Mariabernarda Pitzianti

Attention and executive functions profile in childhood absence epilepsy

Childhood absence epilepsy (CAE) has been associated with executive functions and attention deficits. To clarify the issue of neurocognitive impairments in CAE, we investigated whether specific executive functions and attention deficit patterns were present in a well-defined group of children with CAE who were taking valproic acid. Participants included 15 children with CAE and 15 healthy controls aged 8-15 years and matched for sex, age and IQ. We compared the performances of the two groups in the following neuropsychological domains: planning and problem solving (TOL), verbal fluency (FAS and CAT), verbal short-term memory (DSF), verbal working memory (DSB), visuospatial memory (Corsi Block Tapping Test) and sustained and divided attention (TMT-A and TMT-B). No differences were found between the two groups on measures of intellectual functioning, verbal short-term memory and visuospatial memory. By contrast, significant differences were found in total time of planning task, phonological and category fluency and sustained and divided attention. Future studies that systematically examine different aspects of attention and executive functions are needed to outline a clear and specific neuropsychological profile in CAE.

Attention impairment in childhood absence epilepsy: An impulsivity problem?

Although attention problems have often been described in children with childhood absence epilepsy (CAE), the use of different methodological approaches, neuropsychological tests, and heterogeneous experimental groups has prevented identification of the selective areas of attention deficit in this population. In this study, we investigated several components of attention in children with CAE using a unique computerized test battery for attention performance. Participants included 24 patients with CAE and 24 controls matched for age and sex. They were tested with a computerized test battery, which included the following tasks: selective attention, impulsivity, focused attention, divided attention, alertness, and vigilance. Compared with healthy controls, patients with CAE made more commission errors in the Go/No-Go task and more omission errors in the divided attention task. Childhood absence epilepsy patients also showed decreased reaction times in measures of selective attention and a great variability of reaction times in alertness and Go/No-Go tasks. Our findings suggest that patients with CAE were impaired in tonic and phasic alertness, divided attention, selective attention, and impulsivity.

Human endogenous retroviruses and ADHD

Abstract Objectives. Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD. Methods. The expression of retroviral mRNAs from the three HERV families was evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with ADHD and 30 healthy controls by quantitative RT-PCR. Results. The expression levels of HERV-H are significantly higher in patients with ADHD compared to healthy controls, while there are no differences in the expression levels of HERV-K and W. Conclusions. Since the ADHD aetiology is due to a complex interaction of environmental, biological and genetic factors, HERVs may represent one link among these factors and clinical phenotype of ADHD. A future confirmation of HERV-H overexpression in a larger number of ADHD patients will make possible to identify it as a new parameter for this clinical condition, also contributing to deepen the study on the role of HERVs in the neurodevelopment diseases.

Motor examination in children with Attention-deficit/hyperactivity Disorder and Asperger Syndrome.

Aim:  Evaluating whether motor skills could differentiate drug‐naive subjects with two neurodevelopmental disorders: Attention‐Deficit Hyperactivity Disorder (ADHD) and Asperger Syndrome (AS).

Detecting anxiety symptoms in children and youths with neurofibromatosis type I

Children with Neurofibromatosis type 1 (NF1) are known to have cognitive, social, and behavioral deficits. Fifteen NF1‐subjects (5 boys, 10 girls, mean age = 13.4), and 15 healthy controls matched for age and sex were assessed on the presence of anxiety symptoms, using the Multidimensional Anxiety Scale for Children (MASC), self‐report questionnaire. Significant group differences emerged with regard to MASC total (Z = −2.058, P = 0.041) and anxiety disorder index (ADI; Z = −2.202, P = 0.026), but not with regard to single scales. When the severity and visibility of NF1 were considered, correlation between severity and social anxiety, and severity and MASC total was found. This is the first study assessing anxiety symptoms in NF1 children and youths. A precocious psychological survey and intervention in NF1 subjects, may contribute to reduce the risk of psychiatric disorders in adulthood.

Neurological soft signs are associated with attentional dysfunction in children with attention deficit hyperactivity disorder

ABSTRACT Introduction: Inattention is one of the core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Most of patients with ADHD show motor impairment, consisting in the persistence of neurological soft signs (NSS). Our aim was to evaluate attentional and motor functioning in an ADHD sample and healthy children (HC) and possible link between attentional dysfunction and motor impairment in ADHD. Method: Twenty-seven drug-naive patients with ADHD and 23 HC were tested with a test battery, measuring different aspects of attention. Motor evaluation has provided three primary variables: overflow movements (OM), dysrhythmia and total speed of timed activities. Results: Compared to HC, patients were impaired in a considerable number of attentional processes and showed a greater number of NSS. Significant correlations between disturbances of attention and motor abnormalities were observed in ADHD group. Conclusion: Our findings suggest that attentional processes could be involved in the pathophysiology of the NSS and add scientific evidence to the predictive value of NSS as indicators of the severity of functional impairment in ADHD. Given the marked improvement or complete resolution of NSS following treatment with methylphenidate, we suggest that evaluation of NSS is useful to monitor the effectiveness of pharmacological treatment with MPH in ADHD.

