Cortico-spinal pathways and inhibitory mechanisms in hepatic encephalopathy M. Nolano a , M.A. Guardascione b , L. Amitrano b , A. Perretti c , F. Fiorillo c , A. Ascione b , L. Santoro c , G. Caruso c, * a Fondazione Salvatore Maugeri, IRCCS, Campoli (BN), Italy b Liver Pathophysiology Unit, A. Cardarelli Hospital, Naples, Italy c Dipartimento di Scienze Neurologiche, Clinica Neurologica I, Universita’ di Napoli Federico II, ‘Nuovo Policlinico’, via S. Pansini, 80131 Naples, Italy Accepted for publication: 30 October 1996 Abstract Transcranial magnetic stimulation of the cerebral cortex was used to study motor system function in 31 cirrhotics (29 post-necrotic and 2 cryptogenic) with and without hepatic encephalopathy (HE). The results were compared with those of 14 healthy subjects matched for age. A significant increase of central motor conduction time, a significant raising of the motor evoked potential (MEP) threshold at rest and a significant reduction of the MEP/muscle action potential (MAP) amplitude ratio were found only in patients with chronic stable (12 patients) and recurrent (9 patients) HE. Vice versa, a significant shortening of the central silent period was observed in all 31 cirrhotic patients. The peripheral silent period was normal in all instances. These results indicate that the damage to the cortico-spinal pathways is related to the progression of cirrhosis to HE, and that cirrhotic patients present a dysfunction of the inhibitory motor mechanisms before HE is clinically manifest.  1997 Elsevier Science Ireland Ltd. All rights reserved Keywords: Motor evoked potentials; Silent period; Hepatic encephalopathy; Liver cirrhosis 1. Introduction Hepatic encephalopathy (HE) is a complex syndrome that includes behavioural, mental and motor disturbances (Capocaccia et al., 1988). It can occur during acute liver failure of any aetiology or it can complicate the course of chronic liver disease (Sherlock et al., 1954). In the latter case it may be: 1. Latent or ‘subclinical’, manifesting only as impairment of psychometric performances and/or slowing of EEG mean cycle frequency (Morgan, 1991), 2. Recurrent, occurring after precipitating events, 3. Stable or permanent. Motor abnormalities are common in HE. Indeed, move- ment disorders such as tremor, bradykinesia, flapping, ataxia, apraxia, and hyperactive stretch reflexes are well known in these patients (Adams and Foley, 1953a; Adams and Foley, 1953b; Tsukiyama et al., 1961; Leavitt and Tyler, 1964; Conn, 1973), and suggest extensive involve- ment of the cerebral cortex and subcortex. In fact, patho- logical findings – mostly degenerative changes of astrocytes and Alzheimer type II astrocytosis (Adams and Victor, 1985) – transient in acute HE and persistent in chronic HE, are found in the deep layers of the cerebral cortex as well as in the cerebellar cortex, in thalamic and lenticular nuclei and in many other nuclear structures of the brainstem. Neuronal damage occurs later. So far, apart from EEG recordings (Parson-Smith et al., 1957), electro- physiological studies of HE have explored the visual, brainstem auditory and somato-sensory pathways (Zener- oli et al., 1984; Yang et al., 1985; Yang et al., 1986; Davies et al., 1990). To our knowledge, no studies have been performed to evaluate central motor pathways function in HE. The aim of the present study was to examine motor Electroencephalography and clinical Neurophysiology 105 (1997) 72–78 0924-980X/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0921-884X(96)96571-6 EEM 96571 * Corresponding author. Tel.: +39 81 7462663; fax: +39 81 5469861.