1. Blaylock RL. {{A possible central mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity}}. {Altern Ther Health Med};2009 (Jan-Feb);15(1):60-67.
In this section, I explore the effects of mercury and inflammation on transsulfuration reactions, which can lead to elevations in androgens, and how this might relate to the male preponderance of autism spectrum disorders (ASD). It is known that mercury interferes with these biochemical reactions and that chronically elevated androgen levels also enhance the neurodevelopmental effects of excitotoxins. Both androgens and glutamate alter neuronal and glial calcium oscillations, which are known to regulate cell migration, maturation, and final brain cytoarchitectural structure. Studies have also shown high levels of DHEA and low levels of DHEA-S in ASD, which can result from both mercury toxicity and chronic inflammation. Chronic microglial activation appears to be a hallmark of ASD. Peripheral immune stimulation, mercury, and elevated levels of androgens can all stimulate microglial activation. Linked to both transsulfuration problems and chronic mercury toxicity are elevations in homocysteine levels in ASD patients. Homocysteine and especially its metabolic products are powerful excitotoxins. Intimately linked to elevations in DHEA, excitotoxicity and mercury toxicity are abnormalities in mitochondrial function. A number of studies have shown that reduced energy production by mitochondria greatly enhances excitotoxicity. Finally, I discuss the effects of chronic inflammation and elevated mercury levels on glutathione and metallothionein.
2. Downs JA, Bebbington A, Jacoby P, Msall ME, McIlroy O, Fyfe S, Bahi-Buisson N, Kaufmann WE, Leonard H. {{Gross motor profile in rett syndrome as determined by video analysis}}. {Neuropediatrics};2008 (Aug);39(4):205-210.
Movement impairment is a fundamental but variable component of the Rett syndrome phenotype. This study used video supplemented by parent report data to describe the gross motor profile in females with Rett syndrome (n=99) and to investigate the impact of age, genotype, scoliosis and hand stereotypies. Factor analysis enabled the calculation of general and complex gross motor skills scores. Most subjects were able to sit, slightly less than half were able to walk and a minority were able to transfer without assistance. General gross motor skills declined with age and were poorer in those who had surgically treated scoliosis but not conservatively managed scoliosis. Complex gross motor skills did not decline with age and were better in those without scoliosis. Those with a p.R133C, p.R294X, or a p.R255X mutation appear to have better motor skills overall than those with a p.R270X or large deletion mutation. Motor scores were not related to the frequency of hand stereotypies. This information is useful for the clinician and family when planning support strategies and interventions.
3. He Q, Karsch K, Duan Y. {{Abnormalities in MRI traits of corpus callosum in autism subtype}}. {Conf Proc IEEE Eng Med Biol Soc};2008;2008:3900-3903.
A number of studies have documented that autism has a neurobiological basis, but the anatomical extent of these neurobiological abnormalities is largely unknown. In this paper, we apply advanced computational techniques to extract 3D models of the corpus callosum (CC) and subsequently analyze the volumetric deficit of the total CC and its five sub-regions in a homogeneous group of autistic children. Moreover, we explore new MRI traits based on the oriented bounding rectangle of the CC, which are the length, width and aspect ratio of the bounding rectangle. These measurements as well as the volumes are compared between patients and controls using t-tests. The results reveal significant reduction in all sub-regions of the CC and some MRI traits in the patients.
4. Herbrecht E, Poustka F, Birnkammer S, Duketis E, Schlitt S, Schmotzer G, Bolte S. {{Pilot evaluation of the Frankfurt Social Skills Training for children and adolescents with autism spectrum disorder}}. {Eur Child Adolesc Psychiatry};2009 (Jun);18(6):327-335.
The objective of this pilot study was to evaluate the effectiveness of a group-based intervention aiming at improving social and communication skills in individuals with autism spectrum disorder. Over a period of 11 months, N = 17 children and adolescents received treatment according to the manualised Frankfurt Social Skills Training (KONTAKT). Parent, teacher, expert and blind expert ratings were assessed to judge outcome regarding peer interaction, autistic behaviours, adaptive functioning and family burden. The participants exhibited improvements pre to follow-up treatment, particularly in the area of autistic symptomatology. Effect sizes (partial eta squared) ranged from 0.02 to 0.69. Among other things, regression models showed a positive influence of IQ and language skills on gains in social skills. Findings indicate that KONTAKT might be useful for enhancing social skills and reducing autism-related psychopathology over time in different contexts. Nevertheless, controlled trials are needed to reassure its effectiveness.
