Search Results (36)

Periventricular nodular heterotopia (PVNH) is a genetically heterogeneous malformation of cortical development with variable neurological outcomes. Among recessive forms, ARFGEF2-related disorder is uniquely characterised by the association of diffuse PVNH and progressive microcephaly. We describe a two-year-old boy born to consanguineous parents who presented with severe developmental delay, hypotonia, progressive microcephaly, and infantile-onset epileptic spasms with developmental regression. Brain MRI showed extensive bilateral PVNH associated with callosal hypoplasia and ventriculomegaly. EEG revealed dysmature background activity with multifocal epileptiform discharges and runs of asynchronous fast activity during sleep. Genetic testing identified a novel homozygous nonsense variant in ARFGEF2. The clinical course was characterised by drug-resistant epilepsy and multisystemic involvement, including feeding difficulties and recurrent respiratory infections. To contextualise this case, we performed a comprehensive review of previously reported patients, further delineating the clinical, neuroradiological, and electroclinical spectrum of ARFGEF2-related disorder. This case highlights progressive microcephaly as a key distinguishing feature of ARFGEF2-related PVNH and underscores the importance of early genetic diagnosis to guide targeted surveillance for extra-CNS complications and multidisciplinary care. Full article

Background: Gender differences in adolescent mental health are well documented; however, the extent to which modifiable behavioral and psychosocial factors account for the excess of mental health problems in females remains insufficiently quantified. Methods: Data from the 2025 Corona and Psyche South Tyrol (COP-S) survey comprised a base sample of 2428 adolescents aged 11–19 years (51.4% males) with valid self-reported data. Multivariable regression analyses were conducted on 1448–1603 adolescents (depending on the outcome) who provided complete responses to the relevant predictor and outcome measures. Gender differences in depressive symptom scores (PHQ-2), generalized anxiety symptom scores (SCARED-GAD), and emotional/behavioral difficulties (SDQ) were examined using Mann–Whitney U and chi-square tests. Multivariable linear regression models were used to assess the associations between mental health outcomes and the ten predictors. Gender effects were quantified by comparing standardized regression coefficients from unadjusted and adjusted models. Results: Female adolescents reported higher generalized anxiety symptoms (median 6 vs. 4; rank-biserial r = 0.24), depressive symptoms (r = 0.13), and emotional/behavioral (r = 0.08) scores than male adolescents. School stress, problematic Internet use, and sleep-onset difficulties were the factors most strongly associated with all three outcomes (all p < 0.001). After multivariable adjustment, gender remained significantly associated with generalized anxiety symptoms (β = 0.18) and depressive scores (β = 0.09) but no longer reached significance for emotional/behavioral scores (β = 0.04, p = 0.078). The attenuation of the gender effect ranged from 25.3% for generalized anxiety symptoms to 37.1% for depressive symptoms and 58.5% for emotional/behavioral difficulties. Conclusions: Gender differences in adolescent mental health were substantially attenuated after adjustment for modifiable behavioral and psychosocial factors, with the gender difference in emotional/behavioral scores no longer statistically significant after adjustment. Persistent gender disparities in generalized anxiety symptoms suggest that mechanisms beyond the measured behavioral correlates may contribute to this gender difference and warrant further investigation. Full article

Background/Objectives: This longitudinal study examined the association between sleep duration, sleep difficulties, and sleeping place at one year (t1) and corresponding characteristics at 4/5 years of age (t2). Methods: Data were collected from 2018 to 2021 (t1) and from 2021 to 2024 (t2) in the LIFE Child cohort study conducted in Leipzig, Germany. Parents completed the Brief Infant Sleep Questionnaire at t1 and the Child Sleep Habits Questionnaire at t2. Associations between sleep characteristics at t1 and t2 were estimated using linear and logistic regression models. All associations were adjusted for child sex, age at t2, and maternal education. Results: The analyses showed significant associations between shorter sleep durations, later sleep onset times, more frequent nightly awakenings and bed sharing and room sharing at t1 and more sleep difficulties at t2. A shorter sleep duration at t2 was predicted by shorter sleep and more parent-perceived sleep difficulties at t1. Bed sharing and room sharing at t1 were significantly associated with a lower probability of sleeping alone at t2. Conclusions: These results indicate that sleep duration, sleep difficulties, and sleeping places are already stable in early childhood. Full article

