INTRODUCTION

 

Neurological syndromes commonly occur in patients with liver diseases. Neurological deficits associated with liver diseases may affect the central nervous system, the peripheral nervous system, or both¹.

The occurrence of a demyelinating peripheral neuropathy in liver diseases was first described by Dayan and Williams².

Although peripheral neuropathy is reported to occur in patients with liver diseases, there is controversy regarding a cause and effect  relationship³. While some authors doubt the existence of hepatic neuropathy, others report an incidence ranging from 19 to 100%. Most authors agree that the neuropathy seen in liver diseases is generally mild or sub-clinical but detailed characterization of the nature of neuropathy are lacking⁴. Additionally, autonomic neuropathy has been reported in patients with alcoholic and non-alcoholic liver diseases^5,6,7. though this has not been characterized in the context of peripheral neuropathy. For many years, previous reports stated that  both liver diseases and neuropathies are systemic disorders in which both liver and nerves are damaged in the evolution of the primary process⁸. In the last years many reports suggested that certain neuropathies arise as a consequence rather than a concomitant of liver diseases⁹.

 

Aim of the study:

*      To define the prevalence of peripheral neuropathy and autonomic neuropathy in patients with chronic liver diseases and to correlate the severity of neuropathy with the severity of liver diseases.

*      To determine whether neuropathy is related to the cause of liver diseases, and to determine the relationship between the prevalence of autonomic neuropathy and sensory-motor neuropathy in liver diseases.

 

PATIENTS AND METHODS

 

Sixty patients with chronic liver diseases, were evaluated for the presence of peripheral (sensorimotor) and autonomic neuropathy. Other causes of peripheral neuropathy as diabetes mellitus, alcoholism, renal dysfunction and those with hereditary peripheral neuropathy were excluded.

                The severity of liver diseases was graded using the Child-Paugh classification (Table 1):

 

Table 1. Child-Paugh classification¹⁰.

 

 

 

Parameters under column (I): take score 1, Parameters under column (II): take score 2, Parameters under column (III): take score 3. Patients with score <7 are graded as class A (mild), Patients with score 7- 9 are graded as class B (moderate), Patients with score 10-15 are graded as class C (severe). In our study; 13 patients were class A, 18 patients were class B, and 29 patients were class C.

 

All patients were subjected to:

1-     Full clinical assessment (general, abdominal and neurological), the neurological evaluation including a history and neurological examination which was relevant to the peripheral neuropathy. A history to elicit sensory or motor symptoms of neuropathy and a neurological examination testing for pin prick sensibilities, vibration sense, muscle strength and deep tendon reflexes.

2-     Laboratory evaluation, in the form of:

A-  Liver function tests, including liver enzymes (SGPT & SGOT), total serum bilirubin and direct bilirubin

B-  Blood sugar and renal function tests.

C-  Serology using the ELISA technique for the determination of the cause of the liver disease (viral and non-viral cause).

3-     Abdominal ultrasonography was done for all patients to assess the liver size, echogenicity, portal vein diameter, splenic size and presence of ascites.

4-     Nerve conduction studies were done for the right and left median nerves, right and left ulnar nerves and right and left common peroneal nerves.

-     For sensory nerves (median and ulnar) distal latencies, sensory conduction velocities and peak to peak amplitude were measured.

-     For motor nerves (median, ulnar and common peroneal) distal latencies, motor conduction velocities, baseline to peak amplitude and F-wave latencies were measured. 

5-     E.M.G- was done in abductor policis muscle bilaterally during rest, minimal contraction, maximum contraction to detect denervation pattern as positive sharp wave, fibs, giant waves and interference pattern.   

6-     Autonomic function tests included determination of blood pressure in response to standing, heart rate variations to rapid deep respirations and Valsalva maneuver.

 

The presence of neuropathy was defined by the presence of abnormalities in at least 2 of 4 categories of symptoms, signs, NCS and autonomic function tests.

 

T-test and Chi square test were used for comparing our groups of data, P-value less than 0.05 is considered as significant and less than 0.01 is considered as highly significant.

 

 

RESULTS

 

 

Table 2. Demographic data.

