Introduction
Despite the development of new therapies and related neurological complications, the two main considerations in patients with a history of cancer presenting with a brachial or lumbar plexopathy is neoplastic plexopathy or radiation-induced plexopathy. A focused cancer history and neurological examination can aid in localization and in narrowing down the differential diagnosis. Cancer-related plexopathies are more common, tend to be painful, and have a more rapid onset than radiation-induced plexopathies, which present in a more indolent fashion over the course of months to years following radiation therapy. Although imaging is helpful to visualize the degree of plexus involvement and to assess for locoregional disease, it is difficult to distinguish the two on the basis of imaging alone. Nerve conduction studies (NCS) and electromyography (EMG) can be useful if myokymic changes are present, as these are associated with radiation-induced plexopathies. Unfortunately, both types of plexopathies are treated with supportive measures, and survival and quality of life may be limited in many of the affected patients.
Approach to plexopathies
Cancer and cancer-associated treatments can have direct and indirect effects on all parts of the nervous system including the brachial and lumbar plexus. In a patient with a known history of cancer, plexopathies can be caused by trauma from surgery or anesthesia, metastatic tumor spread, radiation therapy, chemotherapy, immunotherapy, and radiation-induced tumors. Cancer patients are also susceptible to acute plexopathies that are unrelated to their malignancy or its treatment. A thorough understanding of neuroanatomy is essential, as the clinical examination and diagnostic studies can help with localization and point to a specific etiology. Cancer history with particular attention to pathology, prior treatments for cancer including any surgeries, radiation therapy (including type, field, and dose delivered), conventional chemotherapies, targeted molecular therapies, and immunotherapies, as well as any clinical trial protocol should be noted. In patients without a known history of cancer, a family history of cancer and risk factors for malignancies should be investigated (e.g., smoking history, HIV or immunosuppression, prior history of radiation, and tumor predisposition syndromes among others). Relevant history for non–cancer-related causes of plexopathies including diabetes, recent vaccinations, and intercurrent illnesses should also be determined. Imaging modalities, including magnetic resonance imaging (MRI) or computed tomography (CT) scans, and electrophysiologic testing with NCS and EMG are useful adjuncts to aid the diagnosis of plexopathies.
Brachial plexopathy
Anatomy
The brachial plexus consists of the ventral rami of the C5–C8 nerve roots ( Fig. 22.1 ). These later form three distinct trunks: superior (C5, C6), medial (C7), and inferior (C8–T1), which are then further subdivided into dorsal and ventral divisions. The dorsal divisions converge to form the posterior cord from which emerge the thoracodorsal nerve (to the latissimus dorsi), the subscapular nerve (to the subscapularis), the axillary nerve (to the deltoid), and the radial nerve (motor innervation to the triceps, brachioradialis, biceps, wrist extensor, finger extensors, and sensory innervation to the posterior aspect of the arm and forearm). The ventral divisions give off the lateral and the medial cords. The lateral cord branches into the musculocutaneous nerve (motor innervation to the biceps, brachialis, coracobrachialis, and sensation to the radial aspect of the forearm). The lateral cord also converges later on with the medial cord to form the median nerve (with motor innervation to the forearm flexors, pronator teres and pronator quadratus, thumb flexors and lumbricals, and sensation to the medial palm and first three and a half fingers). The medial cord also supplies the ulnar nerve, which in turn supplies the intrinsic muscles of the hand and some of the flexors of the hand and digits (flexor carpi ulnaris, flexor digitorum profundus II and IV, abductor, opponens and flexor of the fifth digit, and sensation to the ulnar aspect of the palm).
The sympathetic chain connects to the brachial plexus through the gray rami communicantes, and involvement of the brachial plexus, especially of the C8 and T1 nerve roots, can present with Horner syndrome consisting of ptosis, miosis, and anhidrosis through the disruption of second order sympathetic fibers.
