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1
Cologan, Victor, Xavier Drouot, Silvia Parapatics, et al. "Sleep in the Unresponsive Wakefulness Syndrome and Minimally Conscious State." Journal of Neurotrauma 30, no. 5 (2013): 339–46. http://dx.doi.org/10.1089/neu.2012.2654.
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Kondratyeva, Ekaterina A., Nataliya A. Lesteva, Elena V. Verbitskaya, et al. "Possibilities of endoscopic evaluation of swallowing function in patients with chronic disorders of consciousness." Physical and rehabilitation medicine, medical rehabilitation 4, no. 3 (2022): 140–53. http://dx.doi.org/10.36425/rehab110856.
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BACKGROUND: The period of coma in some patients after severe brain damage ends with a transition to one of the forms of chronic disorders of consciousness ― a vegetative state/unresponsive wakefulness syndrome or a minimally conscious state. Almost all patients with chronic disorders of consciousness have dysphagia of varying severity, and therefore nutrition of this category of patients is carried out initially through a nasogastric tube, and then through a gastrostomy. Early tracheostomy cannula removal may lead to the development of aspiration and pneumonia. Dysphagia is often not diagnosed in chronic disorders of consciousness patients.
 AIMS: Analysis of the results of fibrooptic endoscopic assessment of swallowing in chronic disorders of consciousness patients to identify the relationship between the presence and severity of dysphagia with the level of consciousness, data on the coma recovery scale, as well as the duration of consciousness disorders and dynamics of recovery of consciousness.
 MATERIALS AND METHODS: The study was of a prospective type, conducted in the period from 2019 to 2021. 39 chronic disorders of consciousness patients (18 ― vegetative state/unresponsive wakefulness syndrome, 18 ― minimally conscious state "minus" and minimally conscious state "plus" and 3 patients with a level of consciousness corresponding to the emergence from the minimally conscious state). The average duration of chronic disorders of consciousness was 7.79.4 months. All patients underwent a neurological examination using the CRS-R upon admission to the hospital and a month later, an endoscopic examination of the swallowing function was performed with scores calculated according to the Federal Endoscopic Dysphagia Severity Assessment Scale (FEDSS) and aspiration assessment scale in accordance with the Rosenbek criteria.
 RESULTS: Dysphagia of varying severity was detected in 36 patients (92.3%). The correlation of the total CRS-R score with the degree of dysphagia (Ro=-0.481, p=0.002) was found. The degree of dysphagia did not depend on the chronic disorders of consciousness duration.
 CONCLUSION: Regardless of the chronic disorders of consciousness severity (vegetative state/unresponsive wakefulness syndrome, minimally conscious state "minus", minimally conscious state "plus") before tracheostomy removing and switching to the oral feeding, it is necessary to perform fibrooptic endoscopic studies of swallowing to detect dysphagia, determine its degree, which is a method of preventing complications of the decanulation consequences.
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Laureys, S. "K1 Neurophysiology of minimally conscious and vegetative state/unresponsive wakefulness syndrome." Clinical Neurophysiology 122 (June 2011): S5. http://dx.doi.org/10.1016/s1388-2457(11)60017-5.
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Pan, Jiahui, Qiuyou Xie, Pengmin Qin, et al. "Prognosis for patients with cognitive motor dissociation identified by brain-computer interface." Brain 143, no. 4 (2020): 1177–89. http://dx.doi.org/10.1093/brain/awaa026.
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Abstract Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients’ behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness.
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Naro, Antonino, Antonino Leo, Antonino Cannavò, et al. "Audiomotor Integration in Minimally Conscious State: Proof of Concept!" Neural Plasticity 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/391349.
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Patients suffering from chronic disorders of consciousness (DOC) are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI) in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS) delivered over the left primary motor area (M1), paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS) but in none of those suffering from unresponsive wakefulness syndrome (UWS). Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment.
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Cacciola, Alberto, Antonino Naro, Demetrio Milardi, et al. "Functional Brain Network Topology Discriminates between Patients with Minimally Conscious State and Unresponsive Wakefulness Syndrome." Journal of Clinical Medicine 8, no. 3 (2019): 306. http://dx.doi.org/10.3390/jcm8030306.
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Consciousness arises from the functional interaction of multiple brain structures and their ability to integrate different complex patterns of internal communication. Although several studies demonstrated that the fronto-parietal and functional default mode networks play a key role in conscious processes, it is still not clear which topological network measures (that quantifies different features of whole-brain functional network organization) are altered in patients with disorders of consciousness. Herein, we investigate the functional connectivity of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) patients from a topological network perspective, by using resting-state EEG recording. Network-based statistical analysis reveals a subnetwork of decreased functional connectivity in UWS compared to in the MCS patients, mainly involving the interhemispheric fronto-parietal connectivity patterns. Network topological analysis reveals increased values of local-community-paradigm correlation, as well as higher clustering coefficient and local efficiency in UWS patients compared to in MCS patients. At the nodal level, the UWS patients showed altered functional topology in several limbic and temporo-parieto-occipital regions. Taken together, our results highlight (i) the involvement of the interhemispheric fronto-parietal functional connectivity in the pathophysiology of consciousness disorders and (ii) an aberrant connectome organization both at the network topology level and at the nodal level in UWS patients compared to in the MCS patients.
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Kondratyeva, Ekaterina A., Alina O. Ivanova, Maria I. Yarmolinskaya, et al. "Evaluation of structural variations in the pituitary gland, hormonal status and laboratory markers of the central nervous system functioning in patients with chronic disorders of consciousness." Journal of obstetrics and women's diseases 70, no. 5 (2021): 23–36. http://dx.doi.org/10.17816/jowd77930.
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BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation.
 AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness.
 MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid.
 RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state.
 CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.
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Johnson, L. Syd M., and Kathy L. Cerminara. "All things considered: Surrogate decision-making on behalf of patients in the minimally conscious state." Clinical Ethics 15, no. 3 (2020): 111–19. http://dx.doi.org/10.1177/1477750920927177.
