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Concept: Persistent vegetative state

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Background The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. Methods From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to “upper good recovery” [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. Results The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). Conclusions At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).

Concepts: Clinical trial, Traumatic brain injury, Intracranial pressure, Intracranial hemorrhage, Neurotrauma, Brain herniation, Persistent vegetative state, Decompressive craniectomy

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Patients lying in a vegetative state present severe impairments of consciousness [1] caused by lesions in the cortex, the brainstem, the thalamus and the white matter [2]. There is agreement that this condition may involve disconnections in long-range cortico-cortical and thalamo-cortical pathways [3]. Hence, in the vegetative state cortical activity is ‘deafferented’ from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity [3]. The likelihood of consciousness recovery depends on the extent of brain damage and patients' etiology, but after one year of unresponsive behavior, chances become low [1]. There is thus a need to explore novel ways of repairing lost consciousness. Here we report beneficial effects of vagus nerve stimulation on consciousness level of a single patient in a vegetative state, including improved behavioral responsiveness and enhanced brain connectivity patterns.

Concepts: Psychology, Neuroanatomy, Traumatic brain injury, Cerebral cortex, Neurology, Cerebrum, Vagus nerve stimulation, Persistent vegetative state

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Life-extending treatment, in the form of artificial nutrition and hydration, is often provided to people in permanent vegetative states (PVS) in England and Wales for many years, even when their family believes the patient would not want it and despite the fact that no court in the UK has ever found in favour of continuing such treatment for a patient with a confirmed PVS diagnosis. The first half of this article presents a close analysis of the recent case of Cumbria NHS Clinical Commissioning Group v Miss S and Ors [2016] EWCOP 32. It examines the causes of delay in bringing this case to court and reaching a final judgment. It draws not only on the published judgment, but also on the two authors' involvement in supporting the family (before, during and subsequent to the court hearings) as a result of their academic and policy-related work in this area. This includes conversations with the family and with members of the clinical and legal teams, and observations in court. The second part of the article draws out the ethical and practical implications of the findings for theory and policy and suggests ways forward in relation to (a) the provision and inspection of care for these patients; (b) legal practice in relation to ‘best interests’ and © the perceived requirement under English law for a court application before life-prolonging treatment can be withdrawn from PVS patients-even in the absence of any ‘in principle’ opposition.

Concepts: Scientific method, Patient, United Kingdom, England, Appeal, Wales, English law, Persistent vegetative state

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In W v M, family members made an application to the Court of Protection for withdrawal of artificial nutrition and hydration from a minimally conscious patient. Subsequent scholarly discussion has centred around the ethical adequacy of the judge’s decision not to authorise withdrawal. This article brings a different perspective by drawing on interviews with 51 individuals with a relative who is (or was) in a vegetative or minimally conscious state (MCS). Most professional medical ethicists have treated the issue as one of life versus death; by contrast, families-including those who believed that their relative would not have wanted to be kept alive-focused on the manner of the proposed death and were often horrified at the idea of causing death by ‘starvation and dehydration’. The practical consequence of this can be that people in permanent vegetative state (PVS) and MCS are being administered life-prolonging treatments long after their families have come to believe that the patient would rather be dead. We suggest that medical ethicists concerned about the rights of people in PVS/MCS need to take this empirical data into account in seeking to apply ethical theories to medico-legal realities.

Concepts: Scientific method, Death, Consciousness, Empiricism, Coma, Persistent vegetative state, Brain death, Minimally conscious state

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BACKGROUND:: To investigate the efficacy and indications of zolpidem, a nonbenzodiazepine hypnotic, inducing arousal in vegetative state patients after brain injury. METHODS:: One hundred sixty-five patients were divided into 4 groups, according to area of brain damage and injury mechanism. All patients' brains were imaged by Tc-ECD single-photon emission computerized tomography (SPECT), before and 1 hour after treatment with 10 mg of zolpidem. Simultaneously, 3 quantitative indicators of brain function and damage were obtained using cerebral state monitor. Thirty-eight patients withdrew from the study after the first zolpidem dose. The remaining 127 patients received a daily dose of 10 mg of zolpidem for 1 week and were monitored again at the end of this week. RESULTS:: One hour after treatment with zolpidem, cerebral state index was increased and burst suppression reduced in both brain contrecoup contusion and space-occupying brain compression groups (P < 0.05). SPECT showed, 1 hour after medication, that cerebral perfusion was improved in both brain contrecoup contusion and space-occupying brain compression groups, but no changes were seen in primary and secondary brain stem injury groups. In the 127 patients' group, after 1 week of zolpidem treatment, all parameters obtained from cerebral state monitor were not statistically different compared with those after the initial medication (P > 0.05). CONCLUSIONS:: Zolpidem is an effective medicine to restore brain function in patients in vegetative state after brain injury, especially for those whose brain injuries are mainly in non-brain-stem areas. Improvement of brain function is sudden rather than gradual.

