Early motor signs of attention-deficit hyperactivity disorder: a systematic review.

ADHD is a common neurodevelopmental disorder with onset of symptoms typically in early childhood. First signs of the disorder, including language delay, motor delay and temperament characteristics, may be evident as early as infancy. The present review describes published evidence about early motor signs of either children with later symptoms of ADHD or a later diagnosis of the disorder. Nine published cohort studies were included after a systematic search of related terms in PubMed and PsycInfo databases. Study eligibility criteria included: (1) report on early motor function or any motor-related signs; (2) the presence of a participants' assessment by/at 12 months of age; (3) report of a later presence of ADHD symptoms. The limited number of reports included suggests an association between mild early neurological markers and later developmental coordination disorder and motor overflow movements. Unfortunately, due to their small sample sizes and focus on group reports rather than individuals, they have limited power to find strong associations. Early motor indicators of ADHD, if present, appear to be non-specific, and therefore not yet useful in clinical screening. Spontaneous motility seems to be a promising measure for early ADHD detection, although further studies with large cohorts are recommended to determine its clinical role in children at risk for ADHD.

[Practical strategies for promoting breastfeeding in neonatal intensive care]. / Strategie pratiche di promozione del latte materno in TIN.

Strategies for promoting the use of human milk in NICU Human milk has several advantages in the nutrition of very-low-birthweight (VLBW) and high risk infants admitted to neonatal intensive care unit (NICU). Limited data available demonstrate that at discharge from NICU breastfeeding rate is relatively low. In a recent italian study (Davanzo R et aL; Pediatric and Perinatal Epidemiology 2009) only 30.5% of VLBW infants were exclusively breast fed and among the exclusively breastfed infants only 10% sucked directly at the breast. Strategies to promote breastfeeding and the use of human milk in NICUs are needed. They are well known, yet limitedly applied. Among them current literature lists: (1) access at anytime for both parents to NICU; (2) specific knowledge of the science of lactation and multidisciplinary breastfeeding training as provided by the Baby Friendly Hospital Training package; (3) peer support in hospital; (4) kangaroo mother care; (5) breastmilk expression using simultaneous pumping with an electric pump particularly in the first 2 weeks. On the contrary, pharmaceutical galactagogues and cup feeding have little benefit.

Italian neuropsychological instruments to assess memory, attention and frontal functions for developmental age.

In this study, a series of tests exploring long-term verbal memory (the Short Story Test), attention (a modified version of Attentional Matrices and the Trail Making Test) and frontal functions (a modified version of the Frontal Assessment Battery) have been standardised on an Italian population of 283 children aged 5-14. Raw scores for each test have been adjusted for a series of variables (child's age, years of parents' education, handedness, gender) and transformed in equivalent scores enabling direct comparison across measures. This study was promoted by LICE (the Italian League Against Epilepsy) in order to provide Italian instruments standardised on the developmental age population and to study some of the most frequently impaired cognitive functions in epilepsy.

Atypical language lateralization and early linguistic development in children with focal brain lesions.

The effects of congenital, unilateral, focal brain lesions on early linguistic development and hemispheric lateralization for language were investigated longitudinally in 24 preschool children with hemiplegia (14 males, 10 females), 12 with left hemisphere damage (LHD) and 12 with right hemisphere damage (RHD). A comprehensive linguistic assessment was performed at 2 and 3 years of life; cerebral lateralization for language was measured by the Fused Dichotic Words Listening Test. An early left-side specificity for language was indicated by the presence of lexical and grammatical delay in most children with LHD. In the dichotic listening test all 12 children with LHD showed a shift of language lateralization from the left to the right hemisphere. Atypical lateralization coefficients (lambda), i.e. values falling more than two standard deviations from the mean of a normative sample, were associated with a delay in lexical and grammatical development, especially after LHD. In addition, cortical-subcortical-periventricular lesions rather than solely periventricular damage, and larger lesions rather than small, were associated with the most atypical lateralization coefficients, irrespective of lesion side. Results of this study suggest that language and lateralization data are closely related and that reallocation of language functions in alternative regions of the brain has a cost in terms of a slow rate of language acquisition.

Autosomal dominant cortical myoclonus and epilepsy (ADCME) with complex partial and generalized seizures: A newly recognized epilepsy syndrome with linkage to chromosome 2p11.1-q12.2.

