Effects of combined Transcranial direct current stimulation with cognitive training in girls with Rett syndrome

Background: Transcranial Direct Current Stimulation (tDCS) combined with traditional rehabilitative techniques has not been widely applied to Rett Syndrome (RTT). The aim of this study was to examine the effects of combined cognitive traditional training with tDCS applied to attention and language measures in subjects with RTT. Methods: 31 subjects with RTT were randomly allocated into two groups: Non-sham tDCS (n = 18) and sham tDCS (n = 13). The former received the integrated intervention non-sham tDCS plus cognitive empowerment during the treatment phase. The latter received sham stimulation plus cognitive empowerment. All participants underwent neurological and cognitive assessment to evaluate attention and language measures: Before integrated treatment (pre-test phase), at the conclusion of the treatment (post-test phase), and at 1 month after the conclusion of the treatment (follow-up phase). Results: The results indicated longer attention time in the non-sham tDCS group compared to the sham tDCS group with a stable trend also in the follow-up phase; an increase of the number of vowel/phoneme sounds in the non-sham tDCS group; and an improvement in the neurophysiological parameters in the non-sham tDCS group. Conclusions: This study supports the use of tDCS as a promising and alternative approach in the RTT rehabilitation field

Movement cognition and narration of the emotions treatment versus standard speech therapy in the treatment of children with borderline intellectual functioning: A randomized controlled trial

Background: Borderline intellectual functioning (BIF) is defined as a "health meta-condition... characterized by various cognitive dysfunctions associated with an intellectual quotient (IQ) between 71 and 85 which determines a deficit in the individual's functioning both in the restriction of activities and in the limitation of social participation". It can be caused by many factors, including a disadvantaged background and prematurity. BIF affects 7-12% of primary school children that show academic difficulties due to poor executive functioning. In many children with BIF, language, movement and social abilities are also affected, making it difficult to take part in daily activities. Dropping out of school and psychological afflictions such as anxiety and depression are common in children with BIF. This study investigates whether an intensive rehabilitation program that involves all of the areas affected in children with BIF (Movement, Cognition and Narration of emotions, MCNT) is more effective than Standard Speech Therapy (SST). Methods: This is a multicenter interventional single blind randomized controlled study. Children aged between 6 to 11years who attend a mainstream primary school and have multiple learning difficulties, behavioral problems and an IQ ranging between 85 to 70 have been enrolled. Participants are randomly allocated to one of three groups. The first group receives individual treatment with SST for 45min, twice a week for 9months. The second group receives the experimental treatment MCNT for 3h per day, 5days/ week for 9months and children work in small groups. The third group consists of children on a waiting list for the SST for nine months. Discussion: BIF is a very frequent condition with no ad hoc treatment. Over the long term, there is a high risk to develop psychiatric disorders in adulthood. Due to its high social impact, we consider it very important to intervene during childhood so as to intercept the remarkable plasticity of the developing brain. Trial registration: "Study Let them grow: A new intensive and multimodal Treatment for children with borderline intellectual functioning based on Movement, Cognition and Narration of emotions", retrospectively registered in ISRCTN Register with ISRCTN81710297 at 2017-01-09

The synaptic vesicle proteins synapsin I and synaptophysin (protein P38) are concentrated both in efferent and afferent nerve endings of the skeletal muscle

Synapsin I and synaptophysin (protein p38) are 2 major protein components of the membranes of small synaptic vesicles of virtually all presynaptic nerve endings. Synapsin I, a phosphoprotein regulated by both Ca2+ and cAMP, is a peripheral protein of the cytoplasmic surface of the vesicle membrane. It is thought to anchor the vesicle surface to the cytoskeleton of the terminal and to play a regulatory role in neurotransmitter release. Synaptophysin is an intrinsic transmembrane glycoprotein. We report here that both proteins are present and concentrated also in afferent nerve endings, which provide the sensory innervation of the skeletal muscle and of the tendon. The distribution of both antigens in sensory nerve endings is consistent with their localization on the microvesicles that have been described in such endings. Thus, our results suggest the existence of important biochemical, and possibly functional, similarities between small synaptic vesicles of presynaptic nerve endings and microvesicles of sensory endings. Such findings provide new clues to the understanding of the physiology of sensory endings

Ambiguous emotion recognition in temporal lobe epilepsy: The role of expression intensity

The lateralization of emotion processing is currently debated and may be further explored by examining facial expression recognition (FER) impairments in temporal lobe epilepsy (TLE). Furthermore, there is also debate in the literature whether FER deficits in individuals with TLE are more pronounced in the right than in the left hemisphere. Individuals with TLE were tested with an FER task designed to be more sensitive than those classically used to shed light on this issue. A total of 25 right- and 32 left-TLE patients, candidates for surgery, along with controls, underwent an FER task composed of stimuli shown not only at full-blown intensities (100 %), but also morphed to lower-intensity display levels (35 %, 50 %, and 75 %). The results showed that, as compared to controls, right-TLE patients showed deficits in the recognition of all emotional categories. Furthermore, when considering valence, right-TLE patients were impaired only in negative emotion recognition, but no deficits for positive emotions were highlighted in left-TLE patients. Finally, only the right-TLE patients’ impairment was found to be related to the age of epilepsy onset. Our work demonstrates that the FER deficits in TLE span multiple emotional categories and show manifestations dependent on the laterality of the epileptic focus. Taken together, our findings provide the strongest evidence for the right-hemisphere model, but they also partially support the valence model. We suggest that current models are not exhaustive at explaining emotional-processing cerebral control, and further that multistep models should be developed

