Cognitive and psychiatric phenotypes of movement disorders in children: a systematic review.

AIM: The cognitive and psychiatric aspects of adult movement disorders are well established, but specific behavioural profiles for paediatric movement disorders have not been delineated. Knowledge of non-motor phenotypes may guide treatment and determine which symptoms are suggestive of a specific movement disorder and which indicate medication effects. METHOD: The goal of this review is to outline the known cognitive and psychiatric symptoms associated with paediatric movement disorders. We used a systematic approach, via PubMed, and reviewed over 400 abstracts of studies of selected disorders, of which 88 papers reporting paediatric non-motor symptoms are summarized. RESULTS: Obsessive-compulsive disorder was manifest in children with paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and Sydenham chorea. Children with opsoclonus-myoclonus syndrome had, for the most part, cognitive and behavioural problems, and attention-deficit-hyperactivity disorder was reported as a major comorbidity in Tourette syndrome, stereotypies, and restless legs syndrome. Symptoms of depression and anxiety were more frequent in individuals with idiopathic dystonia. Affective disorders were suggestive of Wilson disease. Cognitive decline was common in children with juvenile Huntington disease. A limitation of this review was the lack of systematic assessment in paediatric movement disorders for evaluation and uniform definitions. INTERPRETATION: Although the literature in non-motor phenomena is still emerging, recognition of salient cognitive and psychiatric phenomena may facilitate management of paediatric movement disorders.

Emotional and behavioral characteristics over a six-year period in youths with persistent and nonpersistent dyscalculia.

The authors examined behavior problems in a matched sample of 58 youths with persistent dyscalculia (PD) and nonpersistent dyscalculia (NPD). Participants were classified as having dyscalculia at age 10-11 years. Parents completed the Child Behavior Checklist for their children at ages 10-11, 13-14, and 16-17 years, while the youths did so at the last two age periods. Only at age 16-17 years were there significantly more problems, particularly attention problems and externalizing problems, reported by parents for PD youths compared to NPD youths. A higher percentage in the PD group than in the NPD group received scores in the clinical range for externalizing problems. However, the mean levels of behavior problems at this age and the earlier ages were within the normal range for both groups. For youth-reported problems, the only significant difference was for attention problems at 16-17 years. Therapeutic interventions should focus on the academic domain and improving and altering behavioral patterns.

Parenting style impacts on quality of life in children with cerebral palsy.

OBJECTIVE: To assess the impact of parenting style and disease severity on quality of life (QOL) in children with cerebral palsy (CP). STUDY DESIGN: Thirty-nine children with CP, their siblings, and their parents participated in the study. Probands and siblings, ages 6 to 18 years, completed questionnaires on parenting style (accepting, rejecting, controlling, and autonomy allowing) using the Children's Report of Parental Behavior Inventory. Parents completed generic (Child Health Questionnaire [CHQ]) and disease-specific (Pediatric Outcomes Data Collecting Instrument [PODCI]) QOL questionnaires for both children. A physician determined disease severity with the Gross Motor Function Classification System. RESULTS: In children with CP, parenting style positively correlated with the CHQ scores: physical summary and psychosocial summary (r = 0.40, P = .01) and family activities scale (r = 0.34, P = .03). Autonomy allowing parenting style impacted on psychosocial aspects of QOL, as reflected by CHQ scores, more than the degree of disability. In other domains of QOL, the effect of parenting style was greater than IQ, anxiety, and socioeconomic status. CONCLUSIONS: Parenting style is a significant factor in QOL in CP and the only known factor to impact on the psychosocial domains of the CHQ, exceeding the effect of disease severity. Because QOL is an important treatment goal in children with CP, early family interventions, particularly those focusing on parenting style, should be considered.

ADHD and dysgraphia: underlying mechanisms.