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The minimally conscious state presents unique ethical, legal, and decision-making challenges because of the combination of diminished awareness, phenomenal experience, and diminished or absent communication. As medical expertise develops and technology advances, it is likely that more and more patients with disorders of consciousness will be recognized as being in the minimally conscious state, with minimal to no ability to participate in medical decision-making. Here we provide guidance useful for surrogates and medical professionals at any medical decision point, not merely for end-of-life decision-making. We first consider the legal landscape: precedent abounds regarding unconscious patients in coma or the vegetative state/Unresponsive Wakefulness Syndrome (VS/UWS), but there is little legal precedent involving patients in the minimally conscious state. Next we consider surrogates’ ethical authority to make medical decisions on behalf of patients with disorders of consciousness. In everyday medical decision-making, surrogates generally encounter few, if any, restrictions so long as they adhere to an idealized hierarchy of decision-making standards designed to honor patient autonomy as much as possible while ceding to the reality of what may or may not be known about a patient’s wishes. We conclude by proposing an ethically informed, practical guide for surrogate decision-making on behalf of patients in the minimally conscious state.
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Guldenmund, P., J. Stender, L. Heine, and S. Laureys. "Mindsight: Diagnostics in Disorders of Consciousness." Critical Care Research and Practice 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/624724.
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Diagnosis of patients with disorders of consciousness (comprising coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state) has long been dependent on unstandardized behavioral tests. The arrival of standardized behavioral tools, and especially the Coma Recovery Scale revised, uncovered a high rate of misdiagnosis. Ancillary techniques, such as brain imaging and electrophysiological examinations, are ever more often being deployed to aid in the search for remaining consciousness. They are used to look for brain activity patterns similar to those found in healthy controls. The development of portable and cheaper devices will make these techniques more widely available.
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Naro, Antonino, Rocco Salvatore Calabrò, Margherita Russo, et al. "Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients?" Restorative Neurology and Neuroscience 33, no. 2 (2015): 159–76. http://dx.doi.org/10.3233/rnn-140448.
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Hermann, Bertrand, Amina Ben Salah, Vincent Perlbarg, et al. "Habituation of auditory startle reflex is a new sign of minimally conscious state." Brain 143, no. 7 (2020): 2154–72. http://dx.doi.org/10.1093/brain/awaa159.
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Abstract Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)—also coined unresponsive wakefulness syndrome (UWS)—and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15–20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.
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Wutzl, Betty, Stefan M. Golaszewski, Kenji Leibnitz, et al. "Narrative Review: Quantitative EEG in Disorders of Consciousness." Brain Sciences 11, no. 6 (2021): 697. http://dx.doi.org/10.3390/brainsci11060697.
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In this narrative review, we focus on the role of quantitative EEG technology in the diagnosis and prognosis of patients with unresponsive wakefulness syndrome and minimally conscious state. This paper is divided into two main parts, i.e., diagnosis and prognosis, each consisting of three subsections, namely, (i) resting-state EEG, including spectral power, functional connectivity, dynamic functional connectivity, graph theory, microstates and nonlinear measurements, (ii) sleep patterns, including rapid eye movement (REM) sleep, slow-wave sleep and sleep spindles and (iii) evoked potentials, including the P300, mismatch negativity, the N100, the N400 late positive component and others. Finally, we summarize our findings and conclude that QEEG is a useful tool when it comes to defining the diagnosis and prognosis of DOC patients.
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Gosseries, Olivia, Francesca Pistoia, Vanessa Charland-Verville, Antonio Carolei, Simona Sacco, and Steven Laureys. "The Role of Neuroimaging Techniques in Establishing Diagnosis, Prognosis and Therapy in Disorders of Consciousness." Open Neuroimaging Journal 10, no. 1 (2016): 52–68. http://dx.doi.org/10.2174/1874440001610010052.
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Non-communicative brain damaged patients raise important clinical and scientific issues. Here, we review three major pathological disorders of consciousness: coma, the unresponsive wakefulness syndrome and the minimally conscious state. A number of clinical studies highlight the difficulty in making a correct diagnosis in patients with disorders of consciousness based only on behavioral examinations. The increasing use of neuroimaging techniques allows improving clinical characterization of these patients. Recent neuroimaging studies using positron emission tomography, functional magnetic resonance imaging, electroencephalography and transcranial magnetic stimulation can help assess diagnosis, prognosis, and therapeutic treatment. These techniques, using resting state, passive and active paradigms, also highlight possible dissociations between consciousness and responsiveness, and are facilitating a more accurate understanding of brain function in this challenging population.
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Carrière, Manon, Roberto Llorens, María Dolores Navarro, José Olaya, Joan Ferri, and Enrique Noé. "Behavioral signs of recovery from unresponsive wakefulness syndrome to emergence of minimally conscious state after severe brain injury." Annals of Physical and Rehabilitation Medicine 65, no. 2 (2022): 101534. http://dx.doi.org/10.1016/j.rehab.2021.101534.
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Kondratyeva, E., M. Aybazova, N. Lesteva, S. Kondratyev, A. Kondratev, and N. Dryagina. "Unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) patients with myoclonus - Pathological variant organization of brain's function." Journal of the Neurological Sciences 405 (October 2019): 98. http://dx.doi.org/10.1016/j.jns.2019.10.1748.
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Stender, Johan, Ron Kupers, Anders Rodell, et al. "Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients." Journal of Cerebral Blood Flow & Metabolism 35, no. 1 (2014): 58–65. http://dx.doi.org/10.1038/jcbfm.2014.169.
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The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS ( n=14), MCS ( n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers ( n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.
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Formaggio, Emanuela, Marianna Cavinato, Silvia Francesca Storti, Paolo Tonin, Francesco Piccione, and Paolo Manganotti. "Assessment of Event-Related EEG Power After Single-Pulse TMS in Unresponsive Wakefulness Syndrome and Minimally Conscious State Patients." Brain Topography 29, no. 2 (2015): 322–33. http://dx.doi.org/10.1007/s10548-015-0461-3.
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Magrassi, Lorenzo, Giorgio Maggioni, Caterina Pistarini, et al. "Results of a prospective study (CATS) on the effects of thalamic stimulation in minimally conscious and vegetative state patients." Journal of Neurosurgery 125, no. 4 (2016): 972–81. http://dx.doi.org/10.3171/2015.7.jns15700.
