Sex Differences in Insomnia and Circadian Rhythm Disorders: A Systematic Review.

Insomnia and circadian rhythm disorders are increasingly common in modern society and lead to significant challenges for people's health and well-being. Some studies suggests that men and women differ in neurohormonal secretion, biological processes, and brain morphology. Thus, such differences may affect the etiology, manifestation, and course of sleep disorders, including insomnia and circadian rhythm. This systematic review aims to synthesize the existing literature on sex differences in insomnia and circadian rhythm disorders. PubMed, MEDLINE, Epistemonikos, and Cochrane databases were searched for articles published from inception until 5 September 2023, not older than five years. We performed a systematic search using MESH and non-MESH queries: (sex differences) or (male and female differences) or (men and women differences) or (men and women) AND (insomnia) or (sleep wake disorder*) or (sleep wake rhythm disorder*) or (circadian rhythm disorder*) or (sleep cycle disruption) or (sleep cycle disorder*). Out off 2833 articles screened, 11 studies were included. The prevalence of insomnia is higher among women, and their sleep is more regular and stable compared to men. Studies evaluating the impact of the stressful situation associated with the lockdown on women's and men's insomnia present discordant results concerning sex differences. Women's circadian rhythm was found to be more stable and less fragmented than men's. However, the progression of peak activity time with age was more pronounced in men. The current literature suggests that risk factors for insomnia and circadian rhythm disorders affect men and women differently. These include cerebrovascular and cardiometabolic factors, shift work, and infections. The long-term effects of insomnia seem to be more relevant for the male sex, shortening lifespan more than in women. By summarizing and analyzing existing studies, we highlight the need for further research to improve understanding of the interaction between sex and sleep.

Diurnal variation of clock genes expression and other sleep-wake rhythm biomarkers among acute ischemic stroke patients.

There is accumulating evidence about sleep-wake rhythm disturbances as potential modifiable risk factors of both incident and recurrent stroke and less favorable outcomes after stroke. To our best knowledge this is the first study designed to investigate clock genes expression profiles in ischemic stroke patients and their relations to other biological and behavioral sleep-wake rhythm biomarkers, sleep structural and clinical stroke features. Altogether, 27 ischemic stroke patients (20 males) with the median age of 56 years and 25 gender and age matched controls were investigated with neurological and objective examination, scales, polysomnography, actigraphy and 24-h blood sampling for melatonin and clock genes profiles. Median melatonin plasma concentrations at four time points at 7, 11 p.m., 3 a.m. and 12 p.m. did not differ significantly between patients and controls, only early morning melatonin concentration at 7 a.m. was significantly lower and cortisol plasma concentration - significantly higher among stroke patients. All four clock genes (ARNTL (BMAL1), NR1D1 (Rev-erbα/ß), PER1, and PER3) showed significant time-of-day variation in both patients' and controls' groups, except expression of NR1D1 (Rev-erbα/ß) at 7 a.m. and PER1 at 12 p.m. differed significantly. In conclusion, acute ischemic stroke patients tended to preserve most of diurnal variation of sleep-wake rhythm molecular patterns. Nevertheless, early morning time point showing higher cortisol and lower melatonin concentrations and lower NR1D1 (Rev-erbα/ß) expression, as well as lower PER1 midday expression reflect specific circadian desynchrony features in different loops of the molecular circadian clock system.

Mapping of European activities on the integration of sex and gender factors in neurology and neuroscience.

BACKGROUND: Neurological disorders pose a profound unmet medical need for which new solutions are urgently needed. The consideration of both biological (sex) and socio-cultural (gender) differences between men and women is necessary to identify more efficacious, safer and tailored treatments. Approaches for putting sex and gender medicine into practice have gathered momentum across Europe, but it is currently unclear to what extent they have been implemented in the field of neurology and neuroscience. METHODS: We mapped current activities in research, funding and education aimed at integrating sex and gender consideration in neuroscience and neurology in Europe. We examined and analyzed data gathered from (1) literature searches, (2) policy documents and reports by the European Commission and national funding agencies, (3) web-based searches, (4) "Web of Science", and (5) searches of project databases of funding agencies. An informative / non-systematic search was performed for sections on policies and funding, education, basic research, while a systematic literature and database review was conducted forquantitative analysis of research output and funded projects in terms of sex and gender analysis. RESULTS: Our mapping shows that there is a growing interest and attention towards sex and gender consideration in neurological fields, both from funding agencies and researchers. However, most activities, especially for education, are limited to the individual motivation of researchers and are not organically built within curricula and strategic research priorities. DISCUSSION: We recommend actions that might help increase the consideration of sex and gender specifically in the field of neuroscience and neurology.

