Introduction
Detecting recovery of consciousness in severely brain-injured patients relies on the observation of their motor behavior and responsiveness to sensory stimuli according to standardized scales. Although structured behavioral examinations, such as the Coma Recovery Scale-Revised (CRS-R) (Giacino et al. , 2004), represent the gold standard for diagnosing recovery of consciousness (American Congress of Rehabilitation Medicine, Brain Injury-Interdisciplinary Special Interest Group, Disorders of Consciousness Task Force et al. , 2010), impairment of sensory, executive and motor function may result in false-negatives. Indeed, several neurological conditions, such as cranial nerve palsies, lesions affecting afferent sensory and efferent motor pathways, cortical blindness, aphasia or frontal akinetic syndrome can directly interfere with the production of reproducible and appropriate behavioral responses to external stimuli, thus reducing the sensitivity of standard clinical tests (Pincherle et al. , 2019, 2021).
To address these limitations, the last American (Giacino et al. , 2018) and European (Kondziella et al. , 2020) guidelines on diagnosis of disorders of consciousness (DoC) recommended the integration of advanced diagnostic technologies with clinical evaluation whenever behavioral evidence for consciousness is inconclusive. These strategies complement bedside clinical testing by employing tools such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), sensory-motor evoked potentials (EP), event-related potentials (ERPs), transcranial magnetic stimulation-evoked potentials (TEP), or positron emission tomography (PET), to derive brain-based markers of consciousness that are independent of overt behavior. Collectively, studies employing these approaches both in the intensive care unit (ICU) and rehabilitation settings have provided evidence that up to 20% of patients may retain a capacity for consciousness that may not be expressed in behavior (Monti et al. , 2010; Sitt et al. , 2014; Casarotto et al. , 2016; Claassen et al. , 2019; Edlowet al. , 2021). Given the complexity of this emerging landscape, operational workflows designed to hierarchically combine conventional and advanced multimodal techniques and systematize their use at the patient’s bedside along the course of disease have been recently proposed (Comanducci et al. , 2020; Monti & Schnakers, 2022).
The present case-report represents a practical implementation of such a proposal in an intensive rehabilitation unit (IRU) setting. We present the trajectory of a patient with a large bilateral fronto-subcortical vascular injury who was initially diagnosed as being in a vegetative state/unresponsive wakefulness syndrome (VS/UWS) on repeated CRS-R assessments. The patient underwent an unprecedented multimodal battery encompassing currently recommended paraclinical tests for DoC diagnosis, including EEG, EP, ERP, TMS-EEG measures of complexity, advanced structural MRI (sMRI) as well as fMRI with an active task-based paradigm. Furthermore, the assessment was repeated at multiple time points along the clinical evolution of the patient from the sub-acute to the chronic phase.
Overall, the multimodal paraclinical tests, subsequently confirmed by the clinical evolution, provided complementary and compelling evidence that the patient was not unconscious but rather unresponsive, due to a complete akinetic mutism (AM) syndrome. This exploration, combining state-of-the-art sMRI, EEG, EP, ERP, TMS-EEG and fMRI approaches, confirms that, in some presentations, AM, which may occur when bilateral fronto-subcortical circuits are massively disrupted, can mimic an unconscious VS/UWS state, whereby the patient is unresponsive, albeit awake. More generally, the present case provides an opportunity to reflect on the significance of multiple evidence of dissociations between clinical and paraclinical markers of consciousness.