Lumbosacral plexopathy
Anatomy
The lumbosacral plexus consists of the ventral rami of L1–S2 nerve roots and is subdivided into the lumbar and sacral plexus ( Fig. 22.2 ). The lumbar plexus has anterior and posterior divisions, with the anterior division giving rise to the iliohypogastric, ilioinguinal, and genitofemoral nerves (supplied by L1 and L2), which provide sensory innervation to the lower abdomen, upper thigh, and lateral perineum; and the obturator nerve (supplied by L2–L4), which provides motor innervation to the adductors and gracilis muscles. The posterior division of the lumbar plexus is made up of the iliohypogastric and lateral femoral cutaneous nerves (L2–L3) with sensory afferents from the lateral hip and thigh; and the femoral nerve (L2–L3), which provides motor fibers to the psoas, iliacus, sartorius, and quadriceps. It also receives sensory afferents from the anterior thigh and medial upper leg. The sacral plexus consists of the ventral rami of S1–S4, as well as a branch of the lower lumbar plexus (L4–L5). The sacral plexus is further subdivided into the anterior division, which provides motor fibers to the quadratus femoris and hamstrings; and the tibial nerve (L4–S3), which provides motor fibers for the foot dorsiflexors and intrinsic foot muscles. The posterior division branches into the common peroneal nerve (supplied by L2–S2) to the peroneal muscles, tibialis anterior, extensor digitorum, and extensor hallucis and has sensory afferents from the lateral leg, dorsal foot, and toes. It also gives off the superior (L4–S1) and inferior (L5–S2) gluteal nerves supplying the gluteus muscles. The posterior division is the origin of the sciatic nerve, which divides into the common peroneal and tibial nerves, and the posterior femoral cutaneous nerve (S1–S3), which carries sensory information from the posterior thigh. The perineum is innervated by another branch of the sacral plexus, the pudendal nerve (S2–S4).
Clinical cases
Case. A 60-year-old right-handed female with history of epidermal growth factor receptor (EGFR)-wildtype non–small-cell lung cancer (NSCLC) was referred for worsening right arm pain. Her oncologic history begins 9 years ago when she was diagnosed with locally advanced (stage 3B unresectable) right lung adenocarcinoma. She was treated with concurrent cisplatin and etoposide chemotherapy and right lung and mediastinal radiation. She thereafter received two adjuvant cycles of cisplatin and pemetrexed and her systemic disease remained well controlled until she presented with right posterior shoulder pain radiating down her arm into her fourth and fifth digits. She had noted some difficulty with fine finger movements with the right hand, although no focal weakness had been observed. A few weeks following the onset of her pain, she also started noticing numbness and tingling in her right hand.
Neurological examination revealed normal mental status, right-sided ptosis, and miosis but no other cranial nerve deficit. Muscle bulk was normal except for right thenar and first dorsal interosseous (FDI) atrophy. The remainder of the neurological examination, including sensory examination and reflexes, was within normal limits.
NCS and EMG showed electrophysiologic evidence of denervation to axons supplied by the right C8 and T1 nerve roots and lower trunk of the brachial plexus. MRI of the cervical spine and brachial plexus showed a nodular heterogeneously enhancing soft tissue lesion extending from the right lung apex and pleural surface into the supraclavicular fossa, surrounding the right brachial plexus ( Fig. 22.3 ). This finding was felt to be consistent with involvement of the brachial plexus by pulmonary and pleural metastasis. Interval enlargement of several mediastinal and axillary lymph nodes was also observed.
Her clinical presentation and electrodiagnostic studies were indicative of a neoplastic brachial plexopathy, predominantly involving the lower trunk. Given her locoregional progression, she was started on ramucirumab and docetaxel. Palliative radiation to the brachial plexus was discussed but deferred for the time being. She was started on gabapentin and lidocaine transdermal patch for pain relief. She was also referred to a palliative care specialist and started physical therapy with some improvement of her symptoms.
Clinical Pearls
- 1.
The presentation of a neoplastic brachial plexopathy is frequently in the form of worsening pain in the neck, shoulder, or arm over the span of weeks to months.
- 2.
In such cases, Horner syndrome may be present, especially with the involvement of the lower trunk.
- 3.
The lower plexus is most often involved in cancer-related brachial plexopathies, and electrodiagnostic studies can be helpful to confirm localization.
- 4.
MRI images of the cervical spine and plexus are required to assess for bulky locoregional disease that may be amenable to treatment with surgery or radiation therapy.
