Infantile autism begins early in life, usually
before the child is 30 months of age. While "in the past"
a rare condition with a "disputed" incidence of just
2-5 in 10,000 live births, it is seen as a devastating handicap
on psychologic and neurologic development, with potentially long-term
serious consequences. As described in the past, Autistic infants
did not demand attention, they did not enjoy being picked up,
nor did they cuddle or cling when someone held them. They rarely
smile at other people or look directly at them. In fact they often
appear to be the happiest when they are left alone. Mothers of
autistic children have noted an understandable lessened pleasure
in their maternal efforts. They complain that they feel they are
caring for an "object" rather than a person. Sometimes
this condition is not noticed at first, because physical development
generally appears normal in the autistic infant. These infants
are often viewed as "placid" babies. These children
begin to display various abnormal behaviors in the preschool years
1. A need to preserve sameness
2. Marked language abnormalities
3. Indexes of developmental disorder - strange body movements,
"soft" signs of neurological impairment
While the cause of autism is speculative different theories have
surfaced in the past including:
a) Brain injury
b) Constitutional vulnerability
c) Developmental aphasia
d) Deficits in the reticular activating system
e) An unfortunate interplay between psychogenic and neurodevelopmental
f) Structural cerebellar changes
With several different etiologies or biological
cause's, autism is considered a syndrome rather than a disease.
Some researchers have proposed genetic causes, viral causes, and
immunological ties, to be the cause. An increased incidence of
two or more miscarriages and infertility, as well as preeclampsia
and bleeding during pregnancy, have been shown to occur in mothers
of autistic children. Perhaps the disorders occurring in pregnancy
are affecting the fetus and showing up as autism in the children.
Studies have also been done comparing the maternal antibodies
of mothers with their autistic children. These findings suggest
that abnormal maternal immunity may be associated with autism
because plasma reactivity against lymphocytes was found in several
of the mothers. Antibodies reactive with lymphocytes of the father
were also found, suggesting the target antigen of the reactivity
was a parental antigen inherited from the father. Assuming maternal
antibodies may be associated with the development of autism, McConnachie
and McIntyre suggested maternal antibodies of mothers with repeated
pregnancy losses caused fetal demise, causing immunopathy by reacting
with antigens expressed on the trophoblasor extraembryonic tissues
of the developing embryo. It has been shown by some researchers
that antigens on the trophoblast cross-react with antigens found
Conceivably, maternal antibodies could react with
trophoblastic tissue, causing a transitory obstruction of blood
flow to the fetus resulting in nonlethal brain damage. Equally,
the abnormal behavior seen in autism might be caused by the immunopathological
damage done to the developing neural tissue of the fetus by the
maternal antibodies. 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. Whether
due to an underlying viral, retro-viral, other related entity,
a likely underlying genetic disposition, and/or other "environmental"
changes, 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,
Similarities between behavioral deficits reported in animals with
hippocampal lesions and autistic behavior have been noted by Boucher
and Warrington. 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. 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. While the rationale for an age limit
for the onset of autism has been discussed, it has been pointed
out that there is no firm evidence that similar or identical syndromes
might not develop in older children.
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. While these autistic features resolved
after clinical recovery, 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. 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. This case contributes circumstantial
evidence that a full blown autistic syndrome may be produced by
temporal (and parietal lobe) damage. (This author would note that
this is consistent with the areas of decreased function being
seen on NeuroSPECT scans with Dr. Ismael Mena - clinical research
in progress.) It also furthers the evidence that herpes simplex
encephalitis can cause an autistic syndrome. In 1975 an article
was published in Cortex 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,
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, 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. Confusion and differences may be
due to the heterogeneity (differences) in possible etiologies
or time/duration effects within this varied syndrome we label
"autistic". However, since Herpes virus has a predilection
for the temporal lobes it is possible to hypothesize that there
is an association
between temporal lobes and autism, but not necessarily a direct
cause and effect relationship. 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.
NeuroSPECT scans are becoming extremely informative,
as they show blood flow through areas of the brain. Blood flow
implies function/activity., As noted, the Autistic children that
I ave been able to obtain NeuroSPECT scans on (limited by age
and affordability), have shown a decrease in blood flow in the
temporal (and parietal) areas. Consistent with the reports of
temporal lobe dysfunction in Autistic kids, this is a very logical
finding. Surprisingly, and without good explanation, is the finding
of increased blood flow in the frontal lobes which is consistent
with ADD on the hyperactivity end. (Note: While this may explain
occasional success in the usage of Ritalin with some Autistic
children, Ritalin has the effect of decreasing blood flow on the
whole brain. Therefore, while helping the child if there is too
much flow in the frontal area, you may not be helping "over
all" if you are cutting low in areas that are already low,
such as in the temporal or parietal areas).
It is also interesting to note that in my working
with Chronic Fatigue Syndrome, "Immune Dysregulation"
for the past 12 years, in a recent study (pending publication)
we have observed a significant diminution of blood flow in children
suffering from CFS/CFIDS in both temporal and, to a lesser degree,
the parietal lobes. It is this researcher's opinion that there
is a strong connection between various immune dysfunctional/dysregulatory
states appearing over the last 12 - 13 years and the emergence
of an onslaught of "atypical" autism.
