A Systematic Review on Autism and Hyperserotonemia: State-of-the-Art, Limitations, and Future Directions.

Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies.

The Hidden Impact of ADHD Symptoms in Preschool Children with Autism: Is There a Link to Somatic and Sleep Disorders?

Neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), do often present in comorbidity among them and with other medical conditions, including sleep and gastrointestinal (GI) disorders and somatic complaints. An anonymous online survey based on standardized questionnaires (SDSC, KL-ASD, APSI, ROME V CRITERIA, CPRS, CBCL) was completed by the parents of 46 preschoolers diagnosed with ASD. A high prevalence (47%) of ADHD symptoms in this population was found, surpassing previous estimates. Sleep disturbances, especially difficulties in initiating and maintaining sleep and sleep-wake transition, are more pronounced in ASD patients with comorbid ADHD. Additionally, in patients over 4 years old, there is a high prevalence of functional GI symptoms (Rome V criteria: 38%). Parental stress is significantly associated with ADHD symptoms, sleep disorders, and GI symptoms. Comprehensive assessments considering both core symptoms of neurodevelopmental disorders and associated comorbidities are crucial for more effective treatment strategies and improved wellbeing in affected individuals and their families.

Misdiagnosis of functional neurological symptom disorders in paediatrics: Narrative review and relevant case report.

Functional neurological symptom disorders (FNSD) pose a common challenge in clinical practice, particularly in pediatric cases where the clinical phenotypes can be intricate and easily confused with structural disturbances. The frequent coexistence of FNSDs with other medical disorders often results in misdiagnosis. In this review, we highlight the distinctions between FNSD and various psychiatric and neurological conditions. Contrary to the misconception that FNSD is a diagnosis of exclusion, we underscore its nature as a diagnosis of inclusion, contingent upon recognizing specific clinical features. However, our focus is on a critical learning point illustrated by the case of a 14-year-old male initially diagnosed with FNSD, but subsequently found to have a rare primary monogenic movement disorder (paroxysmal kinesigenic dyskinesia, PKD). The crucial takeaway from this case is the importance of avoiding an FNSD diagnosis based solely on psychiatric comorbidity and suppressible symptoms. Instead, clinicians should diligently assess for specific features indicative of FNSD, which were absent in this case. This emphasizes the importance of making a diagnosis of inclusion. Extended follow-up and clinical-oriented genetic testing might help identify comorbidities, prevent misdiagnosis, and guide interventions in complex cases, which cannot be simply classified as "functional" solely because other conditions can be excluded.

Understanding and Avoiding Mistakes in Diagnosing Children with Functional Neurological Symptom Disorders: A Review and Case Report: This article discusses Functional Neurological Symptom Disorders (FNSDs), focusing on misdiagnosis, differential diagnosis, and other diagnostic challenges, particularly in pediatric cases. FNSDs involve motor or sensory symptoms that are inconsistent over time and unexplained by neurological disease, often associated with psychosocial factors. The article highlights the complexity of distinguishing FNSDs from other neurological and psychiatric conditions, emphasizing the importance of careful evaluation. The authors review various conditions that can mimic FNSDs, such as epileptic seizures, syncope, and different motor disorders. They emphasize the need to consider psychiatric conditions in the differential diagnosis, including factitious disorders, and malingering. The article presents a case study of a 14-year-old with involuntary movements, initially diagnosed as having a Functional Movement Disorder. After careful evaluation, the patient was diagnosed with a genetic dystonia (PRRT2 mutation). The case shows the importance of not rely solely on psychological problems, bizarre presentations or suppressible symptoms when diagnosing FNSDs.

Serrated polyps <10 mm cannot reliably be characterized by i-Scan without magnification at routine colonoscopy.

