Cardiac Contractility Modulation Therapy in Patients with Amyloid Cardiomyopathy and Heart Failure, Case Report, Review of the Biophysics of CCM Function, and AMY-CCM Registry Presentation.

Cardiac amyloidosis may result in an aggressive form of heart failure (HF). Cardiac contractility modulation (CCM) has been shown to be a concrete therapeutic option in patients with symptomatic HF, but there is no evidence of its application in patients with cardiac amyloidosis. We present the case of TTR amyloidosis, where CCM therapy proved to be effective. The patient had a history of multiple HF hospitalizations due to an established diagnosis of wild type TTR-Amyloidosis with significant cardiac involvement. Since he was highly symptomatic, except during continuous dobutamine and diuretic infusion, it was opted to pursue CCM therapy device implantation. At follow up, a significant improvement in clinical status was reported with an increase of EF, functional status (6 min walk test improved from zero meters at baseline, to 270 m at 1 month and to 460 m at 12 months), and a reduction in pulmonary pressures. One year after device implantation, no other HF hospital admission was needed. CCM therapy may be effective in this difficult clinical setting. The AMY-CCM Registry, which has just begun, will evaluate the efficacy of CCM in patients with HF and diagnosed TTR amyloidosis to bring new evidence on its potential impact as a therapeutic option.

The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study.

The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study is a prospective registry of morbidity and mortality in initially untreated patients with essential hypertension whose initial diagnostic evaluation included 24-hour ambulatory blood pressure (ABP) monitoring according to a standardized protocol. The present article summarizes the main results of the PIUMA Study. The PIUMA Study is conducted in three hospitals in Umbria, Italy. After their initial assessment at entry, patients are followed in the outpatient clinic of the referring hospital and in collaboration with their family doctors. Telephone interviews with patients and meetings with family doctors are periodically conducted to ascertain the incidence of major complications of hypertension. The PIUMA Study gave us a tremendous opportunity to investigate several aspects related to hypertension: 1) cross-sectional studies focused on the association between clinic and 24-hour ABP and organ damage; 2) longitudinal studies focused on the association between 24-hour ABP and hypertensive organ damage at cardiac level and other levels with the subsequent incidence of major cardiovascular events and mortality; 3) longitudinal studies exploring the prognostic impact of other risk factors in hypertensive patients (i.e. diabetes, dyslipidemia, atrial fibrillation, left ventricular dysfunction, etc.). The PIUMA Study provided the first ever evidence of the prognostic value of: 1) 24-hour ambulatory blood pressure monitoring; and 2) regression of echocardiographic left ventricular hypertrophy in hypertensive patients. The PIUMA Registry gave us an enormous opportunity for investigating several pathophysiologic, diagnostic and therapeutic aspects related to management of hypertensive patients. Some of our studies have been mentioned in several hypertension guidelines to support some specific statements.

[ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus]. / ACE-inibitori, sartani e sindrome respiratoria acuta da coronavirus 2.

Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.

Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE - LY Trial.

Background Cardiac biomarkers and left ventricular hypertrophy ( LVH ) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes. Methods and Results Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE - LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. NT -proBNP (N-terminal pro-B-type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor-15 were determined using high-sensitivity (hs) assays. LVH was defined by ECG . Cox models were adjusted for baseline characteristics, LVH , and biomarkers. LVH was present in 1257 patients. During a median follow-up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly ( P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT -pro BNP , 1.32 (1.25-1.38); hs cardiac troponin I, 1.67 (1.57-1.78); hs troponin T, 1.38 (1.32-1.44); and growth differentiation factor-15, 1.09 (1.05-1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT -pro BNP, 1.09 (1.00-1.19); hs cardiac troponin I, 1.09 (1.03-1.15); hs troponin T, 1.14 (1.06-1.24); and growth differentiation factor-15, 1.22 (1.08-1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT -pro BNP , 1.24 (1.17-1.31); hs cardiac troponin I, 1.13 (1.10-1.17); hs troponin T, 1.28 (1.23-1.34); and growth differentiation factor-15, 1.31 (1.22-1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers. Conclusions Cardiac biomarkers are significantly associated with LVH . The prognostic value of biomarkers for stroke and death is not affected by LVH . The prognostic information of LVH is attenuated in the presence of cardiac biomarkers. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00262600.

