Autism and Autistic Symptoms Associated with Childhood Lead Poisoning

Lidsky-vol5no1 3/5/05 6:17 PM Page 80
Autism and Autistic Symptoms
Associated with Childhood Lead
Poisoning
Theodore I. Lidsky, PhD*
Jay S. Schneider, PhD†
*Department of Psychobiology, New York State Institute for Basic Research in Developmental
Disabilities, Staten Island, New York
†Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University College of
Medicine, Philadelphia, Pennsylvania
impairments of the development of
KEY WO R D S : a u t i s m , pervasive
both nonverbal and verbal communica-
developmental disorders, l e a d ,
tion and reciprocal social interactions
p l u m b i s m
seen in association with an abnormally
restricted range of interests.2 Current
ABSTRACT
diagnostic schema indicate an onset of
Autism is a developmental disorder that
symptoms before the age of 3 years.
impairs both nonverbal and verbal com-
Although Kanner generally excluded
munication and reciprocal social interac-
cases with known brain dysfunction, it is
tions and is seen in association with an
now recognized that, in addition to the
abnormally restricted range of interests.
idiopathic form, autistic disorder can
Although symptoms typically develop
also be caused by a number of condi-
without clear etiological cause, some
tions that negatively impact brain devel-
cases are associated with disorders or
opment (eg, tuberous sclerosis,
conditions that negatively impact brain
neurofibromatosis, postnatal herpes).3,4
development. Lead is a neurotoxin to
One of the most common causes of
which the developing brain is particular-
neurodevelopmental impairment is
ly vulnerable. Moreover, lead poisoning
childhood lead poisoning. Pediatric lead
in children is known to negatively affect
poisoning has deleterious effects on the
brain systems implicated in cognitive,
development of widespread brain areas
communication, and social functioning.
including those implicated in cognitive,
The present paper presents two case his-
communication, and social functioning.5
tories of children who, during periods of
In several cases, a temporal association
severe lead poisoning, developed autism
was noted between elevated blood lead
or autistic symptoms. These cases under-
levels and the emergence of autistic
score that there are multiple causes of
symptoms.6,7 The present paper
autism and the importance of environ-
describes two children who, during peri-
mental influences in some cases.
ods of elevated blood lead levels, dis-
played the symptoms of autistic
INTRODUCTION
disorder. Several unique elements of
The key features of autism, first
these cases differentiate them from
described by Kanner in 1943,1 are
idiopathic autism and indicate that
80
Vol. 5, No. 1, 2005 • The Journal of Applied Research

---

Lidsky-vol5no1 3/5/05 6:17 PM Page 81
Figure 1. Blood lead levels of patient 1 as a function of age.
brain damage from plumbism can cause
age appropriate fashion. For example, he
the symptoms of autism.
sat unassisted at 8 months, stood at 9
months, walked at 10 months, and spoke
Case 1
single words at 12 months. He was noted
Patient 1 is an Hispanic child raised in
to show normal interactive behavior at 9
an English/Spanish bilingual household.
months and to indicate his wants at 15
He has two older brothers who were
months.
described as developmentally normal
The patient was found to have an
and doing well in school. When pregnant
elevated blood-lead level at about 15
with him, his mother began prenatal
months of age; elevated levels continued
care during the latter part of the first
to be reported for at least 26 months. He
trimester. The patient was born full term
underwent chelation treatment at about
via normal spontaneous vaginal delivery
24 months of age. The available records
without complications; Apgars were 9 at
concerning his blood lead levels are
1 minute and at 5 minutes, reflexes and
summarized in Figure 1.
cry were described as good, and physical
According to his mother, he had a
examination showed all systems to be
vocabulary of about 10 words when 16
normal. The nursing assessment noted
to 20 months of age, but lost the ability
adequate bonding between the mother
to speak around the time that lead poi-
and her child. The patient was admitted
soning was detected. She expressed her
to the Neonatal Intensive Care Unit
concerns about his communication prob-
(NICU) due to poor feeding and sepsis.
lems, and also the emergence of temper
He was treated and discharged home to
tantrums, to his pediatrician, who subse-
his parents. Subsequent medical records
quently referred the patient for assess-
show that early developmental mile-
ment.
stones in all areas were attained in an
A speech and language evaluation,
The Journal of Applied Research • Vol. 5, No. 1, 2005
81