5. Keary CJ, Minshew NJ, Bansal R, Goradia D, Fedorov S, Keshavan MS, Hardan AY. {{Corpus callosum volume and neurocognition in autism}}. {J Autism Dev Disord};2009 (Jun);39(6):834-841.
The corpus callosum has recently been considered as an index of interhemispheric connectivity. This study applied a novel volumetric method to examine the size of the corpus callosum in 32 individuals with autism and 34 age-, gender- and IQ-matched controls and to investigate the relationship between this structure and cognitive measures linked to interhemispheric functioning. Participants with autism displayed reductions in total corpus callosum volume and in several of its subdivisions. Relationships were also observed between volumetric alterations and performance on several cognitive tests including the Tower of Hanoi test. These findings provide further evidence for anatomical alterations in the corpus callosum in autism, but warrant additional studies examining the relationship of this structure and specific measures of interhemispheric connectivity.
6. Larsson EL, Aaro S, Ahlinder P, Normelli H, Tropp H, Oberg B. {{Long-term follow-up of functioning after spinal surgery in patients with Rett syndrome}}. {Eur Spine J};2009 (Apr);18(4):506-511.
In a prospective study, 23 consecutive girls with Rett syndrome and neuromuscular scoliosis were evaluated for functioning at a long-term follow-up. The patients had mostly improved, which was confirmed by their parents. Rett syndrome is associated with neuromuscular scoliosis and has a typically long C-shaped thoracolumbar kyphoscoliosis. Prospective long-term follow-up studies related to these patients’ total situation are sparse. Most studies focus on the Cobb angle of the scoliosis, whereas parents are mainly concerned about the girls’ continued functioning. Twenty-three patients with Rett syndrome and neuromuscular scoliosis were evaluated preoperatively from 1993 to 2002. At follow-up, 19 patients remained in the study. Three patients died (not due to surgery), and one patient could not participate because it was too far to travel. Mean follow-up time was 74 months (range 49-99 months). The assessments comprised the sitting balance, seating supports in wheelchair, weight distribution, time used for rest, care given, and angle of scoliosis. Follow-up questionnaires and two-open-ended questions about the positive and negative effects of surgery were sent to parents. Sitting balance, number of seating supports in wheelchair, weight distribution, time used for rest, and the Cobb angle had all improved after surgery. The parents assessed improvement in seating position, daily activities, time used for rest, and cosmetic appearance. We can conclude that the stabilized spine resulted in sufficient strength to keep the body upright with the possibility of looking around at the surroundings more easily. The girls got better seating position with less need for seating adaptations in the wheelchair and with reduced time needed for resting during the day. Finally we can conclude that the indication for surgery is to get a better posture which lead to less risk of pressure sores, and that un upright position lead to better possibility to easily breath with fewer episodes of pneumonia and a better general health as result. The evidence of positive surgical effects for girls with Rett syndrome is of great importance in indication for surgery in the decision-making process.
7. Sartori S, Di Rosa G, Polli R, Bettella E, Tricomi G, Tortorella G, Murgia A. {{A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome}}. {Am J Med Genet A};2009 (Feb);149A(2):232-236.
Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures.
8. Schwartz CB, Henderson HA, Inge AP, Zahka NE, Coman DC, Kojkowski NM, Hileman CM, Mundy PC. {{Temperament as a predictor of symptomotology and adaptive functioning in adolescents with high-functioning autism}}. {J Autism Dev Disord};2009 (Jun);39(6):842-855.
Variation in temperament is characteristic of all people but is rarely studied as a predictor of individual differences among individuals with autism. Relative to a matched comparison sample, adolescents with High-Functioning Autism (HFA) reported lower levels of Surgency and higher levels of Negative Affectivity. Variability in temperament predicted symptomotology, social skills, and social-emotional outcomes differently for individuals with HFA than for the comparison sample. This study is unique in that temperament was measured by self-report, while all outcome measures were reported by parents. The broader implications of this study suggest that by identifying individual variability in constructs, such as temperament, that may influence adaptive functioning, interventions may be developed to target these constructs and increase the likelihood that individuals with HFA will achieve more adaptive life outcomes.
