Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

Linguistic feature of anorexia nervosa: a prospective case-control pilot study.

PURPOSE: Attention has recently been paid to Clinical Linguistics for the detection and support of clinical conditions. Many works have been published on the "linguistic profile" of various clinical populations, but very few papers have been devoted to linguistic changes in patients with eating disorders. Patients with Anorexia Nervosa (AN) share similar psychological features such as disturbances in self-perceived body image, inflexible and obsessive thinking and anxious or depressive traits. We hypothesize that these characteristics can result in altered linguistic patterns and be detected using the Natural Language Processing tools. METHODS: We enrolled 51 young participants from December 2019 to February 2020 (age range: 14-18): 17 girls with a clinical diagnosis of AN, and 34 normal-weighted peers, matched by gender, age and educational level. Participants in each group were asked to produce three written texts (around 10-15 lines long). A rich set of linguistic features was extracted from the text samples and the statistical significance in pinpointing the pathological process was measured. RESULTS: Comparison between the two groups showed several linguistics indexes as statistically significant, with syntactic reduction as the most relevant trait of AN productions. In particular, the following features emerge as statistically significant in distinguishing AN girls and their normal-weighted peers: the length of the sentences, the complexity of the noun phrase, and the global syntactic complexity. This peculiar pattern of linguistic erosion may be due to the severe metabolic impairment also affecting the central nervous system in AN. CONCLUSION: These preliminary data showed the existence of linguistic parameters as probable linguistic markers of AN. However, the analysis of a bigger cohort, still ongoing, is needed to consolidate this assumption. LEVEL OF EVIDENCE III: Evidence obtained from case-control analytic studies.

Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up.

INTRODUCTION: Corticosteroid treatment is the standard of care in Duchenne muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage pattern remain a matter of discussion. METHODS: We performed a long-term study of alternate-day corticosteroids in five 2- to 4-year-old DMD patients. The primary outcome measure was prolongation of the ability to walk. RESULTS: One patient lost ambulation at age 10. Four patients, aged 16 to 18 were fully ambulant, and 3 of them could still climb stairs. Respiratory function was moderately reduced in 2. Left ventricular ejection fraction was > 45%. Short stature and delayed puberty were the most relevant side effects. Although the negative impact of corticosteroid treatment on growth rate remained their major concern, parents and patients stated that they preferred corticosteroid therapy. CONCLUSIONS: Long-term corticosteroid treatment is effective in prolonging function but not in recovering lost function, and its early use seems appropriate.

Anorexia nervosa among first- and second-generation immigrant children and adolescents in Italy: treatment and clinical outcomes.

PURPOSE: Cultural and environmental factors have frequently been implicated in the pathogenesis of Eating Disorders (ED). Although ED have been considered as "Western culture-bound syndromes", increasing rates of ED among non-Western groups are being documented. The present study aims to investigate treatment and clinical outcomes among first-generation immigrant children and adolescents (FGI) (patients born abroad) and second-generation immigrant youth (SGI, patients born in Italy) with Anorexia Nervosa (AN). METHODS: The study retrospectively compares treatment, hospitalizations, traumatic past events, clinical features, and treatment outcome (improvement in percentual body-mass index - %BMI) between FGI and SGI young patients with AN (10-18 years). Correlations were adjusted for age and severity (%BMI) at presentation. Treatments and outcomes were investigated at the baseline (T0), 2 weeks (T1), one month (T2), 3 months (T3), 6 months (T4), and 12 months (T5). RESULTS: Thirty-six patients (50% FGI) were enrolled. At T1 (F(1.26)=6.335, p=0.018), and at T2 (F(1.30)=18.752, p<0.001) FGI presented a significantly higher %BMI improvement than SGI. FGI required significantly less (OR=0.379, p=0.017), and shorter (F(1.32)=5.827, p=0.022) hospitalizations, when compared with SGI. CONCLUSIONS: When compared to SGI, FGI with AN required fewer and shorter hospitalizations and had a better early-treatment weight outcome. Larger nationwide studies should investigate the need for and access to treatment of immigrant populations with AN.

Association among Autistic Traits, Treatment Intensity and Outcomes in Adolescents with Anorexia Nervosa: Preliminary Results.

The present study investigates the impact of Autism Spectrum Disorder (ASD) traits on the treatment intensity and outcomes (psychopathology and weight) of 22 adolescent inpatients with Anorexia Nervosa (AN), who were selected on the basis of suspected ASD traits. ASD traits were measured at admission (T0) using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and the Autism-Spectrum Quotient (AQ). Psychopathology was measured with Eating Disorder Inventory-3 (EDI-3) and Self-Administered Psychiatric Scales for Children and Adolescents (SAFA) at admission and discharge (T0, T1). Percentage BMI was assessed at admission, discharge, first follow-up (T2, 7-22 days) and second follow-up (T3, 22-45 days). Results were controlled for age and EDI-3 global psychological maladjustment. When compared with other patients with AN, AN individuals with ADOS-2 and AQ diagnostic scores for ASD showed overlapping types of treatments, as well as psychopathological and weight outcomes. ASD total scores were not correlated with treatment intensity or treatment outcomes. Preliminary results show that ASD traits do not impact treatment intensity and outcomes in adolescents with AN and suspected ASD traits.

