Metabolic Brain Disease

, Volume 31, Issue 5, pp 1065–1070 | Cite as

Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study

  • Raffaele Nardone
  • Pierpaolo De Blasi
  • Yvonne Höller
  • Francesco Brigo
  • Stefan Golaszewski
  • Vanessa N. Frey
  • Andrea Orioli
  • Eugen Trinka
Original Article


Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits,  but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.


Transcranial magnetic stimulation Minimal hepatic encephalopathy Short-latency intracortical inhibition Intracortical facilitation Electroencephalography Magnetic resonance imaging 




Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Raffaele Nardone
    • 1
    • 2
  • Pierpaolo De Blasi
    • 3
  • Yvonne Höller
    • 1
  • Francesco Brigo
    • 2
    • 4
  • Stefan Golaszewski
    • 1
  • Vanessa N. Frey
    • 1
  • Andrea Orioli
    • 2
  • Eugen Trinka
    • 1
  1. 1.Department of Neurology, Christian Doppler KlinikParacelsus Medical UniversitySalzburgAustria
  2. 2.Department of NeurologyFranz Tappeiner HospitalMeranoItaly
  3. 3.University of Torino and Collegio Carlo AlbertoTorinoItaly
  4. 4.Department of Neurological and Movement Sciences, Section of Clinical NeurologyUniversity of VeronaVeronaItaly

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