Patients In Persistent Vegetative State Research Articles

WAKEFULNESS AND LOSS OF AWARENESS: BRAIN AND BRAINSTEM INTERACTION IN THE VEGETATIVE STATE

Objective: The ascending reticular activating system (ARAS) modulates circadian wakefulness, which is preserved in a persistent vegetative state (PVS). Its metabolism is preserved. Impairment of metabolism in the polymodal associative cortices (i.e., precuneus) is characteristic of PVS where awareness is abolished. Because the interaction of these 2 structures allows conscious sensory perception, our hypothesis was that an impaired functional connectivity between them participates in the loss of conscious perception. Methods: 15 O-radiolabeled water PET measurement of regional cerebral blood flow (rCBF) was performed at rest and during a proprioceptive stimulation. Ten patients in PVS and 10 controls were compared in a cross-sectional study. The functional connectivity from the primary sensorimotor cortex (S1M1) and the ARAS in both groups was also investigated. Results: Compared with controls, patients showed significantly less rCBF in posterior medial cortices (precuneus) and higher rCBF in ARAS at rest. During stimulation, bilateral Brodmann area 40 was less activated and not functionally correlated to S1M1 in PVS as it was in controls. Precuneus showed a lesser degree of deactivation in patients. Finally, ARAS whose activity was functionally correlated to that of the precuneus in controls was not in PVS. Conclusions: Global neuronal workspace theory predicts that damage to long-distance white matter tracts should impair access to conscious perception. During persistent vegetative state, we identified a hypermetabolism in the ascending reticular activating system (ARAS) and impaired functional connectivity between the ARAS and the precuneus. This result emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network.

Wakefulness and loss of awareness

The ascending reticular activating system (ARAS) modulates circadian wakefulness, which is preserved in a persistent vegetative state (PVS). Its metabolism is preserved. Impairment of metabolism in the polymodal associative cortices (i.e., precuneus) is characteristic of PVS where awareness is abolished. Because the interaction of these 2 structures allows conscious sensory perception, our hypothesis was that an impaired functional connectivity between them participates in the loss of conscious perception. (15)O-radiolabeled water PET measurement of regional cerebral blood flow (rCBF) was performed at rest and during a proprioceptive stimulation. Ten patients in PVS and 10 controls were compared in a cross-sectional study. The functional connectivity from the primary sensorimotor cortex (S1M1) and the ARAS in both groups was also investigated. Compared with controls, patients showed significantly less rCBF in posterior medial cortices (precuneus) and higher rCBF in ARAS at rest. During stimulation, bilateral Brodmann area 40 was less activated and not functionally correlated to S1M1 in PVS as it was in controls. Precuneus showed a lesser degree of deactivation in patients. Finally, ARAS whose activity was functionally correlated to that of the precuneus in controls was not in PVS. Global neuronal workspace theory predicts that damage to long-distance white matter tracts should impair access to conscious perception. During persistent vegetative state, we identified a hypermetabolism in the ascending reticular activating system (ARAS) and impaired functional connectivity between the ARAS and the precuneus. This result emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network.

Heart rate variability changes induced by auditory stimulation in persistent vegetative state

Previous studies, using neuroimaging and electrophysiology, have identified the presence of cerebral responses to auditory stimulation in clinically unresponsive persistent vegetative state (PVS) patients. In normal individuals, it has been shown that stimulation with emotional content has a strong influence on autonomic cardiovascular regu­lation tested by heart rate variability (HRV). In this paper, we assessed responses to auditory stimulation with emotion­al content in PVS and minimally conscious (MCS) cases by HRV. We found a pattern of changes induced by auditory stimulation in three of our patients (decreased heart rate, increased HRV, decrease power in the low and increased power in high frequencies) consistent with increased cardiovagal stimulation. Both time and frequency domain changes were more pronounced during affective than during non-affective auditory stimulation, suggesting that PVS patients are able to discriminate between stimuli of different content and are more reactive to emotional than non-emotional stimulation. Our results demonstrate (is a conclusion, should be in present) that auditory stimulation can induce recordable changes in HRV in some PVS cases, providing evidence that these patients retain some preserved cognitive function examined by cardiovascular correlates. The use of HRV to study residual cognitive functions could have practical implications for the management of PVS and MCS.