Teaching Points: Approach to Neoplastic Brachial Plexopathy
Pathophysiology of neoplastic brachial plexopathies
Although primary tumors arising from the brachial plexus can cause neurological symptoms, the vast majority of cancer-related brachial plexopathies are due to local extension of an adjacent tumor or metastasis of a more distant neoplasm. These plexopathies can occur due to the direct pressure of a local mass but more frequently are caused by the invasion of cancer cells along nerves or connective tissue surrounding the brachial plexus. The brachial plexus is in close proximity to the lung, breast, and lymphatic system and is therefore at higher risk of involvement from metastases compared to other parts of the peripheral nervous system ( Fig. 22.4 ). Although some tumors may directly extend from adjacent tissue and organs into the nervous plexus, secondary invasion from metastases through regional lymph nodes or through tracking along the epineurium can also occur. A large retrospective review at a single institution in the 1980s identified about 2% of patients with cancer being referred for neurological evaluation as having a brachial plexopathy. Of these, up to 75% were due to direct metastasis from lung, breast cancer, or systemic lymphoma. Non-Hodgkin lymphoma in particular has been associated with 90% of neurolymphomatosis, which can involve the brachial plexus in a variable presentation of neuropathy, radiculopathy, or plexopathy.
Primary tumors of the brachial plexus include schwannomas or neurofibromas (see Chapter 9 , Case 9.1 for imaging features of brachial plexus peripheral nerve sheath tumors), which are both rare when occurring sporadically. In the context of neurofibromatosis type 1 (NF1), neurofibromas are the most common benign tumor to occur in this familial tumor predisposition syndrome (see Chapter 16 for further discussion of NF1). In NF1, a mutation of the tumor suppressor gene neurofibromin leads to overactivity of the p21 ras, which in turn causes cell growth, differentiation, and benign tumor formation. Although these neurofibromas can occur in a plexiform distribution (e.g., involving fascicles of a nerve or branches of a large nerve), the term plexiform neurofibroma does not indicate involvement of a nerve plexus and their location can be varied across the peripheral nervous system. Malignant transformation of a neurofibroma can lead to development of malignant peripheral nerve sheath tumors (MPNST) in which early diagnosis and surgical management can improve survival outcomes (also see Chapter 16 for discussion of NF1 and Chapter 9 , Case 9.3 for imaging of MPNST).
Clinical Presentation
Brachial plexopathy from direct invasion of a primary or metastatic tumor typically presents with signs and symptoms related to the anatomic location of involvement. The most common symptom described is pain, which is present in about 75% of patients, followed by sensory changes in up to 25%. The distribution of pain may vary from patient to patient. It is typically described as arising in the shoulder or axilla when the upper plexus is involved from metastases originating from cervical lymph nodes or other head and neck tumors. Pain arising from the elbow and radiating to the medial arm and hands, however, is felt to be more common and is often the presenting symptom if the lower plexus is involved, as is the case in some Pancoast tumors that arise from the region around the superior sulcus of the lung. Up to 75% of patients affected by a painful neoplastic plexopathy present with involvement of either the lower or upper brachial plexus, with the remaining 25% of patients with global involvement of the entire plexus involving C5–T1.
Progressive weakness, atrophy, and sensory changes of the upper extremity may also evolve over time. In primary tumors of the brachial plexus, sensory changes may be more gradual and present in the form of progressive paresthesia without significant pain. A unilateral Horner syndrome may also be present in about 25% of patients, when the sympathetic trunk or sympathetic ganglia are affected, especially when the upper thoracic or lower cervical roots are involved. About 30% of cases with a unilateral Horner syndrome will also have concurrent epidural involvement and MRI of the cervical and thoracic spine is therefore recommended for such presentations.
Diagnostic Imaging
Imaging of the brachial plexus has evolved with the advent of higher resolution MRI and new applications of ultrasound methods. MRI of the brachial plexus can provide high spatial resolution and contrast delineation, allowing for determination of location and degree of involvement of brachial plexus pathologies.
Benign peripheral nerve sheath tumors . Benign primary neoplasms of the brachial plexus such as peripheral nerve sheath tumors can have specific features on MRI. These tumors are usually well-circumscribed, avidly enhancing ovoid lesions along the parent nerve. Characteristic appearance of peripheral nerve sheath tumors include the target sign, split fat sign, fascicular sign, and string sign. Although these radiologic signs apply both to schwannomas and neurofibromas, schwannomas tend to be eccentric to the parent nerve without infiltrating within the fascicles, whereas neurofibromas are not encapsulated and typically infiltrate the nerve fascicles. Plexiform neurofibromas are usually readily identifiable on MRI due to the diffuse enlargement of several nerve branches, often referred to as a “bag of worms.” Enhancement of plexiform neurofibromas can be heterogeneous and appear much larger in size than solitary neurofibromas. MPNSTs can have a similar imaging profile as other soft tissue sarcomas, but can be distinguished from benign peripheral nerve sheath tumors due to their size (typically larger than 7 cm), perilesional edema, peripheral enhancement, and intratumoral cystic change.
