scholarly journals Serum BDNF Levels Are Reduced in Patients with Disorders of Consciousness and Are Not Modified by Verticalization with Robot-Assisted Lower-Limb Training

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sergio Bagnato ◽  
Giuseppe Galardi ◽  
Francesco Ribaudo ◽  
Cristina Boccagni ◽  
Teresa Valentina Fiorilla ◽  
...  
Keyword(s):  
Lower Limb ◽  
Brain Injuries ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Robot Assisted ◽  
Rehabilitative Treatment ◽  
Before And After ◽  
Plastic Changes ◽  
Serum Bdnf

Little is known about plastic changes occurring in the brains of patients with severe disorders of consciousness (DOCs) caused by acute brain injuries at rest and during rehabilitative treatment. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity whose production is powerfully modulated by physical exercise. In this study, we compared serum BDNF levels in 18 patients with unresponsive wakefulness syndrome (UWS) and in a minimally conscious state (MCS) with those in 16 sex- and age-matched healthy controls. In 12 patients, serum BDNF levels before and after verticalization with ErigoPro robot-assisted lower-limb training were compared. Serum BDNF levels were significantly lower in patients (median, 1141 pg/ml; 25th and 75th percentiles, 1016 and 1704 pg/ml) than in controls (median, 2450 pg/ml; 25th and 75th percentiles, 2100 and 2875 pg/ml; p<0.001). BDNF levels measured before and after verticalization with robot-assisted lower-limb training did not change (p=0.5). Moreover, BDNF levels did not differ between patients with UWS and MCS (p=0.2), or between patients with traumatic and nontraumatic brain injuries (p=0.6). BDNF level correlated positively with the time since brain injury (p=0.025). In conclusion, serum BDNF levels are reduced in patients with UWS and MCS and cannot be improved by verticalization associated with passive lower-limb training. Additional studies are needed to better understand the mechanisms underlying BDNF reduction in patients with DOCs and to determine the best rehabilitative strategies to promote restorative plastic changes in these patients.

scholarly journals Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness

2019 ◽  
Author(s):  
Bertrand Hermann ◽  
Federico Raimondo ◽  
Lukas Hirsch ◽  
Yu Huang ◽  
Mélanie Denis-Valente ◽  
...  
Keyword(s):  
Electric Fields ◽  
Brain Injuries ◽  
Causal Effect ◽  
Brain Activity ◽  
Vegetative State ◽  
Behavioral Assessment ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Open Label

ABSTRACTSevere brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

scholarly journals Music Stimulation for People with Disorders of Consciousness: A Scoping Review

2021 ◽  
Vol 11 (7) ◽  
pp. 858
Author(s):  
Giulio E. Lancioni ◽  
Nirbhay N. Singh ◽  
Mark F. O’Reilly ◽  
Jeff Sigafoos ◽  
Lorenzo Desideri
Keyword(s):  
Scoping Review ◽  
Brain Injuries ◽  
Vegetative State ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Intervention Programs ◽  
Interactive Music ◽  
Minimally Conscious ◽  
The Impact

Music stimulation is considered to be a valuable form of intervention for people with severe brain injuries and prolonged disorders of consciousness (i.e., unresponsive wakefulness/vegetative state or minimally conscious state). This review was intended to provide an overall picture of work conducted during the last decade to assess the impact of music on behavioral and non-behavioral responses of people with disorders of consciousness. Following the PRISMA-ScR checklist, a scoping review was carried out to identify and provide a synthesis of eligible studies published in English during the 2010–2021 period. Three databases (i.e., PubMed, PsycINFO, and Web of Science) were employed for the literature search. Thirty-four studies met the inclusion criteria. Those studies were grouped into three categories based on whether they assessed the effects of: (i) recorded music, (ii) interactive music, or (iii) response-contingent music. A narrative synthesis of the studies of each of the three categories was eventually provided. While the studies of all three categories reported fairly positive/encouraging results, several methodological questions make it difficult to draw conclusions about those results and their implications for intervention programs in daily contexts.

scholarly journals Treating Traumatic Brain Injuries with Electroceuticals: Implications for the Neuroanatomy of Consciousness

NeuroSci ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 254-265
Author(s):  
Jihad Aburas ◽  
Areej Aziz ◽  
Maryam Butt ◽  
Angela Leschinsky ◽  
Marsha L. Pierce
Keyword(s):  
Brain Stimulation ◽  
Brain Injuries ◽  
Vegetative State ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Permanent Disability ◽  
United States Food ◽  
Control And Prevention ◽  
Minimally Conscious

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.