MEDIA COVERAGE OF THE PERSISTENT VEGETATIVE STATE AND END-OF-LIFE DECISION-MAKING

Racine et al.1 described some aspects of Terri Schiavo’s life and death. Dr. Bernat’s2 accompanying editorial comments on the media aspects of this case. In 1991, I was part of a team at the University of California, San Francisco, that evaluated the brain and cognitive functions of Terri Schiavo and other patients in persistent vegetative states (PVS). These evaluations were carried out as part of an experimental treatment protocol conducted by Hosobuchi and Yingling.3 After presurgical evaluations were complete, Dr. Hosobuchi implanted 2 patients with stimulating electrodes in the high cervical spinal cord, and he implanted 4 patients with electrodes in the centrum medianum of the thalamus. Unfortunately, most of the patients in the study did not exhibit improvement because the extent of their brain damage was too severe to allow recovery of normal functions. Because Terri Schiavo was a member of the nonresponsive group, I agree with Michael Schiavo’s decision to end his wife’s life in 2005. Fifteen years seems long enough—too long, some might argue—to remain in such a state with no chance for improvement. I was motivated to write this correspondence by stories I have heard about several different individuals who unexpectedly entered a comatose state. In each of these cases, within 1 week of the onset of coma, physicians told family members …

Reply to the Jesuit Consortium*

Abstract Earlier this year, seven directors of bioethics programs at Jesuit universities, calling themselves the Consortium of Jesuit Bioethics Programs, published in Commonweal a critique of papal teaching on the moral requirement to provide food and water to patients in the so-called persistent vegetative state (PVS). 1 Their aim is to influence the American bishops against amending the Ethical and Religious Directives for Catholic Health Care Services (ERDs) to bring the directives in line with the March 2004 teaching of Pope John Paul II on PVS. 2 The amendment will be considered at the bishops' June 2009 meeting.

안락사와 연명치료중단에 관한 우리나라의 최근 동향*

Progress in biomedical technology has resulted in a number of patients experiencing painfully slow deaths by means of artificial ventilators or other inhumane treatments. Such experiences give rise to the question of whether it is right to provide these life-sustaining treatments when no effective or curative therapies are available. The purpose of this study is to examine respective views on this issue given by criminal law experts, the courts, medical professionals, and the public. In Korea, there is still disagreement on the definition of the terms “euthanasia” and “death with dignity.” The current criminal law prohibits euthanasia for a dying patient with incurable disease and the withdrawal of life-sustaining treatment for a patient in a persistent vegetative state (PVS). However, a group of judicial and bioethics experts and policy-makers think that euthanasia or the withdrawal of life-sustaining treatment can be permitted under certain conditions. A recent court decision, which permitted the withdrawal of life-sustaining treatment on a PVS patient based on the patient’s right to self-determination and medical futility has stimulated a nationwide discussion for developing a legal framework for dealing with this issue. However, this article argues that care is needed in drafting the appropriate legislation as many unsolved problems related to this issue remain.

Cortical sources of resting-state alpha rhythms are abnormal in persistent vegetative state patients

High power of pre-stimulus cortical alpha rhythms (about 8-12 Hz) underlies conscious perception in normal subjects. Here we tested the hypothesis that these rhythms are abnormal in persistent vegetative state (PVS) patients, who are awake but not aware of self and environment. Clinical and resting-state, eyes-closed electroencephalographic (EEG) data were taken from a clinical archive. These data were recorded in 50 PVS subjects (level of cognitive functioning--LCF score: I-II) and in 30 cognitively normal subjects. Rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical sources were estimated by low-resolution electromagnetic tomography (LORETA). Based on LCF score at 3-months follow-up, PVS patients were retrospectively divided into three groups: 30 subjects who did not recover (NON-REC patients; follow-up LCF: I-II), 8 subjects classified as minimally conscious state patients (MCS patients; follow-up LCF: III-IV), and 12 subjects who recovered (REC patients; follow-up LCF: V-VIII). Occipital source power of alpha 1 and alpha 2 was high in normal subjects, low in REC patients, and practically null in NON-REC patients. A Cox regression analysis showed that the power of alpha source predicted the rate of the follow up recovery, namely the higher its power, the higher the chance to recover consciousness. Furthermore, the MCS patients showed intermediate values of occipital alpha source power between REC and NON-REC patients. These results suggest that cortical sources of alpha rhythms are related to the chance of recovery at a 3-months follow-up in patients in persistent vegetative state. Cortical sources of resting alpha rhythms might predict recovery in PVS patients.

