| SUMMARY
Autism is a syndrome characterized by impairments in social relatedness
and communication, repetitive behaviors, abnormal movements, and
sensory dysfunction. Recent epidemiological studies suggest that
autism may affect 1 in 150 U. S. children. Exposure to mercury can
cause immune, sensory, neurological, motor, and behavioral dysfunctions
similar to traits defining or associated with autism, and the similarities
extend to neuroanatomy, neurotransmitters, and biochemistry. Thimerosal,
a preservative added to many vaccines, has become a major source
of mercury in children who, within their first two years, may have
received a quantity of mercury that exceeds safety guidelines. A
review of medical literature and U.S. government data suggests that
(i) many cases of idiopathic autism are induced by early mercury
exposure from Thimerosal; (ii) this type of autism represents an
unrecognized mercurial syndrome; and (iii) genetic and non-genetic
factors establish a predisposition whereby Thimerosal adverse effects
occur only in some children.
INTRODUCTION
Autistic Spectrum Disorder (ASD) is a neurodevelopment syndrome
with onset prior to age 36 months. Diagnostic criteria consist of
impairments in sociality and communication plus repetitive and stereotypic
behaviors (1). Traits strongly associated with autism include movement
disorders and sensory dysfunction's (2). Although autism may be
apparent soon after birth, most autistic children experience at
least several months, even a year or more of normal development
-- followed by regression, defined as loss of function or failure
to progress (2,3,4).
The neurotoxicity of mercury (Hg) has long been recognized (5).
Primary data derive from victims of contaminated fish (Japan - Minamata
Disease) or grain (Iraq, Guatemala, Russia); from acrodynia (Pink
Disease) induced by Hg in teething powders; and from individual
instances of mercury poisoning (HgP), many occurring in occupational
settings (e.g., Mad Hatter's Disease). Animal and in vitro studies
also provide insights into the mechanisms of Hg toxicity. More recently,
the Food and Drug Administration (FDA) and the American Academy
of Pediatrics (AAP) have determined that the typical amount of Hg
injected into infants and toddlers via childhood immunizations has
exceeded government safety guidelines on an individual (6) and cumulative
vaccine basis (7). The mercury in vaccines derives from Thimerosal
(TMS), a preservative which is 49.6% ethyl mercury (eHg) (7).
Past cases of HgP have presented with much inter-individual variation,
depending on the dose, type of mercury, method of administration,
duration of exposure, and individual sensitivity. Thus, while commonalties
exist across the various instances of HgP, each set of variables
has given rise to a different disease manifestation (8,9,10,11).
It is hypothesized that the regressive form of autism represents
another form of mercury poisoning, based on a thorough correspondence
between autistic and HgP traits and physiological abnormalities,
as well as on the known exposure to mercury through vaccines. Furthermore,
other phenomena are consistent with a causal Hg-ASD relationship.
These include (a) symptom onset shortly after immunization; (b)
ASD prevalence increases corresponding to vaccination increases;
(c) similar sex ratios of affected individuals; (d) a high rate
for autism paralleling a genetic predisposition to Hg sensitivity
at low doses; and (e) parental reports of autistic children with
elevated Hg.
TRAIT COMPARISON
ASD manifests a constellation of symptoms with much inter-individual
variation (3,4). A comparison of traits defining, nearly universal
to, or commonly found in autism with those known to arise from mercury
poisoning is given in Table I. The characteristics defining or strongly
associated with autism are also more fully described.
Autism has been conceived primarily as a psychiatric condition;
and two of its three diagnostic criteria are based upon the observable
traits of (a) impairments in sociality, most commonly social withdrawal
or aloofness, and (b) a variety of preservative or stereotypic behaviors
and the need for sameness, which strongly resemble obsessive-compulsive
tendencies. Differential diagnosis may include childhood schizophrenia,
depression, obsessive-compulsive disorder (OCD), anxiety disorder,
and other neuroses. Related behaviors commonly found in ASD individuals
are irrational fears, poor eye contact, aggressive behaviors, temper
tantrums, irritability, and inexplicable changes in mood (1,2,12-17).
