The Myth of Autism
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A HISTORY OF MEDICAL RESEARCH
A REVIEW OF THE EXISTING MEDICAL LITERATURE relative to autism research reveals evidence of an emerging medical disease process in these children. For instance, research indicates that autism can follow infectious disorders affecting the central nervous system including encephalitis.1, 2, 3, 4 Multiple studies have focused on various anatomic locations of suspected dysfunction.5, 6, 7, 8 It is important to note that emphasis is often put on the medial temporal lobe. Pertinent to this new “model” of dysfunction are the multiple published reports of autistic symptoms developing in association with encephalitis in children.9 Most of these reports cite injury to the temporal lobes as part of their findings. This is consistent with the areas of decreased function identified on NeuroSPECT scans initially working with a Dr. Ismael Mena and a Dr. Bruce Miller at HGH-UCLA, and now continuing with Dr. Mena (long distance from Chile, no less) and a Dr. Michael Uszler, based in Santa Monica. Interestingly, along the way we’ve had a few doctors involved who, with some exposure to our research seemed to go from open skeptics to scientists recognizing the existence of a problem worth further research and investigation. It all comes back to restrictions of our system; we can’t open up new answers, get to understanding, if we are not willing to use or accept new tools, offering potentially new, objective information about the “black box” we have called the brain. Restricting most studies, particularly the very large NIH-sponsored study looking at a large number of children and their families, to MRIs, or CAT scans, or other markers and tests I was taught to use thirty years ago, is saying that while we have a major crisis, and while we are going to commit major resources to it, we are going to make sure we cannot get any really new information or new data that might undermine old ideas. This approach is frightening and should be of great concern to others out there looking for help and potential new answers.
New research techniques are increasing the rates at which herpes simplex virus (HSV) sequences are being identified in temporal lobe tissues 10, 11, (i.e., locales likely to be substrates for various aspects of autism). In 1975, an article was published in Cortex12 describing a syndrome similar to autism in adult psychiatry. The condition involves the loss of emotional significance of objects, the inability to adapt in social settings, the loss of recognition of the significance of persons, and the absence of sustained purposeful activity after temporal lobe damage.
The literature also comments on the cognitive and behavioral deficits caused by temporal lobe damage in herpes encephalitis. There are many reports, particularly in the British literature,13 suggesting a connection to coxsackie/enteroviruses, while in the United States it has been suggested that many cases may be linked to the herpes family of viruses (i.e., EBV, HHV6, HHV7, CMV, etc.). 14, 15, 16, 17, 18 Neither theory has been conclusively proven, nor has the evidence for a contagious disorder been conclusive (although some have inferred it based upon incidents related to epidemic outbreaks19, 20). However, HSV in humans has long been known to prefer temporal lobe and limbic sites. One theory focuses on the olfactory nerves as a possible route for infection, but oral cavities may also provide entry. In 1996, O’Meara et al. postulated the following: “Inoculation of murine tooth pulp with HSV selectively infected the mandibular division of the trigeminal nerve and caused encephalitis predominantly affecting the temporal cortex and limbic system, a pattern of disease similar to human HSE [herpes simplex encephalitis]”.21
While other studies have also implicated the temporal lobes in the pathogenesis of autism,22, 23 a direct association between temporal lobe pathology and autism has not yet been proven conclusively. In fact, research has found a variety of lesions in the “autistic” brain, particularly in the cerebellum.24 These variable findings may be due to the heterogeneity (differences) in the possible etiologies or time/duration effects within this syndrome.
Although herpes viruses have a predilection for the temporal lobes,25 the course of autism does not suggest an acute infection with traditional herpes viruses.26 However, delayed temporal lobe development early in life may produce different symptoms from those arising from deterioration or destruction of previously normal lobes.
In summary, although not conclusive, past research further strengthens the linkage of the temporal lobe and “autistic” symptoms. Boucher and Warrington noted similarities between behavioral deficits reported in animals with hippocampal lesions and autistic behavior.27 Medial temporal lobe damage on pneumoencephalograms was reported in a subset of autistic children.28 Damasio and Mauer proposed that “the syndrome results from dysfunction in a system of bilateral neural structures that includes the ring of mesolimbic cortex located in the mesial frontal and temporal lobes, the neostriatum, and the anterior and medial nuclear groups of the thalamus.” At least two other studies have also implicated the temporal lobes in the pathogenesis of autism.29, 30
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THE EVIDENCE
WITH NEW AND MORE PRECISE TOOLS and technology available to us now, the medical anatomy of “autism” is gaining definition after years of conflicting findings. Currently, EEG abnormalities,1 immune markers, and NeuroSPECT findings support the concept of a medical disease process occurring in these children’s brains. For example, it is generally recognized that an EEG finding of “slow” waves or “abnormal” brain wave activity is often consistent with the idea of an underlying and unknown encephalopathy/encephalitis.
