Background
The use of valproate in the treatment of Anorexia Nervosa (AN) in children and adolescents is currently not recommended by clinical guidelines, due to lack of evidence. Nonetheless, ...valproate is used to treat a series of psychiatric and neurologic conditions. To date, only six cases of patients with Feeding and Eating Disorders (three with AN) have been described.
Methods
Case series of 14 children and adolescent patients hospitalized for AN and treated with valproate as an adjunctive treatment. Reasons for introduction, dosages, plasma levels, adverse drug reactions (ADR) and modifications of liver enzymes, platelets levels, abdominal and pelvic ultrasounds, and concurrent drugs plasma levels were assessed.
Results
Reasons for the introduction of valproate included unstable mood (57.1%), lack of compliance (50%) and aggressive behaviour (21.4%). In 71.4% of patients an improvement on target symptoms was observed. Valproate was started at 241.7 (± 73.3) mg, up to 521.4 (± 204.5) mg; the most frequent scheme was twice-daily. The mean plasmatic concentration was 66.3 (± 25.0) mg/L. One patient (7.1%) experienced side effects (somnolence). No major modifications of liver enzymes, platelet levels, abdominal and pelvic ultrasounds emerged after the introduction of valproate. Low concurrent olanzapine and quetiapine levels were documented.
Conclusions
This is the largest sample of patients with AN treated with valproate. Valproate was administered to improve psychiatric symptoms impairing compliance with inpatient treatment programs. The majority of patients experienced an improvement on target symptoms after being administered valproate, with minor ADR. These data should be investigated in wider populations and controlled studies.
Level of evidence
Level IV, case series.
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.
Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship ...between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs.
Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important ...to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables.
This retrospective cross-sectional study considered the following five categories of symptoms at onset: language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered: a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the entire sample and statistically analyzed for several clinical variables. Statistical analysis was performed utilizing Fisher Exact test and Chi Square test.
The first symptoms between 7 and 12 months were evident in 41.9% of cases, and between 13 and 24 months in 27.6%; no significant differences for the age at onset related to diagnosis, etiopathogenesis, early onset epilepsy, and intelligence quotient level emerged. Social interaction and relationships (93.3%) and language (92.4%) were the categories of early signs more represented in our sample. Delay in spoken language (to be understood as both verbal production and verbal comprehension) was one of the most common (even though not specific) symptoms prompting initial medical consultation for a possible diagnosis of autism spectrum disorder. At onset, patients without intellectual disability manifested stagnation more often than delay or regression of development; patients with a severe/profound intellectual disability more frequently showed delay or regression of development. Language signs at onset were less frequent in cases with regression, whereas motor skill disorders prevailed in cases with delay at onset. Feeding problems were more numerous in cases with delay and stagnation of development.
These data contribute to identifying an early trend of autism spectrum disorder, useful also for pediatricians.
Summary
Objective
To report on six patients with SCN1A mutations and malformations of cortical development (MCDs) and describe their clinical course, genetic findings, and electrographic, imaging, ...and neuropathologic features.
Methods
Through our database of epileptic encephalopathies, we identified 120 patients with SCN1A mutations, of which 4 had magnetic resonance imaging (MRI) evidence of MCDs. We collected two further similar observations through the European Task‐force for Epilepsy Surgery in Children.
Results
The study group consisted of five males and one female (mean age 7.4 ± 5.3 years). All patients exhibited electroclinical features consistent with the Dravet syndrome spectrum, cognitive impairment, and autistic features. Sequencing analysis of the SCN1A gene detected two missense, two truncating, and two splice‐site mutations. Brain MRI revealed bilateral periventricular nodular heterotopia (PNH) in two patients and focal cortical dysplasia (FCD) in three, and disclosed no macroscopic abnormality in one. In the MRI‐negative patient, neuropathologic study of the whole brain performed after sudden unexpected death in epilepsy (SUDEP), revealed multifocal micronodular dysplasia in the left temporal lobe. Two patients with FCD underwent epilepsy surgery. Neuropathology revealed FCD type IA and type IIA. Their seizure outcome was unfavorable. All four patients with FCD exhibited multiple seizure types, which always included complex partial seizures, the area of onset of which co‐localized with the region of structural abnormality.
Significance
MCDs and SCN1A gene mutations can co‐occur. Although epidemiology does not support a causative role for SCN1A mutations, loss or impaired protein function combined with the effect of susceptibility factors and genetic modifiers of the phenotypic expression of SCN1A mutations might play a role. MCDs, particularly FCD, can influence the electroclinical phenotype in patients with SCN1A‐related epilepsy. In patients with MCDs and a history of polymorphic seizures precipitated by fever, SCN1A gene testing should be performed before discussing any epilepsy surgery option, due to the possible implications for outcome.