Concepts: Traumatic brain injury, Medical imaging, Intracranial pressure, Neurology, Neurotrauma, Zolpidem, Persistent vegetative state, Nonbenzodiazepine

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Withdrawal of artificially delivered nutrition and hydration (ANH) from patients in a permanent vegetative state (PVS) requires judicial approval in England and Wales, even when families and healthcare professionals agree that withdrawal is in the patient’s best interests. Part of the rationale underpinning the original recommendation for such court approval was the reassurance of patients' families, but there has been no research as to whether or not family members are reassured by the requirement for court proceedings or how they experience the process. The research reported here draws on in-depth narrative interviews with 10 family members (from five different families) of PVS patients who have been the subject of court proceedings for ANH-withdrawal. We analyse the empirical evidence to understand how family members perceive and experience the process of applying to the courts for ANH-withdrawal and consider the ethical and practice implications of our findings. Our analysis of family experience supports arguments grounded in economic and legal analysis that court approval should no longer be required. We conclude with some suggestions for how we might develop other more efficient, just and humane mechanisms for reviewing best interests decisions about ANH-withdrawal from these patients.

Concepts: Family, Health care provider, Patient, United States, Consciousness, Empiricism, Experience, Persistent vegetative state

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Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation, enabled by efficient networks of information transfer across multiple scales. Here, we apply graph theory to compare key signatures of such networks in high-density electroencephalographic data from 32 patients with chronic disorders of consciousness, against normative data from healthy controls. Based on connectivity within canonical frequency bands, we found that patient networks had reduced local and global efficiency, and fewer hubs in the alpha band. We devised a novel topographical metric, termed modular span, which showed that the alpha network modules in patients were also spatially circumscribed, lacking the structured long-distance interactions commonly observed in the healthy controls. Importantly however, these differences between graph-theoretic metrics were partially reversed in delta and theta band networks, which were also significantly more similar to each other in patients than controls. Going further, we found that metrics of alpha network efficiency also correlated with the degree of behavioural awareness. Intriguingly, some patients in behaviourally unresponsive vegetative states who demonstrated evidence of covert awareness with functional neuroimaging stood out from this trend: they had alpha networks that were remarkably well preserved and similar to those observed in the controls. Taken together, our findings inform current understanding of disorders of consciousness by highlighting the distinctive brain networks that characterise them. In the significant minority of vegetative patients who follow commands in neuroimaging tests, they point to putative network mechanisms that could support cognitive function and consciousness despite profound behavioural impairment.

Concepts: Psychology, Brain, Cognition, Consciousness, Graph theory, Functional magnetic resonance imaging, Graph, Persistent vegetative state

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One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject’s ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain’s ability to support complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI). PCI is calculated by (i) perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration) and (ii) compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information). We test PCI on a large data set of TMS-evoked potentials recorded in healthy subjects during wakefulness, dreaming, nonrapid eye movement sleep, and different levels of sedation induced by anesthetic agents (midazolam, xenon, and propofol), as well as in patients who had emerged from coma (vegetative state, minimally conscious state, and locked-in syndrome). PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness. PCI can potentially be used for objective determination of the level of consciousness at the bedside.

Concepts: Cerebral cortex, Anesthesia, Consciousness, Transcranial magnetic stimulation, Coma, Persistent vegetative state, Brain death, Minimally conscious state

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Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI).

Concepts: Death, Positron emission tomography, Neuroimaging, Consciousness, Coma, Persistent vegetative state, Brain death, Minimally conscious state

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The Vegetative State (VS) is a severe disorder of consciousness in which patients are awake but display no signs of awareness. Yet, recent functional magnetic resonance imaging (fMRI) studies have demonstrated evidence for covert awareness in VS patients by recording specific brain activations during a cognitive task. However, the possible existence of incommunicable subjective emotional experiences in VS patients remains largely unexplored. This study aimed to probe the question of whether VS patients retain a brain ability to selectively process external stimuli according to their emotional value and look for evidence of covert emotional awareness in patients.

Concepts: Psychology, Brain, Brain tumor, Nuclear magnetic resonance, Magnetic resonance imaging, Mind, Consciousness, Persistent vegetative state