Timing of Psychopharmacological and Nutritional Interventions in the Inpatient Treatment of Anorexia Nervosa: An Observational Study.

This study aims to investigate possible different outcomes in the inpatient treatment of anorexia nervosa (AN) related to different timings of psychopharmacological and nutritional interventions. A retrospective observational study was conducted, involving young patients hospitalized for AN, treated with naso-gastric tube feeding (NGT). Participants were divided into five groups according to early (0-7 days) or late (8+ days) introduction of atypical antipsychotics (AAP) and NGT: early AAP-early NGT (EE), early AAP-late NGT (EL), late AAP-early NGT (LE), late AAP-late NGT (LL) and a control group treated with NGT only (NGT). Concurrent clinical and treatment variables were analyzed. AN psychopathology was measured with the Eating Disorder Inventory-3 (EDI-3) EDRC score. Outcomes were assessed as admission-discharge body-mass index (BMI) improvement and length of hospital stay (LOS). Contributions of variables related to outcomes were assessed with multifactorial-analyses of variance (MANOVA). Seventy-nine patients were enrolled in the study. LOS was different among treatment groups (F (4, 75) = 5.993, p < 0.001), and EE patients showed lower LOS than LE (p < 0.001) and LL (p = 0.025) patients. BMI improvement was not significantly different among treatment groups but correlated negatively with age (F (1, 72) = 10.130, p = 0.002), and admission BMI (F (1, 72) = 14.681, p < 0.001). In conclusion, patients treated with early AAP and early NGT showed lower LOS than those treated with late AAP. Prognostic treatment variables should be investigated in wider samples.

Autism spectrum disorder and anorexia nervosa: an Italian prospective study.

BACKGROUND: Potential overlaps exist between psychopathological features of Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD). The impact of malnutrition on autistic traits in patients with AN should be considered. This study investigates possible associations among the psychopathology of Eating Disorders (EDs), ASD traits and BMI in a group of young patients with AN, using the EDI-3 (Eating Disorder Inventory-3) test and gold-standard measures for ASD. METHODS: Prospective study involving 23 inpatients admitted to an Italian Centre for paediatric ED. ASD traits and ED psychopathology were assessed administering the ADOS-2 (Autism Diagnostic Observation Schedule-2), AQ (Autism Quotient) and EDI-3 tests. Both present and past autistic traits were investigated using different versions of AQ. Correlations were adjusted for BMI, Obsessive Compulsive Disorder (OCD) comorbidity and concurrent antipsychotic treatments. RESULTS: An ASD diagnosis was possible in 22% of patients. Significant correlations were documented between ASD traits and ED psychopathology: AQ total-Interpersonal problems (IPC) (p = 0.041); AQ total-Global psychological maladjustment (GMPC) (p = 0.027); AQ social skills-Ineffectiveness (IC) (p = 0.018); AQ social skills-IPC (p = 0.019); AQ social skills-Affective problems (APC) (p = 0.025); AQ social skills-GMPC (p = 0.007); AQ attention switching-IPC (p = 0.020); ADOS-2 imagination-IC (p = 0.035). These correlations were independent of BMI, OCD and antipsychotic treatments. CONCLUSIONS: ASD traits presented high prevalence in a group of young inpatients with AN. These traits were significantly correlated to 4 specific EDI-3 subscales and independent of BMI. This is the first study to investigate the relationship between ASD traits as measured with gold-standard measures, EDI-3 scores, and BMI.

No kinetic interaction between levetiracetam and cyclosporine: a case report.

Levetiracetam is a new antiepileptic drug reported to be effective and well-tolerated in adults and children affected by epilepsy. Its lack of hepatic cytochrome metabolism is the theoretic basis for the absence of interactions with other drugs that follow this pathway. We present a 14-year-old girl who underwent orthotopic heart transplantation, followed by antirejection therapy including cyclosporine. Symptomatic occipital lobe epilepsy developed that was successfully treated with oxcarbazepine, but cyclosporine plasma levels decreased to below the antirejection threshold. Oxcarbazepine was replaced by levetiracetam. Levetiracetam did not affect the metabolism of cyclosporine, and cyclosporine plasma levels have remained in the therapeutic range up to now. The patient is still seizure-free and does not complain of any side effects after a 1-year follow-up. Further studies are necessary to confirm the lack of interactions between these drugs, which would make levetiracetam a useful therapeutic option in managing seizure control during antirejection therapy with cyclosporine.

Unusual diagnosis in a child suffering from juvenile Alexander disease: clinical and imaging report.

