Insights into cognitive and behavioral comorbidities of SLC6A1-related epilepsy: five new cases and literature review

IntroductionSLC6A1 pathogenic variants have been associated with epilepsy and neurodevelopmental disorders. The clinical phenotype includes different seizure types, intellectual disability, and psychiatric symptoms affecting mood and behavior. Few data regarding neuropsychological features have been described, and details on cognitive profiles are often missing due to the lack of standardized tests.MethodsWe retrospectively reviewed the neuropsychological assessments of five subjects carrying heterozygous missense genetic variants in SLC6A1. We also collected data on epileptic features, EEGs, and brain MRIs. Additionally, we reviewed neuropsychological data from 204 previously reported patients with SLC6A1 pathogenic variants.ResultsIn our series, at the last evaluation (median 12.6 years), three patients had borderline intellectual functioning, one patient had mild cognitive impairment, and one patient presented with a moderate cognitive disability. Three out of five patients underwent at least two neuropsychological evaluations, which revealed a worsening of cognitive functions over time. We detected attention deficits in all patients. In addition, we observed anxiety, disruptive behavior disorder, emotional instability, and hetero aggressiveness. We also performed a literature review that highlighted that most of the patients with SLC6A1 pathogenic variants have mild-to-moderate intellectual disability and that one-third of cases have autistic traits.DiscussionBased on the literature review and the detailed description of our cases, we conclude that patients with SLC6A1-related epilepsy mostly present with mild-to-moderate intellectual disability, often associated with attention disorders. Such symptoms may worsen over time. Periodic standardized neuropsychological tests may be useful tools to follow development over time, and patient-specific rehabilitation programs could be tailored consistently

Neurotrophins: Expression of Brain–Lung Axis Development

Neurotrophins (NTs) are a group of soluble growth factors with analogous structures and functions, identified initially as critical mediators of neuronal survival during development. Recently, the relevance of NTs has been confirmed by emerging clinical data showing that impaired NTs levels and functions are involved in the onset of neurological and pulmonary diseases. The alteration in NTs expression at the central and peripheral nervous system has been linked to neurodevelopmental disorders with an early onset and severe clinical manifestations, often named "synaptopathies" because of structural and functional synaptic plasticity abnormalities. NTs appear to be also involved in the physiology and pathophysiology of several airway diseases, neonatal lung diseases, allergic and inflammatory diseases, lung fibrosis, and even lung cancer. Moreover, they have also been detected in other peripheral tissues, including immune cells, epithelium, smooth muscle, fibroblasts, and vascular endothelium. This review aims to provide a comprehensive description of the NTs as important physiological and pathophysiological players in brain and lung development

Bio-Inspired Systems in Nonsurgical Periodontal Therapy to Reduce Contaminated Aerosol during COVID-19: A Comprehensive and Bibliometric Review

Background: On 30 January 2020, a public health emergency of international concern was declared as a result of the new COVID-19 disease, caused by the SARS-CoV-2 virus. This virus is transmitted by air and, therefore, clinical practices with the production of contaminant aerosols are highly at risk. The purpose of this review was to assess the effectiveness of bio-inspired systems, as adjuvants to nonsurgical periodontal therapy, in order to formulate bio-inspired protocols aimed at restoring optimal condition, reducing bacteremia and aerosols generation. Methods: A comprehensive and bibliometric review of articles published in English. Research of clinical trials (RCTs) were included with participants with chronic or aggressive periodontal disease, that have compared benefits for nonsurgical periodontal therapy (NSPT). Results: Seventy-four articles have been included. For probing depth (PPD) there was a statically significant improvement in laser, probiotic, chlorhexidine groups, such as gain in clinical attachment level (CAL). Bleeding on probing (BOP) reduction was statistically significant only for probiotic and chlorhexidine groups. There were changes in microbiological and immunological parameters. Conclusions: The use of bio-inspired systems in nonsurgical periodontal treatment may be useful in reducing risk of bacteremia and aerosol generation, improving clinical, microbiological and immunological parameters, of fundamental importance in a context of global pandemic, where the reduction of bacterial load in aerosols becomes a pivotal point of clinical practice, but other clinical trials are necessary to achieve statistical validity

<i>PHF21A</i> Related Disorder: Description of a New Case

PHF21A (PHD finger protein 21A) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates PHF21A variants with Potocki–Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of PHF21A, ALX4, and EXT2 genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the EXT2 involvement), biparietal foramina (due to the ALX4 involvement), intellectual disability, and craniofacial anomalies (due to the PHF21A involvement). To date, to the best of our knowledge, a detailed description of PHF21A-related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only PHF21A gene have been reported. All reported cases did not present ALX4 or EXT2 variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the PHF21A gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype–phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with PHF21A-related disorder

Semi-Automatic Analysis of Specific Electroencephalographic Patterns during NREM2 Sleep in a Pediatric Population after SARS-CoV-2 Infection

