Showing papers in "Journal of Child Neurology in 2006"

Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis.

Abstract: The evidence base for the efficacy of the ketogenic diet was assessed among pediatric epileptic patients by application of a rigorous statistical meta-analysis. Nineteen studies from 392 abstracts met the inclusion criteria. The sample size was 1084 patients (mean age at initiation 5.78 +/- 3.43 years). The pooled odds ratio, using a random effects model, of treatment success (> 50% seizure reduction) among patients staying on the diet relative to those discontinuing the diet was 2.25 (95% confidence interval = 1.69-2.98). The reasons for diet discontinuation included 50% seizure reduction within 3 months tend to remain on the diet longer. Although no class I or II studies have been published regarding the efficacy of the ketogenic diet, this meta-analysis shows that current observational studies reporting on the therapeutic effect of the ketogenic diet contain valuable statistical data. Future observational studies should aim for long-term follow-up, patient dropout analysis, and improved seizure type characterization.

Fetal testosterone and sex differences in typical social development and in autism

Abstract: Experiments in animals leave no doubt that androgens, including testosterone, produced by the testes in fetal and/or neonatal life act on the brain to induce sex differences in neural structure and function. In human beings, there is evidence supporting a female superiority in the ability to read nonverbal signals, specific language-related skills, and theory of mind. Even more striking than the sex differences seen in the typical population is the elevated occurrence of social and communicative difficulties in human males. One such condition, autism, occurs four times more frequently in boys than in girls. Recently, a novel theory known as the "extreme male brain" has been proposed. It suggests that the behaviors seen in autism are an exaggeration of typical sex differences and that exposure to high levels of prenatal testosterone might be a risk factor. In this article, we argue that prenatal and neonatal testosterone exposures are strong candidates for having a causal role in sexual dimorphism in human behavior, including social development, and as risk factors for conditions characterized by social impairments, particularly autism spectrum conditions.

Tourette syndrome : The self under siege

Abstract: Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.

Intensive Pediatric Constraint-Induced Therapy for Children With Cerebral Palsy: Randomized, Controlled, Crossover Trial

Abstract: A randomized crossover trial of a new form of pediatric rehabilitation was conducted with 18 children with hemiparesis. Half were randomly assigned to receive pediatric constraint-induced therapy involving constraint of the functional upper extremity and intensive therapy with the hemiparetic upper extremity. Controls received conventional physical and occupational therapy and then were crossed over to receive pediatric constraint-induced therapy. Pediatric constraint-induced therapy produced significantly greater gains than conventional rehabilitation services.

Risperidone in children with autism: randomized, placebo-controlled, double-blind study.

Abstract: Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Children's Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated.

Brief review of habit reversal training for Tourette syndrome.

Abstract: It is well established that Tourette syndrome has a neurobiologic origin. Although pharmacotherapy is the most commonly prescribed intervention, there is considerable evidence to support the use of behavior therapy, specifically habit reversal training, as an alternative or adjunct treatment for some individuals with Tourette syndrome. Unfortunately, many professionals are unfamiliar with habit reversal training. The purpose of this review is to provide readers with a brief review of empiric studies on habit reversal training, update readers on the current state and future of behavior therapy for Tourette syndrome, and provide resources for those readers interested in additional information.

Developmental Regression and Mitochondrial Dysfunction in a Child With Autism

Abstract: Autistic spectrum disorders can be associated with mitochondrial dysfunction. We present a singleton case of developmental regression and oxidative phosphorylation disorder in a 19-month-old girl. Subtle abnormalities in the serum creatine kinase level, aspartate aminotransferase, and serum bicarbonate led us to perform a muscle biopsy, which showed type I myofiber atrophy, increased lipid content, and reduced cytochrome c oxidase activity. There were marked reductions in enzymatic activities for complex I and III. Complex IV (cytochrome c oxidase) activity was near the 5% confidence level. To determine the frequency of routine laboratory abnormalities in similar patients, we performed a retrospective study including 159 patients with autism (Diagnostic and Statistical Manual of Mental Disorders-IV and Childhood Autism Rating Scale) not previously diagnosed with metabolic disorders and 94 age-matched controls with other neurologic disorders. Aspartate aminotransferase was elevated in 38% of patients with autism compared with 15% of controls (P <.0001). The serum creatine kinase level also was abnormally elevated in 22 (47%) of 47 patients with autism. These data suggest that further metabolic evaluation is indicated in autistic patients and that defects of oxidative phosphorylation might be prevalent.

