Emergence of lingual dystonia and strabismus in early-onset SCN8A self-limiting familial infantile epilepsy.

Pathogenic variants in SCN8A are associated with a broad phenotypic spectrum, including Self-Limiting Familial Infantile Epilepsy (SeLFIE), characterized by infancy-onset age-related seizures with normal development and cognition. Movement disorders, particularly paroxysmal kinesigenic dyskinesia typically arising after puberty, may represent another core symptom. We present the case of a 1-year-old girl with a familial disposition to self-limiting focal seizures from the maternal side and early-onset orofacial movement disorders associated with SCN8A-SeLFIE. Brain MRI was normal. Genetic testing revealed a maternally inherited SCN8A variant [c.4447G > A; p.(Glu1483Lys)]. After the introduction of valproic acid, she promptly achieved seizure control as well as complete remission of strabismus and a significant decrease in episodes of tongue deviation. Family history, genetic findings, and epilepsy phenotype are consistent with SCN8A-SeLFIE. Movement disorders are an important part of the SCN8A phenotypic spectrum, and this case highlights the novel early-onset orofacial movement disorders associated with this condition. The episodes of tongue deviation and protrusion suggest focal oromandibular (lingual) dystonia. Additionally, while infantile strabismus or esophoria is a common finding in healthy individuals, our case raises the possibility of an ictal origin of the strabismus. This study underscores the importance of recognizing and addressing movement disorders in SCN8A-SeLFIE patients, particularly the rare early-onset orofacial manifestations. It adds to the growing body of knowledge regarding the diverse clinical presentations of SCN8A-associated disorders and suggests potential avenues for clinical management and further research.

The impact of the two-year COVID-19 pandemic on hospital admission and readmissions of children and adolescents because of mental health problems.

Purpose: This study aimed to investigate the specific risk factors and psycho-social and clinical features of hospitalized neuropsychiatric patients during the COVID pandemic and to analyze the hospital readmission phenomenon, which, according to recent studies, increased in frequency during the first pandemic period. Patients and methods: This observational retrospective cohort study examined 375 patients aged between 0 and 17 years who were hospitalized between 1 February 2018 and 31 March 2022 due to neuropsychiatric issues. The majority of the patients were girls: there were 265 girls compared to 110 boys (M = 13.9 years; SD 2.30 years). The total sample was divided into two groups: the pre-COVID-19 group (160 inpatients hospitalized between February 2018 and February 2020) and the COVID-19 group (215 inpatients hospitalized between March 2020 and March 2022). To explore the readmission phenomenon (second aim), we selected from the two groups of patients with at least one hospital readmission within 365 days after the first discharge. Multiple variables (sociodemographic, clinical, psychological, and related to hospitalization) were collected for each patient by reviewing their medical records. Results: The risk factors for mental health disorders were similar between the two groups, except for the significantly increased use of electronic devices in the COVID-19 group, increasing from 8.8% in the pre-COVID-19 group to 29.2% in the COVID-19 group. Patients suffering from eating disorders increased from 11.3% in the pre-COVID-19 group to 23.8% in the COVID-19 group. Hospital readmissions nearly increased from 16.7% in the 2-year pre-COVID-19 period to 26.2% in the 2-year COVID-19 period. A total of 75% of patients hospitalized three or more times in the last 2 years and 85.7% of the so-called "revolving door" patients (with relapse within 3 months after discharge) were identified in the COVID-19 group. However, the comparison between the two groups of patients readmitted before and during the COVID-19 pandemic did not show any differences in terms of sociodemographic and clinical characteristics. Conclusion: In conclusion, there was a significant increase in hospital readmissions, but these results suggest the need for better coordination between hospital and territorial services in managing the complexity of mental health problems related to situations arising from the COVID-19 pandemic and the necessity to implement prevention strategies and services.

Electroclinical Features in Two Novel STRADA Patients and a Functional Yeast Assay for the Validation of Missense STRADA Mutations.

Loss of function of the STRADA gene, an upstream mTOR inhibitor, causes a rare neurodevelopmental disorder characterized by polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE syndrome). Patients display a homogeneous phenotype including early-onset drug-resistant epilepsy, severe psychomotor delay, multisystemic comorbidities, and increased risk of premature death. The administration of sirolimus, an mTOR inhibitor, is helpful in controlling seizures in this syndrome. We report the electroclinical phenotype of two novel patients and the development of a yeast model to validate the pathogenicity of missense variants. Patient 1 harbored a missense STRADA variant and had a peculiar electroclinical phenotype with a relatively mild epilepsy course. Patient 2 harbored a truncating STRADA variant and showed a typical PMSE phenotype and a favorable response to early treatment with sirolimus. When we modeled the p.(Ser264Arg) STRADA change in its yeast homolog SPS1, it impaired SPS1 function. The results underlie the importance of a timely molecular diagnosis in these patients and show that yeast is a simple yet effective model to validate the pathogenicity of missense variants.

Diagnostic and Therapeutic Challenges of Catatonia in an Adolescent With High Functioning Autism Spectrum Disorder: A Case Report.

Catatonia is a psychomotor syndrome with specific clusters of speech, behavioral and motor features. Although potentially life-threatening, especially in its malignant form accompanied with autonomic dysregulation and medical complications, it is a treatable condition, when promptly identified. For a long time catatonia was considered a marker of schizophrenia, thus limiting the possibility of diagnosis and treatment. Due to growing awareness and studies on the subject, it is now known that catatonia can occur in the context of a number of diseases, including psychotic, affective and neurodevelopmental disorders. In recent years, there's been a renewed interest in the recognition and definition of catatonia in neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), where the differential diagnosis poses great challenges, given the considerable overlapping of signs and symptoms between the conditions. We present the case of a 15 year old boy with High Functioning ASD with a sudden onset of severe catatonic symptoms and the co-existence of psychotic symptoms, whose complex clinical course raises many questions on the differentiation and relation of said disorders.

Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S(+)-ibuprofen.

S(+)-ibuprofen (S-IBU) and R(-)-ibuprofen (R-IBU) concentrations were measured in 16 neonates with patent ductus arteriosus during a cycle of therapy (three intravenous doses of 10-5-5 mg kg-1 at 24-h intervals), at the end of the first infusion and 6, 24, 48, and 72 h later. Data were analyzed with a PK model that included enantiomer elimination rate constants and the R- to S-IBU conversion rate constant. The T½ of S-IBU in the newborn was much longer than in adults (41.8 vs. ≈2 h), whereas the T½ of R-IBU appeared to be the same (2.3 h). The mean fraction of R- to S-IBU conversion was much the same as in adults (0.41 vs. ≈0.60). S-IBU concentrations measured 6 h after the first dose were higher than at the end of the infusion in 10 out of 16 cases, and in five cases, they remained higher even after 24 h. This behavior is unprecedented and may be attributable to a rapid R-to-S conversion overlapping with a slow S-IBU elimination rate. In 13 of the 16 neonates, S-IBU concentrations at 48 and/or 72 h were lower than expected, probably due to the rapid postnatal maturation of the newborn's liver metabolism.