Sleep Spindle-Related EEG Connectivity in Children with Attention-Deficit/Hyperactivity Disorder: An Exploratory Study.

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder with known brain abnormalities but no biomarkers to support clinical diagnosis. Recently, EEG analysis methods such as functional connectivity have rekindled interest in using EEG for ADHD diagnosis. Most studies have focused on resting-state EEG, while connectivity during sleep and spindle activity has been underexplored. Here we present the results of a preliminary study exploring spindle-related connectivity as a possible biomarker for ADHD. We compared sensor-space connectivity parameters in eight children with ADHD and nine age/sex-matched healthy controls during sleep, before, during, and after spindle activity in various frequency bands. All connectivity parameters were significantly different between the two groups in the delta and gamma bands, and Principal Component Analysis (PCA) in the gamma band distinguished ADHD from healthy subjects. Cluster coefficient and path length values in the sigma band were also significantly different between epochs, indicating different spindle-related brain activity in ADHD.

Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort.

Background: Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6-10% of all childhood strokes and transient ischemic attacks (TIAs). Methods: We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country. Results: A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58-13.88%). At last follow-up (median 4 years after diagnosis, range 0.5-15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively). Conclusions: Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2).

ADHD symptoms and school impairment history in parents of ADHD children are a fundamental diagnostic and therapeutic clue.

BACKGROUND: Attention Deficit and Hyperactivity Disorder (ADHD) is a multi-factorial condition, with inheritance playing a major role. Recognizing parents' ADHD represents a clue not only for an earlier diagnosis of the disease in their children, but also to optimize psycho-educational therapy outcomes, by addressing the impairment of parenting related to untreated ADHD. This study aimed to assess the frequency of features suggestive of ADHD during childhood among parents of affected children, and the presence of school and emotional impairment. METHODS: We administered the Wender Utah Rating Scale-25, a self-assessment tool for the retrospective identification of symptoms consistent with ADHD during childhood, to a cohort of 120 parents of 60 children with ADHD, and to a consistent number of "controls". RESULTS: The WURS-25 proved positive in 49.1% of fathers and 30.0% of mothers of ADHD patients, compared to 1.7% of fathers and 1.7% of mothers of non-ADHD patients (p < 0.0001). The questions addressing learning and emotional impairment provided significantly higher scores in parents with an overall positive test compared to those with negative test (p < 0.0001). CONCLUSIONS: This study demonstrates a remarkably high rate of symptoms consistent with ADHD during childhood in parents of affected children. Physicians should be aware that this is a relevant anamnestic clue and, given the relevance of parents' role in the management of children with ADHD, an important issue to address in order to optimize patients' treatment.

Does a standard triage tool adequately detect the needs of children and adolescents admitted for mental health problem?

BACKGROUND: the visits to the paediatric emergency department for mental problems are increasing exponentially, but the emergency department team in not ready enough to manage them, due to the lack of adequate training. This study aimed to evaluate how the Italian Society of Paediatric Emergency Medicine and Urgency triage system was able to estimate urgency in patients accessing the paediatric emergency department for a mental health problem. METHODS: We conducted a retrospective study at the emergency department of the Institute for Maternal and Child Health, IRCCS Burlo garofolo of Trieste (Italy), from December 2015 to April 2017. During the study period, we identified all the patients undergoing an urgent psychiatric consultation. We collected demographic variables, triage code, diagnosis, and outcomes of each patient. Subsequently, we have assigned a degree of psychiatric urgency, based on Gail and Rosenn's classificationwhich is a specific tool to evaluate psychiatric urgency. The primary study outcome was the comparison between the degree of urgency assigned using the triage system and the Gail and Rosenn's classification. RESULTS: In this series, 567 patients underwent an urgent psychiatric consultation, and 280 of them received a diagnosis of a mental health problem. The degree of urgency assigned at the triage was: emergency for 5 cases (2%), urgency for 96 (34%) and non-urgency for 179 (64%). Instead, the degree assigned with GRC was: emergency for 95 cases (34%), urgency for 112 (42%) and non-urgency for 73 (26%). The number of patients, detected as emergency and urgency by the two tools, was significantly different (p = 0.0001). CONCLUSIONS: In this study, we demonstrated that the Italian Society of Paediatric Emergency Medicine and Urgency triage system underestimated the urgency of patients with mental health problems compared to a specific tool to assess the degree of psychiatric urgency.

Emergency department attendance for injury and behaviours suggestive of attention deficit hyperactivity disorder (ADHD): a cross-sectional study.