The post-COVID-19 condition is defined by the World Health Organization as the persistence of symptoms or development of new symptoms three months after the initial SARS-CoV-2 infection, lasting for at least two months without a clear explanation. Neuropsychiatric disorders associated with this condition include asthenia, memory and concentration problems, and sleep disturbances. Our study aims to investigate sleep patterns following SARS-CoV-2 infection using EEG findings and a sleep quality questionnaire completed by parents (Sleep Disturbance Scale for Children—SDSC). Notably, our investigation is based on a convenience sample. The patients in our sample, aged 1 to 14 years, are not currently taking any medications; rather, they are undergoing follow-up assessments at the Child Neuropsychiatry department of the University Hospital of Messina for neurodevelopmental evaluations. Specifically, we are analyzing amplitude and power spectrum data in the first five minutes of NREM2 sleep, calculated from EEG recordings obtained via bipolar leads within three months after the onset of the disease. These results will be compared with controls performed on the same subjects in the six months preceding the infection. The focus of the study was sleep spindles, which are generated by the thalamocortical systems and play a role in sleep modulation, memory, and learning. Preliminary analysis suggests a predominant increase in the slow component of the spindles in the right-frontal lead

Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review

During pregnancy, there are several metabolic changes and an alteration in the composition of microorganisms that inhabit the oral cavity, with an increase in pathogenic bacteria that promote the onset of gingival diseases. This review is based on research in reference to the PICO model (Problem/Intervention/Comparison/Outcome), related to changes in the oral microbiome of pregnant women and possible oral consequences in patients with COVID-19. The results showed a growth of some pathogenic bacteria in pregnant women, including Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, and the selective growth of the Prevotella intermedia, Porphyromonas gingivalis and Tannerella species, probably due to the fact that these bacteria use progesterone as a source of nutrition. These same bacteria are implicated in the development of periodontal disease. Periodontal pockets have bidirectional interactions between the oral cavity and the systemic circulatory system through the peripheral gingival blood vessels. The affinity of the SARS-CoV-2 virus to specific membrane receptors is now clear, and could involve the internal and external epithelial lining or the fibroblasts of the periodontal ligament. According to the results of the present review, the control of oral microbiome changes during pregnancy would be welcomed. The use of probiotics could help clinicians manage pregnant patients, reducing inflammatory indexes. Future studies should focus not only on changes in the level of the oral microbiome in pregnancy or the correlation between periodontal disease and COVID-19, but also on oral changes induced by both clinical situations

Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review

During pregnancy, there are several metabolic changes and an alteration in the composition of microorganisms that inhabit the oral cavity, with an increase in pathogenic bacteria that promote the onset of gingival diseases. This review is based on research in reference to the PICO model (Problem/Intervention/Comparison/Outcome), related to changes in the oral microbiome of pregnant women and possible oral consequences in patients with COVID-19. The results showed a growth of some pathogenic bacteria in pregnant women, including Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, and the selective growth of the Prevotella intermedia, Porphyromonas gingivalis and Tannerella species, probably due to the fact that these bacteria use progesterone as a source of nutrition. These same bacteria are implicated in the development of periodontal disease. Periodontal pockets have bidirectional interactions between the oral cavity and the systemic circulatory system through the peripheral gingival blood vessels. The affinity of the SARS-CoV-2 virus to specific membrane receptors is now clear, and could involve the internal and external epithelial lining or the fibroblasts of the periodontal ligament. According to the results of the present review, the control of oral microbiome changes during pregnancy would be welcomed. The use of probiotics could help clinicians manage pregnant patients, reducing inflammatory indexes. Future studies should focus not only on changes in the level of the oral microbiome in pregnancy or the correlation between periodontal disease and COVID-19, but also on oral changes induced by both clinical situations

Assessment of Genetical, Pre, Peri and Post Natal Risk Factors of Deciduous Molar Hypomineralization (DMH), Hypomineralized Second Primary Molar (HSPM) and Molar Incisor Hypomineralization (MIH): A Narrative Review

Objectives: Analyze defects in the state of maturation of the enamel result in an adequate volume of enamel, but in an insufficient mineralization, which can affect both deciduous teeth and permanent teeth. Among the most common defects, we recognize Deciduous Molar Hypominerlization (DMH), Hypomineralized Second Primary Molar (HSPM), and Molar Incisor Hypomineralization (MIH). These, in fact, affect the first deciduous molars, the second deciduous molars and molars, and permanent incisors, respectively, but their etiology remains unclear. The objective of the paper is to review studies that focus on investigating possible associations between genetic factors or prenatal, perinatal, and postnatal causes and these enamel defects. Materials and methods: A comprehensive and bibliometric search for publications until January 2021 was conducted. The research question was formulated following the Population, Intervention, Comparison, Outcome strategy. Case-control, cross-sectional, cohort studies, and clinical trials investigating genetic and environmental etiological factors of enamel defects were included. Results: Twenty-five articles are included. For genetic factors, there is a statistical relevance for SNPs expressed in the secretion or maturation stage of amelogenesis (16% of studies and 80% of studies that investigated these factors). For prenatal, perinatal, and postnatal causes, there is a statistical relevance for postnatal factors, such as the breastfeeding period (2%), asthma (16%), high fever episodes (20%), infections/illnesses (20%), chickenpox (12%), antibiotic intake (8%), diarrhea (4%), and pneumonia (4%). Conclusions: The results are in agreement with the multifactorial idea of the dental enamel defects etiology, but to prove this, further studies enrolling larger, well-diagnosed, and different ethnic populations are necessary to expand the investigation of the genetic and environmental factors that might influence the occurrence of DMH, HPSM, and MIH