Abnormalities in the plasma amino acid and/or urinary organic acid profile have been reported in autism spectrum disorder (ASD). An imbalance between excitatory and inhibitory neuronal activity has been proposed as a mechanism to explain dysfunctional brain networks in ASD, as also suggested by the increased risk of epilepsy in this disorder. This study explored the possible association between presence of EEG paroxysmal abnormalities and the metabolic profile of plasma amino acids and urinary organic acids in children with ASD. In a sample of 55 children with ASD (81.8% male, mean age 53.67 months), EEGs were recorded, and 24 plasma amino acids and 56 urinary organic acids analyzed. EEG epileptiform discharges were found in 36 (65%) children. A LASSO regression, adjusted by age and sex, was applied to evaluate the association of plasma amino acids and urinary organic acids profiles with the presence of EEG epileptiform discharges. Plasma levels of threonine (THR) (coefficient = −0.02, p = 0.04) and urinary concentration of 3-Hydroxy-3-Methylglutaric acid (HMGA) (coefficient = 0.04, p = 0.02) were found to be associated with the presence of epileptiform discharges. These results suggest that altered redox mechanisms might be linked to epileptiform brain activity in ASD.

Innovative targeted treatments for neuromuscular disorders (NMDs) can dramatically improve the course of illness. Diagnostic delay, however, is a major impediment. Here, we present a pilot project aimed at assessing the feasibility of a screening program to identify children at high risk for NMDs within the first 30 months of life. The Promoting Early Diagnosis for Neuromuscular Disorders (PEDINE) project implemented a three-step sequential screening in an area of about 300,000 people with (1) an assessment of the motor development milestones to identify “red flags” for NMDs by primary care pediatricians (PCPs) as part of the routine Health Status Check visits; (2) for the children who screened positive, a community neuropsychiatric assessment, with further referral of suspected NMD cases to (3) a hospital-based specialized tertiary care center. In the first-year feasibility study, a total of 10,032 PCP visits were conducted, and twenty children (0.2% of the total Health Status Check visits) screened positive and were referred to the community neuropsychiatrist. Of these, four had elevated creatine kinase (CK) serum levels. This pilot study shows that screening for NMDs in primary care settings is feasible and allows children at high risk for muscular disorder to be promptly identified.

The post-operative pediatric cerebellar mutism syndrome (CMS) affects about one-third of children and adolescents following surgical removal of a posterior fossa tumor (PFT). According to the Posterior Fossa Society consensus working definition, CMS is characterized by delayed-onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricle tumor surgery in children, and is frequently accompanied by additional features such as hypotonia and oropharyngeal dysfunction/dysphagia. The main objective of this work was to develop a diagnostic scale to grade CMS duration and severity. Thirty consecutively referred subjects, aged 1–17 years (median 8 years, IQR 3–10), were evaluated with the proposed Post-Operative Pediatric CMS Survey after surgical resection of a PFT and, in case of CMS, for 30 days after the onset (T0) or until symptom remission. At day 30 (T1), CMS was classified into mild, moderate, or severe according to the proposed scale. CMS occurred in 13 patients (43%, 95% C.I.: 25.5–62.6%), with mild severity in 4 cases (31%), moderate in 4 (31%), and severe in 5 (38%). At T1, longer symptom persistence was associated with greater severity (p = 0.01). Greater severity at T0 predicted greater severity at T1 (p = 0.0001). Children with a midline tumor location and those aged under 5 years at diagnosis were at higher risk of CMS (p = 0.025 and p = 0.008, respectively). In conclusion, the proposed scale is a simple and applicable tool for estimating the severity of CMS at its onset, monitoring its course over time, and providing an early prognostic stratification to guide treatment decisions. What is Known:• Post-operative pediatric Cerebellar Mutism Syndrome (CMS) is a complex phenomenon with a wide spectrum of symptoms that may manifest in children undergoing the resection of a posterior fossa tumor (PFT) and that can result into long-term impairment. What is New:• This study developed and pilot-tested an easily applicable diagnostic and severity scale to grade the duration and the severity of symptoms of the CMS.• The proposed scale was found to be a sensitive instrument to identify even mild CMS presentations.• By scoring not only the duration but also the severity of symptoms the scale allows a more accurate prognostic stratification for an optimal planning of clinical and rehabilitative interventions.

BACKGROUND: The post-operative Pediatric Cerebellar Mutism Syndrome (CMS) affects about one-third of children and adolescents following surgical removal of a posterior fossa tumor (PFT). According to the Posterior Fossa Society consensus working definition, CMS is characterized by delayed onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricle tumor surgery in children, with additional common features that include hypotonia and oropharyngeal dysfunction/dysphagia. The main objective of this work was to propose a diagnostic scale to grade CMS duration and severity.METHOD: Thirty consecutive subjects, aged 1-17 years (median 8 years, IQR 7) were evaluated with the proposed Post-Operative Pediatric CMS Survey after surgical resection of a PFT and, in cases of CMS, for the next 30 days after the onset (T0) or until symptom remission. At day 30th (T1), CMS was classified into mild, moderate, or severe according to the proposed Scale.RESULTS: CMS occurred in 13 patients (43.3%, 95% C.I.: 25.5-62.6%), with mild severity in 4 cases (31%), moderate in 4 (31%), and severe in 5 (38%). At T1, longer symptom persistence was associated with greater severity (p=0.01). Greater severity at T0 predicted greater severity at T1 (p=0.0001). Children with a midline tumor location and those aged under 5 years at diagnosis were at higher risk of CMS (p=0.025 and p=0.008, respectively).CONCLUSIONS: The proposed scale is a simple and applicable tool for estimating the severity of CMS at its onset, monitoring its course over time, and providing an early prognostic stratification to guide treatment decisions.