Neurological soft signs, but not theory of mind and emotion recognition deficit distinguished children with ADHD from healthy control

Attention Deficit Hyperactivity Disorder (ADHD) is associated with social cognition impairment, executive dysfunction and motor abnormalities, consisting in the persistence of neurological soft signs (NSS). Theory of mind (ToM) and emotion recognition (ER) deficit of children with ADHD have been interpreted as a consequence of their executive dysfunction, particularly inhibitory control deficit. To our knowledge, there are not studies that evaluate the possible correlation between the ToM and ER deficit and NSS in the population with ADHD, while this association has been studied in other psychiatric disorders, such as schizophrenia. Therefore, the aim of this study was to evaluate ToM and ER and NSS in a sample of 23 drug-naïve children with ADHD and a sample of 20 healthy children and the possible correlation between social cognition dysfunction and NSS in ADHD. Our findings suggest that ToM and ER dysfunction is not a constant feature in the population with ADHD, while NSS confirmed as a markers of atypical neurodevelopment and predictors of the severity of functional impairment in children with ADHD.

A Child with a c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 Mutation Associated with a Severe Early Infantile Epileptic Encephalopathy

Early infantile epileptic encephalopathies (EIEEs) are a group of neurological disorders characterized by early-onset refractory seizures, severe electroencephalographic abnormalities, and developmental delay or intellectual disability. Recently, genetic studies have indicated that a significant portion of previously cryptogenic EIEEs are single-gene disorders. SPTAN1 is among the genes whose mutations are associated with EIEE development (OMIM# 613477). Here, a case of the c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 mutation associated with a severe EIEE is reported. This case shows that mutations in the α20 repeat in the C-terminal of αII spectrin can be associated with EIEE. Duplication seems essential to cause EIEE. This causation is not demonstrated for amino acid deletions in the same spectrin residues. Reportedly, children with p.(Asp2303_Leu2305del) and p.(Gln2304_Gly2306del) deletions have childhood-onset epilepsy and no or marginal magnetic resonance imaging abnormalities, suggesting that not only the location but also the type of mutation plays a role in conditioning nervous system damage. Further studies are needed for a better understanding of the phenotype/genotype correlation in SPTAN1-related encephalopathies.

A Small Supernumerary Marker Derived from the Pericentromeric Region of Chromosome 5: Case Report and Delineation of Partial Trisomy 5p Phenotype

A 17-year-old girl presented with a distinct phenotype mainly featuring craniofacial dysmorphism, including a disproportioned large, round, elongated face; hypertelorism; deep-set eyes with short palpebral fissures; obesity (BMI 37), and a neuropsychiatric disorder with high-functioning autism. Postnatal conventional cytogenetic analyses from peripheral blood revealed a mosaic small supernumerary marker chromosome (sSMC) with a mos 47,XX,+mar[7]/46,XX[43] karyotype. By cenM-FISH technique, the sSMC was identified as a ring derivative of chromosome 5. Metaphase FISH analysis with a set of dedicated probes defined its origin from the pericentromeric region of chromosome 5, including the NIPBL gene at 5p13.2. Such sSMCs, exceedingly rare in the literature, underlie proximal trisomy 5p. In order to delineate a core phenotype of proximal trisomy 5p, we compared our patients features with those of 6 patients found in the literature with similar der(5) chromosomes. Furthermore, a dozen individuals with 5p13 (micro)duplication syndrome was compared and discussed. We identified highly distinctive craniofacial dysmorphism, obesity, and intellectual disability and/or autism spectrum disorder as typical features of proximal 5p trisomy. In the critical region (band 5p13), the NIPBL gene is likely to be a major determinant of the neurobehavioral phenotype, and its presence at the sSMC level may be relevant to predict clinical outcome.

Timing and clinical characteristics of topiramate-induced psychosis in a patient with epilepsy and tuberous sclerosis.

AbstractSeveral lines of scientific evidence showed that topiramate may induce psychotic symptoms when used as monotherapy. It has been postulated that this topiramate effect may be caused by the inhibition of frontal and prefrontal areas induced by topiramate. The clinical history of the patient described shows that topiramate may also induce psychosis when used in polytherapy. A 34-year-old man, with epilepsy associated to tuberous sclerosis complex and without a previous history of mental disorders, presented an acute onset of florid psychotic symptoms, including visual and auditory hallucinations, derealization, and depersonalization. These symptoms appeared 1 month after the introduction of topiramate, added to levetiracetam and carbamazepine, when topiramate reached the dose of 200 mg daily. Once topiramate was discontinued, the psychotic symptoms disappeared, with no recurrence in a 4-month follow-up. Psychotic symptoms were associated with topiramate administration. We hypothesized that psychotic symptoms appeared a month after the topiramate introduction because of the slow topiramate titration and protective effect of carbamazepine.