Ramona Cordani

Experiences in which the sense of the body becomes distorted offer a unique window into how the brain constructs the bodily self. Despite their clinical relevance in conditions such as depersonalization and body-image disorders, large-scale brain dynamics underlying unusual bodily experiences (UBEs) remain poorly understood, and no prior study has examined them systematically across wakefulness and sleep. Here, we analyzed a high-density EEG dataset including 36 UBE episodes, such as floating sensations, distorted body boundaries, and out-of-body experiences, recorded across rapid eye-movement (REM) sleep, light sleep, sleep arousals, and wakefulness during meditation (N=20). We quantified the temporal irreversibility of neural dynamics, a marker of cortical hierarchical organization, and complemented these analyses with whole-brain signal complexity measures following a within-subject design. UBEs were consistently associated with a global reduction in neural irreversibility and cortical hierarchical differentiation relative to non-UBEs and wakefulness, along with a concurrent increase in whole-brain complexity to levels comparable to wakefulness. Together, these findings suggest that UBEs reflect a neural state combining high informational richness with a transient flattening of cortical hierarchy, a profile that resembles that observed in psychedelic states.

Background: Actigraphy is a wearable accelerometry method widely used in sleep research and clinical practice, yet its diagnostic and phenotypic value remains uncertain due to methodological heterogeneity and inconsistent reporting. This systematic review and meta-analysis determined whether actigraphy-derived metrics distinguish primary sleep disorders from healthy controls, and characterised reporting and methodological practices.Methods: Electronic databases were searched for observational studies published in 1990–2025 using actigraphy in patients with insomnia disorder (ID), central disorders of hypersomnolence (CDH), or circadian rhythm sleep–wake disorders (CRSWD), alongside healthy controls. Standardised mean differences (Hedges' g) were pooled using random-effects models. This study is registered with PROSPERO (CRD420251231134).Findings: 37 studies met eligibility criteria, of which 34 contributed to the meta-analysis. The sample comprised 1517 patients with ID, 105 with narcolepsy type 1 (NT1), 110 with delayed sleep–wake phase disorder (DSWPD), and 1647 healthy controls; no studies were identified for other CDH or CRSWD subtypes. In ID, actigraphy showed prolonged sleep onset latency (0·53 [95% CI 0·40–0·66]), reduced sleep efficiency (−0·65 [−0·83 to −0·47]), and increased wake after sleep onset (0·55 [0·34–0·75]). In NT1, nocturnal disruption was more severe (sleep efficiency −1·77 [−2·63 to −0·90]; wake after sleep onset 1·83 [1·09–2·56]), with reduced daytime activity (−0·90 [−1·19 to −0·61]) and increased napping. In DSWPD, sleep onset time (2·10 [1·56–2·63]) and offset time (1·45 [0·96–1·94]) were delayed, with modestly reduced total sleep time but preserved sleep efficiency. Heterogeneity was moderate-to-high for most estimates. Reporting concentrated on nocturnal continuity parameters, while diurnal and night-to-night variability metrics remained underrepresented. Devices, algorithms, and acquisition protocols varied substantially.Interpretation: Actigraphy identified disorder-specific signatures: impaired sleep continuity in ID, nocturnal disruption with daytime impairment in NT1, and delayed timing with preserved sleep efficiency in DSWPD, supporting pathophysiology-aligned metric selection. Standardised reporting and acquisition protocols are needed to advance clinical translation.

Purpose of Review: Sleep disturbances are a common, heterogeneous comorbidity of autism spectrum disorder (ASD). This systematic review updates the field on sleep in ASD over 2022–2026, with attention to how the evidence has evolved. Recent Findings: Eighty-nine studies met inclusion criteria. Sleep disturbance remained more prevalent in autistic individuals than in typically developing peers (47–84%), confirmed by actigraphic and polysomnographic measures. The most distinctive recent advance is in sleep microstructure: spindles, slow-oscillation–spindle coupling, and oscillatory EEG features are emerging as candidate neurophysiological markers. Behavioural and parent-mediated programmes remain the most consistent intervention evidence, while pharmacological trials produced largely null effects; neuromodulation, microbiota-targeted, and physical-activity interventions are preliminary but expanding. Summary: The question of whether individuals with ASD sleep worse than peers appears largely settled. Future priorities are harmonized objective sleep protocols, adequately powered trials in emerging intervention categories, and broader inclusion of adults with ASD, who remain markedly under-represented.

