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.

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.

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.

Number development and developmental dyscalculia.

There is a growing consensus that the neuropsychological underpinnings of developmental dyscalculia (DD) are a genetically determined disorder of 'number sense', a term denoting the ability to represent and manipulate numerical magnitude nonverbally on an internal number line. However, this spatially-oriented number line develops during elementary school and requires additional cognitive components including working memory and number symbolization (language). Thus, there may be children with familial-genetic DD with deficits limited to number sense and others with DD and comorbidities such as language delay, dyslexia, or attention-deficit-hyperactivity disorder. This duality is supported by epidemiological data indicating that two-thirds of children with DD have comorbid conditions while one-third have pure DD. Clinically, they differ according to their profile of arithmetic difficulties. fMRI studies indicate that parietal areas (important for number functions), and frontal regions (dominant for executive working memory and attention functions), are under-activated in children with DD. A four-step developmental model that allows prediction of different pathways for DD is presented. The core-system representation of numerical magnitude (cardinality; step 1) provides the meaning of 'number', a precondition to acquiring linguistic (step 2), and Arabic (step 3) number symbols, while a growing working memory enables neuroplastic development of an expanding mental number line during school years (step 4). Therapeutic and educational interventions can be drawn from this model.

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.

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.

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.

The impact of sex and subtypes on cognitive and psychosocial aspects of ADHD.

We compared the effect of sex and attention-deficit-hyperactivity disorder (ADHD) subtyping in groups of females and males. One hundred and one females with ADHD (mean age 10y 4mo [SD 2y 8mo]; range 5y-18y) were classified according to subtype by Diagnostic and Statistical Manual of Mental Disorders (4th edn) criteria (inattentive [ADHD-I]; combined [ADHD-C]) and balanced by subtype to 101 males (mean age 10y 5mo [SD 2y 9mo]; range 5y 4mo-17y 6mo). All children underwent IQ and reading assessment, and 109 underwent the continuous performance task (Test Of Variables of Attention [TOVA]). Parents completed the Conners' Abbreviated Rating Scale (ABRS), the Child Behavior Checklist (CBCL), learning disability questionnaires, and reported use and efficacy of methylphenidate. Teachers completed the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale. Sex differences were found only on the CBCL; females were more impaired on the attention (p<0.001) and somatization (p=0.028) subscales but not for IQ, other questionnaires, TOVA scores, methylphenidate treatment, or demographics. Females with ADHD-C, but not males, had significantly higher T-scores than females with ADHD-I on social, attention, delinquent, and aggressive behaviours. Regardless of sex, children with ADHD-C had higher scores on all CBCL subscales (p=0.047), ABRS (p<0.001), and SKAMP (p=0.03) than children with ADHD-I. The results support the supposition that ADHD in females is the same disorder as in males. ADHD subtyping was the important determinant of ADHD core symptoms; females with ADHD were found to have significant risk of psychopathology.

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.

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.

Developmental dyscalculia: a prospective six-year follow-up.

To determine the natural history of developmental dyscalculia (DC) and factors impacting on its prognosis, we performed a prospective six-year longitudinal study. One hundred and forty children of normal intelligence diagnosed with DC in the fifth grade of elementary school were re-examined for dyscalculia three and six years later, in eighth (n=123) and eleventh (n=104; 41 males, 63 females) grades respectively. Mean age of the children in fifth grade was 11 years 1 month (SD 4 months), in eighth grade 14 years 2 months (SD 1 month), and in eleventh grade 17 years 2 months (SD 5 months). The assessment included standardized arithmetic, reading and writing tests, behavioural rating scales, information on socioeconomic status, educational interventions, and familial learning problems. Participants in eleventh grade were recategorized as having DC if their score on the arithmetic test was not more than the fifth centile for grade. At the six-year follow-up, 99/104 (95%) children diagnosed with dyscalculia in fifth grade were still performing poorly in arithmetic, scoring within the lowest quartile for their grade, and 42/104 (40%) were recategorized with DC. Chronicity of DC was associated with severity of the dyscalculia in fifth grade (p<0.05), lower IQ (p<0.01), inattention (p<0.01), and writing problems (p<0.01). Thus, DC is an enduring specific learning difficulty, persisting into late adolescence in almost half of affected individuals.

