Papers by Caroline Schnakers
Brain : a journal of neurology, Jan 27, 2017
Recent advances in functional neuroimaging have demonstrated novel potential for informing diagno... more Recent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric i...
Neuropsychological rehabilitation, Jan 11, 2017
Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefu... more Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefulness syndrome from patients in minimally conscious state (MCS). The Coma Recovery Scale-Revised (CRS-R) is the most sensitive scale to differentiate the different altered states of consciousness and eleven items detect the MCS. The aim of this study is to document the prevalence of these items. We analysed behavioural assessments of 282 patients diagnosed in MCS based on the CRS-R. Results showed that some items are particularly frequent among patients in MCS, namely fixation, visual pursuit, and reproducible movement to command, which were observed in more than 50% of patients. These responses were also the most probably observed items when the patients only showed one sign of consciousness. On the other hand, some items were rarely or never observed alone, e.g., object localisation (reaching), object manipulation, intelligible verbalisation, and object recognition. The results also sh...
Functional neurology
Zolpidem has been reported as an "awakening drug" in some patients with disorders of co... more Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-b...
NeuroRehabilitation, 2011
Following a coma, some patients may "awaken" without voluntary interaction or communica... more Following a coma, some patients may "awaken" without voluntary interaction or communication with the environment. More than 40 years ago this condition was coined coma vigil or apallic syndrome and later became worldwide known as "persistent vegetative state". About 10 years ago it became clear that some of these patients who failed to recover verbal or non-verbal communication did show some degree of consciousness--a condition called "minimally conscious state". Some authors questioned the usefulness of differentiating unresponsive "vegetative" from minimally conscious patients but subsequent functional neuroimaging studies have since objectively demonstrated differences in residual cerebral processing and hence, we think, conscious awareness. These neuroimaging studies have also demonstrated that a small subset of unresponsive "vegetative" patients may show unambiguous signs of consciousness and command following inaccessible to be...
Set temperature, 35°C AH (mgH 2 O/l) 26.7 ± 0.3* 37.4 ± 0.6 38.0 ± 0.9 RH (%) 83.7 ± 1.0* 97.7 ± ... more Set temperature, 35°C AH (mgH 2 O/l) 26.7 ± 0.3* 37.4 ± 0.6 38.0 ± 0.9 RH (%) 83.7 ± 1.0* 97.7 ± 1.4 93.2 ± 1.5 Set temperature, 37°C AH (mgH 2 O/l) 34.5 ± 1.6* 38.7 ± 2.2 † 43.1 ± 1.1 RH (%) 91.8 ± 3.2 87.7 ± 7.4 † 94.6 ± 0.9 *P < 0.05 vs DAR HC and MR 730, † P < 0.05 vs MR 730.
Neurorehabilitation and Neural Repair, 2014
Background. Despite recent evidence suggesting that some severely brain-injured patients retain s... more Background. Despite recent evidence suggesting that some severely brain-injured patients retain some capacity for top-down processing (covert cognition), the degree of sparing is unknown. Objective. Top-down attentional processing was assessed in patients in minimally conscious (MCS) and vegetative states (VS) using an active event-related potential (ERP) paradigm. Methods. A total of 26 patients were included (38 ± 12 years old, 9 traumatic, 21 patients >1 year postonset): 8 MCS+, 8 MCS−, and 10 VS patients. There were 14 healthy controls (30 ± 8 years old). The ERP paradigm included (1) a passive condition and (2) an active condition, wherein the participant was instructed to voluntarily focus attention on his/her own name. In each condition, the participant’s own name was presented 100 times (ie, 4 blocks of 25 stimuli). Results. In 5 MCS+ patients as well as in 3 MCS− patients and 1 VS patient, an enhanced P3 amplitude was observed in the active versus passive condition. Rela...
