Traumatic Disorders Of Consciousness Research Articles

Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in a cohort of patients with traumatic disorders of consciousness.

Neuroimaging studies have suggested an important role for the default mode network (DMN) in disorders of consciousness (DoC). However, the extent to which DMN connectivity can discriminate DoC states-unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS)-is less evident. Particularly, it is unclear whether effective DMN connectivity, as measured indirectly with dynamic causal modelling (DCM) of resting EEG can disentangle UWS from healthy controls and from patients considered conscious (MCS+). Crucially, this extends to UWS patients with potentially "covert" awareness (minimally conscious star, MCS*) indexed by voluntary brain activity in conjunction with partially preserved frontoparietal metabolism as measured with positron emission tomography (PET+ diagnosis; in contrast to PET- diagnosis with complete frontoparietal hypometabolism). Here, we address this gap by using DCM of EEG data acquired from patients with traumatic brain injury in 11 UWS (6 PET- and 5 PET+) and in 12 MCS+ (11 PET+ and 1 PET-), alongside with 11 healthy controls. We provide evidence for a key difference in left frontoparietal connectivity when contrasting UWS PET- with MCS+ patients and healthy controls. Next, in a leave-one-subject-out cross-validation, we tested the classification performance of the DCM models demonstrating that connectivity between medial prefrontal and left parietal sources reliably discriminates UWS PET- from MCS+ patients and controls. Finally, we illustrate that these models generalize to an unseen dataset: models trained to discriminate UWS PET- from MCS+ and controls, classify MCS* patients as conscious subjects with high posterior probability (pp > .92). These results identify specific alterations in the DMN after severe brain injury and highlight the clinical utility of EEG-based effective connectivity for identifying patients with potential covert awareness.

Cerebrospinal fluid metabolite alterations in patients with different etiologies, diagnoses, and prognoses of disorders of consciousness.

Medical management of disorders of consciousness (DoC) is a growing issue imposing a major burden on families and societies. Recovery rates vary widely among patients with DoC, and recovery predictions strongly influence decisions on medical care. However, the specific mechanisms underlying different etiologies, consciousness levels, and prognoses are still unclear. We analyzed the comprehensive cerebrospinal fluid (CSF) metabolome through liquid chromatography-mass spectrometry. Metabolomic analyses were used to identify the metabolic differences between patients with different etiologies, diagnoses, and prognoses. We found that the CSF levels of multiple acylcarnitines were lower in patients with traumatic DoC, suggesting mitochondrial function preservation in the CNS, which might contribute to the better consciousness outcomes of these patients. Metabolites related to glutamate and GABA metabolism were altered and showed a good ability to distinguish the patients in the minimally conscious state and the vegetative state. Moreover, we identified 8 phospholipids as potential biomarkers to predict the recovery of consciousness. Our findings shed light on the differences in physiological activities underlying DoC with different etiologies and identified some potential biomarkers used for DoC diagnosis and prognosis.

Against Futility Judgments for Patients with Prolonged Disorders of Consciousness

Against Futility Judgments for Patients with Prolonged Disorders of Consciousness

Влияние курса нейромодуляции на профиль нейротрофических факторов у пациентов с хроническими нарушениями сознания

Transcranial magnetic stimulation (TMS) is one of rehabilitation approaches for patients with chronic disorders of consciousness (DOC). The aim of our study was to assess neurotrophic factors and the changes of those after TMS course in patients with chronic DOC. We enrolled 26 patients with chronic DOC of various etiology and 21 heathy volunteers. Blood serum and cerebrospinal fluid (CSF) were collected from all patients before and after the TMS course, the levels of BDNF, NSE, NGF, РDGF, GDNF and NT3 were assessed in the biomaterial. The blood BDNF, NSE, PDGF, GDNF and NT3 in patients with chronic DOC were higher compared to healthy volunteers (p < 0.05). We found no correlations between the type of DOC and neurotrophic factors concentrations in blood and CSF. The CSF level of BDNF in patients after traumatic brain injury (TBI) was higher compared to patients with non-traumatic chronic DOC (p < 0.05). We also found the increase of CSF BDNF after the TMS course in patients after TBI (p < 0.05). No other significant differences between groups and another blood and cerebrospinal fluid biomarker levels were detected. Thus, the serum BDNF, NSE, PDGF, GDNF and NT3 levels in patients with chronic DOC were higher compared to healthy volunteers. The BDNF level in CSF was higher in patients with traumatic DOC, and it also increased after the course of high-frequency TMS in this group. This fact may indicate the long-term neuronal plasticity processes in patients after TBI, as well as more favorable rehabilitation prognosis.

