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    Inpatient treatment of anorexia nervosa with adjunctive valproate: a case series of 14 young and adolescent patients

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    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

    Early onset anorexia nervosa: Multidisciplinary hospital intervention in a 1‐year follow‐up study

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    Background: Early onset anorexia nervosa (EOAN) is a subclassification of AN, defined by an onset before 14 years, and characterized by specific demographic, neuropsychological, and clinical features. The present study aims to provide naturalistic data on a wide sample with EOAN, focusing on psychopathological and nutritional changes occurring in the context of a multidisciplinary hospital intervention, as well as the rate of rehospitalizations during a 1-year follow-up. Method: Observational, naturalistic study adopting standardized criteria for EOAN (onset before 14 years). EOAN were compared to adolescent-onset AN (AOAN) patients (onset after 14 years) by demographic, clinical, psycho and treatment variables. Psychopathology was assessed at admission (T0) and discharge (T1) with self-administered psychiatric scales for children and adolescents (SAFA) subtests for Eating Disorders, Anxiety, Depression, Somatic symptoms, and Obsessions. Then, potential differences of T0–T1 changes in psychopathological and nutritional variables were assessed. Finally, rates of re-hospitalizations at 1-year post-discharge follow-up were assessed with Kaplan–Meier analyses. Results: Two-hundred thirty-eight AN individuals (EOAN = 85) were enrolled. When compared to AOAN, EOAN participants were more frequently males (X2 = 5.360, p = .021), more frequently received nasogastric-tube feeding (X2 = 10.313, p = .001), and risperidone (X2 = 19.463, p < .001), obtained a greater T0-T1 improvement in bodymass index percentage (F[1.229] = 15.104, p < .001, η2 = 0.030), with higher 1-year freedom from re-hospitalization (hazard ratio, 0.47; Log-rank: X2 = 4.758, p = .029). Conclusion: In this study, describing the broadest EOAN sample available in literature so far, EOAN patients received specific interventions and obtained better outcomes at discharge and follow-up when compared to AOAN. Longitudinal, matched studies are required

    General psychopathological symptoms in children, adolescents, and young adults with anorexia nervosa—a naturalistic study on follow‐up and treatment

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    Recent research has assessed the role of general psychopathological symptoms in the natural history of mental health conditions, including anorexia nervosa (AN) in adults and obesity in children. Nevertheless, literature assessing general psychopathological symptoms in young patients with AN and their potential prognostic role in long-term outcomes is lacking. Observational, naturalistic study, involving young patients hospitalized for AN. General psychopathological symptoms were assessed by administering Symptom Check List-90-R (SCL-90-R) at admission (T0) and discharge (T1). AN-specific psychopathology was assessed with Eating Disorders Inventory-3 Eating Disorder Risk (EDRC) and Body Uneasiness Test Global Severity Index (BUT-GSI). Potential T0-T1 modifications of general psychopathological symptoms and their possible associations with baseline psychopathological, weight, and psychopharmacological variables were assessed with a generalized linear model (GLM), corrected for baseline SCL-90-R scores. Then, possible associations between T0 general psychopathological symptoms and the risk of re-hospitalization at 1 year were assessed with the Kaplan–Meier method and Cox regression. This study enrolled 133 patients (mean age 16.9 ± 2.9 years, F = 91.8%). A significant T0-T1 reduction (p < 0.001) in almost all the general psychopathological symptoms (except paranoia) emerged. The GLM revealed that higher EDI-3 EDRC scores were associated with higher T1 SCL-90-R scores in multiple domains. Cox regressions revealed a predictive role of SCL-90-R interpersonal sensitivity (B = 0.113, hazard ratio = 1.119, p = 0.023) on the risk of re-hospitalization at 1 year. Conclusion: General psychopathological symptoms in young patients with AN may be influenced by hospital treatment interventions and have a potential prognostic role on post-discharge outcomes. Further longitudinal studies are required

    Should Echolalia Be Considered a Phonic Stereotypy? A Narrative Review

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    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

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

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    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, plasma levels, adverse drug reactions (ADR) and modifications of electrocardiogram (EKG) and plasma levels of glucose, cholesterol, creatinine, urea, sodium, and thyroid-stimulating hormone (TSH) were assessed. Results. Reasons for the introduction of lithium included unstable mood, insufficient compliance with nutritional 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 patient experienced polyuria, polydipsia and dry mouth, and another showed increased creatinine kinase. No major modifications of EKG, glucose, cholesterol, creatinine, 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 administered lithium. ADR were reported in 2 cases. These data should be investigated in wider populations and controlled studies

    Premenarchal anorexia nervosa: clinical features, psychopharmacological interventions, and rehospitalization analysis in a 1‐year follow‐up, controlled study

