Pupil dilation response elicited by violations of auditory regularities is a promising but challenging approach to probe consciousness at the bedside.

Pupil dilation response (PDR) has been proposed as a physiological marker of conscious access to a stimulus or its attributes, such as novelty. In a previous study on healthy volunteers, we adapted the auditory "local global" paradigm and showed that violations of global regularity elicited a PDR. Notably without instructions, this global effect was present only in participants who could consciously report violations of global regularities. In the present study, we used a similar approach in 24 non-communicating patients affected with a Disorder of Consciousness (DoC) and compared PDR to ERPs regarding diagnostic and prognostic performance. At the group level, global effect could not be detected in DoC patients. At the individual level, the only patient with a PDR global effect was in a MCS and recovered consciousness at 6 months. Contrasting the most regular trials to the most irregular ones improved PDR's diagnostic and prognostic power in DoC patients. Pupillometry is a promising tool but requires several methodological improvements to enhance the signal-to-noise ratio and make it more robust for probing consciousness and cognition in DoC patients.

A juvenile ALS-like phenotype dramatically improved after high-dose riboflavin treatment.

Riboflavin transporter deficiency (RTD) was recently characterized as a cause of genetic recessive childhood-onset motor neuron disease (MND) with hearing loss, formerly described as Brown-Vialetto-Van-Lear syndrome. We describe a 18-year-old woman with probable RTD mimicking juvenile Amyotrophic Lateral Sclerosis (ALS) who presented with an inaugural respiratory failure and moderate distal four limbs weakness. Only one heterozygous SLC52A3 mutation was detected, but presence of a sub-clinical auditory neuropathy and dramatic improvement under high dose riboflavin argued for a RTD. As RTD probably has a larger phenotypic spectrum than expected, a high dose riboflavin trial should be discussed in young-onset MND.

Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness.

Improving our ability to detect conscious processing in non communicating patients remains a major goal of clinical cognitive neurosciences. In this perspective, several functional brain imaging tools are currently under development. Bedside cognitive event-related potentials (ERPs) derived from the EEG signal are a good candidate to explore consciousness in these patients because: (1) they have an optimal time resolution within the millisecond range able to monitor the stream of consciousness, (2) they are fully non-invasive and relatively cheap, (3) they can be recorded continuously on dedicated individual systems to monitor consciousness and to communicate with patients, (4) and they can be used to enrich patients' autonomy through brain-computer interfaces. We recently designed an original auditory rule extraction ERP test that evaluates cerebral responses to violations of temporal regularities that are either local in time or global across several seconds. Local violations led to an early response in auditory cortex, independent of attention or the presence of a concurrent visual task, while global violations led to a late and spatially distributed response that was only present when subjects were attentive and aware of the violations. In the present work, we report the results of this test in 65 successive recordings obtained at bedside from 49 non-communicating patients affected with various acute or chronic neurological disorders. At the individual level, we confirm the high specificity of the 'global effect': only conscious patients presented this proposed neural signature of conscious processing. Here, we also describe in details the respective neural responses elicited by violations of local and global auditory regularities, and we report two additional ERP effects related to stimuli expectancy and to task learning, and we discuss their relations to consciousness.

Prognosis value of plasma S100B protein levels after subarachnoid aneurysmal hemorrhage.

BACKGROUND: S100B has been described as a biologic marker of neuronal damage. The purpose of this study was to assess its prognostic value in patients with subarachnoid aneurysmal hemorrhage. METHODS: Seventy-four patients (32 men and 42 women; age, 48 +/- 11 yr) admitted within 48 h after subarachnoid hemorrhage onset and treated by surgical clipping or coiling within 2 days after admission were included. World Federation of Neurological Surgeons, Fisher, and Glasgow outcome scores at intensive care unit discharge and at 6 months were evaluated. Blood concentrations of S100B were determined at admission and daily up to day 8. RESULTS: The time course of S100B was increased in patients with high World Federation of Neurological Surgeons and Fisher scores. Patients who underwent surgical clipping had an S100B time course longer than that of those who underwent coiling. This difference remained true after stratification for World Federation of Neurological Surgeons and Fisher scores. The threshold of mean daily value of S100B predicting a poor outcome at 6 months was 0.4 microg/l (sensitivity = 0.50 [95% confidence interval (CI), 0.29-0.71], specificity = 0.87[corrected] [95% CI, 0.76-0.95]). In multivariate analysis, high World Federation of Neurological Surgeons score (odds ratio = 9.5 [95% CI, 3.1-29.4]), mean daily S100B value above 0.4 microg/l (odds ratio = 7.3 [95% CI, 2.3-23.6]), and age (odds ratio = 1.08 per year [95% CI, 1.01-1.15]) were independent predictors of a poor 6-month outcome (Glasgow outcome score 1-3). CONCLUSION: Mean daily value of S100B assessed during the first 8 days is a prognostic tool complementary to initial clinical evaluation in subarachnoid hemorrhage patients.