Alcohol-dependency Unit and
1 Unit of Clinical Neurophysiology, Fondazione S. Maugeri, Clinica del Lavoro e della Riabilitazione, IRCCS, Istituto Scientifico di Pavia, Via A. Ferrata 4, 27100 Pavia and
2 Department of Preventive Occupational and Community Health, University of Pavia School of Medicine, Via S. Boezio 13, 27100 Pavia, Italy
Received 25 September 2000; in revised form 26 February 2001; accepted 14 March 2001
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ABSTRACT |
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INTRODUCTION |
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The pathogenesis of alcoholic polyneuropathy is still under debate. While some have argued that it results from a nutritional deficiency, and especially from a deficiency of thiamine, there is both clinical and experimental evidence of a direct toxic effect of alcohol (Pinelli, 1985). The issue is not easily resolved, because there are no direct estimates of nutritional status that are independent of the patient's history. A number of studies have shown that alcoholism can cause both nutritional deficiencies and nervous system disease, and almost invariably ethanol neurotoxicity is encountered in heavy drinkers presenting with nutritional deficits (Martin et al., 1986
; Charness et al., 1989
; Charness, 1993
). In Victor's (1984) study of hundreds of cases of neuropathy associated with alcoholism, dietary deficiency was always found to be present when a reliable clinical history could be obtained. Behese and Buchtal (1977) made a painstaking attempt to separate out the relative effects of alcohol toxicity and malnutrition. They compared 37 alcoholics with six post-gastrectomy patients, all with polyneuropathy. In the alcoholic group, 23 patients showed no signs of malnutrition and 14 had a history of weight loss (>10 kg). All six of the post-gastrectomy patients reported severe weight loss. The alcoholics drank mainly beer, and these authors pointed out that Danish beer contains 3040 µg of thiamine and 400 µg of pyridoxine per litre. Deficiency of these vitamins was deemed unlikely in beer drinkers, and measured blood levels of the vitamins, when obtained, were within normal limits. Beer also contains 500700 calories per litre; thus the beer-drinking alcoholic is rarely calorie-deficient. On clinical and electrophysiological grounds, the post-gastrectomy patients, the malnourished alcoholics and the adequately nourished alcoholics could not be differentiated. However, nerve biopsy studies of the post-gastrectomy patients revealed a greater relative contribution of segmental demyelination to the development of polyneuropathy. This finding, along with the evidence that the alcoholic subjects with alcohol-related polyneuropathy were not malnourished, led Behese and Buchtal (1977) to conclude that polyneuropathy secondary to malnutrition was distinct from that associated with alcohol, and that malnutrition alone does not cause an alcohol-related neuropathy. This study contributes important data regarding the pathogenesis of alcohol-related polyneuropathy and demonstrates that it is probably not caused by a single vitamin B or a calorie deficiency, but by a B complex deficiency associated with the direct neurotoxicity of alcohol (Victor, 1984
; Windebank, 1993
; Pessione et al., 1995
). Alcohol-induced vitamin deficiency may occur by a combination of mechanisms such as inadequate dietry intake (since calorie intake is largely constituted by the consumption of alcohol), the relative preponderance of carbohydrates in an alcoholic's diet (a high thiamine intake is required for their metabolism), general malabsorption due to the frequent chronic calcific pancreatitis suffered by alcoholics, and thiamine malabsorption due to the direct effect of alcohol on the gastrointestinal mucosa (Pinelli, 1985
).
Several studies have explored these mechanisms. It has been shown that, during binge drinking, chronic alcoholics may markedly reduce their essential nutrient intake due to decreased appetite. Additionally, ethanol is a rich source of non-nutritive calories and an alcoholic may consume more than a third of the body's daily energy requirements as ethanol, and thus have a significantly reduced demand for food to meet his caloric needs (Charness et al., 1989; Lieber, 1990
). Nutritional deficiencies ranging from undernutrition to severe malnutrition may also occur as complications of alcoholism. Both chronic and acute ethanol consumption have direct negative effects on the gastrointestinal mucosa and the pancreas. As a result, absorption of such nutrients as amino acids and vitamins may be hindered (Persson, 1991
). Additionally, alcohol misuse may alter metabolism, transport, use, activation, and storage of many essential nutrients. Such alterations are partially attributable to the direct toxic effect of ethanol on the liver (Lieber, 1991
). Chronic alcoholics frequently suffer from illnesses such as infection, anaemia, and bleeding related to peptic ulcers, which may exacerbate the nutritional deficiency and increase the patient's overall metabolic demands. Most of the neurological syndromes related to alcohol misuse arise from a complex interaction of events involving direct ethanol neurotoxicity, nutritional deficiencies due to heavy drinking, and possibly genetic predisposition (Martin et al., 1986
; Charness et al., 1989
; Manzo et al., 1994
; Pessione et al., 1995
). Despite the complex interactions between alcohol and diet, there is a consistent clinical pattern of polyneuropathy in chronic alcoholics (Victor, 1984
). Alcoholics with polyneuropathy commonly show the typical features of alcoholic misuse including disordered social relationships, skin changes, memory disorders and ataxia. Neuropathy may be a minor aspect of the neurological presentation of Wernicke's encephalopathy or Korsakoff's syndrome. When polyneuropathy is the main complaint, the early symptoms are usually distal and symmetric, dysaesthetic sensory disorders in the feet. If present, the pain tends to be described as cramp-like, burning or stabbing. Sensory symptoms progress from distal to proximal regions in the lower limbs and in severe cases may involve the hands. Symptoms in the hands, characterized by sensory loss or electric tingling, are typically less painful than those in the feet. Walking becomes increasingly problematic because of the weakness of the distal muscles and manual dexterity is progressively reduced due to the combination of muscle weakness, sensory loss and ataxia. Clinical examination reveals signs of symmetric and distal sensory motor and autonomic loss. Sensory loss tends to begin with a loss of superficial pain sensation, which in the severest cases progresses to the loss of all types of sensation in a glove-and-stocking distribution. Often, such sensory symptoms are accompanied by increased painful sensitivity of the limbs initially to superficial light touch, and, as the neuropathy evolves, to deep palpation of muscles and tendons (Victor, 1984
). When present, autonomic skin changes give rise to reddening, atrophy, and hair loss in the same distribution as the sensory damage.
