Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies.

OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.

Epilepsy with auditory features: Contribution of known genes in 112 patients.

Epilepsy with Auditory Features (EAF) is a focal epilepsy syndrome mainly of unknown aetiology. LGI1 and RELN have been identified as the main cause of Autosomal Dominant EAF and anecdotally reported in non-familial cases. Pathogenic variants in SCN1A and DEPDC5 have also been described in a few EAF probands belonging to families with heterogeneous phenotypes and incomplete penetrance. We aimed to estimate the contribution of these genes to the disorder by evaluating the largest cohort of EAF. We included 112 unrelated EAF cases (male/female: 52/60) who underwent genetic analysis by next-generation sequencing (NGS) techniques. Thirty-three (29.5%) were familial cases. We identified a genetic diagnosis for 8% of our cohort, including pathogenic/likely pathogenic variants (4/8 novel) in LGI1 (2.7%, CI: 0.6-7.6); RELN (1.8%; CI: 0.2-6.3); SCN1A (2.7%; CI: 0.6-7.6) and DEPDC5 (0.9%; CI 0-4.9).This study shows that the contribution of each of the known genes to the overall disorder is limited and that the genetic background of EAF is still largely unknown. Our data emphasize the genetic heterogeneity of EAF and will inform the diagnosis and management of individuals with this disorder.

Application of intravoxel incoherent motion (IVIM) magnetic resonance imaging in the evaluation of primitive brain tumours.

Intravoxel incoherent motion is a potential non-invasive diagnostic tool in brain tumours, without any clear guidelines for its evaluation yet. In our study, we compare intravoxel incoherent motion with dynamic susceptibility contrast magnetic resonance imaging in the quantification of tumour tissue blood perfusion in 28 patients affected by brain tumours, highlighting the issues encountered during the acquisition set-up and post-processing steps. Intravoxel incoherent motion is a new imaging tool and an alternative technique to dynamic susceptibility contrast-magnetic resonance imaging which is of considerable interest at present. This is partly because it does not require the use of a contrast agent and relies on the intrinsic properties of motion in the capillaries of the spins. Compared to dynamic susceptibility contrast-magnetic resonance imaging, the intravoxel incoherent motion technique is also characterised by better resolution because the gadolinium-based contrast agent bolus used in the standard technique results in a variation by more than 50% of the signal coming from the brain. Finally, intravoxel incoherent motion is more sensitive to the incoherent motion that originates from small capillary vessels, while the dynamic susceptibility contrast signal is also contaminated by the input from larger arteries and veins, which may result in an overestimation of the blood volume. Although there are limitations due to the heterogeneity of the sample considered in our study, intravoxel incoherent motion has been shown to be an accurate noninvasive radiological biomarker, useful to distinguish between low and high grade glial tumours.

Effect of organizational features on patient satisfaction with care in Italian multiple sclerosis centres.

BACKGROUND AND PURPOSE: Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients' satisfaction with healthcare. METHODS: Eighty-one centres and 707 patients (502 women, mean age 40.5 years, SD 10.2; mean education 12.2 years, SD 3.6; time since diagnosis 5.9 years, SD 1.5) were included in the analysis. The care organization and service provided by each centre were evaluated in comparison with the National Institute for Health and Care Excellence (NICE) guidelines on management of MS. Patients' satisfaction with care was measured using the patient self-assessed questionnaire 'Comunicazione medico-paziente nella Sclerosi Multipla, revised' section 2 (COSM-R section 2). RESULTS: The clinical characteristics of patients significantly affected their satisfaction. A multivariate regression model showed that higher patients' satisfaction (COSM-R score) was inversely associated with hospital size (number of patients under care) (ß = -0.21, 95% confidence interval -0.35; -0.07) and directly associated with psychological interventions (ß = 2.44, 95% confidence interval 0.29; 4.59). CONCLUSIONS: Multiple sclerosis patients from larger hospitals are less satisfied with the information received and the relationship with HPs. Building an individualized relationship between patients and HPs and tailoring the communication of information improve patients' satisfaction. Such a goal is probably less likely to be accomplished in larger centres with many incoming patients. Moreover, when the centres also provide structured psychological interventions, the patients are more satisfied.

Effects of a school based intervention to promote healthy habits in children 8-11 years old, living in the lowland area of Bologna Local Health Unit.

BACKGROUND: A school based health promotion intervention was performed with the aim of increasing physical activity and improving the dietary habits of primary school pupils, using integrated educational strategies involving schools, families, public bodies, sports associations and public health operators. METHODS: The intervention concerned 11 classes during 3 school years from 2009-10 (231 third-year school children) to 2011-12 (234 fifth-year school children). Information was collected both before and after the intervention about the dietary habits and the physical activities practised by the children, using the questionnaires of the project !OKkio alla Salute! which were administered to both children and parents. At the same time anthropometric measurements were taken (height, weight, BMI) and motor skills were assessed using standardized tests: Sit & Reach, medicine-ball forward throw, standing long jump, 20 m running speed, and forward roll. At the end of the intervention 12 different expected outcomes were assessed (5 about dietary habits, 5 about motor habits, 1 about anthropometric characteristics, 1 about motor skills). RESULTS: At baseline, 35.8% of the children show excess weight (23.4% overweight; 12.4% obese); this percentage falls to 29.3% (25.3% overweight; 4% obese) after the intervention (p <0.05). The dietary habits improve from the pre- to the post-intervention: there is a rise in the percentage of children who receive an adequate mid-morning snack (p <0.0001), a fall in the percentage of children who consume snacks and drinks after the dinner (p <0.01), and an increase in the percentage of those who take five or more portions of fruits and vegetables daily. The motor habits do not improve in the same way, since there is the increasing tendency with age to skip from a regular daily practice of physical exercise to favour of the occasional practice of a sport. The motor performances, compared after normalization for modifications due to the process of growth, improve between the third and fifth years of primary school, but with no significant differences. To achieve this objective more focused measures are necessary in the administration of moderate to intense physical exercise. CONCLUSIONS: The results point to a positive assessment of the intervention, thus highlighting the importance of planning integrated and multisectorial actions in school-based programmes to promote correct dietary and motor habits and for the control of body weight, also involving non scholastic areas.