seconds-administration-guidelines-fast-tool-to-assess-consciousness

SECONDs Administration Guidelines: A Fast Tool to Assess Consciousness in Brain-injured Patients

Establishing an accurate diagnosis is crucial for patients with disorders of consciousness (DoC) following a severe brain injury. The Coma Recovery ...

University of Liège

University Hospital of Liège

Groupe Hospitalier Saint-Luc

UCLouvain

Detection and interpretation of signs of "covert command following" in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in 12 patients without behavioral command following, attempting to establish "covert command following." These results were then confronted to cerebral metabolism preservation as measured with glucose PET (FDG-PET). One patient showed "covert command following" (i.e., above-threshold BCI performance) during the active tactile paradigm. This patient also showed a higher cerebral glucose metabolism within the language network (presumably required for command following) when compared with the other patients without "covert command-following" but having a cerebral glucose metabolism indicative of minimally conscious state. Our results suggest that the P3-based BCI might probe "covert command following" in patients without behavioral response to command and therefore could be a valuable addition in the clinical assessment of patients with DOC.

BCI Performance and Brain Metabolism Profile in Severely Brain-Injured Patients Without Response to Command at Bedside.

 There are few available therapeutic options to promote recovery among patients with chronic disorders of consciousness (DOC). Among pharmacological treatments, apomorphine, a dopamine agonist, has exhibited promising behavioral effects and safety of use in small-sample pilot studies. The true efficacy of the drug and its neural mechanism are still unclear. Apomorphine may act through a modulation of the anterior forebrain mesocircuit, but neuroimaging and neurophysiological investigations to test this hypothesis are scarce. This clinical trial aims to (1) assess the treatment effect of subcutaneous apomorphine infusions in patients with DOC, (2) better identify the phenotype of responders to treatment, (3) evaluate tolerance and side effects in this population, and (4) examine the neural networks underlying its modulating action on consciousness.  This study is a prospective double-blind randomized parallel placebo-controlled trial. Forty-eight patients diagnosed with DOC will be randomized to receive a 30-day regimen of either apomorphine hydrochloride or placebo subcutaneous infusions. Patients will be monitored at baseline 30 days before initiation of therapy, during treatment and for 30 days after treatment washout, using standardized behavioral scales (Coma Recovery Scale-Revised, Nociception Coma Scale-Revised), neurophysiological measures (electroencephalography, body temperature, actigraphy) and brain imaging (magnetic resonance imaging, positron emission tomography). Behavioral follow-up will be performed up to 2 years using structured phone interviews. Analyses will look for changes in behavioral status, circadian rhythmicity, brain metabolism, and functional connectivity at the individual level (comparing before and after treatment) and at the group level (comparing apomorphine and placebo arms, and comparing responder and non-responder groups).  This study investigates the use of apomorphine for the recovery of consciousness in the first randomized placebo-controlled double-blind trial using multimodal assessments. The results will contribute to define the role of dopamine agonists for the treatment of these challenging conditions and identify the neural correlates to their action. Results will bring objective evidence to further assess the modulation of the anterior forebrain mesocircuit by pharmacological agents, which may open new therapeutic perspectives.  EudraCT n°2018-003144-23; Clinicaltrials.gov n°NCT03623828 (https://clinicaltrials.gov/ct2/show/NCT03623828).

Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments.

The Nociception Coma Scale-Revised (NCS-R) was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute noxious stimuli. However, they failed to determine a reliable cut-off score that could be used to infer pain processing in these patients. This retrospective cross-sectional study aimed to determine a NCS-R cut-off score supporting preserved neural basis for pain experience, based on brain metabolism preservation as measured by fluorodeoxyglucose positron emission tomography (FDG-PET). We included patients in unresponsive wakefulness syndrome (UWS) confirmed by the FDG-PET and examined the NCS-R total scores. As the highest score was 4, we defined the cut-off to be 5 and compared the brain metabolism of these patients to matched patients with DOC and a NCS-R cut-off score ≥5 (ie, potential pain), as well as healthy subjects. We found a higher global cerebral metabolism in healthy subjects compared to both patient groups and also in patients with potential pain compared with FDG-PET confirmed UWS. We observed a preserved metabolism in the left insula in patients with potential pain compared with FDG-PET confirmed UWS. PERSPECTIVES: Our data suggest that using the cut-off score of 5 could be helpful to improve pain management in patients with DOC. Future studies should focus on patients showing scores below this cut-off to better characterize their profile and improve care.

Nociception Coma Scale-Revised Allows to Identify Patients With Preserved Neural Basis for Pain Experience.

To investigate the influence of the presence of a tracheostomy tube to assess pain with the Nociception Coma Scale-Revised (NCS-R) in patients with disorders of consciousness (DOC).

Can the Nociception Coma Scale-Revised Be Used in Patients With a Tracheostomy?

Transcranial direct current stimulation (tDCS) may promote the recovery of severely brain-injured patients with disorders of consciousness (DOC). Prior tDCS studies targeted single brain regions rather than brain networks critical for consciousness recovery.

Behavioral and electrophysiological effects of network-based frontoparietal tDCS in patients with severe brain injury: A randomized controlled trial.

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.

Article	Year
BCI Performance and Brain Metabolism Profile in Severely Brain-Injured Patients Without Response to Command at Bedside. Frontiers in neuroscience\| PubMed ID: 29910708	2018
Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments. Frontiers in neurology\| PubMed ID: 30941094	2019
Nociception Coma Scale-Revised Allows to Identify Patients With Preserved Neural Basis for Pain Experience. The journal of pain\| PubMed ID: 31733361	2020
Can the Nociception Coma Scale-Revised Be Used in Patients With a Tracheostomy? Archives of physical medicine and rehabilitation\| PubMed ID: 31765612	2020
Behavioral and electrophysiological effects of network-based frontoparietal tDCS in patients with severe brain injury: A randomized controlled trial. NeuroImage. Clinical\| PubMed ID: 32977212	2020
Covert Cognition in Disorders of Consciousness: A Meta-Analysis. Brain sciences\| PubMed ID: 33276451	2020

Nicolas Lejeune

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