Clinical Vignette

A 54-year-old man developed acute-onset right thigh, hip, and buttock pain. He also noted right knee “buckling” when he stepped off a curb, resulting in a fall. He also noted right foot drop. Paresthesias developed over the right thigh, shin, and foot. He required oral narcotics for pain relief.

His past medical history was remarkable for type II diabetes mellitus, for which he took an oral hypoglycemic. His blood sugars had been under fair control. His review of systems was remarkable for a 30-pound weight loss over the past 3 months, which he attributed to renewed efforts at dieting. He doesn’t smoke or drink heavily. He is an attorney. Family history is negative.

His general examination was unremarkable. His neurologic examination was notable for moderate weakness of right hip flexion, hip extension, knee extension, and ankle dorsiflexion. He has an absent right knee and ankle reflex, but reflexes are normal on the left lower extremity and upper extremities. Sensory testing demonstrates reduced vibration sensation at the right great toe and ankle. His gait is hesitant and reveals a right foot drop.

Electromyography (EMG) demonstrated borderline right peroneal and tibial compound motor action potentials with normal velocities and distal latencies. The sural and superficial peroneal sensory nerve action potentials were absent on the right and normal on the left. Active denervation was present in right femoral and sciatic innervated muscles, and to a lesser extent in lumbosacral paraspinals and gluteal muscles.

Magnetic resonance imaging (MRI) of the lumbosacral spine and pelvis was unremarkable, except for signal changes in denervating muscles. Lumbar puncture demonstrated an elevated cerebrospinal fluid (CSF) protein with normal cell count. Glycosylated hemoglobin was slightly elevated but otherwise his laboratory studies were normal.

He was diagnosed with diabetic lumbosacral radiculoplexus neuropathy (also known as diabetic amyotrophy). After discussion of the pros and cons he was prescribed an empiric treatment trial of intravenous methylprednisolone.

Clinical Presentation

Plexus lesions commonly result in unilateral or asymmetric extremity muscle weakness and sensory complaints that do not conform to the distributions of single roots or nerves. Brachial plexopathies cause shoulder girdle weakness if the upper plexus is involved and hand weakness if the lower, or medial plexus is principally involved. Sensory loss is usually variable but follows a similar pattern; for example, a medial plexus lesion causes numbness of the fourth and fifth fingers. Autonomic disturbances, caused by disruption of the sympathetic fibers traversing the lower trunk to the superior cervical ganglia of the brachial plexus, may be present and include trophic skin changes, edema, reflex sympathetic dystrophy (complex regional pain syndrome), and Horner syndrome (miosis, ptosis, ipsilateral facial anhidrosis).

Upper plexus lesions of the lumbar plexus cause weakness of thigh flexion, adduction, and leg extension. Lower sacral plexus lesions result in weakness of thigh extension, knee flexion, and foot dorsiflexion and plantar flexion, and sensory changes. Complete lumbosacral plexopathy produces weakness and muscle atrophy throughout the lower extremity, with total areflexia and anesthesia. Concurrent autonomic loss results in warm, dry skin and peripheral edema.

In addition to considering etiologies for plexopathy, the clinician needs to consider whether processes that may be mimicking plexopathy are likely considerations. The presence of neuropathic pain can reasonably exclude pure motor processes, such as motor neuronopathies (e.g., amyotrophic lateral sclerosis), disorders of neuromuscular junction transmission (e.g., myasthenia gravis), and myopathies. Orthopedic injuries can sometimes mimic plexopathy, usually only when symptoms are relatively mild; the examination and electrodiagnostic testing usually identifies the plexopathy. The most important mimic of plexopathy is polyradiculopathy; nerve root lesions also present with both weakness and pain. The mechanism of nerve root injury may be structural (e.g., neural foraminal stenosis or disk herniation), infectious (e.g., Lyme neuroborreliosis), or neoplastic (e.g., carcinomatous meningitis).

Anatomy

Brachial Plexus

The brachial plexus is formed from the ventral rami of cervical roots 5–8 and thoracic root 1 (Fig. 64-3). The ventral rami of the fifth and sixth cervical roots together form the upper trunk, the seventh cervical root ventral ramus becomes the middle trunk, and the eighth cervical and first thoracic root ventral rami join to become the lower trunk. The trunks of the brachial plexus are located above the clavicle between the scalenus anterior and scalenus medius muscles, in the posterior triangle of the neck, posterior and lateral to the sternocleidomastoid muscle. The dorsal scapular, long thoracic, and suprascapular nerves originate from the brachial plexus above the clavicle. Behind the clavicle and in front of the first rib, each trunk separates into anterior and posterior divisions. The anterior divisions of the upper and middle trunks unite to become the lateral cord, whereas the anterior division of the lower trunk forms the medial cord. The posterior divisions of all three trunks unite to become the posterior cord. The three cords are named for their positions relative to the axillary artery. Below the clavicle, the upper extremity nerves arise from the cords. From the lateral cord arises the musculocutaneous, the lateral head of the median, and the lateral pectoral nerves. From the medial cord comes the ulnar, the medial head of the median, the medial pectoral, and the medial brachial and medial antebrachial nerves. From the posterior cord arise the radial, axillary, subscapular, and thoracodorsal nerves.