 

 

 

 

Table 3. Classification of patients according to etiology of liver disease.

  

	Non viral	HCV	HCV&HBV	HBV
Number of patients (%)	13 (21.6%)	38 (63.3%)	5 (8.3%)	4 (6.6%)

 

Table 4. Clinical and Autonomic Manifestations in Different. Classes.

 

 

Table 5. Motor Conduction Study.

   

Lt. Side				Rt. Side
F-wave	Amp.	MCV	DL	F-wave	Amp.	MCV	DL
26 43.3%	21 35%	20 33.3%	19 31.6%	28 46.6%	17 28.3	20 33.3%	19 31.6%	Median n.
4   30.7%	2 15.3%	5 38.4%	2 15.3%	6 46.1%	0  0%	4 30.7%	4 30.7%	Class A
7   38.8%	9 50%	6 33.3%	7 38.8%	7 38.8%	4 22.2%	6 33.3%	4 22.2%	Class B
15 51.7%	10 34.5%	9 31.1%	10 34.5%	15 51.7%	13 44.8%	10 34.5%	11 37.9%	Class C
0.09	0.000	0.8	0.002	0.09	0.000	0.7	0.2	Pv A & B
0.02	0.003	0.18	0.003	0.08	0.000	0.6	0.18	Pv A & C
0.05	0.02	0.96	0.8	0.05	0.003	0.9	0.041	Pv B & C
15 25%	10 16.6%	21 35%	8 13.3%	19 31.6%	8 13.3%	29 48.3%	1 1.6%	Ulnar n.
1 7.6%	1 7.6%	3 23%	0 0%	4 30.7%	0 0%	4 30.7%	0 0%	Class A
4 22.2%	3 16.6%	5 27.7%	1 5.5%	4 22.2%	2 11.1%	8 44.4%	0 0%	Class B
10 34.4%	6 20.7%	13 44.8%	7 24.1%	11 37.9%	6 20.7%	17 58.6%	1 3.44%	Class C
0.02	0.05	0.6	0.01	0.06	0.001	0.04	-	Pv A & B
0.06	0.02	0.003	0.000	0.07	0.000	0.0003	0.003	Pv A & C
0.01	0.4	0.03	0.006	0.02	0.02	0.02	0.003	Pv B & C
33 55%	49 81.6%	51 85%	16 26.6%	33 55%	43 71.6%	50 83.3%	18 30%	Common P. n.
5 38.4%	8 61.5%	11 84.6%	2 15.3%	6 46.1%	5 38.4%	8 61.5%	3  23%	Class A
9  50%	16 88.8%	16 88.8%	6 33.3%	8 44.4%	16 88.8%	14 77.7%	8 44.4%	Class B
19 65.5%	25 86.2%	24 82.75%	8 27.6%	17 58.6%	22 75.8%	28 96.5%	7 24.1%	Class C
0.006	0.03	0.4	0.003	0.4	0.000	0.04	0.003	Pv A & B
0.003	0.04	0.8	0.008	0.05	0.001	0.009	0.9	Pv A & C
0.81	0.5	0.1	0.6	0.04	0.09	0.01	0.003	Pv B & C

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 6. Sensory Conduction Study.

 

	Rt. Side			Lt. Side
	DL	SCV	Amp.	DL	SCV	Amp.
Median n.	22 (36.6%)	51 (85%)	7 (11.6%)	18 (30%)	47 (78.3%)	5 (8.3%)
Class A	2 (15.3%)	10 (76.9%)	2 (15.3%)	2 (15.3%)	9 (69.2%)	1 (7.6%)
Class B	6 (33.3%)	15 (83.3%)	1 (5.5%)	6 (33.3%)	13 (72.2%)	0        (0%)
Class C	14 (48.3%)	26 (89.6%)	4 (13.7%)	10 (34.5%)	25 (86.2%)	4 (13.7%)
Pv (A & B)	0.003	0.3	0.03	0.003	0.5	0.007
Pv (A & C)	0.000	0.2	0.4	0.003	0.2	0.07
Pv (B & C)	0.02	0.1	0.05	0.9	0.3	0.000
Ulnar n.	22 (36.6%)	21 (35%)	2 (3.3%)	21 (35%)	26 (43.3%)	3 (5%)
Class A	2 (15.3%)	2 (15.3%)	0 (0%)	3 (23%)	3 (23%)	0 (0%)
Class B	7 (38.8%)	5 (27.7%)	1 (5.5%)	8 (44.4%)	3 (16.6%)	3 (16.6%)
Class C	13 (44.8%)	14 (48.3%)	1 (3.44%)	10 (34.5%)	20 (68.9%)	0 (0%)
Pv (A & B)	0.002	0.05	0.01	0.003	0.14	0.000
Pv (A & C)	0.000	0.000	0.003	0.04	0.0001	-
Pv (B & C)	0.4	0.007	0.3	0.2	0.000	0.000