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OBJECTIVE Deep brain stimulation of the thalamus was introduced more than 40 years ago with the objective of improving the performance and attention of patients in a vegetative or minimally conscious state. Here, the authors report the results of the Cortical Activation by Thalamic Stimulation (CATS) study, a prospective multiinstitutional study on the effects of bilateral chronic stimulation of the anterior intralaminar thalamic nuclei and adjacent paralaminar regions in patients affected by a disorder of consciousness. METHODS The authors evaluated the clinical and radiological data of 29 patients in a vegetative state (unresponsive wakefulness syndrome) and 11 in a minimally conscious state that lasted for more than 6 months. Of these patients, 5 were selected for bilateral stereotactic implantation of deep brain stimulating electrodes into their thalamus. A definitive consensus for surgery was obtained for 3 of the selected patients. All 3 patients (2 in a vegetative state and 1 in a minimally conscious state) underwent implantation of bilateral thalamic electrodes and submitted to chronic stimulation for a minimum of 18 months and a maximum of 48 months. RESULTS In each case, there was an increase in desynchronization and the power spectrum of electroencephalograms, and improvement in the Coma Recovery Scale–Revised scores was found. Furthermore, the severity of limb spasticity and the number and severity of pathological movements were reduced. However, none of these patients returned to a fully conscious state. CONCLUSIONS Despite the limited number of patients studied, the authors confirmed that bilateral thalamic stimulation can improve the clinical status of patients affected by a disorder of consciousness, even though this stimulation did not induce persistent, clinically evident conscious behavior in the patients. Clinical trial registration no.: NCT01027572 (ClinicalTrials.gov)
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Soler-Toscano, Fernando, Javier A. Galadí, Anira Escrichs, et al. "What lies underneath: Precise classification of brain states using time-dependent topological structure of dynamics." PLOS Computational Biology 18, no. 9 (2022): e1010412. http://dx.doi.org/10.1371/journal.pcbi.1010412.
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The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, most efforts of capturing the causal mechanistic generating principles have supposed underlying stationarity, being unable to describe the non-stationarity of brain dynamics, i.e. time-dependent changes. Here, we present a novel framework able to characterise brain states with high specificity, precisely by modelling the time-dependent dynamics. Through describing a topological structure associated to the brain state at each moment in time (its attractor or ‘information structure’), we are able to classify different brain states by using the statistics across time of these structures hitherto hidden in the neuroimaging dynamics. Proving the strong potential of this framework, we were able to classify resting-state BOLD fMRI signals from two classes of post-comatose patients (minimally conscious state and unresponsive wakefulness syndrome) compared with healthy controls with very high precision.
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Szymkowicz, Emilie, Olga Neumann, Leandro R. D. Sanz, et al. "Recovery of Acute Leukoencephalopathy Documented by Neuroimaging." Neurology: Clinical Practice 13, no. 6 (2023): e200203. http://dx.doi.org/10.1212/cpj.0000000000200203.
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ObjectivesWe describe an atypical delayed neurologic recovery from coma and unresponsive wakefulness syndrome (i.e., persistent vegetative state) in a patient with severe drug-induced toxic leukoencephalopathy (presumably due to synthetic cannabinoid intake).MethodsThe patient underwent standardized behavioral and multimodal neuroimaging assessments to monitor clinical evolution and brain function over a 5-month period after presumed intoxication.ResultsA progressive clinical recovery was observed, from an initial state of coma to emergence from a minimally conscious state after 2 months. Despite the stability of extensive white matter lesions documented by CT and structural MRI, fluorodeoxyglucose PET showed partial recovery of cortical metabolism after 5 months.DiscussionThis case report illustrates that the temporal dynamics of recovery from toxic acute leukoencephalopathy may be atypical and delayed. Multimodal monitoring with repeated behavioral and functional neuroimaging assessments tends to improve the prognosis reliability, while early prognosis based on structural damage may result in misleading statements.
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Russell, Mary E., Flora M. Hammond, and Brooke Murtaugh. "Prognosis and enhancement of recovery in disorders of consciousness." NeuroRehabilitation 54, no. 1 (2024): 43–59. http://dx.doi.org/10.3233/nre-230148.
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Disorders of consciousness after severe brain injury encompass conditions of coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. DoC clinical presentation pose perplexing challenges to medical professionals, researchers, and families alike. The outcome is uncertain in the first weeks to months after a brain injury, with families and medical providers often making important decisions that require certainty. Prognostication for individuals with these conditions has been the subject of intense scientific investigation that continues to strive for valid prognostic indicators and algorithms for predicting recovery of consciousness. This manuscript aims to provide an overview of the current clinical landscape surrounding prognosis and optimizing recovery in DoC and the current and future research that could improve prognostic accuracy after severe brain injury. Improved understanding of these factors will aid healthcare professionals in providing optimal care, fostering hope, and advocating for ethical practices in the management of individuals with DoC.
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Schnetzer, Laura, Verena S. Schätzle, Lisa Kronbichler, et al. "Diagnosis and Prognosis in Disorders of Consciousness: An Active Paradigm fMRI Study." Acta Neurologica Scandinavica 2023 (November 13, 2023): 1–14. http://dx.doi.org/10.1155/2023/3991087.
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Diagnoses in patients with disorders of consciousness are prone to misdiagnosis; thus, research has sought approaches to increase reliability, for instance, with functional MRI. By applying a motor imagery task, patients showing covert command following despite the absence of behavioural signs of awareness can be identified as being in a cognitive motor dissociation. This study seeks to determine the proportion of patients, with unresponsive wakefulness syndrome and minimally conscious state, who display covert command following. Moreover, the prognostic value of the improved diagnosis and different methodical approaches to analyse the functional MRI data were evaluated. 73 disorder of consciousness patients (35 unresponsive, 35 minimally conscious, and three already recovered) underwent weekly standardized behavioural assessments with the coma-recovery scale—revised and one functional MRI examination comparing their brain activations in the supplementary motor area between phases of imaging playing tennis and rest. 27 healthy controls served as a control group. The data was evaluated using different region-of-interest analyses (one- and two-tailed small-volume correction and region-of-interest exploration approaches) and a whole-brain analysis. Based on the one-tailed small volume correction data, seven patients, all of nontraumatic aetiology, showed covert command following. The one-tailed region-of-interest exploration identified three additional responders. 10 patients showed significantly more activation during rest than during the imagery paradigm (negative responders). 40% of patients (minimally conscious patients being three times more likely) showed significant activations in the whole brain analysis. Besides, no significant further associations were found between covert command following and clinical parameters. The analyses showed that the tennis paradigm could identify patients with cognitive motor dissociation with a nontraumatic aetiology, but our data failed to show any short-term prognostic validity. The relevance of negative responders and activated regions outside of the region of interest should be further investigated.
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Degtiareva, S. A., E. A. Kondratieva, I. G. Smirnova, I. S. Polukhin, Y. S. Andreev, and V. E. Bougrov. "Visual control and data transmission system by Li-Fi technology for patients in a vegetative state/unresponsive wakefulness syndrome and minimally conscious state." Journal of Physics: Conference Series 1697 (December 2020): 012172. http://dx.doi.org/10.1088/1742-6596/1697/1/012172.
