The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioral responses to standardized sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behavior-based diagnoses. One of these is Akinetic Mutism (AM), a rare neurological syndrome characterized by the inability to initiate volitional motor responses, sometimes associated with clinical presentations overlapping with those of DoC. Here we describe the case of a patient with large bilateral mesial frontal lesions showing a prolonged behavioral unresponsiveness and a severe disorganization of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented battery of multimodal longitudinal measurements encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation-evoked potentials, and structural and functional MRI, we provide (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of a complete AM, (ii) a plausible neurophysiological explanation of behavioral unresponsiveness and of its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case provides proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow combining conventional and advanced techniques to detect covert signs of consciousness in unresponsive patients.

The analysis of spontaneous EEG is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Alterations in specific frequency bands have been reported, including a predominance of delta power in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients in contrast with a predominance of alpha activity in minimally conscious state patients (MCS). Although preserved EEG patterns are highly suggestive of consciousness even in unresponsive patients, moderately or severely abnormal patterns are difficult to interpret. Indeed, growing evidence shows that consciousness can be present despite either large delta or reduced alpha activity in spontaneous EEG. Quantifying the complexity of EEG responses to direct cortical perturbations (Perturbational Complexity Index; PCI) may complement the observational approach and provide a reliable assessment of consciousness even when spontaneous EEG features are inconclusive. To systematically test this hypothesis, we compared PCI to EEG spectral measures in the same population of MCS patients (n=40) hospitalized in rehabilitation facilities. We found a remarkable EEG background variability across MCS patients as compared to healthy controls and a non-negligible number of patients with predominant delta and highly reduced alpha power in spontaneous EEG. Conversely, PCI values invariably suggested a capacity for consciousness in all MCS patients, consistent with the presence of clearly discernible, albeit fleeting, behavioral signs of awareness. These results confirm that spontaneous EEG rhythms may dissociate from the actual capacity for consciousness and suggest that a perturbational approach can effectively compensate for this pitfall with practical implications for the individual patient’s stratification and tailored rehabilitation.