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. Congenital
rubella virus and congenital cytomegalovirus 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, antibodies
against putative brain serotonin receptors, and neuron-axon filament
proteins of the nerve cell. About 67% of the autistic sera contained
antibodies to NAFP. They were present in almost all patients with
abnormal cell-mediated immunity(CMI). An interesting observation
was that the sera from household contacts was also positive for
anti-NAFP (46% of the siblings or 55% of the parents). Antibodies
to NAFP have been previously reported in neurotropic "slow
virus" diseases (Kuru and Creutzfeld-Jacob disease) in man.
Other studies of household contacts of patients with degenerative
disorders of the brain have revealed ti-NAFP to be highly prevalent,
suggesting an association of an infectious agent (i.e. slow virus)
in the etiology of these diseases. With this hypothesis, eight
patients (six with abnormal CMI and two without the defect) were
placed on immunomodulant therapy. In six patients, parameters
in T-cell function and defects in AMLR were partially corrected.
Improvement was noted in terms of clinical status, speech, sleep,
and attention. After 8 weeks they could speak more than one command;
after 16 weeks they were able to write a complete sentence; and
all had increased attention span and or ability to sleep. The
two patients without abnormal CMI were nonresponders.
This research has also shown a significant depression
of CD4+ T helper cells and their suppresser- inducer subset, with
an increased frequency of the null allele at the complement C4B
locus in children with autism. As similar changes have been known
to occur in other autoimmune diseases, these researchers postulate
that the increase of serum concentrations of sIL-2 (soluble interleukin
2) and sT8 antigens indicates immune activation of a T-cell subpopulation
that may be important in the etiology of the disorder in some
children with autism. In a fashion similarly proposed for Alzheimer's
disease, it is possible that an anatomical alteration in the brain,
particularly the hypothalamus (because of its role in controlling
emotions and behaviors) of autistic children, may result in a
functional disturbance of the neuroendocrine-immune axis. Further
investigation is necessary. Many of the Autistic children I have
been evaluating have shown very high T-4 and T-8 counts.
While reactions to MMR (measles/mumps/rubella)
vaccine are in general mild, cases of meningoencephalitis occurring
in the third and fourth week post-vaccination have been reported
in the UK and elsewhere.,,,, Starting in February of 1990 the
British Pediatric Surveillance Unit asked all paediatricians to
report all cases with one or more reactions occurring within six
weeks of MMR vaccination. Reactions they were asked to look for
included neck stiffness (or sign of meningism), extreme irritability,
convulsions, altered consciousness, unexplained screaming attacks,
motor or sensory deficit, visual disturbance, visual deficit or
speech disturbance. In some of these cases mumps virus was cultured
from cerebrospinal fluid (CSF) .
Nucleotide sequencing of virus isolates has enabled
strains of vaccine origin to be separated from wild strains. Definite
cases of a vaccine-like strain of mumps virus were cultured from
CSF. While there was no sex differences in the cases reported
overall, an excess of males (2:1) were reported in the definite
or probable categories. Even though mumps occurs equally in both
sexes, complications of meningoencephalitis following both mumps
vaccination or wild infection has been reported more frequently
among males than the males,, with ratios ranging from 3:1 to 5:1.
One must bear in mind that the natural occurrence of meningoencephalitis
following mumps infection is estimated to be 1 in 400 cases. Before
the MMR vaccine was introduced in the UK, mumps was responsible
for a fifth of all reported cases of viral meningitis. Mumps vaccine
related meningoencephalitis is generally short lived or mild,
but some permanent sensorineural deafness has been reported. Published
evidence indicates that vaccine reactions are rare and unlike
the natural disease, does not lead to permanent sequel.
In this author's opinion, while the UK and Canada
have focused on the MMR vaccine, both its mumps component and
Rubella, there is much skepticism regarding the "true"
incidence of mumps meningoencephalitis as reported above, and
vaccine risk remains very doubtful, if existent at all. This country
has not experienced or reported any significant problems with
the MMR vaccine. While there may be a possible "triggering"
factor with Rubella and an immune active state, this remains an
unlikely cause of Autism. Unless further research creates a stronger
connection, it remains safer to vaccinate a child than not. Consistent
with the question of whether there is a peculiar or unusual immune
reactivity when a child is younger, waiting till a child is 3
or 4 could not be faulted, but with ongoing measles outbreaks
occurring at times, it is not something easy to recommend routinely
at this time.
Another difficult position to address, is the
possible role of fungi in the pathophysiology of Autistic dysfunction.
Candida albicans is arguably the single most important fungal
pathogen. Because it is a commensal organism present in virtually
all human beings from birth, it is ideally positioned to take
immediate advantage of any weakness or debility in the host, and
probably has few equals in the variety and severity of the infections
for which it is responsible. Clinically, there is abundant inferential
evidence that both mucocutaneous and systemic candidiasis are
typically associated with defects or weaknesses in the cell-mediated
immune response. They may reflect specific deficiencies in this
context, such as in chronic vaginal candidiasis, or chronic mucocutaneous
candidiasis. (One must note, that while one might anticipate neuro-cognitive
dysfunction in these states, it is not a primary focus of discussion.