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Olaya, José, Enrique Noé, María Dolores Navarro, et al. "When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Functional Independence." Brain Sciences 10, no. 12 (2020): 990. http://dx.doi.org/10.3390/brainsci10120990.
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Accurate estimation of the functional independence of patients with unresponsive wakefulness syndrome (UWS) is essential to adjust family and clinical expectations and plan long-term necessary resources. Although different studies have described the clinical course of these patients, they have methodological limitations that could restrict generalization of the results. This study investigates the neurobehavioral progress of 100 patients with UWS consecutively admitted to a neurorehabilitation center using systematic weekly assessments based on standardized measures, and the functional independence staging of those patients who emerged from a minimally conscious state (MCS) during the first year post-emergence. Our results showed that one year after emergence, most patients were severely dependent, although some of them showed extreme or moderate severity. Clinically meaningful functional improvement was less likely to occur in cognitively-demanding activities, such as activities of daily living and executive function. Consequently, the use of specific and staging functional independence measures, with domain-specific evaluations, are recommended to detect the functional changes that might be expected in these patients. The information provided by these instruments, together with that obtained from repeated assessments of the preserved consciousness with standardized instruments, could help clinicians to adjust expectations and plan necessary resources for this population.
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Ihalainen, Riku, Jitka Annen, Olivia Gosseries, et al. "Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in a cohort of patients with traumatic disorders of consciousness." PLOS ONE 19, no. 7 (2024): e0298110. http://dx.doi.org/10.1371/journal.pone.0298110.
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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.
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Noé, Enrique, Joan Ferri, José Olaya, et al. "When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress." Brain Sciences 11, no. 1 (2021): 126. http://dx.doi.org/10.3390/brainsci11010126.
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Accurate estimation of the neurobehavioral progress of patients with unresponsive wakefulness syndrome (UWS) is essential to anticipate their most likely clinical course and guide clinical decision making. Although different studies have described this progress and possible predictors of neurobehavioral improvement in these patients, they have methodological limitations that could restrict the validity and generalization of the results. This study investigates the neurobehavioral progress of 100 patients with UWS consecutively admitted to a neurorehabilitation center using systematic weekly assessments based on standardized measures, and the prognostic factors of changes in their neurobehavioral condition. Our results showed that, during the analyzed period, 34% of the patients were able to progress from UWS to minimally conscious state (MCS), 12% of the total sample (near one third from those who progressed to MCS) were able to emerge from MCS, and 10% of the patients died. Transition to MCS was mostly denoted by visual signs, which appeared either alone or in combination with motor signs, and was predicted by etiology and the score on the Coma Recovery Scale-Revised at admission with an accuracy of 75%. Emergence from MCS was denoted in the same proportion by functional communication and object use. Predictive models of emergence from MCS and mortality were not valid and the identified predictors could not be accounted for.
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Sontheimer, Anna, Bénédicte Pontier, Béatrice Claise, Carine Chassain, Jérôme Coste, and Jean-Jacques Lemaire. "Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness." Brain Sciences 11, no. 3 (2021): 356. http://dx.doi.org/10.3390/brainsci11030356.
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Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.
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Kondratyeva, E. A., M. V. Sinkin, E. V. Sharova, S. Laureys, and A. N. Kondratyev. "Zolpidem Action During Prolonged Disorders of Consciousness (Case Report)." General Reanimatology 15, no. 5 (2019): 44–60. http://dx.doi.org/10.15360/1813-9779-2019-5-44-60.
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The paper describes two patients with prolonged disorders of consciousness (PDC) because of non-traumatic brain injury, in whom a clear neurodynamic response to Zolpidem was observed.In order to illustrate systemic cerebral responses to administration of this drug in LIC patients, an analysis of clinical and electrophysiological changes has been undertaken.It has been shown that the result of Zolpidem applications in patients with prolonged disorders of consciousness (PDC) should be assessed not only by consciousness dynamics, but with the help of electroencephalogram (EEG) monitoring, too. Distinct response to Zolpidem during different periods of recovery in one patients was found.Zolpidem can render various effects in patients in vegetative state/with unresponsive wakefulness syndrome (VS/UWS) and in minimally conscious state (MCS). In one patient, sedation with EEG activation was observed, which was a sign of favorable prognosis. The other patient developed more than once local convulsions after Zolpidem administration followed by contact augmentation on the next day.The mechanism of action, necessary doses of drugs, and markers of forecasting the successful effect of that drug are yet to be further studied.
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Bonfiglio, Luca, Andrea Piarulli, Umberto Olcese, et al. "Spectral Parameters Modulation and Source Localization of Blink-Related Alpha and Low-Beta Oscillations Differentiate Minimally Conscious State from Vegetative State/Unresponsive Wakefulness Syndrome." PLoS ONE 9, no. 3 (2014): e93252. http://dx.doi.org/10.1371/journal.pone.0093252.
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Zhang, Ye, Jie Lu, Jubao Du, Su Huo, Ran Li, and Weiqun Song. "Neural correlates of different behavioral response to transcranial direct current stimulation between patients in the unresponsive wakefulness syndrome and minimally conscious state." Neurological Sciences 41, no. 1 (2019): 75–82. http://dx.doi.org/10.1007/s10072-019-04034-8.
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Leboutte, Francois, Christian Engesser, Leutrim Zahiti, et al. "Prevalence of Unfavorable Video-Urodynamic Findings and Clinical Implications in Patients with Minimally Conscious State/Unresponsive Wakefulness Syndrome: A Retrospective Descriptive Analysis." Biomedicines 11, no. 9 (2023): 2432. http://dx.doi.org/10.3390/biomedicines11092432.
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The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective chart review was conducted to screen for patients diagnosed with MCS/UWS at our rehabilitation center between 2011 and 2020. Patients 18 years or older were included and underwent baseline VUDS after being diagnosed with MCS/UWS. We analyzed urodynamic parameters and subsequent changes in LUT management in this cohort. In total, 32 patients (7 females, 25 males, median age 37 years) with MCS/UWS were included for analysis. While at least one unfavorable VUDS finding (i.e., neurogenic detrusor overactivity [NDO], detrusor sphincter dyssynergia {DSD, high maximum detrusor pressure during storage phase [>40 cmH2O], low-compliance bladder [<20 mL/cmH2O], and vesico–uretero–renal reflux [VUR]) was found in each patient, NDO (78.1%, 25/32) and DSD (68.8%, 22/32) were the two most frequent unfavorable VUDS findings. Following baseline VUDS, new LUT treatment options were established in 56.3% (18/32) of all patients. In addition, bladder-emptying methods were changed in 46.9% (15/32) of all patients, resulting in fewer patients relying on indwelling catheters. Our retrospective exploratory study revealed a high prevalence of NDO and DSD in patients with MCS/UWS, illustrating the importance of VUDS to adapt LUT management in this cohort accordingly.