Figure 64-3 Anatomy of Brachial Plexus.

Lumbosacral Plexus

The femoral nerve, innervating the iliopsoas and the quadriceps femoris muscles, is the predominant derivative of the lumbar portion of the lumbosacral plexus (Fig. 64-4). Its sensory supply includes the anterior and lateral thigh, and the medial foreleg as the saphenous nerve. The obturator nerve innervating the adductor magnus also originates from the lumbar plexus. The sacral portion of the lumbosacral plexus innervates the remainder of the lower extremity muscles, including posterior thigh and buttocks muscles and all leg musculature below the knee. The superior and inferior gluteal nerves, the most proximal nerves originating from the sacral derivative of the lumbosacral plexus, innervate the gluteal muscles (medius, minimus, and maximus). The sciatic nerve innervates the hamstring group and bifurcates into the peroneal and tibial nerves, providing all motor innervation below the knee. The sciatic nerve provides sensory innervation to the posterior thigh and the entire leg below the knee, with the exception of the medial foreleg, which is supplied only by the saphenous nerve. The peroneal nerve is derived from the lateral portion of the sciatic nerve within the thigh; it supplies only one muscle above the knee, the short head of the biceps femoris. This site provides a means to differentiate electrodiagnostically atypical proximal peroneal or sciatic nerve lesions from common peroneal nerve compression or entrapment syndromes at the fibular head. The peroneal nerve bifurcates into the superficial and deep peroneal nerves, the latter innervating all anterior compartment muscles. The superficial peroneal motor nerve supplies the lateral compartment. The tibial nerve, the other primary sciatic nerve derivative, supplies the calf. The superficial peroneal sensory, the sural, and the medial and lateral plantar nerves are the primary superficial sensory nerves below the knee, in addition to the saphenous.

Figure 64-4 Anatomy of Lumbar, Sacral, and Coccygeal Plexuses.

Diagnostic Approach

The neurologic examination should focus on identifying any motor, sensory, and reflex impairment referable to the different components of the plexus. A diminished or absent biceps reflex would be expected for a brachial plexopathy involving the upper trunk, for example. Weakness involving the hand and wrist would point toward lower trunk/medial cord brachial plexus involvement. In addition to localizing a lesion to particular trunks and cords, the examination can sometimes help determine whether lesions are preganglionic (e.g., root avulsion) or postganglionic (e.g., upper trunk plexopathy). Weakness of the rhomboid muscles (from C4 and C5 roots) and the serratus anterior muscle (from C5, C6, and C7 roots) would suggest involvement as proximal as the cervical root. Needle examination of these muscles and cervical paraspinal muscles, discussed below, will be helpful also in determining where the lesions are along the length of the nerve.

