Other than diseases of the lumbosacral nerve roots and plexus, polyneuropathies and mononeuropathies can affect the leg. Polyneuropathy affects both legs, usually in a symmetrical manner. Polyneuropathy which involves the small sensory fibers usually results in distal pain and burning. Mononeuropathies affect only one nerve and thus only affect one leg at a time. Depending on the type of injury, mononeuropathy may also result in significant pain in the distribution of the nerve. The diagnosis of mononeuropathy is usually based on the pattern of weakness and numbness. The more common neuropathies affecting the lower extremities are the following.
Lateral femoral cutaneous neuropathy (‘Meralgia paresthetica’)
The lateral femoral cutaneous nerve runs as a direct extension off the lumbar plexus, around the pelvic brim to pass under the inguinal ligament to supply an oval area of skin over the lateral thigh. Entrapment of the lateral femoral cutaneous nerve may occur under the inguinal ligament resulting in a painful burning patch in the anterior lateral thigh. This is known as Meralgia paresthetica. As the nerve supplies no muscle, there is no reflex loss, no muscle atrophy or weakness. Obesity, tight clothing and diabetes are risk factors for this entrapment neuropathy.
The femoral nerve is derived from the L2–L4 nerve roots. The femoral nerve first supplies the iliopsoas muscle before running under the inguinal ligament where it divides into motor and sensory branches. The motor fibers supply the sartorius and pectineus muscles and the four heads of the quadriceps femoris muscle. Sensory fibers branch into three divisions supplying the anterior medial thigh, intermediate thigh, and medial calf.
Isolated femoral neuropathy is rare. It most often occurs as the result of compression from traction or stretch during pelvic surgery. In addition, the femoral nerve can become entrapped under the inguinal ligament if the leg is maintained in a lithotomy position for a prolonged period, as often happens during pelvic surgery. Iatrogenic femoral neuropathy can occur in the inguinal region from misguided femoral catheterizations or subsequent to hematoma formation. Patients with femoral neuropathy develop buckling of their knee (due to quadriceps weakness), loss of the knee jerk, and sensory disturbance over the anterior thigh and medial calf.
The saphenous nerve is the terminal extension of the femoral nerve supplying sensation to the medial calf. An isolated lesion of the saphenous nerve does not result in any motor weakness but only disturbed sensation over the medial calf. Although a saphenous neuropathy may be part of a larger femoral neuropathy, it may occur as an isolated finding as a result of trauma to the knee, or as an iatrogenic complication following orthopedic surgery at the knee or venous grafting for coronary artery bypass operations.
The tibial nerve is derived from the distal sciatic nerve above the popliteal fossa. The tibial nerve provides motor innervation to the muscles which plantarflex and invert the ankle as well as supplying most of the intrinsic foot muscles. Tibial sensory fibers supply the lateral foot, posterior calf and the sole of the foot. Patients with tibial neuropathy will have difficulty walking and will be unable to walk on their tiptoes. The ankle jerk will be depressed or absent and sensation may be abnormal over the posterior calf, lateral foot, and sole. Isolated tibial neuropathies are uncommon; they may result from unusual mass lesion in the popliteal fossa (Baker’s cyst, popliteal aneurysm, hemorrhage).
The peroneal nerve, like the tibial nerve, is derived from the distal sciatic nerve in the popliteal fossa. The common peroneal nerve shortly bifurcates into the deep and superficial peroneal nerves. The deep peroneal nerve innervates the muscle which dorsiflexes the ankle and toes, and supplies sensation to the webspace between the great and second toe. The superficial peroneal nerve supplies muscles which evert the ankle as well as providing sensation to the lateral calf and dorsum of the foot. The peroneal nerve is vulnerable to injury and compression at the level of the fibular neck where it is quite superficial. Patients with peroneal neuropathy may develop pain about the lateral knee associated with foot drop and numbness over the lateral calf and dorsum of the foot.
The sciatic nerve is the largest nerve in the body receiving nerve fibers from the L4–S3 nerve roots. The sciatic nerve leaves the pelvis under the piriformis muscle to supply the lateral and medial hamstrings before terminating in the peroneal and tibial nerves. Patients with sciatic neuropathy develop a combination of peroneal and tibial neuropathy in addition to weakness of hamstrings. All movement around the ankle will be weak or paralyzed. Sensory disturbance will develop over the lateral calf, dorsum and sole of the foot. The ankle jerk will commonly be absent. Acute sciatic neuropathies are usually the result of trauma, missile injury, prolonged immobilization, or infarction. Slowly progressive sciatic neuropathies often suggest slowly grow-ing mass lesions, usually a tumor.
