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PubMed2004

Epileptic encephalopathies and their relationship to developmental disorders: do spikes cause autism?

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without seizures. Thirty percent of children with PDD have regression of social behavior and language at 2-3 years of age. Some authors speculate that the regression is caused by epileptiform activity even in the absence of overt clinical seizures ("autism with epileptic regression") and suggest that elimination of the epileptiform activity, either medically or surgically, should lead to improvement in behavior. This review examines the data showing that interictal epileptiform discharges are associated with transient clinical dysfunction and discusses the implications of these observations for autistic behavioral abnormalities. The results of resective surgery, vagal nerve stimulation, and multiple subpial transaction on children with autism and epileptiform EEG abnormalities are also discussed. I conclude that there is no evidence that interictal discharges per se cause (or contribute to) the complex behavioral phenotype of autism. There is no justification to support the use of anticonvulsant medication or surgery in children with PDD without seizures; that is, there is no evidence that treatment to eliminate EEG spikes will have a therapeutic effect on the behavioral abnormalities of PDD and autism.

Anticonvulsants↗
PubMed1988

[Health behavior of developmentally disordered students--or the need for cooperation between teachers and physicians].

Presented are the findings of an examination of 28 students from the secondary school sector, level I, grades 7-9, undertaken at the special school for children with developmental disorders (= behavioural disorders) at the Fritz-Gansberg-Street in Bremen. Results show that the students, who generally speaking not only are known to display socially deviant behaviour but often also suffer from minimal brain dysfunction (MCD) and, occasionally, organic cerebral damage, increasingly "neglect themselves" in a medical sense, in particular relative to uncontrolled consumption of drugs and neglect of their overall physical development. Pertinent special educational problems should therefore not be dealt with within the school alone, but should equally be addressed from a social or even preventive medicine angle. Close cooperation between teachers at special schools and medical doctors should therefore be sought, and possibly introduction of outpatient services at the school or initiation of doctor/school sponsorships.

Adolescent↗
PubMedDate not supplied

Treatment outcome and outcome associations in children with pervasive developmental disorders treated with selective serotonin reuptake inhibitors: a chart review.

PURPOSE: The aim of this study was to determine the outcome and predictors of outcome with selective serotonin reuptake inhibitors (SSRIs) in outpatient children and adolescents with pervasive developmental disorders (PDDs). METHOD: Clinic charts were reviewed for 89 outpatient youths with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of a PDD who were treated with SSRIs. Response was determined using the Clinical Global Impressions (CGI) scale. Side-effect and demographic data, including family history, were recorded. RESULTS: Forty-four point nine percent (44.9%) were determined to be much improved and considered responders. Fifty-four percent (54%) of the subjects demonstrated activation side effects. In 35.4% of these subjects, the activation side effects led to drug discontinuation. Pearson chi-squared and regression analysis demonstrated an association between SSRI response and a family history of PDD. There were no significant associations between clinical variables and activation side effects. CONCLUSIONS: SSRI treatment led to modest response rate in this group of youths with PDDs. Activation side effects were frequent, often leading to treatment dropouts. Potential outcome associations include a family history of PDDs.

Adolescent↗
PubMed1998

Symptoms of pervasive developmental disorders as observed in prediagnostic home videos of infants and toddlers.

OBJECTIVES: The objectives of this study were (1) to show prediagnostic abnormalities in social and communicative behaviors on home videos of children who later received a diagnosis of one of the pervasive developmental disorders (PDD) and (2) to demonstrate that prediagnostic abnormalities in social and communicative behaviors for children with PDD not otherwise specified will be less prominent than those in children with autistic disorder but still distinguishable from those of typically developing peers. STUDY DESIGN: Parents of children with PDD each submitted home videos of social events that were made when their child was between the ages of 12 and 30 months, before diagnosis. Two independent observers, unaware of the subjects' diagnoses or purpose of the study, scored the rates of specific anomalies in social and communicative behavior. Two additional observers scored the percentage of time the children were engaged socially or with objects. Data from the experimental group were compared with those of 25 age-matched children with no developmental disabilities. RESULTS: Significant differences were found between the rates of social engagement and 8 of the 25 specific behaviors of the children in whom PDD was later diagnosed and those of the typical children. The children later given the diagnosis of PDD not otherwise specified had mean frequencies of some social interactions and communicative skills that fell between those of children later given the diagnosis of autistic disorder and those of children with typical development. CONCLUSION: In our sample children in whom PDD was later diagnosed could be differentiated from their typically developing peers on the basis of specific anomalies noted in their social and communicative behaviors, especially joint attention. In our sample children with PDD not otherwise specified could have been further differentiated on the basis of the rates of social interaction. Careful assessment of social interaction and communicative behaviors may help to identify children with PDD before the age of 30 months.

