A Neuropsychological Profile of Developmental Dyscalculia: The Role of Comorbidity.

Developmental dyscalculia (DD) has long been thought to be determined by multiple components. Dyscalculia has high comorbidity with other learning and developmental disabilities, including reading and writing disorders, attention deficits, and problems in visual/spatial skills, short memory, and working memory. This study aims to assess prevalence rates for isolated as well as comorbid DD in a sample of Italian-speaking children. In addition, we studied the neuropsychological profile of children with isolated or combined dyscalculia. We tested 380 children (176 males and 204 females) between the ages of 8.17 and 9.33 years using an extensive battery to determine the neuropsychological profile. The assessment included an arithmetic battery and nonverbal intelligence, short-term memory, reading, and writing tests. The results indicated that children with DD more frequently have a reading disorder and writing disorder. They also have a lower nonverbal intelligence quotient (IQ) and obtain significantly lower scores in short-term memory tests and on a visuospatial skills questionnaire. They also had significantly higher scores (indicative of greater attentional difficulties) on the Conners subscale for attentional problems. Children with DD present different cognitive and neuropsychological profiles.

Psychopathology, Dissociation and Somatic Symptoms in Adolescents Who Were Exposed to Traumatic Experiences.

Background: The direct and long-term effects of children's exposure to traumatic events can be seen in a complex continuum, based first of all on the type of trauma. Children's reactions to trauma may have different manifestations from the clinical picture of the PTSD, exhibiting dissociative, somatic, depressive or anxiety symptoms, and/or disruptiveness. Aim: we conducted a cross-sectional study in a psychiatric patients sample to determine the extent to which complex trauma history is associated with disease-related characteristics (diagnosis, dissociative symptoms, somatic symptomatology, impairment degree). Methods: We have enrolled 107 subjects, aged between 12 and 18 years, who consecutively referred for a psychiatric evaluation to the Child Neuropsychiatry Unit of the Del Ponte Hospital in Varese. All subjects underwent a clinical evaluation performed by infantile neuropsychiatrists. The battery of tests that was administered to patients included CGI and CGAS (filled out by the clinician), CBCL (filled out by parents), MMPI-A and TSSC-A (filled out by patients), and Wechsler scale. Results: We found out that 35.5% of subjects had a mood disorder, 23.4% a personality disorder, 13.1% a psychotic disorder, 20.6% a post-traumatic stress disorder, while 26.2% were classified as other diagnostic categories (more frequently ADHD, DOP and conduct disorders). 58.9% of patients had at least one comorbidity. 33.6% of subjects also experienced a complex trauma. In multivariate logistic regression analyses, subgroup fellows were collapsed to compare the single trauma and no trauma versus complex trauma group. Gender, age and affective disorders were generally unrelated to subjects', clinicians', and parents' scores. About subjects' self-assessment (MMPI-A Structural Summary Factors), complex trauma history was a statistically significant contributor to high scores on the Immaturity, Health Concerns, Familial Alienation and Psychoticism Factors, followed by presence of dissociative symptoms (except for Familial Alienation factor). Presence of dissociative symptoms, personality and psychotic disorder diagnosis was related to higher clinician impairment scores (CGI-S > 4). Conclusion: These results reinforce available evidence that in trauma-exposed adolescents, the full burden of trauma, including other psychiatric diagnosis than PTSD (such as affective, personality, and psychotic disorders), dissociative and somatic symptomatology, is substantial and needs appropriate assessment and therapeutic interventions.

A Regional ADHD Center-Based Network Project for the Diagnosis and Treatment of Children and Adolescents With ADHD.

OBJECTIVE: We aimed to define the sociodemographic, clinical, and prescription profiles of the participants enrolled in the Italian Lombardy ADHD Register. METHOD: Data on patients evaluated by the 18 regional ADHD reference centers in the 2012 to 2013 period were analyzed. RESULTS: Seven hundred fifty-three of 1,150 (65%) suspected patients received a diagnosis of ADHD. In 24% of cases, there was a family history of ADHD. Four hundred eighty-three (64%) patients had at least one psychopathological disorder, the more common of which were learning disorders (35%). Eighty-four percent of patients received a prescription for psychoeducational interventions, 2% received only pharmacological treatment, and 14% a combination of both. Compared with patients treated with psychoeducational intervention alone, patients with drug prescriptions more commonly presented values of Clinical Global Impressions - Severity scale (CGI-S) of 5 or higher ( p < .0001). CONCLUSION: A continuous and systematic monitoring of patterns of care is essential in promoting significant improvements in clinical practice and ensuring an efficient and homogeneous quality of care.

Impact of co-morbid attention-deficit and hyperactivity disorder on cognitive function in male children with Tourette syndrome: A controlled study.

