Unveiling vocal profiles in adolescent anorexia nervosa: a Software Based, Multiparametric Analysis.

Dysphonia, characterized by disturbances in voice quality and modulation, has been sporadically observed in individuals with Anorexia Nervosa (AN), potentially stemming from both organic and psychopathological factors. This study seeks to employ software-based voice analysis to compare the voices of girls with AN to those of female healthy controls (HC). Case-control study adopting "Praat" software to assess voices. Various parameters, including Acoustic Voice Quality Index (AVQI), Fundamental Frequency (F0), Yanagihara's Spectrographic Dysphonia Classifications, and "GIRBAS" perceptual qualitative voice rating, were investigated. Participants completed questionnaires for Vocal Fatigue Index (VFI) and the Reflux Symptoms Index (RSI). Puberty-related voice spectrum changes were considered, and Bonferroni-corrected BMI-adjusted Analyses of Covariance (ANCOVAs) were conducted. The study enrolled 15 girls with AN and 23 girls with HC. AN patients demonstrated greater impairment in voice tiredness/voice avoidance (VFI-1, p < 0.001), vocal physical discomfort (VIF-2, p = 0.002), and rest as alleviation (VFI-3, p = 0.012). Reflux-related scores were higher in AN (p < 0.001). Differences were observed in voice quality (AVQI) (p = 0.001), and GIRBAS scales showed alterations in multiple parameters. Spectrograms documented more frequent pathological findings in AN patients (p = 0.021). No difference was observed in Fundamental Frequency. These group (AN/HC) differences were independent of weight measures. This study is the first to connect voice irregularities in AN by employing standardized, non-invasive tools and accounting for weight-related factors. Young AN patients demonstrated substantial voice quality changes and heightened self-reported symptoms. Future research should expand on these findings with prospective designs and invasive investigations.

Avoidant-restrictive food intake disorder in a male patient with Goldenhar syndrome.

BACKGROUND: Goldenhar syndrome (GS) is a rare congenital condition characterized by the underdevelopment of structures deriving from the first and second branchial arches. Clinical phenotype might encompass extra-craniofacial abnormalities, and patients may experience neuropsychiatric disorders with a higher prevalence than healthy controls. To the best of our knowledge, an association between GS and Feeding and Eating Disorders (FED) has never been reported in the literature. CASE REPORT: A 15-year-old boy with GS was referred to our outpatient clinic due to severe underweight (BMI of 12.7 kg/m2) and food intake disorder with avoidant restrictive features. After a diagnosis of avoidant-restrictive food intake disorder (ARFID) was made, an inpatient multidisciplinary intervention and outpatient follow-up program were provided, which resulted in the improvement of the boy's weight and FED psychopathology. CONCLUSIONS: The current report describes the first case of a young male with GS and ARFID. We suggest that ARFID may present itself as part of the spectrum of neuropsychiatric disorders associated with the syndrome; since traumatic experiences and gastrointestinal discomfort play a pivotal role in the development of ARFID among children, attention should be paid to those affected by GS that involves crucial structures in the swallowing process. Further literature evidence will help portray the complex relationship between ARFID and GS more precisely. LEVEL OF EVIDENCE: Level V, case report.

Whole-exome sequencing in adult patients with developmental and epileptic encephalopathy: It is never too late.

Developmental and epileptic encephalopathies (DEE) encompass rare, sporadic neurodevelopmental disorders and usually with pediatric onset. As these conditions are characterized by marked clinical and genetic heterogeneity, whole-exome sequencing (WES) represents the strategy of choice for the molecular diagnosis. While its usefulness is well established in pediatric DEE cohorts, our study is aimed at assessing the WES feasibility in adult DEE patients who experienced a diagnostic odyssey prior to the advent of this technique. We analyzed exomes from 71 unrelated adult DEE patients, consecutively recruited from an Italian cohort for the EPI25 Project. All patients underwent accurate clinical and electrophysiological characterization. An overwhelming percentage (90.1%) had already undergone negative genetic testing. Variants were classified according to the American College of Medical Genetics and Genomics guidelines. WES disclosed 24 (likely) pathogenic variants among 18 patients in epilepsy-related genes with either autosomal dominant, recessive or X-linked inheritance. Ten of these were novel. We obtained a diagnostic yield of 25.3%, higher among patients with brain malformations, early-onset epilepsy and dysmorphisms. Despite a median diagnostic delay of 38.7 years, WES analysis provided the long-awaited diagnosis for 18 adult patients, which also had an impact on the clinical management of 50% of them.

Epilepsy after acute central nervous system complications of pediatric hematopoietic cell transplantation: A retrospective, multicenter study.

BACKGROUND: Acute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT. METHODS: This retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up. RESULTS: Ninety-four patients (63 males, 31 females, median age 10 years, range 1-21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87-68.97). CONCLUSIONS: A higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT.

The role of risperidone in the treatment of children and adolescents with anorexia nervosa.