We describe a pedigree in which eight individuals presented with a non-progressive disorder with onset between the ages of 12 and 50 years. It was characterized by predominantly distal, semi-continuous rhythmic myoclonus (all patients), generalized tonic-clonic seizures (all patients) and complex partial seizures (three patients). Most individuals had rarely suffered seizures and had a normal cognitive level, but three individuals with intractable seizures had mild mental retardation. The pattern of inheritance was autosomal dominant with high penetrance. We defined this disorder as autosomal dominant cortical myoclonus and epilepsy (ADCME). All patients had frontotemporal as well as generalized interictal EEG abnormalities. A neurophysiological study of the myoclonus suggested a cortical origin. Back-averaging of the data generated a series of waves with a frequency that mirrored the frequency of EMG bursts. Frequency analysis identified significant peaks with coherence between EMG and EEG, which were recorded over the contralateral rolandic area in five patients. The frequency of coherence was 8-25 Hz and phase spectra confirmed that EEG activity preceded EMG activity by 8-15 ms. In two individuals there was also significant coherence between the ipsilateral EEG and EMG, consistent with the transcallosal spread of myoclonic activity. The C-reflex at rest was enhanced and somatosensory and visual evoked potentials were of high amplitude. The resting motor threshold intensity to transcranial magnetic stimulation was significantly reduced (38%; SD +/- 7; P = 0.01) and the post-motor evoked potential silent period (101 ms; SEM +/- 10) was significantly shortened compared with the controls (137 ms; SEM +/- 18). These clinical and neuro- physiological characteristics suggest diffuse cortical hyperexcitability and high propensity for intra-hemispheric and inter-hemispheric cortical spread, as well as rhythmic myoclonic activity. Genome-wide linkage analysis identified a critical region spanning 12.4 cM between markers D2S2161 and D2S1897 in 2p11.1-q12.2, with a maximum two-point LOD score of 3.46 at Theta 0.0 for marker D2S2175. Multipoint LOD score values, reaching 3.74 around D2S2175, localize the ADCME gene to the centromeric region of chromosome 2. The exclusion of the locus for familial adult myoclonic epilepsy on chromosome 8q23.3-q24 from linkage to our family and the new localization of the responsible gene to chromosome 2cen, together with the different phenotype, define a new epilepsy syndrome. We hypothesize that the responsible gene causes cortical hyperexcitability that is widespread but particularly involves the frontotemporal circuits.

Open trial of risperidone in 24 young children with pervasive developmental disorders.

OBJECTIVE: To describe tolerability and efficacy of risperidone in very young children with pervasive developmental disorders. METHOD: Twenty-four children aged 3.6 to 6.6 years (mean 4.6 years +/- 8 months) enrolled during 1999 and 2000 participated in a 16-week open-label trial with risperidone monotherapy. Outcome measures included the Children's Psychiatric Rating Scale (CPRS), Childhood Autism Rating Scale (CARS), Clinical Global Impression-Improvement (CGI-I), and Children's Global Assessment Scale (C-GAS). RESULTS: Two subjects did not complete the trial because of side effects. The optimal dose was 0.5 mg/day. After the treatment a 21% improvement in CPRS and a 14% improvement in CARS total scores was found. Items related to behavioral control (hyperactivity, fidgetiness, rhythmic motions) and affect regulation (lability of affect, angry affect) improved more than 25%. Based on improvement of at least 25% on the CPRS and a score of 1 or 2 on the CGI-I, eight subjects were considered responders. Functional impairment (C-GAS) improved more than 25%. Thirteen subjects (54%) were free of any side effects; in the other participants risperidone was well tolerated. Only three subjects had a weight gain greater than 10%. CONCLUSIONS: Low-dose risperidone may positively affect symptoms in young autistic children, improving disruptive/hyperactive behavior and affective dysregulation. Further controlled studies in this age group are warranted.

Tourette's syndrome in children: neurobiological issues in pathophysiology.

In recent decades significant advances in the understanding of neurobiological substrates of Tourette's Syndrome (TS) have led to the formulation of hypotheses regarding the ways in which the most salient features of the syndrome may occur. Pathophysiology of TS involves multiple intertwined neurobiological issues in different areas of the Central Nervous System. This review considers neuroimaging studies (MRI, PET, SPECT) in patients with TS. Neurochemical neurophysiological and electrophysiological studies are also reviewed. The role of the neuroendocrine and neuroimmunologic mechanism on pathogenesis of the disease is discussed. Advances in diagnostic techniques (fMRI, mMRI, PET, SPECT) and in neurophysiological research on neurotransmitter systems will allow us to better understand the pathophysiology of TS and to use more specific treatments.

Tourette's syndrome in children: neurological, neuropsychological and psychiatric issues.

