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See detailDifferent beliefs about pain perception in the vegetative and minimally conscious states: a European survey of medical and paramedical professionals.
Demertzi, Athina ULg; Schnakers, Caroline ULg; Ledoux, Didier ULg et al

in Progress in Brain Research (2009), 177

Pain management in severely brain-damaged patients constitutes a clinical and ethical stake. At the bedside, assessing the presence of pain and suffering is challenging due to both patients' physical ... [more ▼]

Pain management in severely brain-damaged patients constitutes a clinical and ethical stake. At the bedside, assessing the presence of pain and suffering is challenging due to both patients' physical condition and inherent limitations of clinical assessment. Neuroimaging studies support the existence of distinct cerebral responses to noxious stimulation in brain death, vegetative state, and minimally conscious state. We here provide results from a European survey on 2059 medical and paramedical professionals' beliefs on possible pain perception in patients with disorders of consciousness. To the question "Do you think that patients in a vegetative state can feel pain?," 68% of the interviewed paramedical caregivers (n=538) and 56% of medical doctors (n=1166) answered "yes" (no data on exact profession in 17% of total sample). Logistic regression analysis showed that paramedical professionals, religious caregivers, and older caregivers reported more often that vegetative patients may experience pain. Following professional background, religion was the highest predictor of caregivers' opinion: 64% of religious (n=1009; 850 Christians) versus 52% of nonreligious respondents (n=830) answered positively (missing data on religion in 11% of total sample). To the question "Do you think that patients in a minimally conscious state can feel pain?" nearly all interviewed caregivers answered "yes" (96% of the medical doctors and 97% of the paramedical caregivers). Women and religious caregivers reported more often that minimally conscious patients may experience pain. These results are discussed in terms of existing definitions of pain and suffering, the remaining uncertainty on the clinical assessment of pain as a subjective first-person experience and recent functional neuroimaging findings on nociceptive processing in disorders of consciousness. In our view, more research is needed to increase our understanding of residual sensation in vegetative and minimally conscious patients and to propose evidence-based medical guidelines for the management of possible pain perception and suffering in these vulnerable patient populations. [less ▲]

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See detailDiagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment.
Schnakers, Caroline ULg; Vanhaudenhuyse, Audrey ULg; Giacino, Joseph et al

in BMC Neurology (2009), 9

BACKGROUND: Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies ... [more ▼]

BACKGROUND: Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). METHODS: We prospectively followed 103 patients (55 +/- 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' RESULTS: Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. CONCLUSION: Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus. [less ▲]

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See detailA new era of coma and consciousness science.
Owen, Adrian M.; Schiff, Nicholas D.; Laureys, Steven ULg

in Progress in Brain Research (2009), 177

In the past ten years, rapid technological developments in the field of neuroimaging have produced a cornucopia of new techniques for examining both the structure and function of the human brain in vivo ... [more ▼]

In the past ten years, rapid technological developments in the field of neuroimaging have produced a cornucopia of new techniques for examining both the structure and function of the human brain in vivo. In specialized centers, many of these methods are now being employed routinely in the assessment of patients diagnosed with disorders of consciousness, mapping patterns of residual function and dysfunction and helping to reduce diagnostic errors between related conditions such as the vegetative and minimally conscious states. Moreover, such efforts are beginning to provide important new prognostic indicators, helping to disentangle differences in outcome on the basis of a greater understanding of the underlying mechanisms responsible and providing information that will undoubtedly contribute to improved therapeutic choices in these challenging populations. Of course, these emerging technologies and the new information that they provide will bring new ethical challenges to this area and will have profound implications for clinical care and medical-legal decision-making in this population of patients. We review the most recent work in this area and suggest that the future integration of emerging neuroimaging techniques with existing clinical and behavioral methods of assessment will pave the way for new and innovative applications, both in basic neuroscience and in clinical practice. [less ▲]

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See detailComa, Persistent Vegetative States, and Diminished Consciousness
Demertzi, Athina ULg; Laureys, Steven ULg; Boly, Mélanie ULg

in Encyclopedia of Consciousness (2009), 1

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See detailLocked-in syndrome in children: report of five cases and review of the literature
Bruno, Marie-Aurélie ULg; Schnakers, C.; Damas, François ULg et al

in Pediatric Neurology (2009), 41

The locked-in syndrome is a rare neurologic disorder defined by (1) the presence of sustained eye opening; (2) preserved awareness; (3) aphonia or hypophonia; (4) quadriplegia or quadriparesis; and (5) a ... [more ▼]