Significantly, these states do not account for or induce an "Autistic"
state of CNS dysfunction, seeming to negate many metabolic theories
that abnormal metabolic products, seen in exceptionally high volume
in these type of patients, induce Autism.)
Epidemiological studies of C. albicans have been
hampered by the lack of precise and reproducible methods for identifying
isolates. Whatever the ultimate role and pathogenesis of Candida,
there seems to be no doubt that it can play a role in many pathologic
conditions. Yeast is certainly a potential pathogen in any immune
dysfunction/dysregulated state. Yeast may be seen as a secondary
phenomenon due to a generalized immune dysfunctional state. A
yeast "overgrowth" in the GI tract can interfere with
nutrient absorption, altering Amino Acid and protein metabolism
and thereby altering multiple body functions. I do believe that
it is logical, if you are in an immune dysregulatory state, you
may get an overgrowth in the G.I. tract. It is likely Candida
may play a role in what is referred to as the "leaky-gut"
phenomena. Some physicians believe you actually have a toxin released
by the yeast and absorbed into the body, affecting the nervous
Typical characteristics include:
a) nondeveloped or poorly developed verbal and
nonverbal communication skills
b) abnormalities in speech patterns
c) impaired ability to sustain a conversation
d) abnormal social play
e) lack of empathy
f) an inability to make friends
Also frequent seen are:
g) stereotypic body movements
h) a marked need for sameness
I) very narrow interests
j) preoccupation with parts of the body
k) changes handness or becomes ambidextrous, as they turn autistic.
Role of food allergens/sensitivities:
From the Department of Biochemistry, Birmingham University, United
Kingdom, Dr. R.H. Waring, along with B.A. O'Reilly, coordinator
of the Allergy-induced Autism Support and Self-Help Group is doing
some exciting work (pending pub.). They are currently carrying
out studies to see if children with known food/chemical sensitivities,
along with autism, have a deficiency of phenolsulphotransferase-P
enzyme and/or a low capability to oxidize sulfur compounds. From
the results they have obtained so far, all 18 children showed
to have a low enzyme level, and some had little capacity to oxidize
sulfur compounds. Now, after 40 children have been tested, the
results show the enzyme is low in every child. This enzyme is
necessary to metabolize amines and phenols. So it makes sense
that with a reduced level children will not be capable to fully
metabolize chemicals and foods that contain phenol. Autistic children
typically have adverse reactions to many medications. Sedatives
keep children awake, antibiotics woen behavior even anesthesia
may be a problem. Equally, a build-up of substances such as dopamine,
serotonin, and noradrenaline is possible as amines are also metabolized
with the same enzyme. As it is well documented that high serotonin
levels are found in some autistic children, if other body chemicals
build-up they may be metabolized and produce a substance similar
to phytoxins (plant toxins). In unpublished results Dr. Waring
ran blood tests on 14 children and found that all had low levels
of sulfate (the substrate which is used by the phenol-sulphotransferase-P
enzyme). These results show that there may be a fault in the manufacture
of sulfate, or it is being used up by an unknown toxic substance
the children are producing. [The test for this enzyme is simple;
one administers a dose of paracetamol (acetaminophen) followed
by a urine collection test for eight hours.] Parents reported
feverish, off-color children who's urine output was limited. Moreover,
some children were not able to urinate too cse to the eight hour
point. [Caretakers should be aware of the potential side effects
of this drug on autistic children , as it is given freely for
Many autistic children have major allergies or
intolerances to many chemicals and foods. The main offenders appear
to be wheat, cow's milk, and salicylates. Occasionally these reactions
may turn into urticaria or asthma, but in the majority of these
children the effect is the worsening of autistic-like behavior.
Interestingly, family history reveals eczema, migraines (especially
in mothers), hay fever, and asthma. These children crave the very
thing that does them damage. They do this not only with foods,
but also non-food items they ingest, mouth suck or chew (e.g.
metal, plastic, perfume, soap, plastic, etc.). Nearly all autistic
children become picky eaters at the time they "change,"
eating only a few different foods and both craving some and avoiding
some. Some autistic children begin to eat non-foods items with
notable immoderation. There has been speculation that diet may
effect other factors of the body. In a double blind placebo controlled
trial children were put on a restricted diet for a period of three
to four weeks. The foods allowed were two meats, two carbohydrate
sources, two fruits, a range of green and root vegetables, bottled
water, sunflower oil, and milk free margarine. The child's preference
was taken into consideration, and suspect foods or foods the child
craved were avoided. Worsening of behavior was connected to all
relapses with reintroduction of foods, except for four relapses
caused by cow's milk and two by cheese, which produced physical
symptoms only. This trial proved diet can contribute to behavior
disorders in children, and that their parents were able to report
on a behavior change caused by food that could be reproduced in
a placebo controlled trial. Although the way in which the diet
works is not clear, allergic, toxic or pharmacological mechanisms
may be involved. It is possible that diet (foods) ght induce changes
in brain perfusion similar to those found by Lou et al. reporting
on attention deficit disorder. Many parents have commented after
just the initial food/dietary phase, that their children had become
more manageable and more amenable to reason. Some to the extreme
of beginning to talk, that did not talk before. One should not
underestimate or ignore the potential reactivity of the immune
system, and various foods, proteins, peptides, or other sensitivities.