Tourette syndrome (TS) and attention-deficit and hyperactivity disorder (ADHD) are co-morbid neurodevelopmental conditions affecting more commonly male patients. We set out to determine the impact of co-morbid ADHD on cognitive function in male children with TS by conducting a controlled study. Participants included four matched groups of unmedicated children (age range 6-15 years): TS (n=13), TS+ADHD (n=8), ADHD (n=39), healthy controls (n=66). Following clinical assessment, each participant completed a battery of tests from the Wechsler Intelligence Scale for Children-III, the Italian Battery for ADHD, the Tower of London test, the Corsi test, and the Digit Span test. All patient groups reported significantly lower scores than healthy controls across the neuropsychological tests involving executive functions. The TS+ADHD group was the most severely affected, followed by the ADHD group and the TS group, particularly in the tests assessing planning ability, inhibitory function, working memory and visual attention, but not auditory attention. Problems in executive functions are more common in patients with neurodevelopmental disorders than controls. Deficits in planning ability, inhibitory function, working memory and visual attention reported by children with TS appear to be more strongly related to the presence of co-morbid ADHD symptoms than core TS symptoms.

Personality Profile of Male Adolescents With Tourette Syndrome: A Controlled Study.

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and commonly associated with behavioral problems, especially obsessive-compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The presence of specific personality traits has been documented in adult clinical populations with Tourette syndrome but has been underresearched in younger patients. We assessed the personality profiles of 17 male adolescents with Tourette syndrome and 51 age- and gender-matched healthy controls using the Minnesota Multiphasic Personality Inventory-Adolescent version, along with a standardized psychometric battery. All participants scored within the normal range across all Minnesota Multiphasic Personality Inventory-Adolescent version scales. Patients with Tourette syndrome scored significantly higher than healthy controls on the Obsessiveness Content Scale only (P = .046). Our findings indicate that younger male patients with Tourette syndrome do not report abnormal personality traits and have similar personality profiles to healthy peers, with the exception of obsessionality traits, which are likely to be related to the presence of comorbid obsessive compulsive symptoms rather than tics.

Confrontation Naming and Reading Abilities at Primary School: A Longitudinal Study.

BACKGROUND: Confrontation naming tasks are useful in the assessment of children with learning and language disorders. OBJECTIVES: The aims of this study were (1) providing longitudinal data on confrontation naming; (2) investigating the role of socioeconomic status (SES), intelligence, age, and gender in confrontation naming; (3) identifying relationship between confrontation naming and reading abilities (fluency, accuracy, and comprehension). METHOD: A five-year longitudinal investigation of confrontation naming (i.e., the Boston Naming Test (BNT)) in a nonclinical sample of Italian primary school children was conducted (n = 126), testing them at the end of each school year, to assess nonverbal intelligence, confrontation naming, and reading abilities. RESULTS: Performance on the BNT emerged as a function of IQ and SES. Significant correlations between confrontation naming and reading abilities, especially comprehension, were found; BNT scores correlated better with reading fluency than with reading accuracy. CONCLUSIONS: The longitudinal data obtained in this study are discussed with regard to reading abilities, intelligence, age, gender, and socioeconomic status.

A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy.

OBJECTIVE: To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy. METHODS: Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values. RESULTS: Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers. SIGNIFICANCE: Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.

Mother-child agreement on behavioral ratings in Tourette syndrome: a controlled study.

In Tourette syndrome, motor and phonic tics are associated with a spectrum of psychiatric disorders. As proxy report instruments are commonly used to assess children with Tourette syndrome, we investigated the relationship between child and mother ratings of behavioral problems. We enrolled 28 children with Tourette syndrome (25 males; mean age, 13.9 years) and 61 gender- and age-matched healthy controls (55 males; mean age, 14.7 years). Clinicians completed measures of tic severity, and all children completed the Youth Self-Report version of the Child Behavior Checklist, while their mothers completed the Child Behavior Checklist. In the clinical group, Youth Self-Report scores were significantly lower than mothers' Child Behavior Checklist scores across the majority of subscales (especially affect and somatization). In contrast, for the control group, mother and child ratings only differed for the externalizing behavior subscales. Clinicians should be aware of these differences between self and mother ratings for specific behavioral problems in Tourette syndrome.

The Gilles de la Tourette Syndrome-Quality of Life Scale for children and adolescents (C&A-GTS-QOL): development and validation of the Italian version.