Electrocardiography for diagnosis of left ventricular hypertrophy in hypertensive patients with atrial fibrillation.

Left ventricular (LV) hypertrophy at electrocardiography (ECG) predicts incident atrial fibrillation (AF). However, the diagnostic performance of ECG for diagnosis of LV hypertrophy in patients with AF is still not well characterized. We analyzed 563 hypertensive patients enrolled in the Umbria-Atrial Fibrillation (Umbria-FA) registry, an ongoing prospective observational registry in patients with AF. All patients underwent ECG and standard echocardiography at their entry in the Register. Mean age was 74 years and 43% of patients were women. Prevalence of ECG-LV hypertrophy, defined by Perugia criterion corrected for body mass index, was 23%. Echocardiographic LV mass was the reference standard. Sensitivity, specificity and diagnostic accuracy of ECG-LV hypertrophy were 37.4% (95% confidence interval [CI]: 31.6-43.4), 90.0% (95% CI: 86.0-93.2) and 64.5% (95% CI: 60.4-68.3), respectively. Performance was comparable in patients with AF or sinus rhythm at ECG recording. The area under the receiver-operating characteristic (ROC) curve was 0.622 (95% CI: 0.580-0.664) in the group with AF and 0.662 (95% CI: 0.605-0.720) in that with sinus rhythm (p â€‹= â€‹0.266 for comparison). These data suggest that standard ECG is reliable for diagnosis of LV hypertrophy in patients with a history of AF, regardless of the presence of AF or sinus rhythm at the time of ECG recording.

Dabigatran vs. warfarin in relation to the presence of left ventricular hypertrophy in patients with atrial fibrillation- the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) study.

Aim: We tested the hypothesis that left ventricular hypertrophy (LVH) interferes with the antithrombotic effects of dabigatran and warfarin in patients with atrial fibrillation (AF). Methods and results: This is a post-hoc analysis of the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) Study. We defined LVH by electrocardiography (ECG) and included patients with AF on the ECG tracing at entry. Hazard ratios (HR) for each dabigatran dose vs. warfarin were calculated in relation to LVH. LVH was present in 2353 (22.7%) out of 10 372 patients. In patients without LVH, the rates of primary outcome were 1.59%/year with warfarin, 1.60% with dabigatran 110 mg (HR vs. warfarin 1.01, 95% confidence interval (CI) 0.75-1.36) and 1.08% with dabigatran 150 mg (HR vs. warfarin 0.68, 95% CI 0.49-0.95). In patients with LVH, the rates of primary outcome were 3.21%/year with warfarin, 1.69% with dabigatran 110 mg (HR vs. warfarin 0.52, 95% CI 0.32-0.84) and 1.55% with 150 mg (HR vs. warfarin 0.48, 95% CI 0.29-0.78). The interaction between LVH status and dabigatran 110 mg vs. warfarin was significant for the primary outcome (P = 0.021) and stroke (P = 0.016). LVH was associated with a higher event rate with warfarin, not with dabigatran. In the warfarin group, the time in therapeutic range was significantly lower in the presence than in the absence of LVH. Conclusions: LVH was associated with a lower antithrombotic efficacy of warfarin, but not of dabigatran, in patients with AF. Consequently, the relative benefit of the lower dose of dabigatran compared to warfarin was enhanced in patients with LVH. The higher dose of dabigatran was superior to warfarin regardless of LVH status. Clinical trial registration: http:www.clinicaltrials.gov. Unique identifier: NCT00262600.

Impact of Chamber Dilatation on the Prognostic Value of Left Ventricular Geometry in Hypertension.

