A Systematic Review and Meta-Analysis of the Relationship Between Brain Data and the Outcome in Disorders of Consciousness

Boris Kotchoubey, Yuri G. Pavlov

A systematic search revealed 68 empirical studies of neurophysiological [EEG, event-related brain potential (ERP), fMRI, PET] variables as potential outcome predictors in patients with Disorders of Consciousness (diagnoses Unresponsive Wakefulness Syndrome [UWS] and Minimally Conscious State [MCS]). Data of 47 publications could be presented in a quantitative manner and systematically reviewed. Insufficient power and the lack of an appropriate description of patient selection each characterized about a half of all publications. In more than 80% studies, neurologists who evaluated the patients' outcomes were familiar with the results of neurophysiological tests conducted before, and may, therefore, have been influenced by this knowledge. In most subsamples of datasets, effect size significantly correlated with its standard error, indicating publication bias toward positive results. Neurophysiological data predicted the transition from UWS to MCS substantially better than they predicted the recovery of consciousness (i.e., the transition from UWS or MCS to exit-MCS). A meta-analysis was carried out for predictor groups including at least three independent studies with N > 10 per predictor per improvement criterion (i.e., transition to MCS versus recovery). Oscillatory EEG responses were the only predictor group whose effect attained significance for both improvement criteria. Other perspective variables, whose true prognostic value should be explored in future studies, are sleep spindles in the EEG and the somatosensory cortical response N20. Contrary to what could be expected on the basis of neuroscience theory, the poorest prognostic effects were shown for fMRI responses to stimulation and for the ERP component P300. The meta-analytic results should be regarded as preliminary given the presence of numerous biases in the data.