If a parent notices a good effect from a diet elimination, effort
should be made to support the family in their search for other
"logical" exclusions. Again, unlessthere is another
significant jump, "extremes" are usually not necessary
or justified. What I have experienced clinically, is that as a
child begins to do better, it is easier to judge what throws him/her
off. You should be expecting a continuous upswing and if there
is a fall back, try to think what did he/she have to eat before
the decline. What was done differently? Stay "tuned-in"
that way . It is also useful to keep a diary, particularly tracking
At the Autism conference in Las Vegas, July 1994,
Dr. Luke Y. Tsai presented information on neurotransmitters and
psychopharmacology in autism. While identifying and looking at
different neurotransmitters, neuroscientists have also found different
problems with too much or too little of one or the other. Too
much dopamine in the brain's limbic system ( the brain's emotion
center) , and too little in the cortex (the seat of reason), may
cause suspiciousness and an inability to process the information
in the rhythms and cues of social interaction. Inhibited children
may have excessive levels of norepinephrine. In people with too
much norepinephrine everything is pumped up; every stimulation
demands a response. The other side of the coin is that a shortage
of norepinephrine seems to rob people of the ability to know what's
important. Working memory (the part that stores information while
the mind considers if it is worth keeping and where to file it)
fails without enough dopamine. Altered central dopanergic function
in the midbrain has been implicated in the pathogenesis of Tourette's
Syndrome. Shortage of serotonin in the frontal lobes and in the
brain's limbic system (where emotions come from) seems to relate
to impulsivity; the person may not be able to connect disagreeable
consequences or what provoked them Obsessive-compulsive symptoms
may be caused by a serotonergic defect involving the basal ganglia.
Several drugs which either enhance or block the action of neurotransmitters
have been looked at in Autism and other neuro-processing disorders.
Haloperidol (Haldol) is a dopaminergic blocking
agent Diphenylbutylpiperdine (Pimozide or Orap) is a dopamine
antagonist Methylphenidate (Ritalin) may enhance CNS catecholamine
(dopamine and norepinephrine) release from sympathetic nerve terminals
and cause inhibition of re-uptake in the caudate nucleus Clonidine
(Catapres) is a alpha-adrenergic agonist Trycyclic antidepressants
inhibit the uptake of neurotransmitters at adrenergic nerve terminals
- this results in an increase of monoamine neurotransmission.
Clomipramine (Anafranil) and Fluoxetine (Prozac) are selective
inhibitors of serotonin re-uptake in the CNS Naltrexone - an opiate
Also at the Las Vegas conference, Dr. E. Gene
Stubbs hypothesized that interferon alpha (INF), a product of
many cells, but especially cells of the immune system, may be
a major factor in the cause of autism. When INF is given in large
doses to children with cancer, the result is that they withdraw
and become noncommunicative. These are primary symptoms of autism.
Also, children with autism have higher pain thresholds, and elevated
endorphins in their cerebral spinal fluid. INF can activate endorphin
receptors and is a potent analgesic. In addition, INF has been
reported to contribute to autoimmune disorders and allergies.
An increased incidence of antinuclear antibodies has also been
reported in these children. Children with autism frequently have
an impaired immune function: high levels of INF could impair the
In a preliminary study, 10 autistic children were
tested for their level of serum INF. All 10 children with autism
had a higher incidence of serum INF than the control adults. Normally,
levels of INF are not detectable unless one had an infectious
disease or illness. While the levels of the autistic children
were high, they were not as high as expected. (Note: My experience
thus far has shown inconsistent/scattered levels, with some Autistic
children being high, while others are low or normal. Interferon
could possibly be a potential marker to distinguish different
groups, but is routinely subject to multiple influences.) Other
preliminary evidence suggests that a subgroup of autistic children
have elevated levels of other cytokines (INF is considered a cytokine,
a soluble substance that is secreted by cells that affects other
cell functions). It is this author's opinion, that the "true"
pathophysiology lies in these other cytokines, rather than alpha
interferon. Research is urgently needed to sort these factors
out and open new doors for potentially dramatic therapeutic changes
within the next year or two, longer if not pursued urgently and
William Shaw, Ph.D., presented Organic Acid testing
which showed abnormal metabolites
in the urine of autistic children. Closely resembling normal products
of metabolism, these metabolites are presumably toxic and may
interfere with normal cellular energy production. Also, an increase
in the yeast-specific sugars arabinose and arabinitol has-been
Several explanations are possible:
a) These metabolites are due to a metabolic block
caused by a new inborn error in metabolism analogous to PKU.
b) These abnormal metabolites are produced by systemic or gastrointestinal
yeast in the human host due to yeast overgrowth caused by a deficiency
in cellular immunity and/or extensive antibiotic use. If so:
1. These metabolites are toxic and may be involved in causing
worsening some of its manifestations .