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

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.

scholarly journals Practice guideline update recommendations summary: Disorders of consciousness

Neurology ◽  
2018 ◽  
Vol 91 (10) ◽  
pp. 450-460 ◽  
Author(s):  
Joseph T. Giacino ◽  
Douglas I. Katz ◽  
Nicholas D. Schiff ◽  
John Whyte ◽  
Eric J. Ashman ◽  
...  
Keyword(s):  
Vegetative State ◽  
Persistent Vegetative State ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Case Definition ◽  
Disorders Of Consciousness ◽  
Family Counseling ◽  
Delphi Consensus ◽  
Post Injury ◽  
Term Care

ObjectiveTo update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition on minimally conscious state (MCS) and provide care recommendations for patients with prolonged disorders of consciousness (DoC).MethodsRecommendations were based on systematic review evidence, related evidence, care principles, and inferences using a modified Delphi consensus process according to the AAN 2011 process manual, as amended.RecommendationsClinicians should identify and treat confounding conditions, optimize arousal, and perform serial standardized assessments to improve diagnostic accuracy in adults and children with prolonged DoC (Level B). Clinicians should counsel families that for adults, MCS (vs vegetative state [VS]/unresponsive wakefulness syndrome [UWS]) and traumatic (vs nontraumatic) etiology are associated with more favorable outcomes (Level B). When prognosis is poor, long-term care must be discussed (Level A), acknowledging that prognosis is not universally poor (Level B). Structural MRI, SPECT, and the Coma Recovery Scale–Revised can assist prognostication in adults (Level B); no tests are shown to improve prognostic accuracy in children. Pain always should be assessed and treated (Level B) and evidence supporting treatment approaches discussed (Level B). Clinicians should prescribe amantadine (100–200 mg bid) for adults with traumatic VS/UWS or MCS (4–16 weeks post injury) to hasten functional recovery and reduce disability early in recovery (Level B). Family counseling concerning children should acknowledge that natural history of recovery, prognosis, and treatment are not established (Level B). Recent evidence indicates that the term chronic VS/UWS should replace permanent VS, with duration specified (Level B). Additional recommendations are included.

Non-Invasive Rhythmic Musical-Electric Trigeminal Nerve Stimulation Improves Consciousness in Patients with Disorders of Consciousness

2021 ◽  
Author(s):  
Min Wu ◽  
Benyan Luo ◽  
Yamei Yu ◽  
Xiaoxia Li ◽  
Jian Gao ◽  
...  
Keyword(s):  
Trigeminal Nerve ◽  
Nerve Stimulation ◽  
Brain Activity ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Non Invasive ◽  
Trigeminal Nerve Stimulation ◽  
Novel Approach ◽  
Minimally Conscious

Abstract Disorders of consciousness (DOC) are often accompanied by aberrant oscillatory neural activity in the thalamus and cerebral cortex. Patient-friendly non-invasive treatments targeting this functional anomaly are still missing. We propose and validate a novel approach that aims to restore DOC patients’ thalamocortical oscillations by combining rhythmic trigeminal-nerve stimulation (TNS) with comodulated musical stimulation. In a cluster-randomized, placebo-controlled, double-blinded, pretest-posttest clinical study, we show that application of this multisensory approach for 40 min on five consecutive days reliably leads to long-lasting improvements in DOC patients’ consciousness (assessed with Coma Recovery Scale-Revised) and oscillatory brain activity at the musical-electric TNS frequency (assessed with electroencephalography and a novel rhythmic auditory-speech paradigm). We found diagnostic improvement in 47% of patients in minimally conscious state and a positive relationship between patients’ behavioral and neural improvements. Based on this evidence we argue that non-invasive musical-electric TNS may serve as an effective patient-friendly DOC treatment and suggest frequency-specific oscillatory neural enhancement as its mode of action.

scholarly journals Covert Cognition in Disorders of Consciousness: A Meta-Analysis

