Search

Complex mixtures of substances are in the atmosphere and they can cause diseases in humans and biological communities after acute or chronic exposition. This paper focuses on the physical measurement of particulate matter, a proxy for air pollution, and a biological method for mutation assessment due to plants’ exposure to air pollution. The objective of this research was to characterize the air pollution seasonality in municipalities in southern Brazil, and also to understand the relation between air pollution and the biological response of the Tradescantia sp. clone 4430. The optical sensor SDS011 was used for measurements of particulate matter (PM) and the Trad-SHM bioassay was chosen to quantify the mutagenic alterations that occurred in stamen hairs during the study period, with PM data being measured every 5 seconds and the flowers being harvested approximately every two weeks for laboratory analysis. The Pearson test was applied to verify the correlation between PM and mutations in stamen hair as a result of which it was observed that there is a positive correlation between these data, with the highest value found being r = 0.61. Also, the period with the highest occurrence of pink cells was between autumn and spring, the same period in which an unusual increase in PM concentrations was also observed, a period that corresponds to a less favorable dispersion of pollutants in the atmosphere. The use of Tradescantia sp. clone 4430 showed sensitivity to the environments in which it was exposed. Biomonitoring is an important tool for understanding the effects of pollutants on the ecosystem.

The carbon and water fluxes and their inter-relations are key aspects of ecosystem dynamics. In this study, regionalization was used in transferring parameters from the GR4J-Cemaneige model calibrated in Reola hydrographic basin to predict daily flows in Kalli basin; both watersheds are located in the southeast of Estonia. Evapotranspiration data was collected from the MODIS sensor of the Terra satellite and from the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR Estonia). Precipitation data was collected from Tartu–Tõravere and SMEAR Estonia stations and river flow from Reola hydrometric station. The year 2011 was used for model warm-up, model calibration was done in 2012–2017 and the 2018–2020 period was used for validation. The GR4J-Cemaneige model was calibrated at Reola Basin, with a Nash-Sutcliffe Efficiency index of 0.73. The 6 constants of Reola subbasin were transferred to Kalli subbasin for river flow simulation. Net ecosystem exchange (NEE) was measured at the 70 m SMEAR tower with the eddy covariance technique. The balances indicate that the ecosystem at Kalli watershed is slowly becoming a source of carbon and less water is available at the catchment reservoir. NEE has increased from -1.23 μmol m-2 s-1 in 2015 to -0.62 μmol m-2 s-1 in 2020, while the delta water storage decreased from 0.24 mm in 2015 to -0.05 mm in 2020. This behavior may increase soil drying and oxidation, and it will probably release more carbon in the future. This research allows a better understanding of the Järvselja hemi-boreal forest water-carbon dynamics.

Introduction: Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers' perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively)., Methods: In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers' impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses., Results: MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90-2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30-1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase)., Conclusion: These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD., Trial Registration Number: ClinicalTrials.gov identifier, NCT05096221., Competing Interests: Declarations. Conflict of Interest: Jacob S. Elkins, Sai Dharmarajan, Katherine Gooch, Ivana Audhya: Employees of Sarepta Therapeutics, Inc., and may hold stock/options in the company. Teofil Ciobanu: Employee of F. Hoffmann-La Roche Ltd. Claire J. Lansdall: Employee of F. Hoffmann-La Roche Ltd. and shareholder of F. Hoffmann-La Roche Ltd. Alexander P. Murphy: Employee of Roche Products UK and may hold shares in F. Hoffmann-La Roche Ltd. Fiona McDougall: Employee of Genentech, Inc.and shareholder of F. Hoffmann-La Roche Ltd. Craig M. McDonald: Reports grants from Capricor Therapeutics, Catabasis, Edgewise Therapeutics, Epirium Bio, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals, Sarepta Therapeutics; and has a consultancy/advisory role with Biomarin, Capricor Therapeutics, Catalyst, Edgewise Therapeutics, Italfarmaco, PTC Therapeutics, F. Hoffmann-La Roche Ltd, Santhera Pharmaceuticals and Sarepta Therapeutics. He has received honoraria from PTC Therapeutics and Sarepta Therapeutics. Eugenio M. Mercuri: Reports receiving fees from AveXis, Biogen, and F. Hoffmann-La Roche Ltd. Ethical Approval: EMBARK was conducted in accordance with the provisions of the Declaration of Helsinki and Good Clinical Practice guidelines. Trial protocol and all amendments were approved by an institutional review board and ethics committee at each site. The full list of institutional review boards and ethics committees is available in the Supplementary Information. Informed consent, including consent to publish, was obtained from parent(s)/legal guardian(s), and patients’ assent was obtained when indicated., (© 2024. The Author(s).)