Multiple complaints in the domain of writing are common among children with Attention Deficit Hyperactivity Disorder (ADHD). In this work we sought to characterize the writing disorder by studying dysgraphia in twenty 6th grade boys with ADHD and normal reading skills matched to 20 healthy boys who served as a comparison group. Dysgraphia, defined as deficits in spelling and handwriting, was assessed according to neuropsychological explanatory processes within 3 primary domains: linguistic processing, motor programming and motor kinematics. Children with ADHD made significantly more spelling errors, but showed a unique pattern introducing letter insertions, substitutions, transpositions and omissions. This error type, also known as graphemic buffer errors, can be explained by impaired attention aspects needed for motor planning. Kinematic manifestations of writing deficits were fast, inaccurate and an inefficient written product accompanied by higher levels of axial pen pressure. These results suggest that the spelling errors and writing deficits seen in children with ADHD and normal reading skills stem primarily from non-linguistic deficits, while linguistic factors play a secondary role. Recommendations for remediation include educational interventions, use of word processing and judicious use of psychostimulants.

Neuropsychological functioning of siblings of children with autism, siblings of children with developmental language delay, and siblings of children with mental retardation of unknown genetic etiology.

Neuropsychological functioning of 30 siblings of children with autism (AU-S), 28 siblings of children with mental retardation of (MR-S), and 30 siblings of children with developmental language delay (DLD-S) was compared. Two siblings, both AU-S, received diagnoses of pervasive developmental disorder (PDD). More siblings with cognitive disabilities were found in DLD-S than in AU-S. However, these differences disappeared after excluding diagnosed siblings or after accounting for family membership. In sum, despite the elevated incidence of PDD among AU-S, the neuropsychological functioning of the remaining siblings did not convey specific characteristics related to the genetic risk associated with autism, in contrast to the cognitive functioning of the DLD-S, which did reflect a genetic risk.

Do Prenatal Corticosteroids Affect Brain Maturation of the Premature Infant? An Electroencephalography Study.

OBJECTIVE: To assess whether prenatal treatment with betamethasone has a significant influence on cerebral maturation indices as measured by electroencephalographic (EEG) indices. STUDY DESIGN: Infants born less than 35 weeks postmenstrual age (PMA) were prospectively enrolled if their mother received a full course of bethametasone prior to delivery (study group) or not (control group); infants with major intracranial abnormalities were excluded as well as those who were sedated or needed assisted ventilation. EEG was recorded during the first 10 days of life. Interburst intervals and maximal amplitudes of theta and delta bandwidths were calculated by a signal processing software. A multivariate general linear model was used to analyze the relationship between the 2 groups and the different electrophysiologic parameters, adjusting for PMA and mode of delivery. RESULTS: Thirty-eight infants were included in the study group and 36 in the control group. Univariate analysis demonstrated a negative correlation between PMA at test and EEG indices (interburst interval and delta and theta frequencies). Multivariate analysis demonstrated a less robust correlation of PMA and EEG indices and a positive correlation of prenatal betamethasone treatment with Theta frequencies. Repeating the data analysis separately for each study group, the above results remained significant mainly in the study group. CONCLUSIONS: Our findings suggest a possible stabilization effect of corticosteroids on the central nervous system and a possible delay of the maturation of cerebral activity related to prenatal corticosteroids use. These findings may relate to a better neurodevelopmental outcome of infants treated prenatally with corticosteroids.

Age and medication effects on rhythmic responses in ADHD: possible oscillatory mechanisms?

Voluntary motor responses in children with attention-deficit hyperactivity disorder (ADHD) may reflect underlying neuronal oscillatory mechanisms. The aims of this study were: (1) to corroborate the presence of rhythmic motor abnormalities on tapping test in children with attention-deficit hyperactivity disorder, shown in previous studies; (2) to delineate the characteristics of ADHD children demonstrating these rhythmic abnormalities; (3) to assess the impact of methylphenidate (Ritalin) on this abnormal motor phenomenon. The study was designed in a double blind manner. Sixty-four ADHD children aged 6-12 years and 60 matched controls underwent a finger tapping test (1-5 Hz). We measured the abnormal rhythmic tapping with and without methylphenidate treatment in a double blind design. Conventional statistical analysis was used to assess the correlation of the presence of motor abnormality with various clinical characteristics (such as degree of hyperactivity/impulsivity). Fifty-six percent of children with ADHD compared to 8% of controls demonstrated abnormal rhythmic responses at a mean frequency of 3.1+/-0.9 Hz. These erroneous voluntary movements were more common in children with a greater degree of hyperactivity, in younger children but not significantly altered by methylphenidate treatment. Surprisingly, abnormal rhythmic responses showed less variability than found for responses for which the tapping was adequately paced, suggesting different motor control processes for normal and abnormal paced tapping. We speculate that rhythmic tapping responses reflect abnormal oscillatory mechanisms involved in ADHD, exacerbated in younger children with ADHD and in those in whom the hyperactivity/impulsivity is more pronounced.

