219
Drug and Alcohol Dependence, 27 (1991) 219-222 Elsevier Scientific Publishers Ireland Ltd.
Autonomic and peripheral neuropathy in chronic alcoholic liver disease E. Gonzalez-Reimers* , M. Alonso-Socas, F. Santolaria-Fernandez, J. Hernandez-Pena, A. Conde-Martel and F. Rodriguez-Moreno Dpto do Medicina Znterna, Hospital
Universitario (Received
de Canarias, La Laguna, Tenetife, Canary Islands December
20th,
(Spain)
1990)
Peripheral and autonomic neuropathy has been evaluated, both by clinical and neurophysiological and by clinical methods, respectively, in 33 alcoholics, 20 of them cirrhotics. Nerve dysfunction was compared with liver function parameters, the ChildPugh score, and parameters derived from ethanol consumption. Few relationships were obtained between the autonomic and peripheral nerve dysfunction, and between these and liver function impairment, although Pugh’s score was higher when hyporeflexia and altered heart rate response to orthostatism were present. Thus, in the alcoholic, autonomic and peripheral neuropathy, seem not to be dependent on each other, whereas there appears to be a weak correlation between liver function and both autonomic and peripheral neuropathy. Key words;
alcoholic
neuropathy
Introduction
tients with liver disease, and also in patients with non-alcoholic liver diseases when compared with controls. The aim of the present study was to determine whether autonomic and/or peripheral neuropathy are related or not to liver failure.
Chronic alcohol consumption leads to the development of neuronal damage [ 11,affecting the central 121 and peripheral nervous system [ 31. Both peripheral and autonomic neuropathy may become disabling disorders. Paresthesia, anesthesia, weakness, and hyporeflexia, especially in the lower limbs are hallmarks of peripheral neuropathy. Abnormal sudoration, depressed reflex heart rate responses, orthostatic hypotension, dysphonia and dysphagia are derived from autonomic dysfunction. Parasympathetic seems to be more affected than sympathetic activity [ 41, and is associated with high mortality rates [ 51. One has speculated about the existence of a direct link between liver function derangement and autonomic neuropathy [ 6,7 I, with clinical manifestations being more marked in alcoholic pa-
Patients
Thirty-three patients were studied, 29 men and 4 women, aged 47.9 (f 11.7) years. All of them had been heavy drinkers (more than 80 g ethanol/day) during at least 5 years before admission. Twenty were cirrhotics, aged 49.2 (f 2.2) years, drinkers of 1.4 ( f 20) g ethanol daily, and 13 non-cirrhotics, aged 45.9 (k3.9) years, drinkers of 1’71 (f 15) g ethanol daily. The following parameters were recorded: Presence of not of weakness in lower limbs. Presence or not of weakness in upper limbs. Presence of muscle atrophy (by clinical inspection of muscle masses).
*Correspondence to: E. Gonzalez-Reimers, Dpto de Medicina Interna, Hospital Universitario de Canarias, La Laguna, Tenerife, Canary Islands, Spain.
0376-8716/91/$03.50 0 1991 Elsevier Printed and Published in Ireland
Scientific
Publishers
and methods
Ireland
Ltd.
220
Presence of paresthesia either in lower or upper limbs. Presence of achillean, rotulian, and bicipital hyporeflexia.
Bicipital and rotulian tendon reflexes were normal in all patients, but achillean reflexes were diminished or absent in 40% of our patients, 52% of cirrhotics and 18% of non-cirrhotics (NS). Lower limbs’ muscle atrophy was slightly more frequent among cirrhotics (21%) than in noncirrhotics (9%) (NS). Paresthesia in lower limbs was also more frequently observed among cirrhotics (52%) than in non-cirrhotics (27%) differences being not statistically significant. Altered blood pressure response to orthostatism was slightly more frequent among cirrhotics (50% vs. 26.7%; NS). A statistically significant association was found between the presence of encephalopathy and altered blood response to orthostatism (x2 = 3.94, P < 0.05).’ No significant association was found between altered heart rate after Valsalva manoeuvre and cirrhosis, ascites, or encephalopathy. No relation was found between altered heart response to orthostatism and cirrhosis, ascites and encephalopathy. Nerve conduction velocity of the aforementioned nerves were not significantly different in patients with and without cirrhosis, with and
The following clinical tests exploring autonomic dysfunction were performed 181. Heart rate response to Vaisalva manoeuvre. Immediate heart rate response to standing. Blood pressure response to standing. Sural, sciatic, and median nerves conduction velocity was also assessed. These parameters were compared with those derived from progression of liver disease and alcohol intake. Results None of our patients showed weakness in upper limbs, whereas one third of them showed some degree of weakness in lower limbs (42% of chirrhotics and 27% of non-cirrhotics; nonsignificant (NS)).