Sleep Dysfunction and Grey Matter Volume.

PURPOSE OF REVIEW: With the voxel-based morphometry (VBM), structural imaging studies turned into new directions aiming to explore neurological disorders differently. This approach helps identify possible pathophysiological correlations between neuroanatomical grey matter (GM) structures in patients with sleep dysfunction. This article reviews recent findings on GM structure in various sleep disorders and possible causes of disturbed sleep and discusses the future perspectives. RECENT FINDINGS: At present, research on the effect of GM volume changes in specific brain areas on the pathogenesis of sleep disturbances is incomplete. It remains unknown if the GM thickness reduction in patients with REM sleep behaviour disorder, obstructive sleep apnea, restless legs syndrome, and insomnia is due to complex disease presentation or direct response to disturbed sleep. Additionally, many VBM studies have yielded inconsistent results showing either reduction or increase in GM. The spatiotemporal complexity of whole-brain networks and state transitions during sleep and the role of GM changes increase new debates. Having multimodal data from large sample studies can help model sleep network dynamics in different disorders and provide novel data for possible therapeutic interventions.

Primary Headaches and Sleep Disturbances: A Cause or a Consequence?

AIMS: To evaluate the possible relationship between sleep disturbances and primary headaches. METHODS: This prospective study was carried out in a random group of patients with active primary headaches (case group) and a control group. Patients with active primary headaches were further stratified into two groups: patients with migraine and patients with tension-type headache (TTH). Participants were questioned using the following standardized tests: Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Berlin Sleep Apnea Questionnaire (BSAQ), and a custom-made headache questionnaire. The results of the questionnaires were compared among patients with TTH, patients with migraine, and age- and sex-matched controls. RESULTS: Of the 143 participants, 22.4% had TTH, 30.8% were diagnosed with migraine, and 46.9% did not have a diagnosed headache disorder. Patients with TTH were more likely to have insomnia (ISI score > 7) than patients with migraine (75% vs 50%, respectively) or controls (75% vs 37.3%, respectively) (P = .002). Frequency of poor sleep quality (global PSQI score ≥ 6) was significantly highest in the TTH group (87.5%), while the migraine and control groups had better sleep quality (47.7% and 43.3%, respectively) (P = .0001). TTH patients were more likely to have insufficient sleep (sleep efficiency < 85%) (53.1%) than those with migraine (25%) or the control group (29.9%) (P = .025). CONCLUSION: Patients who suffered from TTH were more likely to have insomnia than patients with migraine or controls. Nearly all patients with TTH had poor sleep quality, which was also observed in approximately half of the individuals in the migraine and control groups. Three-quarters of patients in the TTH group and more than half in the migraine group indicated inadequate sleep as a trigger factor for headache.

Subjective and objective features of sleep disorders in patients with acute ischemic or haemorrhagic stroke: It is not only sleep apnoea which is important.