 

Table 7. Clinical and autonomic manifestations in non viral and post HCV chronic liver diseases.

 

	Non viral	HCV	p-value between non viral & post. HCV
Symptoms
Tingling and numbness in UL	23.1%	30.6%	0.2
Tingling and numbness in LL	23.1%	26.2%	0.6
Cramps in UL	11.6%	16.2%	0.3
Cramps in LL	11.6%	15.9%	0.3
Weakness in UL	7.7%	5.2%	0.3
Weakness in LL	7.7%	5.2%	0.3
Signs
Glove hypothesia	46.1%	39.4%	0.3
Stock hypothesia	46.1%	55.2%	0.2
Diminished or lost deep reflexes
Biceps	53.8%	39.4%	0.03
Brachioradialis	53.8%	39.4%	0.03
Triceps	53.8%	39.4%	0.03
Knee	76.9%	52.6%	0.003
Ankle	76.9%	63.1%	0.3
Deep sensory loss UL	23%	10.5%	0.02
Deep sensory loss LL	30.7%	10.5%	0.001
Distal weakness UL	7.6%	5.2%	0.3
Distal weakness LL	7.6%	5.2%	0.3
Muscle wasting	0	0	-
Autonomic dysfunction	38.4%	44.3%	0.4

 

DISCUSSION

 

In our study we prospectively evaluated 60 patients with chronic liver diseases to assess the presence of peripheral and autonomic neuropathies regarding their types, prevalence, relation to severity and etiology of liver diseases.  13   patients were in Class A, 18 patients were in class B and 29 patients were class C, as shown in table (3) .Patients with liver diseases of non viral causes were 13(21.6%) and those due to viral causes (virus C, virus A, virus B) were 47patients (78.4%)  .Manual workers were more reported in class C 41.3%,while employee were more in class A. 15.35%.

Most authors agree that the neuropathy seen in liver disease is generally mild or subclinical but detailed characterization of the nature of neuropathy are lacking⁴ .Additionally, autonomic neuropathy has been reported in patients with alcoholic and non-alcoholic liver disease^5,6,7 though this has not been characterized in the context of peripheral neuropathy.

There has been no systematic characterization of peripheral neuropathy in the context of coexisting liver failure⁴. Regarding  neurological findings, we reported that 48 patients (80%) were presented with signs of peripheral neuropathy in the form of glove hypoesethia, stocke hypoesethia, diminished or lost deep reflexes, deep sensory loss, and lastly distal weakness. Our findings regarding signs of peripheral neuropathy were reported more in lower limbs than upper limbs, more in patients with viral causes, and were related to severity of liver diseases, where in class C reported in 93% of patients, in 83% in class B, and in only 23% of patients in class A.

As shown in table (4), glove hypoesthesia was present in 30% of patients of class A, 38.8% of patients of class B and in 51.7% of patients of class C, As regard stock hypoesthesia, it was present in 30% of patients of class A, 61% of patients of class B and in 74.2% of patients of class C, Lost or diminished deep reflexes were detected in the upper limb  in 30% of patients of class A, in 44.4%  of patients of class B and in 59.5% of patients of class C, lost or diminished knee reflexes were detected in 46.1% of patients of class A, in 61% of patients of class B and in 75.8% of patients of class C, lost or diminished ankle reflexes were detected in 53.8% of patients of class A, in 77.7% of patients of class B and in 82.7% of patients of class C, deep sensory loss in the upper limbs was detected in 15.3% of patients of class A, in 16.6% of patients of class B, and in 24.1% of patients of class C, as regard deep sensory loss in the lower limbs, it was detected in 23% of patients of class A, in 23.9% of patients of class B, and in 24.1% of patients of class C, distal weakness either in the upper and lower limbs was detected in only 6.9% of patients of class C. No muscle wasting was detected in  patients of the study.

