Ataxia, autism, and the cerebellum: a clinical study of 32 individuals with congenital ataxia

The suggested link between autism and cerebellar dysfunction formed the background for a Swedish clinical study in 2001. Thirty-two children (17 females, 15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of non-progressive congenital ataxia were examined, and parents were interviewed about the presence of neuropsychiatric problems in the child. Twelve children had simple ataxia, eight had ataxic diplegia, and 12 had 'borderline' ataxia. All but one of the 32 children had a mild to moderate gross motor disability according to Gross Motor Function Classification System (15 were categorized as level I, 16 as level II, and one child as level IV). Neuroimaging and neuropsychological testing were achieved in most cases. There was a strong association between learning disability* and autism spectrum disorder (often combined with hyperactivity disorder) on the one hand, and both simple and borderline 'ataxia' on the other, but a weaker link between ataxic diplegia and neuropsychiatric disorders. A correlation between cerebellar macropathology on neuroimaging and neuropsychiatric disorders was not supported. Congenital ataxia might not be a clear-cut syndrome of cerebellar disease, but one of many signs of prenatal events or syndromes, leading to a complex neurodevelopmental disorder including autism and learning disability.     

Attention deficits in children with 22q.11 deletion syndrome

This study examined attention abilities of children with 22q.11 deletion syndrome. Thirty children (14 males, 16 females; age range 7 to 13y) were given comprehensive neuropsychological and neuropsychiatric assessments. Learning disability was found in 13 children. Superiority in verbal over performance IQ was very common. Attention-deficit-hyperactivity disorder (mainly of inattentive subtype) was diagnosed in 13 children. There appeared to be a relation between low IQ and presence of autism spectrum problems. The presence of attention deficits was clearly supported by the scores on the Child Behavior Checklist and the Conners Questionnaire. On the Becker attention tests the reaction times were significantly longer in the two visual and auditory tests, indicating that the ability to sustain attention is critically impaired in this group. A tendency of inferiority on auditory compared with visual tests was noted but there were no specific problems with the focus-execute aspect of attention.     

Asperger Syndrome: Familial and Pre- and Perinatal Factors

Objective: Study familial and pre- and perinatal factors in Asperger Syndrome (AS).Methods: Hundred boys with AS had their records reviewed. Pathogenetic subgroups were defined according to presence of medical syndromes/chromosomal abnormalities, indices of familiarity, and pre- and perinatal risk factors predisposing to brain damage. Results: No major index of pathogenetic factors was found in 13%, a syndrome/chromosomal abnormality in 8%, pre- or perinatal risk 13%, combined pre- or perinatal risk and family history in 11%, and family history only in 55% Comment: A bout 50% of all boys with AS have a paternal family history of autism spectrum disorder. Pre- and perinatal risks appear to be important in about 25% cases.     

A prospective, multicenter, open-label assessment of atomoxetine in non-North American children and adolescents with ADHD

OBJECTIVE: The aim of this study was to study treatment response to atomoxetine in a large, multicenter study of non-North American patients with ADHD. METHODS: A total of 604 children and adolescents with ADHD were enrolled in a 10-week open-label trial with atomoxetine prior to randomization to a double-blind relapse prevention phase at 33 sites in the United Kingdom, continental Europe, Israel, South Africa, and Australia. All patients had ADHD symptom severity at least 1.5 standard deviations above United States age and gender norms for their diagnostic subtype as measured by the investigator-scored ADHD Rating Scale (ADHD RS). Outcomes were assessed by analysis of change in the ADHD RS; functional and psychosocial outcomes were assessed using the Child Health Questionnaire (CHQ). RESULTS: At endpoint, ADHD RS total scores decreased by an average of 56.7%, and 69% of patients were rated as having no or minimal symptoms. Significant improvement was observed in psychosocial and functional outcomes. Discontinuations attributed to adverse events were < 4%. CONCLUSION: These open-label data, gathered in an international setting, add to our knowledge of the value of atomoxetine in treating ADHD symptoms, as well as its safety and tolerability.     

Personality disorders in a total population twin cohort with eating disorders

Findings regarding the occurrence of personality disorders (PDs) in eating disorders (EDs) have been contradictory. Most previous studies have been clinic-based. The aims of the current study were to assess the prevalence of PD in ED in a population-based twin group and to establish the distribution of PD in three subgroups of ED. A two-step screening and diagnostic study of ED was performed in a large Danish twin population. Axis I and axis II DSM-III-R and DSM-IV ED diagnoses were made on the basis of results obtained at clinical investigations and interviews. Forty-nine percent of the participants with ED had at least one PD, compared to 26% in those with no ED (P <.001). Cluster C PD was the most common type of PD in all subgroups of ED, and cluster B PD was found only in participants with bulimic symptoms. Genetic factors appeared to contribute significantly to the variance of cluster C PD in ED, which was evaluated as a possibly important background factor in ED.     

