Contextual priors do not modulate action prediction in children with autism.

Bayesian accounts of autism suggest that this disorder may be rooted in an impaired ability to estimate the probability of future events, possibly owing to reduced priors. Here, we tested this hypothesis within the action domain in children with and without autism using a behavioural paradigm comprising a familiarization and a testing phase. During familiarization, children observed videos depicting a child model performing actions in diverse contexts. Crucially, within this phase, we implicitly biased action-context associations in terms of their probability of co-occurrence. During testing, children observed the same videos but drastically shortened (i.e. reduced amount of kinematics information) and were asked to infer action unfolding. Since during the testing phase movement kinematics became ambiguous, we expected children's responses to be biased to contextual priors, thus compensating for perceptual uncertainty. While this probabilistic effect was present in controls, no such modulation was observed in autistic children, overall suggesting an impairment in using contextual priors when predicting other peoples' actions in uncertain environments.

Electrical status epilepticus during sleep in Mowat-Wilson syndrome.

AIM: Mowat-Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present in 70-75% of Patients and an age-dependent electroclinical pattern has been described. Up to date, there are studies with overnight sleep EEGs, probably because of the severe intellectual disability (ID) and hyperactivity of these Patients. Our purpose was to verify the hypothesis that MWS Patients might have electrical status epilepticus in slow wave sleep (ESES pattern). METHODS: A retrospective analysis of anamnestic and electrographic data was performed on 7 consecutive MWS Patients followed between 2007 and 2016. Only Patients with at least one overnight sleep EEG were included in the study. RESULTS: Five out of 7 Patients had overnight sleep EEG studies and were included in this study. All of them had an anterior ESES pattern with spike-and-wave index>85%. The architecture of sleep was abnormal. An ESES related regression of cognitive and motor functions with impact on daily activities (ESES-related syndrome) was demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of cognitive and motor performances was observed when the epileptiform activity during sleep was successfully controlled or it was spontaneously reduced. CONCLUSIONS: The clinical significance of the ESES pattern is hard to assess in MWS Patients due to severe ID, but changing in behaviour or in motor and cognitive functions should mandate sleep EEG investigation and, if ESES is present, an appropriate treatment should be tried. Furthermore, overnight sleep EEG recordings, if regularly performed in the follow up, might help to understand if ESES pattern hampers the cognitive and communicative profile in MWS.

Anterior thalamic nucleus deep brain Stimulation (DBS) for drug-resistant complex partial seizures (CPS) with or without generalization: long-term evaluation and predictive outcome.

BACKGROUND: Drug-resistant epileptic patients account for 40 % of cases of epilepsy. Consequently, specific therapeutic options could be surgical resection or, if not indicated, deep brain stimulation (DBS). The aim of this study is to review data from patients affected by drug-resistant complex partial epilepsy with or without generalization treated by anterior thalamic nucleus (AN) DBS to evaluate the efficacy and potential future applications of this approach as a standard method for palliative seizure control. METHODS: Six patients affected by drug-resistant complex partial seizures underwent AN DBS from March 2007 to February 2011. The preoperative tests consisted of electroencephalography (EEG), video EEG, morphologic and functional magnetic resonance imaging (MRI), non-acute positron emission tomography (PET), neuropsychological evaluation, Liverpool seizure scale, and Quality Of Life In Epilepsy (QOLIE). These tests and a seizure diary were also administered during a follow-up of at least 3 years. RESULTS: The improvement in terms of decrease of seizures was more than 50 % in patients affected by complex partial seizures strictly related to limbic system origin. The amelioration was unsatisfactory for patients having anatomical lesions outside the limbic structures with evidence of late diffusion in limbic areas. One patient died 40 days after surgery for reasons not concerned with DBS. CONCLUSIONS: Although the limited number of enrolled patients limits the reliability of data, the results are in accordance with those found in the recent literature and deserve to be considered for further studies regarding real efficacy, indications, stimulation parameters, side effects, and complications.

Nocturnal frontal lobe epilepsy in mucopolysaccharidosis.

Nocturnal frontal lobe epilepsy (NFLE) is an epileptic syndrome that is primarily characterized by seizures with motor signs occurring almost exclusively during sleep. We describe 2 children with mucopolysaccharidosis (MPS) who were referred for significant sleep disturbance. Long term video-EEG monitoring (LT-VEEGM) demonstrated sleep-related hypermotor seizures consistent with NFLE. No case of sleep-related hypermotor seizures has ever been reported to date in MPS. However, differential diagnosis with parasomnias has been previously discussed. The high frequency of frontal lobe seizures causes sleep fragmentation, which may result in sleep disturbances observed in at least a small percentage of MPS patients. We suggest monitoring individuals with MPS using periodic LT-VEEGM, particularly when sleep disorder is present. Moreover, our cases confirm that NFLE in lysosomal storage diseases may occur, and this finding extends the etiologic spectrum of NFLE.