From the above results we conclude that signs of peripheral neuropathy are more frequent in patients with more severe liver disease, also the lower limbs are affected more than the upper limbs.

These results are in agreement but higher than a previous study¹¹ which  reported that at neurological examination of cirrhotic patients a sensitive distal deficit was clinically observed in 25.8% of patients, a distal motor involvement in 41.9%, and a mixed sensorimotor impairment in 6.5%. Deficit was mainly appreciable in the lower limbs.

Our results are also in agreement but higher than another study¹² which reported that clinical signs of peripheral nerve involvement were found in 21% of patients with chronic liver diseases. Another study⁴  reported that 29% of patients had abnormalities on examination consisting of distal sensory loss to vibration in 20.6% patients, and pin in 12.6% of patients; reduced or absent ankle reflexes in 20.6%of patients; and toe extensor weakness in 1.7% of patients. In  accordance with our results one of the Egyptian studies at 2002¹³, signs of peripheral neuropathy were reported in 86.7% of there patients that agree with our results.

Regarding symptoms of peripheral neuropathy (table 4), 45% of patients were presented with mild non disabling symptoms in the form of mild cramps, paraesethia, and numbness, and only 6.6% of patients were presented with distal weakness. The sensory symptoms were more common than the motor ones. These symptoms were reported in lower limbs more than upper limbs, and were related to severity of liver disease,  where in class C 49.1% of patients were suffering from the previous symptoms compared with 15.3% of patients in class A. Distal paresthesias (tingling and numbness) in upper limbs were present in 15.3% of patients of class A, in  33.3% of patients of class B  and in 49.1% of patients of class C, whereas distal paresthesias in lower limbs were present in 15.3% of patients of class A, in  38.8%of patients of class B and in 53.5% of patients of class C. Distal cramps in  upper limbs were not present in patients of class A, present in  33.3% of patients of class B and in 50.9% of patients of class C, also distal cramps in  lower limbs were not present in patients of class A, present in  38.8% of patients of class B and in 49.9% of patients of class C. None of the patients related to class A  reported history of distal weakness neither in the upper limbs nor in the lower limbs, however, 5.5% of patients in class B had reported distal weakness in both upper and lower limbs. As regard class C 10.3% of the patients had reported distal weakness in both upper and lower limbs. These results show obvious increase in the symptoms with the increase of the severity of the liver disease with a highly statistically significant difference in the majority of them. Our  results are in agreement  but higher than that of a previous study.⁴, which  reported that 22% of patients had symptoms of neuropathy consisting of mild cramps, paraesthesia, or numbness. Also our results are higher than another one¹³ which reported that 26.7% of their patients were suffering from symptoms of peripheral neuropathy.

Regarding autonomic neuropathy, autonomic dysfunctions were reported in 53.3% of our patients in varying degrees according to severity of liver disease. Several autonomic function tests were done for all patients and showed that one or more of all tests used was found to be abnormal in 15.3% of patients of class A, in 72.2% of patients of class B and in 76.4% of patients of class C. Abnormal heart rate variations in response to rapid deep respiration were found in 23% of patients of Class A, in 61.1% of patients of Class B and in 72.4% of patients of Class C. As regard abnormality in heart rate variations in response to Valsalva maneuver it was found in 15.3% of patients of Class A, in 44.4% of patients of Class B and in 68.9% of patients of Class C. Abnormal blood pressure response to standing was present in 7.6% of patients of Class A, in 16.6% of patients of Class B and in 17.2% of patients of Class C. No patient with abnormal autonomic function tests (AFTs) had symptoms related to autonomic dysfunction. Autonomic dysfunctions were reported in patients with viral liver diseases  61.6% more than those of non viral causes 38.4%. 

