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

Background 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. Methods 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. Results 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. Conclusions 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.