Interrater Reliability of Modified Ashworth Scale and Modified Tardieu Scale in Children With Spastic Cerebral Palsy

Abstract: Resistance to passive movement in children with spastic cerebral palsy was assessed by two raters using the Modified Ashworth Scale and the Modified Tardieu Scale. Four muscle groups in the lower limbs were tested using a standardized procedure. Interrater reliability of the scales was evaluated by the intraclass correlation coefficient. Seventeen children, with a mean age of 7 years 9 months, were included. Two children were rated twice. The intraclass correlation coefficients of both scales were low and did not reach the acceptable limit of 0.75. Caution should be used when these scales are applied.

Craniocervical Arterial Dissection in Children: Clinical and Radiographic Presentation and Outcome:

Abstract: Craniocervical arterial dissection is a recognized cause of arterial ischemic stroke in children. Whether children with craniocervical arterial dissection have dissection characteristics different from those of adults is unclear. A retrospective review of children, 1 month to 18 years of age, with dissection from two Canadian pediatric ischemic stroke registry centers was conducted. From 213 patients with arterial ischemic stroke, 16 (7.5%) were identified with dissection, 37.5% had warning symptoms, and 50% had a history of head or neck trauma. The clinical presentation included headache (44%), altered consciousness (25%), seizures (12.5%), and focal deficits (87.5%). Dissection involved extracranial vessels in 75% and anterior circulation in 56%. Follow-up included complete recovery in 43%, mild to moderate deficits in 44%, and severe deficits in 13%. Fourteen (87.5%) children received antithrombotic treatment. Follow-up angiography showed resolution of abnormalities in 60% of vessels. Total occlusion had the worst outcome for recanalization. In conclusion, the etiology of arterial dissection in the majority of children appears to be either trauma or idiopathic. Long-term angiography shows variable outcomes, depending on the initial findings. The relationship of angiographic outcomes with recurrent strokes requires further study in pediatric dissection. (J Child Neurol 2006;21:8-16).

Association between amygdala volume and anxiety level: magnetic resonance imaging (MRI) study in autistic children.

Abstract: Our objective was to evaluate brain-behavior relationships between amygdala volume and anxious/depressed scores on the Child Behavior Checklist in a well-characterized population of autistic children Volumes for the amygdala, hippocampus, and whole brain were obtained from three-dimensional magnetic resonance images (MRIs) captured from 42 children who met the criteria for autistic disorder Anxious/depressed symptoms were assessed in these children by the Anxious/Depressed subscale of the Child Behavior Checklist To investigate the association between anxious/depressed scores on the Child Behavior Checklist and amygdala volume, data were analyzed using linear regression methods with Pearson correlation coefficients A multivariate model was used to adjust for potential covariates associated with amygdala volume, including age at MRI and total brain size We found that anxious/depressed symptoms were significantly correlated with increased total amygdala volume (r = 386, P = 012) and right amygdala volume (r = 469, P = 002) The correlation between anxious/depressed symptoms and left amygdala volume did not reach statistical significance (r = 249, P = 112) Child Behavior Checklist anxious/depressed scores were found to be a significant predictor of amygdala total (P = 014) and right amygdala (P = 002) volumes In conclusion, we have identified a significant brain-behavior relationship between amygdala volume and anxious/depressed scores on the Child Behavior Checklist in our autistic cohort This specific relationship has not been reported in autism However, the existing literature on human psychiatry and behavior supports our reported evidence for a neurobiologic relationship between symptoms of anxiety and depression with amygdala structure and function Our results highlight the importance of characterizing comorbid psychiatric symptomatology in autism The abundance of inconsistent findings in the published literature on autism might reflect differences between study populations regarding age at MRI, level of impairment within autistic subjects, and underlying anxiety level in the selected study groups

Pediatric Epstein-Barr virus-associated encephalitis: 10-year review.

