Presence of neurologic signs in children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 is a common neurogenetic disorder affecting nervous system, caused by germiline mutations of the NF1 gene. Although the clinical diagnosis of NF1 is defined by presence of cafe-au-laits spots, freckling and benign tumors (neurofibromatosis), neurocognitive impairment and neuropsychiatric disorders are reported in comorbidity. Children with NF1 show higher incidence of executive deficits, such attention, response inhibition, executive planning and problem solving, working memory, and learning impairment. In this study we examine the presence of neurological soft signs and planning function in subjects with NF1. The NSS are minor motor and sensory abnormalities without focal brain damage. METHODS: Eleven drug naïve children between 7-15 years with clinical and molecular diagnosis of NF are matched to 11 healthy controls to ass the presence of neurological soft signs and planning executive functions. NSS were assessed using Physical and Neurological Examination for Subtle Signs and the Tower of London task is performance test to assess the capacity of planning, organization and execution of a work. RESULTS: Our results revealed highest rate of NSS and planning deficit in children with NF1 compared to healthy controls. CONCLUSIONS: The motor abnormalities and planning deficit are possible markers to confirm that NF1 could be considering a neurodevelopmental disorder.

New Insights on the Effects of Methylphenidate in Attention Deficit Hyperactivity Disorder.

This narrative review describes an overview of the multiple effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) and its potential neurobiological targets. It addressed the following aspects: 1) MPH effects on attention and executive functions in ADHD; 2) the relation between MPH efficacy and dopamine transporter gene (DAT) polymorphism; and 3) the role of MPH as an epigenetic modulator in ADHD. Literature analysis showed that MPH, the most commonly used psychostimulant in the therapy of ADHD, acts on multiple components of the disorder. Marked improvements in attentional and executive dysfunction have been observed in children with ADHD during treatment with MPH, as well as reductions in neurological soft signs. MPH efficacy may be influenced by polymorphisms in the DAT, and better responses to treatment were associated with the 10/10 genotype. Innovative lines of research have suggested that ADHD etiopathogenesis and its neuropsychological phenotypes also depend on the expression levels of human endogenous retrovirus (HERV). In particular, several studies have revealed that ADHD is associated with HERV-H over-expression and that MPH administration results in decreased expression levels of this retroviral family and a reduction in the main symptoms of the disorder. In conclusion, there is a confirmed role for MPH as an elective drug in the therapy of ADHD alone or in association with behavioral therapy. Its effectiveness can vary based on DAT polymorphisms and can act as a modulator of HERV-H gene expression, pointing to targets for a precision medicine approach.

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.

Comorbidity of ADHD and High-functioning Autism: A Pilot Study on the Utility of the Overflow Movements Measure.

OBJECTIVES: Children with attention-deficit/hyperactivity disorder (ADHD) and high-functioning autism (HFA) commonly show neurological soft signs (NSS) and impairment in executive functioning (EF). Many children with HFA may experience ADHD-like symptoms, and the 2 disorders may be comorbid. Evaluating NSS and EF in drug-naive subjects with ADHD, HFA, and ADHD+HFA compared with healthy children may be critical in understanding and differentiating the biological substrates and cognitive phenotypes associated with these disorders. The goal of this study was to evaluate possible differences among these groups in motor and EF and the effects of comorbidity. METHODS: Thirty-eight drug-naive patients (13 with ADHD, 13 with HFA, 12 with ADHD+HFA) and 13 healthy controls (HC) were evaluated on measures of planning, verbal working memory, and response inhibition. Evaluation of NSS involved 3 primary variables: overflow movements (OM), dysrhythmia, and speed of timed activities. RESULTS: The group with ADHD and the group with HFA both showed impairment on measures of planning, response inhibition, and verbal working memory compared with the HC group. Moreover, the group with ADHD showed a greater number of NSS compared with the HC group, whereas the group with HFA showed greater dysrhythmia and slowness compared with the HC group. The group with ADHD+HFA showed deficits of planning and response inhibition and a greater number of NSS compared with the HC group. The group with ADHD+HFA showed greater impairment of planning compared with the other clinical groups and greater dysrhythmia compared with the group with ADHD. CONCLUSION: According to our data, the OM measure revealed a gradient in which ADHD was at one extreme (more OM) and HFA at the other extreme (less OM), whereas ADHD+HFA showed a number of OM that fell in the middle between the numbers for the ADHD and HFA groups.