BACKGROUND: The different geometric patterns of the left ventricle may or may not coexist with chamber dilatation. The prognostic impact of such a combination is unclear. METHODS AND RESULTS: We studied a cohort of 2635 initially untreated patients with hypertension, mean age 50 years. At entry, 24-hour ambulatory blood pressure progressively increased across the patterns of normal geometry, concentric left ventricular (LV) remodeling, eccentric nondilated LV hypertrophy (LVH), eccentric dilated LVH, concentric nondilated LVH, and concentric dilated LVH. During a mean follow-up of 9.7 years, 360 patients developed a first major cardiovascular event at a rate (×100 patient-years) of 1.41. The event rate was 0.93 in the group with normal LV geometry, 1.10 in the group with LV concentric remodeling, 1.40 in the group with nondilated eccentric LVH, 2.10 in the group with eccentric dilated LVH, 2.34 in the group with nondilated concentric LVH, and 4.67 in the group with dilated concentric LVH (log-rank test: P<0.001). In a Cox model, after adjustment for several independent covariables (age, sex, diabetes mellitus, current smoking, total cholesterol, estimated glomerular filtration rate, and average 24-hour systolic blood pressure), concentric dilated LVH was associated with a 98% excess risk of cardiovascular events (P=0.0037). However, LV geometric pattern lost statistical significance when LV mass was entered into the model. CONCLUSIONS: In initially untreated patients with hypertension, LV dilatation adds an adverse prognostic burden to the patterns of eccentric and concentric LVH. This phenomenon is explained by the greater LV mass associated with LV chamber dilatation.

Survey on treatments for primary headaches in 13 specialized juvenile Headache Centers: The first multicenter Italian study.

AIM: The purpose of this retrospective multicenter study was to evaluate the use and the self-perceived efficacy and tolerability of pharmacological and non-pharmacological treatments in children and adolescents with primary headaches. METHODS: Study of a cohort of children and adolescents diagnosed with primary headache, consecutively referred to 13 juvenile Italian Headache Centers. An ad hoc questionnaire was used for clinical data collection. RESULTS: Among 706 patients with primary headaches included in the study, 637 cases with a single type of headache (migraine 76% - with and without aura in 10% and 67% respectively; tension-type headache 24%) were selected (mean age at clinical interview: 12 years). Acetaminophen and non-steroidal anti-inflammatory drugs (in particular ibuprofen) were commonly used to treat attacks, by 76% and 46% of cases respectively. Triptans were used overall by 6% of migraineurs and by 13% of adolescents with migraine, with better efficacy than acetaminophen and non-steroidal anti-inflammatory drugs. Preventive drugs were used by 19% of migraineurs and by 3% of subjects with tension-type headache. In migraineurs, flunarizine was the most frequently used drug (18%), followed by antiepileptic drugs (7%) and pizotifen (6%), while cyproheptadine, propanolol and amitriptyline were rarely used. Pizotifen showed the best perceived efficacy and tolerability. Melatonin and nutraceuticals were used by 10% and 32% of subjects, respectively, both for migraine and tension-type headache, with good results in terms of perceived efficacy and tolerability. Non-pharmacological preventive treatments (i.e. relaxation techniques, biofeedback, cognitive-behavioral therapy, acupuncture) were used only by 10% of cases (migraine 9%, tension-type headache 15%). DISCUSSION: Non-steroidal anti-inflammatory drugs, especially ibuprofen, should be preferred to acetaminophen for acute attacks of migraine or tension-type headache, because they were usually more effective and well tolerated. Triptans could be used more frequently as first or almost second choice for treating migraine attack in adolescents. Non-pharmacological preventive treatments are recommended by some pediatric guidelines as first-line interventions for primary headaches and their use should be implemented in clinical practice. Prospective multicenter studies based on larger series are warranted to better understand the best treatment strategies for young people with primary headaches.

Five children with deletions of 1p34.3 encompassing AGO1 and AGO3.

Small RNAs (miRNA, siRNA, and piRNA) regulate gene expression through targeted destruction or translational repression of specific messenger RNA in a fundamental biological process called RNA interference (RNAi). The Argonaute proteins, which derive from a highly conserved family of genes found in almost all eukaryotes, are critical mediators of this process. Four AGO genes are present in humans, three of which (AGO 1, 3, and 4) reside in a cluster on chromosome 1p35p34. The effects of germline AGO variants or dosage alterations in humans are not known, however, prior studies have implicated dysregulation of the RNAi mechanism in the pathogenesis of several neurodevelopmental disorders. We describe five patients with hypotonia, poor feeding, and developmental delay who were found to have microdeletions of chromosomal region 1p34.3 encompassing the AGO1 and AGO3 genes. We postulate that haploinsufficiency of AGO1 and AGO3 leading to impaired RNAi may be responsible for the neurocognitive deficits present in these patients. However, additional studies with rigorous phenotypic characterization of larger cohorts of affected individuals and systematic investigation of the underlying molecular defects will be necessary to confirm this.