Abstract: Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. Since 1994, The Hospital for Sick Children has maintained a prospective registry of all children admitted with acute encephalitis. This report summarizes all cases of Epstein-Barr virus-associated encephalitis compiled from 1994 to 2003. Twenty-one (6%) of 216 children, median age 13 years (range 3-17 years), in the Encephalitis Registry were identified as having evidence of Epstein-Barr virus infection. This evidence consisted of convincing Epstein-Barr virus serology and/or positive cerebrospinal fluid polymerase chain reaction (PCR). One patient had symptoms of classic infectious mononucleosis; all others had a nonspecific prodrome, including fever (n = 17; 81%) and headache (n = 14; 66%). Slightly less than half (n = 10; 48%) had seizures and often had electroencephalograms showing a slow background (n = 12; 57%). Many demonstrated cerebrospinal fluid pleocytosis (n = 17; 81%), and 71% (n = 15) had abnormal magnetic resonance imaging findings. Two patients died, 2 suffered mild deficits, and 16 were neurologically normal at follow-up. Most patients with Epstein-Barr virus encephalitis do not show typical symptoms of infectious mononucleosis. Establishing a diagnosis of Epstein-Barr virus encephalitis can be difficult, and, consequently, a combination of serologic and molecular techniques should be used when investigating a child with acute encephalitis. Most children make full recoveries, but residual neurologic sequelae and even death can and do occur.

High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression.

Abstract: Autism is characterized by restricted, repetitive behaviors and impairment in socialization and communication. Although no neuropathologic substrate underlying autism has been found, the findings of brain overgrowth via neuroimaging studies and increased levels of brain-derived neurotrophic factor (BDNF) in neuropathologic and blood studies favor an anabolic state. We examined acetylcholinesterase, plasma neuronal proteins, secreted beta-amyloid precursor protein (APP), and amyloid-beta 40 and amyloid-beta 42 peptides in children with and without autism. Children with severe autism and aggression expressed secreted beta-amyloid precursor protein at two or more times the levels of children without autism and up to four times more than children with mild autism. There was a trend for children with autism to show higher levels of secreted beta-amyloid precursor protein and nonamyloidogenic secreted beta-amyloid precursor protein and lower levels of amyloid-beta 40 compared with controls. This favors an increased alpha-secretase pathway in autism (anabolic), opposite to what is seen in Alzheimer disease. Additionally, a complex relationship between age, acetylcholinesterase, and plasma neuronal markers was found.

Clinical characteristics of childhood-onset (juvenile) Huntington disease: report of 12 patients and review of the literature.

Abstract: Whereas adult-onset Huntington disease is a well-characterized clinical entity, childhood-onset cases have not received as much attention. In this report, the clinical, demographic, and genetic characteristics in 12 patients with childhood-onset Huntington disease are presented and compared with data in the literature. The patients were divided into two groups based on age at onset of symptoms ( or = 10 years old). The majority of patients had onset of symptoms before 10 years of age and most at or below 5 years of age. The delay in diagnosis was longer in those with earlier onset of symptoms. Inheritance was paternal in all patients with onset beyond 10 years of age. We found a preponderance of male patients in the younger age at onset group and of female patients in the older age at onset group. The most frequent heralding symptom was cognitive decline in the group with earlier onset and oropharyngeal dysfunction in the later-onset group. Seizures occurred only in the younger age at onset group. Chorea was not a presenting sign but developed later in the course of the disease and, with dystonia, was more prevalent in the early age at onset group, whereas rigidity and bradykinesia were more prevalent in the older age at onset group. Patients in both groups developed gait, cognitive, and behavioral disorders at some point during the course of the disease. Furthermore, a slow and steady decline in IQ was observed on serial neuropsychologic testing in patients from both groups. Imaging studies were normal early and most commonly revealed neostriatal atrophy later in the course of the disease. In this report, we describe the characteristics of 12 patients with childhood-onset Huntington disease and review those previously reported, expanding our knowledge about the features of childhood-onset Huntington disease, underlining the differences with patients with adult-onset Huntington disease, and suggesting a differential phenotype within patients with childhood-onset Huntington disease depending on the age at onset.