Evidence of a developmental cerebello-cerebral disorder.

The objective of this study was to examine the cognitive and neuroanatomical features of an adolescent with developmental hypoplastic left cerebellum who presented with executive and visuo-spatial deficits, nonverbal learning disabilities and interpersonal difficulties. He underwent a neuropsychological assessment, MRI and diffusion tensor imaging MRI. The neuropsychological impairments were primarily in executive functions, spatial and visual perception, graphomotor skills, arithmetic, social perception and comprehension. Fractional anisotropy, which is measured by diffusion tensor imaging and enables assessment of axonal integrity, was reduced in the right cerebral peduncle and right hemisphere white matter (p < 0.001). Based on the results, we hypothesize that disruption of neural circuits linking the hypoplastic left cerebellum to the right hemisphere may contribute to the evolution of a neurocognitive syndrome with characteristics of the developmental right hemisphere syndrome and suggestive of the cerebellar cognitive-affective syndrome.

Retinal function abnormalities in patients treated with vigabatrin.

OBJECTIVE: To evaluate central and peripheral retinal function in patients treated with vigabatrin, an antiepileptic drug associated with peripheral visual field constriction (VFC). METHODS: Six patients with epilepsy treated with vigabatrin as add-on therapy for at least 3 years were included in this observational case series. All patients underwent a clinical ophthalmologic examination, color vision testing, standard perimetry, and full-field and focal foveal cone electroretinography. Four patients, 3 of whom had VFC, completed specialized computerized static light- and dark-adapted perimetry. RESULTS: In 9 of 11 eyes tested, foveal cone electroretinographic amplitudes were at or below the lower limit of normal. Dark-adapted perimetry demonstrated abnormal rod-derived visual fields in the 3 patients with vigabatrin-attributed VFC, whereas rod-derived thresholds were within normal limits throughout the visual field in the patient who did not have VFC. CONCLUSIONS: Our results suggest that vigabatrin not only impairs peripheral cone-derived function as manifested by VFC but also affects foveal cone electroretinographic amplitudes and rod-derived visual fields. The clinical dilemma regarding the use of vigabatrin therapy is further complicated since central as well as peripheral visual function seems to be adversely affected.

Developmental dyscalculia.

Developmental dyscalculia is a specific learning disability affecting the normal acquisition of arithmetic skills. Genetic, neurobiologic, and epidemiologic evidence indicates that dyscalculia, like other learning disabilities, is a brain-based disorder. However, poor teaching and environmental deprivation have also been implicated in its etiology. Because the neural network of both hemispheres comprises the substrate of normal arithmetic skills, dyscalculia can result from dysfunction of either hemisphere, although the left parietotemporal area is of particular significance. The prevalence of developmental dyscalculia is 5 to 6% in the school-aged population and is as common in girls as in boys. Dyscalculia can occur as a consequence of prematurity and low birthweight and is frequently encountered in a variety of neurologic disorders, such as attention-deficit hyperactivity disorder (ADHD), developmental language disorder, epilepsy, and fragile X syndrome. Developmental dyscalculia has proven to be a persisting learning disability, at least for the short term, in about half of affected preteen pupils. Educational interventions for dyscalculia range from rote learning of arithmetic facts to developing strategies for solving arithmetic exercises. The long-term prognosis of dyscalculia and the role of remediation in its outcome are yet to be determined.

Efficacy of methylphenidate in patients with cerebral palsy and attention-deficit hyperactivity disorder (ADHD).