BACKGROUND: The study aimed to investigate if the behaviours suggestive of ADHD were more frequent in a population of children attending the Emergency Department (ED) for injuries, rather than for other causes. METHODS: A cross-sectional study was carried out. Patients, aged 6 to 17 years, attending the ED for acute injuries and other causes were considered cases and controls, respectively. We used a questionnaire, which investigates the presence in the child of inattention, hyperactivity, and impulsivity. The primary outcome was the number of children with behaviours suggestive of ADHD in cases and controls. RESULTS: Five hundred forty-five children were enrolled, 251 with injuries and 294 with other complains. Twenty two out of two hundred fifty one (9%) children visited for injuries, and 30 out of 294 (10%) visited for other causes had behaviours suggestive of ADHD (p = 0.661). Among these cases, children with evocative ADHD scores had a higher probability (OR 4.52; 95% CI 1.45-14.04; p = 0.009) of having had more than five previous ED accesses due to injury, compared to the others. CONCLUSIONS: This study did non shown a difference in behaviours suggestive of ADHD between cases and controls, but identified a population of children with behaviours suggestive of ADHD who more frequently access the ED for injuries.

An evaluation of the Movement ABC-2 Test for use in Italy: A comparison of data from Italy and the UK.

BACKGROUND: The standardized test within the Movement Assessment Battery for Children-2nd edition (MABC-2) is used worldwide to assess motor problems in children. Ideally, any country using a test developed in another country should produce national norms to ensure that it functions effectively in the new context. AIM: The first objective of this study was to explore the differences in motor performance between Italian and British children. The second was to examine the structural validity of the test for the Italian sample. METHOD: A total of 718 Italian (IT) and 765 British (UK) children, aged 3-10 years, were individually tested on the age-appropriate items of the MABC-2 Test. RESULTS: Developmental trends emerged on every task and differences between IT and UK children were obtained on 11 of 27 task comparisons. Interactions between age and country indicated that differences were not consistently in favor of one culture. Confirmatory factor analysis generally supported the proposed structure of the MABC-2 Test. CONCLUSION: Although the differences between the IT and the UK children were relatively few, those that did emerge emphasize the need for population specific norms and suggest that cultural diversity in motor experiences should be considered when evaluating motor abilities in children.

Atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis: two case reports.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is a rare autoimmune disease characterized by severe neurological and psychiatric symptoms and a difficult diagnosis. The disease is often secondary to a neoplastic lesion, seldom diagnosed years later. Psychiatric symptoms are prevalent in adults; neurologic symptoms are more evident in children, who typically present primarily with neurological symptoms. To the best of our knowledge, the association with juvenile idiopathic arthritis has not been described. CASE PRESENTATION: We report the cases of two caucasian girls with an atypical presentation. The first patient was an 8-year-old girl with normal psychomotor development. Over a 4-month period she developed behavioral problems, speech impairment, and deterioration in academic skills. Within 8 months from the onset of symptoms, choreic movements gradually appeared. Hematological, neuroradiological, and neurophysiological examinations were negative; however, her symptoms worsened and treatment with prednisone was started. Although her choreic movements improved within 1 month, her neuropsychological and behavioral symptoms continued. Anti-N-methyl-D-aspartate receptor antibodies in cerebrospinal fluid and in blood were detected. Therapy with intravenously administered immunoglobulins was administered, without improvement of symptoms. After 2 months of steroid treatment, she suddenly started to pronounce some words with a progressive improvement in language and behavior. The second patient was a 14-year-old girl with classic anti-N-methyl-D-aspartate receptor encephalitis, treated successfully with intravenously administered immunoglobulins and methylprednisolone, followed by orally administered prednisone, who developed chronic arthritis of the hip. The arthritis was confirmed by magnetic resonance imaging and associated to antinuclear antigen antibody positivity. One year after the encephalitis presentation, an ovarian cystic mass was identified as a teratoma. The surgical resection of the mass was followed by the resolution of the psychotic spectrum and arthritis. CONCLUSIONS: Anti-N-methyl-D-aspartate receptor encephalitis in pediatric patients can present initially with neuropsychological and behavioral symptoms. In the literature, the association of anti-N-methyl-D-aspartate receptor encephalitis with juvenile idiopathic arthritis is not yet described: to the best of our knowledge, this is the first case reported. The link to a neoplastic lesion can explain the favorable course of encephalitis and arthritis, after the surgical resection of the mass. Early diagnosis and treatment can improve the patient's outcome.