BACKGROUND: More than half of stroke patients present with a sleep-related breathing disorder including both central and obstructive forms of sleep apnoea. A cerebral infarction in different brain areas can disrupt sleep regulating pathways and cause insomnia, hypersomnia, circadian rhythm disturbances and other sleep disorders. Therefore, there is a need of objective data about various sleep disorders arising after ischemic or haemorrhagic stroke in order to implement practical recommendations how to suspect, diagnose and treat these conditions. Our medical hypothesis is that non-breathing sleep disorders are common among patients with acute ischemic or haemorrhagic stroke. OBJECTIVE: To investigate the subjective and objective sleep parameters in the patients with an acute ischemic or haemorrhagic stroke. METHODS: In the acute period (from 3 to 10 days after the first symptoms) of stroke all the patients completed questionnaires about sleep complaints and symptoms experienced before and after stroke, Epworth Sleepiness Scale (ESS), National Institute of Health Stroke Scale, Hospital Anxiety and Depression Scale and Modified Rankin Scale. Patients were included for further polysomnography (PSG) and sleep electroencephalography according to these criteria: (1) patients expressing severe sleep related complaints and/or symptoms that are new or have exacerbated after the stroke; and/or (2) patients having the ESS score equal or >10. RESULTS: 66 patients were examined in the acute period of stroke. 33 (50%) patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mostly related to obstructive sleep apnoea (OSA) and insomnia. Finally, 13 (19.7% of the whole sample) patients were selected for performing PSG. 12 of 13 patients were diagnosed with sleep disorder: 1 patient got the diagnosis of mild OSA, 1 - central sleep apnoea (CSA), 2 - combination of OSA and CSA, 1 - combination of mild OSA, periodic limb movement disorder (PLMD) and REM sleep behaviour disorder (RBD), 1 - combination of mild OSA and PLMD, 3 - combination of PLMD and insomnia, 3 - insomnia. There were no significant relations between type, location or treatment of stroke and various PSG measures, as well as type of a diagnosed sleep disorder. CONCLUSIONS: Half of our acute stroke patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mainly related to OSA or insomnia. In the selected PSG group almost all patients were diagnosed with a sleep disorder, half of them having non-breathing sleep disorder, such as PLMD, RBD and insomnia.

Sleep patterns among patients with chronic fatigue: A polysomnography-based study.

OBJECTIVES: The purpose of this study was to detect treatable sleep disorders among patients complaining of chronic fatigue by using sleep questionnaires and polysomnography. METHODS: Patients were referred to hospital for investigations and rehabilitation because of a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The criteria for further referral to full-night polysomnography (PSG) were symptoms of excessive daytime sleepiness and/or tiredness in the questionnaires. RESULTS: Of a total of 381 patients, 78 (20.5%) patients underwent PSG: 66 women and 12 men, mean age 48.6 years, standard deviation ±9.9 years. On the basis of the PSG, 31 (40.3%) patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) patients with periodic limb movement disorder, 32 (41.0%) patients with restless legs syndrome and 54 (69.3%) patients had one or more other sleep disorder. All patients were grouped into those who fulfilled the diagnostic criteria for ME/CFS (n = 55, 70.5%) and those who did not (n = 23, 29.5%). The latter group had significantly higher respiratory (P = .01) and total arousal (P = .009) indexes and a higher oxygen desaturation index (P = .009). CONCLUSIONS: More than half of these chronic fatigue patients, who also have excessive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syndrome. Patients with such complaints should undergo polysomnography, fill in questionnaires and be offered treatment for sleep disorders before the diagnose ME/CFS is set.

Patterns of acute whiplash-associated disorder in the Lithuanian population after road traffic accidents.

OBJECTIVE: To investigate acute whiplash-associated disorder in the Lithuanian population who are unaware of the phenomenon. DESIGN: Controlled cohort study. SUBJECTS/PATIENTS: Seventy-one patients were enrolled from the emergency departments of the Kaunas region of Lithuania following road traffic accidents, examined within 3-14 days after the accident, and compared with 53 matched controls. METHODS: Clinical neurological examination, including range of motion and motion-evoked pain or stiffness in the neck; spontaneous pain and pain pressure threshold. Questionnaires: Quebec Task Force questionnaire (QTFQ); Disability Rating Index (DRI); Cognitive Failures Questionnaire (CFQ); Hospital Anxiety and Depression Scale (HADS) and health perception. RESULTS: Sixty-six of 71 (93%) patients developed acute symptoms. The most frequent symptoms found after road traffic accidents were neck or shoulder pain; reduced or painful neck movements, including decreased range of motion; multiple subjective symptoms according to QTFQ and significantly reduced pain threshold. Perceived health status was decreased and DRI was increased, while HADS showed a significantly higher risk of developing anxiety. Higher grade whiplash-associated disorder was linked with a greater reduction in range of motion and more prominent neck pain. CONCLUSION: Road traffic accidents induce whiplash-associated disorder in patients who seek help, but who are unaware of the condition whiplash-associated disorder. Whiplash-associated disorder should be considered and treated as an entity per se.