RT Journal Article
SR Electronic
T1 A disorder of consciousness rather than complete locked-in may be the final stage of ALS
JF medRxiv
FD Cold Spring Harbor Laboratory Press
SP 2024.06.21.24307994
DO 10.1101/2024.06.21.24307994
A1 Gobert, F.
A1 Merida, I.
A1 Maby, E.
A1 Seguin, P.
A1 Jung, J.
A1 Morlet, D.
A1 André-Obadia, N.
A1 Dailler, F.
A1 Berthomier, Ch.
A1 Otman, A.
A1 Bars, D. Le
A1 Scheiber, Ch.
A1 Hammers, A.
A1 Bernard, E.
A1 Costes, N.
A1 Bouet, R.
A1 Mattout, J.
YR 2024
UL http://medrxiv.org/content/early/2024/06/24/2024.06.21.24307994.abstract
AB The end-stage of amyotrophic lateral sclerosis [ALS] is presumed to be a complete Locked-In Syndrome [cLIS], assuming an internally preserved consciousness that would not be accessible anymore from the outside. However, whether consciousness persists at this stage of ALS remains to be demonstrated. Shifting the perspective from cLIS (presupposed consciousness) to Cognitive Motor Dissociation (to-be-demonstrated consciousness), we attempted to demonstrate consciousness and communication with two cLIS-ALS patients using a multimodal awareness assessment battery. It involved complete neurophysiological assessments, passive and active auditory oddball paradigm (Subject-Own-Name/P300), an auditory-based Brain-Computer-Interface [BCI] and activation-task imaging using functional MRI or [15O]H2O PET. Wakefulness (long-term EEG), brain morphology (CT or MRI scans) and resting brain metabolism ([18F]fluoro-deoxy-glucose PET) were used to describe the underlying cLIS brain function.While Patient 1 could initially follow simple commands, he failed twice to control the BCI. At follow-up, he showed no more evidence of command following and his oddball (Own Name - P300) cognitive responses has disappeared. At his unique evaluation, Patient 2 was neither able to follow simple commands nor to control the BCI.Both patients had altered wakefulness, brain atrophy, and a global cortico-sub-cortical hypometabolism pattern compatible with a disorder of consciousness, regarded as an extreme form of an ALS-associated fronto-temporal dementia.While it is not possible to firmly demonstrate the absence of awareness, each independent measure concurred with suggesting that a “degenerative disorder of consciousness” rather than a cLIS might be the final stage of ALS. In future cases, this dramatic cognitive decline should be anticipated before communication disappears to enable precise advance directives regarding end-of-life issues in case complete – and neurophysiologically confirmed – unresponsiveness occurs.Altogether, the neuroimaging features distinguishing the mechanisms in this rare condition is a significant milestone to understand end-stage ALS. The present clinical study calls for further exploration of this terminal stage to determine the prevalence of this profile in whom communication seems hopeless.Competing Interest StatementThe authors have declared no competing interest.Funding StatementAO was funded by the Fondation pour la Recherche Medicale (FRM, ING20121226307). PS, JM, EM were funded by one grant from the Fondation pour la Recherche Medicale (FRM, FDM201906008524). JM, EM and PS were funded by ANR-17-CE40-0005, MindMadeClear & ANR-20-CE17-0023, ANR HiFi. PS was funded by Perce-Neige Fondation. The teams of the Lyon Neurocience Research Center are funded by the Labex cortex.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:IRB of Hospices Civils de LYON CSE-HCL - IRB 00013204; Pr Cyrille Confavreux gave ethical approval for this work (approval N. 24-310).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present work are contained in the manuscript.Act-PassActive-Passive auditory oddball paradigmALSAmyotrophic Lateral SclerosisANCOVAAnalysis of Co-VarianceBCIBrain Computer InterfaceCJDCreutzfeldt-Jakob DiseasecLIScomplete Locked-In SyndromeCTComputerised TomographyEEGElectroencephalogramEPEvoked PotentialFGDFluoro-Deoxy-GlucosefMRIfunctional MRIFTDFronto-Temporal DementiaMAABMultimodal Awareness Assessment BatteryMCSMinimal Conscious StateMMNMismatch NegativityPETPositron Emission TomographySONSubject Own NameSUVStandardized Uptake ValueSWSSlow Wave Sleep