Our objective was to study the short-term efficacy and safety of methylphenidate in patients with the dual diagnosis of cerebral palsy and attention-deficit hyperactivity disorder (ADHD). Twenty-nine patients (8.0 +/- 4.0 years old) with cerebral palsy and ADHD completed the study. In a prospective, crossover, double-blind paradigm, patients were treated with methylphenidate or placebo, each for 4 weeks. Parents and teachers completed a modified Abbreviated Conners' Rating Scale at the beginning of the study and the end of the first and second months of treatment with methylphenidate or placebo. Parents were contacted weekly to report side effects. Methylphenidate treatment, as assessed by teachers' ratings, resulted in a significant improvement in ADHD symptomatology (t = 2.29, df = 27, P < .05); however, a trend for improvement was noted only on the parents' ratings. After the conclusion of the study, 12 patients continued methylphenidate for 20 +/- 10 months. Side effects were minimal, with the exception of transient hallucinations in one patient. In children with cerebral palsy and ADHD, methylphenidate is effective, rendering it a valuable adjunct to their overall medical therapy.

Speed of performance of children with developmental right hemisphere syndrome and with attention-deficit hyperactivity disorder.

Slowness is a common complaint in children with attention-deficit hyperactivity disorder (ADHD) and with developmental right hemisphere syndrome. However, it was our clinical impression that slowness in developmental right hemisphere syndrome was more prominent than in ADHD. Our objective was to assess slowness as operationalized by speed of performance in children with developmental right hemisphere syndrome, children with ADHD, and controls. The research sample comprised 19 children in each group, matched for age, gender, socioeconomic status, IQ, and handedness. The subjects were administered a reaction time battery assessing speed of performance. Overall, the average performance differed among the three study groups (F(2,53) = 2.40, P < .01). Children with developmental right hemisphere syndrome were slower than their peers with ADHD (t(35) = 1.99, P < .05) and slower than controls (t(35) = 4.55, P < .001). Children with ADHD performed more slowly than controls, although for the majority of tasks, this was nonsignificant. We conclude that slowness is an integral and consistent component of developmental right hemisphere syndrome and cannot be attributed only to the ADHD symptomatology.

Use of complementary medicine in children with attention deficit hyperactivity disorder and epilepsy.

We retrospectively studied use of complementary medicine in children with Attention Deficit Hyperactivity Disorder, epilepsy, and controls. Parents of patients with Attention Deficit Hyperactivity Disorder (n = 120; mean age 11.0 +/- 3.1 years), epilepsy (n = 115; 10.9 +/- 5.5), and healthy children seen in the emergency room during an acute illness (n = 115; 5.0 +/- 4.9) were individually interviewed regarding past and present use of complementary medicine. We found that 34 children with Attention Deficit Hyperactivity Disorder, 37 with epilepsy, and 24 controls had, at some time during their life, received complementary medicine: diet (n = 50), homeopathy (n = 46), acupuncture (n = 23), and biofeedback (n = 9). Current use was significantly less: Attention Deficit Hyperactivity Disorder- 7.5%, epilepsy-14%, and controls-7%. No differences among groups were found for either past use or method of complementary medicine employed. However, the most significant predictor for current use of complementary medicine was past use (OR 3.2, P < 0.001), followed by level of father's education (OR = 1.16, P = 0.01). There was a trend for more children with epilepsy (OR = 1.7) and children from religious families (OR = 1.51) to be currently receiving complementary medicine. In summary, only a small minority of patients with either Attention Deficit Hyperactivity Disorder or epilepsy used complementary medicine as part of their current medical regimen, although during their lifetime a third had received complementary medicine. Complementary medicine was more consistently used in children who had previously received complementary medicine, regardless of their medical diagnosis.

Malignant migrating partial seizures in infancy.