2. These abnormal metabolites are produced by yeast in the host
but are nontoxic
and their presence is insignificant.
c) The abnormal metabolites are fake due to yeast or microbial
urine. (This last possibility is not very plausible because the
normal children only
excreted very minute quantities of these compounds in their urine.)
Dr. Shaw's test may prove valuable in the diagnosis
and/or treatment choices in autism.
THIS AUTHOR'S CURRENT POSITION ON AUTISM:
It has been my direction to "backdoor" into working
with Autistic children (and other learning disorders). While ADHD
(Attention Deficit Disorder) caught my interest in medical school
and during my Pediatric training in the mid-seventies, we had
very few answers, and very little objective data to make decisions
on within the field. Therapy was very "symptomatic"
with little understanding or knowledge of the physiologic events
occurring within the brain. During this time, Autism was considered
a psychiatric disorder, with most children assumed to be "untrainable"
or "barely" trainable, to have low IQ's, and little
reason, if any, for optimism in the future.
In 1983 my wife came down with an undefined illness,
marked by recurrent flu symptoms, fatigue, sore throat, cervical
lymph glands, and, as was ultimately noted by researchers studying
my wife and other adults with this disorder, cognitive dysfunction,
characterized by short-term memory loss and decreased "processing"
ability. While desperately trying to figure out how to help my
spouse, and by that time other "mothers" and children
within my practice, I took a strong look at the principle of nutritional
supplementation and amino acid metabolism. During this time, some
Autistic children were referred in from West LA. To my surprise,
upon testing they had "Candida" titers higher than most
patients I was evaluating at the time, and Amino Acid profiles
with many similarities to those I was seeing in other patients,
with this "mysterious" new phenomena. As I was already
beginning to view this phenomena as "immune system"
related, it made no sense based on all previous teaching, What
did Autism have to do with the Immune system?
As I began attending and taking part in conferences
looking at advanced work on neuro-cognitive dysfunction, NeuroSPECT,
other advanced neuro imaging techniques and newer quantitative
measurements, there was/is an emerging understanding of the Neuro-Immune
axis and the concept of PsychoNeuroImmunology (the rapidly developing
field concerned with complex multi-dimensional interactions between
the immune system and the central nervous system). These discussions
and presentations raised the idea within me what if a more extreme
version of this was "Autism"? The idea of Autism being
linked to a severe Neuro-Immune Cognitive Dysfunction is logical,
one can say more than probable, at this point.
In addition to the articles noted above, there
are many papers already in the literature, noting various immune
abnormalities or potential markers. With each passing day, there
is less reason to doubt the potential significance of this for
"Autistic" syndrome children (?? all or some) and probably
other cognitive learning disorders. While metabolic factors certainly
play a role in these children, and need to be approached and understood
far better than they are now, it is extremely unlikely that the
origin of this dysfunction lies in a metabolic/genetic defect
as we currently understand them. At this time, I would propose
that these metabolic abnormalities are secondary to a dysfunctional
body. [ A process affecting the mitochondria (energy factories)
of potentially all cells in the body.] It seems likely that the
linkage here is a dysregulated immune system, and the effects
created by "out of control" cytokines. As noted above,
the ultimate origin or etiology may lie anywhere from genetic
factors, a "genetic disposition", to viral, retro-viral,
or "other" environmental factors. The good news is that
patients do not need to wait years for these answers to emerge,
and then years longer for testing of potential agents to develop/occur
and gain approval; thanks to research of the last 10 - 12 years
there are agents developed as "immune-modulators' which can
"adjust" various cytokine levels and other factors.
However, these newer, generally extremely safe pharmaceutical
agents, cannot be used without first eablishing a "justified"
population to try them with. While the literature and my personal
experience and observations supports without question the concept
of an "Immune Dysregulatory" dysfunction within Autism,
there exists no solid, medically valid publication, showing "controlled"
differences in Autistic Syndrome children. Within my own practice,
in running a series of tests including Immune markers and general
function, viral titers/exposure, general chemistry and metabolic
markers, one sees informally the branching of this group of children
labeled "autistic" into at least 3 patterns, maybe more.
It is important to define appropriate metabolic and immunologic
markers/parameters, so that we might better separate and understand
children's different response to therapy, etc.
In reality, most "antedotal" reports
of "successful" therapies for autistic children can
be understood through the concept of a dysregulatory Immune System
and/or altered metabolic sensitivities and dysfunction. In fact,
I would dare say that the only unanswered question in this concept
is whether one will be able to correct all neuro and metabolic
abnormalities via "Immune-Modulator Therapies", or whether
there will be a need for combined Immune and Metabolic approaches
Seeing children make dramatic cognitive progress
on modified Elimination diets, anti-fungal therapies, and anti-viral/immune
active therapy heightens the urgency to move forward into controlled
trials with definable markers. With the recent recognition of
the fact that if the brain "misses" certain stages of
development, you may never make that up fully in the future, the
urgency of helping these children can not be overstated. As noted
above, we can "accelerate" the medical/therapeutic process
greatly, but only if approached with the correct resources and
manner. In the meantime, there is some logic worth following in
approaching a child therapeutically at this time.