Table I “t” values
“r” values
Prothrombin Bilirubin Albumin ASAT ALAT MCV GGT LDH Pugh score Ethanol/years Ethanol/day SNCV MNCV CNCV
SNCV
MNCV
CNCV
Atrophy
Weakness
Hypor
0.45** -0.15 0.08 0.13 0.26 0.03 0.24 -0.19 - 0.24 0.15 - 0.02 -
0.25 0.06 -0.06 0.10 0.16 0.06 0.12 -0.26 0.19 -0.02 - 0.25 0.32 -
0.42: -0.14 0.04 0.18 0.27 0.11 0.25 -0.21 -0.11 0.13 -0.12 0.89*** 0.50* *
1.16 1.29 1.70 2.76’* 3.14** 2.57” 4.17*** 0.68 1.31 0.78 0.73 0.87 0.73 0.45
0.01 0.67 2.20* 2.63* 0.91 0.81 2.07’ 1.81 0.68 1.28 0.34 0.34 0.01 0.23
1.98 1.87 2.68** 1.63 0.66 0.37 2.24’ 0.10 2.31* 0.26 0.91 0.37 0.27 0.99
‘P < 005. . , +*p < 001. . , ***p < 0.001. Abbreviation.s: SNCV, sural nerve conduction velocity; MNCV, median nerve conduction velocity; CNCV, sciatic nerve conduction velocity; Hypor, hyporeflexia.
Table
I1 “t” value Orthost
Valsalva
Orthpulse
Prothrombin Bilirubin
1.20 1.34
1.24 1.34
2.55* 2.01”
Albumin ALAT ASAT MCV GGT LDH Pugh score Ethanol/years
0.70 0.09 0.17 0.53 1.00 1.18 1.62 1.73
0.38 1.87 0.95 0.07 2.33* 0.35 1.08 0.39
1.83 0.61 0.83 0.45 1.27 1.01 2.02* 0.62
Ethanol/day SNCV MNCV CNCV
1.99* 0.20 2.20* 0.23
0.22 0.18 0.73 0.24
1.27 0.69 0.48 0.81
*P < 0.05. Abbreviations: thpulse,
altered
Orthost, heart
altered rate
after
blood pressure
response
to orthostatism;
Valsalva,
altered
heart
rate
after
Valsalva
manoeuvre;
orthostatism.
without ascites, and with and without encephalopathy. Relationships between parameters derived from liver function and ethanol consumption, and nerve conduction velocity and other parameters derived from peripheral or autonomic nerve dysfunction are listed in Tables I and II. Discussion
The results of our study point to the absolute independence of liver function derangement and neuropathy, both peripheral and autonomic. No associations were found between cirrhosis and parameters derived from peripheral or autonomic nerve dysfunction, although they became altered more frequently among the cirrhotics. These results are fully in accordance with those of Thuluvath and Trigger [9]. Moreover, in that study, no relation was found between peripheral and autonomic nerve dysfunction, nor with liver function impairment. We formed a weak relationship with liver function impairment, but signifi-
cant ones between higher Pugh’s score [ 101 (i.e., more severe liver failure) and hyporeflexia and altered heart rate response to orthostatism, whereas no relationship was observed between Pugh’s score and the objective neurophysiological tests. As with liver failure, there are some weak, inconclusive relations between nerve dysfunction and amount of ethanol or in the case of lower limbs’ muscle atrophy, ethanol-related biochemical parameters (MCV and GGT). Thus, from our study, it can be concluded that there is a weak correlation between liver function impairment and both autonomic and peripheral neuropathy, and, in agreement with other authors between autonomic and [91, no correlation peripheral neuropathy. References 1 2
Nordman, R. et al., Alcohol Alcoholism, Pratt, O.E. et al., Alcohol Alcoholism,
3
Behse,
F. and Buchthal,
25 (1990) 231. 25 (1990) 217.
F., Ann. Neurol.,
2 (1977) 95.
(
222 4 5 6 7
(Editorial) Lancet, II (1989) 721. Kempler, P., Varadi, A. and Szalay, F., Lancet, II (1989) 1332. Johnson, R.H., Robinson, B.J., J. Neurol. Neurosurg. Psychiatry, 51 (1988) 476. Tan, E.T.H. et al., J. Neurol. Neurosurg. Psychiatry, 47 (1984) 1335.
8 9 10
Ewing, D.J. and Clarke, B.F., Br. Med., J., 285 (1982) 916. Thuluvath, P.J. and Triger, D.R., Q. J. Med., 72 (1989) 737. Infante-Rivard, C. et al., Hepatology, 4 (1987) 660.
