Neuropathic leg pain – Disease of the nerve root
Diseases of the nerve roots are among the most common afflictions of man. Each nerve root contains sensory and motor fibers supplying a specific area of skin (dermatome), and a specific number of muscles (myotome). However, any particular area of skin may receive innervation from several overlapping dermatomes, and all muscles receive innervation from more than one myotome. Accordingly, with disease of a single nerve root, dense sensory loss does not develop. Patients with radiculopathy who complain of sensory symptoms in one dermatome more often have vague and ill-defined sensory loss on examination (due to the wide overlap of adjacent dermatomes).
Likewise, dysfunction of one nerve root never leads to paralysis but only to weakness. For instance, the quadriceps is innervated by L2–L4 nerve roots via the femoral nerve. A severe lesion of the femoral nerve will result in severe weakness of the quadriceps (the quadriceps are only innervated by the femoral nerve). However, any equally severe L4 radiculopathy will result in only mild to moderate weakness of the quadriceps. Paralysis does not develop due to the contribution of L2 and L3.
Radiculopathy is usually caused by compression as the nerve root leaves the intervertebral foramen. This most often results from a herniated intervertebral disc (especially in younger individuals) or as a result of hyper-trophy of bone or ligaments in older individuals (i.e. spondylosis). By far the most common sites for disc herniation are at L4–5 with compression of the L5 nerve root and at L5–S1 with compression of the S1 root. In addition, radiculopathy may result from other mass lesions, including metastatic diseases of the spine, or rarely abscess within the epidural space. In the two latter conditions, radiculopathy usually occurs prior to frank spinal cord compression.
Radiculopathy is the most common source of neuropathic pain in the leg. Though the lesion is at the nerve root level, pain is often referred into the leg in a radiating manner in the distribution of the nerve root. However, the majority of the pain is proximal, usually in the back, buttocks, and upper thigh. Upper lumbar radiculopathies (L2–4) may refer pain anteriorly into the thigh whereas lower lumbosacral (L5–S1) radiculopathies refer pain posterior and lateral, generally to a level below the knee. Patients characteristically find prolonged sitting and standing difficult. Coughing and sneezing can exacerbate the radiating pain down the leg. This occurs as coughing and sneezing both increase intraspinal pressure. Simple movement or manipulation of the back is painful. Patients often find that the most comfortable position is lying on their side with their hips and knees in a flexed posture.
Radiculopathy should be suspected in any patient with leg pain who also has coexistent back pain with radiation of that pain down the leg. Pain from
the ligaments and joints of the back and hip may radiate into the proximal lower extremity but not below the knee. Mechanical movements that increase the pain such as bending or straightening the leg also suggest the presence of radiculopathy, and there are a number of tests that rely on this principle, including straight leg raising and the ‘bowstring’ sign. The level of radiculopathy can often be deduced by the distribution of muscle weakness, which reflexes are depressed or in what areas the patient reports altered or disturbed sensation.
Beyond an isolated radiculopathy, root disease may manifest by many or all the lumbosacral nerve roots being affected at the same time (lumbosacral polyradiculopathy). This can occur in several situations. The first is the cauda equina syndrome, which can occur either acutely or chronically. Anatomically, the spinal cord ends at the L1 vertebra with the lumbosacral nerve roots running caudally through the thecal sac before exiting at their appropriate level (grossly, these nerve roots resemble a horse’s tail, hence, cauda equina). Compression of the cauda equina may occur acutely as a result of either massive disc herniation or hemorrhage; it may occur gradually with tumor affecting all the lumbosacral nerve routes. In the acute syndrome, the patient develops significant back pain, a rapidly progressive paralysis of both legs, numbness of both legs including the genital and anal regions (the sacral dermatomes), and bladder and bowel dysfunction. An acute cauda equina syndrome is a neurological emergency requiring urgent imaging of the lower spine to exclude a compressive lesion which may require surgical decompression. Rarely an acute cauda equina syndrome may develop with a normal computed tomography (CT) or magnetic resonance imaging (MRI). These are the result of infiltration by tumor or granulomatous tissue, or more often from infection, especially HSV and CMV viruses. CMV has a predilection to cause this syndrome in immunosuppressed patients, especially those with HIV.