BACKGROUND: Colorectal lesions (CRLs) <10 mm found at colonoscopy tend towards "diagnose-and-leave" or "resect-and-discard" strategies based on real-time Kudo glandular pit-pattern's assessment using i-Scan. However, i-Scan has not yet been validated for Kudo's classification. We aimed to assess whether, in routine colonoscopy, i-Scan without magnification and optical enhancement (M-OE) reliably differentiates hyperplastic polyps (HPs) from other serrated lesions (SLs) and conventional adenomas (CAs), and, among SLs, HPs from sessile serrated lesions (SSLs) and traditional or unknown serrated adenomas (TSAs, USAs), in Kudo type II CRLs<10 mm, according to ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) recommended negative predictive value (NPV) threshold for adenomas. METHODS: Prospectively recorded CRLs over 12 months, classified according to Kudo pit-pattern using i-Scan, were retrospectively compared with histology. RESULTS: Overall, 898 ≤5-mm and 704 6- to 9-mm CRLs were included. Type II pit-pattern was found in 76.6% and 38.7% of HPs and SSLs-TSAs/CAs (P<0.000001), and in 84.1% and 26.6% of SLs and CAs (P<0.000001). Among SLs, it was found in 81.9% and 86.6% of HPs and SSLs-TSAs. In CRLs≤5 mm, HPs were prevalent over other SLs (P=0.00001); in CRLs 6-9 mm, CAs were prevalent (P<0.000001). About 77% of SLs in right colon were SSLs-TSAs; 82% in left colon were HPs. PIVI ≥90% NPV threshold for adenomas was reached for CRLs 6-9mm (92.1%), nearly achieved for CRLs≤5 mm (88.2%), and not reached for SLs independently on the size. CONCLUSIONS: A strategy of "diagnose-and-leave" or "resect-and-discard" cannot be recommended for SLs<10 mm with Kudo type II pit-pattern using i-Scan, especially in right colon, if M-OE unavailable.

Endoscopic vacuum therapy versus self-expandable metal stent for treatment of anastomotic leaks < 30 mm following oncologic Ivor-Lewis esophagectomy: a matched case-control study.

BACKGROUND: Management of anastomotic leaks after Ivor-Lewis esophagectomy remains a challenge. Although intracavitary endoscopic vacuum therapy (EVT) has shown great efficacy for large dehiscences, the optimal management of smaller leaks has not been standardized. This study aims to compare EVT versus self-expandable metal stent (SEMS) in the treatment of leaks < 30 mm in size, due to the lack of current data on this topic. METHODS: Patients undergoing EVT (cases) or SEMS (controls) between May 2017 and July 2022 for anastomotic leaks < 3 cm following oncologic Ivor-Lewis esophagectomy were enrolled. Controls were matched in a 1:1 ratio based on age (± 3 years), BMI (± 3 kg/m2) and leak size (± 4 mm). RESULTS: Cases (n = 22) and controls (n = 22) showed no difference in baseline characteristics and leak size, as per matching at enrollment. No differences were detected between the two groups in terms of time from surgery to endoscopic treatment (p = 0.11) or total number of procedures per patient (p = 0.05). Remarkably, the two groups showed comparable results in terms of leaks resolution (90.9% vs. 72.7%, p = 0.11). The number of procedures per patient was not significant between the two cohorts (p = 0.05). The most frequent complication in the SEMS group was migration (15.3% of procedures). CONCLUSION: EVT and SEMS seem to have similar efficacy outcomes in the treatment of anastomotic defects < 30 mm after Ivor-Lewis esophagectomy. However, larger studies are needed to corroborate these findings.

Tension-Type Headache in Children and Adolescents.

In pediatric neurology, tension-type headache (TTH) represents a very common type of primary headache during the pediatric age. Despite the high prevalence of TTH, this diagnosis is often underestimated in childhood, with relevant difficulties in the differential diagnosis of TTH from secondary and primary headache manifestations. Even among primary headaches, a clinical overlap is not so infrequent in children: migraine attacks could present tension headache-like features while tension-type headaches may display migraine-like symptoms as well. Several variables play a role in the complex trajectory of headache evolution, such as hormonal changes during adolescence, triggers and genetic and epigenetic factors. The trajectories and outcomes of juvenile migraine and TTH, as well as the transition of one form to the other, have been investigated in several long-term prospective studies. Thus, the aim of this paper is to review the current literature on the differential diagnosis workout of TTH in pediatrics, the possible outcomes during the developmental age and the appropriate therapeutic strategies. Indeed, TTH represents a challenging diagnostic entity in pediatrics, both from a clinical and a therapeutic point of view, in which early diagnosis and appropriate treatment are recommended.