Anxiety and depression levels in prepubertal obese children: a case-control study.

INTRODUCTION: Childhood obesity has become a worldwide epidemic in Western and in developing countries and has been accompanied by many serious and severe comorbidities, such as diabetes, hypertension, sleep apnea syndrome, depression, dyslipidemia, impaired glucose homeostasis, steatohepatitis, and intracranial hypertension, as well as medical concerns unique to youth, such as accelerated pubertal and skeletal development and orthopedic disorders. To date, no specific studies about the psychological assessment in pediatric obesity are present. Therefore, the aim of this study was to evaluate the putative relationship between psychological troubles and obesity in a sample of school-aged children. MATERIALS AND METHODS: The study population consists of 148 obese subjects (body mass index [BMI] >95th percentile) (69 males, mean age 8.9±1.23 years) consecutively referred from clinical pediatricians to the Child and Adolescent Neuropsychiatry department at the Second University of Naples. In all subjects, weight, height, and BMI z-score were evaluated. In order to assess the anxiety levels and the presence of depressive symptoms, the Children Depression Inventory (CDI) and the Italian Self-Administered Psychiatric Scales for Children and Adolescents (SAFA) were administered. The control group consisted of 273 healthy children (129 males and 144 females) (mean age 9.1±1.8 years), enrolled in schools within the Campania region of Italy. RESULTS: No significant differences between the two study groups were found for age (8.9±1.23 years in the obese sample and 9.1±1.8 years in the control group) (P=0.228) or sex (ratio male/female: 69/79 in the obese group versus 129/144 in the control group) (P=0.983). Obviously, significant difference was found for the BMI z-score (2.46±0.31 in the obese group vs 0.73±0.51 in the control group) (P<0.001). The obese subjects showed significant higher level of depressive symptoms (CDI total score) (16.82±7.73 vs 8.2±2.9) (P<0.001) and anxiety (SAFA - Anxiety [SAFA-A]) scale score (58.71±11.84 vs 27.75±11.5) (P<0.001) compared with the control group. Moreover, the Pearson's correlation analysis showed a significantly positive relationship between the BMI z-score and both the CDI (r=0.677; P<0.001) and SAFA-A scores (r=0.591; P<0.001). CONCLUSION: Our findings highlighted the importance of assessing the presence of internalizing problems, such as anxiety and depression, in the common management of childhood obesity.

Brief report: functional MRI of a patient with 7q11.23 duplication syndrome and autism spectrum disorder.

The duplication of the Williams-Beuren syndrome (WBS) region (7q11.23) is a copy number variant associated with autism spectrum disorder (ASD). One of the most intriguing aspects is that the reciprocal microdeletion causes WBS, characterized by hypersociability, marked empathy, and a relative capacity in verbal short-term memory and language. Herein, we studied, by using functional morphological and volumetric magnetic resonance, a 17-year-old male patient who displays a de novo 7q11.23 duplication and ASD. The limbic system of the patient appeared hypo-functional, while the total brain volume was increased, thus contrasting, in an opposite and intriguing manner, with the global brain volume reduction reported in WBS. Even if these findings come from the analysis of a single patient and, therefore, have to be considered preliminary results, they encourage carrying on further functional and volumetric studies in patients with 7q11.23 duplication, to fully elucidate the role of this gene-dosage alteration on brain development and limbic system function.

Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).

It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF.

Psychomotor approach in children affected by nonretentive fecal soiling (FNRFS): a new rehabilitative purpose.