Disorders of arousal (DOAs) and sleep-related hypermotor epilepsy (SHE) share overlapping clinical features, making differential diagnosis challenging. Although video polysomnography remains the gold standard, EEG patterns to distinguish these conditions are not yet well defined. Slow-wave sleep (SWS) fragmentation is a key marker of DOA, but its characteristics in SHE remain unexplored. The aim of this study was to assess SWS fragmentation in DOAs and SHE, its potential diagnostic value, and overnight dynamics. Eighty-seven patients with DOAs (n = 47; mean age 23.90 ± 13.10 years; 44.7% children) or SHE (n = 40; mean age 25.11 ± 13.08 years; 27.5% children) underwent overnight polysomnography with blinded scoring. SWS fragmentation was quantified, distinguishing fast, mixed, and slow arousals, and its overnight evolution was evaluated. Groups were compared and diagnostic SWS fragmentation cutoff values were defined using receiver-operating characteristic curves. Total sleep time and sleep efficiency did not differ between groups. N2 sleep percentage was significantly lower in DOAs than in SHE (p = 0.008), whereas REM sleep percentage was higher in DOAs (p = 0.008). SWS percentage was comparable between groups (DOA: 23.50% ± 6.01; SHE: 21.11% ± 6.78). SWS fragmentation was significantly higher in DOAs than SHE (p < 0.001), particularly in slow and mixed components (p < 0.001), whereas SHE showed more fast interruptions (p = 0.006). Regarding overnight dynamics, linear mixed models revealed significant group × period interactions for SWS fragmentation index and slow/mixed arousal index, indicating distinct overnight patterns, with DOAs showing a marked reduction at the end of the night. In adults, the highest area under the curve (AUC) values were obtained for SWS Fragmentation and slow/mixed arousal indices with satisfactory classification performances (AUC 0.81 and 0.84, respectively). The SWS Fragmentation Index cutoff value of 6.64/h and slow/mixed arousal index cutoff of 2.40/h reached a sensitivity of 80.8% and specificity of 86.2%. In children, SWS Fragmentation Index ≥5.06/h achieved 76.2% sensitivity and 90.9% specificity (AUC 0.84) while slow/mixed arousal index showed excellent discriminative performance (AUC 0.96) with a cutoff of 2.10/h reaching 95.2% sensitivity and 90.9% specificity. SWS fragmentation, especially mixed and slow arousals, represents a supportive neurophysiologic marker that may assist the differential diagnostic process between DOAs and SHE. Quantitative SWS microstructure parameters may improve diagnosis and provide insight into pathophysiologic mechanisms.

This study investigated structural connectivity in Alternating Hemiplegia of Childhood (AHC) using advanced tractography and connectome analysis, as characterizing brain network alterations in this rare disorder may clarify its cognitive and motor impairments. This prospective monocentric study included 10 individuals with AHC (mean age 23.2 years) and 20 matched healthy controls. All participants underwent 3T MRI with 3D T1-weighted and high-angular resolution diffusion sequences. Brain structural networks were evaluated using global and nodal graph measures, modular organization, and network-based statistics. Associations with motor and cognitive performance were examined using the Wechsler scales, Vineland Adaptive Behavior Scales-II, International Cooperative Ataxia Rating Scale, and the Movement and Disability sections of the Burke-Fahn-Marsden Dystonia Rating Scale. At the global level, AHC participants exhibited reduced network integration, reflected by higher characteristic path length (P = 0.04) and lower global efficiency (P = 0.04) compared to controls. Mean degree (P = 0.03) and normalized betweenness (P = 0.04) were also decreased. Network-based statistics revealed a single subnetwork of reduced connectivity involving basal ganglia, frontal, and insular regions bilaterally (P = 0.01). At the nodal level, 21 of 84 nodes showed reduced degree, mainly within frontal, limbic, temporal, occipital lobes, and basal ganglia. Nodal graph-theoretical metrics showed widespread, region-specific correlations with motor severity and cognitive performance, particularly involving sensorimotor, fronto-striatal, temporal, limbic, cerebellar, and subcortical regions. In summary, AHC is characterized by a globally less integrated and sparser structural brain network, with prominent disruption of cortico-striatal and associative circuits and region-specific nodal alterations that correlate with motor severity and cognitive impairment.