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Sinitsyn, Dmitry O., Alexandra G. Poydasheva, Ilya S. Bakulin, et al. "Detecting the Potential for Consciousness in Unresponsive Patients Using the Perturbational Complexity Index." Brain Sciences 10, no. 12 (2020): 917. http://dx.doi.org/10.3390/brainsci10120917.
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The difficulties of behavioral evaluation of prolonged disorders of consciousness (DOC) motivate the development of brain-based diagnostic approaches. The perturbational complexity index (PCI), which measures the complexity of electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS), showed a remarkable sensitivity in detecting minimal signs of consciousness in previous studies. Here, we tested the reliability of PCI in an independently collected sample of 24 severely brain-injured patients, including 11 unresponsive wakefulness syndrome (UWS), 12 minimally conscious state (MCS) patients, and 1 emergence from MCS patient. We found that the individual maximum PCI value across stimulation sites fell within the consciousness range (i.e., was higher than PCI*, which is an empirical cutoff previously validated on a benchmark population) in 11 MCS patients, yielding a sensitivity of 92% that surpassed qualitative evaluation of resting EEG. Most UWS patients (n = 7, 64%) showed a slow and stereotypical TMS-EEG response, associated with low-complexity PCI values (i.e., ≤PCI*). Four UWS patients (36%) provided high-complexity PCI values, which might suggest a covert capacity for consciousness. In conclusion, this study successfully replicated the performance of PCI in discriminating between UWS and MCS patients, further motivating the application of TMS-EEG in the workflow of DOC evaluation.
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Billeri, Luana, Serena Filoni, Emanuele Francesco Russo, et al. "Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology." Brain Sciences 10, no. 1 (2020): 42. http://dx.doi.org/10.3390/brainsci10010042.
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The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including advanced EEG analyses, can allow achieving a more reliable diagnosis, that is, discovering residual traces of awareness in patients with UWS (namely, functional Locked-In Syndrome (fLIS)). These approaches aim at capturing the residual brain network models, at rest or that may be activated in response to relevant stimuli, which may be appropriate for awareness to emerge (despite their insufficiency to generate purposeful motor behaviors). For this, different brain network models have been studied in patients with DoC by using sensory stimuli (i.e., passive tasks), probing response to commands (i.e., active tasks), and during resting-state. Since it can be difficult for patients with DoC to perform even simple active tasks, this scoping review aims at summarizing the current, innovative neurophysiological examination methods in resting state/passive modality to differentiate and prognosticate patients with DoC. We conclude that the electrophysiologically-based diagnostic procedures represent an important resource for diagnosis, prognosis, and, therefore, management of patients with DoC, using advance passive and resting state paradigm analyses for the patients who lie in the “greyzones” between MCS, UWS, and fLIS.
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Young, Michael J., Yelena G. Bodien, and Brian L. Edlow. "Ethical Considerations in Clinical Trials for Disorders of Consciousness." Brain Sciences 12, no. 2 (2022): 211. http://dx.doi.org/10.3390/brainsci12020211.
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As the clinical trial landscape for patients with disorders of consciousness (DoC) expands, consideration of associated ethical challenges and opportunities is of ever-increasing importance. Responsible conduct of research in the vulnerable population of persons with DoC, including those with coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), covert cortical processing (CCP), and cognitive motor dissociation (CMD), demands proactive deliberation of unique ethical issues that may arise and the adoption of robust protections to safeguard patients, surrogates, and other key stakeholders. Here we identify and critically evaluate four central categories of ethical considerations in clinical trials involving participants with DoC: (1) autonomy, respect for persons and informed consent of individuals with liminal consciousness; (2) balancing unknown benefits and risks, especially considering the epistemological gap between behavior and consciousness that complicates ordinary ascription of subjective states; (3) disclosure to surrogates and clinical teams of investigational results pertaining to consciousness; and (4) justice considerations, including equitable access to clinical trial enrollment across communities and geographies. We outline guiding principles and research opportunities for clinicians, neuroethicists, and researchers engaged in DoC clinical trials to advance ethical study design and deployment in this complex yet crucial area of investigation.
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Blume, Christine, Julia Lechinger, Nayantara Santhi, et al. "Significance of circadian rhythms in severely brain-injured patients." Neurology 88, no. 20 (2017): 1933–41. http://dx.doi.org/10.1212/wnl.0000000000003942.
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Objective:To investigate the relationship between the presence of a circadian body temperature rhythm and behaviorally assessed consciousness levels in patients with disorders of consciousness (DOC; i.e., vegetative state/unresponsive wakefulness syndrome or minimally conscious state).Methods:In a cross-sectional study, we investigated the presence of circadian temperature rhythms across 6 to 7 days using external skin temperature sensors in 18 patients with DOC. Beyond this, we examined the relationship between behaviorally assessed consciousness levels and circadian rhythmicity.Results:Analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5–26.3 hours). We found that especially scores on the arousal subscale of the Coma Recovery Scale–Revised were closely linked to the integrity of circadian variations in body temperature. Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in 2 out of 8 patients.Conclusion:The study provides evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness. Our findings also make a case for circadian rhythms as a target for treatment as well as the application of diagnostic and therapeutic means at times when cognitive performance is expected to peak.
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Riganello, Francesco, Martina Vatrano, Simone Carozzo, et al. "The Timecourse of Electrophysiological Brain–Heart Interaction in DoC Patients." Brain Sciences 11, no. 6 (2021): 750. http://dx.doi.org/10.3390/brainsci11060750.