From our results we found that autonomic dysfunctions are common in patients with chronic liver diseases and the majority of abnormalities were related to patients of class C, followed by those of class B and lastly those of class A, and the differences were statistically significant.

Our result agree with those of Bajaj et al.¹⁴, who reported that autonomic dysfunction was significantly more frequent in advanced liver disease compared with early liver damage. Nine (75%) out of 12 cirrhotic subjects  belonging to Child class B and six (85.7%) of the seven patients belonging to Child class C had autonomic neuropathy while only one patient with Child class A had early parasympathetic damage, and  also with those of McDougall et al.¹⁵, who reported that autonomic neuropathy were common (occurring in 50%)  in patients with endstage liver disease and were more frequent than previously reported. One of the previous studies¹⁶. reported that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggest that the neurological defect may be secondary to the disturbed liver function. 

Also in agreement  with our results  Hendrikse et al.¹⁷,  reported that, autonomic impairment was closely associated with hepatic function with 23% of Child-pugh class A and 69% of class B and C. Also shaza et al.¹³, reported 63.3% of their patients were suffering from autonomic dysfunctions. Returning to our results, we can notice that, most of the autonomic dysfunctions reported were in the form heart rate variations denoting predominant parasympathetic dysfunctions in patients with chronic liver diseases, this notice are supported by previous results^5,13 . 

 

Nerve Conduction Study (tables 5 & 6):

Patients with abnormal  sensory conduction study(median nerve) were 85% of all patients compared with 33.3% with abnormal motor conduction study with significant statistical difference, while the motor conduction study of the common peroneal nerve was more affected  (83.3%90) than that of nerves of the upper limbs.   

(a)    Distal latency: prolonged motor and sensory distal latencies were very common in the median nerve and entrapment neuropathy were detected in about 35.7% of patients, these findings agree the results of Chaudhry et al.⁴, who reported that entrapment neuropathy can occur in about one third of patients.

Prolonged motor distal latency of the ulnar nerve was a rare finding, occurring in the right ulnar nerve in 1.6% of patients of and in the left ulnar nerve in 13.3% of patients. On the other hand the prolonged sensory distal latency of the ulnar nerve was found in 36.6% of patients on the right side and in 35% of patients on the left side. Prolonged  motor distal latency of the right common peroneal nerve were found in 30% of patients and in 26.6% on the left side. The incidence of prolonged distal latency was found to be increased with the severity of liver disease with the highest incidence in class C patients and the least incidence in class A patients. And the difference was statistically significant.

(b)    Conduction Velocity:  the highest incidence of reduced motor conduction velocity(MCV) was found in both right (83.3% of patients) and left (85% of patients) common peroneal nerves, and this agree the results of Lani et al.¹¹, who reported that, in neurophysiologically evaluated patients with chronic liver disease, at least 87% of patients featured different degrees of nerve impairment, mostly located in  peroneal nerves.

Reduced MCV was found in 33.3% of patients in the right median nerve, in 33.3% in the left median nerve, 48.3% of patients in the right ulnar nerve, and in 35% of patients in the left ulnar nerve. However, reduced sensory conduction velocity (SCV) was found in 85% of patients in the right median nerve, 78.3% of patients in the left median nerve, 35% of patients in the right ulnar nerve and in 43.3% of patients in the left ulnar nerve. Also the incidence of reduced conduction velocity was found to be increased with the severity of liver disease with the highest incidence in class C patients and the least incidence in class A patients. And the difference was statistically significant.

(c)    Amplitude: the highest incidence of reduced motor amplitude was found in both the right (71.6% ) and left (81.6% ) common peroneal nerves. However it was reduced in 28.3% of patients in the right median nerve, in 35% of patients in the left median nerve,13.3% of patients in the right ulnar nerve and in 16.6% of patients in the left ulnar nerve.

