Abstract
Behavioral assessments could not suffice to provide accurate diagnostic information in individuals with disorders of consciousness (DoC). Multimodal neuroimaging markers have been developed to support clinical assessments of these patients. Here we present findings obtained by hybrid fludeoxyglucose (FDG-)PET/MR imaging in three severely brain-injured patients, one in an unresponsive wakefulness syndrome (UWS), one in a minimally conscious state (MCS), and one patient emerged from MCS (EMCS). Repeated behavioral assessment by means of Coma Recovery Scale-Revised and neurophysiological evaluation were performed in the two weeks before and after neuroimaging acquisition, to ascertain that clinical diagnosis was stable. The three patients underwent one imaging session, during which two resting-state fMRI (rs-fMRI) blocks were run with a temporal gap of about 30 min. rs-fMRI data were analyzed with a graph theory approach applied to nine independent networks. We also analyzed the benefits of concatenating the two acquisitions for each patient or to select for each network the graph strength map with a higher ratio of fitness. Finally, as for clinical assessment, we considered the best functional connectivity pattern for each network and correlated graph strength maps to FDG uptake. Functional connectivity analysis showed several differences between the two rs-fMRI acquisitions, affecting in a different way each network and with a different variability for the three patients, as assessed by ratio of fitness. Moreover, combined PET/fMRI analysis demonstrated a higher functional/metabolic correlation for patients in EMCS and MCS compared to UWS. In conclusion, we observed for the first time, through a test-retest approach, a variability in the appearance and temporal/spatial patterns of resting-state networks in severely brain-injured patients, proposing a new method to select the most informative connectivity pattern.
Highlights
The improvements of medical interventions in the acute and post-acute phase of severe acquired brain injury and the failure of treatments to restore brain functions keep increasing the number of patients with prolonged disorders of consciousness (DoC) [1]
We screened for the study severely brain-injured patients consecutively admitted to the neurorehabilitation Unit at Maugeri Clinical and Scientific Institutes, in Telese Terme (Italy) from February 2017 to July 2017, fulfilling the following inclusion criteria: (i) clinical diagnosis of unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS) or emerged from MCS (EMCS) according to standard diagnostic criteria [5, 6]; (ii) time from onset longer than 1 month; (iii) traumatic, vascular or anoxic brain injury
From a sample of nine severely brain-injured patients, we could consider for positron emission tomography (PET)/functional magnetic resonance imaging (fMRI) analysis two representative patients with prolonged DoC and one patient emerged from MCS (Figure 1)
Summary
The improvements of medical interventions in the acute and post-acute phase of severe acquired brain injury and the failure of treatments to restore brain functions keep increasing the number of patients with prolonged disorders of consciousness (DoC) [1]. These severe clinical conditions entail heavy ethical and social implications, impact health care policies and determine strong psychological distress in patients’ families [2,3,4]. Patients’ clinical signs of consciousness are frequently variable across days and even within the same day [13] These inconsistencies have been often linked to temporal fluctuations of vigilance/awareness. At least five repeated behavioral assessments by means of validated assessment tools, such as Coma Recovery Scale-Revised (CRS-R) [14], are strongly recommended for improving diagnostic accuracy [15]
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