Neurotoxic Brainstem Impairment as Proposed Threshold Event in Autistic Regression

McGinnis, Woody R.; Miller, Veronica M.; Audhya, Tapan; Edelson, Stephen M.

doi:10.1201/9781420068870-c9

Cited by 5 publications

(11 citation statements)

References 130 publications

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“…“Drunk” reflects a toxic state. “Regulatory” evokes a brainstem locale that McGinnis indicated was a principle target of toxicity in autism 10 . The principle etiologic factors 11 of autism are now generally acknowledged to be environmental toxins.…”

Section: Discussionmentioning

confidence: 99%

Gender Differences among Children with Autism Spectrum Disorder: Differential Symptom Patterns

Baker

Milivojevich²

2013

Glob Adv Health Med

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The gender ratio among children in the autism spectrum of more than four boys to every girl is widely recognized. The authors present an analysis of gender differences among 79 482 symptoms and strengths in 1495 boys and 336 girls aged 2 to 18 years from parent-identified autistic children reported to a structurally novel anonymous parent-entered online database, Autism360. The data reveal differences that provide previously undetected clues to gender differences in immune and central nervous system and gastrointestinal functional disturbances. Together with published observations of male/female differences in inflammation, oxidative stress, and detoxication, these findings open doors to research focusing on gender physiology as clues to etiologic factors in autism. This study exemplifies a research method based on a large, detailed, patient-entered, structured data set in which patterns of individual illness and healing may answer collective questions about prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Gender Differences among Children with Autism Spectrum Disorder: Differential Symptom Patterns

Baker

Milivojevich²

2013

Glob Adv Health Med

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“…Brain region-specific expression of some antioxidant enzymes has been observed in AD [14]. Brain region-selective uptake of toxins and toxicant, possibly related to the presence or absence of the blood-brain barrier (BBB), has been suggested [28]. It was proposed that these substances are more accessible to regions of brain which fail to develop the BBB surrounding the primitive brain stem.…”

Section: Discussionmentioning

confidence: 99%

Brain Region-Specific Changes in Oxidative Stress and Neurotrophin Levels in Autism Spectrum Disorders (ASD)

Sajdel-Sulkowska

McGinnis³

et al. 2010

Cerebellum

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122

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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by social and language deficits, stereotypic behavior, and abnormalities in motor functions. The particular set of behavioral impairments expressed in any given individual is variable across the spectrum. These behavioral abnormalities are consistent with our current understanding of the neuropathology of ASD which suggests abnormalities in the amygdala, temporal and frontal cortexes, hippocampus, and cerebellum. However, regions unrelated to these behavioral deficits appear largely intact. Both genetic predisposition and environmental toxins and toxicants have been implicated in the etiology of autism; the impact of these environmental triggers is associated with increases in oxidative stress, and is further exacerbated when combined with genetic susceptibility. We have previously reported increased levels of 3-nitrotyrosine (3-NT), a marker of oxidative stress, in ASD cerebella. We have also shown that this increase was associated with an elevation in neurotrophin-3 (NT-3) levels. The objectives of the current study were to determine whether the increase in oxidative stress in ASD is brain region-specific, to identify the specific brain regions affected by oxidative stress, and to compare brain region-specific NT-3 expression between ASD and control cases. The levels of 3-NT and NT-3 were measured with specific ELISAs in individual brain regions of two autistic and age- and postmortem interval (PMI)--matched control donors. In the control brain, the levels of 3-NT were uniformly low in all brain regions examined ranging from 1.6 to 12.0 pmol/g. On the other hand, there was a great variation in 3-NT levels between individual brain regions of the autistic brains ranging from 1.7 to 281.2 pmol/g. The particular brain regions with the increased 3-NT and the magnitude of the increase were both different in the two autistic cases. In the older autistic case, the brain regions with highest levels of 3-NT included the orbitofrontal cortex (214.5 pmol/g), Wernicke's area (171.7 pmol/g), cerebellar vermis (81.2 pmol/g), cerebellar hemisphere (37.2 pmol/g), and pons (13.6 pmol/g); these brain areas are associated with the speech processing, sensory and motor coordination, emotional and social behavior, and memory. Brain regions that showed 3-NT increase in both autistic cases included the cerebellar hemispheres and putamen. Consistent with our earlier report, we found an increase in NT-3 levels in the cerebellar hemisphere in both autistic cases. We also detected an increase in NT-3 level in the dorsolateral prefrontal cortex (BA46) in the older autistic case and in the Wernicke's area and cingulate gyrus in the younger case. These preliminary results reveal, for the first time, brain region-specific changes in oxidative stress marker 3-NT and neurotrophin-3 levels in ASD.

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“…Dr McGinnis and his coauthors provide a strong argument for the importance of the natural openness to the blood of mid-brain structures that are responsible for autonomic regulatory functions. 15 When confronted by a systems problem, we are confined to a large extent to a linear process of tailoring therapy to the individual. We can expect, however, that the priorities we choose will benefit from nature's capacity to spread benign influences throughout biological systems just as malign signals can push our virtuous cycles down into vicious ones.…”

Section: The Targets Of Toxinsmentioning

confidence: 99%

Section: The Targets Of Toxinsmentioning

confidence: 99%

Learning about Autism

Baker

2013

Glob Adv Health Med

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A medical essay written in 1923 pointed out the fallacy of blaming a chronic illness on the name of a disease. The focus of treatment should be the individual, not the disease. With a focus on options based on the individuality of each patient, I ask a simple two-part question: Does my patient need to avoid or be rid of substances and/or to be provided with substances that would favor nature's impulse toward healing?In my academic training as a physician, I learned that a clinically effective stance favored an optimistic intent combined with the objective application of my skills—refined though the practice of listening, prescribing, and observing outcome. My understanding of autism has rested on a foundation of the individuality of every living thing, the rhythmicity of life, and the balance that characterizes healthy systems. The first autistic child I examined struck me with a nonverbal message: “I am in here; see me.”The recognition of the role of bacterial toxins amplified my notion that a general disorder of the microbiome underlies the loss of immune tolerance that accompanies the global state of sensitivity found in individuals in the autism spectrum. Depletion of organisms that have populated the human gut since before the dawn of our species arises as the most recent elevation of my learning curve.

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Neurotoxic Brainstem Impairment as Proposed Threshold Event in Autistic Regression

Cited by 5 publications

References 130 publications

Gender Differences among Children with Autism Spectrum Disorder: Differential Symptom Patterns

Gender Differences among Children with Autism Spectrum Disorder: Differential Symptom Patterns

Brain Region-Specific Changes in Oxidative Stress and Neurotrophin Levels in Autism Spectrum Disorders (ASD)

Learning about Autism

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