Abstract The occurrence of epilepsy in autism is variable; nevertheless, EEG paroxysmal abnormalities (PA) are frequently recorded in patients with autism, although the influence of epilepsy and/or ...EEG PA on the autistic regression has not been clarified yet. We examine a large sample of 345 inpatients with autism, divided into three groups: (1) patients without epilepsy and EEG PA; (2) patients with EEG PA but no seizures; (3) patients with epilepsy including febrile convulsions. The prevalence of epilepsy (24.9%) and EEG PA (45.5%) was higher than that reported in the general population. The significant differences among the three groups concerned autistic regression (comparison between groups 1 and 2, p < 0.05; comparison between groups 1 and 3, p < 0.01), cerebral lesions (comparison between groups 1 and 2, p < 0.05; between groups 1 and 3, p < 0.001), and symptomatic autism (comparison between groups 1 and 2 as much as comparison between groups 1 and 3, p < 0.001), which were prevalent in groups 2 and 3; while severe/profound mental retardation was more frequent in group 3 compared to group 1 ( p < 0.01). Focal epilepsy (43.0%) and febrile convulsions (33.7%) were frequent in the third group with epilepsy. EEG PA were mainly localized in temporal and central areas (31.4%). Only 2.6% of patients had subcontinuous/continuous EEG PA during sleep. Seizures and EEG PA were not related to autistic regression. EEG PA occurred mainly in childhood, while epilepsy tended to occur ( p < 0.001) as age increased. The age at onset of seizures had two peaks: between 0 and 5 and between 10 and 15 years with no difference between idiopathic and symptomatic cases. In 58.5% of subjects aged ⩾20 years, epilepsy including febrile seizures occurred at some point of their lives, while cases with only EEG PA were less frequent (9.7%). The relationship among autism, EEG PA and epilepsy should be clarified and investigated. In autism, seizures and EEG PA could represent an epiphenomenon of a cerebral dysfunction independent of apparent lesions.
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) defines echolalia as a pathological, parrotlike, and apparently senseless repetition (echoing) of a word or phrase ...just uttered by another person and classifies this condition among the “restrictive and repetitive behaviours” of Autism Spectrum Disorder (ASD). The authors reviewed the existing literature on echolalia and its role in the development of children with ASD. Current conceptualizations include echolalia among repetitive behaviors and stereotypies and thus interpret this symptom as lacking any communicative significance, with negative effects on learning and sensory processing. Echoic behaviors, however, have been described in neurotypical infants and children as having a substantial effect on the consequent development of language and communication. Relevant research has documented a functional role of echolalia in ASD children as well since it facilitates the acquisition of verbal competencies and affords a higher degree of semantic generalization. This developmental function could be restricted to specific contexts. Considering echolalia as stereotypy and treating it as a disturbing symptom could impair the development of ASD-specific learning and communication processes. In light of this evidence, the authors propose a different conceptualization of echolalia and suggest that this symptom be considered among atypical communication patterns in children with ASD, with implications for treatment and prognosis.
Abstract
Background
Recent research has documented the potential associations existing between the use of social media (SM) and the occurrence/development and treatment of Eating Disorders (ED). ...However, the literature directly addressing the use of SM TikTok among children and adolescents with ED is still scarce.
Methods
In January–February 2021, during the second Italian national lockdown due to the SARS-CoV-2 pandemic, an anonymous paper survey was conducted in an Italian third-level center for ED in childhood and adolescence. Demographics, frequency of use of TikTok, frequently viewed topics and hashtags, experienced body-shaming, as well as the use of TikTok (active search, use of proposed contents) and perceived influences of this SM on eating attitudes and self-esteem were assessed. Groups of patients with different perceived SM-induced effects were compared to determine the frequency of their interaction with 3 specific contents (diet, Pro-Anorexia Nervosa (pro-Ana) and pro-ED recovery).
Results
Seventy-eight patients (93.6% females, mean age 14.5 ± 2.1 years) were enrolled in the study. For 62.8%, TikTok represented the main SM, used for 1.4 ± 1.0 h/day, with diet (21.8%) as the most frequently used topic category. Pro-Ana and pro-ED recovery contents (“#foryou” and “#edrecovery” as the most frequent, respectively) were both actively searched by patients and proposed by the SM in a significant number of cases. For 59.0%, using TikTok reduced self-esteem, while 26.9% reported TikTok-related significant changes in their daily lives, and 3.8% reported experiences of body-shaming. Patients describing a negative effect of TikTok on their self-esteem more frequently searched and browsed “diet” (
p
= 0.007) and pro-ED recovery (
p
= 0.007) contents. Positive qualitative feedback on the SM was also reported.
Conclusions
This study documents the use of the SM TikTok among children and adolescents with ED. Individuals with a perceived negative effect of this SM on their self-esteem may show greater interaction with specific content. Further studies are needed to investigate the psychopathological factors influencing the relationship between ED and the use of SM.
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.
Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding α2δ-2 subunit of Voltage Dependent Calcium Channels, is unclear. To date only one CACNA2D2 mutation altering channel ...functionality has been identified in a single family. In the same family, a rare CELSR3 polymorphism also segregated with disease. Involvement of CACNA2D2 in EE is therefore not confirmed, while that of CELSR3 is questionable. In a patient with epilepsy, dyskinesia, cerebellar atrophy, psychomotor delay and dysmorphic features, offspring to consanguineous parents, we performed whole exome sequencing (WES) for homozygosity mapping and mutation detection. WES identified extended autozygosity on chromosome 3, containing two novel homozygous candidate mutations: c.1295delA (p.Asn432fs) in CACNA2D2 and c.G6407A (p.Gly2136Asp) in CELSR3. Gene prioritization pointed to CACNA2D2 as the most prominent candidate gene. The WES finding in CACNA2D2 resulted to be statistically significant (p = 0.032), unlike that in CELSR3. CACNA2D2 homozygous c.1295delA essentially abolished α2δ-2 expression. In summary, we identified a novel null CACNA2D2 mutation associated to a clinical phenotype strikingly similar to the Cacna2d2 null mouse model. Molecular and statistical analyses together argued in favor of a causal contribution of CACNA2D2 mutations to EE, while suggested that finding in CELSR3, although potentially damaging, is likely incidental.
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