From a diagnostic viewpoint, the clinical manifestations of polyneuropathy in isolation are not distinctive. Hence the importance of obtaining an accurate clinical history of alcohol misuse, and of nutritional deficits, because many cases of polyneuropathy present asymptomatically (Victor, 1984; Wetterling et al., 1999
). Behse and Buchtal (1977) have proposed that 100 ml of ethyl alcohol (3 l of beer or 300 ml of spirits) per day for 3 years represents the minimal amount of alcohol consumed by patients with polyneuropathy. The aim of the present study was to evaluate the occurrence of symptomatic and asymptomatic polyneuropathy in a group of alcoholic subjects. Polyneuropathy is in fact a frequent complication of chronic alcoholism and may involve symmetric paraesthesia and/or dysaesthesia associated with sensory, motor, and sometimes vegetative deficits. A further aim of this study was to correlate the presence and severity of polyneuropathy with other clinical and laboratory manifestations of chronic alcoholism, such as liver disease, macrocytosis and changes in hepatic enzymes. The type of alcohol consumed, the duration of alcohol misuse, and other current or past dependencies, such as psychoactive drug dependence, were also taken into account.
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PATIENTS AND METHODS |
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RESULTS |
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DISCUSSION |
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As shown in Table 3, 48 of our subjects (16.2%) showed symptoms of polyneuropathy. These were predominantly muscle cramps and paraesthesiae (Fig. 3
). On ENG grounds, the absence of neuropathy was documented in 51.4% of the subjects, whereas the remaining 48.6% had abnormal ENG signs suggestive of varying degrees of polyneuropathy: 3% severe, 17.6% moderate, 13.9% mild, and 14.2% borderline (Table 4
). The rate of polyneuropathy was significantly higher in men than in women, as has recently been reported in the literature (Wetterling et al., 1999
). The frequency of both subjective and objective symptoms increased significantly with age in our sample (Tables 3 and 4
). These results clearly show that some of our asymptomatic subjects had signs of polyneuropathy on ENG, whereas some of the symptomatic subjects had none (Fig. 3
). The former finding may be related to the fact that alcoholics tend to treat negative symptoms such as hypostenia and hypoaesthesia as of no account, whereas the latter result may be explained by the presence of generally hyperalgic forms of polyneuropathy that selectively involve small nerve fibres whose alterations are not revealed by routine ENG investigations. There was, however, a highly significant correlation between the referred symptoms and the polyneuropathy documented with the use of ENG. As demonstrated in previous studies (Behese and Buchtal, 1977
; Wetterling et al., 1999
) the duration of alcohol misuse was one of the most important contributing factors to the occurrence of polyneuropathies. Subjective symptoms were found to occur after relatively short durations of misuse (15 years), whereas the development of severe polyneuropathy required 10 or more years of excessive drinking (Fig. 2
). As shown, the longer the duration of excessive alcohol consumption, the greater the number of subjects with neuropathy. The task of the physician, therefore, is carefully to evaluate both the symptoms referred by the patient and the ENG findings, even when there is a relatively short history of alcohol misuse. Early observation of subtle signs of the disease will allow prompt therapeutic intervention, of course in association with the subject's abstinence from alcohol. The cessation of drinking remains the principal if not only means of preventing the progression of the disease. Moreover, it should be recalled that early forms of neuropathy may be completely reversed by stopping drinking (Savoldi, 1995
). In our alcoholic subjects, the presence of concomitant substance misuse (tobacco smoking, heroin, cocaine, cannabinols) was not significantly related to the presence of polyneuropathy (Table 6
). The severity of polyneuropathy showed a significant correlation with the presence of macrocytosis (Table 3
) and hepatic disease (Fig. 1
), both of which are well-known features of chronic alcoholism. Some authors attribute the concomitant presence of macrocytosis, liver disease and polyneuropathy in chronic alcoholism to vitamin B deficiency (pyridoxine and thiamine), due to the malabsorption and malnutrition occurring in chronic alcoholics (Victor, 1984
; Windebank, 1993
; Manzo et al., 1994
). From our data, the contemporaneous presence of HCV infection doesnt seem to be an important element for the genesis or aggravation of polyneuropathy in alcoholics. In conclusion, the present results confirm that polyneuropathy occurs in a high percentage of chronic alcoholics and that many cases may be clinically asymptomatic. Both the duration of alcohol misuse and the type of alcoholic beverage consumed are particularly relevant. In fact, wine appears to be the main factor for the development of polyneuropathy, perhaps not only in relation to the amount consumed but also the possible toxicants it contains (lead in particular). However, we were unable to examine correlations between the presence of polyneuropathy and daily alcohol intake, due to the lack of sufficiently reliable information provided by the patients under examination. However, we were able to establish that their daily intake was always >100 ml alcohol. The finding of a strong correlation between polyneuropathy and the presence of liver disease and macrocytosis confirms yet again the plethora of diseases related to alcohol misuse.
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FOOTNOTES |
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