In addition, ongoing work with the NeuroSPECT strengthens the connection of blood flow abnormalities and neurodysfunctional states, particularly in situations in which patients appear to have immune and/or possible viral etiologies. NeuroSPECT scans capture blood flow through specific areas of the brain. Blood flow correlates with function/activity.2, 3 As noted, NeuroSPECT scans on children with autism have shown a decrease in blood flow in the temporal and occipital areas, which is consistent with past reports of temporal lobe dysfunction in such children. Neurological models of the brain correlate right temporal lobe areas with social skills and left temporal lobe areas with speech and auditory processing, all of which are compromised in autistic children. It should also be noted that there is no good explanation for our finding of increased blood flow in the frontal lobes of a group of these children, which is more consistent with ADD and hyperactivity. Further research is required relative to this finding.
When monitoring the emerging body of evidence related to the immune system and its interactive messengers, interleukins and cytokines, it appears that a dysregulated immune system state—whether triggered by a virus, genetic disposition, or intrauterine, prenatal, or neonatal stress or trauma—may account for the cognitive processing and other deficits seen in some children with autism. This concept is supported by the lack of consistent neurological/anatomical abnormalities and metabolic abnormalities in these children. We now know that neuropolypeptides called cytokines can and do restrict brain blood flow under certain conditions. In these children, we may be looking at an immune system continually sending out signals to restrict brain blood flow. Whether this continues as an autoimmune reaction (whereby the immune system continues this pathway with no active reason to do so) or is due to the presence of a retroviral or other viral process is open to further research. However, the concept of an immune-related disease process in a large number of these children appears unquestionable at this point in time.
Many autistic children have major allergies or intolerances to many chemicals and foods. While occasionally these reactions may turn into urticaria or asthma, the effect in the majority of these children is the worsening of autistic-like behavior. Family history often reveals eczema, migraines (especially in mothers), hay fever, asthma, and histories of other disorders, which are often immune-mediated. These external symptoms may well prove to be signs of a hyper-reactive/stressed/dysfunctional immune system underlying the biochemistry of these children. Many anecdotal reports of successful therapies for autistic children (e.g., gammaglobulin, allergy-free diets) can most likely
be explained through the concept of regulating a dysfunctional immune system and/or altering metabolic sensitivities and dysfunction.
Examples of autism’s probable connection to immune dysfunctional states are seen in the following:
Extensive clinical work over the last four to five years further supports the hypothesis that we are facing an immune-mediated disease state affecting the central nervous system (CNS) in these children. The literature is replete with articles connecting immune system abnormalities to autism, ADD, ADHD, CFS, and CFIDS. Here are several main examples:
Multiple researchers have found evidence that autoimmunity is a possible mechanism to explain autistic symptoms.4, 5, 6, 7, 8
An increased incidence of two or more miscarriages and infertility9, as well as preeclampsia10 and bleeding during pregnancy11 has been shown to occur in mothers of autistic children. There are also multiple studies in the obstetrical literature connecting these events to immune autoantibody production.
Studies have been done comparing the maternal antibodies of mothers with their autistic children, 12 suggesting an association of abnormal maternal immunity with autism. Antibodies reactive with lymphocytes of fathers of autistic children have also been found.
Multiple researchers have shown an interaction of maternal antibodies with trophoblast or embryonic tissue antigens, and a cross-reaction with antigens found on lymphocytes.13, 14, 15, 16
Researchers have also shown a significant depression of CD4+ T helper cells and their suppresser-inducer subset17, 18 with an increased frequency of the null allele at the complement C4B locus19 in children with autism. As similar changes have been known to occur in other autoimmune diseases,20, 21 these researchers have postulated that immune activation of a T cell subpopulation may be important in the etiology of the disorder in some children with autism. Note: Many of the autistic children evaluated in studies and within my practice have shown very high CD4 and CD8 counts, low natural killer (NK) cells, or other “markers” consistent with immune dysfunction/dysregulation.
Abnormalities of cell adhesion molecules (NCAM)22 have been reported.
Antibodies to neurofilament axonal proteins (NFAP) have been noted in autistic children 23 and have been reported in neurotropic “slow virus” diseases (kuru and Creutzfeldt-Jakob disease) in adults.24 Other studies25, 26 have suggested an association of an infectious agent (slow virus) in the etiology of these diseases. This is considered indirect evidence that some cases of autism may also be associated with the concept of a slow virus.
Anti–central nervous system serum immunoglobin reactivity has been reported that was specifically directed against the cerebellum. 27
A small percentage of autistic children with demonstrable immunologic abnormalities have normalized their autistic symptoms with intravenous immunoglobulin treatment.28, 29 This result shows that immune abnormalities can cause autism in a subset of children and that acquired autism can be effectively treated.