Tic Disorders: Neural Circuits, Neurochemistry, and Neuroimmunology

Abstract: The neuroanatomy and neurochemistry underlying tic disorders are thought to involve corticostriatothalamocortical circuits and dysregulation of their component neurotransmitter systems. Tourette syndrome is a tic disorder that begins in childhood and follows a waxing and waning course of tic severity. Although it is generally believed to have a genetic component, its etiology has not been fully elucidated. The clinical entity pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) has led some to suggest that the pathophysiology of tics in some individuals might involve a postinfectious autoimmune component. We review the neural circuits and neurochemistry of Tourette syndrome and evaluate the evidence for and against a role for autoimmunity in the expression of tics.

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

Abstract: Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31(1/2) years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the premature aging, but why patients with mutations in xeroderma pigmentosum genes present with the Cockayne syndrome phenotype is still not known.

Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury

Abstract: Periventricular white-matter injury is the major form of brain injury associated with prematurity and the leading cause of cerebral palsy in survivors of premature birth. Progress in understanding the pathogenesis of periventricular white-matter injury requires the development of animal models that are relevant to the unique physiology of the preterm human brain and that replicate the major neuropathologic features of human injury. The sheep is the most extensively studied true fetal preparation. The neurodevelopment of the preterm sheep fetus (0.65 gestation) is comparable to that of the preterm human between approximately 24 and 28 weeks. The size of the fetal sheep permits chronic instrumentation so that well-defined insults can be studied with reliable measurements of blood flow and metabolism in cerebral white-matter. We review here recent developments in the understanding of the role of cerebral hypoxia-ischemia and vulnerable oligodendrocyte progenitors in the pathogenesis of periventricular white-matter injury in the immature sheep fetus. We focus on recent developments in high-resolution spatially defined cerebral blood flow measurements in utero. We determined ovine white-matter maturation between 90 and 120 days' gestation, as defined by immunohistochemical localization of oligodendrocyte lineage-specific antibodies. There was considerable spatial and temporal heterogeneity in oligodendrocyte maturation in the immature periventricular white-matter. Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided with that of the preterm human during the high-risk period for white-matter injury. Hence, the immature state of the 90- to 105-day fetal periventricular white-matter is an optimal and dynamic developmental window to study the role of cellular-maturational factors in the pathogenesis of white-matter injury. We conclude with a review of the significant advantages of the instrumented fetal sheep to accelerate progress in the translation of preventive therapies for periventricular white-matter injury and cerebral palsy.

Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates.

Abstract: We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [18F]fluorodeoxyglucose (FDG) and α-[11C]methyl-L-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 ± 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 ± 0.10) and increased (1.04 ± 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning...

Safety of high-dose botulinum toxin type A therapy for the treatment of pediatric spasticity.

Abstract: This retrospective chart review examines the safety of high-dose (> or = 15 U/kg body weight or > or = 800 total units) botulinum toxin type A (BOTOX, Allergan Inc., Irvine, CA) in children and young adults with spasticity. Ninety-four children weighing or = 45 kg received a mean total dose of 927.3 U or 15.2 U/kg. Adverse events were reported by 3 of the 108 patients (2.8%) and included single instances of rash and enuresis. The only serious adverse event consisted of mild, generalized botulism in a 13-year-old patient who received a 23 U/kg dose to the hamstrings and gastrocnemius/soleus bilaterally. No serious adverse events were noted in children weighing or = 45 kg who received total doses of 800 to 1200 U in a single injection protocol. High-dose botulinum toxin type A is safe for the treatment of spasticity in children and young adults.

Corpus callosum size and neuropsychologic impairment in adolescents who were born preterm.