Few studies have investigated sleep features in people with alternating hemiplegia of childhood (AHC). In this study, we present a bespoke survey of individuals with AHC to characterize sleep disturbances in this condition. A cross-sectional survey was disseminated through the UK and Italian AHC family associations, addressing their registered families with at least 1 child or adult with a confirmed diagnosis of AHC by their national reference centers and who had consented to be contacted by email. The entire questionnaire implemented in the online surveys was organized into 3 main sections and included the Pittsburgh Sleep Quality Index (PSQI) scale. This scale ranges from 0 to 21, with higher scores indicating poorer sleep quality. Internal consistency of the questionnaire was assessed using Cronbach alpha statistic. Forty-eight of 54 families with AHC (88.89%) filled out at least 1 item of the AHC-Sleep Questionnaire, and 36 of 54 (66.67%) completed the whole questionnaire. Eighteen of 44 people (40.91%) from our cohort reported having a problem with sleep, which was persistent for 10 of 44 (22.7%). Twenty-five of 44 people (56.82%) reported multiple arousals during a typical night, and for 9 of 25 (36%), these could be very prolonged. For 16 of 40 (40%) and 19 of 40 (47.5%), plegic spells resolved or improved, respectively, during sleep, whereas 5 of 40 (12.5%) reported no effect of sleep on these spells. The mean global PSQI score in 40 people was 5.40 (SD ± 4.69). Fifteen of 40 individuals (37.5%) had a global PSQI score ≥5. PSQI scores were significantly higher in those individuals who completed the questionnaire during summer (n = 6) compared with those who completed them during winter (n = 33) (p = 0.011, Mann-Whitney test). We found a strong correlation between AHC paroxysmal spell burden and PSQI score (Spearman r = 0.39, p < 0.01). The survey demonstrated a high degree of internal consistency, with a Cronbach alpha of 0.88 (95% CI 0.83–0.91). We dissected sleep issues and reported sleep disruption, including elevated global PSQI scores, in a significant proportion of individuals with AHC. The main implication of this study is the importance of conducting comprehensive and regular assessments of sleep in both children and adults with AHC.

Background: Alternating Hemiplegia of Childhood (AHC) is a severe channelopathy that manifests before 18 months of age, primarily caused by pathogenic variants in the ATP1A3 gene. It is characterized by recurrent and disabling episodes of plegia, dystonia, dysautonomia, along with chronic neurological features and cardiac arrhythmias. About 50% of AHC patients have epilepsy, and a subset of them may develop refractory or super‐refractory status epilepticus. Currently, there are no specific available therapeutic guidelines, particularly for managing life‐threatening paroxysmal and epileptic episodes in the Intensive Care Unit (ICU).Case report: This report aims to illustrate a comprehensive treatment approach and clinical management of a young boy with AHC and multiple episodes of super‐refractory status epilepticus throughout his lifetime. The patient was diagnosed with AHC at the age of 6 months, carrying the most severe ATP1A3 gene mutation—p.Glu815Lys. Epileptic seizures started at 24 months of age, and after a relatively stable clinical course, he experienced a first super‐refractory status epilepticus at the age of 16. Subsequently, he presented two additional episodes of status epilepticus and faced progressive neurological deterioration until death at the age of 20.Discussion: AHC management is a substantial challenge due to the coexistence of multiple paroxysmal events, epilepsy, chronic neurological impairments, and the possibility of cardiac abnormalities, including short QTc or cardiac rhythm complications. Tailored treatment and deep knowledge of this complex disease are imperative for effective management.

Background Kleefstra's syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described. The syndrome can be either caused by a microdeletion in 9q34.3 or by pathogenic variants in the euchromatin histone methyltransferase 1 gene (EHMT1, *607001). Although epilepsy has been reported in 20 to 30% of subjects, a detailed description of epileptic features and underlying etiology is still lacking. The purpose of this study is to investigate epilepsy features in a cohort of epileptic patients with KS. Methods This multicenter study investigated eight patients with KS and epilepsy. Our findings were compared with literature data. Results We included five patients with 9q or 9q34.33 deletions, a subject with a complex translocation involving EHMT1, and two with pathogenic EHMT1 variants. All patients presented with moderate to severe developmental delay, language impairment, microcephaly, and infantile hypotonia. Although the epileptic manifestations were heterogeneous, most patients experienced focal seizures. The seizure frequency differs according to the age of epilepsy onset, with patients with early-onset epilepsy (before 36 months of age) presenting more frequent seizures. An overtime reduction in seizure frequency, as well as in antiseizure drug number, was observed in all patients. Developmental delay degree did not correlate with seizure onset and frequency or drug resistance. Conclusion Epilepsy is a frequent finding in KS, but the underlying pathogenetic mechanism and specific features remain elusive. The data that support the findings of this study are reported in the manuscript. ^* T.G. and R.C. contributed equally to this work. Received: 11 June 2023 Accepted: 12 September 2023 Article published online: 06 October 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany