Disorder of consciousness rather than complete Locked-In Syndrome for end stage Amyotrophic Lateral Sclerosis: a case series

TL;DR

This study challenges the assumption that end-stage ALS patients are fully conscious, suggesting some may have a degenerative disorder of consciousness instead.

Contribution

The paper introduces evidence that end-stage ALS may involve a disorder of consciousness rather than complete Locked-In Syndrome.

Findings

Multimodal assessments in two end-stage ALS patients showed no reliable signs of covert awareness.

Both patients exhibited brain atrophy and hypometabolism consistent with a disorder of consciousness.

Findings suggest end-stage ALS may represent a degenerative disorder of consciousness, distinct from typical Locked-In Syndrome.

Abstract

The end-stage of amyotrophic lateral sclerosis (ALS) is commonly regarded as a complete Locked-In Syndrome (cLIS). Shifting the perspective from cLIS (assumed consciousness) to Cognitive Motor Dissociation (potentially demonstrable consciousness), we aimed to assess the preservation of covert awareness (internally preserved but externally inaccessible) using a multimodal battery.

We evaluate two end-stage ALS patients using neurophysiological testing, passive and active auditory oddball paradigms, an auditory Brain-Computer Interface (BCI), functional activation-task imaging, long-term EEG, brain morphology, and resting-state metabolism to characterize underlying brain function.

Patient 1 initially follows simple commands but fails twice at BCI control. At follow-up, command following is no longer observed and his oddball cognitive responses disappear. Patient 2, at a single evaluation, is unable to follow commands or control the BCI. Both patients exhibit altered wakefulness, brain atrophy, and a global cortico–subcortical hypometabolism pattern consistent with a disorder of consciousness, regarded as an extreme manifestation of ALS-associated fronto-temporal dementia.

Although it is not possible to firmly prove the absence of awareness, each independent measure concurred with suggesting that a “degenerative disorder of consciousness” rather than a cLIS may constitute the final stage of ALS. This condition appears pathophysiologically distinct from typical tetraplegia and anarthria, in which behavioural communication and BCI use persist to enhance quality of life. Identifying the neuroimaging signatures of this condition represents a substantial milestone in understanding end-stage ALS. Large-scale longitudinal investigations are warranted to determine the prevalence of this profile among patients whose communication appears impossible.

Some patients with amyotrophic lateral sclerosis become progressively paralyzed to the extent that they can no longer communicate. This raises a critical question: does consciousness remain despite a complete loss of interaction? To address this issue, we analysed brain activity in two patients at the late stage of this disease. Our findings indicate that no reliable signs of awareness could be detected, even when employing advanced methods to assess brain function, including approaches designed to enable communication without movement. Two hypotheses may account for this outcome: either prolonged paralysis progressively leads to the disappearance of consciousness, or the degeneration of brain function itself directly underlies its loss. However, our conclusions ultimately depend on the reliability of consciousness assessment tools, even when used in combination.

Gobert et al. investigate whether consciousness persists in end-stage Amyotrophic Lateral Sclerosis, traditionally assumed as being fully aware but unable to communicate. Multimodal assessments, including Brain-Computer Interface, suggest some individuals may show degenerative disorder of consciousness rather than a complete Locked-In Syndrome.

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