Mercury poisoning, when undetected, is often initially diagnosed
as a psychiatric disorder (18). Commonly occurring symptoms include
(a) "extreme shyness," indifference to others, active
avoidance of others, or "a desire to be alone"; (b) depression,
"lack of interest" and "mental confusion;" (c)
irritability, aggression, and tantrums in children and adults; (d)
anxiety and fearfulness; and (e) emotional liability. Neuroses,
including schizoid and obsessive-compulsive traits, problems in
inhibition of preservation, and stereotyped behaviors, have been
reported in a number of cases; and lack of eye contact was observed
in one 12 year old girl with mercury vapor poisoning (18-35).
The third diagnostic criterion for ASD is impairment in communication
(1). Historically, about half of those with classic autism failed
to develop meaningful speech (2), and articulation difficulties
are common (3). Higher functioning individuals may have language
fluency but still show semantic and pragmatic errors (3,36). In
many cases of ASD, verbal IQ is lower than performance IQ (3). Similarly,
mercury-exposed children and adults show a marked difficulty with
speech (9,19,37). In milder cases scores on language tests may be
lower than those of unexposed controls (31,38). Iraqi children who
were postnatally poisoned developed articulation problems, from
slow, slurred word production to an inability to generate meaningful
speech; while Iraqi babies exposed prenatally either failed to develop
language or presented with severe language deficits in childhood
(23,24,39). Workers with Mad Hatter's disease had word retrieval
and articulation difficulties (21).
Nearly all cases of ASD and HgP involve disorders of physical movement
(2,30,40). Clumsiness or lack of coordination has been described
in many higher functioning ASD individuals (41). Infants and toddlers
later diagnosed with autism may fail to crawl properly or may fall
over while sitting or standing; and the movement disturbances typically
occur on the right side of the body (42). Problems with intentional
movement and imitation are common in ASD, as are a variety of unusual
stereotypic behaviors such as toe walking, rocking, abnormal postures,
choreiform movements, spinning; and hand flapping (2,3,43,44). Noteworthy
because of similarities to autism are reports in Hg literature of
(a) children in Iraq and Japan who were unable to stand, sit, or
crawl (34,39); (b) Minamata disease patients whose movement disturbances
were localized to one side of the body, and a girl exposed to Hg
vapor who tended to fall to the right (18,34); (c) flapping motions
in an infant poisoned from contaminated pork (37) and in a man injected
with Thimerosal (27); (d) choreiform movements in mercury vapor
intoxication (19); (e) toe walking in a moderately poisoned Minamata
child (34); (f) poor coordination and clumsiness among victims of
acrodynia (45); (g) rocking among infants with acrodynia (11); and
(h) unusual postures observed in both acrodynia and mercury vapor
poisoning (11,31). The presence of flapping motions in both diseases
is of interest because it is such an unusual behavior that it has
been recommended as a diagnostic marker for autism (46).
Virtually all ASD subjects show a variety of sensory abnormalities
(2). Auditory deficits are present in a minority of individuals
and can range from mild to profound hearing loss (2,47). Over- or
under-reaction to sound is nearly universal (2,48), and deficits
in language comprehension are often present (3). Pain sensitivity
or insensitivity is common, as is a general aversion to touch; abnormal
sensation in the extremities and mouth may also be present and has
been detected even in toddlers under 12 months old (2,49). There
may be a variety of visual disturbances, including sensitivity to
light (2,50,51,52). As in autism, sensory issues are reported in
virtually all instances of Hg toxicity (40). HgP can lead to mild
to profound hearing loss (40); speech discrimination is especially
impaired (9,34,). Iraqi babies exposed prenatally showed exaggerated
reaction to noise (23), while in acrodynia, patients reported noise
sensitivity (45). Abnormal sensation in the extremities and mouth
is the most common sensory disturbance (25,28). Acrodynia sufferers
and prenatally exposed Iraqi babies exhibited excessive pain when
bumping limbs and an aversion to touch (23,24,45,53). A range of
visual problems has been reported, including photophobia (18,23,34).
