agents, brachial plexus blocks, and spinal cord stimulation. They are offered when the severe pain is unresponsive to medical treatment and it hampers day-to-day activities of the patient.
Surgical treatment is indicated when the pain is unresponsive to conservative therapy, and there is associated progressive motor weakness. The commonly used procedure is external neurolysis, wherein the perineural fibrosis and scar is excised around the nerves of brachial plexus [Figure 3]. Often, omental fat is wrapped around the neurolysed brachial plexus to prevent further fibrosis and scarring. In selected cases, neurotization procedures can also be considered to improve motor weakness.,,,,,,,,,,
Psychological counseling is often an important part of management of patients with chronic pain due to RIBPN. The associated malignant disease and severe neuropathic pain compounded with motor weakness involving the upper limb make this problem extremely difficult to manage. It directly affects the patient's psyche and often the patient develops a suicidal tendency.
In our small series from 2006–2017 of patients with RIBPN, 11 female patients were treated previously for carcinoma of breast. Their mean age was 48 years (age range: 42–65 years). All patients presented with severe, continuous neurogenic pain (visual analog scale of 9–10) and severe paresthesia. The neurogenic pain had worsened over a period of time to become unbearable and agonizing and had disturbed the day-to-day activities. It was worse in the night to disturb the sleep. In our series, all 11 patients had pan-brachial plexus neuropathy with weakness involving all groups of muscles in the upper limb. In all the patients, distal muscle weakness involving the grip was more severely affected than proximal muscles weakness. Lymphodema in the arm was present in seven patients at the time of surgery. All the patients had received adjuvant local radiotherapy (50–55 Gy) and chemotherapy following the carcinoma breast surgery. The mean duration of clinical symptoms was 8.4 months, and the average onset of symptoms was 18.7 months following the radiation therapy. All the patients were initially treated conservatively with oral analgesics and pregabalin for a minimal period of 3–4 months. Surgery was offered to all patients when medications failed to relieve their clinical symptoms. In all the patients, a preoperative MRI and EMG-NC study of the brachial plexus were performed. The MRI in all the patients failed to conclusively differentiate and demonstrate recurrence of tumor or post-radiation fibrosis. The EMG-NC study revealed severe brachial plexopathy with denervation changes in the affected brachial plexus. The FDG-PET CT scan failed to demonstrate any increase in metabolism involving the brachial plexus and metastasis elsewhere in the body. In all the patients, external neurolysis of the supra- and infraclavicular brachial plexus was performed. The perineural scar tissue was excised and the neural elements were freed from the surrounding soft tissues. In all the patients, multiple biopsies were taken from the suspected areas and they failed to reveal any tumor tissue. The histopathological report in all the patients confirmed the presence of a fibrotic scar tissue. The follow-up ranged from 6 to 22-months with a mean follow up of 11 months. At a 6-month follow-up period after surgery, significant improvement in neurogenic pain and paresthesia was seen in nine patients. In two patients, there was no significant relief in sensory symptoms following surgery and the agonizing pain persisted. Morphine was needed to alleviate this pain. The motor weakness improved proximally at shoulder and arm in three patients. In nine patients, the distal motor weakness failed to improve and deteriorated significantly over a 6-month duration [Table 1].
RIBPN is a difficult problem due to its varied presentation and limited management options. The goal of treatment is to reduce the patient's suffering. The most important aspect is to differentiate it from tumor-induced brachial plexopathy. The radiation oncologist should be aware of this side effect, and patients should be followed up regularly for clinical assessment after radiotherapy. Management should be aimed at alleviating symptoms and at improving function, thus providing a better quality of life.
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[Figure 1], [Figure 2], [Figure 3]