BACKGROUND: According to the Rome III criteria, encopresis without constipation was defined as nonretentive fecal soiling (FNRFS) with not yet well understood etiology. Treatment approaches reported in the literature with varying results include biofeedback, hypnosis, reflexology, and Internet-based educational programs. In developmental age, another behavioral treatment could be identified in the psychomotor approach, which is called psychomotricity in the European countries, or is also known as play therapy. The aim of the present study was to verify the safety and efficacy of play therapy plus toilet training in a small sample of prepubertal children affected by FNRFS. MATERIALS AND METHODS: Twenty-six patients (group 1; 16 males, mean age of 5.92 ± 0.84 years) underwent a psychomotor approach therapy program in association with toilet training for 6 months, and the other 26 subjects (group 2; 17 males, mean age of 5.76 ± 0.69) underwent the sole toilet training program for 6 months. During the observational time period (T0) and after 6 months (T1) of both treatments, the patients were evaluated for FNRFS frequency and for the behavioral assessment. RESULTS: At T0, the FNRFS mean frequency per month for group 1 was 20.115 episodes/month (standard deviation [SD] ± 3.024) and for group 2 was 20.423 (SD ± 1.879) (P = 0.661). At T1 the mean frequency per month was 6.461 (SD ± 1.333) episodes/month and 12.038 (SD ± 1.341), respectively (P < 0.001). Moreover, the delta percent average of the frequency between T0 and T1 was 67.121 ± 8.527 for group 1 and 40.518 ± 9.259 for group 2 (P < 0.001). At T1, a significant improvement in scores on the behavioral scale was identified. CONCLUSION: Our preliminary results show the importance of a multidisciplinary approach, and suggest the positive effect of an additional psychomotor approach, as this holds a new and interesting rehabilitative purpose for children in a toilet training program, even if further research is necessary.

Executive dysfunction in children affected by obstructive sleep apnea syndrome: an observational study.

INTRODUCTION: The role of sleep in cognitive processes can be considered clear and well established. Different reports have disclosed the association between sleep and cognition in adults and in children, as well as the impact of disturbed sleep on various aspects of neuropsychological functioning and behavior in children and adolescents. Behavioral and cognitive dysfunctions can also be considered as related to alterations in the executive functions (EF) system. In particular, the EF concept refers to self-regulatory cognitive processes that are associated with monitoring and controlling both thought and goal directed behaviors. The aim of the present study is to assess the impact of the obstructive sleep apnea syndrome (OSAS) on EF in a large sample of school aged children. MATERIALS AND METHODS: The study population comprised 79 children (51 males and 28 females) aged 7-12 years (mean 9.14 ± 2.36 years) with OSAS and 92 healthy children (63 males and 29 females, mean age 9.08 ± 2.44 years). To identify the severity of OSAS, an overnight respiratory evaluation was performed. All subjects filled out the Italian version of the Modified Card Sorting Test to screen EFs. Moreover, to check the degree of subjective perceived daytime sleepiness, all subjects were administered the Pediatric Daytime Sleepiness Scale (PDSS). RESULTS: No significant differences between the two study groups were found for age (P = 0.871), gender (P = 0.704), z-score of body mass index (P = 0.656), total intelligence quotient (P = 0.358), and PDSS scores (P = 0.232). The OSAS children showed a significantly higher rate of total errors (P < 0.001), perseverative errors (P < 0.001), nonperseverative errors (P < 0.001), percentage of total errors (P < 0.001), percentage of perseverative errors (P < 0.001), and percentage of nonperseverative errors (P < 0.001). On the other hand, OSAS children showed a significant reduction in the number of completed categories (P = 0.036), total correct sorts (P = 0.001), and categorizing efficiency (P < 0.001). The Pearson's correlation analysis revealed a significant positive relationship between all error parameters and apnea-hypopnea index, oxygen desaturation index, and percentage of mean desaturation of O2 with a specular negative relationship between the error parameters and the mean oxygen saturation values, such as a significant negative relationship between apnea-hypopnea index, oxygen desaturation index, percent of mean desaturation of O2, and the number of completed categories. CONCLUSION: Our study identified differences in the executive functioning of children affected by OSAS and is the first to identify a correlation between alteration in respiratory nocturnal parameters and EF that has not yet been reported in developmental age. These findings can be considered as the strength and novelty of the present report in a large pediatric population.