2020 ◽  
Vol 10 (12) ◽  
pp. 930
Author(s):  
Caroline Schnakers ◽  
Michaela Hirsch ◽  
Enrique Noé ◽  
Roberto Llorens ◽  
Nicolas Lejeune ◽  
...  
Keyword(s):  
Observational Studies ◽  
Functional Neuroimaging ◽  
Vegetative State ◽  
Meta Analysis ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Demographic Variables ◽  
Disorders Of Consciousness ◽  
Minimally Conscious ◽  
Increase Sample Size

Covert cognition in patients with disorders of consciousness represents a real diagnostic conundrum for clinicians. In this meta-analysis, our main objective was to identify clinical and demographic variables that are more likely to be associated with responding to an active paradigm. Among 2018 citations found on PubMed, 60 observational studies were found relevant. Based on the QUADAS-2, 49 studies were considered. Data from 25 publications were extracted and included in the meta-analysis. Most of these studies used electrophysiology as well as counting tasks or mental imagery. According to our statistical analysis, patients clinically diagnosed as being in a vegetative state and in a minimally conscious state minus (MCS−) show similar likelihood in responding to active paradigm and responders are most likely suffering from a traumatic brain injury. In the future, multi-centric studies should be performed in order to increase sample size, with similar methodologies and include structural and functional neuroimaging in order to identify cerebral markers related to such a challenging diagnosis.

Disorders of Consciousness and Neuro-Palliative Care

2015 ◽  
Author(s):  
Joseph J. Fins ◽  
Maria Masters
Keyword(s):  
Palliative Care ◽  
Brain Injury ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Right To Die ◽  
Severe Brain Injury ◽  
Brain States ◽  
The Right ◽  
Minimally Conscious

This chapter explains how neuro-palliative care can be provided to patients with severe brain injury. Before arguing that the right to die must be preserved and that the right to care for patients who are minimally conscious must be supported, it defines and reviews brain states that constitute disorders of consciousness along with their differential biology. It then gives an overview of palliative care for patients with severe brain injury and the challenges involved in diagnosing the minimally conscious state. It proceeds by discussing advances in technology, particularly neuroimaging, that may help meet the needs of such patients. It also considers the neuroethics of diagnosis and concludes by suggesting ways to integrate the needs of individuals suffering from disorders of consciousness in both the local and national palliative care infrastructure.

scholarly journals Neuroimaging Studies on Disorders of Consciousness: A Meta-Analytic Evaluation

2019 ◽  
Vol 8 (4) ◽  
pp. 516 ◽  
Author(s):  
Manuela Berlingeri ◽  
Francesca Giulia Magnani ◽  
Gerardo Salvato ◽  
Mario Rosanova ◽  
Gabriella Bottini
Keyword(s):  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Subcortical Region ◽  
Specific Category ◽  
Estimate Method ◽  
Large Heterogeneity ◽  
Methodological Approaches ◽  
Minimally Conscious ◽  
Dorsal Attentional Network

Neuroimaging tools could open a window on residual neurofunctional activity in the absence of detectable behavioural responses in patients with disorders of consciousness (DOC). Nevertheless, the literature on this topic is characterised by a large heterogeneity of paradigms and methodological approaches that can undermine the reproducibility of the results. To explicitly test whether task-related functional magnetic resonance imaging (fMRI) can be used to systematically detect neurofunctional differences between different classes of DOC, and whether these differences are related with a specific category of cognitive tasks (either active or passive), we meta-analyzed 22 neuroimaging studies published between 2005 and 2017 using the Activation Likelihood Estimate method. The results showed that: (1) active and passive tasks rely on well-segregated patterns of activations; (2) both unresponsive wakeful syndrome and patients in minimally conscious state activated a large portion of the dorsal-attentional network; (3) shared activations between patients fell mainly in the passive activation map (7492 voxels), while only 48 voxels fell in a subcortical region of the active-map. Our results suggest that DOCs can be described along a continuum—rather than as separated clinical categories—and characterised by a widespread dysfunction of brain networks rather than by the impairment of a well functionally anatomically defined one.

All things considered: Surrogate decision-making on behalf of patients in the minimally conscious state

2020 ◽  
Vol 15 (3) ◽  
pp. 111-119
Author(s):  
L Syd M Johnson ◽  
Kathy L Cerminara
Keyword(s):  
Decision Making ◽  
Medical Decision Making ◽  
Vegetative State ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Medical Decision ◽  
Surrogate Decision Making ◽  
Surrogate Decision ◽  
Minimally Conscious

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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