Background: The study of women exposures and child outcomes occurring in the first 1,000 days of life since conception enhances understanding of the relationships between environmental factors, epigenetic changes, and disease development, extending beyond childhood and spanning the entire lifespan. Generation Gemelli is a recently launched case-control study that enrolls mother-newborns pairs in one of the largest university hospitals in Italy, in order to examine the association between maternal environmental exposures and intrauterine growth restriction (IUGR) and the risk of premature birth. The study will also evaluate the association of maternal exposures and the health and growth of infants and children up to 24 months of age., Methods: The study entails the set-up of a case-control study within a birth cohort. With approximately 4,000 annual deliveries, we aim to enroll 140 cases (newborns with IUGR and premature birth) and 280 controls per year, from September 2022. A comprehensive questionnaire will be used to gather information about various types of maternal environmental exposures before and during pregnancy. We will collect biological samples from both mothers and newborns (including vaginal swab, placenta sample, blood, saliva, meconium, and bronchoalveolar lavage fluid) at birth and within the early hours of the newborn's life. We will perform laboratory examinations including dosage of heavy metals and essential elements, investigation of placental distress and fetal brain damage of biomarkers, analysis of microbiota and of DNA methylation profile. We will conduct clinical follow-up assessments in both cases and controls at months 12 and 24 and we will collect anthropometric data, feeding types with particular reference to breastfeeding and its duration, pediatric emergency room visits, hospitalizations, medication usage, known allergies, and neuropsychological development., Discussion: The Generation Gemelli case-control study holds the promise of significantly enhancing our comprehension of how maternal environmental exposures relate to the health of children and the broader population. The study of the exposome will provide insights into the relationships between environmental exposures, epigenetic changes and health outcomes during the first 1000 days of life and onward., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2025 Villani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 10 14 vector genomes per kilogram; n = 63) or placebo (n = 62). At week 52, the primary endpoint, change from baseline in NSAA score, was not met (least squares mean 2.57 (delandistrogene moxeparvovec) versus 1.92 (placebo) points; between-group difference, 0.65; 95% confidence interval (CI), -0.45, 1.74; P = 0.2441). Secondary efficacy endpoints included mean micro-dystrophin expression at week 12: 34.29% (treated) versus 0.00% (placebo). Other secondary efficacy endpoints at week 52 (between-group differences (95% CI)) included: Time to Rise (-0.64 (-1.06, -0.23)), 10-meter Walk/Run (-0.42 (-0.71, -0.13)), stride velocity 95th centile (0.10 (0.00, 0.19)), 100-meter Walk/Run (-3.29 (-8.28, 1.70)), time to ascend 4 steps (-0.36 (-0.71, -0.01)), PROMIS Mobility and Upper Extremity (0.05 (-0.08, 0.19); -0.04 (-0.24, 0.17)) and number of NSAA skills gained/improved (0.19 (-0.67, 1.06)). In total, 674 adverse events were recorded with delandistrogene moxeparvovec and 514 with placebo. There were no deaths, discontinuations or clinically significant complement-mediated adverse events; 7 patients (11.1%) experienced 10 treatment-related serious adverse events. Delandistrogene moxeparvovec did not lead to a significant improvement in NSAA score at week 52. Some of the secondary endpoints numerically favored treatment, although no statistical significance can be claimed. Safety was manageable and consistent with previous delandistrogene