Founder effects are important population genetic mechanisms that influence the distribution of inherited neurological diseases. To review the global distribution of founder mutations across the spectrum of inherited movement disorders, summarize the molecular mechanisms, and discuss their clinical implications for diagnosis, genetic counselling, and emerging precision therapies. A scoping review was conducted following PRISMA-ScR principles, searching PubMed/MEDLINE and secondary reference lists for studies reporting founder mutations, shared haplotypes, or population-specific mutation enrichment in inherited movement disorders; studies lacking genetic or epidemiological evidence for a founder effect were excluded. Seventy-one studies described 53 founder-mutation entries across 40 movement-disorder phenotypes and 48 genes or repeat-expansion loci (Table 1), most frequently spinocerebellar ataxias, dystonia, and NBIA syndromes. Shared haplotypes, mutation-age estimation, and genealogical evidence consistently supported a founder origin (e.g., TOR1A dystonia in Ashkenazi Jews, LRRK2/GBA1-associated Parkinson disease in Ashkenazi Jewish and North African populations, SCA2 in Cuba, SCA3 in the Azores and Brazil). These founder mutations enable ancestry-targeted diagnostic testing, inform genetic counselling and carrier screening in endogamous populations, and identify genetically homogeneous cohorts increasingly used for natural-history studies and precision therapeutic trials, including antisense and gene-silencing approaches. Founder effects, driven predominantly by endogamy, geographic isolation, and migration-associated bottlenecks, account for a disproportionate share of the mutational spectrum in spinocerebellar ataxias, dystonia, and NBIA syndromes. Ancestry-informed testing algorithms, targeted carrier screening, and enrolment of genetically homogeneous founder cohorts into precision therapeutic trials represent the most immediate translational applications of these findings.

Surrogacy includes traditional surrogacy, in which the carrier contributes her own oocyte, and gestational surro-gacy, in which the embryo is derived exclusively from the gametes of the intended parents or donors. In Brazil, only gestational surrogacy is legally recognized. It is governed by resolutions of the Federal Council of Medicine and the national health surveillance agency in the absence of spe-cific federal legislation, and it requires altruistic, unpaid participation and compliance with carrier eligibility crite-ria. This Position Statement, developed by the Strategic Committee on Gestational Surrogacy of the Brazilian As-sociation of Assisted Reproduction, addresses the clinical, bioethical, legal, and psychological dimensions of the prac-tice and is intended to guide specialists throughout Brazil. Clinical indications include uterine absence or anomalies, contraindications to pregnancy, medical conditions that may be aggravated by pregnancy, and biological inability to conceive or carry a pregnancy. No universally validated protocol for carrier selection exists; current requirements include a maximum age of 50 years, at least one previous live birth, and satisfactory physical and mental health. Peri-natal outcomes are comparable to those of conventional in vitro fertilization, although long-term data on cross-border arrangements remain scarce. The bioethical framework is based on autonomy, beneficence, non-maleficence, and justice. SBRA opposes simultaneous surrogacy arrange-ments because they are incompatible with the altruistic na-ture of the practice and supports gradual, age-appropriate disclosure of the child's gestational origin. Legal challenges include the absence of statutory regulation, cross-border reproductive tourism, and the child's right to know their origins. Continuous psychological support for all parties is mandatory and central to favorable long-term outcomes. Gestational surrogacy is a valid reproductive option for se-lected patients but requires rigorous oversight and must prioritize the best interests of the child within the Brazilian regulatory framework.