Genetic and environmental factors shape infant sleep patterns: a study of 18-month-old twins.

OBJECTIVE: Between 25% and 30% of children and adolescents experience sleep disorders. These disorders are complex phenotypes that are regulated by many genes, the environment, and gene-environment interactions. The objective of this study was to evaluate the contribution of genetic and environmental factors to sleep behaviors in early childhood and to contribute to the knowledge on appropriate therapeutic approaches, using a twin design. PATIENTS AND METHODS: Data on sleeping behavior were collected from 314 18-month-old twin pairs (127 monozygotic and 187 dizygotic)using a parent-rated questionnaire. We used structural equation modeling to estimate genetic and environmental variance components for different sleep behaviors (cosleeping, sleep duration, and night awakenings). RESULTS: Shared environment explained almost all (98.3%) of the total variance in cosleeping. Sleep duration was substantially influenced by shared environmental factors (64.1% nocturnal sleep and 61.2% diurnal sleep), with a moderate contribution of additive genetic effects (30.8% and 36.3% for nocturnal and diurnal sleep, respectively). For nocturnal waking episodes, we found a shared environmental contribution of 63.2% and a heritability estimate of 35.3%. CONCLUSIONS: Most sleep disturbances during early childhood are explained by common shared environmental factors, and behavioral interventions adopted by parents and focused on modifying sleep behavior could contribute to solving sleep disturbances in this age group. However, the influence of genetic factors should not be underestimated, and research in this area could clarify the physiologic architecture of sleeping and contribute to selecting appropriate personalized therapeutic approaches.

Probabilistic diffusion tractography of the optic radiations and visual function in preterm infants at term equivalent age.

Children born prematurely have a high incidence of visual disorders which cannot always be explained by focal retinal or brain lesions. The aim of this study was to test the hypothesis that visual function in preterm infants is related to the microstructural development of white matter in the optic radiations. We used diffusion tensor imaging (DTI) with probabilistic diffusion tractography to delineate the optic radiations at term equivalent age and compared the fractional anisotropy (FA) to a contemporaneous evaluation of visual function. Thirty-seven preterm infants (19 male) born at median (range) 28(+4) (24(+1)-32(+3)) weeks gestational age, were examined at a post-menstrual age of 42 (39(+6)-43) weeks. MRI and DTI were acquired on a 3 Tesla MR system with DTI obtained in 15 non-collinear directions with a b value of 750 s/mm(2). Tracts were generated from a seed mask placed in the white matter lateral to the lateral geniculate nucleus and mean FA values of these tracts were determined. Visual assessment was performed using a battery of nine items assessing different aspects of visual abilities. Ten infants had evidence of cerebral lesions on conventional MRI. Multiple regression analysis demonstrated that the visual assessment score was independently correlated with FA values, but not gestational age at birth, post-menstrual age at scan or the presence of lesions on conventional MRI. The occurrence of mild retinopathy of prematurity did not affect the FA measures or visual scores. We then performed a secondary analysis using tract-based spatial statistics to determine whether global brain white matter development was related to visual function and found that only FA in the optic radiations was correlated with visual assessment score. Our results suggest that in preterm infants at term equivalent age visual function is directly related to the development of white matter in the optic radiations.

Lack of evidence for association between D2S124 and D2S111 polymorphisms of the SCN2A gene and idiopathic generalized epilepsy with generalized tonic clonic seizures.

Idiopathic generalized epilepsy syndromes are generally considered as brain channelopathies due to alteration of several genes. The aim of our study was to compare the distribution of D2S124 and D2S111 genetic polymorphisms of the SCN2A gene between cases with a specific idiopathic generalized epilepsy subtype (with generalized tonic-clonic seizures) and healthy controls. Allele frequencies of both the D2S111 and the D2S124 polymorphisms were not significantly different between cases and control. Further studies are needed to investigate if possible polymorphic variants of SCN2A gene may influence seizures susceptibility of idiopathic generalized epilepsy with tonic-clonic seizures.

Association between D18S474 locus on chromosome 18q12 and idiopathic generalized epilepsy.

Idiopathic generalized epilepsy is one of the most common forms of epilepsy. The aetiology of IGE is genetically determined, but the pattern of inheritance is still undefined. Recent studies in common IGE showed evidence for linkage on chromosome 18q12 at the D18S474 locus. The aim of our study was to compare the distribution of allelic variants of D18S474 locus in children affected by generalized tonic-clonic seizures and in healthy controls. We studied 295 children: 121 cases and 174 controls. We found that the D18S474(8) allele was significantly more frequent and D18S474(9) significantly less frequent in cases compared with controls (p<.001). In conclusions, our findings show the association between the D18S474 marker and IGE in which early onset GTCS represent the most prevalent seizure type.

