Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients?

Patients with Prolonged Disorders of Consciousness (PDOC) have catastrophic disabilities and very complex needs for care. Therapeutic options are very limited, and patients often show little functional improvement over time. Neuroimaging studies have demonstrated that a significant number of PDOC patients retain a high level of cognitive functioning, and in some cases even awareness, and are simply unable to show this with their external behavior - a condition known as cognitive-motor dissociation (CMD). Despite vast implications for diagnosis, the discovery of covert cognition in PDOC patients is not typically associated with a more favorable prognosis, and the majority of patients will remain in a permanent state of low responsiveness. Recently, transcranial direct current stimulation (tDCS) has attracted attention as a potential therapeutic tool in PDOC. Research to date suggests that tDCS can lead to clinical improvements in patients with a minimally conscious state (MCS), especially when administered over multiple sessions. While promising, the outcomes of these studies have been highly inconsistent, partially due to small sample sizes, heterogeneous methodologies (in terms of both tDCS parameters and outcome measures), and limitations related to electrode placement and heterogeneity of brain damage inherent to PDOC. In addition, we argue that neuroimaging and electrophysiological assessments may serve as more sensitive biomarkers to identify changes after tDCS that are not yet apparent behaviorally. Finally, given the evidence that concurrent brain stimulation and physical therapy can enhance motor rehabilitation, we argue that future studies should focus on the integration of tDCS with conventional rehabilitation programmes from the subacute phase of care onwards, to ascertain whether any synergies exist.

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When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress

Brain Sciences ◽

10.3390/brainsci11010126 ◽

2021 ◽

Vol 11 (1) ◽

pp. 126

Author(s):

Enrique Noé ◽

Joan Ferri ◽

José Olaya ◽

María Dolores Navarro ◽

Myrtha O’Valle ◽

...

Keyword(s):

Clinical Decision Making ◽

Minimally Conscious State ◽

Clinical Decision ◽

Total Sample ◽

Conscious State ◽

Accurate Estimation ◽

Functional Communication ◽

Unresponsive Wakefulness Syndrome ◽

Object Use ◽

Minimally Conscious

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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Functional Brain Network Topology Discriminates between Patients with Minimally Conscious State and Unresponsive Wakefulness Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm8030306 ◽

2019 ◽

Vol 8 (3) ◽

pp. 306 ◽

Cited By ~ 12

Author(s):

Alberto Cacciola ◽

Antonino Naro ◽

Demetrio Milardi ◽

Alessia Bramanti ◽

Leonardo Malatacca ◽

...

Keyword(s):

Functional Connectivity ◽

Network Topology ◽

Minimally Conscious State ◽

Conscious State ◽

Clustering Coefficient ◽

Unresponsive Wakefulness Syndrome ◽

Topological Network ◽

Functional Brain Network ◽

Minimally Conscious ◽

Nodal Level

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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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 ◽

10.17816/jowd77930 ◽

2021 ◽

Vol 70 (5) ◽

pp. 23-36

Author(s):

Ekaterina A. Kondratyeva ◽

Alina O. Ivanova ◽

Maria I. Yarmolinskaya ◽

Elena G. Potyomkina ◽

Natalya V. Dryagina ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Blood Serum ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Unresponsive Wakefulness Syndrome ◽

Level Of Consciousness ◽

Chronic Disorders ◽

Minimally Conscious ◽

Chronic Disorders Of Consciousness

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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When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Functional Independence

Brain Sciences ◽

10.3390/brainsci10120990 ◽

2020 ◽

Vol 10 (12) ◽

pp. 990

Author(s):

José Olaya ◽

Enrique Noé ◽

María Dolores Navarro ◽

Myrtha O’Valle ◽

Carolina Colomer ◽

...

Keyword(s):

Minimally Conscious State ◽

Functional Independence ◽

Conscious State ◽

Functional Improvement ◽

Accurate Estimation ◽

Unresponsive Wakefulness Syndrome ◽

Functional Changes ◽

Domain Specific ◽

One Year ◽

Minimally Conscious

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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