COMPARISON OF BIOLOGICAL ABNORMALITIES
The biological abnormalities commonly found in autism are listed
in Table II, along with the corresponding pathologies arising from
mercury exposure. Especially noteworthy similarities are described.
Autism is a neurodevelopmental disorder which has been characterized
as "a disorder of neuronal organization, that is, the development
of the dentritic tree, synaptogenesis, and the development of the
complex connectivity within and between brain regions" (54).
Depressed expression of neural cell adhesion molecules (NCAMs),
which are critical during brain development for proper synaptic
structuring, has been found in one study of autism (55). Organic
mercury, which readily crosses the blood-brain barrier, preferentially
targets nerve cells and nerve fibers (56); primates accumulate the
highest Hg-levels in the brain relative to other organs (40). Furthermore,
although most cells respond to mercurial injury by modulating levels
of glutathione (GSH), metallothionein, hemoxygenase, and other stress
proteins, neurons tend to be "markedly deficient in these responses"
and thus are less able to remove Hg and more prone to Hg-induced
injury (56). In the developing brain, mercury interferes with neuronal
migration, depresses cell division, disrupts microtubule function,
and reduces NCAMs (28, 57-59).
While damage has been observed in a number of brain areas in autism,
many nuclei and functions are spared (36). HgP's damage is similarly
selective (40). Numerous studies link autism with neuronal atypicalities
within the amygdala, hippocampi, basal ganglia, the Purkinje and
granule cells of the cerebellum, brainstem, basal ganglia, and cerebral
cortex (36,60-69). Each of these areas can be affected by HgP (10,34,40,70-73).
Migration of Hg, including eHg, into the amygdala is particularly
noteworthy, because in primates this brain region has neurons specific
for eye contact (74) and it is implicated in autism and in social
behaviors (65,66,75).
Autistic brains show neurotransmitter irregularities which are
virtually identical to those arising from Hg exposure: both high
or low serotonin and dopamine, depending on the subjects studied;
elevated epinephrine and norepinephrine in plasma and brain; elevated
glutamate; and acetylcholine deficiency in hippocampus (2,21,76-83).
Gillberg and Coleman (2) estimate that 35-45% of autistics eventually
develop epilepsy. A recent MEG study reported epileptiform activity
in 82% of 50 regressive autistic children; in another study, half
the autistic children expressed abnormal EEG activity during sleep
(84). Autistic EEG abnormalities tend to be non-specific and have
a variety of patterns (85). Unusual epileptiform activity has been
found in a number of mercury poisoning cases (18,27,34,86-88). Early
mHg exposure enhances tendencies toward epileptiform activity with
a reduced level of seizure-discharge amplitude (89), a finding consistent
with the subtlety of seizures in many autism spectrum children (84,85).
The fact that Hg increases extracellular glutamate would also contribute
to epileptiform activity (90).
Some autistic children show a low capacity to oxidize sulfur compounds
and low levels of sulfate (91,92). These findings may be linked
with HgP because (a) Hg preferentially binds to sulfhydryl molecules
(-SH) such as cysteine and GSH, thereby impairing various cellular
functions (40), and (b) mercury can irreversibly block the sulfate
transporter NaSi cotransporter NaSi-1, present in kidneys and intestines,
thus reducing sulfate absorption (93). Besides low sulfate, many
autistics have low GSH levels, abnormal GSH-peroxidase activity
within erythrocytes, and decreased hepatic ability to detoxify xenobiotics
(91,94,95). GSH participates in cellular detoxification of heavy
metals (96); hepatic GSH is a primary substrate for organic-Hg clearance
from the human (40); and intraneuronal GSH participates in various
protective responses against Hg in the CNS (56). By preferentially
binding with GSH, preventing absorption of sulfate, or inhibiting
the enzymes of glutathione metabolism (97), Hg might diminish GSH
bioavailability. Low GSH can also derive from chronic infection
(98,99), which would be more likely in the presence of immune impairments
arising from mercury (100). Furthermore, mercury disrupts purine
and pyrimidine metabolism (97,10). Altered purine or pyrimidine
metabolism can induce autistic features and classical autism (2,101,102),
suggesting another mechanism by which Hg can contribute to autistic
traits.
