The Myth of Autism
Page 6
These 2007 studies measured the presence of autoantibodies (directed against neural antigens) in ASD patients and explored the possible role of autoimmunity in the pathogenesis of ASD (“Brain-Specific Autoantibodies in the Plasma of Subjects with Autistic Spectrum Disorder,” Annals of the New York Academy of Science, 2007 Jun; 1107:92–103 and “Autoantibodies in Autism Spectrum Disorders,” Annals of the New York Academy of Science, 2007 Jun: 1107:79–91).
During embryogenesis, unregulated VIP may have major and permanent consequences on the formation of the brain and may be a participating factor in disorders of neurodevelopment. VIP has been linked to autism, Down syndrome, and fetal alcohol syndrome (“Vasoactive Intestinal Peptide in Neurodevelopmental Disorders: Therapeutic Potential,” Current Pharmaceutical Design. 2007 13[11]: 1079–89).
This research indicates that there is potential that aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dysfunction characteristic of ASD (“The Immune Response in Autism: A New Frontier for Autism Research,” Journal of Leukocyte Biology. 2006 80[1]: 1–15. Epub May 12 2006).
In this 2006 review, immune abnormalities are also commonly observed in this disorder. Given 5-HT’s role as an immunomodulator, possible connections between 5-HT and immune abnormalities in autism are explored (“Hyperserotoninemia and Altered Immunity in Autism,” Journal of Autism and Developmental Disorders. 2006 July 36 [5] : 697–704).
The presence of both BDNF AAs and elevated BDNF levels in some children with autism and childhood disintegrative disorder suggests a previously unrecognized interaction between the immune system and BDNF (“Brain-Derived Neurotrophic Factor and Autoantibodies to Neural Antigens in Sera of Children with Autism Spectrum Disorders, Landau-Kleffner Syndrome, and Epilepsy,” Biology Psychiatry. 2006 Feb 15; 59(4): 354–63. Epub September 21 2005).
Two main immune dysfunctions in autism are immune regulation involving proinflammatory cytokines (immunomodulating agents) and autoimmunity. Studies showing elevated brain specific antibodies in autism support an autoimmune mechanism. Viruses may initiate the process but the subsequent activation of cytokines is the damaging factor associated with autism .34
Among the main immune abnormalities reported:
Changes in T cells (and T cell function)
CD4/CD8—increased/decreased
Low (and elevated) NK cells
B cells—increased/decreased
Increased DR+ T cells
Increased interleukin-2 receptors
Decreased mitogen response
Altered delayed hypersensitivity
Antibodies to serotonin receptors
Antibodies to neuro elements
Based on the evidence presented herein, I believe that developing a focus on the interrelationship of autism, ADD, ADHD, CFS, CFIDS, and other immune-modulated conditions is a key to helping groups of these children in ways never before possible. If we can address the physiologic part of the dysfunction in these children (irrespective of its specific etiology), educational therapy, counseling, study techniques, and most/all other current therapies have a far greater probability of success. In addition, research focused on developing and initiating new therapies for “autism” is likely to be useful in treating these other interrelated childhood disorders.
Seizures—Relationship to Viruses, Immune Attacks on Brain
Years ago in medical school, we were taught that a certain number of pediatric patients were going to have febrile seizures. They were otherwise presumed to be healthy, and they would progress to develop correctly, and essentially outgrow their tendency to “febrile seizures.” Most seizures, even in later childhood, were considered idiopathic (from an unknown cause).
In the last few years, besides all the children now diagnosed as having “autism with seizures,” I began to meet parents of children presenting with one hundred or more seizures a month, sometimes one hundred a week. As any doctor will tell you—this many childhood seizures would ordinarily be diagnosed as a neurological (not psychiatric) disorder called epilepsy. Yet, to my surprise and dismay, these parents were distraught, as lost as parents of “autistic” children, for they were being told by the top pediatric neurologists in the country that their children’s seizures were idiopathic.
I knew there was an enlarging body of good, peer-reviewed evidence that a new family of higher-order herpes viruses, HHV-6, HHV-7, HHV-8 and more, were unlike the herpes simplex viruses so many of us were taught about in medical school. These viruses wanted to go to the brain, but unlike previous models, previous teaching, they smoldered at a low grade (below the radar—stealthily). Since I had never been told a virus living on my brain was good for me, besides the explanation for the neurodysfunction evolving in adults and then children, the idea of viruses was a perfect explanation for increased seizures. As noted below, the addition of the immune system itself attacking the brain completed a picture, compatible with medical school teaching, of what we were told were “irritable foci.” When they fire off inappropriately the brain could then fire off inappropriately at large, creating a seizure!