The locked-in syndrome is a rare neurologic disorder defined by (1) the presence of sustained eye opening; (2) preserved awareness; (3) aphonia or hypophonia; (4) quadriplegia or quadriparesis; and (5) a primary mode of communication that uses vertical or lateral eye movement or blinking. Five cases are reported here, and previous literature is reviewed. According to the literature, the most common etiology of locked-in syndrome in children is ventral pontine stroke, most frequently caused by a vertebrobasilar artery thrombosis or occlusion. In terms of prognosis, 35% of pediatric locked-in syndrome patients experienced some motor recovery, 26% had good recovery, 23% died, and 16% remained quadriplegic and anarthric. These findings raise important ethical considerations in terms of quality of life and end-of-life decisions in such challenging cases. [less ▲]

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See detailBispectral index correlates with regional cerebral blood flow during sleep in distinct cortical and subcortical structures in humans.
Noirhomme, Quentin ULg; Boly, Mélanie ULg; Bonhomme, Vincent ULg et al

in Archives Italiennes de Biologie (2009), 147(1-2), 51-7

The relationship between the Bispectral Index (BIS), an EEG-based monitor of anesthesia, and brain activity is still unclear. This study aimed at investigating the relationship between changes in BIS ... [more ▼]

The relationship between the Bispectral Index (BIS), an EEG-based monitor of anesthesia, and brain activity is still unclear. This study aimed at investigating the relationship between changes in BIS values during natural sleep and regional cerebral blood flow (rCBF) variations, as measured by Positron Emission Tomography (PET). Data were obtained from six young, healthy, right-handed, male volunteers (20-30 years old) using the H2(15)O infusion method. PET scans were performed both during waking and various stages of sleep. BIS values were monitored continuously and recorded during each PET scan. Positive correlations were detected between BIS and rCBF values in dorsolateral prefontal, parietal, anterior and posterior cingulate, precuneal, mesiofrontal, mesiotemporal and insular cortices. These areas belong to a frontoparietal network known to be related to awareness of self conscious sensory perception, attention and memory. BIS values also positively correlated with activity in brainstem and thalami, both structures known to be involved in arousal and wakefulness. These results show that BIS changes associated with physiological sleep depth co-vary with the activity of specific cortical and subcortical areas. The latter are known to modulate arousal, which in turn allows sustained thalamo-cortical enhancement of activity in a specific frontoparietal network known to be related to the content of consciousness. Thus, although mainly derived from frontal EEG, BIS could represent a wider index of cerebral activity. [less ▲]

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See detailTowards a neuro-scientific explanation of near-death experiences?
Vanhaudenhuyse, Audrey ULg; Thonnard, Marie ULg; Laureys, Steven ULg

in Vincent, Jean-Louis (Ed.) Yearbook of intensive care and emergency medecine (2009)

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See detailPrélèvement d'organes après euthanasie: expérience belge
Ysebaert, Dirk; Detry, Olivier ULg; Squifflet, Jean-Paul ULg et al

Conference (2008, October 10)

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See detailThe changing spectrum of coma
Laureys, Steven ULg; Boly, Mélanie ULg

in Nature Clinical Practice Neurology (2008), 4(10), 544-546

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See detailOrgan donation after physician-assisted death
Detry, Olivier ULg; Laureys, Steven ULg; Faymonville, Marie ULg et al

in Transplant International (2008), 21(9), 915

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See detailThe boundaries of consciousness: lessons from coma and related states
Laureys, Steven ULg; Boly, Mélanie ULg; Moonen, Gustave ULg

in Advances in Clinical Neuroscience and Rehabilitation [=ACNR] (2008), 8(2),

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See detailThe Effect of Clonidine Infusion on Distribution of Regional Cerebral Blood Flow in Volunteers
Bonhomme, Vincent ULg; Maquet, Pierre ULg; Phillips, Christophe ULg et al

in Anesthesia and Analgesia (2008), 106(3), 899-909

BACKGROUND: Through their action on the locus coeruleus, alpha2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this ... [more ▼]