Endoscopic Vacuum Therapy (EVT) versus Self-Expandable Metal Stent (SEMS) for Anastomotic Leaks after Upper Gastrointestinal Surgery: Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic treatment of post-esophagectomy/gastrectomy anastomotic dehiscence includes Self-Expandable Metal Stents (SEMS), which have represented the "gold standard" for many years, and Endoscopic Vacuum Therapy (EVT), which was recently introduced, showing promising results. The aim of the study was to compare outcomes of SEMS and EVT in the treatment of post-esophagectomy/gastrectomy anastomotic leaks, focusing on oncologic surgery. METHODS: A systematic search was performed on Pubmed and Embase, identifying studies comparing EVT versus SEMS for the treatment of leaks after upper gastro-intestinal surgery for malignant or benign pathologies. The primary outcome was the rate of successful leak closure. A meta-analysis was conducted, performing an a priori-defined subgroup analysis for the oncologic surgery group. RESULTS: Eight retrospective studies with 357 patients were eligible. Overall, the EVT group showed a higher success rate (odd ratio [OR] 2.58, 95% CI 1.43-4.66), a lower number of devices (pooled mean difference [pmd] 4.90, 95% CI 3.08-6.71), shorter treatment duration (pmd -9.18, 95% CI -17.05--1.32), lower short-term complication (OR 0.35, 95% CI 0.18-0.71) and mortality rates (OR 0.47, 95% CI 0.24-0.92) compared to stenting. In the oncologic surgery subgroup analysis, no differences in the success rate were found (OR 1.59, 95% CI 0.74-3.40, I2 = 0%). CONCLUSIONS: Overall, EVT has been revealed to be more effective and less burdened by complications compared to stenting. In the oncologic surgery subgroup analysis, efficacy rates were similar between the two groups. Further prospective data need to define a unique management algorithm for anastomotic leaks.

Sleep habits and sleep disorders in Italian children and adolescents: a cross-sectional survey.

STUDY OBJECTIVES: The aim was to describe sleep habits and epidemiology of the most common sleep disorders in Italian children and adolescents. METHODS: This was a cross-sectional study in which parents of typically developing children and adolescents (1-18 years) completed an online survey available in Italy, gathering retrospective information focusing on sleep habits and disorders. RESULTS: Respondents were 4,321 typically developing individuals (48.6% females). Most of our sample did not meet the age-specific National Sleep Foundation recommendations for total sleep duration (31.9% of toddlers, 71.5% of preschoolers, 61.6% of school-age children, and 41.3% of adolescents). Napping was described in 92.6% of toddlers and in 35.2% of preschoolers. Regarding geographical differences, children and adolescents of northern Italy showed more frequent earlier bedtimes and rise times than their peers of central and southern Italy. The most frequently reported sleep disorder in our sample was restless sleep (35.6%), followed by difficulties falling asleep (16.8%), > 2 night awakenings (9.9%), and bruxism (9.6%). Data also suggest that longer screen time is associated with later bedtimes on weekdays in all age groups. CONCLUSIONS: The current study shows that Italian children are at risk of sleep disorders, particularly insufficient sleep, restless sleep, and difficulty falling asleep. The study also provides normative sleep data by age group in a large cohort of typically developing Italian children, emphasizing the importance of the developmentally, ecologically, and culturally based evaluation of sleep habits and disorders. CITATION: Breda M, Belli A, Esposito D, et al. Sleep habits and sleep disorders in Italian children and adolescents: a cross-sectional survey. J Clin Sleep Med. 2023;19(4):659-672.

Gastric peroral endoscopic myotomy (G-POEM) for refractory gastroparesis.

