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.