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Disorders of Consciousness (DOC) are a spectrum of pathologies affecting one’s ability to interact with the external world. Two possible conditions of patients with DOC are Unresponsive Wakefulness Syndrome/Vegetative State (UWS/VS) and Minimally Conscious State (MCS). Analysis of spontaneous EEG activity and the Heart Rate Variability (HRV) are effective techniques in exploring and evaluating patients with DOC. This study aims to observe fluctuations in EEG and HRV parameters in the morning/afternoon resting-state recording. The study enrolled 13 voluntary Healthy Control (HC) subjects and 12 DOC patients (7 MCS, 5 UWS/VS). EEG and EKG were recorded. PSDalpha, PSDtheta powerband, alpha-blocking, alpha/theta of the EEG, Complexity Index (CI) and SDNN of EKG were analyzed. Higher values of PSDalpha, alpha-blocking, alpha/theta and CI values and lower values of PSD theta characterized HC individuals in the morning with respect to DOC patients. In the afternoon, we detected a significant difference between groups in the CI, PSDalpha, PSDtheta, alpha/theta and SDNN, with lower PSDtheta value for HC. CRS-R scores showed a strong correlation with recorded parameters mainly during evaluations in the morning. Our finding put in evidence the importance of the assessment, as the stimulation of DOC patients in research for behavioural response, in the morning.
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Kremneva, Elena I., Liudmila A. Legostaeva, Sofya N. Morozova, et al. "Feasibility of Non-Gaussian Diffusion Metrics in Chronic Disorders of Consciousness." Brain Sciences 9, no. 5 (2019): 123. http://dx.doi.org/10.3390/brainsci9050123.
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Diagnostic accuracy of different chronic disorders of consciousness (DOC) can be affected by the false negative errors in up to 40% cases. In the present study, we aimed to investigate the feasibility of a non-Gaussian diffusion approach in chronic DOC and to estimate a sensitivity of diffusion kurtosis imaging (DKI) metrics for the differentiation of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) from a healthy brain state. We acquired diffusion MRI data from 18 patients in chronic DOC (11 VS/UWS, 7 MCS) and 14 healthy controls. A quantitative comparison of the diffusion metrics for grey (GM) and white (WM) matter between the controls and patient group showed a significant (p < 0.05) difference in supratentorial WM and GM for all evaluated diffusion metrics, as well as for brainstem, corpus callosum, and thalamus. An intra-subject VS/UWS and MCS group comparison showed only kurtosis metrics and fractional anisotropy differences using tract-based spatial statistics, owing mainly to macrostructural differences on most severely lesioned hemispheres. As a result, we demonstrated an ability of DKI metrics to localise and detect changes in both WM and GM and showed their capability in order to distinguish patients with a different level of consciousness.
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Xu, Gang, Qianqian Sheng, Qinggang Xin, et al. "EEG Assessment in a 2-Year-Old Child with Prolonged Disorders of Consciousness: 3 Years’ Follow-up." Computational Intelligence and Neuroscience 2020 (November 24, 2020): 1–8. http://dx.doi.org/10.1155/2020/8826238.
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A 2-year-old girl, diagnosed with traumatic brain injury and epilepsy following car trauma, was followed up for 3 years (a total of 15 recordings taken at 0, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 14, 19, 26, and 35 months). There is still no clear guidance on the diagnosis, treatment, and prognosis of children with disorders of consciousness. At each appointment, recordings included the child’s height, weight, pediatric Glasgow Coma Scale (pGCS), Coma Recovery Scale-Revised (CRS-R), Gesell Developmental Schedule, computed tomography or magnetic resonance imaging, electroencephalogram, frequency of seizures, oral antiepileptic drugs, stimulation with subject’s own name (SON), and median nerve electrical stimulation (MNS). Growth and development were deemed appropriate for the age of the child. The pGCS and Gesell Developmental Schedule provided a comprehensive assessment of consciousness and mental development; the weighted Phase Lag Index (wPLI ) in the β-band (13–25 Hz) can distinguish unresponsive wakefulness syndrome from minimally conscious state and confirm that the SON and MNS were effective. The continuous increase of delta-band power indicates a poor prognosis. Interictal epileptiform discharges (IEDs) have a cumulative effect and seizures seriously affect the prognosis.
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Aburas, Jihad, Areej Aziz, Maryam Butt, Angela Leschinsky, and Marsha L. Pierce. "Treating Traumatic Brain Injuries with Electroceuticals: Implications for the Neuroanatomy of Consciousness." NeuroSci 2, no. 3 (2021): 254–65. http://dx.doi.org/10.3390/neurosci2030018.
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According to the Centers for Disease Control and Prevention (CDC), traumatic brain injury (TBI) is the leading cause of loss of consciousness, long-term disability, and death in children and young adults (age 1 to 44). Currently, there are no United States Food and Drug Administration (FDA) approved pharmacological treatments for post-TBI regeneration and recovery, particularly related to permanent disability and level of consciousness. In some cases, long-term disorders of consciousness (DoC) exist, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) characterized by the exhibition of reflexive behaviors only or a minimally conscious state (MCS) with few purposeful movements and reflexive behaviors. Electroceuticals, including non-invasive brain stimulation (NIBS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS) have proved efficacious in some patients with TBI and DoC. In this review, we examine how electroceuticals have improved our understanding of the neuroanatomy of consciousness. However, the level of improvements in general arousal or basic bodily and visual pursuit that constitute clinically meaningful recovery on the Coma Recovery Scale-Revised (CRS-R) remain undefined. Nevertheless, these advancements demonstrate the importance of the vagal nerve, thalamus, reticular activating system, and cortico-striatal-thalamic-cortical loop in the process of consciousness recovery.
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Hakiki, Bahia, Francesca Cecchi, Silvia Pancani, et al. "Critical Illness Polyneuropathy and Myopathy and Clinical Detection of the Recovery of Consciousness in Severe Acquired Brain Injury Patients with Disorders of Consciousness after Rehabilitation." Diagnostics 12, no. 2 (2022): 516. http://dx.doi.org/10.3390/diagnostics12020516.
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Background: Disorders of consciousness (DoCs) include unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Critical illness polyneuropathy and myopathy (CIPNM) is frequent in severe acquired brain injuries and impacts functional outcomes at discharge from the intensive rehabilitation unit (IRU). We investigated the prevalence of CIPNM in DoCs and its relationship with the consciousness assessment. Methods: Patients with DoCs were retrospectively selected from the database including patients admitted to the IRU of the IRCCS Don Gnocchi Foundation, Florence, from August 2012 to May 2020. Electroneurography/electromyography was performed at admission. Consciousness was assessed using the Coma Recovery Scale-Revised (CRS-R) at admission and discharge. Patients transitioning from a lower consciousness state to a higher one were classified as improved responsiveness (IR). Results: A total of 177 patients were included (UWS: 81 (45.8%); MCS: 96 (54.2%); 78 (44.1%) women; 67 years (IQR: 20). At admission, 108 (61.0%) patients had CIPNM. At discharge, 117 (66.1%) patients presented an IR. In the multivariate analysis, CRS-R at admission (p = 0.006; OR: 1.462) and CIPNM (p = 0.039; OR: −1.252) remained significantly associated with IR only for the UWS patients. Conclusions: CIPNM is frequent in DoCs and needs to be considered during the clinical consciousness assessment, especially in patients with UWS.