Plantar neuropathy (tarsal tunnel syndrome)
The tibial nerve terminates in the medial ankle dividing into the medial and lateral plantar nerves and the calcaneal nerves. The plantar nerves supply the intrinsic foot musculature and sensation to the medial and lateral sole, respectively. As the nerve enters the foot, it runs under the flexor retinaculum on the medial ankle, known as the tarsal tunnel. Entrapment of the distal tibial in this tunnel results in local ankle pain with loss of sensation or neuropathic symptoms involving the sole of the foot.
Polyneuropathies are probably the most common of all nerve lesions affecting the leg and usually present in a symmetric pattern, affecting both legs. Toxic, metabolic, and genetic polyneuropathies all present in a length-dependent fashion. The longest nerve, which carries the greatest metabolic demand, is the first to be affected. Accordingly, patients with polyneuropathy present with sensory disturbance on the soles of the feet which then slowly advances up the foot and into the ankle. Only when the level of sensory disturbance reaches the upper calf do patients start to develop sensory disturbance in their fingers (i.e. the stocking glove pattern). This occurs as the distance between the cervical spinal cord and the fingers is the same as between the lumbosacral spinal cord and the upper calf.
There are a vast number of conditions which can cause polyneuropathy. The differential diagnosis of polyneuropathy is often narrowed by knowing the following:
1 Tempo of the disease (acute, subacute, chronic, progressive or relapsing/ remitting).
2 Fiber types involved (motor, sensory-large fiber, sensory-small fiber, autonomic).
3 Axonal or demyelinating or mixed (usually based on nerve conduction studies or biopsy).
4 Family history of polyneuropathy.
5 History of medical conditions often associated with polyneuropathy (diabetes, cancer, connective tissue disease, malnutrition, HIV infection).
6 Toxic exposure history (chemicals, medicines, alcohol).
Polyneuropathies are often associated with some degree of pain or unpleas-ant dysesthesias. However, several neuropathies predominantly affect small sensory fibers and are significantly associated with neuropathic pain. Patients present with distal burning and dysesthetic pain, and in some cases, distal autonomic changes in the foot and lower leg. Among these, the most common is the polyneuropathy associated with diabetes. Diabetes is the most common cause of neuropathy in North America and can affect peripheral nerve in a variety of ways: polyneuropathy, lumbosacral plexopathy, radiculopathy, and various mononeuropathies. Although diabetic polyneuropathy affects large sensory fibers as well, there is usually a distinct small-fiber component causing burning dysesthetic pain.
Several toxic and metabolic conditions (e.g. arsenic, thallium, thiamine deficiency) can result in a small-fiber polyneuropathy. Among them, the most common is polyneuropathy due to alcohol.
Inflammatory conditions may cause a painful neuropathy. Ischemia due to vasculitis often results in frank infarction of nerve. A patient may describe deep boring pain often at the infarction site followed by clear nerve dysfunction distally. In the leg, the sciatic nerve is most prone to nerve infarction in the proximal thigh, a watershed area for nerve ischemia. In contrast to nearly all polyneuropathies, vasculitic polyneuropathy usually presents in an asymmetrical pattern. Individual nerves are infarcted in a step-wise manner (i.e. the mononeuritis multiplex pattern). Over time, a confluent pattern develops that can be difficult to differentiate from the common stocking glove pattern. Other than vasculitis, polyneuropathy may occur from ischemia of other causes. Compartment syndromes, if not treated acutely, result in both nerve and muscle ischemia associated with significant pain. Rarely, major ischemic vascular disease of the leg may result in distal nerve damage and pain.
Some inherited conditions may be associated with painful distal neuro-pathy. Various infections infiltrate nerve and may cause a painful neuropathy. One of the most common is herpes zoster (i.e. shingles) that presents with pain and rash in a radicular pattern. After the rash has resolved, a significant number of patients are left with disabling neuropathic pain (postherpetic neuralgia). Lastly, amyloidosis is frequently associated with a small fiber painful neuropathy. Amyloidosis can occur as a familial disease or as an acquired condition. Amyloid deposits in nerve and may have a direct toxic effect or secondary vascular effect. The result is dysfunction of the small myelinated and unmyelinated axons. Patients typically present with painful polyneuropathy associated with loss of pain and temperature sensation and autonomic dysfunction.
