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Parenting Children With Asperger's And High-functioning Autism

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Age (years)

Figure 8 Two- to 4-year-old autistic and normal males (circles) are plotted showing overall whole brain enlargement of the youngest autistic children. As shown, 31 of 36 (86%) of the autistic boys and girls had whole brain volumes larger than the normal mean. In contrast, only 1 of 24 (4%) normal boys and girls in this age range exceeded the autism mean (reproduced with permission from Courchesne et al., 2001).

Figure 9 A case of extreme macrencephaly in autism. Three-dimensional image of 3.4-year-old autistic subject, JW (left), compared to that of a normal male child whose brain volume was scaled to equal normal average size (right). The autistic child's brain volume (1816 ml) was more than 6 SDs above the normal average (1162 ml) for his age (from Courchesne et al., unpublished data).

Figure 9 A case of extreme macrencephaly in autism. Three-dimensional image of 3.4-year-old autistic subject, JW (left), compared to that of a normal male child whose brain volume was scaled to equal normal average size (right). The autistic child's brain volume (1816 ml) was more than 6 SDs above the normal average (1162 ml) for his age (from Courchesne et al., unpublished data).

normal child's brain continues to grow at a strong pace. By older childhood and adolescence, the normal child's cerebrum and cerebellum have reached or

Figure 10 Volumes of cerebral white matter (top) and cerebellar white matter (bottom) are plotted with their best-fit curves for normal and autistic 2- to 16-year-old males. Despite precocious growth by early childhood, in autism, both cerebral and cerebellar white matter growth were smaller than normal by adolescence. (reproduced with permission of Courchesne et al., 2001).

Figure 10 Volumes of cerebral white matter (top) and cerebellar white matter (bottom) are plotted with their best-fit curves for normal and autistic 2- to 16-year-old males. Despite precocious growth by early childhood, in autism, both cerebral and cerebellar white matter growth were smaller than normal by adolescence. (reproduced with permission of Courchesne et al., 2001).

surpassed sizes achieved at an earlier age by the very young autistic child. This explains why postmortem observations of the weight of the autistic brain show it to be normal in the majority (86%) of older children and adult cases, although a few rare cases of extreme weight at that age do exist.

Apparently, after birth but prior to about 2 or 3 years of age in autism, several cerebral and cerebellar anatomical abnormalities rapidly occur, which means that postnatal, biologically guided intervention prior to the full expression of these abnormalities may be a possibility in the future. These observations suggest autism involves an unusual, perhaps unique, developmental neuroanatomic phenotype.

2. Postmortem Evidence

The major strength of postmortem research is that it allows detailed histoanatomical examination unattainable by MRI, and many important observations of the brain of the older child or adult with autism come from such studies. However, currently, there are too few postmortem autism cases in the literature to provide definitive evidence of either age at pathological onset or developmental trajectories for any brain structure. Only six postmortem cases of autism less than 19 years of age have been reported, and only one of these is younger than 9 years of age (i.e., one 4-year-old case). Additionally, postmortem studies of purported ''autistic'' infants and children under the age of 5 years suffer from one obvious drawback: At that young age, the diagnosis of autism remains uncertain, and obviously no longitudinal observations may be per formed to confirm or alter an initial diagnosis of autism suspected at that age.

Nonetheless, some neuropathological features are indicative of early developmental onset. Such features include cells arrested in migration in the inferior cerebellar peduncles, inferior olive malformation, irregular lamina disarray in small focal cerebral regions, reduced numbers of Purkinje neurons in the apparent absence of glial scarring, dysgenesis of facial motor nuclei, and agenesis of the superior olivary nuclei. However, several of these pathologies have only been noted in one or a few cases and not in the majority of postmortem cases, and therefore they do not provide definitive evidence about age of onset of pathology in the majority of autism cases. Interestingly, the different pathological features point to several different prenatal periods of onset.

Other reported pathological features—small cell size, increased cell packing density, and thickened cortices—are not indicative of any particular age of onset, but it is parsimonious to hypothesize onset during early development.

Since cerebellar pathology is ubiquitous among autism cases, knowledge of age of onset would be valuable in seeking causes and effective interventions. Decreased Purkinje neuron number is not accompanied by empty basket cells, which is indicative of early rather than later developmental age at the time of loss. Since the decrease in Purkinje number is evident regardless of history of seizures or seizure medication, the age of onset and cause of cell loss are not explained by seizure onset or seizure treatment. Also, cerebellar folia do not show signs of atrophy (mutant mice with developmental loss of Purkinje cells show cerebellar hypoplasia, not atrophy). In several autism cases, the inferior olives (which are developmentally, structurally, and functionally intimately involved with cerebellar Purkinje neurons) are maldeveloped and neuronal migration errors appear in the inferior cerebellar peduncles. In one postmortem autism case, Purkinje neurons were irregularly aligned, which could not caused by some later postnatal event. The dysplastic olives and migration errors are clear signs of first trimester events but have only been seen in three autism postmortem cases. The developmental ramifications of dysplasia and migration defects are unknown. Despite the reduced number of Purkinje neurons, cerebellar cortex in autism has clearly defined cortical lamina (granule, Purkinje, and molecular layers), even in cases with large distances between single surviving Purkinje neurons. Although Purkinje neuron loss or dysgenesis could occur prenatally along with olivary dysgenesis and the migration errors in the inferior cerebellar peduncle, observations of intact cerebellar lamina seem to argue against a massive dysgenesis or loss of Purkinje neurons before the final phases of granule cell proliferation and migration. Therefore, the possibility cannot be reasonably ruled out that Purkinje neuron loss could occur postnatally, perhaps in the first 1 to 3 years of life.

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Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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