Autistic Disorder↗
PubMed2007

Deregulated Ras signaling in developmental disorders: new tricks for an old dog.

Ras proteins regulate cell proliferation, survival and differentiation and are constitutively activated by somatic point mutations in many cancers. Previous studies of neurofibromatosis type 1 and Noonan syndrome also implicated hyperactive Ras in developmental disorders. Recently, germline mutations in H-RAS and K-RAS and in genes encoding other molecules in the Ras-Raf-MEK-ERK cascade were shown to underlie cases of Noonan, cardio-facio-cutaneous, and Costello syndromes. These disorders share phenotypic traits that include abnormal facial features, heart defects, and impaired growth and development. Many of these germline, disease-associated mutations encode novel Ras, Raf and MEK proteins. These studies underscore a crucial role of Ras signaling in human development.

Germ-Line Mutation↗
PubMed1993

[Karyotyping of fetuses with developmental disorders. A 5-year material 1985-89].

During the period 1985 to 1989 foetal chromosomal analysis was performed in 121 of 318 pregnant women with foetal malformations detected by ultrasound. There were six failures. The percentage of foetuses karyotyped for developmental disorders increased from 13% in 1985 to 62% in 1989. An abnormal chromosomal pattern was found in 28 (24%) of the foetus. The pregnancy was terminated in 86% of cases with abnormal karyotype. The corresponding number in the group with normal chromosomes was 51%. The authors discuss the malformations leading to karyotyping, the methods used for karyotyping, the results of these tests and the consequences for the pregnancies.

Chromosome Aberrations↗
PubMed1996

Children with benign focal sharp waves in the EEG--developmental disorders and epilepsy.

Focal sharp waves (shw) in the childhood EEG with predominantly centrotemporal localization are a diagnostic hallmark of idiopathic partial epilepsy and have been shown to be genetically determined. Absence of neurological and neuropsychological impairment was long considered to be a prerequisite for diagnosis. For years, this diagnostic paradigm obscured the large phenotypic variability of genetically determined focal shw. The purpose of the present review is to survey and critically evaluate the widely dispersed literature on this topic. Two main groups can be distinguished: Idiopathic partial epilepsies and specific developmental disorders such as dysphasia, dyslexia etc. These conditions, however, do not represent clear-cut nosologic entities, but exhibit large symptomatic overlaps. In non-epileptic children, developmental disabilities constitute the main symptoms, in epileptic children-at least in non-selected groups-they are an optional feature. Conversely, epileptic phenomena can dominate the clinical picture or be an optional symptom in developmentally disabled children. The wide spectrum of epileptic and non-epileptic disorders probably represents the multifarious clinical manifestations of a common widespread, genetically determined pathogenetic mechanism. The marked age-dependency of the EEG and clinical symptoms, and the almost regular disappearance of both at puberty appear to justify the hypothesis of a hereditary impairment of brain maturation. The large phenotypic variability can be explained by differences in location and extent of the maturational disturbance as well as by the effect of additional genetic and environmental factors. The nature and cause of the hypothetical maturational disturbance are still unknown.

Adolescent↗
PubMed2004

Methylphenidate for pervasive developmental disorders: safety and efficacy of acute single dose test and ongoing therapy: an open-pilot study.

OBJECTIVE: The aim of this study was to investigate the effects of ongoing methylphenidate (MPH) on ADHD-related and autistic symptoms in Pervasive Developmental Disorders (PDD) in children who did not present any adverse effects to an initial acute dose administered at the clinic. METHODS: Participants included 13 subjects (12 males, with a mean age of 7.9 years) with PDD and moderate to severe hyperactivity/impulsivity. The severity of the symptoms assessment was based on Clinical Global Impression (CGI), Childhood Autism, Child Psychiatric and Conners Parent and Teacher Rating Scales (CPRS). Scores at baseline, and after 1 and 3 months of treatment, were compared to intent-to-treat analyses. RESULTS: One (1) hour after a single MPH dose (0.4 mg/kg), 5 subjects exhibited increased hyperactivity, stereotypes, dysphoria, or motor tics and were rated as minimally or much worse on the CGI Global Improvement Scale. They received no further treatment with MPH. Four (4) of the remaining subjects were rated as improved, and four as unchanged; they proceeded to a 12-week open trial of MPH. Two children remained unchanged: they discontinued treatment after 1 week on maximally tolerated doses. However, in group analyses, behavioral measures of hyperactivity and impulsivity improved significantly, while autism core symptom measures were unaffected. No significant adverse effects were observed in any of the 8 subjects. CONCLUSIONS: Administering a single MPH test dose may be useful in identifying children with PDD who may benefit from prolonged therapy.