Self-concept evaluation and migraine without aura in childhood.

INTRODUCTION: Self-esteem is related to the broadly understood concept of self-schemas and is a crucial mechanism for a correct psychological development in children and adolescents. The impact of the many psychological difficulties linked to the migraine without aura (MoA) and recurrent headache attacks, such as anger and separation anxiety, on self-esteem has not yet been well investigated. The aims of the present study were to assess self-esteem levels in an objective way and to verify their possible relationship and correlation with the frequency and intensity of migraine attacks, in a population of children and adolescents affected by MoA. METHODS: The study population was comprised of 185 children (88 males [M],97 females [F]) aged between 6 and 12 years (mean 9.04 ± 2.41 years) referred consecutively for MoA to the Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Second University of Naples and of 203 healthy controls (95 M, 108 F) with mean age 9.16 ± 2.37 years, recruited from schools in Campania. The monthly headache frequency and the mean headache duration were assessed from daily headache diaries kept by all the children, and MoA intensity was assessed on a VAS (visual analog scale). To further evaluate their level of self-concept, all subjects filled out the Multidimensional Self-Concept Scale (MSCS). RESULTS: The two study groups were comparable for age (P = 0.621), sex (P = 0.960), and z-score BMI (P = 0.102). The MoA group showed a significant reduction in the MSCS total score (P < 0.001) and in the Social (P < 0.001), Affect (P < 0.001), Family (P < 0.001), and Physical (P < 0.001) domains of the MSCS compared with the control group. The Pearson's correlation analysis showed a significantly negative relationship between MoA clinical characteristics and MSCS scores, and similarly the frequency of attacks was significantly negatively related with the Social (r = -0.3176; P < 0.001), Competence (r = -0.2349; P = 0.001), Physical (r = -0.2378; P = 0.001), and total (r = -0.2825; P < 0.001) scores of the MSCS. On the other hand, the MoA duration was significantly negatively related with the Social (r = -0.1878; P = 0.01), Competence (r = -0.2270; P = 0.002), Physical (r = -0.1976; P = 0.007), and total (r = -0.1903; P = 0.009) scores of the MSCS. CONCLUSION: Our study first identified differences in self-esteem levels, with an objective tool, in children affected by MoA compared with controls, suggesting the need for evaluation of self-esteem for better psychological pediatric management of children with migraine.

Temperamental characteristics in childhood migraine without aura: a multicenter study.

BACKGROUND: Children with migraine seem to be more anxious, sensitive, deliberate, cautious, fearful, vulnerable to frustration, tidy, and less physically enduring than comparisons. To the best our knowledge no studies about the temperamental and the characterial dimension aspects in childhood migraine was conducted. Therefore, the aim of the present study was to describe the temperamental and character aspects in a sample of children affected by migraine without aura (MoA) and their relationship with clinical aspects of MoA such as frequency, duration, and severity of attacks. MATERIALS AND METHODS: In our study, 486 children affected by MoA (239 male, 247 female) aged 7-12 years, (mean 10.04 ± 2.53 years) and 518 typical developing children comparable for age (P = 0.227) and sex (P = 0.892) were enrolled to assess their temperamental characteristics. The mothers of all subjects filled out the Junior Temperament and Character Inventory: Parent Version. RESULTS: Children affected by migraine show a higher prevalence of harm avoidance and persistence temperamental domains (P < 0.001) and significantly lower prevalence of the self-directedness character trait (P = 0.023) with respect to the comparisons, according to Cloninger's model. The Spearman rank correlation analysis shows a significant relationship between migraine characteristics and temperamental domains. CONCLUSION: The present study first identified differences in temperamental characteristics in children affected by MoA with respect to the comparisons, suggesting the need for this evaluation in order for better psychological pediatric management of children with migraine, with possible consequences and impact on the future outcomes of these subjects.

Visuomotor competencies and primary monosymptomatic nocturnal enuresis in prepubertal aged children.

