Enrichment and Correlation Analysis of Serum miRNAs in Comorbidity Between Arnold-Chiari and Tourette Syndrome Contribute to Clarify Their Molecular Bases.

Due to its rarity, coupled to a multifactorial and very heterogeneous nature, the molecular etiology of Arnold-Chiari (AC) syndrome remains almost totally unknown. Its relationship with other neuropsychiatric disorders such as Tourette syndrome (TS) is also undetermined. The rare comorbid status between both disorders (ACTS) complicates the framework of diagnosis and negatively affects the patients' quality of life. In this exploratory study, we aimed to identify serum microRNA expression profiles as molecular fingerprints for AC, TS, and ACTS, by using a high-throughput approach. For this aim, 10 AC patients, 11 ACTS patients, 6 TS patients, and 8 unaffected controls (NC) were recruited. Nine miRNAs resulted significantly differentially expressed (DE): let-7b-5p (upregulated in ACTS vs. TS); miR-21-5p (upregulated in ACTS vs. AC; downregulated in AC vs. TS); miR-23a-3p (upregulated in TS vs. NCs; downregulated in AC vs. TS); miR-25-3p (upregulated in AC vs. TS and NCs; downregulated in ACTS vs. AC); miR-93-5p (upregulated in AC vs. TS); miR-130a-3p (downregulated in ACTS and TS vs. NCs); miR-144-3p (downregulated in ACTS vs. AC; upregulated in AC vs. TS); miR-222-3p (upregulated in ACTS vs. NCs); miR-451a (upregulated in AC vs. TS and NCs; in ACTS vs. NCs). Altered expression of miRNAs was statistically correlated to neuroimaging and neuropsychological anomalies. Furthermore, computational analyses indicated that DE miRNAs are involved in AC and TS pathomechanisms. Finally, we propose the dysregulation of the miRNA set as a potential molecular tool for supporting the current diagnosis of AC, TS, and ACTS by using liquid biopsies, in an unbiased and non-invasive way.

Importance of neuropsychiatric evaluation in children with primary monosymptomatic enuresis.

BACKGROUND: Nocturnal enuresis (NE) is an involuntary voiding during sleep. It is a very common disorder in school-age children. Comorbid psychopathologies are common in patients affected by enuresis. According to the ICCS, the rate of behavioral and emotional disorders in children with enuresis is doubled compared with healthy control (HC) children. OBJECTIVE: The aim of the present study was to investigate the prevalence of neuropsychiatric comorbidities in children affected by NE. STUDY DESIGN: Two hundred children with a diagnosis of enuresis were recruited from the Neuropsychiatric Unit of Catania University and 200 age-matched neurologically intact HC children were recruited from local schools. The inclusion criteria were a normal IQ and the absence of other pathological clinical conditions such as diabetes or kidney malformation. The exclusion criteria were failure to complete the initial evaluation or clinical/diagnostic procedures, inability (because of young age) to complete study questionnaires, and severe neurological or physical impairment. RESULTS: Age and gender proportions were not significantly different between the groups. In the NE group, 138 subjects (69%) had a familial history of NE, compared with 24 subjects (12%) in the HC group (p < 0.01). The NE group demonstrated significantly higher scores in the Child Behavior Check List, Conners' Multidimensional Anxiety Scale for Children, and the Child Depression Inventory compared than the HC group as well as the Yale Global Tic Severity Score and Child-Yale-Brown Obsessive Compulsive Scale scores (p < 0.01). Quality of life scores were significantly lower in the NE group than in the HCs group; specifically, between-group differences were significant in the relationship and self domains (p > 0.01 for both comparisons) (Figure). DISCUSSION: The present case-control study evaluates the prevalence of different neuropsychiatric comorbidities in children with NE as diagnosed according to the new ICCS criteria. An important finding was that neuropsychiatric conditions were more prevalent in NE patients than in age-matched HC subjects. To the best of our knowledge, this is the first study to report associations between enuresis and obsessive compulsive disorder as well as tic disorder, and is the first to describe the comparative psychopathological profiles of 200 children with enuresis and 200 matched HC children. CONCLUSION: The results suggest that clinicians should not underestimate the effects of enuresis on psychosocial development. Childhood NE should be managed carefully and comprehensively in order to prevent the development of more serious behavioral problems in the future.