Gastroparesis is a chronic functional disorder characterized by severe symptoms and objective documentation of delayed gastric emptying, in the absence of any mechanical obstruction. The pathogenesis of gastroparesis comprises abnormalities of gastric motility (corpus and fundus dysmotility and antral hypomotility), pyloric resistance to gastric outflow (pyloric lower compliance or hypertone), and lack of antroduodenal motor coordination. Several conditions have been correlated to gastroparesis: diabetes, post-surgical sequelae, medications, neurological/muscular disorders and collagen vascular diseases. Diabetes is the most frequent condition associated with gastroparesis, which has been reported in up to 50% of patients suffering from long-lasting disease. The therapy of gastroparesis is primarily medical, with prokinetic or antiemetic drugs, but response may be limited, and side effects can arise; if medical therapy fails, pyloromyotomy remains the main option, either surgical or endoscopic. Gastric peroral endoscopic myotomy (G-POEM) may be considered nowadays an effective potential therapeutic intervention in alternative to surgery, relatively easy to perform in experienced hands, with a technical success of 100%, a favorable safety profile, and positive outcomes in the short-term as documented in three meta-analyses. However, to date, the definition of clinical success in gastroparesis is still not standardized, the correlation between symptom improvement and the objective documentation of an improvement in gastric emptying remains in some cases uncertain, reliable data to help in predicting which categories of gastroparesis and which symptoms could benefit most from the intervention, and long-term outcomes are still lacking.

Reading and writing difficulties in third- and sixth-grade students: a cross-sectional survey.

BACKGROUND: In Southern Italy and, specifically, in the region of Campania, many surveys show that the average of students with reading difficulties is much higher than in northern Italy and abroad. On the other hand, specific learning disorders (SLDs) in Campania are much less certified. Since there are no etiological reasons that can explain this apparent inconsistency, an objective of this cross-sectional study was to evaluate the extent of reading/writing difficulties in students from a province of Campania and then to assess the ability of teachers to identify such difficulties in their students. METHODS: Of a total of 241 enrolled students, 155 (64.31%), including 73 from primary school and 82 from secondary school, belonging to 5 schools in the province of Salerno (Italy), took part in the survey. Students' reading and writing skills were assessed through standardized tests. The tests results were then compared with teacher judgments and context-related variables. RESULTS: At the reading test, 28.7% of primary school and 13.4% of lower secondary school students fell below the 5th percentile for age. Results of the writing test were even more significant: almost half of the students of both levels of education performed below the 5th percentile. Teacher judgments showed higher agreement with standardized assessments in primary (88%, K of Cohen=0.68) than in secondary school (78%, K=0.23). CONCLUSIONS: Reading and writing difficulties were common in our sample. While reading skills tended to improve with age, writing difficulties apparently persisted to some extent in third and sixth-grade classes. The accuracy of teacher judgments on reading skills is relatively high, but teachers seem to hardly report reading difficulties "requiring attention." Although less "severe" than others, such difficulties should be considered, mainly because of their potential developmental trajectories.

Paediatric sudden unexpected death in epilepsy: From pathophysiology to prevention.

Sudden unexpected death in epilepsy (SUDEP) is a fatal event, occurring in patients with epilepsy, in which seizures may or may not precede the exitus, and no other potential causes of death are identifiable. The proposed pathophysiological mechanisms for SUDEP include cardio-respiratory dysfunctions, brainstem arousal system impairment, and dysregulation in the neurotransmitter/neuromodulator systems. This narrative review provides an overview of primary research on SUDEP in paediatric populations. Some studies report an incidence of paediatric SUDEP which is about five times lower than in adults (between 0.02 and 0,34 per 1,000 person-years) even if more recent studies suggested similar incidence rates than in adulthood (between 1.20 / 1,000 and 1.45 / 1,000 person per years). Risk factors for SUDEP in children include genetic predisposition, neurological comorbidities, epilepsy phenotype, adequacy/adherence to treatment, adequate supervision by caregivers and access to adequate health care support. The early identification of risk factors, the definition of reliable biomarkers and the building of efficacious preventive strategies, including parental/caregiver counselling, novel technological devices, and pharmacological treatments, may reduce the risk of paediatric SUDEP.

Psychological disorders, adverse childhood experiences and parental psychiatric disorders in children affected by headache: A systematic review.