To start with, it's always best to start with
the concept of removing "negatives", clearing away "debris".
In that position, removing potential food sensitizing agents makes
sense, is any agent/protein stimulating a negative immune reaction
in the body will create more CNS dysfunction, via the Neuro-Immune
pathways. It is logical to attempt to normalize a child's nutritional
state, and often, since one is looking at a "stressed"
body, there is logic in providing extra nutritional supplements.
As a pediatrician, I feel it is very important
and logical to provide and replenish the bodies basic nutrients.
However, at present, parents must approach this area with skepticism
and caution. There are no controlled trials showing appropriate
dosing or long term safety of many "harmless" agents.
While there is logic in the concept of nutritional, "supportive"
approaches, there are dangers and there are product concerns (re
absorption, purity, over-dosage, etc.). Any nutritional manipulation
in children is open to dangers or new/induced metabolic problems,
vs. potential gains. It has been this authors experience that
megadosages usually seem to provide little if any gain vs. risk,
and that any "extreme" is subject to many problems in
Basic replenishment certainly includes a good
basic vitamin / mineral / fluoride supplement, additional Iron,
Ca++, Mg++, Zinc++ as indicated, a diet high in protein (the source
of natural amino acids, the "building" blocks of the
body), low in sugar, good nutritional value, but for the concerns
of allergy reactions or sensitivities, best to avoid whole wheat,
whole grains, "health-food" store eating. A product
such as Nu-Thera, while antedotal, has been evaluated and observed
in a reputable manner, such that it seems a good supplement for
most children, with a general caution not to dose at maximum dosing.
The area that a lot of mistakes have been made
in, is that of Candida or yeast. Yeast is not the answer to this
problem/syndrome. or perhaps any clinical syndrome it is frequently
associated with, but seems an opportunistic organism, that can
create or accentuate problems in an already dysfunctional host
or immune system. You can help a child by treating them for yeast
overgrowth or infection, but it and all current therapy should
be viewed as a step along the way of getting them better, it is
not an answer to the whole problem.
As diet plays a large role in the control of Candida,
reducing sugars, wheat products, and other yeast promoting foods
is logical within reason. In general, I do not see enough clinical
gain to justify "extreme" approaches via diet. There
are some children in which "extreme" diet eliminations
or adjustments may be logical.
Once basic diet needs are met, there seems good
logic, although again very little "hard" medical data,
in looking at some type of anti-fungal/anti-Candida approach.
(Tests that are being developed may help monitor therapy progress
with quantifiable markers in the future.) I prefer a trial of
Nizoral (Ketoconazole), using as indicated Diflucan, oral Amphoterecin
B, and occasionally Nystatin. While logical to continue if clinically
successful, care must be taken to monitor these medicines appropriately,
and likely "rotate" around, not stay on any individual
medication for too long a time period. Along with medication,
it is obviously beneficial to avoid sugar loads (e.g.. fruit,
fruit drinks, candies, sugar containing soda, etc.), but, as noted,
I do not believe it is necessary or overall beneficial to go to
"extreme" diets. Again, follow an approach of common
sense. Solving the "yeast" problem is not the answer
to Autism, and yet in some children it may be very helpful. Therefore,
a therapeutic trialchanging one variable or treatment approach
at a time - a critical concept for all therapeutic changes or
steps for any child) is justified per the above discussion.
Until "controlled" groups are identified
and therapies evaluated, any therapy is antedotal. I encourage
each parent to look upon their child as their own control. It
is critical to be patient and allow enough time to thoroughly
evaluate an agent for "gains" or "losses"
(to this author, one should not continue using any agent which
introduce "negative" and should avoid or approach with
great caution, any agent with potential negatives). With the appropriate
urgency to want to help these children, it is nevertheless a great
mistake not to "organize" your approach and proceed
logically, with time for appropriate judgments along the way.
I would again stress the need to remove identifiable "negatives"
if one expects to adequately evaluate "positives".
While there have been many "metabolic"
approaches and remedies discussed over the years, there must be
a far greater effort at controlled trials before any "special"
approach or product can be endorsed. If a parent can be sure of
no harm, then cautiously trying some of the products or supplements
out there may be useful, but must be evaluated closely on an individual
I have great hope for the possibility of what
are called "Immune-modulators". The antedotal reports
of success with DMG (an apparently good product at "low"
dosing) and Isoprinosine (?? Success) are examples of agents working
via the immune system. Zovirax, an anti-viral agent I have used
with some children positive for Herpes viral titers, may be successful
via an anti-viral effect, or an unrecognized immune-modulatory
effect. As noted, most successful antedotal therapies are explainable
or understandable through the immune system. With acceleration
of efforts, it is this author's hope that "controlled"
trials with newer, medically developed "immune modulators"
might be possible in the near future. Until that point, an overall
approach, looking at maximizing the health and function of any
individual patient, remains helpful to many children.