Adolescent↗
PubMed2001

A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders.

OBJECTIVE: The aim of this study was to conduct a naturalistic, open-label examination of the efficacy and tolerability of mirtazapine (a medication with both serotonergic and noradrenergic properties) in the treatment of associated symptoms of autism and other pervasive developmental disorders (PDDs). METHODS: Twenty-six subjects (5 females, 21 males; ages 3.8 to 23.5 years; mean age 10.1 +/- 4.8 years) with PDDs (20 with autistic disorder, 1 with Asperger's disorder, 1 with Rett's disorder, and 4 with PDDs not otherwise specified were treated with open-label mirtazapine (dose range, 7.5-45 mg daily; mean 30.3 +/- 12.6 mg daily). Twenty had comorbid mental retardation, and 17 were taking concomitant psychotropic medications. At endpoint, subjects' primary caregivers were interviewed using the Clinical Global Impressions (CGI) scale, the Aberrant Behavior Checklist, and a side-effect checklist. RESULTS: Twenty-five of 26 subjects completed at least 4 weeks of treatment (mean 150 +/- 103 days). Nine of 26 subjects (34.6%) were judged responders ("much improved" or "very much improved" on the CGI) based on improvement in a variety of symptoms including aggression, self-injury, irritability, hyperactivity, anxiety, depression, and insomnia. Mirtazapine did not improve core symptoms of social or communication impairment. Adverse effects were minimal and included increased appetite, irritability, and transient sedation. CONCLUSIONS: Mirtazapine was well tolerated but showed only modest effectiveness for treating the associated symptoms of autistic disorder and other PDDs.

Adolescent↗
PubMed2006

A retrospective study of memantine in children and adolescents with pervasive developmental disorders.

RATIONALE: There are no drugs that have been shown to effectively treat the core social impairment of autism. OBJECTIVES: The purpose of this study was to examine the effectiveness and tolerability of memantine for social impairment in children and adolescents with pervasive developmental disorders (PDDs). MATERIALS AND METHODS: Medical records of 18 patients with PDDs consecutively treated with open-label memantine were retrospectively reviewed. The data reviewed included prospectively obtained assessments of severity (S) and improvement (I) using the Clinical Global Impressions Scale (CGI). Pretrial and follow-up parent ratings were also available on six patients using the Aberrant Behavior Checklist (ABC). RESULTS: Eighteen patients (15 male, 3 female; mean age=11.4 years, range 6-19 years) received memantine (mean dosage=10.1 mg/day, range 2.5-20 mg/day) over a mean duration of 19.3 weeks (range 1.5-56 weeks). Eleven of 18 (61%) patients were judged responders to memantine based on a rating of "much improved" or "very much improved" on the CGI-I. Significant improvement was also seen on the CGI-S. Improvement was primarily seen clinically in social withdrawal and inattention. Adverse effects occurred in 7 of 18 (39%) patients and led to drug discontinuation in 4 of 18 (22%) patients. Thirteen of 18 (72%) patients received stable doses of concomitant medications during the memantine trial. CONCLUSIONS: In this open-label retrospective study, memantine was effective in a number of patients with PDDs. Controlled studies are warranted to further assess the efficacy and safety of memantine in PDDs.

Adolescent↗
PubMed1992

[Specific developmental disorders and the family--pathogenetic factors in children with behavioral disorders].

121 children aged 5;6 to 8;6 years referred to our center as out-patients because of various types of behavioral problems and showing distinct symptoms of minor neurological dysfunction were investigated with regard to family-related variables, specific developmental disorders, and the extent of the behavioral problems. A comparison of the groups with few and numerous behavioral problems showed a significant difference in the number of familial risk factors, but not in the degree of neurological and cognitive dysfunction. These results indicate the importance of child-independent familial factors, e.g. marital problems and psychosocial stress, in the pathogenesis of behavioral disturbances in children with minor neurological dysfunction. The resulting need for a family-oriented perspective in assessment and therapy is discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Body mass index of children from the United Kingdom diagnosed with pervasive developmental disorders.

BACKGROUND: The aim of the present study was to ascertain the Body Mass Index (BMI) (kg m(-2)) derived from parental reports of height (metres) and weight (kilograms) of a pilot sample of boys born and resident in the UK diagnosed with pervasive developmental disorders (PDD). METHOD: Analysis of parental reporting of height and weight measurements in boys (n=50) diagnosed with PDD and comparison with age and sex-matched reference populations. RESULTS: The majority of patients were above the 50th percentile for height (70%), weight (74%) and BMI (80%) with 21% exceeding cut-off points for overweight and 10% for clinical obesity. There were no significant differences (P < 0.05) found between PDD subgroups for any of the measures. CONCLUSION: Further studies are required to validate findings of skewed height, weight and BMI data in PDD.