BACKGROUND: Current Diagnostic and Statistical Manual of Mental Disorders (DSM)-5-based research provides limited data on the use of risperidone on children and adolescents with anorexia nervosa (AN) mainly in small-sample/case report studies. AIM: To report the use of risperidone in a group of children and adolescents with feeding and eating disorders, specifically with AN. METHODS: Observational, naturalistic study. Psychopathology was assessed with Eating Disorders Inventory-3, Beck's Depression Inventory-II, and Symptom Checklist-90-R. Data were reported for the whole sample, for patients treated with risperidone, and finally compared between patients with AN treated with risperidone and those receiving no atypical antipsychotics. Potential differences in admission-discharge changes in body mass index (BMI) and psychopathology were assessed with analyses of covariance corrected for baseline measures. Kaplan-Meier analyses were conducted to assess retention rates of risperidone (at 3 months and 1 year) and rates of rehospitalization on 1-year follow-up. RESULTS: The study enrolled 120 patients with AN (42 treated with risperidone). Risperidone was used for 116.7 (±122.8) days (total exposure = 3979 days) and well-tolerated (nausea, asthenia in one case). No significantly different admission-discharge improvements for BMI or psychopathology were documented for patients treated with risperidone. Risperidone showed a 3-month retention rate of 50.0% (1 year: 9.5%) and was discontinued mainly for the resolution of target symptoms. Cumulative freedom from rehospitalization at 12 months was comparable for treated and untreated patients (hazard ratio = 1.088; Log-rank p = 0.908). CONCLUSIONS: This study reports real-life evidence of the use of risperidone in AN children and adolescents in the widest described sample so far. Longitudinal research should assess long-term prognostic factors and tolerability.

Status Epilepticus in Chromosomal Disorders Associated with Epilepsy: A Systematic Review.

Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, n = 20), Ring 20 Syndrome (R20, n = 24), and other syndromes (n = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients.

Cannabidiol in the acute phase of febrile infection-related epilepsy syndrome (FIRES).

Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure-free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES.

Antipsychotics in the Treatment of Children and Adolescents with Anorexia Nervosa: A Systematic Review.

Evidence about the use of pharmacologic agents in the treatment of Anorexia Nervosa (AN) is lacking, especially in childhood and adolescence. A systematic scoping review was conducted to outline current literature evidence about the use of antipsychotics in this population. A total of 499 studies were identified with the initial search, and 28 of these studies were selected regarding the use of olanzapine (n = 13), risperidone (n = 4), aripiprazole (n = 3), chlorpromazine (n = 3), pimozide (n = 1) clotiapine (n = 1) and multiple antipsychotics (n = 3) in these patients. Overall, major side effects were reported infrequently; improvements in psychopathology and weight measures have been suggested in the majority of the considered studies. Nonetheless, the lack of RCT or good-quality studies strongly limits the generalizability of results in clinical practice.

Lithium treatment in children and adolescents with anorexia nervosa: clinical use, side effects and tolerability.

PURPOSE: Current guidelines, due to potential toxicity and lack of clinical evidence, do not recommend the use of lithium in the treatment of Anorexia Nervosa (AN). Scarce evidence is available on the use, side effects, and tolerability of this drug in children and adolescents with AN, a population characterized by specific clinical, metabolic, and hydro-electrolytic balance features. Here we report a case series of children and adolescents hospitalized for AN and treated with lithium. METHODS: Case series reporting the use of lithium in 7 female young patients with AN. Reasons for introduction, dosages, formulation, plas-ma levels, adverse drug reactions (ADR) and modifi-cations of electrocardiogram (EKG) and plasma levels of glucose, cholesterol, creatinine, urea, sodium, and thyroid-stimulating hormone (TSH) were assessed. Re-sults. Reasons for the introduction of lithium included unstable mood, insufficient compliance with nutri-tional programs, and psychomotor agitation. In all of the patients an improvement on target symptoms was observed. Lithium was started at 171.4 (+/-56.7) mg/day, up to 600.0 (+/-173.2) mg/day. The most frequent scheme was three times daily. The mean plasmatic concentration was 0.6 (+/-0.3) mmol/L at one month. One pa-tient experienced polyuria, polydipsia and dry mouth, and another showed increased creatinine kinase. No major modifications of EKG, glucose, cholesterol, cre-atinine, urea, sodium emerged. CONCLUSIONS: In this sample of children and adolescents hospitalized for AN, lithium was administered to improve psychiatric symptoms impairing compliance. All the patients experienced an improvement on these symptoms after being admin-istered lithium. ADR were reported in 2 cases. These data should be investigated in wider populations and controlled studies.

SUNCT/SUNA in Pediatric Age: A Review of Pathophysiology and Therapeutic Options.

The International Classification of Headache Disorders, 3rd edition (ICHD3) defines Short-lasting Unilateral Neuralgiform Headache Attacks (SUNHA) as attacks of moderate or severe, strictly unilateral head pain lasting from seconds to minutes, occurring at least once a day and usually associated with prominent lacrimation and redness of the ipsilateral eye. Two subtypes of SUNHA are identified: Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) and Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms (SUNA). These pathologies are infrequent in children and difficult to diagnose. The authors reviewed the existing literature on SUNCT and SUNA, especially in the developmental age, which describes the pathophysiology in detail and focuses on the therapeutic options available to date. SUNHA-type headaches must be considered on the one hand, for the possibility of the onset of forms secondary to underlying pathologies even of a neoplastic nature, and on the other hand, for the negative impact they can have on an individual's quality of life, particularly in young patients. Until now, published cases suggest that no chronic variants occur in childhood and adolescents. In light of this evidence, the authors offer a review that may serve as a source to be drawn upon in the implementation of suitable treatments in children and adolescents suffering from these headaches, focusing on therapies that are non-invasive and as risk-free as possible for pediatric patients.