The interplay between neurologic, neuropsychologic and psychiatric features makes Tourette's syndrome (TS) a paradigmatic model for neuropsychiatric disorders. The aim of this paper is to review this complex interplay of clinical features. After a survey of some epidemiological studies, the natural history of neurological, behavioral and psychological characteristics of the syndrome is described. The problem of high psychiatric comorbidity, firstly with obsessive-compulsive disorder and attention deficit-hyperactivity disorder, is discussed. Neuropsychological features of TS are considered, as they can negatively affect the quality of life of affected patients. Considerations on treatment, pharmacologic as well as educational and psychotherapeutic, conclude this review.

Emotional and cognitive aspects in adolescence-onset school difficulties.

Learning disorders in adolescence can become a significant risk factor for psychopathology. The paper investigates emotional and cognitive patterns in adolescents with learning disorders. The first part of the study describes the impact of child-onset learning disorders on adolescence passage. In the second part four clinical conditions that can determine adolescence-onset learning disorders are outlined. These are adolescent turmoil, intellectual inhibition, delay in reasoning development and metacognitive dysfunctioning. Cognitive, emotional and behavioral features of these conditions are discussed, in terms of diagnostic and therapeutic implications.

Adolescents with congenital heart disease: psychopathological implications.

The psychopathological risks of congenital heart disease in adolescence are described. The emotional development of adolescents with cardiopathy is discussed, including distortions in body image and separation-individuation issues. The consequences of cyanotic and acyanotic cardiopathies for intellectual functioning are noted, and the impact of congenital heart disease on interactions with parents and siblings is presented. Psychopathological implications of heart transplant are also reviewed.

Psychopathological aspects of cryptorchidism in children and adolescents.

In the male sexual and aggressive drives are mostly centered on the penis, whose real or fantasied features strongly affect the way children and adolescents build up their own personal and gender identity. In some clinical conditions a shift of genital centrality from penis to testicles is evident. The most frequent is abnormality in the descent of testicles, especially cryptorchidism, characterized by an arrested descent of one or two testicles that remain in the abdomen. The aim of this paper is to define mechanisms by which cryptorchidism increases psychological vulnerability. Time of diagnosis and treatment, restoration of genital integrity, personality stability and familial interactions are considered as elements affecting psychopathological outcome. Behavioral and psychological features in children and adolescents with cryptorchidism are reviewed. A case report of an adolescent with unilateral cryptorchidism is reported and discussed, as an example of pubertal distortion in bodily and gender identity.

School failure in early adolescence: the psychopathological risk.

School difficulties and learning disorders in adolescence can become significant risk factors for psychopathology. This study investigates emotional and cognitive patterns in adolescents with school difficulties. Four clinical conditions that can determine adolescence-onset learning disorders are outlined. These are adolescent turmoil, intellectual inhibition, delay in reasoning development, and metacognitive dysfunctioning. Cognitive, emotional and behavioral features of these conditions are discussed in terms of diagnostic and therapeutic implications.

[Psychopathology of chronic diseases in children and adolescents. Congenital cardiopathies]. / Psicopatologia delle malattie croniche in età evolutiva. Le cardiopatie congenite.

A most significant life event in the first years of life is a disease, especially if it is of early onset, severe, life threatening, with an uncertain prognosis, and with the necessity of frequent diagnostic and therapeutic interventions. Psychological implications are a significant parts of the illness, not a marginal component; they can affect prognosis and outcome. The authors describe the different psychological implications of an experience of chronic disease in children and adolescents and their families (parents and siblings). Congenital disease (for example congenital heart failure) has a peculiar significance: since it is diagnosed early, it influences mother-infant interactions from the beginning, in a crucial moment of the infant's psychological development; diagnostic and therapeutical interventions are early and frequent; congenital defects determine the strongest guilt feelings in the parents. Some specific psychological aspects can be described: the weakening of the Bodily self, the inhibition of thinking, the theories the child and the family formulates on the disease, the death feelings. Emotional features in children and adolescents with congenital cardiopathy are described: inhibition of emotions, marked anxiety, depressive reaction, with loneliness, low self-esteem and inadequacy, emotional lability, with oscillation between omnipotence and inadequacy; impulsiveness; weakness of self identity; especially in bodily Self. Some psychopathological aspects in children and adolescents with heart transplant and their families are also described. Intellectual level of patients with congenital heart disease is in the normal range, although significantly lower than normal controls. There is a positive correlation between worsening of intellectual functioning and clinical severity of the heart disease; this clinical severity is related both to restrictions in normal daily life activities, and blood oxygen saturation. It is hard to tease apart the role of early physical limitations versus the role of chronic hypoxia, in affecting intellectual development. Some methodological considerations are described, relating to the role of the physician, the psychological support to the children and adolescents and their families, the problem of the shared-cares between main centres and local hospitals, where primary health-care team operates.