Electrodiagnostic (EDX) testing helps confirm the diagnosis and localization of a suspected plexopathy. Rarely, nonneuropathic processes (e.g., rotator cuff tendinitis, hip fracture) can mimic plexopathy, in which case EDX testing and the neurologic examination will be normal. More commonly, EDX testing serves to confirm localization of a neuropathic process to the plexus. A watershed for the localization of plexopathies is the dorsal root ganglia (DRG), with lesions involving segments proximal to the DRG (e.g., root) classified as preganglionic lesions, whereas those distal to the DRG (e.g., trunk) are labeled as postganglionic lesions. Assessment of sensory nerve action potentials (SNAPs) is very helpful with this localization because the preservation of SNAPs favors a preganglionic lesion (e.g., radiculopathy) whereas the diminution or loss of SNAPs favors a postganglionic lesion (e.g., plexopathy). For a unilateral plexopathy, the SNAP abnormality should be on the side of the lesion, and for asymmetric plexopathies, the SNAP abnormalities should theoretically be more severe on the more affected side. Side-to-side differences in SNAP amplitude of greater than 50% are typically considered significant, but repeat testing at the same sitting to confirm that this finding is not simply technical is advisable, particularly given the significance of such a finding for localization. Differentiating preganglionic (e.g., radiculopathy) from postganglionic plexopathy is a particularly important request when trying to differentiate a structural (e.g., spinal stenosis), infectious (e.g., Lyme), or carcinomatous cervical polyradiculopathy from a plexopathy. Determining whether a traumatic plexus injury is preganglionic or postganglionic is also important for surgical management. For instance, preganglionic lesions (e.g., root avulsions) are generally not amenable to direct plexus repair with nerve grafting and hence would more likely be surgically treated with a nerve transfer (e.g., spinal accessory nerve to suprascapular nerve in order to allow shoulder abduction, ulnar nerve fascicle to flexor carpi ulnaris to the musculocutaneous nerve in order to allow elbow flexion). On the other hand, postganglionic lesions (e.g., upper trunk plexopathy) may be directly repaired at the plexus with nerve grafting or internal neurolysis. In the case presented above, the absent sural sensory and superficial peroneal sensory responses were consistent with a postganglionic plexopathy. Motor nerve conduction studies should also be performed, particularly to look for low CMAP amplitudes over muscles innervated by affected nerves. Needle examination helps localize the lesion, both longitudinally (i.e., where along the length of the nerve or root) and specifically to which components of the plexus (e.g., upper trunk). Needle examination should ideally be performed at least 2–3 weeks after onset in order to maximize what data can be collected from the study, but it still can be helpful to perform a study earlier than that because reduced recruitment of motor unit potentials of weak muscles can still help with localization. Abnormalities on needle examination can map out the location of the plexus lesions. The presence of fibrillation potentials in paraspinal muscles would point to involvement of the roots; however, the absence of fibrillation potentials in the paraspinals does not exclude radiculopathy because needle examination of paraspinal muscles will be normal in an estimated half of patients with radiculopathy. It is important to also note that patients with radiculoplexus neuropathies (e.g., DLRPN) will demonstrate evidence of both preganglionic and postganglionic damage, hence the name radiculoplexus neuropathy. Needle examination can also sometimes assist in determining etiology. For example, plexopathies secondary to radiotherapy are sometimes associated with myokymic discharges on needle study, whereas plexopathies due to another cause (e.g., neoplasm) are much less likely to reveal myokymic discharges.

Routine radiographs, CT, and MRI of the lumbosacral spine and pelvis are often required to exclude inflammatory or mass lesions within the spine or pelvis. CSF examination may be indicated to exclude infection. CSF protein is increased in approximately 50% of patients with idiopathic lumbosacral plexopathy. In vasculitic lumbosacral plexopathy, nerve biopsy may reveal ischemic nerve injury caused by microvasculitis or vasculitis. Histopathologic evidence of vasculitis is frequently seen on biopsy of patients with DLRPN, although often the clinical context and other ancillary studies provide enough evidence of the diagnosis so that a nerve biopsy can be avoided.

Differential Diagnosis

Trauma is the most common pathophysiologic mechanism for a brachial plexopathy. The superficial anatomic location of the brachial plexus with close proximity to bony and vascular structures within the shoulder and neck predisposes it to this risk. Traumatic mechanisms for brachial plexopathy include compression, traction, ischemia, laceration, or a combination. Motor vehicle accidents, high-speed cycling accidents, gunshot or knife wounds, and falls can be causative. Some events may be iatrogenic; for example, positioning during cardiothoracic surgery that maximally abducts the arm, may cause stretching of the lateral brachial plexus. Sporting activities causing “burners” or “stingers” are common mechanisms for brachial plexopathy. Despite their relative frequency, their pathophysiology is unclear; these injuries are likely caused by compression, traction or both, usually of the C5–6 cervical nerve roots and upper trunk of the brachial plexus. Trauma to the lumbosacral plexus, on the other hand, is uncommon because the nerves are relatively immobile and protected by the vertebrae, psoas muscle, and pelvis. Most traumatic injuries are associated with pelvic or acetabular fractures, frequently with soft-tissue injuries to other pelvic organs.

Neuralgic amyotrophy (also known as idiopathic brachial plexus neuropathy or Parsonage–Turner syndrome) and diabetic lumbosacral radiculoplexus neuropathy (DLRPN; also known as diabetic amyotrophy) are thought to be autoimmune in origin. Both conditions are likely caused by microvasculitis, in which case the autoimmune attack is directed at small vessels within and near the nerves of the roots, plexus and proximal nerves. Neuralgic amyotrophy of the brachial plexus sometimes occurs after a viral illness, vaccination, or mild trauma or during the immediate postpartum period. Usually, these patients present with relatively acute shoulder pain and partial loss of brachial plexus function. Typically, neuralgic amyotrophy predominantly affects nerves of the shoulder girdle muscles, although other portions of the plexus and its terminal branches are occasionally involved, especially the anterior interosseous segment of the median nerve. Approximately one third of patients with neuralgic amyotrophy have bilateral, asymmetric involvement.