moxeparvovec trials. ClinicalTrials.gov: NCT05096221., Competing Interests: Competing interests: J.R.M. received study funding from Sarepta Therapeutics while at Nationwide Children’s Hospital at the time of the study and is currently an employee of Sarepta Therapeutics. J.R.M. is a co-inventor of AAVrh74.MHCK7.micro-dys technology. F.M. has received honoraria and grants from Sarepta Therapeutics for participating at symposia and advisory boards and is involved as an investigator in Sarepta Therapeutics clinical trials. He reports participation in advisory boards for Novartis, F. Hoffmann-La Roche, Ltd., Edgewise Therapeutics, Dyne Therapeutics, Pfizer, PTC Therapeutics and Italfarmaco. C.M.M. reports grants from Capricor Therapeutics, Catabasis, Edgewise Therapeutics, Epirium Bio, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics and has a consultancy/advisory role with Biomarin, Capricor Therapeutics, Catalyst, Edgewise Therapeutics, Italfarmaco, PTC Therapeutics, F. Hoffmann-La Roche, Ltd., Santhera Pharmaceuticals and Sarepta Therapeutics. He has received honoraria from PTC Therapeutics and Sarepta Therapeutics. E.M.M. has received fees from AveXis, Biogen and F. Hoffmann-La Roche, Ltd. E.C. has received honoraria from Sarepta Therapeutics for participating in advisory boards and research and/or grant support from the Centers for Disease Control and Prevention, CureSMA, the Muscular Dystrophy Association, the National Institutes of Health, Orphazyme, the Patient-Centered Outcomes Research Institute, Parent Project Muscular Dystrophy, PTC Therapeutics, Santhera, Sarepta Therapeutics and the US Food and Drug Administration. H.K. has received grants from Sarepta Therapeutics, Pfizer, PTC Therapeutics, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Nippon Shinyaku Co., Ltd. and Kaneka Corporation. H.K. has received fees from Sarepta Therapeutics, Pfizer, PTC Therapeutics, Chugai Pharmaceutical Co., Nippon Shinyaku Co. and Kaneka Corporation. C.L.-A. is an investigator in Sarepta Therapeutics clinical trials and a sub-investigator in studies sponsored by Pfizer, SolidBioSciences, Edgewise Therapeutics, Italfarmaco and Genentech/Roche. A.N. has received fees from AveXis, Biogen and F. Hoffmann-La Roche, Ltd. C.P. participates on an advisory board and is a consultant for Biogen, Sarepta Therapeutics, AveXis/Novartis Gene Therapies, Genentech/Roche and Scholar Rock; serves as a speaker for Biogen; and is a principal investigator of studies sponsored by AveXis/Novartis Gene Therapies, AMO Pharma, Astellas, Biogen, CSL Behring, Fibrogen, PTC Therapeutics, Pfizer, Sarepta Therapeutics and Scholar Rock. U.S.-S. has received honoraria for counseling and participating in invited talks from Sarepta Therapeutics and F. Hoffmann-La Roche, Ltd. A.V. has a consultancy/advisory role with AMO Pharma, AveXis, Biogen, Edgewise Therapeutics, FibroGen, Novartis, Pfizer, PTC Therapeutics, Sarepta Therapeutics, UCB Pharma, Catalyst and Scholar Rock; has received research funding from AMO Pharma, Capricor Therapeutics, Edgewise Therapeutics, FibroGen, the Muscular Dystrophy Association, Novartis, Parent Project Muscular Dystrophy, Pfizer, RegenxBio and Sarepta Therapeutics; and has other relationship(s) with MedLink Neurology for editorial services. C.M.Z. has received research support from Biogen and Novartis and has served on an advisory board for Sarepta Therapeutics. M.G., C.W. and P.F. are employees of F. Hoffmann-La Roche, Ltd. and may have stock options. A.P.M. and C.R. are employees of Roche Products, Ltd. and may have stock options in F. Hoffmann-La Roche, Ltd. D.R.A., E.D., S.M., R.A.P., T.S., W.Z. and J.S.E. are employees of Sarepta Therapeutics and may have stock options. L.R.R.-K. is an employee of Sarepta Therapeutics and may have stock options. In addition, she is a co-inventor of AAVrh74.MHCK7.micro-dys technology., (© 2024. The Author(s).)