Author response: Disruption of the ascending arousal network in acute traumatic disorders of consciousness.

Dr. Machado's comments on our article1 raise important neuroscientific and clinical issues pertaining to patients with disorders of consciousness. From a neuroscientific perspective, the relationship between mesopontine connectivity and consciousness remains unclear. Specifically, it is unknown which and how many mesopontine connections are needed to support consciousness.2 In patients with severe brain injuries, partial preservation of these connections may be insufficient to generate arousal (i.e., the comatose state) or may be sufficient for arousal but not awareness (i.e., the vegetative state).3 Until the field of ascending arousal network (AAn) connectivity mapping has matured, we caution against using AAn structural connectivity phenotypes to make inferences about the presence or absence of consciousness.

Reader response: Disruption of the ascending arousal network in acute traumatic disorders of consciousness

Snider et al.1 determined that the ascending arousal network (AAn) connectivity is diminished after traumatic brain injury.

EEG Correlates of Language Function in Traumatic Disorders of Consciousness.

Behavioral examinations may fail to detect language function in patients with severe traumatic brain injury (TBI) due to confounds such as having an endotracheal tube. We investigated whether resting and stimulus-evoked electroencephalography (EEG) methods detect the presence of language function in patients with severe TBI. Four EEG measures were assessed: (1) resting background (applying Forgacs' criteria), (2) reactivity to speech, (3) background and reactivity (applying Synek's criteria); and (4) an automated support vector machine (classifier for speech versus rest). Cohen's kappa measured agreement between the four EEG measures and evidence of language function on a behavioral coma recovery scale-revised (CRS-R) and composite (CRS-R or functional MRI) reference standard. Sensitivity and specificity of each EEG measure were calculated against the reference standards. We enrolled 17 adult patients with severe TBI (mean ± SD age 27.0 ± 7.0years; median [range] 11.5 [2-1173] days post-injury) and 16 healthy subjects (age 28.5 ± 7.8years). The classifier, followed by Forgacs' criteria for resting background, demonstrated the highest agreement with the behavioral reference standard. Only Synek's criteria for background and reactivity showed significant agreement with the composite reference standard. The classifier and resting background showed balanced sensitivity and specificity for behavioral (sensitivity = 84.6% and 80.8%; specificity = 57.1% for both) and composite reference standards (sensitivity = 79.3% and 75.9%, specificity = 50% for both). Methods applying an automated classifier, resting background, or resting background with reactivity may identify severe TBI patients with preserved language function. Automated classifier methods may enable unbiased and efficient assessment of larger populations or serial timepoints, while qualitative visual methods may be practical in community settings.

Behavioral Recovery and Early Decision Making in Patients with Prolonged Disturbance in Consciousness after Traumatic Brain Injury.