Association of adenosine deaminase polymorphism with mild mental retardation.

The etiology of mild mental retardation remains undefined in about 60% of cases. Even though the causes of mild mental retardation are likely to be heterogeneous, the evidence for genetic involvement is increasing, along with the development of specific diagnostic techniques. To improve our understanding of the genetic basis of mild mental retardation, we explored the role of polymorphisms of adenosine deaminase, an enzyme that is supposed to act as a neuroregulatory protein. To this end, we conducted an association study comparing children with mild mental retardation of unknown origin with two groups of controls: (1) apparently healthy children and (2) children with moderate or severe mental retardation of known etiology. Overall, 338 participants were enrolled in the study. Cases (ie, 80 children) were more likely than controls (ie, 153 healthy children and 105 children with moderate or severe mental retardation) to have the low-activity ADA-Asn 8 (ADA(1) *2) polymorphism (P < .05) and to present the ADA(1) *2/ ADA(2) *1 haplotype. No significant differences were found with respect to adenosine deaminase polymorphisms when comparing the group with moderate or severe mental retardation of known causes and healthy controls. In conclusion, our findings suggest a possible role for a low-activity genotype (ADA-8Asn) (ADA(1) *2) of adenosine deaminase in the pathogenesis of mild mental retardation.

Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations.

PURPOSE: We describe seven Italian families with generalized epilepsy with febrile seizures plus (GEFS+), in which mutations of SCN1A, SCN1B, and GABRG2 genes were excluded and compare their clinical spectrum with that of previously reported GEFS+ with known mutations. METHODS: We performed a clinical study of seven families (167 individuals). The molecular study included analysis of polymerase chain reaction (PCR) fragments of SCN1A and SCN1B exons by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing of GABRG2 in all families. We excluded SCN1A, SCN1B, and GABRG2 genes with linkage analysis in a large pedigree and directly sequenced SCN2A in a family with neonatal-infantile seizures onset. We compared the epilepsy phenotypes observed in our families with those of GEFS+ families harboring mutations of SCN1A, SCN1B, and GABRG2 and estimated the percentage of mutations of these genes among GEFS+ cases by reviewing all published studies. RESULTS: Inheritance was autosomal dominant with 69% penetrance. Forty-one individuals had epilepsy: 29 had a phenotype consistent with GEFS+; seven had idiopathic generalized epilepsy (IGE); in three, the epilepsy type could not be classified; and two were considered phenocopies. Clinical phenotypes included FS+ (29.2%), FS (29.2%), IGE (18.2%), FS+ with focal seizures (13%) or absence seizures (2.6%), and FS with absence seizures (2.6%). Molecular study of SCN1A, SCN2A, SCN1B, and GABRG2 did not reveal any mutation. Results of our study and literature review indicate that mutations of SCN1A, SCN2A, SCN1B, and GABRG2 in patients with GEFS+ are rare. CONCLUSIONS: The most frequently observed phenotypes matched those reported in families with mutations of the SCN1A, SCN1B, and GABRG2 genes. IGE and GEFS+ may overlap in some families, suggesting a shared genetic mechanism. The observation that 13% of affected individuals had focal epilepsy confirms previously reported rates and should prompt a reformulation of the "GEFS+" concept to include focal epileptogenesis.

Nonsyndromic mental retardation and cryptogenic epilepsy in women with doublecortin gene mutations.

DCX mutations cause mental retardation in male subjects with lissencephalypachygyria and in female subjects with subcortical band heterotopia (SBH). We observed four families in which carrier women had normal brain magnetic resonance imaging (MRI) and mild mental retardation, with or without epilepsy. Affected male subjects had SBH or pachygyria-SBH. In two families, the phenotype was mild in both genders. In the first family, we found a tyr138his mutation that is predicted to result in abnormal folding in the small hinge region. In the second family, we found an arg178cys mutation at the initial portion of R2, in the putative beta-sheet structure. Carrier female subjects with normal MRI showed no somatic mosaicism or altered X-inactivation in lymphocytes, suggesting a correlation between mild mutations and phenotypes. In the two other families, with severely affected boys, we found arg76ser and arg56gly mutations within the R1 region that are predicted to affect DCX folding, severely modifying its activity. Both carrier mothers showed skewed X-inactivation, possibly explaining their mild phenotypes. Missense DCX mutations may manifest as non-syndromic mental retardation with cryptogenic epilepsy in female subjects and SBH in boys. Mutation analysis in mothers of affected children is mandatory, even when brain MRI is normal.