Abstract: Prematurity is associated with cerebral abnormalities that might account for poorer cognitive performance. The aim of our study was to investigate the correlations between corpus callosum reductions and neuropsychologic performance in adolescents who were born preterm. Twenty-five subjects born before 33 weeks' gestation were compared with 25 subjects born at term and of similar age, gender, and sociocultural status. All subjects underwent magnetic resonance imaging and neuropsychologic examinations. Premature subjects performed worse than controls in global cognitive functioning, verbal memory, and verbal fluency. Corpus callosum measurements showed a global reduction owing mainly to thinning in the splenium, posterior midbody, and genu. Corpus callosum size significantly correlated with gestational age, Wechsler Performance IQ, and memory performance. These results suggest that cerebral growth during infancy does not compensate for corpus callosum reduction and that this reduction reflects neuropsychologic deficit. The cognitive impairment can arise from the paucity of the complex interneuronal connections owing to fiber damage, particularly myelinated fibers.

Behavioral and Emotional Problems in Children With Epilepsy

Abstract: The principal purpose of this study was to assess behavioral and emotional problems in children with epilepsy to investigate if specific behavioral and emotional problems are associated with specific medical epilepsy-related factors. The Child Behavior Checklist (CBCL) was used to assess parent-reported behavioral and emotional problems in 108 5- to 18-year-old children with various epilepsy syndromes. Specific medical epilepsy-related factors, such as etiology, age at onset, seizure symptoms, prognosis, seizure frequency, electroencephalography (EEG), and anticonvulsive therapy, were recorded during a regular follow-up examination in our pediatric outpatient epilepsy clinic, and 22.2% of our patients showed moderate to severe behavioral or emotional problems as measured by the Child Behavior Checklist total score. Higher Child Behavior Checklist scores were associated with such specific medical epilepsy-related factors as etiology, age at onset, and polypharmacy. Higher scores on the Social Problem scale were associated with symptomatic epilepsy syndromes and an earlier age at onset. Higher scores on the Social Problems, Attention Problems, and Aggressive Behavior scales were associated with anticonvulsive polytherapy. There were no statistically significant associations between the Child Behavior Checklist scores and seizure symptoms and frequency and EEG at the time of evaluation. The demonstrated frequency of behavioral and emotional problems in children with epilepsy suggests the necessity to address psychosocial issues during the course of clinical treatment.

Treatment of Children and Adolescents With Tics and Tourette Syndrome

Abstract: Tics, patterned movements distinct from stereotypies, myoclonus, and other hyperkinetic movements, are quite common in children, particularly among those with developmental and psychiatric disorders. Thus, tics can indicate the presence of atypical neurodevelopment or broader difficulties with cognition or mood. Tics are also the cardinal feature of Tourette syndrome, a childhood-onset neurobehavioral disorder characterized by a chronic inability to suppress or an urge to perform patterned, repetitive movements. Patients with Tourette syndrome most commonly have, in addition to tics, symptoms of inattention, hyperactivity, obsessiveness, or anxiety. Achieving the most effective treatment of a child with tics is contingent on proper diagnosis of the movement disorder and thorough assessment for other problems, followed by consideration of both nonpharmacologic and pharmacologic interventions for any and all symptoms interfering with the child's function and quality of life. This review focuses primarily on the diagnosis and medical treatment of tics in children and adolescents with Tourette syndrome.

Co-occurring psychiatric disorders in children and adolescents with Tourette syndrome.

Abstract: More than half of all children and adolescents with Tourette syndrome show evidence of psychiatric comorbidity, exhibiting symptoms of attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, and other anxiety and mood disorders. Although the prevalence of co-occurring conditions varies depending on the clinical setting, it is crucial for clinicians to be familiar with these disorders because they are often more impairing than tics and can influence the initial treatment choice. Left untreated, these conditions can negatively affect important developmental outcomes, such as academic and social functioning. We review the most common co-occurring disorders, the relationship of these co-occurring disorders to Tourette syndrome, and treatment recommendations for co-occurring conditions when tic symptoms are present.

Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls.