Sensory amplitude was reduced in 11.6% of patients in the right median nerve, in 8.3% of patients in the left median nerve, in 3.3% of patients in the right ulnar and in 5% of patients in the left median nerve. Again, the incidence of reduced amplitude was found to be increased with the severity of liver disease with the highest incidence in class C patients and the least incidence in class A patients. And the difference was statistically significant.

(d)    F-wave latency: the highest incidence of prolonged F-wave latency was detected in  common peroneal nerves of both sides (55%) ,followed by the right (46.6%) and left (43.3%) median nerves and lastly the right (31.6%) and left (25%) ulnar nerves, however the incidence was more with the  severe cases of liver diseases, but the difference was statistically significant in few cases. The presence of prolonged F-wave latency denote the presence of demyelinating neuropathy.

 

Our results are in agreement with those of Kharbanda et al.¹⁸, who reported that nerve conduction studies were abnormal in 73% patients with liver cirrhosis, and with those of McDougall et al.¹⁵, who reported that nerve conduction study was abnormal in 93% of patients with chronic liver diseases and increase with the severity of liver diseases, also agree those of Fierro et al.¹², who reported that clinical signs of peripheral nerve involvement were found in 21% of patients with chronic liver diseases while electrophysiological impairment were found in 57.8% of patients.

These results are also in agreement with Chaudhry et al.⁴, who reported that in patients with chronic liver diseases 43% had reduced sensory or motor amplitude on the NCS. The most common abnormality was reduced or absent sural sensory amplitudes (in 34%), followed by reduced peroneal amplitudes (in 26%). Median sensory amplitude was reduced in 16 % motor amplitude was decreased in 3%. Peroneal conduction velocity was reduced in 24% of patients. In accordance with our results also, Shaza et al.¹³,  reported 60.5% of their patients with sensory conduction abnormality, and 41.7% with motor conduction abnormality.

 

Electromyographic Findings:

 

Table 8. Percentage of patients with Naturopathic EMG changes in Different Classes.

 

 

Neuropathic electromyographic (EMG) changes in the form of fibrillations and positive waves at rest, giant wave on moderate contraction and poor interference was detected in many cases of our study. In class A   46.1% of patients had neuropathic EMG all of them had giant waves on minimal contraction, 30.1% had poor interference pattern but none had abnormal findings at rest. As regard class B, 61.1% of patients had neuropathic EMG changes 11.1% of patients had fibrillations at rest, 50% of patients had giant waves on minimal contraction and 55.5% of patients had poor interference pattern. 68.9% of patients of class C had neuropathic EMG changes, 20.6% of patients had fibrillations at rest, 62% of patients had giant waves on minimal contraction and 65.5% of patients had poor interference pattern. The differences between class A & B and class A & C were statistically significant (p=0.03 and p=0.02 respectively). but the difference between class B & C was statistically insignificant (p=0.05).

The presence of neuropathic EMG changes increases with the increased severity of liver disease with statistically significant difference. The pathogenesis of peripheral neuropathy with liver disease was discussed in the last few years. Some systemic disorders that cause liver disease also are independent causes of peripheral nerve dysfunction, e.g. alcohol induced cirrhosis, porphyria, polyarteritis nodosa, amylodosis, and certain intoxications, all cause independent liver disease and peripheral neuropathy^3,19, so a cause–effect relationship between both conditions had been questioned. In our study all of these conditions had been excluded.

The presence of neuropathic EMG reflects the axonal element in the pathogenesis of neuropathy (reported in 46.1% up to 68.9% of patients), while the  prolongation of  F-wave latencies (reported in 25% up to 55% of patients) reflects the demyelinating pattern of neuropathy, so the neuropathy of chronic liver disease is both axonal and demyelinating, however the axonal element is the predominant.

Our results agree in agreement with those of  Kharbanda et al.¹⁸, who reported that nerve conduction studies were abnormal in 73% patients with liver cirrhosis and the pattern of involvement was predominantly of an axonal sensory motor polyneuropathy.

Also our results are in agreement with those of Ripault et al.²⁰, who reported that the prevalence of peripheral neuropathy in chronic liver diseases is 8% and it is an axonal neuropathy with diminution of the myelinated fibers. And also are in agreement with those of Lani et al.¹¹, who reported that the neurological impairment in patients with chronic liver diseases is due to demyelinating inflammation which led to segmental demyelination and sever loss large myelinated fibers.