Brachial plexus metastasis or neoplastic invasion . In the setting of involvement of the brachial plexus from direct adjacent mass effect from a locally occurring secondary tumor, or secondary metastasis, lesions of the brachial plexus may be focal or diffusely infiltrating. There can be solid enhancement of bulky or nodular metastasis, and thickening of nerve roots on neuroimaging. In the case of neurolymphomatosis, diffuse enhancement along the perineural space may be visible. Nerve enlargement, isointensity to muscle on T1, hyperintensity on T2, and focal or diffuse enhancement may also be present.
Peripheral nerve ultrasound . Although ultrasound techniques have allowed for a fairly reliable and rapid bedside assessment of the brachial plexus, it has not been routinely integrated in the workup of neoplastic plexopathies. It is the most helpful to visualize elements of the brachial plexus when an MRI is contraindicated, not tolerated due to claustrophobia, or not readily available. Visualization of the nerve roots is limited by the shadowing of the transverse processes of the vertebral bodies, but all other fascicles of the brachial plexus can be mapped by ultrasound, in the hands of an experienced sonographer with good knowledge of brachial plexus anatomy. It is particularly helpful in visualizing loss of integrity in the brachial plexus or adjacent structures caused by trauma, neoplasms, or radiation fibrosis. Ultrasound of benign nerve sheath tumors reveal typically well-defined hypoechoic ovoid masses.
Positron emission tomography . Most patients with brachial plexus metastases have advanced systemic malignancy. Systemic staging with PET-CT of the body, CT chest, and mammogram, among others, is therefore an essential part of the workup of neoplastic plexopathies. In addition, MRI of the cervical or thoracic spine may also be required if proximal root involvement with extension into the spinal cord or epidural space is suspected.
Electrophysiologic testing . Electrodiagnostic studies with NCS and EMG can be helpful in assessing for localization and degree of involvement in neoplastic brachial plexopathies. Sensory or motor involvement may be present, and may specifically point to specific radicular, branch, division, or nerve involvement. NCS may reveal axonal loss with low or absent sensory potentials from the ulnar, medial, or antebrachial nerves. Needle examination can show spontaneous activity and motor units consistent with a denervating process. However, there is no specific feature on nerve conduction or needle EMG that may delineate a neoplastic cause from some other etiologies of brachial plexopathy. Myokymia, which can be seen in radiation-induced brachial plexopathies, is absent in neoplastic brachial plexopathy. Comparing nerve conductions on the affected side to the normal side can provide an estimate for the degree of injury and potential for recovery.
Occasionally, surgical exploration and biopsy may be required to confirm pathologic diagnosis, specifically if no clear primary neoplasm is identified; however, it is usually preferable to biopsy a more accessible lesion if present, as nerve biopsy can result in permanent neurological damage.
Management
Management of neoplastic brachial plexopathies can vary greatly depending on symptom burden and systemic involvement. It is typically focused on treatment of the primary malignancy with systemic agents or with radiation to sites of bulky locoregional metastasis. Surgical debulking is seldom used due to the intricate anatomy of the region involved. Targeted therapies (e.g., with tyrosine kinase inhibitors), in lung cancer, such as the anaplastic lymphoma kinase rearranged (ALK) inhibitors and the EGFR tyrosine kinase inhibitors, have been increasingly used in subtypes of non–small-cell lung cancer. Endocrine therapy and HER2-targeted therapy are also part of the treatment armamentarium for certain types of breast cancer. Radiation therapy is used for locoregional disease for palliative purposes, or after first-line systemic therapy has failed, with some improvement or reversal of pain or neurological deficits.
Survival may be limited for many patients with neoplastic-induced brachial plexopathy due to advanced stage cancer. Symptom control and improvement of quality of life are therefore a primary concern. Pain from neoplastic brachial plexopathies can be challenging, and a multidisciplinary approach is often recommended. Involvement of a pain specialist or palliative care physician may be helpful in managing progressive symptoms. Analgesia for neuropathic pain can be targeted through transcutaneous nerve stimulators, duloxetine, tricyclic antidepressants, gabapentin, or pregabalin. Opiate analgesics, transdermal lidocaine, and occasionally infusion pumps are sometimes required. In particularly severe cases, local anesthetic blocks may also be considered, and in severe intractable pain, dorsal rhizotomy, dorsal root entry zone surgery, plexus dissection, and neurolysis remain salvage options. Physical and occupational therapy can also help with symptom relief and prevention of loss of function and contractures.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