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.

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.

Social and emotional adjustment of siblings of children with autism.

BACKGROUND: Social and emotional adjustment of siblings of children with autism was examined, to explore their risk or resilience to effects of genetic liability and environmental factors involved in having a sibling with autism. METHOD: Social-emotional adjustment, behavior problems, socialization skills, and siblings' relationships were compared among 30 siblings of children with autism, 28 siblings of children with mental retardation of unknown genetic etiology (MR), and 30 siblings of children with developmental language disorders (DLD). Groups were matched by probands' gender, siblings' chronological age, gender, IQ, and birth order, and by family size, ethnicity, and parental income, employment, and stress level. RESULTS: Four siblings of children with autism, three siblings of children with MR, and seven siblings of children with DLD received DSM-IV diagnoses. Nevertheless, most of the siblings were well adjusted. CONCLUSIONS: The adjustment of siblings of children with autism is in sharp contrast to the severe social and emotional disabilities characteristic of autism, and is noteworthy considering the stress involved in having a sibling with autism.

Reversible language regression as an adverse effect of topiramate treatment in children.

Profound language regression developed in three children with epilepsy 4 to 28 weeks after beginning topiramate (TPM). TPM was administered as an adjunctive antiepileptic drug at doses of 2.5 to 6.0 mg/kg/day. Language functions recovered while TPM was being reduced in dose or stopped.

Abnormal rhythmic motor response in children with attention-deficit-hyperactivity disorder.

Children with attention-deficit-hyperactivity disorder (ADHD) have difficulties with motor control, inhibition of motor responses, motor flexibility, and motor preparedness. We proposed that motor abnormalities in ADHD might result, at least in part, from an abnormal neuronal oscillatory mechanism necessary for motor temporal regulation. The aim of this study was to assess pacing in children with ADHD, by testing for rhythmic abnormalities of motor activity using a tapping test. Twenty-seven children (21 males, six females; aged 6 to 14 years 6 months; mean age 11 years 4 months, SD 2 years 2 months) diagnosed with ADHD according to DSM-IV clinical criteria, and 33 controls (25 males, eight females; aged 6 to 14 years 6 months; mean 11 years 1 month, SD 2 years 2 months), underwent a finger-tapping test requiring rhythmic responses to frequencies from 1 to 6 Hz. All participants who were treated on a daily basis with methylphenidate (n = 22) were medication-free on the day of the test. Most of the children with ADHD responded at a constant rate regardless of stimulus frequency, a phenomenon only seen in a small number of the controls. This specific error pattern, also seen in Parkinson's disease, has been attributed to an abnormal oscillatory mechanism mediated by dopaminergic fronto-striatal circuitry, which might also be pathophysiologically relevant for ADHD.

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.

Language abilities of siblings of children with autism.

BACKGROUND: Language abilities of siblings of children with autism were examined to explore the possibility that language abilities are behavioral markers specific to the genetic liability for autism, as part of the broader phenotype. METHOD: Language abilities were compared among 27 siblings of children with autism, 23 siblings of children with mental retardation of unknown etiology (MR), and 22 siblings of children with developmental language disorders (DLD). Groups were matched by siblings' age, gender, birth order, family size, ethnicity, family income and by probands' gender and mental age. RESULTS: Siblings of children with autism achieved higher scores than siblings of children with DLD on receptive, expressive, and total language scales of the Children's Evaluation of Language Fundamentals and on verbal IQ. Moreover, within the DLD group, school problems in the domains of reading and arithmetic were more prevalent than within the other two groups. Only 2 siblings of children with autism received clinical diagnoses based on DSM-IV criteria compared to 3 siblings of children with MR and 7 siblings of children with DLD. CONCLUSIONS: After excluding data of the diagnosed siblings, no differences in language abilities could be discerned among the groups, except that more siblings in the DLD group were identified as having language difficulties. In summary, although language deficits characterize autism, siblings of children with autism were not found to demonstrate deficits in language skills assessed by formal language tests, IQ, or academic skills.