Background: Parkinson’s disease (PD) is clinically heterogeneous, yet the genetic architecture underlying this heterogeneity remains incompletely understood. We examined the genetic correlates of four complementary PD subtyping frameworks: the clinical motor subtype (tremor-dominant [TD] vs. postural instability/gait difficulty [PIGD]), alpha-synuclein seed amplification assay status (SAA+ vs. SAA−), the pathological subtype (brain-first vs. body-first, based on the presence of REM sleep behavior disorder), and the data-driven subtype (diffuse malignant [DM] vs. mild-motor predominant [MMP] vs. intermediate [IM]). Methods: We analyzed 1390 PD patients from the Parkinson’s Progression Markers Initiative (PPMI) with genotypes available for seven PD-associated genes (LRRK2, GBA1, SNCA, PRKN, PINK1, PARK7, VPS35), including specific variant resolutions (LRRK2 G2019S, R1441G/C/H; GBA1 N409S, severe variants; SNCAA53T), and APOE (ε2/ε3/ε4 alleles). Genetic variant frequencies were compared across subtypes using chi-square or Fisher’s exact tests with the Benjamini–Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cramér’s V. multivariable logistic regression estimated adjusted odds ratios with Wald-based 95% confidence intervals. Results: Among genotyped PD patients, LRRK2 carriers constituted 13.7% (190/1390; 170 G2019S, 18 R1441G/C/H), GBA1 8.6% (119/1390; 96 N409S, 23 severe), and SNCA 2.0% (28/1390; all A53T). APOE ε4 carriers comprised 23.4% (323/1380). SAA-negative patients were markedly enriched for LRRK2 variants (37.1% vs. 10.2%, p = 3.7 × 10⁻¹⁹, q < 0.001, V = 0.25), specifically G2019S (28.5% vs. 9.6%, p = 4.9 × 10⁻¹¹, q < 0.001) and R1441G/C/H (7.9% vs. 0.5%, p = 2.7 × 10⁻¹², q < 0.001). Body-first PD was enriched for GBA1 carriers (12.3% vs. 6.7%, p = 0.004, q = 0.021) and had less LRRK2 carriers (7.9% vs. 15.0%, p = 0.002, q = 0.013). The DM subtype had the highest GBA1 frequency (14.0% vs. MMP 5.9%, p < 0.001, q = 0.003). After FDR correction, 10 out of 48 univariate tests remained significant. Clinical subtypes (TD vs. PIGD) showed only nominal LRRK2 differences that did not survive FDR correction. The APOE genotype did not differ across any framework. Conclusions: PD subtypes defined by alpha-synuclein pathology (SAA), pathological onset pattern (brain-first/body-first), and data-driven classification (DM/MMP/IM) show distinct genetic profiles that survive multiple comparison correction. LRRK2 variants strongly associate with SAA negativity (V = 0.25); GBA1 variants associate with the severe body-first onset and the diffuse malignant subtype. Full article

Background/Objective: Dizziness is managed using various therapies, including lifestyle changes, nutritional supplementation, pharmaceutical therapies, and physical therapy, each offering differing efficacy. With legalization of cannabis in Canada, patients are exploring its use in treating their dizziness and related symptoms. Limited knowledge exists regarding usage patterns, forms, doses, and effects on these symptoms. The current study aims to examine cannabis use in patients experiencing dizziness. Methods: We conducted a cross-sectional study at the Ottawa Hospital outpatient neuro-otology clinic. Eligible participants included new patients presenting with a primary complaint of dizziness and follow-up patients reporting new-onset dizziness. Participants completed a questionnaire capturing demographic data, dizziness and related symptoms, attitudes toward cannabis use, consumption patterns, and its perceived effects on their symptoms. Results: Of 154 participants, 118 (77%) expressed willingness to consider cannabis for dizziness and 78 (51%) reported previous cannabis use. Of those patients, 44 (56%) consumed it recreationally, largely via smoking (29/78, 37%). Approximately 21% of these patients reported a moderate–large subjective relief from dizziness after use of cannabis. The most common diagnoses amongst cannabis users were migraine/vestibular migraine (24%), persistent postural perceptive dizziness (22%), and benign paroxysmal positional vertigo (17%). Other related symptoms relieved by cannabis included sleep (28/78, 36%), emotional difficulties (17/78, 22%), neck pain/stiffness (14/78, 18%) and headaches/migraines (9/78, 12%). Conclusions: There is generally a positive attitude towards cannabis use in treating dizziness amongst patients, with a subset of patients reporting a subjective improvement of dizziness and its related symptoms, such as sleep and emotional difficulties. Full article