The other situation in which a lumbosacral polyradiculopathy can occur is the condition of spinal stenosis or neurogenic claudication. Spinal stenosis is a degenerative disease of the lumbosacral spine which usually occurs in older individuals from a combination of degenerative joint disease, ligament and joint facet hypertrophy, abnormal bone formation, and disc bulging/herniation resulting effectively in decreased space in the thecal sac. The nerve roots initially are intermittently compressed when the patient assumes the standing position. Patients give a clear history of pain that develops in the back with radiation into the buttocks and legs with walking. The pain is relieved by rest and often suggests the diagnosis of vascular claudication. The key to separating neurogenic claudication from the more typical vascular claudication is that neurogenic claudication requires that the patient sit for the pain to go away. This is in contrast to the patient with vascular claudication, who can simply rest in a standing posture. In addition, patients with neurogenic claudication often develop some cutaneous sensory symptoms or paresthesias suggesting that their abnormality involves nerve.
Evaluation of radiculopathy/polyradiculopathy
If the history and physical examination suggest a progressive radiculopathy or polyradiculopathy, then further laboratory and radiological investigation is required.
The evaluation of a patient with a suspected radiculopathy or polyradiculopathy involves imaging of the back, selective nerve conduction studies/ EMG, and in some cases, cerebrospinal fluid (CSF) examination. Imaging with CT myelogram or MRI scans can usually identify the presence of a structural lesion entrapping the nerve roots (disc herniation, spinal stenosis, abscess, tumor, or spinal cord malformation). MRI is the most sensitive and useful test to obtain in this setting, and should be obtained urgently if the symptom complex has occurred over hours or days.
It is important to note that radiculopathy and polyradiculopathy may both occur without a structural lesion seen on MRI or CT myelogram. In these cases (suspected radiculopathy clinically, but with normal imaging), further investigation is required, usually with nerve conduction studies/EMG and CSF examination.
Non-mechanical radiculopathy can occur secondarily to nerve infarction (e.g. vasculitis, diabetes) or nerve infiltration (e.g. granulomatous disease such as sarcoid or from direct invasion by malignancy). Several infectious agents can directly infect nerve or cause a secondary inflammation. Infections which can affect the nerve roots include Lyme disease, Herpes Zoster, CMV, HSV, HIV, as well as rare cases of tuberculosis and fungi. Abnormal CSF studies will be found in most of these conditions.
Nerve conduction studies and EMG are often useful in patients with suspected radiculopathy. Nerve conduction and EMG can aid with the localization of the neurological lesion, usually differentiating a nerve root lesion from a peripheral nerve or lumbosacral plexus lesion. However, the EMG may remain normal up to 2 weeks after compression. Often, it is quite difficult to differentiate clinically a lumbosacral plexus lesion from a lumbosacral radiculopathy (another cause of normal imaging). EMG is often useful in making the differentiation between root and plexus disease. Electrical studies also add information about the function of the nerve root. A radiculopathy, severe enough to cause some wallerian degeneration, will result in denervation of the muscle fibers which can be easily seen on EMG.
Therapy of radiculopathy/polyradiculopathy
Therapy is tailored to the type of lesion and the amount of neurological disability. Many cases of disc herniation can be treated conservatively with bed rest and analgesics followed by gentle mobilization and later physical therapy. This should be the first approach unless there is a bowel, bladder or motor deficit on testing. The long-term goal is to reduce pressure on the lumbar spine by a combination of weight loss, proper posture, and an exercise program to increase the strength of the back and abdominal musculature. Indications for surgery usually include lack of improvement with conservative therapy, patient preference or a significant or progressive neurological deficit. There are many surgical procedures now for disc herniation including microscopic discectomy and endoscopic discectomy.
In case of mass lesions other than disc herniation, surgery is usually indicated. Compression by tumor may be treated with steroids and radiation if the tumor source is already known and characterized. If not, surgery is needed not only for decompression, but for definitive diagnosis. Likewise, abscess is usually treated with surgical drainage, culture and systemic antibiotics.
Therapy for neurogenic claudication usually involves surgery as well. How-ever, the timing of surgery needs to be individualized based on the disability of the patient. If the patient who is also a poor surgical candidate develops minor claudication after several blocks of walking, it is probably best to treat such a patient conservatively and to have the patient adjust their behavior accordingly. However, if a patient is otherwise a good surgical risk and the degree of disability is significantly interfering with the quality of the patient’s life, then decompressive therapy is indicated.