Brain Injury, 2014
Background: The assessment of pain and nociception in non-communicative patients with disorders o... more Background: The assessment of pain and nociception in non-communicative patients with disorders of consciousness (DOC) is a real challenge for clinicians. It is, therefore, important to develop sensitive standardized tools usable at the bedside. Objectives: This review aims to provide an overview of the current knowledge about pain processing and assessment in patients with DOC. Methods: A search was performed on PubMed using MeSH terms including vegetative state, unresponsive wakefulness syndrome, minimally conscious state, consciousness disorders, pain, nociception, neuroimaging and pain assessment. Results: Neuroimaging studies investigating pain processing in patients with DOC and their implication for clinicians are reviewed. Current works on the development of standardized and sensitive tools for assessing nociception are described. Conclusion: The suggested pain perception capacity highlighted by neuroimaging studies in patients in a MCS and in some patients in a VS/UWS supports the idea that these patients need analgesic treatment and monitoring. The first tool which has been developed to assess nociception and pain in patients with DOC is the NCS. Its revised version represents a rapid, standardized and sensitive scale which can be easily implemented in a clinical setting. Complementary pain assessments are also under validation in order to offer more options to clinicians.
Brain Injury, 2014
Objective: The aim of the study was to validate the use of electromyography (EMG) for detecting r... more Objective: The aim of the study was to validate the use of electromyography (EMG) for detecting responses to command in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS). Methods: Thirty-eight patients were included in the study (23 traumatic, 25 patients 41 year post-onset), 10 diagnosed as being in VS/UWS, eight in MCSÀ (no response to command) and 20 in MCS+ (response to command). Eighteen age-matched controls participated in the experiment. The paradigm consisted of three commands (i.e. 'Move your hands', 'Move your legs' and 'Clench your teeth') and one control sentence (i.e. 'It is a sunny day') presented in random order. Each auditory stimulus was repeated 4-times within one block with a stimulus-onset asynchrony of 30 seconds. Results: Post-hoc analyses with Bonferroni correction revealed that EMG activity was higher solely for the target command in one patient in permanent VS/UWS and in three patients in MCS+. The use of EMG could help clinicians to detect conscious patients who do not show any volitional response during standard behavioural assessments. However, further investigations should determine the sensitivity of EMG as compared to neuroimaging and electrophysiological assessments.
Coma and Disorders of Consciousness, 2012
ABSTRACT The ethical issues accrued from the study and management of severely brain-injured patie... more ABSTRACT The ethical issues accrued from the study and management of severely brain-injured patients are varied and multi-faceted. The medical, legal and public controversies are partly shaped by how different people think about these issues and in many cases are culturally-dependent. An ethical framework needs to be shaped to guide clinicians and caregivers in terms of clinical diagnosis, prognosis, and medical management. In this chapter, we will give a brief overview of some ethical issues related to the concept of consciousness and the medical management of patients with disorders of consciousness such as comatose, vegetative/unresponsive and minimally conscious states that may be encountered in the intensive care setting. We will emphasize the problem of pain management and end-of-life decision-making.
Science, 2011
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Neurorehabilitation and Neural Repair, 2013
Background. The Nociception Coma Scale–Revised (NCS-R) was recently validated to assess possible ... more Background. The Nociception Coma Scale–Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. Objective. To identify correlations between cerebral glucose metabolism and NCS-R total scores. Methods. [18F]-fluorodeoxyglucose positron emission tomography, NCS-R, and Coma Recovery Scale–Revised assessments were performed in 49 patients with disorders of consciousness. Results. We identified a significant positive correlation between NCS-R total scores and metabolism in the posterior part of the anterior cingulate cortex, known to be involved in pain processing. No other cluster reached significance. No significant effect of clinical diagnosis (vegetative/unresponsive vs minimally conscious states), etiology or interval since insult was observed. Conclusions. Our data support the hypothesis that the NCS-R total scores are related to cortical processing of nociception and may constitute an appropriate behavioral tool to asse...
The Lancet, 2014
Background Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wake... more Background 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 neuroimagingbased 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). Methods For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale-Revised (CRS-R), cerebral ¹⁸F-fl uorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS-R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale-Extended. Findings We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). ¹⁸F-FDG PET had high sensitivity for identifi cation of patients in a minimally conscious state (93%, 95% CI 85-98) and high congruence (85%, 77-90) with behavioural CRS-R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30-61) and had lower overall congruence with behavioural scores (63%, 51-73) than PET imaging. ¹⁸F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64-81), and fMRI in 36 of 65 patients (56%, 43-67). 13 of 42 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS-R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. Interpretation Cerebral ¹⁸F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for diff erential diagnosis, but seems to be less accurate.