Relation of the neuropathy to the etiology of liver disease

In comparing the incidence of peripheral neuropathy in non-viral and post HCV cirrhosis, we have found that:

(A)   Symptoms. Distal paresthesia of upper limbs was present in 23.1% of patients with non viral chronic liver disease and in 30.6% of patients with post HCV cirrhosis. The percentage of the presence of distal paresthesia of lower limbs in patients with non viral chronic liver disease was (23.1%) and of patients with post HCV cirrhosis was (26.2%). 11.6% of patients with non viral aetiology were presented with cramps in the upper limbs in comparison with 16.2% of patients with post HCV cirrhosis. As regard the cramps in the lower limbs they were present in 11.6% of patients with non viral aetiology and in  15.9% of patients with post HCV cirrhosis. 7.7% of patients with non viral aetiology have reported history of distal weakness in the upper limbs and 5.2% of patients with post HCV cirrhosis. Also 7.7% of patients with non viral aetiology have reported history of distal weakness in the lower limbs in comparison with  5.2% of patients with post HCV cirrhosis.

(B)   Signs: Glove hypoesthesia was present in 46.1% of patients with non viral chronic liver disease, and in 39.4% of patients with post HCV cirrhosis. As regard stock hypoesthesia, it was present in 46.1% of patients with non viral chronic liver disease and in 55.2% of patients with post HCV cirrhosis. Lost or diminished deep reflexes were detected in the upper limb (biceps, brachioradialis and triceps) in 53.8% of patients with non viral chronic liver disease and in 39.4% of patients with post HCV cirrhosis and. Lost or diminished knee reflexes were detected in 76.9% of patients with non viral chronic liver disease and in 52.6% of patients with post HCV cirrhosis. Lost or diminished ankle reflexes were detected in 76.9% of patients with non viral chronic liver disease and in 63.1% of patients with post HCV cirrhosis. Deep sensory loss in the upper limbs was detected in 23% of patients with non viral chronic liver disease and in 10.5% of patients with post HCV cirrhosis. As regard deep sensory loss in the lower limbs was detected in 24.1% of patients with non viral chronic liver disease and in 10.5% of patients with post HCV cirrhosis. Distal weakness either in the upper and lower limbs was detected 7.6% of patients with non viral chronic liver disease and in 5.2% of patients with post HCV cirrhosis .From the above results we have found that no significant differences as regard the presence of symptoms and signs of peripheral neuropathy between patients with non viral chronic liver disease and patients with post HCV cirrhosis.

(C)   NCS & EMG: The same as clinical manifestations NCS &EMG in patients with non viral chronic liver disease and patients with post HCV cirrhosis has no significant difference. And so no relation has been found between the aetiology of liver disease and the presence of neuropathy.

(D)   Autonomic dysfunction: Autonomic dysfunction was fount in 38.4% of patients with non viral chronic liver disease and in 44.3% of patients with post HCV cirrhosis with no statistically significant difference between the two groups. So, the presence of autonomic dysfunction has no relation to the aetiology of liver disease. These results are in agreement with those of Kharbanda et al.¹⁸, who reported that a significant number of patients with liver cirrhosis show evidence of peripheral neuropathy, which is present regardless of the etiology of cirrhosis. And also with those of Chaudhry et al.⁴, who found that the prevalence and severity of  peripheral and autonomic neuropathy was related to the severity of hepatic dysfunction and was independent of cause of liver disease. We can conclude that, subclinical peripheral neuropathy is very common in chronic liver diseases mainly the sensory signs, followed by the motor ones with predilection of the lower limbs. Neurophysiological studies showed that the reported neuropathy is both axonal and demyelinating. Also, autonomic dysfunctions are common mainly those  due to parasympathetic disorders.  

 

REEFRENCES

 

1.      E.A. Jones and K Weissenbon, Neurology and liver, Journal of neurology, Neurosurgery and Psychiatry. 1997;63:279-293.