Introduction/aims: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)-assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients., Methods: Fifty-eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US-assisted technique) or Group 2 (nusinersen infusion with landmark-based technique). The number of attempts, number of redirections, periprocedural time, AEs and patient satisfaction were reported. Continuous variables were compared with the Student t-test or Wilcoxon rank sum test. Categorical variables were evaluated with the Chi-square test or Fisher's exact test in case of expected frequencies <5. The p-values <.05 were considered statistically significant., Results: There were no statistical differences in the number of attempts, AEs, or patient satisfaction between the two groups. The number of needle redirections was significantly lower in the ultrasound group versus landmark-based group (p < .05) in both the overall group of patients and in the subgroup with difficult spines. The periprocedural time was about 40 seconds longer in US-group versus landmark-based group (p < .05)., Discussion: In SMA adults, US assistance reduces the number of needle redirections needed for intrathecal drug administration. These results suggest that the US assistance may be advantageous for nusinersen therapy to reduce the therapeutic burden of intrathecal infusion., (© 2024 Wiley Periodicals LLC.)

Background: Sleep disorders have been poorly described in congenital (CDM) and childhood (ChDM) myotonic dystrophy despite being highly burdensome. The aims of this study were to explore sleep disorders in a cohort of Italian CDM and ChDM and to assess their association with motor and respiratory function and disease-specific cognitive and behavioral assessments. Methods: This was an observational multicenter study. Reported sleep quality was assessed using the Pediatric Daytime Sleepiness Scale (PDSS) and Pediatric Sleep Questionnaire (PSQ). Sleep quality was correlated to motor function (6 min walk test, 6MWT and grip strength; pulmonary function (predicted Forced Vital Capacity%, FVC% pred.); executive function assessed by BRIEF-2; autism traits assessed by Autism Spectrum Screening Questionnaire (ASSQ) and Repetitive Behavior Scale-revised (RBS-R); Quality of life (PedsQL) and disease burden (Congenital Childhood Myotonic Dystrophy Health Index, CCMDHI). Results: Forty-six patients were included, 33 CDM and 13 ChDM, at a median age of 10.4 and 15.1 years. Daytime sleepiness and disrupted sleep were reported by 30% children, in both subgroups of CDM and ChDM. Daytime sleepiness correlated with autism traits in CDM ( p < 0.05). Disrupted sleep correlated with poorer executive function ( p = 0.04) and higher disease burden ( p = 0.03). Conclusions: Sleep issues are a feature of both CDM and ChDM. They correlate with behavioral issues and impact on disease burden.

Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic-dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L -related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended.

Introduction/purpose: Nusinersen, the first treatment approved for all spinal muscular atrophy (SMA) types, is administered intrathecally through lumbar puncture. We used ultrasound assistance or a landmark-based technique to access the lumbar intrathecal space in adult SMA patients. This study aimed to evaluate the technical success and adverse events (AEs) in such patients using either technique over a long observation period., Methods: Fifty-one adult patients received 507 consecutive interlaminar nusinersen administrations. Patients presented with both 'uncomplicated spines' or 'complicated spines'; two patients had previous back surgery. Technical success and AEs were recorded using either technique. A generalised linear mixed model was applied to evaluate predictors of technical success and complications., Results: An overall success rate of 99.6%, with only two procedures failing to reach the intrathecal space, and an overall optimal procedure rate of 90.3% have been reported. A total of 455 procedures (89.7%) were uneventfully performed. One (0.2%) case of severe AE (puncture of a bulky abdominal annexal cyst) was recorded. Twenty-seven episodes (5.3%) of post-dural puncture headache (PDPH) and 24 episodes (4.7%) of radicular or back pain, both successfully treated with medical therapy, have also been reported. Technical success was significantly associated with 'complicated spines' (P = 0.022) and the use of ultrasound assistance (P = 0.01), and the use of ultrasound was the only independent predictor of uncomplicated procedures (P = 0.007)., Discussion: In adult patients with SMA both landmark-based and ultrasound-assisted techniques are safe and effective even in the long term. The use of assistance is associated with technical success and can predict uncomplicated procedures., Conclusion: Our results support the use of ultrasonography in order to improve the success and reduce the burden of nusinersen intrathecal administration., Competing Interests: Bruno Antonio Zanfini has served as a paid consultant for BIOGEN S.R.L. outside the submitted work; Agata Katia Patanella has served as a paid consultant for BIOGEN S.R.L. outside the submitted work; Marika Pane has served as a paid consultant for BIOGEN S.R.L. and Novartis outside the submitted work; Eugenio Mercuri has served as a paid consultant for BIOGEN S.R.L., Novartis and Roche outside the submitted work; Mario Sabatelli has served as a paid consultant for BIOGEN S.R.L. outside the submitted work; the remaining authors have no conflicts of interest to disclose., (© 2024 The Author(s). Australasian Journal of Ultrasound in Medicine published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Ultrasound in Medicine.)

Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants., Methods: This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO 2  ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system., Results: A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO 2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO 2 , pO 2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117)., Conclusions: Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Serrao, Tiberi, Verdolotti, Romeo, Corsello, Pede, Cota, Costa, Gallini, Colosimo, Mercuri and Vento.)

Introduction: Specific Learning Disorder (SLD) is a neurodevelopmental disorder characterized by difficulties in perceiving and processing verbal and non-verbal information. It is usually accompanied by impaired academic skills leading to school dropout and emotional disturbances, resulting in significant distress and behavioral problems., Methods: A cognitive, academic, and emotional-behavioral assessment was performed at T0 and T1 in children and adolescents with SLD. Participants received psychotherapy and speech therapy treatment from T0 to T1., Results: In SLD, the most compromised cognitive functions were working memory and writing skills. An impact on academic abilities was found. Children and adolescents with SLD experience greater anxiety and depression levels compared to their control peers., Conclusions: SLD may adversely influence psychological well-being. To counteract such a consequence, more specific cognitive and academic skill-oriented strategies should be taken into consideration.

Background: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children., Aims: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period., Methods: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events., Results: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes)., Conclusion: In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration., (© 2023 John Wiley & Sons Ltd.)

Background: GNAO1-related encephalopathies include a broad spectrum of developmental disorders caused by de novo heterozygous mutations in the GNAO1 gene, encoding the G (o) subunit α of G-proteins. These conditions are characterized by epilepsy, movement disorders and developmental impairment, in combination or as isolated features., Objective: This study aimed at describing the profile of neurovisual competences in children with GNAO1 deficiency to better characterize the phenotype of the disease spectrum., Methods: Four male and three female patients with confirmed genetic diagnosis underwent neurological examination, visual function assessment, and neurovisual and ophthalmological evaluation. Present clinical history of epilepsy and movement disorders, and neuroimaging findings were also evaluated., Results: The assessment revealed two trends in visual development. Some aspects of visual function, such as discrimination and perception of distance, depth and volume, appeared to be impaired at all ages, with no sign of improvement. Other aspects, reliant on temporal lobe competences (ventral stream) and more related to object-face exploration, recognition and environmental control, appeared to be preserved and improved with age., Significance: Visual function is often impaired, with patterns of visual impairment affecting the ventral stream less.

Pregnancy is a unique experience in women's life, requiring a great ability of adaptation and self-reorganization; vulnerable women may be at increased risk of developing depressive symptoms. This study aimed to examine the incidence of depressive symptomatology during pregnancy and to evaluate the role of affective temperament traits and psychosocial risk factors in predicting them. We recruited 193 pregnant women, collected data regarding sociodemographic, family and personal clinical variables, social support and stressful life events and administered the Mood Disorder Questionnaire (MDQ), the Patient Health Questionnaire-9 (PHQ-9), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). In our sample, prevalence of depressive symptomatology was 41.45% and prevalence of depression was 9.85% (6.75% mild and 3.10% moderate depression). We have chosen a cutoff >4 on PHQ-9 to identify mild depressive symptoms which may predict subsequent depression. Statistically significant differences between the two groups were found in the following factors: gestational age, occupation, partner, medical conditions, psychiatric disorders, family psychiatric history, stressful life events, and TEMPS-A mean scores. In our sample mean scores on all affective temperaments but the hyperthymic, were significantly lower in the control group. Only depressive and hyperthymic temperaments were found to be, respectively, risk and protective factors for depressive symptomatology. The current study confirms the high prevalence and complex aetiology of depressive symptomatology during pregnancy and suggests that affective temperament assessment seems to be a useful adjunctive instrument to predict depressive symptomatology during pregnancy and postpartum.