While always feeling the overall approach is far
more constructive by eliminating
negatives, and "positively" helping the body via supplement
or immune modulators; once one has done the best possible at present
with what is available and useful, there are existing "medications"
that may offer help, some of it/them perhaps even "positive"
As controversial a term as it might be, Prozac,
at low dosages, may have a very beneficial effect on cognitive
functioning and sleep cycle (off in so many of these children)
via its serotonin mediated effects and by increasing blood flow
, particularly in the temporal lobe/limbic system areas. Paxil
and Zoloft are in this class of SSRI's (Serotonin Re-uptake Inhibitors)
which may be particularly useful in the child who seems to space
out a lot, loose focus. On the other hand, the child who comes
across as very hyper, if continuing to be so after dietary trials
and therapy approaches noted above, may do very well with the
help of Catapres (preferably via the patch rather than tablets),
or the older children with a low
dose of Cylert. Opioid blockers such as Naltrexone may play a
constructive role in some patients, but have not been investigated
or pursued much by this author to date. While the goal must be
"normalization" of the body by directed therapy, some
of these agents can be useful if used judicusly and appropriately.
It has been my privilege and pleasure to see many
children improve substantially by the above measures. This has
only increased and emphasized the need to take these approaches
into controlled trials, and to hopefully make possible the introduction
of new agents in a very short time. In the meantime, work with
a physician or therapist that will work with you and your child.
Go slowly, with a concept that when things are better, it takes
time for the brain and body to change physiologically. Look for
combining and building upon safe approaches and your child's "positive"
clinical responses, being careful not to create "negative"
effects or to act too quickly to document changes. Any parent's
anxiety and desire "to find the answer for their child"
is understandable and commendable, but at this point, slow/progressive
clinical observation and trial is the best probability of success,
while we hopefully speed up the day of new therapy's and understanding.
I might add that this is not a "pipe" dream or need
be 5 - 10 years off.
Agents exist now that may have tremendous potential to help. They
can become available for trial, as soon as medically credible
protocols and justification exist. There are a lot of us trying
to make this happen.
We all know it is time, we all know it should
happen. We need to make it happen, for all of you as parents,
physicians, and children.
Michael J. Goldberg, M.D.
Literally, as each day and month passes, we are loosing children
who by all recent
indications, are both "savable", and likely "recoverable"
if dealt with soon enough. At a critical time like this, there
is a general slowness in approach, with debate raging louder between
Immune and Metabolic schools of thought, and the "no"
medical problem thinking of most of "Academics" still.
Sadly, much of the accelerated attempt of funding patients are
fighting for, will be spent pursuing "more of the same"
rather than looking at the new possibilities for the future. At
a time like this, with technology and new biomedical advances
at our disposal, there is only one way to succeed (I define "succeed"
as make advances in therapy for "autistic" syndrome
children). If we do not make use of tools and techniques that
have evolved in the last five to seven years appropriately, and
at academic, peer-reviewable levels, we will never succeed in
changing the pace of therapy for these children. Happily, as I
know word is beginninto circulate, I am attempting to initiate
a controlled cytokine project, in an attempt to open the door
for major therapeutic change within twelve to eighteen months
(sooner if resources mobilize faster).
There are many advances possible now, but they
will NOT occur/succeed unless data and studies are done at a peer-reviewable
level (clinically designed and coordinated to speed up the emergence
of new ideas, new concepts). Any other efforts will ultimately
be more "spinning of wheels".
At the DANN conference in Dallas, January 1995,
there was a wonderful coming together of ideas and exciting new
directions, but a sad split between "metabolic" and
"immune" camps. Also evident was the absolute "distaste"
for the mention of academics. I stand strongly behind the convictions
expressed above. I would politely challenge anyone to produce
a model that has succeeded for any disease in the past, without
ultimate evolution and definition by defined studies, acceptable
at Academic levels.