Autistics are more likely to have allergies, asthma, selective
IgA deficiency (sIgAd), enhanced expression of HLA-DR antigen, and
an absence of interleukin-2 receptors, as well as familial autoimmunity
and a variety of autoimmune phenomena. These include elevated serum
IgG and ANA titers, IgM and IgG brain antibodies, and myelin basic
protein (MBP) antibodies (103-110). Similarly, atypical responses
to Hg have been ascribed to allergic or autoimmune reactions (8),
and genetic predisposition to such reactions may explain why Hg
sensitivity varies so widely by individual (88,111). Children who
developed acrodynia were more likely to have asthma and other allergies
(11); IgG brain autoantibodies, MBP, and ANA have been found in
HgP subjects (18,111,112); and mice genetically prone to develop
autoimmune diseases "are highly susceptible to mercury-induced
immunopathological alterations" even at the lowest doses (113).
Additionally, many autistics have reduced natural killer cell (NK)
function, as well as immune-cell subsets shifted in a Th2 direction
and increased urine neopterin levels, indicating immune system activation
(103,114-116). Depending upon genetic predisposition, Hg can induce
immune activation, an expansion of Th2 subsets, and decreased NK
activity (117-120).
POPULATION CHARACTERISTICS
In most affected children, autistic symptoms emerge gradually,
although there are cases of sudden onset (3). The earliest abnormalities
have been detected in 4 month olds and consist of subtle movement
disturbances; subtle motor-sensory disturbances have been observed
in 9 month olds (49). More overt speech and hearing difficulties
become noticeable to parents and pediatricians between 12 and 18
months (2). TMS vaccines have been given in repeated intervals starting
from infancy and continuing until 12 to 18 months. While HgP symptoms,
may arise suddenly in especially sensitive individuals (11), usually
there is a preclinical "silent stage" in which subtle
neurological changes are occurring (121) and then a gradual emergence
of symptoms. The first symptoms are typically sensory- and motor-related,
which are followed by speech and hearing deficits, and finally the
full array of HgP characteristics (40). Thus, both the timing and
nature of symptom emergence in ASD are fully consistent with a vaccine
Hg etiology. This parallel is reinforced by parental reports of
excessive amounts of mercury in urine or hair from younger autistic
children, as well as some improvement in symptoms with standard
chelation therapy (122).
The discovery and rise in prevalence of ASD mirrors the introduction
and spread of TMS in vaccines. Autism was first described in 1943
among children born in the 1930s (123). Thimerosal was first introduced
into vaccines in the 1930s (7). In studies conducted prior to 1970,
autism prevalence was estimated, at 1 in 2000; in studies from 1970
to 1990 it averaged 1 in 1000 (124). This was a period of increased
vaccination rates of the TMS-containing DPT vaccines among children
in the developed world. In the early 1990s, the prevalence of autism
was found to be 1 in 500 (125), and in 2000 the CDC found 1 in 150
children affected in one community, which was consistent with reports
from other areas in the country (126). In the late 1980s and early
1990s, two new TMS vaccines, the HIB and Hepatitis B, were added
to the recommended schedule (7).