Background: CDKL5 deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene cyclin-dependent kinase-like 5. Cerebral visual impairment (CVI) is frequent in patients with CDD. In addition to being recognized as a specific feature of the pathology, it has been suggested that visual impairment may correlate with neurodevelopmental outcome and epilepsy severity, but no systematic behavioral visual assessment has been performed. The aim of our study was to evaluate clinical and electrophysiological profile of CVI in patients with CDD, to correlate various aspects of visual function to neurodevelopmental and epileptic features., Methods: The study included all patients with CDD from the National Pathology Registry. All patients underwent neurological examination, a disease-specific functional assessment, structured clinical evaluation of visual functions, including pattern reversal visual evoked potential (VEP), and a detailed monitoring of epileptic features, including video-EEG., Results: All the 11 patients recorded in the CDKL5 national registry, 10 females and one male, age range of 1.5 to 24 years (mean 9, SD 7.7, median 6.5), were enrolled. Visual function is impaired in all patients; in particular, visual fields, visual acuity, contrast sensitivity, and stereopsis were consistently abnormal whereas other aspects, such as fixing and tracking, were relatively preserved. Pattern reversal VEP was abnormal in nearly 80% of our patients. No correlation was found among CVI severity, age, level of psychomotor development, EEG abnormalities, and pathology stages even if an overall less abnormal EEG pattern was more often associated with better visual results., Conclusion: In conclusion, CVI can be considered as a major feature of CDD with a diffuse involvement in several behavioral and electrophysiological aspects. Larger cohorts will help to better clarify the possible prognostic role of EEG severity in predicting both visual and developmental abnormalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quintiliani, Ricci, Petrianni, Leone, Orazi, Amore, Gambardella, Contaldo, Veredice, Perulli, Musto, Mercuri and Battaglia.)

Late-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelae and iron deficiency. The aim of the study is to assess the positive effect of iron supplementation on psychomotor development in healthy LPT. We designed a randomized placebo-controlled double-blind trial dividing the newborns into two groups. Every patient was assessed using the Griffiths Mental Development Scales (GMDS)-II edition at 12-month post-conceptional age. The study was performed at the Neonatology Unit of our Hospital, in Italy. Sixty-six healthy LPT infants born between 34 0⁄7 and 36 6⁄7  weeks of gestational age were enrolled in the study. One group received martial prophylaxis from the third week of life to 6 months of post-conceptional age (2 mg/kg/day of iron pidolate), the other received placebo. Fifty-two of the enrolled infants were assessed using the GMDS at 12-month of post-conceptional age. Statistical analysis of the mean scores of the Griffiths subscales was performed. There was a difference in the mean developmental quotient (DQ) (p < 0.01) between the two groups: iron group mean DQ 121.45 ± 10.53 vs placebo group mean DQ 113.25 ± 9.70. Moreover, mean scores of the Griffiths subscales A, B, and D showed significant differences between the two groups (scale A p < 0.05, scale B p < 0.02, scale D p < 0.01, respectively).Conclusions: We recommend that all LPT neonates receive iron supplementation during the first 6 months of life in order to improve their 1-year neurodevelopmental quotient. What is Known: • Late-preterm infants (LPT) are at increased risk for long-term neurodevelopmental sequelae and also for iron deficiency. • Iron deficiency is an independent risk factor for adverse neurological outcomes. What is New: • Healthy late-preterm who received iron supplementation during the first 6 months of life achieved better neurological outcomes at 12-month post-conceptional age than LPT who received placebo. • Our study strongly supports the need for the implementation of martial prophylaxis in LPT neonates., (© 2021. The Author(s).)

