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"Patches of Disorganization in the Neocortex of Children with Autism" is a March 27, 2014 New England Journal of Medicine abstract of an article on postmortem findings. The authors/investigators state, "We thank all the parents who have supported brain research through the donation of brain tissue from their loved ones;" a kind and considerate acknowledgement of the courageous, heartbreaking contribution families may make to further understanding of illness and disease for the benefit of all, present and future.

As the Background section of the abstract explains, "Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex"; and Methods, "To systematically examine neocortical architecture during the early years after the onset of autism". Results:

We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children [between the ages of 2 and 15 years]. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches.
with Conclusion:
...Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages...
Medscape's March 28, 2014 article by Pauline Anderson on this study, Autism May Begin Before Birth, Autopsy Study Reveals interprets:
Disorganized neurons in the prefrontal cortex suggest that brain abnormalities in children with autism may begin before birth, a detailed postmortem study shows. The analysis revealed the presence of patches of disorganized neurons in areas that mediate functions that are disturbed in autism, including social, emotional, communication, and language function,
quoting the study authors,
"Such abnormalities may represent a common set of developmental neuropathological features that underlie autism and probably result from dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages...the crucial early developmental step of creating 6 distinct layers with specific types of brain cells ― something that begins in prenatal life ― had been disrupted,"
Anderson continues,
Although the data suggest a novel pathologic mechanism in autism, the exact biological process is unknown.
      "The identified laminar disorganization could result from migration defects resulting in the failure of cells to reach their targeted destination and the accumulation of such cells in nearby regions," the [study]authors write.
      Or, they added, the patches could reflect de novo changes early in neurodevelopmental processes, which yield regions of affected progenitor cells adjacent to regions of unaffected progenitor cells.
      In any case, the data are consistent with an early prenatal origin of autism, or at least prenatal processes, that may confer a predisposition to autism, according to investigators [and] although the sample size was small compared with postmortem studies of adult diseases, it is as large ― or larger ― than most previous such studies of autism, the authors note.                                                              emphasis by diarist
Thomas Frazier, PhD, director, Cleveland Clinic Children's Center for Autism, in Ohio, commented for Medscape Medical News, that
it indicates that in autism, abnormalities in brain cell development occur prior to birth. and ... "The key advance from this research is that it suggests that very early developmental processes lead to autism... The findings support genetic disruptions leading to brain disorganization or possibly very early interactions between genes and the prenatal environment."
      Dr. Frazier predicted that some experts may find the results controversial because the findings "suggest that brain abnormalities begin before birth, making it less likely that a purely environmental insult causes autism."                                        emphasis by diarist
which Anderson interprets to mean that
brain cell activity has been disrupted during pregnancy, which possibly points more to a genetic than an environmental trigger for autism.
Critical readers may see a problem in "brain cell activity" being equated by Anderson with brain cell development; and in "the findings support genetic disruptions...or...early interactions between genes and the prenatal environment...making it less likely that a purely environmental insult causes autism" being equated with "points more to a ... genetic ... trigger".

Fulltext of this NEJM report is only accessible through subscription to the Journal, so the validity of Anderson's interpretation is unverifiable within this diary. Readers are encouraged to examine the full Medscape article and the abstract, and possibly their doctors may be able to obtain for them a fulltext reprint of the research, since

"the features that we describe here may explain some of the heterogeneity of autism: disorganized patches in different locations could disrupt disparate functional systems in the prefrontal and temporal cortexes and potentially influence symptom expression, response to treatment, and clinical outcome," the researchers write.

For an introduction and start in the free use of Medscape, see the large blockquote at this diary.

Additional Medscape articles of similar interest:

Autism Rates Jump 30%, CDC Reports: New estimates put the figure at 1 in 68 children aged 8 years (or 14.7 per 1000) ― roughly 30% higher than previous estimates reported in 2012 of 1 in 88 children (11.3 per 1000)

Autism, Intellectual Disability Linked to Environmental Factors: Pesticides, Other Environmental Factors Possible Autism Culprits

Prenatal Exposure to Antiepileptic {medication} Linked to Autism

New {psychiatry} Practice Guidelines for Autism

Originally posted to KosAbility on Mon Mar 31, 2014 at 05:22 PM PDT.

Also republished by Parenting on the Autism Spectrum.

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