Spontaneous eye blinking as a diagnostic marker in prolonged disorders of consciousness

AbstractClinical diagnosis of patients with prolonged disorders of consciousness is very challenging. As spontaneous eye blink rate (EBR) is reliably correlated with cognitive activity in healthy individuals, we investigated whether EBR could serve as a marker of patients’ level of consciousness. We assessed ten patients in prolonged Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS; three females; mean age = 50.3 ± 17.8 years) and fourteen patients in Minimally Conscious State (MCS; three females; mean age = 52.9 ± 17.5 years) at their admission to a rehabilitation unit after the acute phase. During two separate 3-min rest conditions, we recorded patients’ EBR by integrating on-line visual and off-line electro-oculographic count. We also assessed EBR during two auditory oddball tasks, i.e. passive listening and active counting of target tones in a sub-group of patients. EBR was significantly higher in MCS than in VS/UWS; moreover, EBR positively correlated with a validated index of responsiveness derived from the Coma Recovery Scale-Revised. Patients’ mean EBR showed no significant differences within sessions and across experimental conditions of the oddball task, in both VS/UWS and MCS. Our findings suggest that, at least in the post-acute phase, observing patients’ EBR for 3 min at rest could help to discriminate between VS/UWS and MCS, improving accuracy of clinical diagnosis.

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Practice guideline update recommendations summary: Disorders of consciousness

Neurology ◽

10.1212/wnl.0000000000005926 ◽

2018 ◽

Vol 91 (10) ◽

pp. 450-460 ◽

Cited By ~ 90

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.

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Covert Cognition in Disorders of Consciousness: A Meta-Analysis

Brain Sciences ◽

10.3390/brainsci10120930 ◽

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.

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

Clinical Ethics ◽

10.1177/1477750920927177 ◽

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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Prolonged Disorders of Consciousness

Journal of the Korean Neurological Association ◽

10.17340/jkna.2020.1.2 ◽

2020 ◽

Vol 38 (1) ◽

pp. 9-15

Author(s):

Daeyoung Kim

Keyword(s):

Vegetative State ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Assessment Tools ◽

Impaired Consciousness ◽

Transitional State ◽

Impaired Awareness ◽

Minimally Conscious ◽

Recovery Of Consciousness

Prolonged disorders of consciousness comprise a spectrum of impaired consciousness where arousal is preserved with impaired awareness, which last more than 4 weeks. Vegetative state is a prototype of the prolonged disorders of consciousness. A patient in the vegetative state has no signs of awareness. The minimally conscious state is characterized by inconsistent but reproducible signs of awareness and is regarded as a transitional state of recovery of consciousness. Differentiating patients in minimally conscious state from those in vegetative state is still challenging. Utilizing standardized neurobehavioral assessment tools could improve diagnostic accuracy. Recent advances in neuroimaging and electrophysiologic tools may aid the diagnosis and prognostication. Treatment for recovery of consciousness is still limited. More research on the diagnosis and treatment of prolonged disorders of consciousness is needed not only for improved care of patients with prolonged disorders of consciousness but also a greater understanding of human consciousness.

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Zolpidem Action During Prolonged Disorders of Consciousness (Case Report)

General Reanimatology ◽

10.15360/1813-9779-2019-5-44-60 ◽

2019 ◽

Vol 15 (5) ◽

pp. 44-60 ◽

Cited By ~ 1

Author(s):

E. A. Kondratyeva ◽

M. V. Sinkin ◽

E. V. Sharova ◽

S. Laureys ◽

A. N. Kondratyev

Keyword(s):

Vegetative State ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Eeg Monitoring ◽

Unresponsive Wakefulness Syndrome ◽

Favorable Prognosis ◽

Eeg Activation ◽

Minimally Conscious ◽

Electroencephalogram Eeg

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

10.1101/612309 ◽

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.