Purpose: Preliminary data suggest that patients with Dravet Syndrome (DS) have a reduced heart rate variability (HRV). This seems particularly evident in patients who experienced sudden unexpected death in epilepsy (SUDEP). This study aims at confirming these findings in a larger cohort and at defining clinical, genetic or electroencephalographic predictors of HRV impairment in DS patients., Methods: DS patients followed at our Institution performed a 24h-ECG Holter to derive HRV parameters. We used as control population patients with epilepsy (PWEs) and healthy controls (HCs). In DS patients, we assessed the impact of different clinical, neurophysiological and genetic features on HRV alterations through multiple linear regression. After a mean follow-up of 7.4 ± 3.2 years since the HRV assessment, all DS patients were contacted to record death or life-threatening events., Results: 56 DS patients had a significantly reduced HRV compared to both HCs and PWEs. A recent history of status epilepticus (SE) was the only significant predictor of lower HRV in the multivariate analysis. At follow-up, only one patient died; her HRV was lower than that of all the controls and was in the low range for DS patients., Conclusion: We describe for the first time an association between SE and HRV alterations in DS. Further studies on other SCN1A-related phenotypes and other epilepsies with frequent SE will help clarify this finding. Compared to the literature, our cohort showed better HRV and lower mortality. Although limited, this observation reinforces the role of HRV as a biomarker for mortality risk in DS., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism caused by the instability of a CGG trinucleotide repeat in exon 1 of the FMR1 gene. The co-occurrence of FXS with other genetic disorders has only been occasionally reported. Here, we describe three independent cases of FXS co-segregation with three different genetic conditions, consisting of Duchenne muscular dystrophy (DMD), PPP2R5D --related neurodevelopmental disorder, and 2p25.3 deletion. The co-occurrence of DMD and FXS has been reported only once in a young boy, while in an independent family two affected boys were described, the elder diagnosed with FXS and the younger with DMD. This represents the second case in which both conditions coexist in a 5-year-old boy, inherited from his heterozygous mother. The next double diagnosis had never been reported before: through exome sequencing, a girl with FXS who was of 7 years of age with macrocephaly and severe psychomotor delay was found to carry a de novo variant in the PPP2R5D gene. Finally, a maternally inherited 2p25.3 deletion associated with a decreased level of the MYT1L transcript, only in the patient, was observed in a 33-year-old FXS male with severe seizures compared to his mother and two sex- and age-matched controls. All of these patients represent very rare instances of genetic conditions with clinical features that can be modified by FXS and vice versa .

Background: JAM3 gene, located on human chromosome 11q25, encodes a member of the junctional adhesion molecule (JAM) family. Mutations of this gene are associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC)., Case Report: Herein, we present a newborn male with a prenatal suspicion of bilateral cataracts but without fetal ultrasound findings of cortical malformations. He was postnatally diagnosed with a clinical picture of HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE), associated to a homozygous variant of JAM3 gene., Conclusion: Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child with a JAM3 variant in Italy, from a different ethnic background than the other reported children until now (Saudi Arabian, Turkish, Afghani, and Moroccan origin). JAM3 screening could be requested in prenatal diagnosis of fetal congenital cataracts and included in Next-Generation DNA Sequencing panels., (© 2021. Fondazione Società Italiana di Neurologia.)