Singh et al. hypothesized that autoimmunity secondary to a virus infection may best explain autism in some children.30 Congenital rubella virus 31 and congenital cytomegalovirus32 have been indirectly involved as causative factors in autism.
Given this support and much more from the medical research literature, the concept of immune dysregulation as a medical disease process in childhood neurocognitive dysfunction is an emerging reality. This concept could easily account for a significant portion of the increase of neurocognitive diagnoses over the last twenty to thirty years. Whether the etiology of this dysfunction is related to environmental factors (e.g., ozone layer depletion, local toxins, etc.), new retroviruses, or stealth, spongiform or other viruses (or altered viral responses), we now have a medical hypothesis that can facilitate the definition of clinical subgroups and lead to the treatment of these patients without first determining the exact/specific origin or etiology.
If an infectious etiology indeed exists, it may be as ordinary as the common cold or so rare that we have not yet developed the tools to identify or study it. Whether an ongoing agent is present, or the body simply remains in a dysfunctional state, it seems likely we are confronted with a phenomenon/illness that has multiple etiologies, multiple origins, and various clinical manifestations. At this point, they appear linked by an immune dysfunction or possible viral-mediated state. Genetic predisposition to this syndrome may have a great deal to do with why certain individuals suffer with these symptoms. However, we must begin to consider these apparently heterogeneous expressions as linked and potentially treatable through the common pathway of an immune dysfunctional/CNS dysregulated state. For example, in a study33 on chronic fatigue syndrome (CFS), Dr. Mena and I reported a significant diminution of blood flow in both the temporal and, to a lesser degree, the parietal lobes in children suffering from CFS and chronic fatigue immune dysfunction syndrome (CFIDS). These findings are similar to those previously noted in children with acquired autism.
The ASD medical disease hypothesis began to take form in the 1980s when multiple researchers found evidence that autoimmunity was a possible mechanism to explain autistic symptoms.37,38,39,40,41 Since these initial observations, the body of evidence has grown dramatically—witness this statement from Johns Hopkins Department of Neurology website (December 2009):
Current evidence suggests that neurobiological abnormalities in autism are associated with changes in cytoarchitectural and neuronal organization that may be determined by genetic, environmental, immunological, and toxic factors. Since neuroglia has central roles during brain development, cortical organization, neuronal function and immune responses, we hypothesize that neuroglia may contribute to the pathogenesis of autism in several ways:
Neuroglia may be dysfunctional during the process of neuronal organization and plasticity of cortical and subcortical structures, a change that may contribute to the neuropathological abnormalities observed in autism.
Neuroglia may react to extrinsic factors, such as systemic immune responses, toxins, or infections, and produce disturbances in the CNS microenvironment that facilitate the development of immune-mediated reactions.
Abnormal neuroglial activation may be present in autistic patients due to genetic susceptibility to inflammation, a change that can lead to abnormalities in neuronal-neuroglial interactions.
Neuroglial activation can trigger the development of cellular or humoral immune responses that lead to neuronal/neuroglial dysfunction.
1. Systemic immune responses may trigger abnormal pathogenic reactions in neuroglia.
Our experimental approaches include study of brain tissues obtained from patients with autism, determination of the profile of cytokines and chemokines and characterization of immune-mediated reactions in cortical and subcortical regions of autistic brains. Further understanding of the role of neuroglia and immune reactions in the neurobiology of autism may contribute to the design of therapeutic interventions that minimize the neurological and behavioral abnormalities that occur in this disease.
The cornerstone research was published in two journals (“Brain Inflammation Is a Sign of Autism,” Annals of Neurology, 15 November 2004; 01:18 and “Immunity, Neuroglia and Neuroinflammation in Autism,” Internet Review of Psychiatry, December 2005; 17[6]: 485–495). The study demonstrated the presence of neuroglial and innate neuroimmune system activation in brain tissue and cerebrospinal fluid of patients with autism, findings that support the view that neuroimmune abnormalities occur in the brains of autistic patients and may contribute to the diversity of the autistic phenotypes.
Here are multiple other studies that almost indisputably point to NIDS (or an immune-mediated encephalopathy) as playing a role in children and adults now labeled ASD:
Science reported in October 2009 that a relatively new retrovirus, XMRV, was identified in a higher-than-normal proportion of CFS patients, and also reported similar findings for people with autism, atypical multiple sclerosis, and fibromyalgia (“Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patie
nts with Chronic Fatigue Syndrome,” Science Magazine New York, New York, Published Online, October 8, 2009).
In February 2009, the Journal of Neuroimmunology published a study concluding that ASD patients displayed an increased innate and adaptive immune response through the Th1 pathway, suggesting that localized brain inflammation and autoimmune disorder may be involved in the pathogenesis of ASD (“Elevated Immune Response in the Brain of Autistic Patients,” Journal of Neuroimmunology. 2009 Feb 15: 207 [1–2]: 111–6 Epub 2009 Jan).