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Peripheral neuropathies can be categorized on the basis of the structure primarily affected The predominant pathologic feature may be axonal degeneration (axonal or neuronal neuropathies) or paranodal or segmental demyelination The distinction may be possible on the basis of neurophysiologic findings Motor and sensory conduction velocity can be measured in accessible segments of peripheral nerves In axonal neuropathies, conduction velocity is normal or reduced only mildly and needle electromyography provides evidence of denervation in affected muscles In demyelinating neuropathies, conduction may be slowed considerably in affected fibers, and in more severe cases, conduction is blocked completely, without accompanying electromyographic signs of denervation Nerves may be injured or compressed by neighboring anatomic structures at any point along their course Common mononeuropathies of this sort are considered below They lead to a sensory, motor, or mixed deficit that is restricted to the territory of the affected nerve A similar clinical disturbance is produced by peripheral nerve tumors, but these are rare except in patients with Recklinghausen s disease Multiple mononeuropathies suggest a patchy multifocal disease process such as vasculopathy (eg, diabetes, arteritis), an infiltrative process (eg, leprosy, sarcoidosis), radiation damage, or an immunologic disorder (eg, brachial plexopathy) Diffuse polyneuropathies lead to a symmetric sensory, motor, or mixed deficit, often most marked distally They include the hereditary, metabolic, and toxic disorders; idiopathic inflammatory polyneuropathy (Guillain-Barr syndrome); and the peripheral neuropathies that may occur as a nonmetastatic complication of malignant diseases Involvement of motor fibers leads to flaccid weakness that is most marked distally; dysfunction of sensory fibers causes impaired sensory perception Tendon reflexes are depressed or absent Paresthesias, pain, and muscle tenderness may also occur
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Riluzole, 50 mg orally twice daily, which reduces the presynaptic release of glutamate, may slow progression of amyotrophic lateral sclerosis There is otherwise no specific treatment except in patients with gammopathy, in whom plasmapheresis and immunosuppression may lead to improvement Therapeutic trials of various neurotrophic factors to slow disease progression have yielded generally disappointing results as have trials of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, and pentoxifylline Symptomatic and supportive measures may include prescription of anticholinergic drugs (such as trihexyphenidyl, amitriptyline, or atropine) or use of a portable suction machine if drooling is troublesome, braces or a walker to improve mobility, and physical therapy to prevent contractures Behavioral modification (eg, exercising facial muscles and encouraging frequent swallowing) or over-the-counter decongestants may also help mild drooling Spasticity may be helped by baclofen or diazepam A semiliquid diet or nasogastric tube feeding may be needed if dysphagia is severe Gastrostomy or cricopharyngomyotomy is sometimes resorted to in extreme cases of predominant bulbar involvement, and tracheostomy may be necessary if respiratory muscles are severely affected; however, in the terminal stages of these disorders, the aim of treatment should be to keep patients as comfortable as possible Information on palliative care is provided in 5
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Weakness, sensory disturbances, or both in the extremities Pain sometimes common
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Depressed or absent tendon reflexes May be family history of neuropathy May be history of systemic illness or toxic exposure The cause of polyneuropathy or mononeuritis multiplex is suggested by the history, mode of onset, and predominant clinical manifestations Laboratory workup includes a complete blood count and sedimentation rate, serum protein electrophoresis, and immunophoresis, determination of plasma urea and electrolytes, liver and thyroid function tests, tests for rheumatoid factor and antinuclear antibody, HBsAg determination, a serologic test for syphilis, fasting blood glucose level, urinary heavy metal levels, cerebrospinal fluid examination, and chest radiography These tests should be ordered selectively, as guided by symptoms and signs Measurement of nerve conduction velocity is important in confirming the peripheral nerve origin of symptoms and providing a means of following clinical changes, as well as indicating the likely disease process (ie, axonal or demyelinating neuropathy) Cutaneous nerve biopsy may help establish a precise diagnosis (eg, polyarteritis, amyloidosis) In about half of cases, no specific cause can be established; of these, slightly less than half are subsequently found to be heredofamilial Treatment is of the underlying cause, when feasible, and is discussed below under the individual disorders Physical therapy helps prevent contractures, and splints can maintain a weak extremity in a position of useful function Anesthetic extremities must be protected from injury To guard against burns, patients should check the temperature of water and hot surfaces with a portion of skin having normal sensation, measure water temperature with a thermometer, and use cold water for washing or lower the temperature setting of their hot-water heaters Shoes should be examined frequently during the day for grit or foreign objects in order to prevent pressure lesions Patients with polyneuropathies or mononeuritis multiplex are subject to additional nerve injury at pressure points and should therefore avoid such behavior as leaning on elbows or sitting with crossed legs for lengthy periods Neuropathic pain is sometimes troublesome and may respond to simple analgesics, such as aspirin or nonsteroidal anti-inflammatory agents, and to gabapentin Opioids may be necessary for severe hyperpathia or pain induced by minimal stimuli, but their use should be avoided as much as possible The use of a frame or cradle to reduce contact with bedclothes may be helpful Many patients experience episodic stabbing pains, which may respond to gabapentin, pregabalin, phenytoin, carbamazepine, or tricyclic antidepressants Symptoms of autonomic dysfunction are occasionally troublesome Postural hypotension is often helped by wearing waist-high elastic stockings and sleeping in a semierect position at night Fludrocortisone reduces postural hypotension, but doses as high as 1 mg/d are sometimes necessary in diabetics and may lead to recumbent hypertension Midodrine, an -agonist, is sometimes helpful in a dose of 25 10 mg three times daily Impotence and diarrhea are difficult to treat; a flaccid neuropathic bladder may respond to parasympathomimetic drugs such as bethanechol chloride, 10 50 mg three or four times daily
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