2.      Dayan, A. D., and Williams, R. Demyelinating peripheral neuropathy and liver disease. Lancet 1967; 2:133-134.

3.      Asbury A. Neuropathies with renal failure, hepatic disorders, chronic renal insufficiency, and critical illness. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo J, eds. Peripheral Neuropathy. 3^rd ed. Philadelphia: Saunders, 1993; 1251-1265.

4.      Chaudhry, V.; Corse, A.M.; O`Brian, R. et al. Autonomic and peripheral ( sensorimotor ) neuropathy in chronic liver disease: A clinical and electrophysiological study. Hepatol. (1999):, 29:1698-1703.

5.      Kempler P, Varadi A, Szalay F. Autonomic neuropathy in liver disease. Lancet 1989;2:1332.

6.      Trivisani F, Sica G, Bernardi M. Autonomic neuropathy in advanced liver disease. Hepatology 1996;24:1549.

7.      Oliver MI, Miralles R, Rubies-Prat J, Navarro X, Espadaler JM, Sola R, Andreu M. Autonomic dysfunction in patients with nonalcoholic chronic liver disease. J Hepatol 1997;26:1242-1248.

8.      Asbury, A. Hepatic neuropathy; in: Dyck, P.G.; Themas, P.K. and Lambert, E.H. (Eds): Peripheral neuropathy, 2nd. Ed. Philadelphia, Saunders, pp. 1984; 1826-1832.

9.      Hendrickse, M .T. and Triger, D.R. (1992): Peripheral and cardiovascular autonomic impairment in chronic liver disease: Prevalence and relation to hepatic function. J. Hepatology, 16:177-183.

10.    Sheila Sherlok and James Dooley.Hepatic encephalopathy ch.7. Textbook of Diseases of the Liver and Biliary System. Eleventh edition. Blackwell Science, Oxford 2002; 93-109.

11.    C. Lani, G. Tisone, M. Loberti, G. Oriando, S. Negrini, F. Strsti, G. Bernardi, and C. U. Casciani. Clinical and neurophysiological Evidence of Polyneuropathy in liver Transplant Candidates: Preliminary report. From the departments of neurology and surgery, Tor Vergata University, Rome, Italy. © By Elsevier Science Inc, 1999:404-405.

12.    Fierro B, Raimondo D, Castiglione MG, Migneco G, Scoppa F, Savettieri G. Ital J Neurol Sci 1986 Dec;7(6):589-90.

13.    Shaza A. El-Wahab Salah, Azza A. El-Nasser, Nagia A. Fahmi, Amr S. Amer, Samia Ashour. Peripheral (sensorimotor) and autonomic neuropathy In chronic liver disease: Clinical, neurophysiological and nerve biopsy study.Egypt.J.Neurol.Psychiat.Neurosurg. Vol.39(1)-jan. 2002.

14.    B K Bajaj, M P Agarwal and B Krishna Ram. Autonomic neuropathy in patients with hepatic cirrhosis. Postgraduate Medical Journal 2003;79:408-411© 2003.

15.    McDougall AJ, Davies L, McCaughan GW.  Autonomic and peripheral neuropathy in endstage liver disease and following liver transplantation. Muscle Nerve. 2003 Nov;28(5):595-600.

16.    Thuluvath PJ, Triger DR. Autonomic neuropathy and chronic liver disease. QJM 1989:72:737-47.

17.    Henderickse MT, Triger DR. Autonomic dysfunction and hepatic function in chronic liver disease. Gut 1990: 31:A1164

18.    Kharbanda PS, Prabhakar S, Chawla YK, Das CP, Syal P. Peripheral neuropathy in liver cirrhosis. J Gastroenterol Hepatol. 2003 Aug;18(8):922-926.

19.    Barohn, R.I.; Scanchez, J. A; Anderson, K.E. (1994): Acute peripheral neuropathy due to hereditary coproporphyria. Muscle Nerve, 17:793-799

20.    Ripault MP, Borderie C, Dumas P, Vallat JM, Neuropathies Peripherique et hepatite chronique virale C : Une association frequente ? Gasteroenterol Clin Biol 1998;22:891-896.