BACKGROUND: Gilles de la Tourette syndrome (GTS) is a chronic childhood-onset neuropsychiatric disorder with a significant impact on patients' health-related quality of life (HR-QOL). Cavanna et al. (Neurology 2008; 71: 1410-1416) developed and validated the first disease-specific HR-QOL assessment tool for adults with GTS (Gilles de la Tourette Syndrome-Quality of Life Scale, GTS-QOL). This paper presents the translation, adaptation and validation of the GTS-QOL for young Italian patients with GTS. METHODS: A three-stage process involving 75 patients with GTS recruited through three Departments of Child and Adolescent Neuropsychiatry in Italy led to the development of a 27-item instrument (Gilles de la Tourette Syndrome-Quality of Life Scale in children and adolescents, C&A-GTS-QOL) for the assessment of HR-QOL through a clinician-rated interview for 6-12 year-olds and a self-report questionnaire for 13-18 year-olds. RESULTS: The C&A-GTS-QOL demonstrated satisfactory scaling assumptions and acceptability. Internal consistency reliability was high (Cronbach's alpha > 0.7) and validity was supported by interscale correlations (range 0.4-0.7), principal-component factor analysis and correlations with other rating scales and clinical variables. CONCLUSIONS: The present version of the C&A-GTS-QOL is the first disease-specific HR-QOL tool for Italian young patients with GTS, satisfying criteria for acceptability, reliability and validity.

Disease-specific quality of life in young patients with tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating "pure" Tourette syndrome from Tourette syndrome "plus" behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.

Parent and self-report health-related quality of life measures in young patients with Tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder characterized by tics and comorbid behavioral problems. This study compared child- and parent-reported quality of life and everyday functioning. We assessed 75 children with Tourette syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities = 4). All patients completed psychometric instruments, including the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (child report) and the Child Tourette's Syndrome Impairment Scale (parent report). Data were compared for patients with pure Tourette syndrome, Tourette syndrome + obsessive-compulsive disorder, Tourette syndrome + attention-deficit hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no group differences in quality of life. However, there were differences for total, school, and home activities impairment scores. Children and parents may not share similar views about the impact of Tourette syndrome on functioning. The measurement of health-related quality of life in Tourette syndrome is more complex in children than adults.

Tolerability profile of aripiprazole in patients with Tourette syndrome.

Over the last few years, aripiprazole has been proposed as a potentially useful medication for tics in patients with Tourette syndrome (TS). Aripiprazole has been associated with fewer adverse effects compared with other atypicals; however, little is known about its tolerability profile in the TS population. This study assessed the prevalence and characteristics of adverse effects resulting from the use of aripiprazole in a retrospective chart review of 29 patients with TS. Six patients (20.7%) discontinued aripiprazole because of the severity of specific adverse effects. The most commonly reported adverse effects were sedation (n = 9, 30%) and sleep problems (n = 5, 17%). In the majority of cases, adverse effects were not severe. There were no differences in demographic or clinical variables between the patients who did or did not experience adverse effects. The discontinuation rate of 20.7% suggests that aripiprazole is safe and reasonably well tolerated for use in TS. The prevalence of adverse effects appears to increase with treatment duration.

Chorea mollis: long-term follow-up of an infantile case.

We describe the long-term follow-up of a patient affected by chorea mollis, a rare variant of Sydenham's chorea of which there are very few reports in the literature. Our patient, a previously healthy 8-year-old boy developed progressive clumsiness, gait disturbance, generalised hypotonia and muscle weakness, choreic movements of the limbs and behavioural disturbances. Following the diagnosis of chorea mollis, the patient received prophylaxis (monthly injections of benzathine benzyl penicillin). Within a few weeks, his clinical conditions worsened and he became bedridden and incapable of standing and walking without assistance. The choreic movements were successfully treated with sodium valproate. Independent walking was achieved 14 months after the onset of the disease. At a 4-year follow-up, the patient showed a full neurological and psychiatric recovery. The clinical course observed in our patient shows that chorea mollis may not only have a dramatic course, but also have a good long-term prognosis.

Determinants of health-related quality of life in pharmacoresistant epilepsy: results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments.