BACKGROUND: Through their action on the locus coeruleus, alpha2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this observational study was to map brain regions whose activity is modified by clonidine infusion so as to better understand its loci of action, especially in relation to sedation. METHODS: Six ASA I-II right-handed volunteers were recruited. Electroencephalogram (EEG) was monitored continuously. After a baseline H2(15)O activation scan, clonidine infusion was started at a rate ranging from 6 to 10 microg x kg(-1) x h(-1). A sequence of 11 similar scans was then performed at 8 min intervals. Plasma clonidine concentration was measured. Using statistical parametric mapping, we sought linear correlations between normalized regional cerebral blood flow (rCBF), an indicator of regional brain activity, and plasma clonidine concentration or spindle EEG activity. RESULTS: Clonidine induced clinical sedation and EEG patterns (spindles) comparable to early stage nonrapid eye movement sleep. A significant negative linear correlation between clonidine concentration and rCBF or spindle activity was observed in the thalamus, prefrontal, orbital and parietal association cortex, posterior cingulate cortex, and precuneus. CONCLUSIONS: The EEG patterns and decreases in rCBF of specific brain regions observed during clonidine-induced sedation are similar to those of early stage nonrapid eye movement sleep. Patterns of deactivated brain regions are also comparable to those observed during general anesthesia or vegetative state, reinforcing the hypothesis that alterations in the activity of a common network occur during these modified conscious states. [less ▲]

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See detailAssessment of visual pursuit in post-comatose states: use a mirror
Vanhaudenhuyse, Audrey ULg; Schnakers, Caroline ULg; Brédart, Serge ULg et al

in Journal of Neurology, Neurosurgery & Psychiatry (2008), 79(2),

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See detailIntrinsic brain activity in altered states of consciousness: how conscious is the default mode of brain function?
Boly, Mélanie ULg; Phillips, Christophe ULg; Tshibanda, Luaba ULg et al

in Annals of the New York Academy of Sciences (2008), 1129

Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain-behavior relationships ... [more ▼]

Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain-behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto-cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level-dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark. [less ▲]

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See detailPerception of pain in the minimally conscious state with PET activation: an observational study.
Boly, Mélanie ULg; Faymonville, Marie-Elisabeth ULg; Schnakers, Caroline et al

in Lancet Neurology (2008), 7(11), 1013-20

BACKGROUND: 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 ... [more ▼]

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. [less ▲]

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See detailAre we equal in death?
Laureys, Steven ULg; Fins, Joseph J.

in Neurology (2008), 70

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See detailLe Locked-In Syndrome : la conscience emmurée
Bruno, Marie-Aurélie ULg; Pellas, F.; Schnakers, Caroline ULg et al

in Revue Neurologique (2008), 164

The Locked-In syndrome(LIS) is defined by: (i) the presence of sustained eye opening (bilateral ptosis should be ruled out as a complicating factor);(ii) preserved awareness; (iii) aphonia or hypophonia ... [more ▼]

The Locked-In syndrome(LIS) is defined by: (i) the presence of sustained eye opening (bilateral ptosis should be ruled out as a complicating factor);(ii) preserved awareness; (iii) aphonia or hypophonia; (iv) quadriplegia or quadriparesis; and (v) a primary mode of communication that uses vertical or lateral eye movement or blinking. Acute ventral pontine lesions are its most common cause. Following such brainstem lesions patients may remain comatose for sometime and then gradually awaken, remaining paralyzed and voiceless, superficially resembling the vegetative state. Background. – It has been shown that more than half of the time physicians fail to recognize early signs of awareness in LIS. Given appropriate medical care,life expectancy may be several decades but the chances of good motor recovery remain small. Eye-controlled computer technology now allows LIS patients to communicate and control their environment. Recent studies show that most LIS patients self-report meaningful quality of life and the demand for euthanasia is infrequent. Conclusion. – Patients suffering from LIS should not be denied the right to die – and to die with dignity –but also they should not be denied the right to live–and to live with dignity and the best possible pain and symptom management and revalidation. [less ▲]

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