Alcoholic Neuropathy, the most common of all the nutritional diseases of the nervous system, is characterized by progressive weakness and muscle wasting of varying degrees, involving, symmetrically, the legs more than the arms and the distal muscles more than the proximal ones. Weakness may be almost imperceptible or so severe that the legs are virtually paralyzed and the hands useless. Motor signs and sensory manifestations most frequently occur concomitantly.
Abnormalities of sensation are usually striking. Patients complain of aching, coldness, hotness, deadness, numbness, prickliness, and tenderness, most commonly in the calves, on the plantar surfaces of the feet, and in the fingers. Deep pressure or light touch may be extremely unpleasant. In the most severe cases, the muscles become wasted, atrophic, flabby, and tender, and the skin may be dry, red, and shiny. Excessive perspiration of feet and hands is occasionally noted.
The deep tendon reflexes, which may be exaggerated in some patients at the onset of the illness, are usually greatly diminished or totally abolished. The sensory loss is symmetrical, most severe distally, and diminishes gradually over more proximal parts; all modalities are involved, some more than others. On rare occasions, severe burning, shooting, lightning, or “electric” types of pain can occur in the absence of clear-cut signs of neuropathy. The term “burning feet syndrome” has been applied to this variety of neuropathic disorder. This syndrome has been encountered in inmates of prison .camps, chronic alcoholics, and patients undergoing dialysis for chronic renal failure. In rare instances, nutritional polyneuropathy may be accompanied by vertigo, deafness, aphonia, and amblyopia.
The mode of evolution and the severity of nutritional polyneuropathy can be quite variable. Usually the onset is insidious, and the progression is slow. Sometimes the course is rapid and abrupt, crippling the patient in a matter of weeks. Recovery requires months and is sometimes incomplete.
A temporary worsening of paresthesias and of weakness may follow the start of therapy. In early or mild cases, a prolonged nerve conduction velocity may be the only objective manifestation of the disease. Examination of the cerebrospinal fluid reveals a normal level or a very slight elevation of the protein content.
The salient pathologic changes suggest segmental demyelination of peripheral nerves involving distal parts to a greater degree than proximal ones. Occasionally dorsal root ganglia reveal a loss of nerve cells, and axonal reaction may be seen in some of the anterior horn cells of the spinal cord. It has been speculated that in nutritional polyneuropathy, primary axonal degeneration or a process of “dying back” results in destruction of both the axon and myelin sheaths in the periphery of the largest and longest nerve fibers.
Pathogenesis and Treatment of Alcoholic Neuropathy.
Nutritional depletion probably alters the normal metabolism of peripheral nerves in several different ways. Both experimental and clinical studies support the view that a deficiency of several of the B vitamins can result in neuropathy. Certain neuropathies respond to the administration of thiamin alone. Recent studies have shown decreased levels of thiamin in the blood, urine, and muscles of patients afflicted with alcoholic neuropathy. Prior to nutritional replenishment, the activity of blood transketolase is usually reduced, and blood pyruvate levels, measured before and after the administration of glucose, may be elevated. The fact that biochemical evidence of thiamin deficiency in nutritional polyneuropathy cannot always be obtained is explained by the slow evolution of this disorder.
Whereas the biochemical lesion antedates all clinical manifestations of neuropathy, the latter linger on for many months after the metabolic insult has been removed. A deficiency of pyridoxine has also been blamed for nutritional polyneuropathy. A neuropathic disorder has been observed in patients who were given deoxypyridoxine, a metabolic antagonist of vitamin B6. The neuropathy that develops in the course of isoniazid (isonicotinic acid hydrazide, INH) therapy can be reversed by pyridoxine alone. Isoniazid causes a deficiency of the essential cofactor pyridoxal phosphate by interfering with phosphorylation of the vitamin.
Pyridoxal phosphate is an essential cofactor for a number of enzymatic reactions known to participate in protein metabolism. The specific role of these enzymatic reactions in the metabolism of peripheral nerves .remains to be defined. A deficiency of pyridoxal phosphate results in the inadequate synthesis of nicotinic acid from tryptophan. Reduced blood levels of nicotinic acid and nicotinamide have been measured in some patients with nutritional polyneuropathy. Pantothenic acid deficiency may also be involved in the production of some forms of nutritional polyneuropathy. It has been claimed that the administration of pantothenic acid relieves the burning feet syndrome, regardless of its cause.