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    Premenarchal anorexia nervosa (AN) represents a specific subtype of AN, defined by an onset before the menarche in females, involving unique endocrine and prognostic features. The scarce data on this condition lack case–control and follow-up studies. This is a case–control, observational, naturalistic study, involving participants with premenarchal AN (premenarchal girls presenting to the study center newly diagnosed with AN) treated with a multidisciplinary hospital intervention, compared to postmenarchal AN individuals on clinical, endocrine, psychopathological, and treatment variables. The rate of rehospitalizations on a 1-year follow-up after discharge and respective prognostic factors were assessed with a Kaplan–Meier analysis and Cox regression model. The sample included 234 AN participants (43, 18.4% with premenarchal and 191, 81.6% with postmenarchal AN). When compared to postmenarchal, premenarchal AN individuals presented with lower depressive scores (Self-Administered Psychiatric Scales for Children and Adolescents (SAFA)) (U=1387.0, p=0.010) and lower luteinizing hormone (LH) levels (U=3056.0, p=0.009) and were less frequently treated with antidepressants (X2=5.927, p=0.015). A significant predictive model of the risk of rehospitalization (X2=19.192, p=0.004) identified a higher age at admission (B=0.522, p=0.020) and a day-hospital (vs inpatient) treatment (B=3957, p=0.007) as predictive factors for rehospitalization at 1-year, independent from the menarchal status. Conclusion: This study reports the clinical and treatment characteristics of premenarchal AN in one of the largest samples available in the current literature. Specific clinical features and prognostic factors for rehospitalization at 1-year follow-up were identified. Future studies should longitudinally investigate treatment-dependent modifications in endocrine and psychopathological measures in this population

    Treatment response in children and adolescents with anorexia nervosa: a naturalistic, case–control study

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    Purpose Although a few recent articles describe adults with treatment-resistant anorexia nervosa (TR-AN), no study addresses the specific features of subjects not responding to treatment in the developmental age. This study reports on the clinical and psychopathological variables that distinguish children and adolescents who did not respond to treatment (here “TR-AN”) from good-outcome controls, in a multidisciplinary hospital treatment setting. Methods Naturalistic, case–control study conducted on individuals showing lack of response to treatment and good-outcome controls. TR-AN was defined as two or more incomplete admissions and no complete admissions, consistently with studies in adults. Good-outcome was defined as complete first admission, availability for follow-up visit after 6 months, and maintain- ing at follow-up a %BMI > 70% in the absence of binging or purging in the preceding 3 months. Psychopathological (Eating Disorders Inventory-3 EDI-3; Beck Depression Inventory-II), clinical, and treatment variables at admission were compared. Significant differences in the univariate analyses were included in an exploratory binary logistic regression. Results Seventy-six patients (30 TR-AN, 46 good-outcome AN controls) were enrolled (mean age 14.9±1.9 years, F = 94.7%). TR-AN individuals had a higher age at admission and higher EDI-3 Eating Disorder Risk (EDRC) scores, were treated less frequently with a nasogastric tube (NGT), and achieved a lower BMI improvement at discharge than good- outcome controls. A predictive model for TR-AN status was found (X2 = 19.116; Nagelkerke-R2 = 0.478, p < 0.001), and age at admission (OR = 0.460, p = 0.019), EDI-3 EDRC (OR = 0.938, p = 0.043), and NGT (OR = 8.003, p = 0.019) were associated with a TR-AN status. Conclusions This is the first report on the psychopathological and clinical characteristics of children and adolescents not responding to treatment. These patients showed higher age and eating disorder scores, and were less frequently fed with NGT than controls. Despite the multiple incomplete admissions of our subjects, the short included follow-up limits the pos- sibility for direct comparisons with adult samples of treatment-resistant patients. Thus, the specific features of children and adolescents with TR-AN should be assessed in longitudinal studies

    The Role of the Noradrenergic System in Eating Disorders: A Systematic Review

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    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 E

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

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    The International Classification of Headache Disorders, 3rd edition (ICHD3) defines Shortlasting 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

    Eating disorders in young patients with neurofibromatosis type 1

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    Aim: We describe the association of neurofibromatosis type 1 (NF1) and feeding and eating disorders (FED) in five patients admitted to our third level centre for both FED and NF1. Methods: Case series of five adolescent females with NF1 treated for FED. Results: We collected data from five patients with NF1 aged between 14 and 22 years, all females. The onset of eating disorder symptoms occurred between 13 and 19 years of age and was characterised by food intake restriction, associated with physical hyperactivity in three out of five cases. One patient also reported self-injurious acts and episodic binges. Patients received diagnoses of anorexia nervosa (AN, n = 2), atypical AN (n = 1), bulimia nervosa (n = 1), unspecified feeding and eating disorder (n = 1). Conclusion: The current literature reports a single case of an adult with NF1 and comorbid AN, focusing on the dermatological features of NF1. Our article describes a case series of five patients in developmental age affected by NF1 and FED. Clinical and psychological features of NF1 may play a role in the pathogenesis of FED when these two conditions co-occur. The dermatological alterations of NF1 may contribute to body image distortion that characterises AN. Further research is required to systematically screen populations of patients with NF1 for the presence of FED
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