BACKGROUND: Pediatric headaches have been linked to adverse life events or psychological factors in children and their families, with a complex and bidirectional association. Moreover, it is well-known that psychological stress can trigger headaches. METHODS: We searched three databases for studies focusing on headaches and adverse events or psychological factors in children up to 12 years old or in their caregivers. RESULTS: We included 28 studies. Child psychological factors, including internal and external symptoms, were commonly associated with all types of headaches. Sleep disturbances showed a positive association with headaches in 3 out of 5 studies. Family conflict and unhappiness were frequently found in children suffering with headaches, while single-parent families and divorce were not associated. Stressful environments and adverse life events, particularly bullying, were also found to be linked with headaches. CONCLUSIONS: Childhood headaches represent an alarm bell for clinicians to investigate and treat psychological or psychiatric disorders in children and their family. Further studies are needed to elucidate the role of early-life adverse events in children and their families.

Endoscopic vacuum therapy for post-esophagectomy anastomotic dehiscence as rescue treatment: a single center case series.

BACKGROUND: Endoscopic vacuum therapy (EVT) represents an effective endoscopic technique for the treatment of post-esophagectomy leaks and can be used after failure of primary treatment. We aimed to investigate endoscopic data and success rate of EVT for post-esophagectomy anastomotic leaks, after failed redo surgery or previous endoscopic treatment. METHODS: We retrospectively recruited 12 patients from January 2018 to October 2020. Success was defined as dehiscence closure at radiological and/or endoscopic evaluation. Ethical Committee of our institution approved the study. RESULTS: Twelve patients (66.7% male, mean age 65.08 ± 16.7 years) affected by esophago-gastric (n = 10) or esophago-jejunal (n = 2) anastomosis dehiscences after oncologic surgery were treated with EVT, after failure of previous redo-surgical (n = 3, 25%) or endoscopic management (n = 9, 75%). Technical success rate was 100% (60/60 procedures) and dehiscence closure was achieved in three quarters of patients (9/12, 75%). Regarding complications, one case of sponge dislocation (1/60 = 1.7%) and another case of delayed stricture after post-EVT stent placement (1/60 = 1.7%) were recorded, during a mean follow up of 182.3 days. CONCLUSIONS: EVT is a promising option in the treatment of the most complicated anastomotic dehiscences. Its use could be also considered after failure of previous endoscopic or surgical management.

Children with neurodevelopmental disorders: how do they sleep?

PURPOSE OF REVIEW: In this review we summarized the available evidence on sleep disorders in children with neurodevelopmental disorders (NDDs) in particular: intellectual disability (including some genetic conditions such as Prader-Willi Syndrome, Smith-Magenis Syndrome), Autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), Developmental Coordination Disorder, language disorders, and specific learning disorders. RECENT FINDINGS: Children with NDDs frequently suffer from sleep disturbances, with a higher prevalence than that of the general pediatric population. SUMMARY: These problems tend to be chronic and may cause additional cognitive and behavioral difficulties, often affecting the whole family's well-being. Sleep behaviors are also related to other important developmental skills, such as attention and listening. Investigating sleep disorders in children with NDDs is therefore crucial in clinical practice. For a systematic approach in clinical practice, we propose the use of a short and easy to remember sleep screening tool.

Sleep terrors-A parental nightmare.

Sleep terrors (STs) are sleep disorders characterized by abrupt arousal from sleep with autonomic hyperactivity and inappropriate behavior. Though a common condition in childhood that usually affects children between 4 and 12 years of age, STs, however, may be present even in adulthood. The exact etiology of STs is not known yet, however, several hypotheses have been proposed over the years, identifying some potential genetic, neurodevelopmental, or other causes. Nevertheless, a useful pathophysiological model identified a common cascade of predisposing, priming, and precipitating factors, which could help to explain and sometimes prevent STs. Establishing a correct diagnosis is mandatory for appropriate management, as several conditions (such as other parasomnias or nocturnal seizures) may mimic STs. Furthermore, we also described some conditions which can be comorbid to STs, like some medical or psychological disorders. A number of treatment options have been proposed, ranging from only sleep hygiene practices to pharmacological therapies; we reviewed some of the most prominent ones. In spite of the fact that STs have long been considered benign disorders, which tend to reduce spontaneously over the years, they may have unexpected consequences on the child but also on the caregivers.