PRESERVED NEURAL FUNCTIONS IN POST-ANOXIC COMA AND THEIR ADDED VALUE FOR THE PREDICTION OF COGNITIVE AND FUNCTIONAL OUTCOME

Post-anoxic coma after cardiac arrest poses critical challenges to clinicians and families regarding the severity of cerebral insult and the potential of recovery. In such an altered state of consciousness, electroencephalography (EEG), assessing spontaneous and evoked cerebral activity without patient's active participation, provides crucial information about the brain condition. In particular, previous studies showed preserved neural responses in simple and more complex paradigms involving mainly auditory stimuli in some post-anoxic comatose patients, and in particular in those who will survive. These results suggest that the investigation of brain functions during coma can be used to predict patient's prognosis and that consciousness may be not required for low-level processing of sensory stimuli. However, to which extent the unconscious brain can process complex stimuli, and how brain responses during coma are associated with other clinical markers of cerebral condition and with detailed functional outcome of the survivors remains under-investigated. In the present thesis, I address these points through three experimental studies. In the first one, I assessed the clinical evolution of patients showing an initial non-reactive EEG, defined as the absence of any visible change in the EEG signal in response to strong nociceptive or auditory stimulation. Despite an extremely poor outcome, patients recovering EEG reactivity on the second day of coma were more likely than the others to also regain other brain functions, suggesting at least partial clinical recovery in these patients. In the second study, I investigated whether the progression of cerebral responses to auditory stimuli during coma could be predictive of the functional recovery of the survivors. My results indicate that patients improving auditory discrimination display better cognitive performances and better long-term outcome as compared with the others. In addition, the extent of the progression was directly associated with the extent of the recovery, suggesting a close relation between brain's condition during early coma and subsequent functional recovery. Finally, in the third study, I challenged current opinions regarding the impossibility of learning in the absence of consciousness, by showing that some deeply comatose patients exhibited neural signs of expectancy of a specific stimulus. These patients presented a reactivation of the EEG activity elicited by a sound, precisely when the sound was expected after a tone, indicating the creation of an association between the tone and the following sound. In summary, my results suggest that the comatose brain can process a large variety of stimuli, shedding new light into the cerebral functions in this clinical state, and that its signal may provide reliable and detailed prognostic information. -- Le coma apres arret cardio-respiratoire souleve des questions essentielles pour les proches et l'equipe medicale concernant la severite de l'atteinte cerebrale et le potentiel de recuperation. Dans ce contexte, l'electroencephalographie (EEG), evaluant l'activite cerebrale spontanee et evoquee sans la participation du patient, fournit des informations cruciales concernant l'etat du cerveau. Certains patients comateux, et en particulier ceux qui survivent, montrent une activite neuronale preservee en reponse a des paradigmes simples et plus complexes impliquant des stimuli principalement auditifs. L'investigation des fonctions cerebrales durant le coma peut donc etre utile pour predire le pronostic et la conscience ne semble pas necessaire pour le traitement de certaines tâches simples. Cependant, il est encore inconnu a quel point le cerveau inconscient peut traiter des stimuli complexes, et comment les reponses cerebrales pendant le coma sont associees avec d'autres marqueurs cliniques de l'etat cerebral et avec le devenir fonctionnel (outcome) des survivants. Ce sont ces questions que je vais traiter a travers trois etudes experimentales. Dans la premiere, j'ai examine l'evolution clinique des patients demontrant initialement un EEG non-reactif, definit comme l'absence de changement visible dans le signal EEG en reponse a de fortes stimulations nociceptives ou auditives. En depit d'un outcome extremement sombre, les patients qui recuperent la reactivite EEG au deuxieme jour du coma ont plus de chance que les autres de recuperer egalement d'autres fonctions cerebrales, suggerant un retablissement clinique au moins partiel chez ces patients. Dans la deuxieme etude, j'ai investigue si la progression des reponses cerebrales a des stimuli auditifs pendant le coma pouvait predire la recuperation fonctionnelle des survivants. Mes resultats indiquent que les patients qui ameliorent la discrimination auditive montrent de meilleures performances cognitives et un meilleur outcome a long-terme par rapport aux autres. De plus, l'etendue de la progression est directement associee a l'etendue de la recuperation fonctionnelle, suggerant une forte relation entre l'etat du cerveau dans le coma precoce et l'outcome. Finalement, au cours de la troisieme etude, j'ai remis en question l'opinion selon laquelle il serait impossible d'apprendre de nouvelles informations en l'absence de conscience. J'ai montre que certains patients, alors qu'ils etaient profondement comateux, presentaient une reactivation de l'activite EEG en reponse a un son, precisement au moment ou le son etait attendu apres un bip, indiquant la creation d'une association entre le bip et le son suivant. En resume, mes resultats suggerent que le cerveau comateux peux traiter une large variete de stimuli, amenant de nouvelles perspectives de cet etat clinique, et que son signal peut fournir des informations fiables et detaillees pour le pronostic.