Abstract: Altered brain creatine-phosphocreatine levels might reflect changes in brain energy use and have been implicated in the pathogenesis of obsessive-compulsive disorder and major depressive disorder. We used proton magnetic resonance spectroscopy to measure absolute concentrations of creatine-phosphocreatine in the right and left medial thalami in 18 pediatric patients with major depressive disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were psychotropic drug naive and were not comorbid for the diagnosis of the comparison group. We found significantly increased left and right medial thalamic creatine-phosphocreatine concentrations in patients with obsessive-compulsive disorder compared with both healthy controls and patients with major depression. Creatine-phosphocreatine concentrations did not differ significantly between patients with major depression and healthy controls. Our data suggest that increased medial thalamic creatine-phosphocreatine concentrations in patients with untreated obsessive-compulsive disorder reflect altered energy use in the medial thalamus and might differentiate patients with obsessive-compulsive disorder from healthy controls and patients with major depression. Although these results must be considered preliminary, further study of the diagnostic specificity of creatine-phosphocreatine in obsessive-compulsive disorder is indicated.

Study of the relationship between tuberous sclerosis complex and autistic disorder.

Abstract: There has been increasing awareness that there are behavioral phenotypes in tuberous sclerosis complex with neuropsychiatric symptom complex such as autistic disorder and attention-deficit hyperactivity disorder (ADHD). However, the neurobiologic basis of autistic disorder in tuberous sclerosis complex is still unknown. We studied two cohorts of children followed up since 1986 until 2003, one cohort with tuberous sclerosis complex and another cohort with autistic disorder, to determine the incidence of autistic disorder in tuberous sclerosis complex and the incidence of tuberous sclerosis complex in autistic disorder respectively. We established a Tuberous Sclerosis Complex Registry in 1985 at the University of Hong Kong. In 2004, 44 index cases (the male to female ratio was 0.75:1) were registered. Three had a positive family history of tuberous sclerosis complex. Thus, the total number of tuberous sclerosis complex cases was 47. We adopted the diagnostic criteria of tuberous sclerosis complex for case ascertainment. The period prevalence rate of tuberous sclerosis complex for children and adolescents aged < 20 years is 3.5 per 10,000 (on Hong Kong island, excluding the eastern region with 125,100 aged < 20 years in 2003). Of 44 cases with tuberous sclerosis complex, 7 had autistic disorder. Thus, the incidence of autistic disorder in tuberous sclerosis complex is 16%. During the 17-year period (1986-2003), we collected a database of 753 children (668 boys and 84 girls; male to female ratio 8:1) with autistic disorder and pervasive developmental disorders. For all children with autistic disorder or pervasive developmental disorders, we routinely examined for any features of tuberous sclerosis complex by looking for neurocutaneous markers such as depigmented spots, which appear in 50% of children with tuberous sclerosis complex by the age of 2 years. For those with infantile spasm or epilepsy, the clinical features of tuberous sclerosis complex were monitored regularly during follow-up. Of these, seven had tuberous sclerosis complex. Thus, the incidence of tuberous sclerosis complex in autistic disorder is 0.9%. All of these children are mentally retarded, with moderate to severe grades in an intellectual assessment conducted by a clinical psychologist. Future studies should be directed toward looking at the various behavioral phenotypes in tuberous sclerosis complex and defining these with standardized criteria to look for any real association with the underlying genetic mutation of TSC1 or TSC2 gene or even the site of tubers in the brain.

Systemic and Ocular Findings in 100 Patients With Optic Nerve Hypoplasia

Abstract: To describe associated ocular, neurologic, and systemic findings in a population of children with optic nerve hypoplasia, a retrospective chart review of 100 patients with optic nerve hypoplasia for the presence of neurologic, radiologic, and endocrine abnormalities was performed. Neuroimaging and endocrine studies were obtained in 65 cases. Visual acuity and associated ocular, neurologic, endocrine, systemic, and structural brain abnormalities were recorded. Seventy-five percent had bilateral optic nerve hypoplasia. Conditions previously associated with optic nerve hypoplasia and present in our patients include premature birth in 21%, fetal alcohol syndrome in 9%, maternal diabetes in 6%, and endocrine abnormalities in 6%. Developmental delay was present in 32%, cerebral palsy in 13%, and seizures in 12%. Of those imaged, 60% had an abnormal study. Neuroimaging showed abnormalities in ventricles or white- or gray-matter development in 29 patients, septo-optic dysplasia in 10, hydrocephalus in 10, and corpus callosum abnormalities in 8. There was an associated clinical neurologic abnormality in 57% of patients with bilateral optic nerve hypoplasia and in 32% of patients with unilateral optic nerve hypoplasia. Patients with unilateral and bilateral optic nerve hypoplasia frequently have a wide range and common occurrence of concomitant neurologic, endocrine, and systemic abnormalities.

Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes

Abstract: We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

Intractable intracranial tuberculous infection responsive to thalidomide: report of four cases.

Abstract: Paradoxical enlargement and development of new intracranial tuberculomas and tuberculous brain abscesses on adequate antituberculosis treatment are well recognized and supposedly cytokine mediated. These lesions are often unresponsive to conventional antituberculosis treatment, corticosteroids, and surgery. We therefore assessed the effect of adjunctive thalidomide, a tumor necrosis factor alpha-modulating drug, in intractable intracranial tuberculosis that did not respond to standard medical and surgical therapy. Four consecutive children (three children with bacteriologic proof and one child with clinical evidence of intracranial tuberculosis) were studied. Three patients each had a giant tuberculous abscess, and the fourth had chronic basal arachnoiditis with progressive loss of vision. Three of the four patients had relentless neurologic deterioration, and all showed disease progression on neuroimaging despite full medical and appropriate surgical treatment. Marked clinical and neuroradiologic improvement occurred after thalidomide was added to the antituberculosis treatment regimen of these four patients. Adjunctive thalidomide might have a role in the management of intractable intracranial tuberculosis and needs further investigation in this regard.

Behavioral Therapy for Treatment of Stereotypic Movements in Nonautistic Children

Abstract: Although typically described in autistic, mentally retarded, and sensory-deprived individuals, motor stereotypies also occur in normal children In this preliminary report, the behavior modification techniques of habit reversal and differential reinforcement of other behavior were evaluated as a therapeutic modality for the suppression of stereotypic movements in nonautistic subjects Twelve children, ages 6 to 14 years, with physiologic stereotypies were treated using a standardized treatment protocol Clinical outcomes were based on differences between assessments obtained at baseline and on telephone follow-up Evaluation scales included measures of the frequency, intensity, interference, and number of stereotypies (Stereotypy Severity Scale motor portion and Stereotypy Linear Analog Scale) and assessment of global function (Child Global Assessment Scale and Stereotypy Severity Scale global portion) The results were correlated with the child's level of motivation and the number of treatment sessions After a mean follow-up of 121 months, motor stereotypies showed significant improvement on the Stereotypy Linear Analog Scale and Stereotypy Severity Scale total score, P = 009 and P = 046, respectively Both scales showed a relationship between the number of treatment sessions attended and a reduction in movements The Child Global Assessment Scale also improved with therapy, but there was no correlation with the number of treatment sessions Highly motivated patients had greater improvement on the Stereotypy Linear Analog Scale and Stereotypy Severity Scale scales compared with less motivated patients, but motivation had no impact on the Child Global Assessment Scale The combined use of habit reversal and differential reinforcement of other behavior is beneficial in reducing motor stereotypies in nonautistic children

Randomized trial of parent management training in children with tic disorders and disruptive behavior.

Abstract: Oppositional, defiant, and disruptive behaviors are common in clinical samples of children with tic disorders. In this study, we sought to evaluate the short-term efficacy of a structured parent tr...

Predictors of scoliosis in Rett syndrome.

Abstract: Scoliosis is a common clinical manifestation of Rett syndrome, a neurodevelopmental disorder that almost exclusively affects girls. Following apparently normal development, these girls typically regress and lose previously attained cognitive, social, and motor skills. Severe intellectual and physical disabilities remain throughout life. Mutations in the methyl-CpG-binding protein 2 gene, MECP2, are detected in approximately 80% of cases and are associated with phenotypic variability. Population-based data on Australian cases were used to study the association between early developmental and genetic factors and the onset of scoliosis. The median age at scoliosis onset was 9.80 years, and three quarters of subjects had developed scoliosis by 13 years of age. Children with compromised early development before 6 months, those who were less mobile at 10 months, and those who never walked were more likely to have an earlier onset of scoliosis. When seven common point mutations and large genomic and C-terminal deletions were compared, the R294X mutation appeared to provide some protective effect against the development of scoliosis.