Objective: Bronchopulmonary dysplasia is a chronic respiratory disease that still affects preterm neonates; its association with neurodevelopmental (ND) impairment is already known. Different studies investigated neurodevelopmental outcomes in infants with BPD, often using the old dichotomous definition (BPD vs Non-BPD). This retrospective study aims to evaluate the role of different BPD severity grades on ND outcomes at 24 months of corrected age (CA)., Methods: All preterm infants born between 2011 and 2015 in the study hospital with a gestational age (GA) ≤ 30 weeks and discharged from our NICU were included and were divided in infants with and without BPD. Infants with BPD were divided into three severity groups as defined by NICHD/NHLBI Workshop in 2001, and were compared to their Non-BPD peers, matching them according to the same GA and year of birth. At 24 months postmenstrual age, we assessed general outcomes (growth and hospital readmissions) and neurodevelopmental outcomes (motor, developmental and sensory outcomes) with a standardized assessment., Results: We enrolled 89 patients affected by BPD of different grades of severity and a control group of 89 preterm infants without BPD. Infants with Moderate and Severe BPD showed a significantly higher corrected odds ratio (OR) for cognitive impairment compared to controls. Within the group of infants without severe disability (regarding Griffiths' scales), infants with Moderate and Severe BPD as well as infants with Mild BPD showed a significantly higher risk of a lower total Developmental Quotient (DQ) score, even after correction for confounding factors., Conclusions: Our study evidenced that not only Severe BPD infants, but also Moderate ones showed a higher risk of overall cognitive impairment at 24 months CA. Within the group of infants without severe disability, also those with Mild BPD had lower Griffiths DQ scores than those without. This would suggest that infants with BPD, regardless of severity, warrant neurodevelopmental follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The effects of nusinersen in adults with SMA rely on neuromotor function scales and qualitative assessments. There are limited clinical or imaging data on muscle changes over time., Methods: Two adult SMA patients underwent clinical assessments including measures of upper and lower limb function with Revised Upper Limb Module (RULM) and Hammersmith Function Motor Scale Expanded (HFMSE); both patients were also studied with whole-body muscle MRI (T1-weighted and Diffusion Tensor Imaging/DTI sequences), at baseline and after 10 and 24 months from the beginning of treatment with nusinersen., Results: After two years of treatment, HFMSE and RULM scores were stable in both patients. DTI sequences revealed an increased number, length and organization of muscle fiber tracks, and Fractional Anisotropy (FA) values showed a significant reduction after 10 and 24 months from baseline, in their corresponding maps., Discussion: Muscle DTI imaging seems to play an interesting role to monitor treatment effects over time in adult SMA patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction., Patients and Methods: We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months., Results: At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study., Conclusions: Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy. Children up to the age of 4 years with a visual acuity ≥1/10 were evaluated using the Griffiths' Mental Development Scales. Eighteen children were enrolled (age range 12-48 months). Four were diagnosed by newborn screening (NBS); in the others mean age at diagnosis was 3.5 months (range 0.3-18 months). Eight had seizures: three in the first year, and five after the second year of life. Fourteen had brain lesions on magnetic resonance imaging (MRI). Neurovisual assessment evidenced low visual acuity (<3/10) in 4/18. NBS diagnosed patients had higher general and subquotients neurodevelopmental scores, normal brain MRI, and no epilepsy. The others showed a progressive reduction of the developmental quotient with age and language impairment, which was evident after 24 months of age. Our findings showed a progressive neurodevelopmental deterioration and a specific fall in language development after 24 months in cblC defect. The presence of brain lesions and epilepsy was associated with a worst neurodevelopmental outcome. NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have a protective effect on the development of brain lesions and to promote a more favorable neurodevelopment., (© 2019 SSIEM.)

Objective: To assess whether structured reports (SRs) of MRI in patients with inherited neuromuscular disorders (IND) provide more clinically relevant information than non-structured reports (NSRs) and whether neuroradiologists' expertise affects completeness of reports., Material and Methods: Lower limbs' MRI reports of patients with IND produced by neuroradiologists with different level of expertise (> 15 years vs. < 15 years of experience in reading IND-MRI) before and after implementation of a SR template were included. Reports were assessed for the presence of 9 key features relevant for IND management. Reports and images were evaluated by neurologists who assessed: disease-specific muscular involvement pattern; presence of sufficient information to order the appropriate genetic/diagnostic tests; presence of sufficient information to make therapeutic decision/perform biopsy and necessity to review MRI images. Mann-Whitney and Fisher's exact tests were used to compare the number of key features for NSR and SR and neurologists' answers for reports produced by neuroradiologists with different experience., Results: Thirty-one SRs and 101 NSRs were reviewed. A median of 8 and 6 key features was present in SR and NSR, respectively (p value < 0.0001). When reports were produced by less expert neuroradiologists, neurologists recognized muscular involvement pattern, had sufficient information for clinical decision-making/perform biopsy more often with SR than NSR (p values: < 0.0001), and needed to evaluate images less often with SR (p value: 0.0001). When reports produced by expert neuroradiologists were evaluated, no significant difference in neurologists' answers was observed., Conclusion: SR of IND-MRI contained more often clinically relevant information considered important for disease management than NSR. Radiologist's expertise affects completeness of NSR reports.