Paradoxical interventions involve asking patients to maintain or exaggerate the symptoms they wish to eliminate, with the aim of reducing them. These techniques received empirical support, particularly in the treatment of sleep-onset insomnia, during the 1980s. However, changes in sleep habits over recent decades warrant further research on their current applicability. This article reports a pilot study involving 26 women (aged 40–70) with significant difficulty initiating sleep, who were randomly assigned to either a paradoxical or a non-paradoxical treatment; a prior waiting period was also used as a waitlist control. Both treatments produced statistically significant improvements in insomnia scores between pre- and post-treatment, with no significant differences between groups. These findings suggest that paradoxical interventions may be effective for the current treatment of sleep-onset insomnia and support the need for randomized clinical trials with larger samples. Full article

Background: Tinnitus has been increasingly reported during the COVID-19 pandemic, following both infection and vaccination. While these reports suggest that pandemic-related factors may influence the onset or worsening of tinnitus, the perceptual characteristics and functional consequences of such cases remain poorly understood. This study examined the nature, severity, and communication-related impact of self-reported tinnitus following COVID-19 vaccination. Methods: A total of 770 adults who self-reported new or worsened tinnitus after vaccination completed a structured online survey between August 2021 and May 2023. Standardized instruments included the Tinnitus Functional Index (TFI), the Speech, Spatial and Qualities of Hearing Scale (SSQ), and visual analog scales assessing loudness discomfort and hyperacusis-related symptoms. Analyses included descriptive statistics, chi-square tests, t-tests, and correlation matrices. Results: Respondents reported moderate to severe tinnitus-related distress, with the greatest impacts on emotional control, sleep, and relaxation. Many described communication difficulties in noisy or multi-talker environments, despite relatively preserved spatial hearing and sound quality. A substantial subset endorsed hyperacusis symptoms, including sound-induced annoyance, fear, and intolerance. Correlation analyses revealed strong associations between emotional, cognitive, and auditory domains, underscoring the multidimensional burden of tinnitus in this population. Conclusions: Self-reported tinnitus after COVID-19 vaccination was associated with distress, sleep disruption, and communication difficulties, mirroring patterns commonly observed in tinnitus more broadly. Although causality cannot be determined, these findings highlight the importance of comprehensive audiological and psychological assessment for individuals reporting auditory complaints after vaccination and support the inclusion of functional hearing outcomes in tinnitus evaluation protocols. Full article

Background/Objectives: Smith–Magenis Syndrome (SMS) is a rare neurodevelopmental disorder characterized by severe sleep disturbances and an advanced melatonin rhythm. Current treatments, mainly exogenous melatonin and β-blockers, have not been evaluated in children. This study aimed to characterize the clinical, sleep, and chronobiological profiles of children with SMS under treatment and to assess the effects of melatonin and β-blockers. Methods: In this prospective, single-center study, 20 children with genetically confirmed SMS (aged 5–13 years; 55% female) underwent 15-day home actimetry and 48 h hospitalization, during which questionnaires, polysomnography (PSG), and salivary melatonin/cortisol profiling were performed. Melatonin and psychostimulants were discontinued 36 h before hospitalization. Results: Overall, 95% of children received melatonin and 20% β-blockers. Despite treatment, insomnia was reported in 90%, excessive daytime sleepiness in 65%, and learning problems in 90%. On actimetry, melatonin improved the mean nocturnal awakening duration (1.4 vs. 2.3 min, p = 0.040), wake-up time (06:50 vs. 06:11, p = 0.004), and longest continuous sleep episode (398 vs. 317 min, p = 0.040), but had little effect on the total sleep time, efficiency, and midpoint of sleep. Very high daytime salivary melatonin persisted (median peak 169.50 pg/mL) despite the last exogenous melatonin intake being more than 48 h prior to sampling, suggesting possible iatrogenic accumulation. The median peak in melatonin occurred at 11:57 and that in cortisol at 08:22. In children with β-blockers, there was a tendency toward an earlier melatonin peak but also toward delayed sleep onset, increased nocturnal awakenings, and reduced total sleep. Conclusions: Children with SMS showed persistent sleep difficulties and an advanced circadian phase despite sleep treatments. Exogenous melatonin provides partial benefit but may lead to daytime accumulation, while β-blockers may have adverse sleep effects despite beneficial effects on melatonin peak secretion, warranting further study. Full article