Fragile X syndrome is a monogenic disorder caused by the expansion of CGG trinucleotide repeats in the fragile X mental retardation 1 (FMR1) gene and is a major cause of inherited intellectual disability and reproductive impair-ment. Preimplantation genetic testing for monogenic disor-ders (PGT-M) has become an important strategy in assisted reproduction to prevent the transmission of FMR1-related disorders. This narrative review aimed to summarize cur-rent evidence on the molecular basis, technical approaches, clinical outcomes, and challenges associated with PGT-M for FMR1 CGG repeat expansions. A literature search was performed in the PubMed database, including English-lan-guage original studies, clinical investigations, and reviews. The reviewed studies demonstrate that advances in multi-plex PCR, linked-marker analysis, and next-generation se-quencing have significantly improved diagnostic accuracy, overcoming earlier limitations related to CGG repeat analy-sis, allele dropout, and mosaicism. Although women carry-ing FMR1 premutations frequently present with diminished ovarian reserve and reduced response to ovarian stimula-tion, pregnancy and live birth rates per embryo transfer are comparable to those of non-carriers when individual-ized stimulation protocols are applied. The combined ap-plication of PGT-M and Preimplantation Genetic Testing for Aneuploidy may be considered in selected clinical scenarios to optimize embryo selection, although indications should be individualized. In addition to its clinical benefits, PGT-M raises ethical, psychological, and economic considerations, emphasizing the importance of genetic counseling in re-productive decision-making. Overall, PGT-M represents a safe and effective tool in assisted reproduction for couples at risk of transmitting FMR1 related disorders, with grow-ing relevance in clinical practice and public health.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder frequently accompanied by epilepsy and TSC-associated neuropsychiatric disorders. Psychiatric-predominant seizure presentations may, however, delay recognition. This clinical challenge describes a 26-year-old woman with recurrent panic-like episodes characterized by dyspnea, choking sensations, palpitations, and derealization, followed by depressive symptoms. The episodes persisted despite treatment with selective serotonin reuptake inhibitors and benzodiazepines. Further examination revealed hypomelanotic macules, prompting neurologic and systemic evaluation. Brain imaging demonstrated findings consistent with cortical tubers and subependymal nodules, while video electroencephalography captured frequent focal seizures without impaired awareness arising from the left frontotemporal region. Positron emission tomography/computed tomography identified a corresponding frontal abnormality. Although genetic testing detected a nonclassical TSC1 variant, the TSC diagnosis was established on clinical grounds. Treatment with lacosamide eliminated detectable epileptiform activity and substantially reduced the frequency and severity of her panic-like episodes; depressive and anxiety symptoms also improved with combined lacosamide and duloxetine treatment. This case illustrates how focal seizures involving frontal, temporal, and limbic-autonomic networks may mimic primary panic disorder. Stereotyped, brief, recurrent, and treatment-refractory psychiatric episodes-particularly when accompanied by neurocutaneous findings-should prompt electroencephalography and brain imaging. The case also emphasizes that an uninformative or uncertain genetic result does not exclude clinically established TSC or alter recommended surveillance and multidisciplinary management.

Suicide is the second leading cause of death among youth, with growing evidence linking higher ambient temperatures to increased suicidality - a concerning trend as global temperatures rise. Sleep disruption is a theorized mechanism, though clinical evidence is lacking.

We performed a cross-sectional analysis of 5,590 pediatric patients (3-18 years) presenting to a psychiatric emergency department with and without suicidality (December 2018-March 2023). Seven-day averages of mean and minimum daily ambient temperatures and precipitation were obtained at home addresses from the PRISM Climate Group dataset. Logistic regression assessed insomnia as a moderator and mediator of the temperature-suicidality relationship, controlling for sociodemographic, diagnostic, and environmental variables. Negative controls included modeling suicidality using hypersomnia-temperature and insomnia-precipitation interactions.

Mean and minimum daily temperatures moderated the temperature-suicidality relationship only in those with insomnia (Mean Temperature: RR: 1.06 per 5°C [95% CI 1.01-1.06], p = 0.015; Minimum Temperature: RR: 1.06 per 5°C [95% CI 1.01-1.06], p = 0.010). Minimum temperature, a proxy for nighttime temperature, was associated with suicidality through insomnia in a mediation model (Indirect Pathway: OR: 1.05 [95% CI 1.00-1.11], p = 0.045), though mean temperature was not. No significant moderation occurred modeling suicidality with hypersomnia-temperature or insomnia-precipitation interactions.

This is the first clinical evidence that insomnia influences the heat-suicidality relationship in youth. Limitations include cross-sectional data that cannot establish temporal directionality of associations, heterogeneous suicidality outcomes, self-reported sleep data, and pandemic-era data collection. Larger mechanistic analyses of temperature, sleep, and suicidality are needed to understand climatic mental health impacts and develop interventions.

