Departments of Neurophysiopathology and
1 Clinical Toxicology, Faculty of Medicine II University of Naples, Italy
Received 27 July 2000; in revised form 5 December 2000; accepted 19 January 2001
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ABSTRACT |
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INTRODUCTION |
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Moreover, alcohol-related neuropathy is associated with several risk factors, such as malnutrition, thiamine deficiency, direct toxicity of alcohol and recently family history of alcoholism (Victor, 1975; Bosch et al., 1979
; Claus et al., 1985
; Huas et al., 1993
; Dyck et al., 1994
; Monforte et al., 1995
; Pessione et al., 1995
), but which of these plays a primary role in inducing neuropathy is still unclear (Estruch et al., 1993
; Palliyath and Schwartz, 1993
; Windebank, 1993
).
In the present work, we carried out a retrospective, cross-sectional study on a group of chronic alcoholics to evaluate parameters in alcohol-related neuropathy, such as (1) prevalence of clinical and electrophysiological alterations, (2) type of electrophysiological alterations, (3) presence of correlations between some clinical parameters such as parental history of alcoholism, age, nutritional status, alcoholic disease duration and total lifetime dose of ethanol (TLDE), and peripheral neuropathy.
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PATIENTS AND METHODS |
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Methods
Each patient received assessment for the following aspects. (1) Careful history, paying particular attention to family history of alcoholism, defined as positive when father and/or mother presented alcohol abuse. (2) Clinical and neurological examination: neurological assessment was carried out using a neuropathy symptom score and neurological disability score (Dyck, 1988). Clinical peripheral neuropathy was considered when the patient had two or more of the following clinical abnormalities: muscle weakness, paraesthesia, symmetrically depressed or absent tendon reflexes and sensory deficit. (3) Calculation of TLDE expressed in kg of ethanol/kg of body weight; this was estimated by first multiplying the daily consumption of ethanol by the number of days in the periods exposed to alcohol and then dividing the product by the body weight of the patient when first admitted. Alcoholic disease duration was identified as the number of years corresponding to the sum of alcohol intake periods. (4) Laboratory tests: these included glucose, creatinine, cholesterol, triglycerides, electrolytes, serum aspartate and alanine aminotransferases,
-glutamyl transpeptidase, protein electrophoresis, lactate dehydrogenase, creatine kinase, aldolase, red blood cell, white blood cell and platelet counts, haematocrit, total protein, prealbumin, albumin, iron, transferrin, prothrombin time and ethanol levels in blood and urine. (5) Evaluation of nutritional status: comparison between the actual weight and the ideal weight; study of the lean body mass calculated from the circumference of upper non-dominant arm and the thickness of the tricipital skin fold (expression of total body fat); study of nutritional proteins, evaluating total protein, albumin, prealbumin, total lymphocytes, transferrin, and of serum folate with vitamin B1 by chromatographic method (pathological values <16 ng/ml) and vitamin B12 studied with a fluorimetric enzyme-linked assay (pathological values
226 pg/ml, that is the 5th percentile of our general population). Caloric or protein malnutrition was considered whenever body weight was <90% of the ideal weight or a lean body mass was <90% of the normal value or at least three of the examined nutritional serum parameters were deranged (Durnin and Womersley, 1974
; Blackburn et al., 1977
; Burrit and Anderson, 1984
). (6) Electroneurographic evaluation of the ulnar, median, peroneal and sural nerves: this involved a study of maximum motor conduction velocity of the median and peroneal nerves with their compound action potential amplitude; study of sensory orthodromic conduction velocity of the ulnar and sural nerves with their sensory-evoked potential (SEP) amplitude. The evaluated parameters were considered pathological when they differed from the average value ± 2.0 SD, obtained from a control group of 40 subjects aged between 30 and 60 years, who did not consume alcoholic drinks. Subclinical peripheral neuropathy was considered to be present if the patient had one or more of the above-reported electrophysiological parameters altered at least in two of the examined nerves, but no clinical symptoms or signs.