Background/Objectives: Sleep disturbances are among the most prevalent and persistent comorbidities in children and adolescents with autism spectrum disorder (ASD), affecting up to 83% of this population. These disturbances not only impact the quality of life but are increasingly recognized as significant contributors to behavioral dysregulation. Methods: This systematic review synthesizes evidence from 26 studies published between 2010 and 2024, examining the association between sleep problems and behavioral outcomes in individuals with ASD aged 2 to 18 years. Results: The findings reveal consistent associations between sleep-onset insomnia, night walking, bedtime resistance, and various behavioral difficulties, including aggression, hyperactivity, and emotional dysregulation. Internalizing symptoms and exacerbation of core ASD features were also linked to chronic sleep problems. Studies employing objective sleep measures, such as actigraphy and polysomnography, further supported these associations by identifying disruptions in sleep architecture correlated with behavioral severity. While most included studies were of moderate to high methodological quality, the limited number of randomized controlled trials and heterogeneity of sleep and behavior assessment tools highlight the need for standardization. Conclusions: Overall, the review emphasizes the importance of routine sleep evaluation in ASD clinical care and supports targeted sleep interventions as a potential strategy to reduce behavioral problems and improve developmental outcomes. Full article

Background/Objectives: Sleep is essential for children’s well-being, yet insufficient sleep duration and quality are common among preschoolers. The brain–gut microbiota axis, a bidirectional communication network connecting the brain, the gastrointestinal tract, and the microorganisms living there, known as the gut microbiota, influences sleep regulation, but its role in children remains largely unexplored. Here, we examined the association between gut microbiota and sleep in preschoolers from Étude Longitudinale Française depuis l’Enfance (ELFE) birth cohort study. Methods: This study included 597 children (51.2% boys) with available stool samples and sleep data at 3.5 years. The gut microbiota data was analyzed using bacterial 16S rRNA sequencing. Data on day and night sleep durations and frequencies of sleep onset difficulties and night waking were collected through telephone questionnaires and grouped into ‘optimal’ and ‘suboptimal’ clusters using Latent Class Analysis. Statistical analyses involved multivariate logistic regressions or multivariate permutation analysis of variance, controlling for confounders. Results: In total, 25% of the included children were in the suboptimal sleep cluster. No significant associations were found between gut microbiota diversity and composition and sleep clusters at age 3.5 years. Similarly, no differences were found in the abundance of specific microbiota genera between the two sleep clusters. Conclusions: While emerging evidence suggests correlations between gut microbiota and sleep in preschool children, our results do not confirm such correlations. The data used in this study were obtained from a homogeneous, high socioeconomic population, which must be considered when interpreting the findings. Further research is needed to validate the results of this study. Full article

Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in ASD, may further exacerbate these disturbances by affecting arousal regulation and environmental responsiveness during sleep. Given the fundamental role of sleep in brain maturation, its disruption negatively impacts synaptic plasticity and neurological development, particularly during critical periods. These sleep-related alterations can influence cognitive and behavioral outcomes and may serve as early indicators of ASD, highlighting their potential value in early diagnosis and intervention. Understanding the neurobiological mechanisms linking sleep and ASD is essential for developing targeted therapeutic strategies. Ongoing research increasingly focuses on pharmacological, nutraceutical, and behavioral interventions aimed at mitigating sleep disorders and their cascading effects on neurodevelopment. Optimizing these therapeutic approaches through a multidisciplinary lens is crucial for enhancing clinical outcomes and improving overall quality of life in children with ASD. Full article