Acupuncture has shown clinical benefits in post-stroke rehabilitation, yet its central neural mechanisms remain incompletely understood. In particular, how cortical activation, inter-regional functional connectivity, and brain network topology are modulated during electroacupuncture stimulation has not been systematically characterised. This study aimed to investigate the central effects of verum electroacupuncture (VE) applied to the non-dominant hand in healthy adults. In a randomized, crossover design, functional near-infrared spectroscopy (fNIRS) data were collected from 24 participants during VE and sham electroacupuncture (SE) sessions. Cortical activation was assessed using a general linear model (GLM), functional connectivity (FC) was analysed using lagged cross-correlation, and brain network topology was examined using graph-theoretical metrics. No significant differences in cortical activation were observed between VE and SE. During the needles retention phase, VE significantly reduced functional connectivity between R-MPFC and right primary somatosensory cortex (R-PSC), and between middle MPFC and R-PSC. Graph-theoretical analysis revealed decreased clustering coefficient and increased small-worldness under VE. These findings suggest that VE may optimise brain networks through an connectivity-topology mechanism. Brain networks shifted from excessive localisation toward higher integration. This study establishes a baseline central response profile in healthy individuals and provides theoretical support for the application of electroacupuncture in post-stroke upper-limb rehabilitation. Trial registration: ITMCTR, TRN: ITMCTR2025000595, Registration date: 19 March 2025.

Epilepsy and sleep disorders are highly prevalent conditions that frequently coexist, exerting reciprocal adverse effects through shared neurobiological mechanisms.

We conducted a narrative review of the literature addressing the bidirectional relationship between epilepsy and sleep disorders, aiming to provide a comprehensive synthesis of its neurophysiological basis, clinical implications, and therapeutic consequences.

The epilepsy-sleep relationship is mediated by multiple neurobiological mechanisms, including thalamocortical network dynamics, circadian clock gene regulation, adenosinergic and orexinergic tone, synaptic homeostasis, and glymphatic clearance. A key pathophysiological concept underlying this relationship is that NREM sleep promotes interictal epileptiform discharges and seizure propagation through thalamocortical synchronization, whereas REM sleep exerts a protective effect. Epileptic activity disrupts both sleep macro- and microarchitecture, reducing total sleep time, sleep efficiency, and REM sleep, increasing wake after sleep onset, and destabilizing NREM microarchitecture as reflected by altered cyclic alternating pattern rates. Conversely, sleep disturbances lower the seizure threshold and contribute to disease progression: sleep deprivation is an independent seizure-precipitating factor, and comorbid obstructive sleep apnea further lowers the seizure threshold through intermittent hypoxia and arousal instability. Specific epileptic syndromes with a privileged sleep relationship are also reviewed, including sleep-related hypermotor epilepsy, epileptic encephalopathy with spike-wave activation in sleep, and self-limited childhood focal epilepsies. The differential diagnosis between NREM parasomnias and sleep-related epilepsies remains challenging; the diagnostic workup should always include a thorough clinical history characterizing the episodes, followed by video-polysomnography, which represents the gold standard. From a therapeutic standpoint, antiseizure medications exert heterogeneous effects on sleep architecture, and polytherapy is independently associated with worse sleep quality; targeting sleep disturbances therefore represents a modifiable strategy capable of improving seizure control, cognitive function, and quality of life.

A multidisciplinary approach integrating systematic screening for sleep disorders, optimization of antiseizure medication timing and selection, treatment of comorbid obstructive sleep apnea, and behavioral sleep interventions has the potential to meaningfully improve outcomes in patients with epilepsy. Wider implementation of these strategies in routine clinical practice is both a priority and an opportunity.