Dorsal Column Stimulation in Persistent Vegetative State

Objectives. The problem of treating patients in a vegetative state remains grossly unresolved, and spinal cord stimulation (SCS) had seemed promising in some studies, suggesting, to us, further study. Materials and Methods. A prospective uncontrolled and nonrandomized observational study for 20 consecutive years (1986-2005) was performed on the effect of SCS in 214 patients in persistent vegetative state (PVS) that resulted from global anoxia and/or, stroke and/or head injury. After confirming the condition of PVS, a spinal cord stimulator, at the C2-C4 level, was implanted, stimulating according to a protocol of 15-min on/15-min off during daytime only. The results were evaluated using an efficacy scale designed by us for our study, detecting signs of awareness of self and surrounding. Results. Excellent and positive results were obtained in 109 of 201 patients (54%), but better in those patients below the age of 35, those of PVS of traumatic origin and those patients with regional cerebral blood flow over 20mL/100g/min. Conclusions. These findings, though inconclusive of actual benefit of SCS for PVS, indicate to us that further evidence-based, randomized controlled trials are needed to confirm efficacy of the treatment and define those who are going to benefit from this treatment method.

Defining Human Death: An Intersection of Bioethics and Metaphysics

For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants.

Perception of pain in the minimally conscious state with PET activation: an observational study

Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.

Prevalence and associated factors of pneumonia in patients with vegetative state in Taiwan

The aim of this study was to investigate the prevalence rate and influencing factors of pneumonia associated with long-term tube feeding in special care units for patients with persistent vegetative states (PVS) in Taiwan. Pneumonia is a significant cause of morbidity, hospitalization and mortality in the nursing home population. Tube feeding has been found as a risk factor for the occurrence of pneumonia. Two hundred sixty subjects were chosen from three hospital-based special care units for patients with PVS and 10 nursing facilities for persons in PVS in Taiwan. All subjects, who were diagnosed with PVS, received either financial aid for institutional care or were means-tested from The Bureau of Social Welfare of cities and counties in Taiwan. Data were collected through chart review and observations. The prevalence rate of pneumonia in nursing facilities for patients with PVS was 14.2%. The prevalence rate of tube-feeding in nursing facilities for PVS was 91.2%. The mean duration of tube-feeding was 73.21 SD 55.33 months. A total of 90.4% was fed with a nasogastric (NG) tube. Having a lower intake of food and fluids daily and having been institutionalized for a shorter period were three dominant factors associated with the occurrence of pneumonia. Research findings reveal that the incidence of pneumonia is higher in patients who do not receive adequate food and water. Continuing in-service training to improve caregivers' knowledge and skill in providing care to patients in PVS and monitoring their skills in feeding is needed to decrease the occurrence of pneumonia in this population. Staff needs to be taught to monitor laboratory data and signs and symptoms of malnutrition and hydration deficit, and also be alert to early indicators of pneumonia in patients with PVS.

A MRS-MRI-fMRI exploration of the brain. Impact of long-lasting persistent vegetative state

Background: The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. However, very little is known about the actual degree of perception in these patients and the extent of progressive brain injury induced by very prolonged unawareness.Methods: The authors have conducted a 2-year longitudinal study using a multimodal MRI-MRSI-fMRI protocol in four patients in long-lasting PVS (over 3 years at inclusion) characterized by various brain injuries.Results: Although one subject showed initially preserved local brain metabolism and brain activity related to primary perception suggesting the presence of potential residual brain plasticity even in this critical stage, none of the four patients recovered to consciousness during the 2 years of the protocol. Moreover, significant deterioration of parameters related to brain atrophy, metabolism and functional excitability of primary cortices was observed in all patients during the follow-up.Conclusions: Heterogeneity of brain injury, consequences of long term minimal brain activity and potential factors that prevent recovery to consciousness are discussed.