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Judicial oversight of life-ending withdrawal of assisted nutrition and hydration in disorders of consciousness in the United Kingdom: A matter of life and death

Medico-Legal Journal ◽

10.1177/0025817217702289 ◽

2017 ◽

Vol 85 (3) ◽

pp. 148-154 ◽

Cited By ~ 6

Author(s):

Mohamed Y Rady ◽

Joseph L. Verheijde

Keyword(s):

Vegetative State ◽

Minimally Conscious State ◽

Conscious State ◽

Disabled Persons ◽

Disorders Of Consciousness ◽

Best Interests ◽

Life And Death ◽

Decision Making Capacity ◽

Nutrition And Hydration ◽

Minimally Conscious

Mr Justice Baker delivered the Oxford Shrieval Lecture ‘A Matter of Life and Death’ on 11 October 2016. The lecture created public controversies about who can authorise withdrawal of assisted nutrition and hydration (ANH) in disorders of consciousness (DOC). The law requires court permission in ‘best interests’ decisions before ANH withdrawal only in permanent vegetative state and minimally conscious state. Some clinicians favour abandoning the need for court approval on the basis that clinicians are already empowered to withdraw ANH in other common conditions of DOC (e.g. coma, neurological disorders, etc.) based on their best interests assessment without court oversight. We set out a rationale in support of court oversight of best interests decisions in ANH withdrawal intended to end life in any person with DOC (who will lack relevant decision-making capacity). This ensures the safety of the general public and the protection of vulnerable disabled persons in society.

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Information processing in severe disorders of consciousness: Vegetative state and minimally conscious state

Clinical Neurophysiology ◽

10.1016/j.clinph.2005.03.028 ◽

2005 ◽

Vol 116 (10) ◽

pp. 2441-2453 ◽

Cited By ~ 213

Author(s):

B. Kotchoubey ◽

S. Lang ◽

G. Mezger ◽

D. Schmalohr ◽

M. Schneck ◽

...

Keyword(s):

Information Processing ◽

Vegetative State ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Minimally Conscious

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Is Period3 Genotype Associated With Sleep and Recovery in Patients With Disorders of Consciousness?

Neurorehabilitation and Neural Repair ◽

10.1177/1545968315604398 ◽

2015 ◽

Vol 30 (5) ◽

pp. 461-469 ◽

Cited By ~ 4

Author(s):

Gloria Bedini ◽

Anna Bersano ◽

Davide Rossi Sebastiano ◽

Davide Sattin ◽

Francesca Ciaraffa ◽

...

Keyword(s):

Slow Wave Sleep ◽

Total Sleep Time ◽

Vegetative State ◽

Minimally Conscious State ◽

Sleep Time ◽

Conscious State ◽

Disorders Of Consciousness ◽

Sleep Quantity ◽

Minimally Conscious ◽

Post Hoc

Background. Sleep evaluation is increasingly being used as prognostic tool in patients with disorders of consciousness, but, surprisingly, the role of Period3 (Per3) gene polymorphism has never been evaluated. Objective. The aim of this study was to investigate the contribution of Per3 genotype on sleep quantity and consciousness recovery level in patients with disorders of consciousness (DOC). Methods. In this observational study, we evaluated 71 patients with DOC classified as vegetative state/unresponsive wakefulness syndrome or minimally conscious state. Demographic and clinical data were collected and a standardised diagnostic workup, including a polysomnographic record, was applied. After informed consent provided by proxy, genomic DNA was obtained and Per3 polymorphism was analysed by polymerase chain reaction to identify 5/5, 4/5, or 4/4 genotype. Results. Per35/5genotype was found in 12.7% of our DOC patients. The median total Coma Recovery Scale–revised score in Per35/5carriers was significantly higher than 4/4 genotype (10, range 5-16 vs 7, range 4-11; post hoc P = .036). Moreover, total sleep time seemed to be higher in 5/5 genotype ( 5/5, 221 minutes, range 88-515 minutes; 4/4, 151.5 minutes, range 36-477 minutes; and 4/5, 188 minutes, range 44-422 minutes). Conclusion. For the first time we have shown a possible association between Per3 polymorphism and consciousness recovery level in DOC patients. Even though the exact molecular mechanism has not been defined, we speculate that its effect is mediated by higher total sleep time and slow wave sleep, which would improve the preservation of main cerebral connections.

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Feasibility of Non-Gaussian Diffusion Metrics in Chronic Disorders of Consciousness

Brain Sciences ◽

10.3390/brainsci9050123 ◽

2019 ◽

Vol 9 (5) ◽

pp. 123

Author(s):

Elena I. Kremneva ◽

Liudmila A. Legostaeva ◽

Sofya N. Morozova ◽

Dmitry V. Sergeev ◽

Dmitry O. Sinitsyn ◽

...

Keyword(s):

Vegetative State ◽

False Negative ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Diffusion Kurtosis Imaging ◽

Brain State ◽

Chronic Disorders ◽

Non Gaussian ◽

Chronic Disorders Of Consciousness

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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