Drug and Alcohol Dependence, 27 (1991) 219-222 Elsevier Scientific Publishers Ireland Ltd.
Autonomic and peripheral neuropathy in chronic alcoholic liver disease E. Gonzalez-Reimers* , M. Alonso-Socas, F. Santolaria-Fernandez, J. Hernandez-Pena, A. Conde-Martel and F. Rodriguez-Moreno Dpto do Medicina Znterna, Hospital
Universitario (Received
de Canarias, La Laguna, Tenetife, Canary Islands December
20th,
(Spain)
1990)
Peripheral and autonomic neuropathy has been evaluated, both by clinical and neurophysiological and by clinical methods, respectively, in 33 alcoholics, 20 of them cirrhotics. Nerve dysfunction was compared with liver function parameters, the ChildPugh score, and parameters derived from ethanol consumption. Few relationships were obtained between the autonomic and peripheral nerve dysfunction, and between these and liver function impairment, although Pugh’s score was higher when hyporeflexia and altered heart rate response to orthostatism were present. Thus, in the alcoholic, autonomic and peripheral neuropathy, seem not to be dependent on each other, whereas there appears to be a weak correlation between liver function and both autonomic and peripheral neuropathy. Key words;
alcoholic
neuropathy
Introduction
tients with liver disease, and also in patients with non-alcoholic liver diseases when compared with controls. The aim of the present study was to determine whether autonomic and/or peripheral neuropathy are related or not to liver failure.
Chronic alcohol consumption leads to the development of neuronal damage [ 11,affecting the central 121 and peripheral nervous system [ 31. Both peripheral and autonomic neuropathy may become disabling disorders. Paresthesia, anesthesia, weakness, and hyporeflexia, especially in the lower limbs are hallmarks of peripheral neuropathy. Abnormal sudoration, depressed reflex heart rate responses, orthostatic hypotension, dysphonia and dysphagia are derived from autonomic dysfunction. Parasympathetic seems to be more affected than sympathetic activity [ 41, and is associated with high mortality rates [ 51. One has speculated about the existence of a direct link between liver function derangement and autonomic neuropathy [ 6,7 I, with clinical manifestations being more marked in alcoholic pa-
Patients
Thirty-three patients were studied, 29 men and 4 women, aged 47.9 (f 11.7) years. All of them had been heavy drinkers (more than 80 g ethanol/day) during at least 5 years before admission. Twenty were cirrhotics, aged 49.2 (f 2.2) years, drinkers of 1.4 ( f 20) g ethanol daily, and 13 non-cirrhotics, aged 45.9 (k3.9) years, drinkers of 1’71 (f 15) g ethanol daily. The following parameters were recorded: Presence of not of weakness in lower limbs. Presence or not of weakness in upper limbs. Presence of muscle atrophy (by clinical inspection of muscle masses).
*Correspondence to: E. Gonzalez-Reimers, Dpto de Medicina Interna, Hospital Universitario de Canarias, La Laguna, Tenerife, Canary Islands, Spain.
0376-8716/91/$03.50 0 1991 Elsevier Printed and Published in Ireland
Scientific
Publishers
and methods
Ireland
Ltd.
220
Presence of paresthesia either in lower or upper limbs. Presence of achillean, rotulian, and bicipital hyporeflexia.
Bicipital and rotulian tendon reflexes were normal in all patients, but achillean reflexes were diminished or absent in 40% of our patients, 52% of cirrhotics and 18% of non-cirrhotics (NS). Lower limbs’ muscle atrophy was slightly more frequent among cirrhotics (21%) than in noncirrhotics (9%) (NS). Paresthesia in lower limbs was also more frequently observed among cirrhotics (52%) than in non-cirrhotics (27%) differences being not statistically significant. Altered blood pressure response to orthostatism was slightly more frequent among cirrhotics (50% vs. 26.7%; NS). A statistically significant association was found between the presence of encephalopathy and altered blood response to orthostatism (x2 = 3.94, P < 0.05).’ No significant association was found between altered heart rate after Valsalva manoeuvre and cirrhosis, ascites, or encephalopathy. No relation was found between altered heart response to orthostatism and cirrhosis, ascites and encephalopathy. Nerve conduction velocity of the aforementioned nerves were not significantly different in patients with and without cirrhosis, with and
The following clinical tests exploring autonomic dysfunction were performed 181. Heart rate response to Vaisalva manoeuvre. Immediate heart rate response to standing. Blood pressure response to standing. Sural, sciatic, and median nerves conduction velocity was also assessed. These parameters were compared with those derived from progression of liver disease and alcohol intake. Results None of our patients showed weakness in upper limbs, whereas one third of them showed some degree of weakness in lower limbs (42% of chirrhotics and 27% of non-cirrhotics; nonsignificant (NS)).