PURPOSE: To evaluate the relative contribution of demographic and epilepsy-related variables, depressive symptoms, and adverse effects (AEs) of antiepileptic drugs (AEDs) to health-related quality of life (HRQOL) in adults with pharmacoresistant epilepsy. METHODS: Individuals with epilepsy whose seizures failed to respond to at least one AED were enrolled consecutively at 11 tertiary referral centers. HRQOL was assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), AEs by the Adverse Event Profile (AEP), and depressive symptoms by the Beck Depression Inventory-II (BDI-II). Multivariate linear regression models were used to identify variables associated with QOLIE-31 total score and subscale scores. KEY FINDINGS: Of 933 enrolled individuals aged 16 years or older, 809 (87%) were able to complete the self-assessment instruments and were included in the analysis. Overall, 61% of the variance in QOLIE-31 scores was explained by the final model. The strongest predictors of HRQOL were AEP total scores (ß = -0.451, p < 0.001) and BDI-II scores (ß = -0.398, p < 0.001). These factors were also the strongest predictors of scores in each of the seven QOLIE-31 subscales. Other predictors of HRQOL were age (ß = -0.060, p = 0.008), lack of a driving license (ß = -0.053, p = 0.018), pharmacoresistance grade, with higher HRQOL in individuals who had failed only one AED (ß = 0.066, p = 0.004), and location of the enrolling center. Epilepsy-related variables (seizure frequency, occurrence of tonic-clonic seizures, age of epilepsy onset, disease duration) and number of AEDs had no significant predictive value on HRQOL. The AEP total score was the strongest negative predictor of HRQOL in the subgroup of 362 patients without depressive symptoms (BDI-II score <10), but even in this subgroup the BDI-II score was retained as a significant predictor. SIGNIFICANCE: In individuals with pharmacoresistant epilepsy, AEs of medication and depressive symptoms are far more important determinants of HRQOL than seizures themselves. When seizure freedom cannot be achieved, addressing depressive comorbidity and reducing the burden of AED toxicity is likely to be far more beneficial than interventions aimed at reducing the frequency of seizures.

Self-, parent-, and teacher-reported behavioral symptoms in youngsters with Tourette syndrome: a case-control study.

AIMS: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple tics and associated with co-morbid behavioral problems (TS-plus). We investigated the usefulness of self-report versus parent- and teacher-report instruments in assisting the specialist assessment of TS-plus in a child/adolescent population. METHODS: Twenty-three patients diagnosed with TS (19 males; age 13.9 ± 3.7 years) and 69 matched healthy controls participated in this study. All recruited participants completed a standardized psychometric battery, including the Children's Depression Inventory (CDI), the Self Administrated Psychiatric Scales for Children and Adolescents (SAFA) and the State-Trait Anger Expression Inventory (STAXI). Parents completed the Child Behavior Checklist (CBCL) and Conners' Parent Rating Scales-Revised (CPRS-R). Participants' teachers completed the Conners' Teacher Rating Scales-Revised (CTRS-R). Results were compared with similar data obtained from controls. RESULTS: Nineteen patients (82.6%) fulfilled DSM-IV-TR criteria for at least one co-morbid condition: obsessive-compulsive disorder (OCD, n = 8; 34.8%); attention deficit-hyperactivity disorder (ADHD, n = 6; 26.1%); OCD + ADHD (n = 5; 21.7%). Scores on self-report instruments failed to show any significant differences between TS and controls. Most subscores of the CPRS-R, CTRS-R, and CBCL were significantly higher for the TS group than controls. The TS + OCD subgroup scored significantly higher than the TS-OCD subgroup on the CBCL-Externalizing, Anxious/Depressed and Obsessive-Compulsive subscales. CONCLUSIONS: Self-report instruments appear to have limited usefulness in assisting the assessment of the behavioral spectrum of young patients with TS. However, proxy-rated instruments differentiate TS populations from healthy subjects, and the CBCL can add relevant information to the clinical diagnosis of co-morbid OCD.

BRAF alterations are associated with complex mutational profiles in malignant melanoma.

To evaluate the mutational profiles associated with BRAF mutations in human melanoma, we have studied BRAF, RAS, PTEN, TP53, CDKN2A and CDK4 genes and their expression in melanoma lesions. Owing to the lack of sufficient material from fresh specimens, we employed short-term cell lines obtained from melanoma biopsies. In all, 41 melanoma obtained from eight primary lesions, 20 nodal, 11 cutaneous and two visceral metastases from patients with sporadic (n=31), familial (n=4) and multiple melanoma (n=2) were analysed. The results revealed novel missense mutations in the BRAF, PTEN, CDKN2A and CDK4 genes. Overall, activating mutations of BRAF and loss of functional p16 and ARF were detected in the majority of melanomas (29/41, 36/41 and 29/41, respectively), while PTEN alterations/loss, NRAS and TP53 mutations occurred less frequently (6/41, 6/41 and 10/41, respectively). In the resulting 12 mutational profiles, p16/ARF loss associated with mutated BRAFV599E was the most represented (n=15). In addition, TP53 and PTEN mutations were always accompanied with BRAF alterations, while PTEN loss was found in association with CDKN2A or TP53 mutations in the absence of BRAF activation. The p16/ARFDelta+BRAF/RAS profile was significantly associated with a longer survival, while complex mutational profiles were detected in highly aggressive disease and poor survival. These data support the existence of several molecularly defined melanoma groups which likely reflect different clinical/biological behaviour, thus suggesting that a more extensive molecular classification of melanoma would significantly impact its clinical management.