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Nekrasova, Julia, Mikhail Kanarskii, Ilya Borisov, et al. "One-Year Demographical and Clinical Indices of Patients with Chronic Disorders of Consciousness." Brain Sciences 11, no. 5 (2021): 651. http://dx.doi.org/10.3390/brainsci11050651.
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This work aims to evaluate the prognostic value of the demographical and clinical data on long-term outcomes (up to 12 months) in patients with severe acquired brain injury with vegetative state/unresponsive wakefulness syndrome (VS/UWS/UWS) or a minimally conscious state (MCS). Patients (n = 211) with VS/UWS/UWS (n = 123) and MCS (n = 88) were admitted to the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology after anoxic brain injury (n = 53), vascular lesions (n = 59), traumatic brain injury (n = 93), and other causes (n = 6). At the beginning of the 12-month study, younger age and a higher score by the Coma Recovery Scale-Revised (CRS-R) predicted a survival. However, no reliable markers of significant positive dynamics of consciousness were found. Based on the etiology, anoxic brain injury has the most unfavorable prognosis. For patients with vascular lesions, the first three months after injury have the most important prognostic value. No correlations were found between survival, increased consciousness, and gender. The demographic and clinical characteristics of patients with chronic DOC can be used to predict long-term mortality in patients with chronic disorders of consciousness. Further research should be devoted to finding reliable predictors of recovery of consciousness.
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Naro, Antonino, Alessia Bramanti, Antonino Leo, Placido Bramanti, and Rocco Salvatore Calabrò. "Metaplasticity: A Promising Tool to Disentangle Chronic Disorders of Consciousness Differential Diagnosis." International Journal of Neural Systems 28, no. 06 (2018): 1750059. http://dx.doi.org/10.1142/s0129065717500599.
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The extent of cortical reorganization after brain injury in patients with Vegetative State/Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) depends on the residual capability of modulating synaptic plasticity. Neuroplasticity is largely abnormal in patients with UWS, although the fragments of cortical activity may exist, while patients MCS show a better cortical organization. The aim of this study was to evaluate cortical excitability in patients with disorders of consciousness (DoC) using a transcranial direct current stimulation (TDCS) metaplasticity protocol. To this end, we tested motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). These measures were correlated with the level of consciousness (by the Coma Recovery Scale-Revised, CRS-R). MEP amplitude, SICI, and ICF strength were significantly modulated following different metaplasticity TDCS protocols only in the patients with MCS. SICI modulations showed a significant correlation with the CRS-R score. Our findings demonstrate, for the first time, a partial preservation of metaplasticity properties in some patients with DoC, which correlates with the level of awareness. Thus, metaplasticity assessment may help the clinician in differentiating the patients with DoC, besides the clinical evaluation. Moreover, the responsiveness to metaplasticity protocols may identify the subjects who could benefit from neuromodulation protocols.
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Bagnato, Sergio, Maria Enza D’Ippolito, Cristina Boccagni, et al. "Sustained Axonal Degeneration in Prolonged Disorders of Consciousness." Brain Sciences 11, no. 8 (2021): 1068. http://dx.doi.org/10.3390/brainsci11081068.
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(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.
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Angerer, Monika, Frank H. Wilhelm, Michael Liedlgruber, et al. "Does the Heart Fall Asleep?—Diurnal Variations in Heart Rate Variability in Patients with Disorders of Consciousness." Brain Sciences 12, no. 3 (2022): 375. http://dx.doi.org/10.3390/brainsci12030375.
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The current study investigated heart rate (HR) and heart rate variability (HRV) across day and night in patients with disorders of consciousness (DOC). We recorded 24-h electrocardiography in 26 patients with DOC (i.e., unresponsive wakefulness syndrome (UWS; n = 16) and (exit) minimally conscious state ((E)MCS; n = 10)). To examine diurnal variations, HR and HRV indices in the time, frequency, and entropy domains were computed for periods of clear day- (forenoon: 8 a.m.–2 p.m.; afternoon: 2 p.m.–8 p.m.) and nighttime (11 p.m.–5 a.m.). The results indicate that patients’ interbeat intervals (IBIs) were larger during the night than during the day, indicating HR slowing. The patients in UWS showed larger IBIs compared to the patients in (E)MCS, and the patients with non-traumatic brain injury showed lower HRV entropy than the patients with traumatic brain injury. Additionally, higher HRV entropy was associated with higher EEG entropy during the night. Thus, cardiac activity varies with a diurnal pattern in patients with DOC and can differentiate between patients’ diagnoses and etiologies. Moreover, the interaction of heart and brain appears to follow a diurnal rhythm. Thus, HR and HRV seem to mirror the integrity of brain functioning and, consequently, might serve as supplementary measures for improving the validity of assessments in patients with DOC.
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Morozova, Sofya, Elena Kremneva, Dmitry Sergeev, et al. "Conventional Structural Magnetic Resonance Imaging in Differentiating Chronic Disorders of Consciousness." Brain Sciences 8, no. 8 (2018): 144. http://dx.doi.org/10.3390/brainsci8080144.
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Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.
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Bagnato, Sergio, and Cristina Boccagni. "Cerebrospinal Fluid and Blood Biomarkers in Patients with Post-Traumatic Disorders of Consciousness: A Scoping Review." Brain Sciences 13, no. 2 (2023): 364. http://dx.doi.org/10.3390/brainsci13020364.
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(1) Background: Cerebrospinal fluid (CSF) and blood biomarkers are emerging tools used to obtain information on secondary brain damage and to improve diagnostic and prognostic accuracy for patients with prolonged post-traumatic disorders of consciousness (DoC). We synthesized available data from studies evaluating CSF and blood biomarkers in these patients. (2) Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist to identify and synthesize data from relevant studies. Studies were identified by PubMed and manual searches. Those involving patients with unresponsive wakefulness syndrome or in a minimally conscious state for >28 days, evaluating CSF or blood biomarkers, and conducted on patients with traumatic brain injuries older than 16 years were included in the review. (3) Results: In total, 17 studies were included. Findings on neurofilament light chain, proteins, metabolites, lipids, amyloid-β, tau, melatonin, thyroid hormones, microtubule-associated protein 2, neuron-specific enolase, and brain-derived neurotrophic factor were included in the qualitative synthesis. (4) Conclusions: The most promising applications for CSF and blood biomarkers are the monitoring of secondary neurodegeneration, support of DoC diagnoses, and refinement of prognoses, although current evidence remains too scarce to recommend such uses of these biomarkers in clinical practice.