The extent of behavioral recovery that occurs in patients with traumatic disorders of consciousness (DoC) following discharge from the acute care setting has been under-studied and increases the risk of overly pessimistic outcome prediction. The aim of this observational cohort study was to systematically track behavioral and functional recovery in patients with prolonged traumatic DoC following discharge from the acute care setting. Standardized behavioral data were acquired from 95 patients in a minimally conscious (MCS) or vegetative state (VS) recruited from 11 clinic sites and randomly assigned to the placebo arm of a previously completed prospective clinical trial. Patients were followed for 6 weeks by blinded observers to determine frequency of recovery of six target behaviors associated with functional status. The Coma Recovery Scale-Revised and Disability Rating Scale were used to track reemergence of target behaviors and assess degree of functional disability, respectively. Twenty percent (95% confidence interval [CI]: 13–30%) of participants (mean age 37.2; median 47 days post-injury; 69 men) recovered all six target behaviors within the 6 week observation period. The odds of recovering a specific target behavior were 3.2 (95% CI: 1.2–8.1) to 7.8 (95% CI: 2.7–23.0) times higher for patients in MCS than for those in VS. Patients with preserved language function (“MCS+”) recovered the most behaviors (p ≤ 0.002) and had the least disability (p ≤ 0.002) at follow-up. These findings suggest that recovery of high-level behaviors underpinning functional independence is common in patients with prolonged traumatic DoC. Clinicians involved in early prognostic counseling should recognize that failure to emerge from traumatic DoC before 28 days does not necessarily portend unfavorable outcome.

Functional MRI Motor Imagery Tasks to Detect Command Following in Traumatic Disorders of Consciousness.

Severe traumatic brain injury impairs arousal and awareness, the two components of consciousness. Accurate diagnosis of a patient’s level of consciousness is critical for determining treatment goals, access to rehabilitative services, and prognosis. The bedside behavioral examination, the current clinical standard for diagnosis of disorders of consciousness, is prone to misdiagnosis, a finding that has led to the development of advanced neuroimaging techniques aimed at detection of conscious awareness. Although a variety of paradigms have been used in functional magnetic resonance imaging (fMRI) to reveal covert consciousness, the relative accuracy of these paradigms in the patient population is unknown. Here, we compare the rate of covert consciousness detection by hand squeezing and tennis playing motor imagery paradigms in 10 patients with traumatic disorders of consciousness [six male, six acute, mean ± SD age = 27.9 ± 9.1 years, one coma, four unresponsive wakefulness syndrome, two minimally conscious without language function, and three minimally conscious with language function, per bedside examination with the Coma Recovery Scale-Revised (CRS-R)]. We also tested the same paradigms in 10 healthy subjects (nine male, mean ± SD age = 28.5 ± 9.4 years). In healthy subjects, the hand squeezing paradigm detected covert command following in 7/10 and the tennis playing paradigm in 9/10 subjects. In patients who followed commands on the CRS-R, the hand squeezing paradigm detected covert command following in 2/3 and the tennis playing paradigm in 0/3 subjects. In patients who did not follow commands on the CRS-R, the hand squeezing paradigm detected command following in 1/7 and the tennis playing paradigm in 2/7 subjects. The sensitivity, specificity, and accuracy (ACC) of detecting covert command following in patients who demonstrated this behavior on the CRS-R was 66.7, 85.7, and 80% for the hand squeezing paradigm and 0, 71.4, and 50% for the tennis playing paradigm, respectively. Overall, the tennis paradigm performed better than the hand squeezing paradigm in healthy subjects, but in patients, the hand squeezing paradigm detected command following with greater ACC. These findings indicate that current fMRI motor imagery paradigms frequently fail to detect command following and highlight the need for paradigm optimization to improve the accuracy of covert consciousness detection.

Cerebral FDG-PET Findings in Patients with Traumatic Disorders of Consciousness: Preliminary Results of a Pilot Study (P5.159)

Cerebral FDG-PET Findings in Patients with Traumatic Disorders of Consciousness: Preliminary Results of a Pilot Study (P5.159)

Detecting language processing in traumatic disorders of consciousness: A stimulus-based EEG study (P4.213)

Detecting language processing in traumatic disorders of consciousness: A stimulus-based EEG study (P4.213)

Cerebral FDG-PET Findings in Patients with Traumatic Disorders of Consciousness: Preliminary Results of a Pilot Study

Cerebral FDG-PET Findings in Patients with Traumatic Disorders of Consciousness: Preliminary Results of a Pilot Study