Is interhemispheric transfer time related to age? A developmental study.

In simple visuomotor reaction time tasks, the difference between reaction time (RT) in the uncrossed hand/hemifield condition from RT in the crossed hand/hemifield, known as CUD (crossed-uncrossed difference), has been interpreted as reflecting interhemispheric transmission time (IHTT). Several studies in normal adults have found a CUD of a few milliseconds (3-4), while an abnormally long CUD has been reported in patients who underwent a surgical section of the corpus callosum or in congenital acallosal subjects. The corpus callosum, which is the most important structure for interhemispheric transfer of information, completes its myelination approximately by age ten. It has been hypothesized that the functional maturity of the corpus callosum coincides with the termination of the myelination cycle. No developmental study has focused on the development of IHTT, in relation to callosal maturation. The purpose of our study has been to investigate the development of interhemispheric transfer of visuomotor information in children aged seven to eleven, using a simple RT task with lateralized visual stimuli. The results indicate an age-related decrease of CUD, which we interpret as reflecting the maturation of the corpus callosum during childhood years.

[Neuropsychological development in children with focal brain injury]. / Neuropsicologia delle encefalopatie focali non evolutive dell'infanzia.

The study of children with focal brain injury has important implications from a clinical and theoretical perspective. Clinical data on children with congenital or early acquired lesions indicates that the cognitive sequelae are different from those resulting from similar damage sustained in adulthood. These differences depend in part on the differential effect that damage has on ongoing developmental process and in part on the different recovery capacity of the Central Nervous System of the child. From a theoretical perspective, focal lesion data is important for analyzing the issues of early neuropsychological functioning (especially in terms of early hemispheric specialization) and of plasticity and recovery of function of the CNS. This review analyzes the possible causes of this heterogeneity, that seems in part dependent on the interindividual variability of early neuropsychological organization and in part related to methodological factors such subject inclusion criteria and nature of neuropsychological measures. The review also discusses the role during development of the principal inter and intrahemispheric recovery mechanisms (special attention is given to intrahemispheric mechanisms which have been considered in the past as less determinant with respect to interhemispheric mechanisms). Furthermore, the role of lesion side as a prognostic parameter is discussed, specifically in terms of the evidence of a differential recovery capacity of left hemisphere with respect to the right. Various hypotheses have been put forward as possible interpretations of these data (maturational gradient, different neuropsychological organization of the two hemispheres), yet evidence is still controversial. If one considers the prognostic parameter--age of lesion onset--recent evidence does not confirm the hypothesis that the earlier the lesion, the greatest the recovery of function. Rather, it seems that relating age of lesion onset to other parameters, such as lesion side or size, has a greater and more reliable prognostic value. Another aim of the review is to analyze the effect that focal damage has on the dynamics of development. The fact that the effects of early damage might manifest themselves later in development, when the function in question is reaching a higher level of organization, underlines the importance of a longitudinal approach that assesses the developmental patterns of specific functions. Another issue discussed is the role of lesion side in determining specific cognitive impairment.(ABSTRACT TRUNCATED AT 400 WORDS)

Modulation of event-related potentials (ERPs) by word repetition in a task with inconsistent mapping between repetition and response.

ERPs were recorded during 5 blocks of a continuous recognition memory task. In each block words were shown twice, separated by an average of 6 intervening items, and the task was to respond discriminatively on the basis of whether each word was appearing in that block for the first (first presentations) or the second (second presentations) time. In blocks 2-5, half of the words had also been shown in the immediately preceding block, and half were new to the experiment. Subjects were slower and less accurate at identifying first presentations of words that had appeared in the preceding block, as compared to first presentations of entirely new words. In the latency ranges of the N400 and late positive components, ERPs to words that had previously been presented were more positive-going than were ERPs to new words. These 'across-block' ERP repetition effects were qualitatively very similar to, and additive with, those evoked by words repeated within a block. These findings suggest that the effects of word repetition on ERPs are not dependent on an invariant mapping between repetition and response and are not a consequence of facilitated decision/response processing for repeated items.

[Neonatal hypoxic-ischemic nephropathy and urinary diagnostic indices: the utility of measuring tubular enzymes (NAG and AAP)]. / Nefropatia ipossico-ischemica nel neonato ed indici diagnostici urinari: utilità del dosaggio di enzimi tubulari (NAG ed AAP).