Nearly all US children are immunized, yet only a small proportion
develop autism. A pertinent characteristic of mercury is the great
variability in its effects by individual, so that at the same exposure
level, some will be affected severely while others will be asymptomatic
(9,11,28). An example is acrodynia, which arose in the early 20th
Century from mercury in teething powders and afflicted only 1 in
500-1000 children given the same low dose (28). Studies in mice
as well as humans indicate that susceptibility to Hg effects arises
from genetic status, in some cases including a propensity to autoimmune
disorders (113,34,40). ASD exhibits a strong genetic component,
with high concordance in monozygotic twins and a higher than expected
incidence among siblings (4); autism is also more prevalent in families
with autoimmune disorders (106). Additionally, autism is more prevalent
among boys than girls, with the ratio estimated at 4:1 (2). Mercury
studies in mice and humans consistently report greater effects on
males than females, except for kidney damage (57). At high doses,
both sexes are affected equally; at low doses only males are affected
(38,40,127).
DISCUSSION
We have shown that every major characteristic of autism has been
exhibited in at least several cases of documented mercury poisoning.
Recently, the FDA and AAP have revealed that the amount of mercury
given to infants from vaccinations has exceeded safety levels. The
timing of mercury administration via vaccines coincides with the
onset of autistic symptoms. Parental reports of autistic children
with measurable mercury levels in hair and urine indicate a history
of mercury exposure. Thus the standard primary criteria for a diagnosis
of mercury poisoning - observable symptoms, known exposure at the
time of symptom onset, and detectable levels in biologic samples
(11,31) - have been met in autism. As such, mercury toxicity may
be a significant etiological factor in at least some cases of regressive
autism. Further, each known form of HgP in the past has resulted
in a unique variation of mercurialism - e.g., Minamata disease,
acrodynia, Mad Hatter's disease - none of which has been autism,
suggesting that the Hg source which may be involved in ASD has not
yet been characterized; given that most infants receive eHg via
vaccines, and given that the effect on infants of eHg in vaccines
has never been studied (129), vaccinal Thimerosal should be considered
a probable source. It is also possible that vaccinal eHg may be
additive to a prenatal mercury load derived from maternal amalgams,
immune globulin injections, or fish consumption, and environmental
sources.
CONCLUSION
The history of acrodynia illustrates that a severe disorder, afflicting
a small but significant percentage of children, can arise from a
seemingly benign application of low doses of mercury. This review
establishes the likelihood that Hg may likewise be etiologically
significant in ASD, with the Hg derived from Thimerosal in vaccines
rather than teething powders. Due to the extensive parallels between
autism and HgP, the likelihood of a causal relationship is great.
Given this possibility, TMS should be removed from all childhood
vaccines, and the mechanisms of Hg toxicity in autism should be
thoroughly investigated. With perhaps 1 in 150 children now diagnosed
with ASD, development of HgP-related treatments, such as chelation,
would prove beneficial for this large and seemingly growing population.