Table I “t” values
“r” values
Prothrombin Bilirubin Albumin ASAT ALAT MCV GGT LDH Pugh score Ethanol/years Ethanol/day SNCV MNCV CNCV
SNCV
MNCV
CNCV
Atrophy
Weakness
Hypor
0.45** -0.15 0.08 0.13 0.26 0.03 0.24 -0.19 - 0.24 0.15 - 0.02 -
0.25 0.06 -0.06 0.10 0.16 0.06 0.12 -0.26 0.19 -0.02 - 0.25 0.32 -
0.42: -0.14 0.04 0.18 0.27 0.11 0.25 -0.21 -0.11 0.13 -0.12 0.89*** 0.50* *
1.16 1.29 1.70 2.76’* 3.14** 2.57” 4.17*** 0.68 1.31 0.78 0.73 0.87 0.73 0.45
0.01 0.67 2.20* 2.63* 0.91 0.81 2.07’ 1.81 0.68 1.28 0.34 0.34 0.01 0.23
1.98 1.87 2.68** 1.63 0.66 0.37 2.24’ 0.10 2.31* 0.26 0.91 0.37 0.27 0.99
‘P < 005. . , +*p < 001. . , ***p < 0.001. Abbreviation.s: SNCV, sural nerve conduction velocity; MNCV, median nerve conduction velocity; CNCV, sciatic nerve conduction velocity; Hypor, hyporeflexia.
Table
I1 “t” value Orthost
Valsalva
Orthpulse
Prothrombin Bilirubin
1.20 1.34
1.24 1.34
2.55* 2.01”
Albumin ALAT ASAT MCV GGT LDH Pugh score Ethanol/years
0.70 0.09 0.17 0.53 1.00 1.18 1.62 1.73
0.38 1.87 0.95 0.07 2.33* 0.35 1.08 0.39
1.83 0.61 0.83 0.45 1.27 1.01 2.02* 0.62
Ethanol/day SNCV MNCV CNCV
1.99* 0.20 2.20* 0.23
0.22 0.18 0.73 0.24
1.27 0.69 0.48 0.81
*P < 0.05. Abbreviations: thpulse,
altered
Orthost, heart
altered rate
after
blood pressure
response
to orthostatism;
Valsalva,
altered
heart
rate
after
Valsalva
manoeuvre;
orthostatism.
without ascites, and with and without encephalopathy. Relationships between parameters derived from liver function and ethanol consumption, and nerve conduction velocity and other parameters derived from peripheral or autonomic nerve dysfunction are listed in Tables I and II. Discussion
The results of our study point to the absolute independence of liver function derangement and neuropathy, both peripheral and autonomic. No associations were found between cirrhosis and parameters derived from peripheral or autonomic nerve dysfunction, although they became altered more frequently among the cirrhotics. These results are fully in accordance with those of Thuluvath and Trigger [9]. Moreover, in that study, no relation was found between peripheral and autonomic nerve dysfunction, nor with liver function impairment. We formed a weak relationship with liver function impairment, but signifi-
cant ones between higher Pugh’s score [ 101 (i.e., more severe liver failure) and hyporeflexia and altered heart rate response to orthostatism, whereas no relationship was observed between Pugh’s score and the objective neurophysiological tests. As with liver failure, there are some weak, inconclusive relations between nerve dysfunction and amount of ethanol or in the case of lower limbs’ muscle atrophy, ethanol-related biochemical parameters (MCV and GGT). Thus, from our study, it can be concluded that there is a weak correlation between liver function impairment and both autonomic and peripheral neuropathy, and, in agreement with other authors between autonomic and [91, no correlation peripheral neuropathy. References 1 2
Nordman, R. et al., Alcohol Alcoholism, Pratt, O.E. et al., Alcohol Alcoholism,
3
Behse,
F. and Buchthal,
25 (1990) 231. 25 (1990) 217.
F., Ann. Neurol.,
2 (1977) 95.
(
222 4 5 6 7
(Editorial) Lancet, II (1989) 721. Kempler, P., Varadi, A. and Szalay, F., Lancet, II (1989) 1332. Johnson, R.H., Robinson, B.J., J. Neurol. Neurosurg. Psychiatry, 51 (1988) 476. Tan, E.T.H. et al., J. Neurol. Neurosurg. Psychiatry, 47 (1984) 1335.
8 9 10
Ewing, D.J. and Clarke, B.F., Br. Med., J., 285 (1982) 916. Thuluvath, P.J. and Triger, D.R., Q. J. Med., 72 (1989) 737. Infante-Rivard, C. et al., Hepatology, 4 (1987) 660.