Mental health among medical trainees has typically been framed as an individual deficit, addressed through resilience training and counseling services. This perspective examines how the hidden curriculum within Chinese psychiatry training may shape psychological safety and professional identity formation. Drawing on psychological safety theory, hidden curriculum scholarship, Bronfenbrenner's ecological systems theory, and recent empirical literature on medical trainee distress in China, we propose a theoretically derived and empirically testable conceptual model through which experiences of vulnerability may become socially and professionally invisible. The proposed vulnerability-to-invisibility process describes four interconnected phases: the encounter with vulnerability, perceived or enacted prohibition of emotional expression, internalization of silence, and potential fragmentation of professional identity. Existing evidence supports several constituent components of this pathway, but direct empirical evidence establishing the complete sequence remains limited. We therefore call for institutional reforms that embed psychological safety into clinical training, including protected reflective spaces, reflective faculty modeling, peer support, and curriculum-integrated mentorship, while emphasizing adaptive emotional regulation rather than forced suppression.

Reproductive life stages, menopausal symptoms, and hormonal exposures are increasingly recognized as potential determinants of cognitive outcomes in women. However, these associations remain largely understudied in Latin American and Caribbean (LAC) populations. In this systematic review, we identified 18 observational studies published between 2003 and 2025. Of these, 16 were conducted across 13 LAC countries and two were conducted among latina women in the United States. Evidence was organized across four reproductive life stages domains: reproductive history, menopausal hormone therapy use, type of menopause and menopausal symptoms, and postmenopausal factors. Most LAC studies were cross-sectional and demonstrated substantial methodological heterogeneity. Across studies, shorter reproductive span, earlier menopause, higher parity, surgical menopause, and greater menopausal symptom burden were generally associated with poorer cognitive performance or higher odds of mild cognitive impairment. Some studies suggested favorable associations between menopausal hormone therapy use and cognitive outcomes. Postmenopausal factors, such as sarcopenia and obesity, as well as a longer duration of menopause, were predominantly linked to poorer cognitive outcomes. Only one population-based cohort evaluated incident dementia, underscoring the scarcity of longitudinal evidence in the region. Overall, the evidence suggests that reproductive life stages in LAC women are meaningfully associated with cognitive outcomes, reflecting the influence of hormonal transitions, menopausal characteristics, and postmenopausal health within distinctive regional contexts. However, the predominance of cross-sectional designs and limited regional representativity, coupled with a lack of integrated physiological indicators, reveal a substantial knowledge gap. Longitudinal and regionally representative cohorts incorporating standardized assessments of reproductive life stages alongside comprehensive cognitive measures are essential to understanding how reproductive life stages shape cognitive outcomes in LAC women. Systematic review registration: The systematic review was registered in the Open Science Framework (OSF). Registration DOI/unique identifier: https://doi.org/10.17605/OSF.IO/ME7XK.

Concussion disrupts brain connectivity, and effective treatments remain limited. Mindfulness-based interventions (MBIs) may influence functional connectivity (FC) of networks affected by concussion, but pediatric trials are lacking. This study investigated whether an app-delivered MBI produced greater FC changes than a sham condition across the default mode (DMN), salience (SN), and central executive (CEN) networks.

This randomized clinical trial (NCT05105802) recruited participants aged 12.00-17.99 years from the emergency department or interdisciplinary concussion clinic, then randomly assigned them to MBI or cognitive sham. Brain imaging sessions occurred at 72 h and 4 weeks post-concussion. Region-of-interest and seed-to-voxel analyses examined Group × Time interactions in FC across DMN, SN, and CEN (p < 0.050 _FDR ).

Thirty-six participants were included (MBI: n = 16, median [IQR] age = 14.23 [13.52-15.65] years, 31% female; Sham: n = 20, median [IQR] age = 14.05 [13.13-16.26] years, 45% female). Intention-to-treat analyses revealed significant Group × Time interactions across networks. DMN-CEN FC patterns differed, with MBI participants showing diminished FC. Within DMN, four clusters showed significant interactions (p < 0.050 _FDR ), three exhibiting larger FC reductions at 4 weeks in MBI participants. MBI participants showed greater FC increase in one SN cluster (p = 0.040 _FDR ) and larger FC decrease in one CEN cluster (p = 0.024 _FDR ) at 4 weeks. Per-protocol analyses identified one significant DMN cluster (p < 0.001 _FDR ) where MBI participants exhibited greater FC increases.

Mindfulness-based intervention training led to changes in FC in networks implicated in concussion recovery. Larger studies are needed to support these findings.

https://clinicaltrials.gov/study/NCT05105802, identifier NCT05105802.