Table I: Summary Comparison of
Traits of Autism & Mercury Poisoning
(ASD references in bold; HgP references in italics)
| Psychiatric Disturbances |
| Social deficits, shyness, social withdrawal
(1,2,130,131; 21,31,45,53,132 |
| Repetitive, preservative, stereotypic behaviors;
obsessive-compulsive tendencies (1,2,43,48,133; 20,33-35,132) |
| Depression/depressive traits, mood swings,
flat affect; impaired face recognition (14,15,17,103, 134,135;
19,21,24,26,31) |
| Anxiety; schizoid tendencies; irrational
fears (2,15,16; 21,27,29,31) |
| |
| Irritability, aggression, temper tantrums
(12,13,43; 18,21,22,25) |
| Lacks eye contact; impaired visual fixation
(HgP)/ problems in joint attention (ASD) (3,36,136,137;
18,19,34) |
| Speech and Language Deficits |
| Loss of speech, delayed language, failure
to develop speech (1-3,138,139; 11,23,24,27,30,37) |
| Dysarthria; articulation problems (3;
21,25,27,39) |
| Speech comprehension deficits (3,4,140;
9,25,34,38) |
| Verbalizing and word retrieval problems
(HgP); echolalia, word use and pragmatic errors (ASD) (1,3,36;
21,27,70) |
| Sensory Abnormalities |
| Abnormal sensation in mouth and extremities
(2,49; 25,28,34,39) |
| Sound sensitivity; mild to profound hearing
loss (2,47,48; 19,23-25,39,40) |
| Abnormal touch sensations; touch aversion
(2,49; 23,24,45,53) |
| Over-sensitivity to light; blurred vision
(2,50,51; 18,23,31,34,45) |
| Motor Disorders |
| Flapping, myoclonal jerks, choreiform movements,
circling, rocking, toe walking, unusual postures (2,3,43,44;
11,19,27,30,31,34,39) |
| Deficits in eye-hand coordination; limb
apraxia; intention tremors (HgP)/problems with intentional
movement or imitation (ASD) (2,3,36,181; 25,29,32,38,70,87) |
| Abnormal gait and posture, clumsiness and
incoordination; difficulties sitting, lying, crawling, and
walking; problem on one side of body (4,41,42,123;
18,25,31,34,39,45) |
| Cognitive Impairments |
| Borderline intelligence, mental retardation
- some cases reversible (2,3,151,152; 19,25,31,39,70) |
| Poor concentration, attention, response
inhibition (HgP)/shifting attention (ASD) (4,36,153;
21,25,31,38,141) |
| Uneven performance on IQ subtests; verbal
IQ higher than performance IQ (3,4,36; 31,38) |
| Poor short term, verbal, and auditory memory
(36,140; 21,29,31,35,38,87,141) |
| Poor visual and perceptual motor skills;
impairment in simple reaction time (HgP)/ lower performance
on timed tests (ASD) (4,140,181; 21,29,142) |
| Deficits in understanding abstract ideas
& symbolism; degeneration of higher mental powers (HgP)/sequencing,
planning & organizing (ASD); difficulty carrying out complex
commands (3,4,36,153; 9,18,37,57,142) |
| Unusual Behaviors |
| Self injurious behavior, e.g. head banging
(3,154; 11,18,53) |
| ADHD traits (2,36,155; 35,70) |
| Agitation, unprovoked crying, grimacing,
staring spells 3,154; 11,23,37,88) |
| Sleep difficulties (2,156,157; 11,22,31) |
| Physical Disturbances |
| Hyper- or hypotonia; abnormal reflexes;
decreased muscle strength, especially upper body; incontinence;
problems chewing, swallowing (3,42,145,181; 19,27,31,32,39) |
| Rashes, dermatitis, eczema, itching (107,146;
22,26,143) |
| Diarrhea; abdominal pain/discomfort, constipation,
"colitis" (107,147-149; 18,23,26,27,31,32) |
| Anorexia; nausea (HgP)/vomiting (ASD); poor
appetite (HgP)/restricted diet (ASD) (2,123; 18,22) |
| Lesions of ileum and colon; increased gut
permeability (147,150; 57,144) |
|
Table II: Summary Comparison of Biological
Abnormalities in Autism & Mercury Exposure |
|
| Mercury Exposure |
Autism |
| Biochemistry |
|
| Binds -SH groups; blocks sulfate transporter
in intestines, kidneys (40,93) |
Low sulfate levels (91,92) |
| Reduces glutathione availability; inhibits
enzymes of glutathione metabolism; glutathione needed
in neurons, cells, and liver to detoxify heavy metals;