Without objectivity, no therapy can be appropriately
evaluated, nor will new therapies (already in existence) become
accessible. While metabolic vs. immune discussions are interesting,
the only major change on the near horizon, will be if the idea
of immune-modulators (agents already in existence, but for which
we must provide an objective basis to open the doors to their
usage) can be tried, and is optimistically successful (many researchers
I have been involved with over the last five to ten years, believe
success is likely, but remain skeptical till proven). While we
"debate" other ideas and options, I believe it is urgent
to accelerate efforts to make possible testing of these agents
in autistic syndrome children as soon as possible! As noted, with
increased discussions already appearing relating to "auto-immune",
"inflammatory",origins for "sub-populations"
of children, I would propose without hesitation, that "immune-modulating"
agents if effective, will be far safer than steroids or other
agents nodiscussed, and needless to say, a better alternative
than discussing surgery or severe behavior therapies for these
Examining the last ten to twelve years, it has
become obvious we are looking at new patterns of disease and illness,
that do not fit previously described syndromes, etc. Attending
conferences over the last 7 years, being exposed to many "cutting
edge" technologies and ideas, one trend emerges. We are looking
at a process, appearing to decrease flow/function in the temporal
lobe of the brain (other areas may be affected, but the temporal
lobe I would propose is the key and common denominator in this
process) affecting individuals differently based on their age,
and maturation of their immune system. The common denominator
making sense through these discussions has been the immune system
and a state of "dysregulation". I would propose to all
of you, that while many metabolic and other phenomena, make sense
when thought of in a state of or propensity for immune activation/dysregulation,
no known pediatric or adults metabolic process makes sense as
a model for a "primary" metabolic defect in these children
and related patients. Therefore, while we may to some degree help
the body metabolicly, develop new markers, and even answer some
very interesting questions over the next ten years, we are unlikely
to make major medical changes or even approach a cure while focusing
on and dealing with what appears to be "secondary" metabolic
phenomena, explainable fully by altered cellular metabolism (a
fact brought out in many respectable articles over the last 5
years, and accepted at NIH/Academic levels, etc.). This is a dysfunction
that is logical secondary to altered cellular mitochondria and
immune reactive phenomena. In this light, why are many physicians
and researchers trying to "reinvent the wheel", when
there are models and involving technologies explaining all we
are discussing logically and with more and more factual physiology.
Because, there are still gaps in the above physiologic understanding,
basic science will still take (if left alone) probably five to
ten years to get into any meaningful therapy discussions. These
children do not have "years" to wait. Dr. Gupta and
Dr. Nancy Klimas (Univ. of Miami), are ready to finish and proceed
with a protocol to do a controlled study of cytokine levels in
"Autistic" syndrome children. These are professors,
who if the study is successful, would be unchallenged at the NIH,
Academic levels, many have come to disdain. And yet, as I tried
to say at the DANN conference and in many other discussions, if
we do not move at "Academic" levels, few will listen,
and little will really be done. If we do not unite as physicians
and patients to speed up funding for at least the basic cytokine
project, we are as guilty as the "establishment" at
slowing up, rather than speeding up this process.
Potentially worse, as this "epi-phenomena"
has grown, there are more and more desperate parents and suffering
patients. As noted above, sadly, while there is the potential
to bring into play safe, essentially non-toxic medical agents,
physicians and researchers are turning to "old" ideas,
(i.e. steroids and other potentially toxic metabolic agents) instead
of looking at newer and safer ways to treat this phenomena in
children (and adults). In addition, while agents like Prozac and
Paxil have the ability to actually help the brain if used physiologically
(at low dose they can increase temporal blood flow, and work as
very mild immune modulators), physicians, as has been done in
the past, are using medications at non-physiologic dosages and
accepting multiple side effects or partial results, because something
seems like a good idea. As much as I have become an advocate of
Prozac and Paxil, this has come only after understanding that
they could serve a role in normalizing CNS function, and were
very safe class agents if continued. However, I do not believe
this or any other currently available agent is going to be successful
without an "overall" sound metabolic, nutritional, and
immune approach prior to its usage. Likewise, even with the potential
emergence of immune modulating agents for therapy, I am not sure
whether they will be effective by themselves (as implied by some)
or need to be used in a "combined" approach, something
that could be designed into controlled trials, if we have the
right input and "control" (this is not the usual way
Academic's or Drug companies have wanted to design or fund trials
in the past).
Watching this "epi-phenomena for the last
ten to twelve years, other factors are obvious. If patients are
not appropriately identified by scientifically validated markers,
we will never sort out or be able to understand the reasons why
different patients respond to different agents (pharmaceutical,
nutritional, metabolic, etc.). The truth is what we call Autism,
ADHD, CFIDS, etc. are all "heterogeneous" populations,
in which any drug or therapy trial appears doomed to frustration
and failure, without newer, appropriate "objective"
markers. At the Dann conference, the idea that we needed to pursue
Academically acceptable studies at peer-reviewable levels, was
met with very mixed feelings, and some open hostility. Without
this approach, I challenge anyone to tell me how we are going
to have significant impact for patients on the medical establishment.
In fact, unlike the past, the situation with "restricted"
medicine and "fixed guidelines" by HMO and insurance
companies, is going to deny care to these children and unless
we all help prove the system wrong. Unlike the past, there are
ways to do that now that did not exist.
As noted, parents are desperate, reaching for
straws, and may be directed or advised into long-term negatives,
rather than gain. A metabolic dysfunction by altered cellular
metabolism and immune dysfunction, is not likely to correct by
any excess of agents introduced to the serum of the bodies. A
backup of these agents, may, as noted, be in themselves toxic.
Along with others, I have been looking at the idea of an agent
called Trental. In theory, it could be an excellent temporary
agent, but I have yet to be able to get an answer, regarding long
term safety for children. Any therapy proposed must be safe without
a doubt. Many of the physicians at the DANN conference had questions
with respect to some current therapy usage, and many of us are
aware that while some agents may be helpful, some can be toxic,
even those called nutritional or metabolic.