Marc Guaita

Mutual information measures applied to EEG signals for sleepiness characterization

Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders with a great impact on the patient lives. While many studies have been carried out in order to assess daytime sleepiness, the automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on non-linear dynamical analysis of EEG signal was proposed. Multichannel EEG signals were recorded during five maintenance of wakefulness (MWT) and multiple sleep latency (MSLT) tests alternated throughout the day from patients suffering from sleep disordered breathing. A group of 20 patients with excessive daytime sleepiness (EDS) was compared with a group of 20 patients without daytime sleepiness (WDS), by analyzing 60-s EEG windows in waking state. Measures obtained from cross-mutual information function (CMIF) and auto-mutual-information function (AMIF) were calculated in the EEG. These functions permitted a quantification of the complexity properties of the EEG signal and the non-linear couplings between different zones of the scalp. Statistical differences between EDS and WDS groups were found in β band during MSLT events (p-value < 0.0001). WDS group presented more complexity than EDS in the occipital zone, while a stronger nonlinear coupling between occipital and frontal zones was detected in EDS patients than in WDS. The AMIF and CMIF measures yielded sensitivity and specificity above 80% and AUC of ROC above 0.85 in classifying EDS and WDS patients.

Circadian Impairment of Distal Skin Temperature Rhythm in Patients With Sleep-Disordered Breathing: The Effect of CPAP

Study objectives Our aim was to evaluate the circadian rhythm of distal skin temperature (DST) in sleep-disordered breathing (SDB), its relation to excessive daytime sleepiness and the effect of continuous positive airway pressure (CPAP) on DST. Methods Eighty SDB patients (53.1 ± 1.2 years old, 27.6% women) and 67 healthy participants (52.3 ± 1.6 years old, 26.9% women) wore a temperature data logger for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test (MWT), Multiple Sleep Latency Test, and Sustained Attention to Response Task protocol to objectively quantify daytime sleepiness. A subset of 21 moderate to severe SDB patients were treated with CPAP during at least 3 months and revaluated with the same procedure. A nonparametric analysis was performed to characterize DST to assess differences between groups and associations among DST, polysomnography, and daytime sleepiness measures. Results SDB patients showed an unstable, fragmented, flattened, phase-advanced, and less robust DST rhythm as compared to healthy participants. The more severe the SDB, the worse the DST pattern was, as indicated by the correlation coefficient. Sleepiness, according to MWT sleep latencies, was also associated with the higher fragmentation, lower amplitude, and less robustness of the DST rhythm. Treatment with CPAP improved DST pattern regularity and robustness. Conclusion DST is altered in SDB, exhibiting a direct relationship to the severity of this condition, and improves with CPAP treatment. DST independently correlates with sleepiness, thus, its measurement may contribute to the understanding of the pathophysiology of sleepiness in these patients.

Regularity of cardiac rhythm as a marker of sleepiness in sleep disordered breathing.

Aim The present study aimed to analyse the autonomic nervous system activity using heart rate variability (HRV) to detect sleep disordered breathing (SDB) patients with and without excessive daytime sleepiness (EDS) before sleep onset. Methods Two groups of 20 patients with different levels of daytime sleepiness -sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT) research protocol. The first waking 3-min window of RR signal at the beginning of each nap test was considered for the analysis. HRV was measured with traditional linear measures and with time-frequency representations. Non-linear measures -correntropy, CORR; auto-mutual-information function, AMIF- were used to describe the regularity of the RR rhythm. Statistical analysis was performed with non-parametric tests. Results Non-linear dynamic of the RR rhythm was more regular in the SG than in the AG during the first wakefulness period of MSLT, but not during MWT. AMIF (in high-frequency and in Total band) and CORR (in Total band) yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in classifying SG and AG patients. Conclusion The regularity of the RR rhythm measured at the beginning of the MSLT could be used to detect SDB patients with and without EDS before the appearance of sleep onset.

Chewing-induced segmental myoclonus in a patient with Leigh syndrome

Leigh syndrome (LS) is a mitochondrial disease featuring psychomotor retardation, optic atrophy, ataxia, dystonia, myoclonus, failure to thrive, and seizures. Symptoms may begin any time between birth and adolescence and vary from just noticeable to severe neurologic impairment. Brain magnetic resonance imaging (MRI) in LS typically reveals symmetric lesions involving basal ganglia, thalamus, and brainstem. We report the case of a 19-year-old boy diagnosed with LS who developed chewing-induced segmental myoclonus. His illness started at the age of 2 years with a slowly progressive gait disturbance, dysarthria, and dystonic postures in all 4 limbs. Brain MRI showed symmetric signal hyperintensities on T2-weighted images in basal ganglia. He was diagnosed with probable LS, and a genetic study demonstrated the presence of the T14487C mutation in the mtDNA-ND6 (mitochondrial DNA-nicotinamide adenine dinucleotide dehydrogenase subunit) gene. At the age of 16 years, he developed partial motor seizures involving the left arm with occasional secondary generalization and was treated with oxcarbazepine. He was referred to our Movement Disorders Unit because of his complaints of involuntary movements involving the left face and neck, which appeared when chewing, throughout the previous 2 years. On clinical examination, he showed a gait alteration with dystonic postures on the 4 extremities (video) and mild FIG. 1. A: The predicted binding site for miR-153 in the 30UTR of SNCA and wobbled base pair by the SNCA 30UTR 464 C>A. B: SNCA 30UTR 464 C>A was predicted to change the hybrid structure (green: mir-153; red: SNCA mRNA) and the minimum free energy change by this polymorphism was from 218.7 kcal/mol to 213.8 kcal/mol. C: SNCA 30UTR 464C>A attenuates mir-153 mediated suppression of SNCA. Both in wild-type and SNCA 30UTR 464C>A, mir-153 significantly reduced Renilla/firefly luciferase activity ratio dose-dependently. In both doses of mir-153 tested, reduction in luciferase activity ratio was greater in wild-type. Values 90 ng and 120 ng indicate the amount of pcDNA3 vector containing hsa-mir-153-1 applied. Error bars 5 61.96 obtained from triplicates. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]