Research to support immune dysfunction theory

Similarities between behavioral deficits reported in animals with hippocampal lesions and autistic behavior have been noted by Boucher and Warrington⁽¹⁾. They found memory deficits in infantile autism similar to the memory deficits found in the amnestic syndrome. Medial temporal lobe damage on pneumoencephalograms has previously been reported in a subset of autistic children⁽²⁾. These findings were particularly evident on the left side. Damasio and Mauer have also 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." (Noteworthy, is that much emphasis is put on the medial temporal lobe).

By definition, autism has an early onset before 30 months of age, while disorders appearing later in life have been thought to be symptomatically different from autistic handicap conditions. Publications over the last 13 years have cast some doubt on these relationships. It has been pointed out that there is no firm evidence that similar or identical syndromes might not develop in older children⁽³⁾.

Autism can be associated with a variety of disorders affecting the central nervous system including encephalitis. In 1981, DeLong, Bean, and Brown described three children between 5 and 11 years of age who developed autistic features while having an encephalitic illness. One patient had high serum herpes simplex titers, and a CT scan revealing a lesion of the temporal lobes, mainly on the left side. The other two patients had normal CT scans.

Gillberg in 1986 described the case of a 14-year old girl who developed a "typical" autistic syndrome after an attack of herpes simplex encephalitis⁽⁴⁾. Widespread bilateral destruction of the brain parenchyma and the temporal lobes was found on CT; there was also some involvement of the lower parts of the parietal lobes. The autistic symptoms persisted long after the acute phase of the encephalitic illness.

In 1975 an article was published in Cortex⁽⁵⁾ describing a syndrome similar to autism in adult psychiatry, involving loss of emotional significance of objects, inability to adopt in social relationships, loss of recognition of the significance of persons, and absence of sustained purposeful activity after temporal lobe damage.

In 1989 an article appeared in the Journal of Autism and Developmental Disorders⁽⁶⁾, describing a 14-year old boy, with a normal history until the second grade, when he was admitted to the hospital with herpes simplex encephalitis. Later he developed significant language, social, and memory deficits. The research group commented on the cognitive and behavioral deficits caused by temporal lobe damage in herpes encephalitis. While other studies have also implicated the temporal lobes in the pathogenesis of autism^(7,8) this does not prove a common association between temporal lobe pathology and autism. Research has found a variety of lesions in the brain, particularly the cerebellum⁽⁹⁾ since Herpes virus has a predilection for the temporal lobes⁽¹⁰⁾ it is possible to hypothesize that there is an association between temporal lobes and autism, but not necessarily a direct cause and effect relationship⁽¹¹⁾. It is equally important to note that failure of development in temporal lobes early in life may produce different symptoms from those arising out of a later destruction of previously normal lobes.

From the Journal of Clinical Immunology and Immunopathology, Singh et al. hypothesized that autoimmunity secondary to a virus infection may best explain autism in some children⁽¹²⁾. Congenital rubella virus⁽¹³⁾ and congenital cytomegalovirus⁽¹⁴⁾ have been indirectly involved as causative factors in autism. Researchers found evidence for autoimmunity as a possible mechanism to explain autism, based on a cellular immune response to myelin basic protein⁽¹⁵⁾, antibodies against putative brain serotonin receptors⁽¹⁶⁾, and neuron-axon filament proteins of the nerve cell⁽¹⁷⁾.

Autism and the Immune System

It is our belief that "Autistic Syndrome" probably is a state of dysfunction induced in the brain by a dysregulated immune system. It is possible that this dysfunction may occur in individuals that have a genetic predisposition. In theory, this predisposition could be triggered by various stresses placed on the child’s immune system. It’s severity varies with the individual and age of onset.

It can be compared to blindness. There are many people who are blind, but the cause of their blindness may be very different. For whatever the reasons (genetic, environmental, a combination of viruses, etc.), what is occurring appears to be an immune mediated, abnormal "shut down" of blood flow in the brain and therefore central nervous system function.

In adolescents and adults, this dysfunction may manifest itself as CFIDS (Chronic Fatigue Immune Dysfunction Syndrome), ADHD, and various other atypical auto-immune disorders associated with neuro-immune dysfunction. In older children, it is seen as variants of ADD (Attention Deficit Disorder) / ADHD. And in younger children/infants, it appears as autism, autistic syndrome and PDD (Pervasive Development Disorder).

The multiple metabolic, physiologic, and immune markers that are abnormal in these children, "make sense" when you think of the bigger picture and consider the primary cause of autism as immune dysfunction, creating multiple cellular / mitochondrial dysfunctions.

This offers an explanation for the progressive process of the autistic syndrome that occurs sometime between 15-24 months of age. It is this immune mediated, abnormal "shut down" of blood flow in the brain that affect the language and social skills area of the brain and central nervous system function.

Clinical Manifestations

Typical characteristics include:

• nondeveloped or poorly developed verbal and nonverbal communication skills
• abnormalities in speech patterns
• impaired ability to sustain a conversation
• abnormal social play
• lack of empathy
• an inability to make friends

Also frequent seen are:

• stereotypic body movements
• a marked need for sameness
• very narrow interests
• preoccupation with parts of the body
• change of hand or becomes ambidextrous, as they turn autistic.

• With several different etiologies or biological causes, autism is considered a syndrome rather than a disease. Some researchers have proposed genetic defects⁽¹⁸⁾, viruses^(19,20) and immunological ties^(21,22,23) to be the cause.

  While the literature has speculated regarding the above hypothesis and many others, at this time there appears to be an enlarging group of children, whose origin seems linked to the concept of an Immune-Dysregulatory phenomenon. The dysfunction / lack of blood flow can eventually lead to injury of nerve cells, which offers a possible explanation for the abnormal brain waves and the large numbers of autistic syndrome children suddenly being labeled as "Landau-Kleffner."

  Whether due to an underlying viral, retro-viral, or other related entity, a likely underlying genetic disposition, and/or other "environmental"factors, the number of children affected seems to be rapidly increasing. Many of these children do not fit classic autistic profiles, but are frequently labeled high functioning autistic, atypical autistic, PDD, etc.