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder that not only affects attention and behavior but is also intricately linked with sleep disturbances and immune system dysregulation. Recent research highlights that individuals with ADHD frequently experience sleep problems, which in turn exacerbate ADHD symptoms and contribute to cognitive and emotional difficulties. Immunological alterations, including elevated proinflammatory cytokines and hypothalamic–pituitary–adrenal axis dysfunction, have been observed among ADHD patients, suggesting a biological interplay between inflammation, sleep, and neurodevelopment. Genetic and environmental factors further modulate these relationships, influencing the onset and progression of the disorder. Thus, there is a need to find a key connecting such topics and the most vulnerable subjects in order to contribute towards a more personalized approach. This review examines the complex relationships between sleep, immunology, and ADHD, and explores the underlying mechanisms that involve circadian rhythm genes, neuroinflammation, and neurotransmitter imbalances. Our review outlines therapeutic strategies, emphasizing the importance of integrated pharmacological, behavioral, and lifestyle interventions to improve sleep quality, regulate immune responses, and ultimately enhance the overall management of ADHD. Full article

Sleep is a vital physiological process for recovery and health. In people with knee osteoarthritis (OA), disrupted sleep is common and linked to worse clinical outcomes. Commercial sleep trackers provide an accessible option to monitor sleep in this population, but their accuracy for detecting sleep, wake, and sleep stages remains uncertain. This study compared nighttime sleep data from polysomnography (PSG) and Fitbit Sense in individuals with knee OA and insomnia. Data were collected from 53 participants (60.4% women, mean age 51 ± 8.2 years) over 62 nights using simultaneous PSG and Fitbit recording. Fitbit Sense showed high accuracy (85.76%) and sensitivity (95.95%) for detecting sleep but lower specificity (50.96%), indicating difficulty separating quiet wakefulness from sleep. Agreement with PSG was higher on nights with longer total sleep time, higher sleep efficiency, shorter sleep onset, and fewer awakenings, suggesting better performance when sleep is less fragmented. The device showed limited precision in classifying sleep stages, often misclassifying deep and REM sleep as light sleep. Despite these issues, Fitbit Sense may serve as a useful complementary tool for monitoring sleep duration, timing, and regularity in this population. However, sleep stage and fragmentation data should be interpreted cautiously in both clinical and research settings. Full article

Background/Objectives: Primary insomnia is characterized by persistent sleeplessness that is not caused by medical, psychological, or environmental factors. It is defined by difficulty initiating or maintaining sleep for at least one month, leading to significant distress or impairment in daily functioning. This randomized, crossover, double-blind, placebo-controlled clinical trial aimed to assess the efficacy and tolerability of a Scutellaria lateriflora L. extract-based food supplement in subjects with mild to moderate primary insomnia. Methods: A total of 66 participants, aged 18–70 years, were randomly allocated into two groups (1:1 allocation ratio) and received either the food supplement (400 mg/day) or a placebo for 56 days, separated by a 28-day washout period. The clinical effectiveness of the food supplement was assessed using the Pittsburgh Sleep Quality Index (PSQI) as the primary outcome measure. Secondary outcomes included sleep-wake cycle parameters (sleep onset latency, sleep efficiency, and total sleep time) and a Visual Analog Scale (VAS). Results: A significant improvement in sleep-wake balance following supplementation with S. lateriflora, as reflected by enhanced scores in both primary and secondary outcomes, was observed. Furthermore, none of the participants reported adverse effects from the food supplement. Conclusions: Overall, these findings suggest that a S. lateriflora extract-based food supplement is a safe and effective strategy for restoring the sleep-wake cycle and improving quality of life in individuals with primary insomnia. Full article

The complicated association between sleep apnea and postpartum depression (PPD), two diseases that can have a major influence on a mother’s health and well-being, is examined in this thorough review. An increasing number of people are realizing that sleep apnea, which is defined by repeated bouts of upper airway obstruction during sleep, may be a risk factor for PPD. The literature currently available on the frequency, common risk factors, and possible processes relating these two disorders is summarized in this study. We investigate the potential roles that sleep apnea-related hormone fluctuations, intermittent hypoxia, and fragmented sleep may play in the onset or aggravation of PPD. We also talk about the difficulties in identifying sleep apnea in the postpartum phase and how it can affect childcare and mother–infant attachment. The evaluation assesses the effectiveness of existing screening techniques, available treatments, and how well they manage both illnesses at the same time. Lastly, we identify research gaps and suggest future lines of inquiry to enhance maternal health outcomes. Full article