Somatic symptom disorder was common in children and adolescents attending an emergency department complaining of pain.

AIM: The aim of this study was to quantify the prevalence of somatic pain in a paediatric emergency department (ED). METHODS: We conducted a prospective observational study using patients admitted to the ED of an Italian children's hospital between December 2014 and February 2015. We enrolled children aged 7-17 who turned up at the ED complaining of pain. Patients and parents were asked to fill in a questionnaire to allow the analysis of the patients' medical history and provide contact details for follow-up. We divided the enrolled patients into four groups: post-traumatic pain, organic pain, functional pain and somatic pain. The questionnaire was used to define pain characteristics and to generate an impairment score. RESULTS: Of the 713 patients who met inclusion criteria, 306 (42.9%) were enrolled in the study. Of these, 135 (44.0%) suffered from post-traumatic pain, 104 (34.0%) from organic pain, 41 (13.4%) from functional pain and 26 (8.6%) from somatic pain. Somatic pain patients had endured pain longer, had missed more school days and had suffered severe functional impairment. CONCLUSION: This study highlighted that somatic pain was a significant contributor to paediatric emergency room visits and should be suspected and diagnosed in children reporting pain.

CTNND2 deletion and intellectual disability.

Neurodevelopmental disorders are a group of diseases characterized by either structural or functional alterations. The clinical spectrum can vary from isolated intellectual disability to more complex syndromes. Molecular karyotyping can explain 14%-18% of cases due to the presence of large pathogenic CNVs. Moreover, small CNVs involving single genes might result in a monogenic disease. In this article we report two cases of intragenic CTNND2 deletion, detected by molecular karyotyping, in patients with isolated intellectual disability.

De novo 6.9 Mb interstitial deletion on chromosome 4q31.1-q32.1 in a girl with severe speech delay and dysmorphic features.

Deletion of the terminal part of long arm of chromosome 4 is a condition characterized by facial dysmorphisms, cardiac and limb defects, and developmental delay. Deletions usually involve the terminal part of the chromosome and most frequently are interstitial. Here, we report a de novo interstitial deletion resulting in a microdeletion of 6.9 Mb involving 4q31.3-q32.1 segment, detected by SNPs-Array technique in a 4-year-old female showing severe speech delay, mild facial dysmorphisms, and joint laxity. Phenotype-genotype relationships looking at the genes involved in this part of the chromosome were also carried out and data compared with those previously described.

Contribution of SNP arrays in diagnosis of deletion 2p11.2-p12.

Deletions of the short arm of chromosome 2 are exceedingly rare, having been reported in few patients. Furthermore most cases with deletion in 2p11.2-p12 have been studied using standard karyotype and so it is not possible to delineate the precise size of deletions. Here, we describe a 9-year-old girl with a 9.4 Mb de novo interstitial deletion of region 2p11.2-p12 identified by SNP array analysis. The deleted region encompasses over 40 known genes, including LRRTM1, CTNNA2 and REEP1, haploinsufficiency of which could explain some clinical features of this patient such as mental retardation, speech delay and gait abnormalities. A comparison of our case with previously reported patients who present deletions in 2p11.2-p12 was carried out. Our case adds new information to the deletion of 2p11.2-p12, improving the knowledge on this rearrangement.

Neuromotor deficits in developmental coordination disorder: evidence from a reach-to-grasp task.

Developmental coordination disorder (DCD) has been classified as a specific learning disability, nonetheless the underlying cognitive mechanisms are still a matter of discussion. After a summary of the main hypotheses on the principal neuromotor causes of DCD, this study applies a causal model framework to describe the possible coexistence of more than one deficit in this disorder. For this purpose, kinematic analysis was applied to an ecological task, the reach-to-grasp action, introducing the manipulation of three variables: vision, distance and object size. After a thorough neurological and neuropsychological evaluation, 9 children with DCD (7-9 years old) were selected and compared to 27 age-matched control children. The results suggest that children with DCD have a normal neurological characterization of the reaching and grasping movements, in terms of proximal to distal action, but their grasping aperture (MGA) was always wider with respect to controls, particularly when vision was not allowed. In addition, the performance of children with DCD was always slower, more dependent on vision and more variable than that of controls. The MGA of children with DCD could be explained by a deficit in the internal construction of movement for a forward model, while slowness could be related to a control problem in the neuronal firing of the muscles. The idea of a possible coexistence of these two deficits is discussed in accordance to a causal model framework and also addressed considering recent neurophysiologic evidences.