Acquired Demyelinating Syndromes of the Central Nervous System in Children: The Importance of Regular Follow-up in the First Year After Onset.

AIM: We reviewed the clinical features of a sample of pediatric acquired demyelinating syndromes with the purpose of determining the appropriate protocol for follow-up after the first episode. METHODS: A multicenter retrospective observational study was conducted on a cohort of 40 children diagnosed with a first episode of acquired demyelinating syndrome over the period 2012-2021. Patients were evaluated with clinical and neuroradiologic assessment after 3, 6, and 12 months, with a median follow-up of 4.0 years. RESULTS: At the first acquired demyelinating syndrome episode, 18 patients (45%) were diagnosed with acute disseminated encephalomyelitis, 18 (45%) with clinical isolated syndrome, and 4 (10%) with multiple sclerosis. By month 12, 12 patients (30%) had progressed from an initial diagnosis of acute disseminated encephalomyelitis (2) or clinical isolated syndrome (10) to multiple sclerosis. Of these, 6 had clinical relapse and 6 radiologic relapse only. The first relapse occurred after a median of 3 months. Among the patients who had evolved toward multiple sclerosis, there was a prevalence of females (P = .014), higher oligoclonal bands positivity (P = .009), and older median age (P < .001) as compared with those who had remained stable. INTERPRETATION: Both clinical and radiologic follow-up of children with acquired demyelinating syndromes is crucial, especially during the first year after acute onset, for early identification of multiple sclerosis and prompt initiation of disease-modifying treatment to delay axonal damage and to limit disability.

Sleep disturbances and emotional dysregulation in young children with autism spectrum, intellectual disability, or global developmental delay.

OBJECTIVE: Sleep disturbance and emotional dysregulation (ED) are common and often functionally impairing in young children with neurodevelopmental disorders (NDD). This study investigated the relationship between sleep disturbance and ED in a sample of preschoolers with ASD, intellectual disability, or global developmental delay, and examined possible predictors of their persistence over time. METHODS: All children under 6 years of age clinically referred between July 2018 and May 2022 to two neuropsychiatric specialized centers for NDD received a comprehensive diagnostic evaluation, including the Child Behavior Checklist 1.5-5 (CBCL), the Autism Diagnostic Observation Schedule-2 (ADOS-2), and standardized tests of cognitive and global development. Sleep disturbances were assessed with the CBCL-sleep score, and ED with the CBCL Attention, Aggression, and Anxious/Depressed scales (CBCL-AAA). A reassessment of sleep and ED was conducted after 6 months or longer, including the Child Sleep Habits Questionnaire (CSHQ). Multivariate analyses and mixed linear regression models were conducted. RESULTS: A total of 136 children, 75.7% male, median age 38.27 months, IQR 15.39, 41.2% with global developmental disorder (GDD) or intellectual disability (ID) participated in the study. Of them, 64.7% were diagnosed with autism spectrum disorder (ASD) and 35.3% with other NDD (w/o ASD). Sleep disturbances (CBCL-Sleep) and ED (CBCL-AAA) were positively correlated (p < 0.001), after accounting for age, ID/GDD and autism symptom severity, in both the entire sample and separately in each diagnostic group (ASD and NDD w/o ASD). Seventy-five children (55%) were reassessed a mean 17.2 months afterwards. There was persistence of the positive correlation between sleep problems and ED (p < 0.001) in both the entire sample and each diagnostic group. The longitudinal mixed linear model showed that ED at follow-up was predicted by baseline sleep problems (p = 0.008), ED (p < 0.001), and ASD severity (p = 0.015). CONCLUSIONS: Sleep disturbances are significantly associated with ED in young children with NDD, either with or without ASD, both cross-sectionally and prospectively over time. Sleep problems represent an important comorbidity and a potential treatment target for improving emotional stability in NDD.

Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice.

OBJECTIVES: The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice. METHODS: The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5-20 mg daily, and was reassessed a week later. RESULTS: Eleven patients (2.3%, 95% CI 1.1-4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and 'rebound' behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later. CONCLUSIONS: Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment.

What Do We Know about the Long-Term Course of Early Onset Bipolar Disorder? A Review of the Current Evidence.

AIM: Early onset of psychopathology is often an index of a more severe clinical course and worse prognosis. This review examined the course of bipolar disorder (BD) with onset in childhood and adolescence, with a focus on persistence of symptoms, severity of illness, comorbidity, and functional impairment. METHODS: The databases of PubMed, Embase, and PsycInfo were systematically searched for publications since 1990 reporting on long-term (12 months or longer) assessments of patients with early onset BD. RESULTS: Forty-two relevant publications were identified, which reported on data derived from 15 different patient cohorts, including 7 prospective research psychopathology studies, 4 medical record reviews, 2 follow-ups of clinical trial samples, 1 managed care database, and 1 nationwide registry, for a total of 10,187 patients. The length of follow-ups ranged from 1.0 to 15 years. Diagnostic stability of BD ranged from 73% to 100% over ten years. Recovery rate from an index episode was 81.5-100% and recurrence rate was 35-67%. Suicide attempt cumulative prevalence in five years was 18-20%. Earlier age at the first episode predicted a more severe clinical course. CONCLUSIONS: Early onset BD persists over time through adolescence, with homotypic diagnostic continuity over the years, but heterogeneity in the severity of the clinical course. Whether early identification and treatment improves distal prognosis remains to be further investigated.