Improved vigilance after sodium oxybate treatment in narcolepsy: a comparison between in-field and in-laboratory measurements.

This two-centre observational study of vigilance measurements assessed the feasibility of vigilance measurements on multiple days using the Sustained Attention to Response Task and the Psychomotor Vigilance Test with portable task equipment, and subsequently assessed the effect of sodium oxybate treatment on vigilance in patients with narcolepsy. Twenty-six patients with narcolepsy and 15 healthy controls were included. The study comprised two in-laboratory days for the Maintenance of Wakefulness Test and the Oxford Sleep Resistance test, followed by 7-day portable vigilance battery measurements. This procedure was repeated for patients with narcolepsy after at least 3 months of stable treatment with sodium oxybate. Patients with narcolepsy had a higher Sustained Attention to Response Task error count, lower Psychomotor Vigilance Test reciprocal reaction time, higher Oxford Sleep Resistance test omission error count adjusted for test duration (Oxford Sleep Resistance testOMIS / MIN ), and lower Oxford Sleep Resistance test and Maintenance of Wakefulness Test sleep latency compared with controls (all P < 0.01). Treatment with sodium oxybate was associated with a longer Maintenance of Wakefulness Test sleep latency (P < 0.01), lower Oxford Sleep Resistance testOMIS / MIN (P = 0.01) and a lower Sustained Attention to Response Task error count (P = 0.01) in patients with narcolepsy, but not with absolute changes in Oxford Sleep Resistance test sleep latency or Psychomotor Vigilance Test reciprocal reaction time. It was concluded that portable measurements of sustained attention as well as in-laboratory Oxford Sleep Resistance test and Maintenance of Wakefulness Test measurements revealed worse performance for narcoleptic patients compared with controls, and that sodium oxybate was associated with an improvement of sustained attention and a better resistance to sleep.

Impaired sustained attention in adult patients with type 1 diabetes is related to diabetes per se.

BACKGROUND: Patients with type 1 diabetes have altered sleep characteristics and are thought to have deficits in sustained attention. We compared the sustained attention to response task (SART) of patients with type 1 diabetes to that of healthy controls, and related results with sleep characteristics and disease-related factors. METHODS: SART was applied in 122 patients and 109 controls. Glucoregulation was assessed by HbA1c values and a questionnaire assessing glycaemic history. Clinical parameters were obtained from medical charts. Polyneuropathy was assessed by neurological examination and quantitative sensory testing. Sleep characteristics were assessed with sleep questionnaires. Anxiety and depression scores were assessed by the Hospital Anxiety and Depression Scale. RESULTS: The SART reaction time (RT) was significantly longer than in controls (327 ± 5 vs. 285 ± 3 ms, p < 0.001), although there were no significant differences in error scores. Repeated measurement analyses showed that diabetes per se was associated with prolonged RT (p < 0.001) and more commission errors (p = 0.010). None of the sleep-related and diabetes-related factors were significantly associated with these SART parameters. CONCLUSIONS: Patients with type 1 diabetes had impaired sustained attention, which was associated with diabetes per se but not with disturbed sleep characteristics.

Sustained attention to response task (SART) shows impaired vigilance in a spectrum of disorders of excessive daytime sleepiness.

The sustained attention to response task comprises withholding key presses to one in nine of 225 target stimuli; it proved to be a sensitive measure of vigilance in a small group of narcoleptics. We studied sustained attention to response task results in 96 patients from a tertiary narcolepsy referral centre. Diagnoses according to ICSD-2 criteria were narcolepsy with (n=42) and without cataplexy (n=5), idiopathic hypersomnia without long sleep time (n=37), and obstructive sleep apnoea syndrome (n=12). The sustained attention to response task was administered prior to each of five multiple sleep latency test sessions. Analysis concerned error rates, mean reaction time, reaction time variability and post-error slowing, as well as the correlation of sustained attention to response task results with mean latency of the multiple sleep latency test and possible time of day influences. Median sustained attention to response task error scores ranged from 8.4 to 11.1, and mean reaction times from 332 to 366ms. Sustained attention to response task error score and mean reaction time did not differ significantly between patient groups. Sustained attention to response task error score did not correlate with multiple sleep latency test sleep latency. Reaction time was more variable as the error score was higher. Sustained attention to response task error score was highest for the first session. We conclude that a high sustained attention to response task error rate reflects vigilance impairment in excessive daytime sleepiness irrespective of its cause. The sustained attention to response task and the multiple sleep latency test reflect different aspects of sleep/wakefulness and are complementary.

Vigilance: discussion of related concepts and proposal for a definition.

We reviewed current definitions of vigilance to propose a definition, applicable in sleep medicine. As previous definitions contained terms such as attention, alertness, and arousal, we addressed these concepts too. We defined alertness as a quantitative measure of the mind state governing sensitivity to stimuli. Arousal comprises a stimulus-induced upward change in alertness, irrespective of the subsequent duration of the increased level of alertness. Vigilance is defined as the capability to be sensitive to potential changes in one's environment, ie the capability to reach a level of alertness above a threshold for a certain period of time rather than the state of alertness itself. It has quantitative and temporal dimensions. Attention adds direction towards a stimulus to alertness, requiring cognitive control: it involves being prepared to process stimuli coming from an expected direction. Sustained attention corresponds to a state in which some level of attention is purposefully maintained, adding a time factor to the definition of attention. Vigilance differs from sustained attention in that the latter in addition implies a direction to which attention is cognitively directed as well as a specification of duration. Attempts to measure vigilance, however, are often in fact measurements of sustained attention.