Effect of Lesion Burden on Recovery and Response to Amantadine in Patients with Traumatic Disorders of Consciousness

Effect of Lesion Burden on Recovery and Response to Amantadine in Patients with Traumatic Disorders of Consciousness

Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness

Recent studies suggest that the functional organization of brain networks is altered in patients with severe disorders of consciousness (DOC), including coma [1]. A better characterization of these large-scale disturbances of brain function is fundamental for the understanding and eventual prediction of coma outcome. In this study we apply information theory tools and correlation measures to explore the brain functional connectivity (FC) in functional magnetic resonance imaging (fMRI) data from patients with DOC. In particular we are interested in the functional coherence within and between brain hemispheres as a measure of the integrity of brain function. The data analyzed comprises resting state fMRI data from 5 patients with traumatic DOC in two sessions, one early after the traumatic event and the second later in a stable clinical phase spanning several months. As a control we used similar data obtained from 17 healthy subjects. FC was assessed among time series of the blood oxygenated level dependent (BOLD) signal from 90 regions of interest (ROI) obtained using the Automated Anatomical Labelling (AAL) atlas [2]. These time series were used to estimate FC using two approaches: Partial Linear Correlation (PLC) and Transfer Entropy (TE) [3]. The major findings are summarized in Figure ​Figure1;1; the PLC analysis shows a significant reduction of the inter-hemispheric FC in DOC patients compared to controls. Regarding TE measures, we have found a strong reduction in the total TE of the DOC patients vs controls; mean values of 59.17 bits for DOC vs 123.97 bits for controls, whilst the two groups have a similar standard deviation (62.41 for DOC vs 76.69 for controls). Furthermore, the results based on TE seem to indicate that the inter-hemispheric FC asymmetry reported by the PLC in Figure ​Figure11 might be corresponded with an asymmetry between the TE travelling from to vs the one from to along the same ROI in the AAL. Notice that TE (but not PLC) is a non-symmetric measure. Interestingly, some of the DOC patients presented a FC pattern closer to the healthy subjects, for instance patient 3 who in the second session (i.e., 3' in Figure ​Figure1)1) was fully conscious. These findings might have clinical value for the diagnosis and design of recovery plans for patients with DOC. Figure 1 For each subject it is shown the PLC summed over the 45 regions of the left hemisphere (bottom graph), the right hemisphere (middle graph) or between all right-left homologous ROIs in the AAL (top graph). Numbers on x-axis are indicating the different ...

Functional Outcomes in Traumatic Disorders of Consciousness: 5-Year Outcomes From the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems

ObjectiveTo characterize the 5-year outcomes of patients with traumatic brain injury (TBI) not following commands when admitted to acute inpatient rehabilitation. DesignSecondary analysis of prospectively collected data from the National Institute on Disability and Rehabilitation Research–funded Traumatic Brain Injury Model Systems (TBIMS). SettingInpatient rehabilitation hospitals participating in the TBIMS program. ParticipantsPatients (N=108) with TBI not following commands at admission to acute inpatient rehabilitation were divided into 2 groups (early recovery: followed commands before discharge [n=72]; late recovery: did not follow commands before discharge [n=36]). InterventionsNot applicable. Main Outcome MeasuresFIM items. ResultsFor the early recovery group, depending on the FIM item, 8% to 21% of patients were functioning independently at discharge, increasing to 56% to 85% by 5 years postinjury. The proportion functioning independently increased from discharge to 1 year, 1 to 2 years, and 2 to 5 years. In the late recovery group, depending on the FIM item, 19% to 36% of patients were functioning independently by 5 years postinjury. The proportion of independent patients increased significantly from discharge to 1 year and from 1 to 2 years, but not from 2 to 5 years. ConclusionsSubstantial proportions of patients admitted to acute inpatient rehabilitation before following commands recover independent functioning over as long as 5 years, particularly if they begin to follow commands before hospital discharge.