Alexander disease is a rare, sporadic leukoencephalopathy characterized by white-matter abnormalities with frontal predominance and, as a rule, clinically associated with megalencephaly, seizures, spasticity, and psychomotor deterioration. We describe a boy who was diagnosed as affected by anorexia nervosa because of his refusal to eat, progressive weight loss, and psychologic disturbances. The observation of a hyperintense lesion on T(2)-weighed magnetic resonance images (MRIs) was initially explained as a pontine and extrapontine myelinolysis related to malnutrition. Following MRI and DNA analysis, we diagnosed a juvenile type of Alexander disease. Therefore, we can affirm the importance of the history and clinical examination to look for brainstem dysfunction in patients presenting with atypical anorexia nervosa.

Cytogenetic and molecular characterization of a recombinant X chromosome in a family with a severe neurologic phenotype and macular degeneration.

BACKGROUND: Duplications of MECP2 gene in males cause a syndrome characterized by distinctive clinical features, including severe to profound mental retardation, infantile hypotonia, mild dysmorphic features, poor speech development, autistic features, seizures, progressive spasticity and recurrent infections. Patients with complex chromosome rearrangements, leading to Xq28 duplication, share most of the clinical features of individuals with tandem duplications, in particular neurologic problems, suggesting a major pathogenetic role of MECP2 overexpression. RESULTS: We performed cytogenetic and molecular cytogenetic studies in a previously described family with affected males showing congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration. Microsatellite, FISH and array-CGH analyses identified a recombinant X chromosome with a deletion of the PAR1 region, encompassing SHOX, replaced by a duplicated segment of the Xq28 terminal portion, including MECP2. CONCLUSIONS: Our report describes the identification of the actual genetic cause underlying a severe syndrome that previous preliminary analyses erroneously associated to a terminal Xp22.33 region. In the present family as well as in previously reported patients with similar rearrangements, the observed neurologic phenotype is ascribable to MECP2 duplication, with an undefined contribution of the other involved genes. Maculopathy, presented by affected males reported here, could be a novel clinical feature associated to Xq28 disomy due to recombinant X chromosomes, but at present the underlying pathogenetic mechanism is unknown and this potential clinical correlation should be confirmed through the collection of additional patients.

Early prednisone treatment in Duchenne muscular dystrophy.

The purpose of this long-term, open parallel-group, double-consent study of alternate-day, low-dose prednisone in 2-4-year-old patients with Duchenne muscular dystrophy (DMD) was to determine whether prednisone produces a beneficial effect when given earlier than usual. Muscle function was evaluated by timed tests, and muscle strength with a hand-held myometer. After 55 months of treatment, the five patients (mean age 8.3 years) in the prednisone group were still able to get up from the floor, whereas two of the three in the control group had lost this ability. Side effects included a decline in growth rate in the prednisone-treated patients and excessive weight gain in one control and three treated patients. Because steroids are effective in prolonging function, but not in recovering lost function, we propose that treatment be started with low-dose prednisone in DMD patients as soon as the diagnosis is definite.

Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females.

Subcortical band heterotopia (SBH) or double cortex syndrome is a neuronal migration disorder, which occurs very rarely in males: to date, at least 110 females but only 11 in males have been reported. The syndrome is usually associated with mutations in the doublecortin (DCX) (Xq22.3-q23) gene, and much less frequently in the LIS1 (17p13.3) gene. To determine whether the phenotypic spectrum, the genetic basis and genotype-phenotype correlations of SBH in males are similar to those in females, we compared the clinical, imaging and molecular features in 30 personally evaluated males and 60 previously reported females with SBH. Based on the MRI findings, we defined the following band subtypes: partial, involving one or two cerebral lobes; intermediate, involving two lobes and a portion of a third; diffuse, with substantial involvement of three or more lobes; and pachygyria-SBH, in which posterior SBH merges with anterior pachygyria. Karyo typing and mutation analysis of DCX and/or LIS1 were performed in 23 and 24 patients, respectively. The range of clinical phenotypes in males with SBH greatly overlapped that in females. MRI studies revealed that some anatomical subtypes of SBH, such as partial and intermediate posterior, pachygyria-SBH and diffuse bands with posterior predominance, were more frequently or exclusively present in males. Conversely, classical diffuse SBH and diffuse bands with anterior predominance were more frequent in females. Males had either mild or the most severe band subtypes, and these correlated with the over-representation of normal/borderline intelligence and severe mental retardation, respectively. Conversely, females who had predominantly diffuse bands exhibited mostly mild or moderate mental retardation. Seven patients (29%) had missense mutations in DCX; in four, these were germline mutations, whereas in three there was evidence for somatic mosaicism. A germline missense mutation of LIS1 and a partial trisomy of chromosome 9p were identified in one patient (4%) each. One male each had a possible pathogenic intronic base change in both DCX and LIS1 genes. Our study shows that SBH in males is a clinically heterogeneous syndrome, mostly occurring sporadically. The clinical spectrum is similar to that of females with SBH. However, the greater cognitive and neuroradiological heterogeneity and the small number of mutations identified to date in the coding sequences of the DCX and LIS1 genes in males differ from the findings in females. This suggests other genetic mechanisms such as mutations in the non-coding regions of the DCX or LIS1 genes, gonadal or somatic mosaicism, and finally mutations of other genes.