Paola Visconti

EEG features and epilepsy in patients with autism

Epileptic seizures are frequently reported (4-32%) in autism. These values are higher than in the normal population of children and adolescents (0.5%). In the literature there is no uniform description of epilepsy in autism. We examined 106 patients with autistic disorder divided into three groups on the basis of presence or absence of EEG paroxysmal abnormalities (PA) and / or epilepsy including febrile convulsions (FG). Our patients presented an autistic syndrome unrelated to clear congenital or acquired encephalopathy. The prevalence of epilepsy and EEG PA was 23.6% and 18.9%, respectively. Significant differences between the three groups appeared for (i) familial antecedents for epilepsy / FC and neurologic and psychiatric diseases (P < 0.004), (ii) a different proportion between the three groups for mental retardation (P < 0.03), (iii) and EEG fast activity (P < 0.04). Our patients showed several types of epilepsy, including idiopathic forms with seizure onset after the age of 10 in 45% of cases. Seizures were mainly partial, not frequent and controllable by anti-epileptic drugs. PA were mostly focal and multifocal and in 45% of cases were typical of benign childhood partial epilepsy with centro-temporal spikes. The higher incidence of epilepsy and EEG PA is apparently not related to organic pre-, peri- and postnatal antecedents or cerebral lesions. On the contrary, genetic factors responsible for autism and epilepsy seem important in the genesis of these two disorders.

Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (−66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.

Microduplication 22q11.2 in a child with autism spectrum disorder: clinical and genetic study

Microduplication of the 22q11.2 chromosomal region has been recognized since 1999 and has been associated with a highly variable phenotype. Neurodevelopmental impairment and behavioural problems are very common in patients with 22q11.2 duplication. Autism spectrum disorders (ASDs) have previously been reported in only two patients with 22q11.2 duplication and striking dysmorphic features. We report here on a 4‐year‐old male of healthy consanguineous parents presenting with ASD according to DSMIV, revised, criteria as a primary manifestation. The child walked at 16 months and started to say one word and some sounds. Parents noticed a subsequent developmental arrest. At 4 years his functional development age, evaluated by the Psychoeducational Profile, was roughly 6 months. Mild non‐specific facial dysmorphism was noted. Genetic analyses of the child demonstrated a de novo microduplication of the 22q11.2 chromosomal region. This genetic anomaly was best seen in interphases of blood lymphocytes and in buccal smear nuclei. Our case illustrates once again the clinical heterogeneity of the 22q11.2 duplication as well as the wide genetic complexity of ASD. We suggest that genetic evaluation of ASD should include fluorescence in‐situ hybridization analysis of the 22q11.2 chromosomal region.

Variant of rett syndrome and CDKL5 gene: Clinical and autonomic description of 10 cases

UNLABELLED Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. RESULTS Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. CONCLUSIONS The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant.

Pyrethroid Pesticide Metabolite in Urine and Microelements in Hair of Children Affected by Autism Spectrum Disorders: A Preliminary Investigation

The number of children affected by Autism Spectrum Disorders (ASD) is dramatically increasing as well as the studies aimed at understanding the risk factors associated with the development of ASD. Since the etiology of ASD is partly genetic and partly environmental, factors (i.e., heavy metals, pesticides) as well as lifestyle seem to have a key role in the development of the disease. ASD and Control (CTR) children, aged 5–12 years, were compared. Gas chromatography coupled with trap mass detector was used to measure the level of 3-PBA, the main pyrethroid metabolite in urine in a group of ASD patients, while optical emission spectrometry analysis was employed to estimate the level of metals and microelements in hair in a different group of ASD children. The presence of 3-PBA in urine seems to be independent of age in ASD children, while a positive correlation between 3-PBA and age was observed in the control group of the same age range. Urine concentration of 3-BPA in ASD children had higher values than in the control group, which were marginally significant (p = 0.054). Mg results were significantly decreased in ASD with respect to controls, while V, S, Zn, and Ca/Mg were marginally increased, without reaching statistical significance. Results of Principal Component (PC) analysis of metals and microelements in hair were not associated with either age or health status. In conclusion, 3-PBA in urine and Mg in hair were changed in ASD children relative to control ones.

Perspective Biological Markers for Autism Spectrum Disorders: Advantages of the Use of Receiver Operating Characteristic Curves in Evaluating Marker Sensitivity and Specificity.

Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Recognized causes of ASD include genetic factors, metabolic diseases, toxic and environmental factors, and a combination of these. Available tests fail to recognize genetic abnormalities in about 70% of ASD children, where diagnosis is solely based on behavioral signs and symptoms, which are difficult to evaluate in very young children. Although it is advisable that specific psychotherapeutic and pedagogic interventions are initiated as early as possible, early diagnosis is hampered by the lack of nongenetic specific biological markers. In the past ten years, the scientific literature has reported dozens of neurophysiological and biochemical alterations in ASD children; however no real biomarker has emerged. Such literature is here reviewed in the light of Receiver Operating Characteristic (ROC) analysis, a very valuable statistical tool, which evaluates the sensitivity and the specificity of biomarkers to be used in diagnostic decision making. We also apply ROC analysis to some of our previously published data and discuss the increased diagnostic value of combining more variables in one ROC curve analysis. We also discuss the use of biomarkers as a tool for advancing our understanding of nonsyndromic ASD.

Autism according to diagnostic and statistical manual of mental disorders 5 th edition: The need for further improvements

The fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) introduced significant changes in the classification of autism spectrum disorders (ASD), including the abolition of the diagnostic subcategories proposed by DSM-IV-Text Revision. DSM-5 describes three levels of increasing severity of ASD. The authors report two explanatory cases with ASD (verbal boys, aged about 7 and a half years, without intellectual disability). According to DSM-5, both cases fall into the lowest severity level of ASD. However, their neuropsychological and neurobehavioral profile varies significantly. While the first boy showed a prevalent impairment of visuoconstructional and visuoperceptual abilities, the second one presented a predominant involvement of verbal functions, with qualitative impairments in communication. A further step forward in the definition and classification of ASD, taking into account both intensity and quality of symptoms, is recommended in order to formulate a reliable prognosis, plan an individualized treatment and monitor the clinical course over time.

Autism in 2016: the need for answers.

OBJECTIVE Autism spectrum disorders are lifelong and often devastating conditions that severely affect social functioning and self-sufficiency. The etiopathogenesis is presumably multifactorial, resulting from a very complex interaction between genetic and environmental factors. The dramatic increase in autism spectrum disorder prevalence observed during the last decades has led to placing more emphasis on the role of environmental factors in the etiopathogenesis. The objective of this narrative biomedical review was to summarize and discuss the results of the most recent and relevant studies about the environmental factors hypothetically involved in autism spectrum disorder etiopathogenesis. SOURCES A search was performed in PubMed (United States National Library of Medicine) about the environmental factors hypothetically involved in the non-syndromic autism spectrum disorder etiopathogenesis, including: air pollutants, pesticides and other endocrine-disrupting chemicals, electromagnetic pollution, vaccinations, and diet modifications. SUMMARY OF THE FINDINGS While the association between air pollutants, pesticides and other endocrine-disrupting chemicals, and risk for autism spectrum disorder is receiving increasing confirmation, the hypothesis of a real causal relation between them needs further data. The possible pathogenic mechanisms by which environmental factors can lead to autism spectrum disorder in genetically predisposed individuals were summarized, giving particular emphasis to the increasingly important role of epigenetics. CONCLUSIONS Future research should investigate whether there is a significant difference in the prevalence of autism spectrum disorder among nations with high and low levels of the various types of pollution. A very important goal of the research concerning the interactions between genetic and environmental factors in autism spectrum disorder etiopathogenesis is the identification of vulnerable populations, also in view of proper prevention.

Sensory abnormalities in children with autism spectrum disorder

OBJECTIVE The clinical picture of children with autism spectrum disorder is characterized by deficits of social interaction and communication, as well as by repetitive interests and activities. Sensory abnormalities are a very frequent feature that often go unnoticed due to the communication difficulties of these patients. This narrative review summarizes the main features of sensory abnormalities and the respective implications for the interpretation of several signs and symptoms of autism spectrum disorder, and therefore for its management. SOURCES A search was performed in PubMed (United States National Library of Medicine) about the sensory abnormalities in subjects (particularly children) with autism spectrum disorder. SUMMARY OF THE FINDINGS Sensory symptoms are common and often disabling in children with autism spectrum disorder, but are not specific for autism, being a feature frequently described also in subjects with intellectual disability. Three main sensory patterns have been described in autism spectrum disorder: hypo-responsiveness, hyper-responsiveness, and sensory seeking; to these, some authors have added a fourth pattern: enhanced perception. Sensory abnormalities may negatively impact the life of these individuals and their families. An impairment not only of unisensory modalities but also of multisensory integration is hypothesized. CONCLUSIONS Atypical sensory reactivity of subjects with autism spectrum disorder may be the key to understand many of their abnormal behaviors, and thus it is a relevant aspect to be taken into account in their daily management in all the contexts in which they live. A formal evaluation of sensory function should be always performed in these children.

Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls

Abstract Aims/hypothesis: To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage. Methods: 27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined. Results: Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower–upper quartile]): autistic children – 6.60 nM (4.48–8.91) and 7.00 nM (5.51–8.55), and healthy controls – 6.82 nM (4.47–7.02) and 6.82 nM (5.84–8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81–8.52) versus 9.00 nM (8.41–10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged. Conclusions/interpretation: Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host–microbe homeostasis.