Feto-neonatal hypoxia can cause a functional kidney impairment, which is often temporary and not clinically overt, but sometimes leading to acute renal failure. Hypoxic stress may result in a tubulo-interstitial damage, and kidney tubular enzymes determination has proved to be an easy, early, and non invasive method to define a tubular interstitial lesion. A major target of nephrotoxicity is the proximal tubular cell: alterations in brush-border membrane and cytoplasm result in increased turnover processes in the kidney cortex, following by a corresponding increased excretion of alanine-aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG) from the proximal tubular cells, long before glomerular or tubular functions are impaired. AAP and NAG excretion is directly correlated with the strength and the duration of toxic alteration of the proximal tubule. NAG and AAP have been already studied in the adults and the children; they have been chosen for this investigation with a double aim: 1) to define the amount of their urinary excretion in relation with gestational age at birth; 2) to evaluate if in the newborn, independently of the gestational age, their urinary concentration may be increased by ischaemic conditions caused by hypoxia. We studied 52 healthy newborns (7 preterm of 33-36 weeks and 45 full-term) and 16 newborns with feto-neonatal hypoxia (8 preterm of 26-36 weeks and full-term) at the forth day of life. Urinary NAG and AAP were assayed by colorimetric methods and the results expressed as mU/mg. creatininuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term treatment with thymomodulin reduces airway hyperresponsiveness to methacholine.

We investigated the effect of thymomodulin, a calf thymus acid lysate with immunomodulating activity, on bronchial hyperresponsiveness to methacholine of atopic subjects with asthma. In 16 subjects we measured airway responsiveness at 30, 60, and 90 days after treatment with placebo (eight subjects) or thymomodulin (eight subjects; 80 mg daily orally). The degree of bronchial responsiveness to methacholine was significantly reduced at 90 days during treatment with thymomodulin and remained reduced, even if not significantly, 60 days after cessation of treatment.

Cytogenetic damage in workers exposed to ethylene oxide.

Sister-chromatid exchanges (SECs) and chromosomal aberrations (CAs) were detected in the peripheral lymphocytes of 41 sanitary workers exposed to ethylene oxide (EO) in the sterilizing units of 8 hospitals in the Venice Region. The first group (19 workers) was exposed to 10.7 +/- 4.9 ppm EO, expressed as the time-weighted average concentration for an 8-h working day (TWA/8 h conc.), and the second group (22 workers) to 0.35 +/- 0.12 ppm. Each exposed worker was paired with a control of similar age and smoking habits. A highly significant (P less than 0.001) increase in the mean frequency of SCEs was found in the higher exposure group, 14 (74%) exposed subjects having significantly increased levels of SCEs compared to their matched controls. In the lower exposure group, the increase in mean frequency of SCEs was lower, though still significant (P less than 0.05): 7 (33%) exposed subjects had higher and 1 (5%) had a lower SCE level than the matched controls. From the first group, 10 subjects, 7 of whom had increased SCE levels, were reanalysed 12-18 months after their exposure had been lowered or interrupted: in only 2 of them the SCE level was significantly decreased. A statistically significant correlation between SCE frequency and level of EO exposure (TWA/8 h conc.), as well as a multiple correlation between SCE level and EO exposure, smoking and age were found. However, no interaction could be detected between EO exposure and smoking in the induction of SCEs. In controls, SCE frequency was correlated with smoking and age. In the higher exposure group, the number of both chromatid- and chromosome-type aberrations, independent of gaps, was significantly increased, whereas in the lower exposure group only the frequency of chromosome-type aberrations, excluding gaps, was statistically higher than in controls. The level of CAs remained to a great extent unchanged in the 10 subjects re-examined at a later stage after lowering or halting exposure. Taking the group as a whole, the frequency of cells with total CAs was found to be weakly (P = 0.05) correlated with EO exposure, and was not correlated with smoking, age or SCE frequency.

A cytogenetic study on workers exposed to low concentrations of benzene.

A cytogenetic study was performed on 22 healthy workers engaged in benzene production and exposed to low concentrations of benzene, ranging from 0.2 to 12.4 p.p.m. (threshold limit value 10 p.p.m.). Workers were divided into two groups according to the different levels of exposure, inferrable also from the concentration of benzene in the alveolar air and the levels of urinary phenols. Each exposed subject was paired with a suitable control, living in the same area and of similar smoking habits and age. No statistically significant increase of sister chromatid exchange (SCE) frequency was observed in the exposed groups. In controls, SCE frequency was positively correlated with age and smoking habits. Among structural chromosomal aberrations, only the chromosome-type ones were significantly higher in exposed than in control subjects, and their increase was still significant when gaps were discarded.