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. 2021 May;132(5):1138-1143.
doi: 10.1016/j.clinph.2021.03.001. Epub 2021 Mar 13.

Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19

Viviana Versace  1 , Luca Sebastianelli  2 , Davide Ferrazzoli  2 , Roberto Romanello  2 , Paola Ortelli  2 , Leopold Saltuari  2 , Alessia D'Acunto  3 , Francesco Porrazzini  3 , Valentina Ajello  4 , Antonio Oliviero  5 , Markus Kofler  6 , Giacomo Koch  7
Affiliations

Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19

Viviana Versace et al. Clin Neurophysiol. 2021 May.

Abstract

Objective: A high proportion of patients experience fatigue and impairment of cognitive functions after coronavirus disease 2019 (COVID-19). Here we applied transcranial magnetic stimulation (TMS) to explore the activity of the main inhibitory intracortical circuits within the primary motor cortex (M1) in a sample of patients complaining of fatigue and presenting executive dysfunction after resolution of COVID-19 with neurological manifestations.

Methods: Twelve patients who recovered from typical COVID-19 pneumonia with neurological complications and complained of profound physical and mental fatigue underwent, 9 to 13 weeks from disease onset, a psychometric evaluation including a self-reported fatigue numeric-rating scale (FRS, Fatigue Rating Scale) and the Frontal Assessment Battery (FAB). Intracortical activity was evaluated by means of well-established TMS protocols including short-interval intracortical inhibition (SICI), reflecting GABAA-mediated inhibition, long-interval intracortical inhibition (LICI), a marker of GABAB receptor activity, and short-latency afferent inhibition (SAI) that indexes central cholinergic transmission. TMS data were compared to those obtained in a control group of ten healthy subjects (HS) matched by age, sex and education level.

Results: Post-COVID-19 patients reported marked fatigue according to FRS score (8.1 ± 1.7) and presented pathological scores at the FAB based on Italian normative data (12.2 ± 0.7). TMS revealed marked reduction of SICI, and disruption of LICI as compared to HS. SAI was also slightly diminished.

Conclusions: The present study documents for the first time reduced GABAergic inhibition in the M1 in patients who recovered from COVID-19 with neurological complications and manifested fatigue and dysexecutive syndrome.

Significance: TMS may serve as diagnostic tool in cognitive disturbances and fatigue in post-COVID-19 patients.

Keywords: COVID-19; Executive functions; Fatigue; GABA; TMS.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Results of TMS-protocols. Cortical inhibition tested with different transcranial magnetic stimulation (TMS) protocols in post-COVID-19 patients and in healthy controls. (A) Short-interval intracortical inhibition and facilitation (SICI-ICF) at interstimulus intervals (ISI) 2, 3, 10, and 15 ms; (B) long-interval intracortical inhibition (LICI) at ISIs 50 and 100 ms; (C) short-latency afferent inhibition (SAI) at ISIs N20 + 0 ms and N20 + 4 ms. The columns represent the amplitude of conditioned motor evoked potentials (MEPs) expressed as percentage of the corresponding mean unconditioned response. Whiskers represent standard error. ** = p < 0.01, *** = p < 0.001.
See this image and copyright information in PMC

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