Journal of Rehabilitation Medicine, 2012
Journal of Rehabilitation Medicine is an international peer-review journal published in English w... more Journal of Rehabilitation Medicine is an international peer-review journal published in English with ten regular issues per year. It is owned by a Swedish nonprofit organization: Foundation for Rehabilitation Information. Journal of Rehabilitation Medicine was former called Scandinavian Journal of Rehabilitation Medicine, which was founded by Olle Höök in 1968. The name was changed to Journal of Rehabilitation Medicine in 2001. Journal of Rehabilitation Medicine aims to be a leading worldwide forum for research in physical and rehabilitation medicine, aiming to increase knowledge in evidence-based clinical rehabilitation. Contributions from all parts of the world and from different professions in rehabilitation are encouraged. Original articles, Reviews (including Educational reviews), Special reports, Short communications, Case reports, and Letters to the Editor are published. Clinical studies on rehabilitation in various patients groups, within neurological and musculoskeletal as well as in other relevant rehabilitation areas, reports on physical and behavioural treatment methodology, including rehabilitation technology, development and analysis of methodology for outcome measurements, epidemiological studies on disability in relation to rehabilitation, and studies on vocational and socio-medical aspects of rehabilitation will be considered for publication. The journal emphasizes the need for randomized controlled studies of various rehabilitation interventions, the use of the International Classification of Functioning, Disability and Health (ICF) as a background for reports when appropriate, and the use of modern psychometric methodology in treating and reporting data from ordinal scales.
Journal of Psychophysiology, 2010
The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, an... more The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could help disentangle complex cases and offer new prognostic criteria. These methods can be divided into to three categories: First, new anatomical MRI neuroimaging methods, like diffusion tensor imaging (DTI) or spectroscopy, and passive functional imaging methods (looking at the brain’s activation induced by external stimuli), could provide new diagnostic and prognostic markers. Second, neuroimaging methods based on active collaboration from the patient could help to detect clinically unnoticed signs of consciousness. Third, developments in brain-computer interfaces based on EEG, functional MRI, or EMG offer communication possibilities in brain-damaged patients who can neither verbally nor nonverbally express their thoughts or wishes. These new approaches raise important issues not on...
Journal of Neurology, Neurosurgery & Psychiatry, 2008
Introduction: The effect of pharmacological agents on recovery in chronic disorders of consciousn... more Introduction: The effect of pharmacological agents on recovery in chronic disorders of consciousness remains unsatisfactory. Amantadine, a dopaminergic agonist, has been suggested to behaviorally improve recovery from vegetative (VS) and minimally conscious states (MCS). Here, we report the effect of amantadine in a chronic anoxic MCS patient (i.e., presence of visual pursuit). Methods: An ABAB design was proposed in conjunction with weekly CRS-R (Coma Recovery Scale-Revised) assessment, actimetry monitoring and serial (18F)fluorodeoxyglucose-PET (3 weeks baseline period, amantadine administrated during 6 weeks, stopped during 6 weeks and again resumed for 6 weeks). Results: After 3 weeks of amantadine treatment, the patient showed reproducible movement to command and consistent automatic motor responses permitting mouth feeding. Similarly, actimetry monitoring showed a significant increase in limb movements during treatment periods. Finally, serial FDG-PET scanning objectively measured treatment-related metabolic changes in a widespread fronto-temporo-parietal network and in the sensori-motor area. Conclusion: These data suggest a modulation of polymodal associative cortical metabolism and motor function by amantadine. Large scale studies on the efficiency of amantadine in this challenging patient population are warranted.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
Objective To determine the sensitivity of the Nociception Coma Scale (NCS), the first scale devel... more Objective To determine the sensitivity of the Nociception Coma Scale (NCS), the first scale developed to assess nociceptive pain in vegetative state and minimally conscious state patients, in comparing behavioural changes in response to noxious versus non-noxious stimulation. Methods The NCS was administered to assess patients' responses in three conditions: (1) baseline (observation of spontaneous behaviours), (2) non-noxious/tactile stimulation (taps on the patient's shoulder), and (3) noxious stimulation (pressure on the nail bed). Results We included 64 patients (27 vegetative state and 37 minimally conscious state; age range 20e82 years; 22 traumatic brain injury; 21 in the acute stage). The NCS total scores and subscores (motor, verbal and facial) were higher for the noxious versus the nonnoxious stimulation conditions. We did not observe a difference between the non-noxious and the noxious stimulation conditions for the visual subscale. We also found a NCS cut-off value of 4 differentiating the patients receiving a noxious stimulation from patients receiving a non-noxious stimulation. The exclusion of the visual subscale increased the cut-off sensitivity (from 46% to 73%; specificity of 97% and accuracy of 85%). We propose a new version of the NCS excluding the visual subscale, the NCS-R, which constitutes a highly sensitive tool to assess responses to nociceptive pain in severely brain injured patients.
