EEG Features in Autism Spectrum Disorder: A Retrospective Analysis in a Cohort of Preschool Children

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that can be associated with intellectual disability (ID) and epilepsy (E). The etiology and the pathogenesis of this disorder is in most cases still to be clarified. Several studies have underlined that the EEG recordings in children with these clinical pictures are abnormal, however the precise frequency of these abnormalities and their relationship with the pathogenic mechanisms and in particular with epileptic seizures are still unknown. We retrospectively reviewed 292 routine polysomnographic EEG tracings of preschool children (age < 6 years) who had received a first multidisciplinary diagnosis of ASD according to DSM-5 clinical criteria. Children (mean age: 34.6 months) were diagnosed at IRCCS E. Medea (Bosisio Parini, Italy). We evaluated: the background activity during wakefulness and sleep, the presence and the characteristics (focal or diffuse) of the slow-waves abnormalities and the interictal epileptiform discharges. In 78.0% of cases the EEG recordings were found to be abnormal, particularly during sleep. Paroxysmal slowing and epileptiform abnormalities were found in the 28.4% of the subjects, confirming the high percentage of abnormal polysomnographic EEG recordings in children with ASD. These alterations seem to be more correlated with the characteristics of the underlying pathology than with intellectual disability and epilepsy. In particular, we underline the possible significance of the prevalence of EEG abnormalities during sleep. Moreover, we analyzed the possibility that EEG data reduces the ASD clinical heterogeneity and suggests the exams to be carried out to clarify the etiology of the disorder

GRIA3 missense mutation is cause of an x-linked developmental and epileptic encephalopathy

Purpose: GRIA3, encoding subunit 3 of glutamate ionotropic AMPA receptor, is associated with X-linked intel-lectual disability (ID), dysmorphic features, and non-syndromic epilepsy. We aimed to characterize electroclinical features of patients with GRIA3 variants.Methods: We report a patient carrying a hemizygous missense variant c.2359 G > A (p.Glu787Lys) inGRIA3 gene. Following a literature search, we also reviewed clinical, electrophysiological, radiological, and genetic features of 19 patients with GRIA3 mutations.Results: This 26-month-old boy had developmental delay, early onset refractory myoclonic epilepsy, and non convulsive refractory status epilepticus. In published reports, epilepsy was in 6 of 19 patients carrying different genotypes, though epilepsy and electroencephalogram features were not completely defined. Out of the 6 patients, one presented with generalized tonic-clonic seizures, two with myoclonic and clonic events (one also presented with epileptic spasms), and one with atypical absences and myoclonic jerks. Information on type of epilepsy was unavailable for 3 cases. Epilepsy onset was early in life and there was potential tendency for myoclonic/clonic events. The epilepsy was difficult to treat and prognosis is poor. Severity of ID ranged from mild to severe and was variably associated with bipolar affective disorder and autistic spectrum disorders. Other neurological features included hypotonia, asthenic body habitus with poor muscle bulk, and hyporeflexia.Conclusion: Our report expands knowledge on the electro-clinical and molecular spectrum of GRIA3 variants. Larger investigations will better define the prevalence of epilepsy, the epileptic phenotype, and syndromic features underlying GRIA3 variants

Treatment of infantile spasms. why do we know so little?

Introduction Infantile spasm (IS) is an epileptic syndrome with typical onset within the first 2 years of life. This condition might be caused by several etiologies. IS is associated with pathological neuronal networks; however, definite hypotheses on neurobiological processes are awaited. Areas covered Changes in NMDA and GABA(B)receptors and increase of Ca(2+)conductance are some of the possible pathophysiological mechanisms. Animal models can help, but most have only some features of IS. Outcome is strongly affected by etiology and the timing of treatment, which relies still on ACTH, oral steroids, and vigabatrin. No significant differences in terms of efficacy have been documented, though a combination of ACTH and vigabatrin seems to be associated with better long-term outcomes. Despite the increasing knowledge about the etiology and pathophysiology of IS, in the last years, no new treatment approaches have been recognized to be able to modify the neurobiological process underlying IS. Precision medicine has far to come in IS. Expert opinion Recently, no new therapeutic options for IS have emerged, probably due to the lack of reliable animal models and to the extreme variability in etiologies. Consequently, the outlook for patients and families is poor and early recognition and intervention remain research priorities

Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Background Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopoietic stem cell transplantation. Design and Methods The aim of this retrospective study was to assess the long-term clinical and hematologic results in 26 paroxysmal nocturnal hemoglobinuria patients who received hematopoietic stem cell transplantation in Italy between 1988 and 2006. The patients were aged 22 to 60 years (median 32 years). Twenty-three donors were HLA-identical (22 siblings and one unrelated) and 3 were HLA-mismatched (2 related and one unrelated). Results Fifteen patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide (in all cases from identical donor) and 11 were given a reduced intensity conditioning (8 from identical donor and 3 from mismatched donor). The cumulative incidence of graft failure was 8% (4% primary and 4% secondary graft failure). Transplant-related mortality for all patients was 42% (26% and 63% for patients transplanted following myeloablative or reduced intensity conditioning, respectively). As of October 31, 2009, 15 patients (11 in the myeloablative conditioning group and 4 in the reduced intensity conditioning group) are alive with complete hematologic recovery and no evidence of paroxysmal nocturnal hemoglobinuria following a median follow-up of 131 months (range 30-240). The 10-year Kaplan-Meier probability of disease-Free survival was 57% for all patients: 65% for 23 patients transplanted from identical donor and 73% for 15 patients transplanted with myeloablative conditioning. No thromboembolic event nor recurrence of the disease were reported following transplant. Conclusions The findings of this study confirm that most patients with paroxysmal nocturnal hemoglobinuria may be definitively cured with hematopoietic stem cell transplantation

Retention of Mitochondria in Mature Human Red Blood Cells as the Result of Autophagy Impairment in Rett Syndrome

Rett Syndrome (RTT), which affects approximately 1:10.000 live births, is a X-linked pervasive neuro-developmental disorder which is caused, in the vast majority of cases, by a sporadic mutation in the Methyl-CpG-binding protein-2 (MeCP2) gene. This is a transcriptional activator/repressor with presumed pleiotropic activities. The broad tissue expression of MeCP2 suggests that it may be involved in several metabolic pathways, but the molecular mechanisms which provoke the onset and progression of the syndrome are largely unknown. In this paper, we report that primary fibroblasts that have been isolated from RTT patients display a defective formation of autophagosomes under conditions of nutrient starvation and that the mature Red Blood Cells of some RTT patients retain mitochondria. Moreover, we provide evidence regarding the accumulation of the p62/SQSTM1 protein and ubiquitin-aggregated structures in the cerebellum of Mecp2 knockout mouse model (Mecp2 -/y ) during transition from the non-symptomatic to the symptomatic stage of the disease. Hence, we propose that a defective autophagy could be involved in the RTT clinical phenotype, which introduces new molecular perspectives in the pathogenesis of the syndrome

KETASER01 protocol: What went right and what went wrong

To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies

Ospitalità narrativa e senso della ‘Matria’ Narrative Hospitality and Sense of Homeland

The Myth of Man, his ontological condition of exile, its ontological need to grow, his ontological need to acquire knowledge from others and, therefor, to emigrate is a myth that intercultural education should never stop telling, starting from a “migrant thought”, which could be a cultural model for the era of conflicts in which we leav