Thalamic Stimulation Causes Arousal from a Minimally Conscious State

In a coma, there is no spontaneous organized behavior or even a response to irritating stimuli. Patients in a persistent vegetative state (PVS) are

Effect of Yishen Qiqiao Fang on dopamine content in serum and cerebrospinal fluid of patients in persistent vegetative statec*

Background It has been demonstrated that the attack of persistent vegetative state is associated with the damaged neuron, which produces dopamine, and nervous pathway, the reduce of dopamine or malfunction of dopamine. Objective To observe the effect of self-made traditional Chinese medicine (TCM) Yishen Qiqiao Fang, which has the functions of supplementing qi and nourishing blood, resolving phlegm by promoting blood circulation, restoring consciousness and inducing resuscitation, on the contents of dopamine in serum and cerebrospinal fluid of patients in persistent vegetative state. Design An open randomized controlled clinical trial. Settings Nanjing University of Traditional Chinese Medicine, Nanjing Zijin Hospital. Participants Thirty-eight inpatients of persistent vegetative state were selected from the Department of Neurology, Nanjing Zijin Hospital from August 2005 to November 2006. The patients were diagnosed according to the diagnostic standards set by the summary of a meeting for specialists in Nanjing. Informed contents were obtained from their relatives. According to the order of admission, the enrolled patients were divided into control group ( n =20) and TCM treated group ( n =20). Methods In the control group, the patients were treated with routine treatments for the symptoms. In the TCM treated group, the patients were treated with Yishen Qiqiao Fang besides the same treatments in the control group. TCM dispensing granules: each bag of mongolian milkvetch root, Chinese angelica and peach seed equaled to 10 g crude drug respectively; each bag of grassleaf sweetflag rhizome and dahurian angelica root equaled to 6 g crude drug respectively; Musk 0.05 g. The daily dosage for adults: 4 bags of mongolian milkvetch root, 2 bags of Chinese angelica, 0.05 g musk, 1 bag of peach seed, 2 bags of grassleaf sweetflag rhizome and 2 bags of dahurian angelica root, which should be given though nasal feeding or gastrostogavage before breakfast and supper every day, the course lasted for 2 months. The contents of dopamine in serum and cerebrospinal fluid were determined with enzyme immunoassay analyzer before and after treatment in both groups. Main outcome measures Contents of dopamine in serum and cerebrospinal fluid before and after treatment in both groups. Results Totally 38 patients of persistent vegetative state were enrolled, 33 of them were involved in the final analysis of results, and the other 5 missed. The contents of dopamine in serum and cerebrospinal fluid had no obvious differences between the two groups both before and after treatment ( P > 0.05). In the control group, the contents of dopamine in serum and cerebrospinal fluid had no obvious differences before and after treatment ( P > 0.05). In the TCM treated group, the contents of dopamine in serum and cerebrospinal fluid after treatment were obviously higher than those before treatment ( t =2.174, 2.485, P < 0.05). Conclusion Yishen Qiqiao Fang can significantly increase the contents of dopamine in serum and cerebrospinal fluid of patients in persistent vegetative state, which may be one of the mechanisms for ameliorating persistent vegetative state.

DESIGN OF A NEWLY DEVELOPED NON-ATTACHED APNEA MONITOR FOR PATIENTS IN PERSISTENT VEGETATIVE STATE

The conventional apnea monitor adopts disposable electrodes as sensors for apnea detection and thus inducing the problems of skin irritation and other side effects. To tackle these shortcomings, we develop a non-attached type of apnea monitor. The device monitors the temperature of the breathing airflow by means of thermo sensors. These airflow frequencies linked with respiratory rates are indicated on the monitor. There is absolutely no contact with the patients' skin, avoiding the possibilities of any skin irritation. The system detects temperature changes induced by breathing and analyzes the breathing frequency changes displayed by both LED array and computer monitor. The data are collected and analyzed simultaneously by a personal computer, which can link to the central nursery room. The device provides a convenient way for family or nurses to detect abnormal respiratory rate in real time so they can handle any emergency and give the necessary treatment immediately for those patients in persistent vegetative state. Clinic application is presented and function validation of the device, on the other hand, is performed as well.