Data analysis
All 76 patients were subdivided into two groups: the first group was made up of patients with neuropathy, the second group were subjects without neuropathy. In these two groups, some clinical risk factors such as age, nutritional status, family history of alcoholism, alcoholic disease duration and TLDE were compared. Moreover, considering sural nerve SEP amplitude as a suitable parameter for the evaluation of sensory axonal dysfunction, a comparison and statistical evaluation (Student's t-test) of sural nerve SEP amplitude was performed between alcoholics in toto and the control group and then among neuropathic alcoholics in toto and neuropathic alcoholics respectively with advanced age, altered nutritional status, positive family history of alcoholism, long alcoholic disease duration and high TLDE. Advanced age, long alcoholic disease duration and high TLDE were considered when these parameters exceeded their respective average values obtained from our series of cases. Finally, risk factors for neuropathy (age, nutritional status, positive family history of alcoholism, alcoholic disease duration and TLDE) were correlated with sural nerve SEP amplitude in chronic alcoholics with neuropathy through the Pearson's correlation coefficient multivariate analysis.
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RESULTS |
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DISCUSSION |
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Electroneurographic studies of alcoholic neuropathy show damaged sensory and motor nerve peripheral fibres caused by an axonal degeneration and consisting mainly of decreased sensory- and/or motor-evoked potential amplitudes with light involvement of conduction velocity (Kimura, 1989; Vuadens and Bogouslasky, 1998). Our electroneurographic findings indicate that the most frequent and earliest parameter to be affected is sensory-evoked potential amplitude, followed by sensory conduction velocity, motor-evoked potential amplitude and lastly motor conduction velocity. These results confirm the presence of mostly axonal neuropathy with more frequent and early involvement of sensory nervous fibres specially of the lower limbs.
As for aetiology and pathogenesis, the literature points out that alcoholic neuropathy is related to several factors: malnutrition, thiamine deficiency, direct toxicity of alcohol and, more recently, family history of alcoholism. According to some authors, alcoholic peripheral neuropathy is due mainly to malnutrition (Windebank, 1993), whereas according to other authors, neuropathy is related to the direct toxicity of alcohol on the peripheral nervous system (Estruch et al., 1993
; Palliyath and Schwartz, 1993
). In support of this latter hypothesis, an experimental investigation on animals showed that cytochrome P 4502E1, an ethanol-inducible isoenzyme of the P450-dependent pathway for ethanol oxidation in hepatocytes and neurons, may be involved in alcohol-related neurotoxicity (Wohrle et al., 1998
). Moreover, a recent clinical cross-sectional study postulated that alcohol may have a dose-related toxic effect and could be considered an important risk factor for peripheral neuropathy (Monforte et al., 1995
). With regard to family history of alcoholism and alcohol-related diseases, few studies have reported hereditary factors in chronic alcoholic patients in relation to hepatic (Hrubec and Omenn, 1981) or central nervous system diseases (Begleiter et al., 1983
; Hill et al., 1986
; Polich et al., 1994
).
Our study indicates that, in chronic alcoholics with peripheral neuropathy, there are few cases with malnutrition (less than a quarter), a moderate prevalence of patients with positive family history of alcoholism (more than a half) and a statistically significant correlation between peripheral neuropathy and high TLDE. In agreement with Monforte et al. (1995), these findings suggest that alcohol could be an important risk factor for alcoholic neuropathy. On this basis, we cannot rule out positive family history of alcoholism as an important factor.
Furthermore, the hypothesis of a direct toxicity of alcohol on peripheral nervous fibres is strengthened by the fact that sural nerve SEP amplitude, a suitable parameter to evaluate sensory axonal dysfunction and the most frequently altered among the electroneurographic parameters in our series of cases, is significantly more decreased in neuropathic patients with high TLDE, than in subjects with altered nutritional status or positive family history of alcoholism.
Finally, a multivariate analysis performed to evaluate the independent effect of risk factors for neuropathy in relation to sural nerve SEP amplitude in neuropathic chronic alcoholics seems to support this hypothesis; based on Pearson's correlation coefficient study, SEP amplitude was significantly inversely correlated only to alcoholic disease duration and to TLDE, confirming a dose-dependent relationship between SEP amplitude decrease and increased alcohol consumption. As reported in our previous study (Ammendola et al., 2000) there seems to be a greater female sensitivity to the toxic effects of alcohol on peripheral nerve fibres.
In conclusion, our study indicates that in chronic alcoholism: (1) peripheral neuropathy seems to be very frequent especially when subclinical. Thus a routine use of electrophysiological investigations for chronic alcoholics could be helpful, especially for those patients receiving disulfiram treatment which can occasionally lead to neuropathy; (2) neurogenic damage is mostly characterized by axonal degeneration of sensory and motor nerve fibres with earlier and more frequent involvement of sensory nerves and lower limbs; (3) positive family history of alcoholism, but especially all alcoholic disease duration and TLDE, appear to be more important factors than malnutrition in determining neuropathy.
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FOOTNOTES |
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