Reward biases spontaneous neural reactivation during sleep.

Sleep favors the reactivation and consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information to be reprocessed during sleep remains largely unknown. From an evolutionary perspective, individuals must retain information that promotes survival, such as avoiding dangers, finding food, or obtaining praise or money. Here, we test whether neural representations of rewarded (compared to non-rewarded) events have priority for reactivation during sleep. Using functional MRI and a brain decoding approach, we show that patterns of brain activity observed during waking behavior spontaneously reemerge during slow-wave sleep. Critically, we report a privileged reactivation of neural patterns previously associated with a rewarded task (i.e., winning at a complex game). Moreover, during sleep, activity in task-related brain regions correlates with better subsequent memory performance. Our study uncovers a neural mechanism whereby rewarded life experiences are preferentially replayed and consolidated while we sleep.

Peripheral Neuropathy, Episodic Rhabdomyolysis, and Hypoparathyroidism in a Patient with Mitochondrial Trifunctional Protein Deficiency.

A combination of unexplained peripheral neuropathy, hypoparathyroidism, and the inability to cope with metabolic stress could point to a rare inborn error of metabolism, such as mitochondrial trifunctional protein (MTP) deficiency.Here, we describe a 20-year-old woman who was known since childhood with axonal motor sensory polyneuropathy of unknown origin. She presented with progressive dyspnoea, and increased muscle weakness, preceded by 6 days of fever, vomiting, and diarrhoea. Laboratory testing showed rhabdomyolysis, and hypocalcaemia with low parathyroid levels. The patient was intubated because of respiratory insufficiency and a viral and bacterial pneumonia was diagnosed. She was discharged after 16 days of admission. Metabolic screening, performed at the time of rhabdomyolysis, showed increased concentrations of long-chain 3-hydroxyacyl carnitine species, together with elevated urinary excretion of 3-hydroxy dicarboxylic acids. Decreased activity of long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-ketoacyl-CoA thiolase in peripheral lymphocytes and fibroblasts confirmed a MTP deficiency. Sequence analysis of the HADHB gene showed two heterozygous variants: c.209+1G>C (splicing defect) and c.980T>C (p.Leu327Leu). When the acylcarnitine profile was repeated after the episode of rhabdomyolysis had resolved it showed no abnormalities.Our case illustrates a cluster of peripheral neuropathy, episodic rhabdomyolysis, and hypoparathyroidism in a patient with MTP deficiency caused by mutations in the HADHB gene. It stresses the importance of performing metabolic screening when patients are most symptomatic, as normal results can be found at times when no metabolic stress is present. Screening is relatively easy and timely diagnosis has important implications for treatment.

Comparing Treatment Effect Measurements in Narcolepsy: The Sustained Attention to Response Task, Epworth Sleepiness Scale and Maintenance of Wakefulness Test.

STUDY OBJECTIVES: To validate the Sustained Attention to Response Task (SART) as a treatment effect measure in narcolepsy, and to compare the SART with the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). DESIGN: Validation of treatment effect measurements within a randomized controlled trial (RCT). PATIENTS: Ninety-five patients with narcolepsy with or without cataplexy. INTERVENTIONS: The RCT comprised a double-blind, parallel-group, multicenter trial comparing the effects of 8-w treatments with pitolisant (BF2.649), modafinil, or placebo (NCT01067222). MWT, ESS, and SART were administered at baseline and after an 8-w treatment period. The severity of excessive daytime sleepiness and cataplexy was also assessed using the Clinical Global Impression scale (CGI-C). MEASUREMENTS AND RESULTS: The SART, MWT, and ESS all had good reliability, obtained for the SART and MWT using two to three sessions in 1 day. The ability to distinguish responders from nonresponders, classified using the CGI-C score, was high for all measures, with a high performance for the SART (r = 0.61) and the ESS (r = 0.54). CONCLUSIONS: The Sustained Attention to Response Task is a valid and easy-to-administer measure to assess treatment effects in narcolepsy, enhanced by combining it with the Epworth Sleepiness Scale.

The influences of task repetition, napping, time of day, and instruction on the Sustained Attention to Response Task.

INTRODUCTION: The Sustained Attention to Response Task (SART) helps to quantify vigilance impairments.Previous studies, in which five SART sessions on one day were administered, demonstrated worse performance during the first session than during the others. The present study comprises two experiments to identify a cause of this phenomenon. METHOD: Experiment 1, counting eighty healthy participants, assessed effects of repetition,napping, and time of day on SART performance through a between-groups design. The SART was performed twice in the morning or twice in the afternoon; half of the participants took a 20-minute nap before the second SART. A strong correlation between error count and reaction time (RT) suggested effects of test instruction. Participants gave equal weight to speed and accuracy in Experiment 1; therefore, results of 20 participants were compared to those of 20 additional participants who were told to prefer accuracy (Experiment 2). RESULTS: The average SART error count in Experiment 1 was 10.1; the median RT was 280 ms. Neither repetition nor napping influenced error count or RT. Time of day did not influence error count, but RT was significantly longer for morning than for afternoon SARTs. The additional participants in Experiment 2 had a 49% lower error count and a 14% higher RT than the participants in Experiment 1. Error counts reduced by 50% from the first to the second session of Experiment 2, irrespective of napping or time of day. CONCLUSIONS: Preferring accuracy over speed was associated with a significantly lower error count. The data suggest that a worse performance in the first SART session only occurs when instructing participants to prefer accuracy, which is caused by repetition, not by napping or time of day. NOTE: We advise that participants are instructed to prefer accuracy over speed when performing the SART and that a full practice session is included.