One hundred males with Asperger syndrome: a clinical study of background and associated factors

The objective of this study was to investigate the background and associated factors in a representative group of young males with Asperger syndrome (AS) presenting at a specialized autism clinic. One hundred males aged 5 years 6 months to 24 years 6 months, with a mean age of 11 years 4 months (SD 3y 10mo), who had a clinical diagnosis of AS were included in the study. An in-depth review of their medical records and neuropsychological test data was performed. There was a high rate (51%) of non-verbal learning disability (defined as Verbal IQ more than 15 points higher than Performance IQ), but otherwise there was little or no support for the notion of right-hemisphere brain dysfunction being at the core of the syndrome. There was a very high rate of close relatives with autism spectrum problems, but also high rates of prenatal and perinatal problems, including prematurity and postmaturity. In comparison with general population data, those with AS very often had a combination of genetic and prenatal and perinatal risk factors. Non-verbal learning disability test results applied in about half the group. There was a subgroup of individuals with AS who had macrocephalus. However, there was no support for an association of AS with low body mass index.     

A candidate region for Asperger syndrome defined by two 17p breakpoints

Asperger syndrome (AS) is a mild form of autistic disorder characterised by impairment in social interaction as well as a restricted pattern of behaviour, interests, and activities. Two patients with AS and balanced translocations t(13;17) and t(17;19), respectively, were identified. Fluorescent in situ hybridisation (FISH) analysis with chromosome 17 specific clones to metaphase chromosomes from both patients showed that the chromosome 17 breakpoints are located within a 300 kb region at 17p13. The region spans 14 known genes. The expression of these genes was analysed in lymphoblastoid RNA derived from the patients and healthy control individuals. The CHRNE, DKFZP566H073, LOC90048, PFN1, SPAG7, KIAA0909, ZNF232 and KIF1C genes showed similar levels of expression in cell lines with the translocations when compared with cell lines with normal karyotype. No expression was detected for the MINK, GP1BA, SLC25A11, ENO3, FLJ10060 and USP6 genes in any of the cell lines. The close physical relation of the two 17p breakpoints suggest a common genetic aetiology for the phenotype in the patients. Structural and functional analysis of the genes located around the two 17p breakpoints in t(13;17) and t(17;19) patients may reveal candidate sequences for the AS phenotype.     

Swedish child and adolescent psychiatric out-patients

Publications of Swedish child and adolescent psychiatric out-patients have been scarce. This study is aimed to give a picture of conditions in a child and adolescent psychiatric out-patient setting by reporting five-year data from a five-year cohort of first-time visits. All first-visits, 0-18 years of age, where screened retrospectively for background factors, symptoms, diagnoses and types of treatment. Six hundred and ten patients were registered during the period. The estimated accumulated prevalence for 19-year-olds were 19,7 %. Nearly half of them were seen 1-3 times. A small group, 2,5 %, accounted for about 20 % of all consultations. No or mild psychosocial stress was registered in 37 % of the cases. A neuropsychiatric main diagnosis was found for 27 % (2,1:1, boys:girls) and depression and anxiety for 20 % [0, 5:1] of the index-cases. These findings show that 5,6 % of children applied for child and adolescent psychiatric help during a five-year period. Almost one third had a neuropsychiatric disorder. The results indicate that ADHD is one of the most common causes both among boys and girls to seek help in a child and adolescent out-patient clinic.     

Deficits in attention, motor control, and perception: a brief review

The concept of DAMP (deficits in attention, motor control, and perception) has been in clinical use in Scandinavia for about 20 years. DAMP is diagnosed on the basis of concomitant attention deficit/hyperactivity disorder and developmental coordination disorder in children who do not have severe learning disability or cerebral palsy. In clinically severe form it affects about 1.5% of the general population of school age children; another few per cent are affected by more moderate variants. Boys are overrepresented; girls are currently probably underdiagnosed. There are many comorbid problems/overlapping conditions, including conduct disorder, depression/anxiety, and academic failure. There is a strong link with autism spectrum disorders in severe DAMP. Familial factors and pre- and perinatal risk factors account for much of the variance. Psychosocial risk factors appear to increase the risk of marked psychiatric abnormality in DAMP. Outcome in early adult age was psychosocially poor in one study in almost 60% of unmedicated cases. There are effective interventions available for many of the problems encountered in DAMP.     

Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.