Neurophysiological aspects of the completely locked-in syndrome in patients with advanced amyotrophic lateral sclerosis

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) patients in completely locked-in syndrome (CLIS) are incapable of expressing themselves, and their state of consciousness and awareness is difficult to evaluate. Due to the complete paralysis included paralysis of eye muscles, any assessment of the perceptual and psychophysiological state can only be implemented in passive experimental paradigms with neurophysiological recordings.

Methods: Four patients in CLIS were investigated in several experiments including resting state, visual stimulation (eyes open vs eyes closed), auditory stimulation (modified local-global paradigm), somatosensory stimulation (electrical stimulation of the median nerve), and during sleep.

Results: All patients showed altered neurophysiological metrics, but a unique and common pattern could not be found between patients. However, slowing of the electroencephalography (EEG) and attenuation or absence of alpha wave activity was common in all patients. In two of the four patients, a slow dominant frequency emerged at 4 Hz with synchronized EEG at all channels. In the other two patients slowing of EEG appears less synchronized. EEGs between eyes open and eyes closed were significantly different in all patients. The dominant slow frequency during the day changes during slow-wave sleep (supposedly sleep stage 3) to even slower frequencies below 2 Hz. Somatosensory evoked potentials (SEPs) were absent or significantly altered in comparison to healthy subjects, similarly for auditory evoked potentials (AEPs).

Conclusions: The heterogeneity of the results underscores the fact that no single neurophysiological index is available to assess psychophysiological states in unresponsive ALS patients in CLIS. This caveat may also be valid for the assessment of cognitive processes; a functioning BCI can be the solution.

Significance: Most of the studies of the neurophysiology of ALS patients focused on the early stage of the disease, and there are very few studies on the late stage when patients are completely paralyzed with no means of communication (i.e., CLIS). This study provides quantitative metrics of different neurophysiological aspects of these patients.

Keywords: Amyotrophic lateral sclerosis; Auditory evoked potential; Completely locked-in syndrome; Resting-state; Somatosensory evoked potential.