Body Height↗
PubMed1984

Auditory brainstem responses in pervasive developmental disorders.

Several studies have reported prolonged neural transmission times on auditory brainstem responses (ABRs) measured in autistic children, a finding which implicates CNS dysfunction at the level of the brainstem in autistic conditions. This study measured ABRs in 25 children and adults with pervasive developmental disorders (PDDs), including autism, and 25 age- and sex-matched normal controls. Subjects were carefully evaluated audiometrically and neurologically and artifact was controlled to produce highly reliable measures. Prolonged transmission times were seen in only one PDD subject and in one normal control, while shortened transmission times were seen in four PDD subjects. The majority of PDD subjects showed normal ABRs. Previous reports of a significant incidence of prolonged transmission times among autistic and autisticlike subjects, thus, were not replicated. Possible reasons for this discrepancy are discussed.

Adolescent↗
PubMed2004

[A magnetoencephalographic study of generalised developmental disorders. A new proposal for their classification].

INTRODUCTION: Autistic spectrum disorders (ASD) is a term that is not included in DSM IV or in ICD 10, which are the diagnostic tools most commonly used by clinical professionals but can offer problems in research when it comes to finding homogenous groups. DEVELOPMENT: From a neuropaediatric point of view, there is a need for a classification of the generalised disorders affecting development and for this purpose we used Wing's triad, which defines the continuum of the autistic spectrum, and the information provided by magnetoencephalography (MEG) as grouping elements. Specific generalised developmental disorders were taken as being those syndromes that partially expressed some autistic trait, but with their own personality so that they could be considered to be a specific disorder. ASD were classified as being primary, cryptogenic or secondary. The primary disorders, in turn, express a continuum that ranges from Savant syndrome to Asperger's syndrome and the different degrees of early infantile autism. MEG is a functional neuroimaging technique that has enabled us to back up this classification.

Child Development Disorders, Pervasive↗
PubMed1993

Subclassification of children with autism and pervasive developmental disorder: a questionnaire based on Wing's subgrouping scheme.

A questionnaire (the Wing Subgroups Questionnaire, or WSQ) for subclassifying children with autism into one of Wing's three hypothesized subgroups was developed, and the validity of this measure was assessed. Forty parents of children with autism or pervasive developmental disorder not otherwise specified (PDDNOS) completed the questionnaire. Results indicated that the questionnaire has adequate external criterion-referenced validity with similar subgroup ratings made by clinicians, and good internal consistency. Furthermore, results revealed three distinct and separate subgroups corresponding to Wing's subclassification scheme. Other analyses suggested that Wing assignment based on the WSQ was independent of chronological age and age equivalents for social and daily living skills, but not independent of diagnosis of autism vs. PDDNOS, IQ, severity of autism, sex, receptive language mental age, and age equivalents for communication skills. Finally, a discriminant analysis indicated that, of all the dependent variables examined in the present study, the clinicians' Wing assignment was the best predictor of Wing assignment based on the parent-completed WSQ. These findings provide support for Wing's classification system, and suggest that the WSQ is a valid and useful tool for subclassifying individuals with autism.

Adolescent↗
PubMed1985

Tourette syndrome, atypical pervasive developmental disorder and Ganser syndrome in a 15-year-old, visually impaired, mentally retarded boy.

This is a case report of a 15-year-old visually impaired, mentally retarded male who presents with symptoms consistent with Tourette Syndrome, a Syndrome of approximate answers (Ganser's Syndrome) and Atypical Pervasive Developmental Disorder. The authors feel that this follow-up on the case presented earlier by Parraga and Butterfield raises the possibility of a link between a number of the symptoms of adult schizophrenia, appearing in attenuated form in these two cases, and Tourette Syndrome.

Adolescent↗
PubMed2002

[Early detection and therapeutic rearing for children with mental retardation: II. Assessment of gene analyses for the diagnosis of developmental disorders in Japan].

The authors assessed the present status of gene analysis utilized in Japan. Physicians completed a mail-in questionnaire with their comments regarding the types of gene analyses they used, the perceived effectiveness of the analyses, and how they conducted genetic counselling for the patients. Among the 76 physicians who responded, gene analysis was most often conducted (n = 16, 75.0%) for muscle dystrophies, and considered to be effective by most of them (chi 2 (df = 2) = 11.99, p = 0.003). Many factors including the age of physicians, location of their facilities, and experience in child neurology were related to the utilization of gene analyses. Future studies based on ethical guidelines should establish a network between specialists and facilities and encourage medical approach to developmental disorders.

Child↗