Alcoholic Acute Axonal Neuropathy
abstract & commentary
Source: Wohrle JC, et al. Alcohol-related acute axonal polyneuropathy: A differential diagnosis of Guillain-Barré syndrome. Arch Neurol 1998;55:1329-1334.
Over a three-year period, five chronic alcoholic patients, without a history of diarrheal prodrome or previous symptoms or signs of polyneuropathy, presented with rapidly ascending, flaccid, tetraparesis (n = 4) or paraparesis (n = 1), absent or depressed deep tendon reflexes, glove-stocking loss of multimodal sensation, painful paresthesiae (n = 4) or myalgia (n = 3), and dysautonomia consisting of tachycardia and hyperhydrosis, the latter possibly representing alcohol withdrawal. No patient demonstrated central nervous system signs, sphincteric incontinence, or cranial nerve abnormality, and none required ventilatory support.
Liver function tests were abnormal in all with macrocytic anemia in four, one with deficient B6, and one with decreased folate. Serum glucose, B1, B12, thyroid function, protein and immunoelectrophoresis, and anti-GM1 antibodies were normal or negative. Cerebrospinal fluid protein was slightly elevated in one (0.63 g/L, normal < 0.50), with normal cell count and negative oligoclonal banding in all. Nerve conduction studies demonstrated low or absent compound muscle action potential amplitudes (n = 5) with proportionately slowed motor conduction velocities, normal or mildly prolonged distal motor latencies, and F-wave responses that were mildly prolonged (n = 2) or absent (n = 2) only in the presence of severely reduced motor amplitudes. Sensory nerve conduction studies were abnormal with decreased or absent action potential amplitudes, and slowed conduction velocities, but not to the demyelinating range. Needle electromyography showed positive waves in four patients by three to four weeks and, in all patients, by six weeks. Sural nerve biopsy performed in only one patient showed large and small fiber axonal dropout without signs of demyelination or inflammation.
All patients regained mobility within months while abstinent from alcohol and partaking of a balanced diet, vitamin supplementation and physical therapy, although two received immunotherapy before the extent of the alcohol abuse was appreciated (one course of plasma exchange and immunoglobulin in one patient each). Acute alcoholic axonal neuropathy is a rare complication of chronic alcoholism, which may be differentiated from Guillain-Barré syndrome by a history of significant alcohol abuse (> 250 g/d for > 3 years in these patients), severe objective sensory loss (uncommon in GBS), sparing of cranial nerve and respiratory muscle function in the presence of profound limb weakness, electrodiagnostic studies showing axonal neuropathy, and an unremarkable CSF formula.
Commentary
Half of the adult U.S. population regularly consumes alcohol, the most frequently abused drug in the world. About 15-20 million Americans are alcoholic, 100,000 people die annually from its effects, and, among the elderly, it results in hospitalization as often as myocardial infarction. All this at a bargain: $100 billion annually (Angell M, Kassirer JP. N Engl J Med 1994;331:537-539; Adams WL, et al. JAMA 1993;270:1222-1225; Erratum. JAMA 1993;270:2055).
The cause of alcoholism remains obscure but improved understanding of its pathophysiology has recently emerged. Most of ethanol’s toxic and metabolic effects can be explained by its oxidation, through alcohol dehydrogenase, to acetaldehyde, and then to acetate. NADH is generated by both these conversions and, in excess, results in widespread metabolic abnormalities, including hyperlipidemia, hypoproteinemia, hypoglycemia, hyperlactacidemia, hyperuricemia, and increased collagen synthesis (Lieber CS. N Engl J Med 1995;333:1058-1065). Acetaldehyde has equally wideranging toxicity, including lipid peroxidation (which promotes cell death), microtubular binding (blocks protein secretion), pyridoxine (vitamin B6) depletion, inhibition of DNA repair, and impairment of the mitochondrial electron-transport chain (ibid). Induction of the microsomal ethanol-oxidizing system (MEOS, a P450-dependent pathway for ethanol oxidation in hepatic microsomes) also follows chronic ethanol ingestion, with significant (5- to 10-fold) elevation of cytochrome P-4502E1 (an ethanol-inducible isozyme of P450). Cytochrome P-4502E1, which catalyzes the bulk of MEOS activity, is remarkable for its ability to generate toxic metabolites, carcinogens, hepatotoxins, and free radicals from a wide range of foreign precursors, including anesthetics (enflurane), solvents (bromobenzene), and legitimate and illicit medications (isoniazid, acetaminophen, cocaine). Cytochrome P-4502E1 is also present in rat brain in the basal ganglia and cerebellar cortices. Following ethanol treatment, it increases in the basal ganglia and cerebellar cortices and is induced in the substantia nigra and hippocampus, supporting the notion that the brain metabolizes ethanol by P4502E1 and that it may be involved in the neurotoxic effects of alcohol (Sohda T, et al. Alcohol Alcohol Suppl 1993;1B:69-75). The neurology of alcohol is yet to be fully elucidated but more is surely yet to come.
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