Aggressive behavior and epilepsy : a multicenter study

The aim of this study is to describe aggressiveness in the epilepsy population and to identify possible relationships between this type of behavior and clinical and sociodemographic variables. Aggressive responses were measured by the Aggression Questionnaire (AQ), a standardized and validated instrument, which was administered to 503 patients from nine Italian centers for the care of epilepsy. Aggressive behavior in patients with epilepsy was different from that in the normal Italian population. After adjustment for age and sex, when appropriate, the following variables significantly affected aggressiveness: presence of compromised intellectual functioning, psychiatric disturbances, disability status, number of medications, geographic distribution, education, chronologic age, and disease duration. Our study offers a starting point for further investigations aimed at better understanding the mechanisms connecting aggression and epilepsy

Health-related quality of life in adults with epilepsy : the effect of age, age at onset and duration of epilepsy in a multicentre Italian study

Background: The potential effect of age-related factors on health-related quality of life (HRQOL) of patients with epilepsy has rarely been analyzed in the literature.Methods: We examined this association in a selected population of 815 adults with epilepsy recruited in the context of a multicentre study for the evaluation of Epi-QoL, one of the first Italian epilepsy-specific measures of HRQOL for adults with epilepsy. The Epi-QoL is a 46-item self-administered questionnaire focusing on six domains, which was successfully tested for reproducibility and validity. Ordinary least-squares regression models were used to assess the relationships between age-related factors (patient's age, age at seizure onset, and duration of epilepsy) and overall Epi-QoL score, controlling for the effect of potential confounders. We fitted simple regression models including each age-related factor alone to assess the independent role of each factor on the overall Epi-QoL score. We also fitted multiple regression models including pairs of age-related factors solely, as well as one or two age-related factors together with the same set of confounders.Results: Simple regression models showed that age and duration of epilepsy were significant negative predictors of the overall Epi-QoL score: the higher was each age-related factor, the lower was the overall Epi-QoL score; age at onset alone was a nonsignificant predictor of the overall Epi-QoL score. Multiple regression models including two age-related factors solely showed that duration of epilepsy was still a significant negative predictor of the overall Epi-QoL score in both pairwise models, whereas age was a significant negative predictor only in the model including age at onset. Age at onset emerged as a significant positive predictor of the overall Epi-QoL score only in the model including age: the higher was age at onset, the higher was the overall Epi-QoL score. Adjusted regression models including either one or two age-related factors and controlling for the selected confounding variables showed that the age-related factors had no significant effect on the overall Epi-QoL score anymore.Conclusions: If no other known correlates of the overall Epi-QoL score are considered, age and duration of epilepsy can be expected to have a significant negative association with HRQOL in epilepsy (with the effect of duration being stronger and more consistent across models than the one of age), whereas age at onset is a positive predictor of the overall HRQOL of limited significance. However, demographic and clinical factors, such as seizure frequency in the preceding 12 months, may provide a better explanation of HRQOL in epilepsy

Epilepsy in adult patients with Down syndrome : a clinical-video EEG study

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28-64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6-60 years). Nine out of 22 patients had focal epilepsy, while nine had late-onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp-and-slow waves with frontal predominance. In the patients diagnosed with late-onset myoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode of myoclonic status epilepticus at the beginning or in the course of the disorder. After the first descriptions of late-onset myoclonic epilepsy by Genton and Paglia (1994), this is one of the largest patient cohorts reported. Our data confirm that epilepsy in adult patients with Down syndrome presents peculiar electroclinical characteristics which should be recognized early as prompt, effective treatment may be beneficial. [Published with video sequences]

Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of \u201cself-limited focal epilepsies.\u201d In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 \ub1 11.46. Two independent general linear model models were created for each patient based on the effect of interest: \u201cindividual CTS\u201d in model 1 and \u201cCTS density\u201d in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical\u2013subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood\u2013oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks

Medical care of adolescents and women with Rett syndrome : an Italian study

Rett syndrome (RTT) is a rare neurodevelopmental disorder, linked to MECP2 gene mutations in the majority of cases, which results in severe disability and is associated with several comorbidities. The clinical condition of RTT patients tends to stabilize over time, and prolonged survival has recently been demonstrated. However, limited information is available on the long-term course of older patients with RTT, especially among those in Southern Europe. The aim of our study is to evaluate the main clinical features and state of health of adult Italian patients with RTT and to present their evolution over time, identifying major clinical issues present at different ages. A total of 130 families of patients with RTT aged 6514 years were asked to complete a questionnaire, 84 of which were returned (65%). Among the clinical characteristics of RTT, stereotypies and poor hand function and feeding ability remained stable over time, while nonverbal communication tended to improve. With regard to the main pathologies, sleep, behavioral, and autonomic disorders persisted into adulthood, while epilepsy improved and musculoskeletal problems worsened. In our sample, older patients with R294X and R133C mutations and with C-terminal deletions showed lower levels of clinical severity. The development of guidelines for the clinical management of patients with RTT will assist health care providers in dealing with the complex RTT phenotype. More extensive data about the long-term course of the condition could help in the design of programs for secondary prevention of disabilities for younger females affected by the syndrome