In preparing to give a talk to these parents I was floored, then dismayed, that in peer-reviewed medical journals talking about seizures, the literature was not only full of neuroimmune, chemokines, cytokines, but by the literature at least 25 to perhaps as many as 40 percent of these children had evidence for herpes viruses in their brain, particularly the temporal lobes. The concept of the temporal lobes, herpes viruses, and seizure foci has been strengthened over the years by repeatedly confirmed findings on autopsies in children and adults. As noted above, we know HHV-6 and related viruses go to the brain. A very disturbing finding in the literature was the fact that latent (30 percent) and active (12 percent) forms of HHV-6 were found in supposedly “normal” pediatric brains on autopsy. The article stongly supported the idea that “the glial tropism and anatomical location of HHV-6 may have important implications into the pathogenesis of disease.” How can we tell so many parents their children’s seizures are idiopathic and accept missing so many likely reasons and pathogens? Again, by a system not willing to put any “marker” value on elevated titers, with the fallacies of PCR probes (which will be positive sometimes, but not consistently), short of brain biopsies, how do we verify, prove what should be clinically obvious to many by now?
In using NeuroSPECT for many years now, it has become obvious that “scattered” areas of dysfunction, vasculitis with either increased or decreassd flow, was occurring in areas that could not be correlated to existing tracks or pathways in the brain. The findings over many years now are only consistent with the idea of a virus scattered living in/irritating the brain, and/or the immune system attacking those or other scattered areas of the brain.
Case note: A ten-year-old old girl, presenting with epilepsy and autism, had NK cells of 2.8 percent, a sedimentation rate of one. With those findings alone, irrespective of other parts of her history, the likelihood she was in a neuroimmune state, had a stressed immune system, and an overwhelming probability of viral activation was clinically a sure thing. Whatever the original reason, or insult, this said there was something medically going on that I was likely familiar with, and I could likely try to help this patient. I am pleased to say, over a year later, with The Goldberg Approach (see chapter 7) seizures are almost nonexistent, negative medications are lower or removed, and she is beginning to blossom educationally and physically, as she never could before.
Reviewing the seizure literature, it turned out there were many articles supporting the potential role for herpes-related viruses, including a number on the likely role of HHV-6b in epilepsy, limbic encephalitis, myocarditis, encephalitis, febrile seizures, and MS.
Clinical Note: As a general pediatrician, before subspecializing, I had be come aware that newly identified HHV-6, the common cause of roseola in children, was possibly connected to febrile seizures.
Many articles supported thes
e ideas, these connections, but it was becoming obvious, even for university-based pediatric neurologists, this was a direction they were not pursuing. It is worth noting that often the articles refer to the lack of conventional inflammatory changes, which is to me completely supportive of the idea of neuroimmunity being presented in this book.
With the literature validating that many febrile seizures are occurring without the previous concept of a rapid rise in temperature, understanding that many of these are not benign anymore, that many are forerunners to true epilepsy, potentially lifelong seizure disorders, mean therapy and prevention need to come to the forefront, not just watchful waiting; these “idiopathic” seizures are perhaps no longer really benign.
Along with the multiple articles or various roles of the immune system and chemokine and cytokine abnormalities related to seizures came a very interesting finding. In the “epilepsy and seizure” literature articles showed a direct linkage of the concept of peripheral inflammation mediating or leading to altered CNS excitability.35 36 It was shown that in a mouse or rat given a chemical causing GI inflammation, an increased susceptibility to seizures “strongly correlated with the severity and progression of intestinal inflammation.” If we’re not looking at proper dietary controls, if we’re giving impure supplements or agents that may be allergenic to a child, how much harm will be done? Worse, does the recognition of GI inflammation leading to brain inflammation confirm another likely cause, besides just viral, for the disproportionately large increase in seizures in “autistic” children?
This area needs a full pediatric investigation immediately. Inadvertently, many parents may be being asked to do things that are not only not helping, but may be contributing to increased long-term dysfunction and morbidity. While frustrated (to say the least) by the failure of current research ers to recognize that autism in the past had essentially no association with seizures; now when 35–40 percent of children with “autism” are prone to seizures, how much longer is it going to take to realize there is no relationship between what is happening now, and whatever we thought this was in the past?
Within the seizure literature, they are already looking at creative ways to reduce inflammation and block or prevent the attacks on the brain, I continue to believe that within this medical specialty, stepping back, looking at the bigger picture of that child and his or her general health, immunity, and brain could be a big step forward.
From a disorder being called “autism” in the 1940s and 1950s with no connection of note to seizures in those children presenting then, to the routine statement that 35–40 percent of these children today may develop seizures, is one very large additional finding that should clearly demonstrate this is not Dr. Kanner’s autism.
Pituitary—Hypothalamic Growth
Over the years, consistent with the medical world documenting a significant increase in thyroid disorders in adults and children, growth disorders in children, and other pituitary/endocrine disorders in general, came the recognition and understanding that the findings on NeuroSPECT, the neuroimmune-mediated shutdown of blood flow and function going on in the temporal lobes of the brain could begin to explain some of the enlarging endocrine dysfunction that was occuring. In particular, this could explain the increasing number of cases pediatric endocrinologists were seeing and calling “atypical.” More than a decade ago, I had some very interesting discussion with top pediatric endocrinologists regarding mutual patients that were having “baffling” growth issues. Pituitary markings/ findings might make sense if they thought of the general “pituitaryhypothalamic” system as not broken, but dysfunctional—thankfully this was logical to them.
