Relation Between the Severity of Liver Cirrhosis and Neurological Symptoms, Nerve Conduction Study Results, and Motor Unit Number Estimation

Reem M Gabr; Dina A El Salmawy; Mye A Basheer; Marwa khairy; Saly H Elkholy

Disclosures

J Viral Hepat. 2021;28(9):1312-1318. 

In This Article

Discussion

In the studied cirrhotic patients, the main cause of liver cirrhosis was related to chronic HCV infection, and most of the cirrhotic patients were males. This finding coincides with the high prevalence of HCV in Egypt together with the fact that males have a modestly higher HCV infection rate.[2]

Chronic HCV infection is associated with neurological conditions such as peripheral neuropathy, cognitive impairment and cerebrovascular accidents.[5,6,25] Peripheral neuropathy is the most common and best-established HCV-related neurological complication, affecting more than half of infected patients in some populations.[7,26]

Though, peripheral neuropathy among cirrhotic patients has been studied extensively. The literature reports are not consistent whether there is an association between aetiology of liver cirrhosis and incidence of peripheral neuropathy. Previous studies could not find significant difference in both neurological manifestations and nerve conduction studies' findings among non-viral and viral chronic liver disease.[5,8,27]

Despite peripheral neuropathy was significantly more frequent in HCV patients, some electrophysiological findings support the hypothesis that severity of liver disease rather than HCV is considered as independent cause of that associated neuropathy.[6]

Most patients recruited in the current study had Child-Pugh class A cirrhosis and were without diabetes mellitus, and we did not search for small fibre neuropathy; also, alcohol consumption is postulated to be much less common in our community. Peripheral neuropathy was significantly correlated with the severity of liver cirrhosis as assessed by the Child-Pugh classification and the MELD score. Axonal neuropathy was the dominant lesion in agreement with previous studies.[8,28–30] This axonal pattern could be explained by the pathogenesis of the neuropathy within the cirrhotic patients, which may be similar to that of diabetic neuropathy[31] or metabolic inhibition of axonal membrane function by unidentified toxins.[5]

Interestingly, axonal NCS abnormality was not only related to the presence of peripheral numbness clinically but also to the presence of muscle cramps and fatigue, even in the absence of numbness.

The MUNE has not been performed before in patients with liver cirrhosis. MUNE has been widely implemented in the degenerative diseases, mainly amyotrophic lateral sclerosis, and spinal muscular atrophy. In the current study, we noted a significant decline in motor unit number in cirrhotic patients irrespective of the presence of neurological symptoms. This decline was not correlated with the severity of the liver disease or the presence of peripheral neuropathy or muscle cramps but was significantly related to the presence of fatigue.

The concept of fatigue was introduced in our study as it is common symptom among chronic liver disease that may be reported by up to 50% of the patients.[32] Concerning the pathophysiology of fatigue in chronic liver disease, it is generally poorly understood. However, it could be separated into two entities: peripheral (ie neuromuscular) and central (changes in neurotransmitters).[33,34] In addition, other associative features are believed to affect the motivation of those patients and thus reflecting on their perception of being fatigued such as depression, social dysfunction and sleep deprivation.[32]

In the current study, we are much more concerned with peripheral fatigue through assessing the neuromuscular system both clinically and electro-physiologically (by both nerve conduction studies and MUNE).

According to Henneman's size principle, there are multiple motor unit types, which are recruited in a sequence from small to large units[35] during muscle contraction. In the current study, type I motor units were primarily studied. These are fatigue-resistant motor units, referring to the minimal isometric contraction used to elicit single motor unit potentials.

Healthy older adults display enhanced fatigue resistance during submaximal tasks, which may be correlated with the linear increase in the type I muscle fibre proportion with advanced age.[36,37] In addition, there is evidence of a positive correlation between fatigability and type II muscle fibres (innervated by fast twitch fatigable 'FF' type motor units) at the expense of type I muscle fibres (supplied by highly fatigue-resistant slow twitch 'S' type motor units).[38]

The assumptions of a valid relation between the muscle cramps reported by the cirrhotic patients and the MUNE values, which were based on the theoretical fact that cramps are known to be caused by the hyperexcitability of some motor neurons that can be triggered by the loss of other motor neurons,[4] could not be proved. Finally, MUNE is related to motor function—and thus its decline—may contribute to motor dysfunction, but numbness is sensory dysfunction, less related to motor function and hence to MUNE.

In conclusion, nerve conduction abnormalities were strongly related to the progression of liver disease and the presence of neurological symptoms even in the absence of peripheral numbness. The quantitative EMG method, MUNE, could play a role in the detection of motor units' loss in liver cirrhosis, which could partially explain the pathophysiology of fatigue, a common symptom in patients with liver cirrhosis.

The authors are considering the significance of this work as the initial explanation of the pathophysiology of fatigue in cirrhotic patients by the decline in motor unit number. For future research, even in patients with other than liver diseases, the extension of MUNE to different muscles of both the upper and lower limbs, particularly to those with clinical symptoms, may reveal more correlations, more clarification of fatigue relations to lower motor neuron affections.

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