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

A growing body of evidence suggests that reward may be a powerful determinant of attentional selection. To date, the study of value-based attentional capture has been mainly focused on the visual sensory modality. It is yet unknown how reward information is communicated and integrated across the different senses in order to resolve between competing choices during selective attention. Our study investigated the interference produced by an auditory reward-associated distractor when a semantically-related visual target was concurrently presented. We measured both manual and saccadic response times towards a target image (drum or trumpet), while an irrelevant sound (congruent or incongruent instrument) was heard. Each sound was previously associated with either a high or a low reward. We found that manual responses were slowed by a high-reward auditory distractor when sound and image were semantically congruent. A similar effect was observed for saccadic responses, but only for participants aware of the past reward contingencies. Auditory events associated with reward value were thus capable of involuntarily capturing attention in the visual modality. This reward effect can mitigate cross-modal semantic integration and appears to be differentially modulated by awareness for saccadic vs. manual responses. Together, our results extend previous work on value-driven attentional biases in perception by showing that these may operate across sensory modalities and override cross-modal integration for semantically-related stimuli. This study sheds new light on the potential implication of brain regions underlying value-driven attention across sensory modalities.

Cross-modal integration during value-driven attentional capture.

 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.

Prolonged disorders of consciousness (DOC) are considered to be among the most severe outcomes after acquired brain injury. Medical care for these patients is mainly focused on minimizing complications, given that treatment options for patients with unresponsive wakefulness or minimal consciousness remain scarce. The complication rate in patients with DOC is high, both in the acute hospital setting, as in the rehabilitation or long-term care phase. Hydrocephalus is one of these well-known complications and usually develops quickly after acute changes in cerebrospinal fluid (CSF) circulation after different types of brain damage. However, hydrocephalus may also develop with a significant delay, weeks, or even months after the initial injury, reducing the potential for natural recovery of consciousness. In this phase, hydrocephalus is likely to be missed in DOC patients, given that their limited behavioral responsiveness camouflages the classic signs of increased intracranial pressure or secondary normal-pressure hydrocephalus. Moreover, the development of late-onset hydrocephalus may exceed the period of regular outpatient follow-up. Several controversies remain about the diagnosis of clinical hydrocephalus in patients with ventricular enlargement after severe brain injury. In this article, we discuss both the difficulties in diagnosis and dilemmas in the treatment of CSF disorders in patients with prolonged DOC and review evidence from the literature to advance an active surveillance protocol for the detection of this late, but treatable, complication. Moreover, we advocate a low threshold for CSF diversion when hydrocephalus is suspected, even months or years after brain injury.

The Dilemma of Hydrocephalus in Prolonged Disorders of Consciousness.

The Coma Recovery Scale-Revised (CRS-R) is the gold standard to assess severely brain-injured patients with prolonged disorders of consciousness (DoC). However, the amount of time needed to complete this examination may limit its use in clinical settings.

Article	Year
Cross-modal integration during value-driven attentional capture. Neuropsychologia\| PubMed ID: 30342964	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
The Dilemma of Hydrocephalus in Prolonged Disorders of Consciousness. Journal of neurotrauma\| PubMed ID: 32484029	2020
Simplified Evaluation of CONsciousness Disorders (SECONDs) in individuals with severe brain injury: a validation study. Annals of physical and rehabilitation medicine\| PubMed ID: 32992025	2020

Leandro R. D. Sanz

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