Malignant migrating partial seizures in infancy is a rare, age-specific epileptic encephalopathy. It is characterized by onset before age 6 months, virtually continuous multifocal seizures with ictal electrical encephalographic activity shifting from one hemisphere to the other, no identifiable immediate or remote causes, intractability to antiepileptic drugs, and developmental arrest. This report adds two patients to the 21 previously described in the literature. One infant, microcephalic at birth, developed at age 4 months clusters of nearly continuous multifocal seizures with secondary generalization, refractory to antiepileptic drugs. By age 4.5 years she was seizure-free but remains without any cognitive or motor function. Patient 2, born with a normal head circumference, began seizures at age 3 months, never became seizure-free, and died at age 18 months. Electroencephalograms of both children were characteristic, and the neuroimaging finding was one of progressive cortical and subcortical atrophy. It has been hypothesized that neurotransmitter dysfunction with persistent, pronounced excitatory or cytotoxic mechanisms may explain the continuous, erratic epileptic activity. Awareness of malignant migrating partial seizures in infancy and research focused on its pathophysiologic mechanisms may reveal innovative treatments of this devastating, age-specific disorder.

[Visual field disturbances in epileptic patients treated with vigabatrin (sevril)].

Vigabatrin, one of the newer anti-epileptic drugs (AED), whose effect is mediated via elevated levels of brain GABA, has proved to be effective in drug resistant partial seizures and infantile spasms. Recently, visual field constriction was found in up to 30% of adults, whereas information for the pediatric age group is sparse. We examined 24 visually-asymptomatic children, ages 3.5-18 years, treated for 3.01.6 years at doses of 25-90 mg/kg. These children underwent an ophthalmologic examination, visual evoked potentials, electroretinogram and when possible, perimetry. Over half of the children had at least one abnormal test and 11/17, who were able to undergo perimetric studies, had symmetrical, nasal visual field constriction. In view of the gravity and prevalence of visual field constriction, use of the AED vigabatrin should be weighed against its clinical benefits.

Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia.

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders.

Tourette syndrome-associated psychopathology: roles of comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder.

OBJECTIVE: Individuals with Tourette syndrome (TS) often display comorbid symptoms of attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as well as externalizing and internalizing behaviors. This study was aimed to examine the impacts of tic severity, ADHD symptoms, and OCD on internalizing (e.g., anxiety) and externalizing (e.g., aggression) psychopathology. METHODS: Using linear regressions, we examined how tics, ADHD, and OCD symptoms predicted the externalization and internalization behaviors measured by the Child Behavior Checklist in a clinical sample of children and adolescents with TS. In addition, Child Behavior Checklist scales were compared among children with TS without ADHD, TS and ADHD, ADHD without TS, and unaffected control group. RESULTS: In the TS group, externalizing behaviors were predicted by tic severity, inattention, and hyperactivity/impulsivity but not by OCD symptoms, whereas internalizing behaviors were predicted by inattention and OCD symptoms but not by tic severity or hyperactivity/impulsivity. Comparison among different clinical groups revealed main effects of TS and ADHD on both externalizing and internalizing behaviors. CONCLUSION: These findings suggest that tics, ADHD, and OCD symptoms differentially explain the variance in externalizing and internalizing behavioral problems in individuals with TS. In addition, the data support the notion that TS is itself a risk factor for behavioral problems, mandating that children with TS even without ADHD and OCD still need to be assessed and treated for psychopathology.

The utility of a continuous performance test embedded in virtual reality in measuring ADHD-related deficits.

OBJECTIVE: Continuous performance tasks (CPT) are popular in the diagnostic process of Attention Deficit/Hyperactivity Disorder (ADHD), providing an objective measure of attention for a disorder with otherwise subjective criteria. Aims of the study were to: (1) compare the performance of children with ADHD on a CPT embedded within a virtual reality classroom (VR-CPT) to the currently used Test of Variables of Attention (TOVA) CPT, and (2) assess how the VR environment is experienced. METHODS: Thirty-seven boys, 9 to 17 years, with (n = 20) and without ADHD (n = 17) underwent 3 CPT's: VR-CPT, the same CPT without VR (No VR-CPT) and the TOVA. Immediately following CPT, subjects described their subjective experiences on the Short Feedback Questionnaire. Results were analyzed using analysis of variance with repeated measures. RESULTS: Children with ADHD performed poorer on all CPT's. The VR-CPT showed similar effect sizes to the TOVA. Subjective feelings of enjoyment were most positive for VR-CPT. CONCLUSION: The VR-CPT is a sensitive and user-friendly assessment tool to aid diagnosis in ADHD.