The evaluation of a patient with suspected neuropathy involves first a close and detailed history noting the points above. EMG and nerve conduction studies are then required to confirm the localization is due to a polyneuropathy and not due to a plexopathy or polyradiculopathy. Second, the EMG and nerve conduction studies can often tell whether the neuropathy is primarily demyelinating or axonal. This is a key differentiating factor, as very few neuropathies present with primary demyelination. In some cases, a nerve biopsy is needed for definitive diagnosis. A nerve biopsy is usu-ally required when inflammatory conditions such as vasculitis or infiltrative conditions such as amyloidosis are considered.
Therapy of neuropathic pain
The treatment of peripheral nerve disorders is divided into therapy of the underlying disorder and symptomatic therapy. When the etiology can be found, treatment of the underlying disorder is always preferable (e.g. B12 replacement for pernicious anemia with neuropathy, dialysis/transplantation for uremic neuropathies, immunosuppression for autoimmune inflammatory neuropathy, etc.). If the neuropathy is secondary to a toxic agent (e.g. alcohol), the first step is to prevent any further contact. In patients with entrapment neuropathy, surgical decompression may be useful in selected cases.
In cases where treatment for the underlying condition does not exist (i.e. inherited neuropathies) or the diagnosis is uncertain, symptomatic therapy must be employed. Treatment of painful or other paresthesias is frequently difficult. Simple analgesics (ASA, non-steroidal anti-inflammatory drugs, acetaminophen) are usually tried first, but usually with no benefit. Narcotics are useful in selected cases, but are best avoided. Transcutaneous nerve stimulation and acupuncture are also useful in some patients.
Next employed are the agents which work directly on neuropathic pain. Among them are anticonvulsants (e.g. phenytoin, carbamazepine, neurontin, etc.), the tricyclic antidepressants (especially amitriptyline) and lioresal (baclofen). The agent of choice is usually based on the patient’s other medical problems and their ability to tolerate potential side-effects. Amitriptyline is among the most effective agents in the treatment of chronic neuropathic pain. However, several points must be kept in mind. First, mild anticholinergic side-effects (dry mouth, visual blurring, constipation) and sedation are dealt with by initially using a low dose (typically 10 or 25 mg) at bedtime. The dose can then slowly be titrated up to a more therapeutic level. It is not unusual that patients require 25–100 mg of amitriptyline at bedtime. Second, and more importantly, is the fact that the analgesic properties of amitriptyline are always delayed, usually several weeks. Patients need to be encouraged to stick with their program and not to give up too early. If the anticholinergic side-effects are too bothersome or contraindicated (e.g. urinary retention from prostatic enlargement), then other tricyclics with fewer anticholinergic side-effects (e.g. nortriptyline) can be substituted.
Other than the tricyclic antidepressants, the anticonvulsant medicines (e.g. phenytoin, carbamazepine, and neurontin) have antineuropathic pain qualities. Doses are similar to those used to treat seizures. In each, it is best to start at a low dose, and slowly titrate up to effect or until side-effects occur. Neurontin is particularly easy to use, not being associated with significant side-effects or drug interactions. Patients are usually started on a low dose (e.g. 100 mg tid) and slowly titrated up. Some patients may require total daily doses of 2400 mg or more.
In addition, lioresal (baclofen) has potent analgesic qualities. It is a first-line agent used in cases of trigeminal neuralgia, and is often helpful in neuropathic pain. Dosage is started at 1/2 tablet (5 mg) tid and slowly increased by a 1/2 tablet up to a maximum dose of 20 mg tid or qid.
The anti-arrhythmic, Mexitil (mexiletine), has been shown to be useful in some patients with diabetic polyneuropathy. This drug has significant poten-tial toxicity (especially cardiac) and is best reserved for those familiar with its use and side-effects.
In addition to the oral medicines used to treat neuropathic pain, capsaicin ointment has been affective in some patients with neuropathic pain. It has been helpful in cases of postherpetic neuralgia, and diabetic polyneuropathy. Capsaicin suffers from the fact that it must be applied manually three or four times a day, and often causes increased symptoms during the first several days of therapy.
If patients cannot be managed with the above agents, they are best referred to a multidisciplinary pain center. Rarely, incapacitating neuropathic pain may require invasive, ablative neurosurgical procedures.
Of importance, many patients with neuropathic pain go through a phase where their neuropathy is quite painful. As the neuropathy gets worse, often their pain will get better. This occurs as frank numbness replaces painful paresthesias. Of course, numbness and lack of feeling may create a whole host of new problems. Among them, the most worrisome is injury to the foot without recognition, leading to more serious problems of infection of soft tissues and bone.
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