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Cortese, Maria Daniela, Francesco Arcuri, Martina Vatrano, et al. "Wessex Head Injury Matrix in Patients with Prolonged Disorders of Consciousness: A Reliability Study." Biomedicines 12, no. 1 (2023): 82. http://dx.doi.org/10.3390/biomedicines12010082.
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Introduction: The Wessex Head Injury Matrix (WHIM) was developed to assess patients with disorders of consciousness (DOC) and was tested in terms of inter-rater reliability (IRR) and test–retest reliability (TRR) in the year 2000. The American Congress of Rehabilitation and Medicine reported that IRR and TRR were unproven. We aim to assess the reliability of the WHIM in prolonged DOC patients (PDOC). Methods: A total of 51 PDOC patients (32 unresponsive wakefulness syndrome (UWS/VS) and 19 minimally conscious state (MCS)) who were hosted in a dedicated unit for long-term brain injury care were enrolled. The time from injury ranged from 182 to 3325 days. Two raters administered the Coma Recovery Scale-Revised (CRS-R) and the WHIM to test the IRR and TRR. The TRR was administered two weeks after the first assessment. Results: For the CRS-R, the agreement in IRR and TRR was perfect between the two raters. The agreement for the WHIM ranged from substantial to almost perfect for IRR and from fair to substantial for the TRR. Conclusions: The WHIM showed a strong IRR when administered by expert raters and strongly correlated with the CRS-R. This study provides further evidence of the psychometric qualities of the WHIM and the importance of its use in PDOC patients.
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Ferré, Fabrice, Lizette Heine, Edouard Naboulsi, et al. "Self-processing in coma, unresponsive wakefulness syndrome and minimally conscious state." Frontiers in Human Neuroscience 17 (April 12, 2023). http://dx.doi.org/10.3389/fnhum.2023.1145253.
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IntroductionBehavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness.MethodsHence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject’s own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN (‘SON effect’, primary endpoint assessed by temporal clustering permutation tests).ResultsPatients were either coma (n = 38), unresponsive wakefulness syndrome (UWS, n = 30) or minimally conscious state (MCS, n = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a ‘SON effect’. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients (p = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients (p = 0.013 for comparison between groups). Among the 72 survivors’ patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome.DiscussionAbout 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome.
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Carrière, Manon, Helena Cassol, Charlène Aubinet, et al. "Auditory localization should be considered as a sign of minimally conscious state based on multimodal findings." Brain Communications 2, no. 2 (2020). http://dx.doi.org/10.1093/braincomms/fcaa195.
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Abstract Auditory localization (i.e. turning the head and/or the eyes towards an auditory stimulus) is often part of the clinical evaluation of patients recovering from coma. The objective of this study is to determine whether auditory localization could be considered as a new sign of minimally conscious state, using a multimodal approach. The presence of auditory localization and the clinical outcome at 2 years of follow-up were evaluated in 186 patients with severe brain injury, including 64 with unresponsive wakefulness syndrome, 28 in minimally conscious state minus, 71 in minimally conscious state plus and 23 who emerged from the minimally conscious state. Brain metabolism, functional connectivity and graph theory measures were investigated by means of 18F-fluorodeoxyglucose positron emission tomography, functional MRI and high-density electroencephalography in two subgroups of unresponsive patients, with and without auditory localization. These two subgroups were also compared to a subgroup of patients in minimally conscious state minus. Auditory localization was observed in 13% of unresponsive patients, 46% of patients in minimally conscious state minus, 62% of patients in minimally conscious state plus and 78% of patients who emerged from the minimally conscious state. The probability to observe an auditory localization increased along with the level of consciousness, and the presence of auditory localization could predict the level of consciousness. Patients with auditory localization had higher survival rates (at 2-year follow-up) than those without localization. Differences in brain function were found between unresponsive patients with and without auditory localization. Higher connectivity in unresponsive patients with auditory localization was measured between the fronto-parietal network and secondary visual areas, and in the alpha band electroencephalography network. Moreover, patients in minimally conscious state minus significantly differed from unresponsive patients without auditory localization in terms of brain metabolism and alpha network centrality, whereas no difference was found with unresponsive patients who presented auditory localization. Our multimodal findings suggest differences in brain function between unresponsive patients with and without auditory localization, which support our hypothesis that auditory localization should be considered as a new sign of minimally conscious state. Unresponsive patients showing auditory localization should therefore no longer be considered unresponsive but minimally conscious. This would have crucial consequences on these patients’ lives as it would directly impact the therapeutic orientation or end-of-life decisions usually taken based on the diagnosis.
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Porcaro, Camillo, Idan Efim Nemirovsky, Francesco Riganello, et al. "Diagnostic Developments in Differentiating Unresponsive Wakefulness Syndrome and the Minimally Conscious State." Frontiers in Neurology 12 (January 13, 2022). http://dx.doi.org/10.3389/fneur.2021.778951.
Full textAbstract:
When treating patients with a disorder of consciousness (DOC), it is essential to obtain an accurate diagnosis as soon as possible to generate individualized treatment programs. However, accurately diagnosing patients with DOCs is challenging and prone to errors when differentiating patients in a Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) from those in a Minimally Conscious State (MCS). Upwards of ~40% of patients with a DOC can be misdiagnosed when specifically designed behavioral scales are not employed or improperly administered. To improve diagnostic accuracy for these patients, several important neuroimaging and electrophysiological technologies have been proposed. These include Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), and Transcranial Magnetic Stimulation (TMS). Here, we review the different ways in which these techniques can improve diagnostic differentiation between VS/UWS and MCS patients. We do so by referring to studies that were conducted within the last 10 years, which were extracted from the PubMed database. In total, 55 studies met our criteria (clinical diagnoses of VS/UWS from MCS as made by PET, fMRI, EEG and TMS- EEG tools) and were included in this review. By summarizing the promising results achieved in understanding and diagnosing these conditions, we aim to emphasize the need for more such tools to be incorporated in standard clinical practice, as well as the importance of data sharing to incentivize the community to meet these goals.