To a pediatrician, always aware of growth and development in a child, aware of expected markers or ways to detect dysfunction, it became obvious that not only were there real issues for children from GH (growth hormone) dysfunction, but as I would frequently advice a parent whose child was being evaluated but who we knew had NIDS, neuroimmune issues, that just a “static” test of growth hormone function would often be normal, when a stressed or dynamic one would be abnormal. This becomes logical in terms of a system that is not broken, but is dysfunctional.
Over the years the idea of autoimmune, dysfunctional, but not broken was illustrated by the classical teaching of thyroiditis and its ability to result in increased and/or decreased function, depending upon the disease process, and activity levels. That was not the teaching for much of what we called pituitary disorders, but now the neuroimmune connection may begin to explain a lot of what has certainly been perplexing to pediatric patients and their endocrinologists.
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NEUROSPECT: A NEW TOOL
A NEW DIAGNOSTIC TOOL FOR UNDERSTANDING THE brain has emerged over the past two decades called NeuroSPECT. SPECT stands for single photon emission computed tomography. It is a sophisticated nuclear medicine study that looks directly at the cerebral blood flow in the brain and indirectly at brain activity.
A normal NeuroSPECT scan
How Does It Work?
A radioactive isotope is injected into a patient’s vein and then runs through the bloodstream and is taken up by receptors in the brain. A state-of-the-art camera, designed to detect where the compound has gone in the brain, captures these images and in conjunction with a computer creates maps blood flow, which correlates directly to brain activity. In other words, we can now witness changes in increased and decreased function in different areas of the brain, including deep inside the brain. While now PET scans can give ideas of function also, to this day, NeuroSPECT is considered to be consistently more objective and reproducible overall (especially with new computerized software).
What Does This Mean?
Everyone by now is familiar with CAT scans and MRI scans. These scans offer images of a static brain and its anatomy; they are great for seeing growths and injury but not useful for seeing activity (blood flow) in a working brain—in other words, how a brain functions. By comparing SPECT images of healthy brains with dysfunctional brains, we can accurately identify the disease processes taking place in immune-stressed brains. These SPECT scans illuminate such neuroimmune system dysfunctions as attention deficit disorder (ADD), autism, and chronic fatigue syndrome. We can finally see what is going wrong, which contributes hugely to both our understanding and the development of treatment plans that can treat these problems. What’s more, we can rescan after some appropriate passage of time to see if these treatments have been effective, thus providing physical validation of the efficacy of various treatments!
A child doing very well, with “The Goldberg Approach™” (still some frontal hyperness)
Impact
This is a first in human history. The brain has been a black box sitting on top of our necks, in charge of everything and a complete mystery, because we couldn’t see into it. We have been making inroads over the last few years with such tools as CAT scans and PET scans and MRIs . But this is the first time we can physically correlate brain activity with behavior. Now we can see the part(s) of the brain that are dysfunctional, and so if you have ADD-HD, if your child has autism, if your partner is suffering with chronic fatigue syndrome, we can see how that disease manifests in the brain. While debates continue between proponents of PET and proponents of NeuroSPECT, for now, SPECT continues to have an edge in reproducibility and objectivity for these types of disorders.
With Dr. Ismael Mena and Dr. Bruce Miller, I had a very unique opportunity, not usually possible outside a private practice. When I first began looking at these disorders, it was becoming obvious that the common link with the brain was the immune system. As a clinician, I will state strongly that nothing else could make sense and tie the various presentations together except a common denominator, the brain-immune system. This concept was firmly supported when at the first DAN organizational meeting in Dallas, in 1995, I watched Dr. Sudhir Gupta, a heavily certified adult immunologist, go up to the board and cross out multiple arrows referring to the body and presumed pathways, leaving o
nly: brain—immune system.
When I met Dr. Mena and became aware of his advanced work with NeuroSPECT imaging, it was the end of any further debate. The NeuroSPECT objectively showed blood flow in the brain, which translates accurately to function. As a private physician, I was able to send children and some adults for scans, procedures approved even by Blue Cross-Blue Shield insurance plans at the time, which would have been considered “experimental” and probably never authorized were I working in a university position. And I will never forget when I met Dr. Bruce Miller, considered a world leader, a genius in adult dementias. He took thirty-three scans of children presenting with “autism” (most research studies do ten or twelve scans) and separated them as mild, moderate, or severe, and then told me what was working and not working in each instance—all without meeting a single child. That was the end of my debate regarding the validity and usefulness of these scans.
NeuroSPECT–pinpointing areas of dysfunction–a child with “autism”
Because of this early work, Dr. Mena and I had the fortunate experience of obtaining scans (eventually more than 130) on children with “autism” before they were subjected to many of the anecdotal, potentially harmful therapies being done today. These “clean” children were remarkably consistent with both the adults presenting with CFS/CFIDS and the adolescents and children now presenting with mixed and quiet ADHD. The key repetitive finding was hypoperfusion, decreased function in key areas of the temporal lobes explaining much of this dysfunction in adults and then the children, with patterns that were consistent only with a neuroimmune, disease-type process, not a metabolic or congenital disorder.