BACKGROUND: Primary monosymptomatic nocturnal enuresis (PMNE) is a common problem in the developmental ages; it is the involuntary loss of urine during the night in children older than 5 years of age. Several clinical observations have suggested an association between bedwetting and developmental delays in motricity, language development, learning disability, physical growth, and skeletal maturation. The aim of the present study is to evaluate the prevalence of fine motor coordination and visuomotor integration abnormalities in prepubertal children with PMNE. METHODS: The study population included 31 children (16 males, 15 females; mean age 8.14 years ± 1.36 years), and the control group comprised 61 typical developing children (32 males, 29 females; mean age 8.03 years ± 1.44 years). The whole population underwent a clinical evaluation to assess total intelligence quotient level, visuomotor integration (VMI) skills, and motor coordination performance (using the Movement Assessment Battery for Children, or M-ABC). RESULTS: No significant differences between the two study groups were found for age (P = 0.725), gender (P = 0.886), z-body mass index (P = 0.149), or intellectual abilities (total intelligence quotient) (P = 0.163). The PMNE group showed a higher prevalence of borderline performance on M-ABC evaluation and in pathologic performance on VMI Total Task compared to controls (P < 0.001). No significant differences between the two study groups were found for pathologic performances on the M-ABC (P = 0.07), VMI Visual Task (P = 0.793), and VMI Motor Task (P = 0.213). CONCLUSION: Our findings pinpointed that PMNE should not be considered as a voiding disorder alone and, consequently, the children affected should be referred to specific rehabilitative programs that aim to improve motor coordination and visuomotor integration.

Primary nocturnal enuresis as a risk factor for sleep disorders: an observational questionnaire-based multicenter study.

INTRODUCTION: Primary nocturnal enuresis (PNE) is a common problem in developmental age with an estimated overall prevalence ranging from 1.6% to 15%, and possible persistence during adolescence. There is a growing interest in the sleep habits of children affected by PNE, which is derived from the contradictory data present in clinical literature. The aim of the present study was to evaluate the presence of sleep disturbances in a population of children affected by PNE, and to identify whether PNE could be considered as a risk factor for sleep disturbances among children. MATERIALS AND METHODS: A total of 190 PNE children (97 males, 93 females) aged 7-15 years, (mean 9.64 ± 1.35 years), and 766 typically developing children matched for age (P = 0.131) and gender (P = 0.963) were enrolled. To evaluate the presence of sleep habits and disturbances, all of the subjects' mothers filled out the Sleep Disturbances Scale for Children (SDSC), a questionnaire consisting of six subscales: Disorders in Initiating and Maintaining Sleep (DIMS), Sleep Breathing Disorders (SBD), Disorders of Arousal (DA), Sleep-Wake Transition Disorders (SWTD), Disorders of Excessive Somnolence (DOES), and Nocturnal Hyperhidrosis (SHY). The results were divided into "pathological" and "normal" scores using a cut-off value (pathological score = at least three episodes per week), according to the validation criteria of the test. Then, the Chi-square test was used to calculate the statistical difference and a univariate logistic regression analysis was applied to determine the role of PNE as a risk factor for the development of each category of sleep disorders and to calculate the odds ratio (OR). RESULTS: PNE children show a higher prevalence of all sleep disturbances (41.03% DIMS; 85.12% SBD; 63.29% DA; 67.53% SWTD; 31.28% DOES; 37.92% SHY; 25.33% SDSC total score), and according to OR results (SDSC total score OR = 8.293, 95% confidence interval [CI] = 5.079-13.540; DIMS OR = 7.639, 95% CI = 5.192-11.238; SBD OR = 35.633, 95% CI = 22.717-55.893; DA OR = 13.734, 95% CI = 9.476-19.906; SWTD OR = 14.238, 95% CI = 9.829-20.625; DOES OR = 5.602, 95% CI = 3.721-8.432; SHY OR = 6.808, 95% CI = 4.608-10.059), PNE could be considered as a risk factor for the development of sleep disorders. CONCLUSION: Among PNE children, sleep could be strongly altered, thus helping to affirm the hypothesis that PNE tends to alter sleep architecture, or it could itself be the consequence of an abnormal sleep structure. The findings also point to the existence of a potential increase in the risk of developing sleep disorders in the presence of PNE.