reduces glutathione peroxidase and reductase (97,100,161,162) |
Low levels of glutathione; decreased
ability of liver to detoxify xenobiotics; abnormal glutathione
peroxidase activity in erythrocytes (91,94,95) |
| Disrupts purine and pyrimidine metabolism
(10,97,158,159) |
Purine and pyrimidine metabolism errors
lead to autistic features (2,101,102) |
| Disrupts mitochondrial activities, especially
in brain (160,163,164) |
Mitochondrial dysfunction, especially
in brain (76,172) |
| Immune System |
|
| Sensitive individuals more likely to
have allergies, asthma, autoimmune-like symptoms, especially
rheumatoid-like ones (8,11,18,24,28,31,111,113) |
More likely to have allergies and asthma;
familial presence of autoimmune diseases, especially rheumatoid
arthritis; IgA deficiencies (103,106-109,115) |
| Can produce an immune response in CNS;
causes brain/MBP autoantibodies (18,111,165) |
On-going immune response in CNS; brain/MBP
autoantibodies present (104,105,109,110) |
| Causes overproduction of Th2 subset;
kills/inhibits lymphocytes, T-cells, and monocytes; decreases
NK T-cell activity; induces or suppresses IFNg & IL-2
(100,112,117-120,166) |
Skewed immune-cell subset in the Th2
direction; decreased responses to T-cell mitogens; reduced
NK T-cell function; increased IFNg & IL-12 (103,108,114-116,173,174) |
| CNS Structure |
|
| Selectively targets brain areas unable
to detoxify or reduce Hg-induced oxidative stress (40,56,161) |
Specific areas of brain pathology; many
functions spared (36) |
| Accumulates in amygdala, hippocampus,
basal ganglia, cerebral cortex; damages Purkinje and granule
cells in cerebellum; brain stem defects in some cases
(10,34,40,70-73) |
Pathology in amygdala, hippocampus,
basal ganglia, cerebral cortex; damage to Purkinje and
granule cells in cerebellum; brain stem defects in some
cases (36,60-69) |
| Causes abnormal neuronal cytoarchitecture;
disrupts neuronal migration, microtubules, and cell division;
reduces NCAMs (10,28,57-59,161) |
Neuronal disorganization; increased
neuronal cell replication, increased glial cells; depressed
expression of NCAMs (4,54,55) |
| Progressive microcephaly (24) |
Progressive microcephaly and macrocephaly
(175) |
| Neuro-chemistry |
|
| Prevents presynaptic serotonin release
and inhibits serotonin transport; causes calcium disruptions
(78,79,163,167,168) |
Decreased serotonin synthesis in children;
abnormal calcium metabolism (76,77,103,179) |
| Alters dopamine systems; peroxidine
deficiency in rats resembles mercurialism in humans (8,80) |
Either high or low dopamine levels;
positive response to peroxidine, which lowers dopamine
levels (2,177,178) |
| Elevates epinephrine and norepinephrine
levels by blocking enzyme that degrades epinephrine (81,160) |
Elevated norepinephrine and epinephrine
(2) |
| Elevates glutamate (21,171) |
Elevated glutamate and aspartate (82,176) |
| Leads to cortical acetylcholine deficiency;
increases muscarinic receptor density in hippocampus and
cerebellum (57,170) |
Cortical acetylcholine deficiency; reduced
muscarinic receptor binding in hippocampus (83) |
| Causes demyelinating neuropathy (22,169) |
Demyelination in brain (105) |
| Neurophysiology |
|
| Causes abnormal EEGs, epileptiform activity,
variable patterns, e.g., subtle, low amplitude seizure
activities (27,31,34,86-89) |
Abnormal EEGs, epileptiform activity,
variable patterns, including subtle, low amplitude seizure
activities (2,4,84,85) |
| Causes abnormal vestibular nystagmus
responses; loss of sense of position in space (9,19,34,70) |
Abnormal vestibular nystagmus responses;
loss of sense of position in space (27,180) |
| Results in autonomic disturbance: excessive
sweating, poor circulation, elevated heart rate (11,18,31,45) |
Autonomic disturbance: unusual sweating,
poor circulation, elevated heart rate (17,180) |
|
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