Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom

https://doi.org/10.1016/j.jns.2020.117271Get rights and content

Highlights

  • Neuropsychological and neurophysiological features of fatigue were studied in post-COVID-19 patients.

  • Apathy, deficits in executive functions and reduction in global cognition were found.

  • Abnormal shortening of cortical silent period and lack of MEP depression were demonstrated after a fatiguing task.

  • Disruption of post-exhaustion corticomotor inhibition suggests GABA-ergic dysfunction.

  • GABA-ergic impairment might subtend fatigue and executive deficits in COVID-19.

Abstract

More than half of patients who recover from COVID-19 experience fatigue. We studied fatigue using neuropsychological and neurophysiological investigations in post-COVID-19 patients and healthy subjects. Neuropsychological assessment included: Fatigue Severity Scale (FSS), Fatigue Rating Scale, Beck Depression Inventory, Apathy Evaluation Scale, cognitive tests, and computerized tasks. Neurophysiological examination was assessed before (PRE) and 2 min after (POST) a 1-min fatiguing isometric pinching task and included: maximum compound muscle action potential (CMAP) amplitude in first dorsal interosseous muscle (FDI) following ulnar nerve stimulation, resting motor threshold, motor evoked potential (MEP) amplitude and silent period (SP) duration in right FDI following transcranial magnetic stimulation of the left motor cortex. Maximum pinch strength was measured. Perceived exertion was assessed with the Borg-Category-Ratio scale.

Patients manifested fatigue, apathy, executive deficits, impaired cognitive control, and reduction in global cognition. Perceived exertion was higher in patients. CMAP and MEP were smaller in patients both PRE and POST. CMAP did not change in either group from PRE to POST, while MEP amplitudes declined in controls POST. SP duration did not differ between groups PRE, increased in controls but decreased in patients POST. Patients' change of SP duration from PRE to POST was negatively correlated to FSS.

Abnormal SP shortening and lack of MEP depression concur with a reduction in post-exhaustion corticomotor inhibition, suggesting a possible GABAB-ergic dysfunction. This impairment might be related to the neuropsychological alterations.

COVID-19-associated inflammation might lead to GABAergic impairment, possibly representing the basis of fatigue and explaining apathy and executive deficits.

Keywords

COVID-19
Central fatigue
Peripheral fatigue
Dysexecutive syndrome
TMS

Abbreviations

SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
CNS
Central Nervous System
CMAP
compound muscle action potential
FDI
first dorsal interosseous muscle
RMT
resting motor threshold
MEP
motor evoked potential
SP
silent period
CR100
Borg-Category-Ratio scale
TMS
Transcranial magnetic stimulation
FRS
Fatigue Rating Scale
CRP
C-reactive protein
IL-6
interleukine-6
HC
healthy control
FSS
Fatigue Severity Scale
BDI
Beck Depression Inventory
AES
Apathy Evaluation Scale
MoCA
Montreal Cognitive Assessment
FAB
Frontal Assessment Battery
RT
reaction time
VT
vigilance task
SIT
Stroop Interference Task
NV
Navon Task

Cited by (0)

1

These authors contributed equally to this work.

2

These authors share senior authorship.

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