Ethics Consultants’ Recommendations for Life-Prolonging Treatment of Patients in Persistent Vegetative State: A Follow-up Study

Ethics Consultants’ Recommendations for Life-Prolonging Treatment of Patients in Persistent Vegetative State: A Follow-up Study

Terminating artificial nutrition and hydration in persistent vegetative state patients: Current and proposed state laws

This article presents an overview of current state law governing the right to terminate life-sustaining treatment in the United States as it relates to refusal of artificial nutrition and hydration (ANH) for patients who have been diagnosed as being in a persistent vegetative state (PVS). The article was stimulated by the efforts of Michael Schiavo, Terri Schiavo’s husband and legal guardian, to discontinue ANH for her, and the ensuing controversy. Like many other neurologists, lawyers, and ethicists, we assumed that the law governing withdrawal of ANH in patients diagnosed as being in a PVS had become relatively settled and that the prolonged litigation occurring in Florida was the exception rather than the rule.1,2 We reviewed state laws to ascertain whether this assumption was indeed accurate. End-of-life decision making is largely governed by state law, although the states’ prerogatives are subject to federal constitutional constraints ultimately enunciated by the US Supreme Court. Our analysis focuses mainly on patterns and variations in state statutes and does not encompass a comprehensive review of case law. Fortunately, in the present context, the statutes in most states provide fairly clear guidance to physicians and hospitals about whether ANH may be withdrawn from a patient in a PVS, and there is little need for resort to case law in most states to clarify their meaning. We used Lexis-Nexis and Westlaw legal databases to conduct a search of all state laws governing end-of-life decision making. We used the following search terms: permanent vegetative state , persistent vegetative state , artificial nutrition and hydration , advance directive , living will , health care power of attorney , coma , unconscious , terminally ill , terminal condition , surrogate , and proxy . We reviewed all statutes that contained any of the search terms and saved for analysis …

Does any aspect of mind survive brain damage that typically leads to a persistent vegetative state? Ethical considerations

Recent neuroscientific evidence brings into question the conclusion that all aspects of consciousness are gone in patients who have descended into a persistent vegetative state (PVS). Here we summarize the evidence from human brain imaging as well as neurological damage in animals and humans suggesting that some form of consciousness can survive brain damage that commonly causes PVS. We also raise the issue that neuroscientific evidence indicates that raw emotional feelings (primary-process affects) can exist without any cognitive awareness of those feelings. Likewise, the basic brain mechanisms for thirst and hunger exist in brain regions typically not damaged by PVS. If affective feelings can exist without cognitive awareness of those feelings, then it is possible that the instinctual emotional actions and pain "reflexes" often exhibited by PVS patients may indicate some level of mentality remaining in PVS patients. Indeed, it is possible such raw affective feelings are intensified when PVS patients are removed from life-supports. They may still experience a variety of primary-process affective states that could constitute forms of suffering. If so, withdrawal of life-support may violate the principle of nonmaleficence and be tantamount to inflicting inadvertent "cruel and unusual punishment" on patients whose potential distress, during the process of dying, needs to be considered in ethical decision-making about how such individuals should be treated, especially when their lives are ended by termination of life-supports. Medical wisdom may dictate the use of more rapid pharmacological forms of euthanasia that minimize distress than the de facto euthanasia of life-support termination that may lead to excruciating feelings of pure thirst and other negative affective feelings in the absence of any reflective awareness.

Terminating artificial nutrition and hydration in persistent vegetative state patients: Current and proposed state laws

Terminating artificial nutrition and hydration in persistent vegetative state patients: Current and proposed state laws

1st Place Winner of the Robert Fulton Student Paper Competition of the Annual International Death, Grief, and Bereavement Conference: Social Psychological Perspectives on Altruism in Care Giving: The Schiavo Case and beyond

This article will address altruism in the care giving of an ill person and also consider some of the factors—responsibility, empathy and motivation—that influence helping behavior. A literature review indicates ongoing disagreements among scholars in relation to altruism and its motives. Inquiries are made into empathetic reactions using spoken and unspoken cues, and a transformation of altruism into compassionate action is examined. Assumption of responsibility will be analyzed with special reference to the role of the provider of care for an ill person. Models, theories, and approaches relating to altruism are examined as well as the various causes that contribute to the behavior of the care taker, including cooperation. The impact of altruism on families and in relationships is discussed on a cultural level with respect to norms. Lastly, the research is applied to the Florida Terri Schindler/ Schiavo case and its subjects, relating altruism and care giving to an assumed Persistent Vegetative State (PVS) patient.