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

https://doi.org/10.1016/j.clinph.2021.03.001Get rights and content

Highlights

  • First study applying TMS in patients with fatigue and dysexecutive syndrome in the aftermath of COVID-19.

  • TMS studies revealed marked impairment of GABAergic intracortical inhibitory circuits within primary motor cortex.

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

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
Fatigue
Executive functions
TMS
GABA

Abbreviations

TMS
transcranial magnetic stimulation
GABA
gamma aminobutyric acid
SICI
short-interval intracortical inhibition
LICI
long-interval intracortical inhibition
SAI
short-latency afferent inhibition
FRS
Fatigue Rating Scale
FAB
frontal assessment battery

Cited by (0)

1

These authors share senior authorship.

View Abstract