Journal of Neurology, 2008
Journal of Neurology, 2011
Previous European surveys showed the support of healthcare professionals for treatment withdrawal... more Previous European surveys showed the support of healthcare professionals for treatment withdrawal [i.e., artificial nutrition and hydration (ANH) in chronic vegetative state (VS) patients]. The recent definition of minimally conscious state (MCS), and possibly research advances (e.g., functional neuroimaging), may have lead to uncertainty regarding potential residual perception and may have influenced opinions of healthcare professionals. The aim of the study was to update the end-of-life attitudes towards VS and to determine the end-of-life attitudes towards MCS. A 16-item questionnaire related to consciousness, pain and end-of-life issues in chronic (i.e., [1 year) VS and MCS and locked-in syndrome was distributed among attendants of medical and scientific conferences around Europe (n = 59). During a lecture, the items were explained orally to the attendants who needed to provide written yes/no responses. Chi-square tests and logistic regression analyses identified differences and associations for age, European region, religiosity, profession, and gender. We here report data on items concerning end-of-life issues on chronic VS and MCS. Responses were collected from 2,475 participants. For chronic VS ([1 year), 66% of healthcare professionals agreed to withdraw treatment and 82% wished not to be kept alive (P \ 0.001). For chronic MCS ([1 year), less attendants agreed to withdraw treatment (28%, P \ 0.001) and wished not to be kept alive (67%, P \ 0.001). MCS was considered worse than VS for the patients in 54% and for their families in 42% of the sample. Respondents' opinions were associated with geographic region and religiosity. Our data show that end-of-life opinions differ for VS as compared to MCS. The introduction of the diagnostic criteria for MCS has not substantially changed the opinions on end-of-life issues on permanent VS. Additionally, the existing legal ambiguity around MCS may have influenced the audience to draw a line between expressing preferences for self versus others, by implicitly recognizing that the latter could be a step on the slippery slope to legalize euthanasia. Given the observed individual variability, we stress the importance of advance directives and identification of proxies when discussing end-of-life issues in patients with disorders of consciousness.
Frontiers in Psychology, 2011
Communication and intentional behavior are supported by the brain's integrity at a structural and... more Communication and intentional behavior are supported by the brain's integrity at a structural and a functional level. When widespread loss of cerebral connectivity is brought about as a result of a severe brain injury, in many cases patients are not capable of conscious interactive behavior and are said to suffer from disorders of consciousness (e.g., coma, vegetative state/ unresponsive wakefulness syndrome, minimally conscious states). This lesion paradigm has offered not only clinical insights, as how to improve diagnosis, prognosis, and treatment, but also put forward scientific opportunities to study the brain's plastic abilities. We here review interventional and observational studies performed in severely brain-injured patients with regards to recovery of consciousness. The study of the recovered conscious brain (spontaneous and/ or after surgical or pharmacologic interventions), suggests a link between some specific brain areas and the capacity of the brain to sustain conscious experience, challenging at the same time the notion of fixed temporal boundaries in rehabilitative processes. Altered functional connectivity, cerebral structural reorganization as well as behavioral amelioration after invasive treatments will be discussed as the main indices for plasticity in these challenging patients. The study of patients with chronic disorders of consciousness may, thus, provide further insights not only at a clinical level (i.e., medical management and rehabilitation) but also from a scientific-theoretical perspective (i.e., the brain's plastic abilities and the pursuit of the neural correlate of consciousness).
Expert Review of Neurotherapeutics, 2010
Detecting pain in severely brain-injured patients recovering from coma represents a real challeng... more Detecting pain in severely brain-injured patients recovering from coma represents a real challenge. Patients with disorders of consciousness are unable to consistently or reliably communicate their feelings and potential perception of pain. However, recent studies suggest that patients in a minimally conscious state can experience pain to some extent. Pain monitoring in these patients is hence of medical and ethical importance. In this article, we will focus on the possible use of behavioral scales for the assessment and detection of pain in noncommunicative patients.
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Papers by Caroline Schnakers