Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network.

STUDY OBJECTIVES: The first reports of narcolepsy with cataplexy in Russia were made by Mankovsky (The pathogenesis of narcolepsy (the case of epidemic encephalitis with cataplexy) published in the Sovremennaya psihonevrologia) in 1925. The largest series of patients (n = 110) was reported by A. Vein (doctoral thesis: Hypersomnia Syndrome) in 1964. However, until today, narcolepsy remained relatively unknown in Russia. The aim of this study is to report clinical and polysomnography (PSG)/multiple sleep latency test (MSLT) results in the Russian population and compare them with the European Narcolepsy Network (EU-NN) data (n = 1099) reported. METHODS: Eleven sleep centers from Russia agreed to participate and completed a questionnaire including 58 questions concerning demographic, clinical, PSG, and MSLT data. RESULTS: There were 89 patients with a mean age of 35.6 ± 16.9 years (± here and further indicates standard deviation), 58% males, and 42% females. Narcolepsy started at a mean age of 25.6 ± 14.6 years (range 5-74 years). The mean Epworth Sleepiness Scale score was 18.4 ± 3.5 points (range: 11-24). Sleep paralysis was reported by 59.1%, and hallucinations by 82% of patients. In MSLT, ≥ 2 sleep-onset REM (rapid eye movement) periods (SOREMPs) were found in 81.6%. No center provided human leukocyte antigen (HLA) or cerebral spinal fluid hypocretin data. CONCLUSIONS: Clinical and neurophysiological data from this first study of the Russian Narcolepsy Network suggest a similar profile to the recently reported EU-NN data. The more severe and higher percentage of patients with cataplexy and presenting with both excessive daytime sleepiness and cataplexy may reflect low awareness of narcolepsy in Russia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; URL: https://clinicaltrials.gov/ct2/show/NCT05375890; Name: Clinical and Neurophysiological Characteristics of Narcolepsy; Identifier: NCT05375890. CITATION: Kuts A, Poluektov M, Zakharov A, et al. Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network. J Clin Sleep Med. 2023;19(2):355-359.

How have our clocks evolved? Adaptive and demographic history of the out-of-African dispersal told by polymorphic loci in circadian genes.

The mechanism of the molecular circadian clocks is currently understood as a transcription/translation feedback loop involving more than ten genes. Genetic variation at some of loci in these genes has been shaped by adaptation to environmental factors. In particular, latitudinal clines in allele frequency were documented in several animal species, but the contradictory conclusions were drawn from the results of rare human studies. Here we tested whether the out-of-African dispersal of human populations to higher latitudes of the Eurasian continent was associated with latitude-dependent shifts in allele frequency at polymorphic loci in genes of three (reference, circadian and skin pigmentation) groups. In order to detect the genetics-based signatures left by latitude-driven adaptation and to distinguish them from the confounding effects of population demographic history, we analyzed allele frequencies in 1594 individuals from 5 African and 11 Eurasian populations of the 1000 Genomes Project Phase 3. Up to 80 polymorphisms with global minor allele frequency > 0.2 were sampled from each of 36 genes (1665 polymorphisms in total). As expected, percentage of polymorphisms demonstrating both significantly enlarged differentiation of Eurasian populations on allele frequency and significant correlation between latitude and allele frequency was significantly higher in pigmentation genes compared to circadian genes and in circadian genes compared to reference genes. We also showed that the latitude-driven adaptation can be separated from genetic consequences of demographic perturbations by comparison of results obtained for the whole set of 16 African and Eurasian populations with results for only Eurasian populations that share the common demographic history. The revealed latitudinal clines in allele frequency seemed to be shaped by polygenic selection occurring by small allele frequency shifts spread across many loci in circadian and non-circadian genes. The present results provided a rationale for necessity to facilitate candidate gene studies by prioritizing genetic markers of chronotype.

Age-Related Sleep Changes and its Implication in Neurodegenerative Diseases.

In the article authors discuss the current data on sleep changes with aging focusing on the influence of age-related degenerative changes in orexin-containing and pacemaker brain areas. Pathophysiological mechanisms of sleep disturbances in Parkinson's and Alzheimer's diseases have much in common with normal age neurophysiological changes. Maintenance of the sleep-promoting systems function could positively modify the course of these diseases.