DLRPN is the most common cause of lumbosacral plexopathy (Fig. 64-5). DLRPN typically presents in older patients who have type 2 diabetes mellitus, with abrupt or subacute onset of hip and thigh severe pain (see case presentation above). Weakness and muscle atrophy occur within a week or two, often at the time the pain begins to improve. Muscle stretch reflexes may be lost, especially at the knee. DLRPN often begins unilaterally but frequently progresses to bilateral involvement. This monophasic disorder is usually significantly disabling and is commonly associated with unexplained weight loss. Like neuralgic amyotrophy, DLRPN is thought to originate from peripheral nerve microvasculitis. Idiopathic lumbosacral radiculoplexus neuropathy (LRPN) is a rare primary plexopathy that occurs in nondiabetics. It is also manifested by rapid onset of pain, leg weakness, and atrophy. Patients often experience a viral illness 1–2 weeks before symptoms begin. Lumbar plexus involvement often affects the most proximal musculature, causing weakness of the iliopsoas, quadriceps, and adductor muscles. Often, significant recovery occurs within 3 months.

Figure 64-5 Causes of Lumbosacral Radiculoplexopathies.

Hereditary neuralgic amyotrophy (also known as hereditary brachial plexus neuropathy) is an autosomal dominant disorder characterized by periodic, often recurrent, episodes of unilateral or asymmetric pain, weakness, atrophy, and sensory alterations in the shoulder girdle and upper extremity. Genetically, many cases of HBPN are caused by mutations in the SEPT9 gene. Hereditary neuralgic amyotrophy is also believed to be an immune-mediated disorder and likely a microvasculitis with a strong genetic predisposition caused by an inherited SEPT9 mutation.

Malignant tumors, particularly apical lung or postradiation breast cancer, are common causes of brachial plexus lesions (Fig. 64-6). With apical lung tumors, the lesion may insidiously advance, causing numbness in the fourth and fifth fingers, weakness in the ulnar and median hand intrinsic muscles, and Horner syndrome (Pancoast tumor). Often, pain is significant, secondary to neoplastic infiltration of the brachial plexus. This clinical constellation sometimes precedes recognition of the lung tumor. Every patient who smokes and presents in this fashion requires a chest CT or MRI. Tumors occasionally invade the lumbosacral plexus by primary extension from pelvic, abdominal, or retroperitoneal malignancies (see Fig. 64-5). Pain in the distribution of the affected nerves is the cardinal symptom. Late symptoms and signs may include numbness and paresthesias, weakness and gait abnormalities, and lower extremity edema. Retroperitoneal hematomas can compress the lumbar or sacral plexuses or both. Patients present with unilateral pelvic or groin pain; the patient preferentially has the hip flexed to minimize pressure on the plexus (Fig. 64-7). This condition is typically a complication of anticoagulation therapy, or less commonly bleeding diatheses, and immediate surgical decompression can be beneficial.

Figure 64-6 Apical lung tumor invading left brachial plexus.

Figure 64-7 Large hematoma involves the left iliacus and psoas muscles (arrow) and adjacent region, likely involving the lumbar plexus and femoral nerve.

Compressive lumbosacral plexopathies may also occur from a number of other mechanisms, including late pregnancy or childbirth and abdominal aortic aneurysms. A retroperitoneal infection such as a psoas abscess rarely affects the lumbosacral plexus. Radiation-induced lumbosacral plexopathies develop months to years after radiotherapy to pelvic malignancies. The lumbar plexus is more commonly affected in radiation-induced lesions, whereas the sacral plexus is more frequently affected by neoplastic plexopathies. Painless weakness develops at a variable rate, ultimately causing asymmetric but significant weakness of both lower extremities. Paresthesias and pain are common but usually mild. Sphincter involvement is rare.

Treatment and Prognosis

Treatment of plexus lesions comprises management of the primary condition. Careful glucose control may hasten DLRPN recovery and improve outcome. The efficacy of steroids or intravenous immunoglobulin in the acute or subacute phase of DLRPN is not proven, although anecdotal reports suggest clinical benefit and some evidence is emerging that the pain and other neuropathic symptoms may respond to these treatment options. Most traumatic lesions are treated conservatively, although pelvic fractures and gunshot wounds may necessitate surgery. No effective treatment exists for radiation-induced brachial or lumbosacral plexopathy. Oncologic intervention is necessary for neoplastic brachial or lumbosacral plexopathy. Symptomatic pain management is usually necessary. Pain control with narcotics is often necessary in the acute phase of DLRPN, LRPN, neuralgic amyotrophy, hereditary neuralgic amyotrophy, traumatic plexopathy, and neoplastic plexopathies.