---

Lidsky-vol5no1 3/5/05 6:18 PM Page 82
when the patient was 27 months of age,
either examiner or the translator. He
described severe delays in both expres-
only occasionally made eye contact with
sive and receptive oral communication.
either the examiner or translator and it
Reevaluation about 5 months later
was not clear, based on his unchanging
noted similar impairments and observed:
facial expression, whether he understood
“Deficits are found in both English and
what was being said to him. He never
Spanish, which are not attributable to
engaged in conversation with either the
bilingualism.” Educational evaluations at
examiner, the translator or his mother.
both 27 months and 34 months noted
His only speech consisted of echolalic
delays in all areas except gross motor
repetition of whatever was said to him,
functioning. Psychological evaluation
whether in Spanish or English.
also indicated expressive and receptive
In contrast to his lack of responsive-
language delays as well as decreased
ness to speech, he was overly reactive to
attention span and increased motor
visual stimulation. While he never
activity and impulsivity. Pediatric evalu-
turned his head toward the person who
ations documented a deterioration
was addressing him, he quickly turned to
toward autistic disorder noting, when
face and focus upon any movement in
the patient was 3 years 5 months of age,
the testing room. For example, a slight
Pervasive Developmental Disability
movement of the window blinds due to
(PDD) tendencies and, at 4 years 1
air currents or a pencil that rolled when
month of age, autism. However, several
placed on the table instantly evoked an
observations by his teacher during this
orienting response from the patient fol-
period indicated behavioral characteris-
lowed by an obvious and prolonged
tics that are unusual in autistic children.
visual concentration on the eliciting
For example, he was described as “...a
stimulus.
curious child with a short attention span
Throughout the evaluation, the
for his age who can be very active at
patient was unable or unwilling to
times. He makes more eye contact than
remain seated for more than a few min-
in the past, his temper has improved, he
utes. He repeatedly left his chair and
is using some words... is affectionate and
would only remain seated if physically
plays with others but does not like to be
restrained. The patient appeared contin-
hugged or touched by anyone other than
uously cheerful and hummed a short
his mother.” [The preceding is a quote
tune that he incessantly repeated
from his teacher.]
throughout the evaluation. He only devi-
The patient was first evaluated by
ated from his happy mien on one occa-
the authors of this paper, aided by a
sion when he was prevented from
Spanish/English translator, when he was
getting out of his chair during testing. At
about 4 years 5 months of age and, at
that time, he mercurially became tearful
that time, met DSM-IV criteria for autis-
and, just as quickly, resumed his previ-
tic disorder (marked impairments in
ous good mood when he was permitted
communication, social interactions,
to get up.
restricted interests, and activities).2 He
Although formal cognitive testing
presented as a neatly dressed boy who
was initiated, the attempt was aborted
appeared quite at ease with his sur-
due to both an inability to communicate
roundings. Although he was alert, it was
with the child and also his behavior,
not clear if he was oriented to time and
including his inability or unwillingness
place since, for the duration of the eval-
to remain seated. Moreover during test-
uation (.3 hours), the patient did not
ing he would frequently avert his gaze
engage in comprehensible speech with
from the test materials and focus on
82
Vol. 5, No. 1, 2005 • The Journal of Applied Research

---

Lidsky-vol5no1 3/5/05 6:18 PM Page 83
some other area in the room; attempts
ble with the patient’s communication
to refocus him were futile.
deficiencies, was attempted. He was able
The Childhood Autism Rating Scale
to do the simplest designs (16th per-
(CARS) was used to evaluate his behav-
centile) from the Block Design subtest
ior. The CARS is a standard instrument
from the Wechsler Intelligence Scale for
that quantifies behavior with respect to
Children, Third Edition (WISC-III).
relating to people, imitation, emotional
When asked to copy the design from the
response, body use, object use, adapta-
Rey Complex Figure Test, he did so,
tion to change, visual response, listening
making an accurate reproduction that
response, taste, smell, and touch
was scored at the 32nd percentile for
response and use, fear or nervousness,
children of his age. However, when sub-
verbal communication, nonverbal com-
sequently asked to reproduce the figure
munication, activity level, level and con-
from memory, the patient was either
sistency of intellectual response, and
unable to do so or simply could not
general impressions. The patient’s over-
comprehend what was being asked of
all score was in the range of severe
him. Unfortunately, his verbal communi-
autism.
cation impairments were so severe as to
The authors of this paper reevaluat-
preclude accurate assessment of other
ed the patient when he was 6 years 10
aspects of his neuropsychological
months of age. In the interim, he was
performance including verbal and
enrolled in a special school for develop-
visual memory as well as executive
mentally disabled children, though there
functioning.
was no program specifically designed for
The Vineland Adaptive Behavior
remediation of autistic symptoms. At
Scales was administered to evaluate gen-
this second assessment, he no longer met
eral functionality in communication,
DSM-IV criteria for autistic disorder. 2
daily living skills and socialization. T.
His mother, brother, and his broth-
Lidsky, who was aided by an
er’s friend accompanied the patient to
English/Spanish translator, interviewed
the evaluation. He never engaged in
the patient’s mother. The patient was
conversation with either examiner and,
severely delayed in all domains (com-
as in the previous evaluation, his speech
munication, daily living skills, socializa-
was echolalic. However, he was able to
tion, low adaptive level; percentile rank
respond appropriately to simple com-
< 0.1). However, the pattern of standard
mands.
scores typical of autism, wherein the
During the entire evaluation the
daily living score is significantly superior
patient was not observed engaging in
to both communication and socialization
motor stereotypies or self-stimulatory
scores, was not observed in this child.
behavior. In addition he was affection-
The CARS was again used to evaluate
ate, not only with his mother, but also
his behavior. Unlike the previous rating,
his brother and his brother’s friend. In
the patient’s overall score was incompat-
addition, during several of the rest
ible with a diagnosis of autism.
breaks, when he was in the waiting area,
he was seen happily engaging in recipro-
Case 2
cal play behavior with his brother and
Patient 2, a male, was born by normal
his brother’s friend. At one point, he
spontaneous vaginal delivery following
clearly solicited a hug from his brother’s
an uneventful full-term pregnancy.
friend and was visibly pleased when he
Apgar scores were 8 at 1 minute and 9
received it.
at 5 minutes. No delivery or postpartum
Limited cognitive testing, compati-
problems were noted and he was judged
The Journal of Applied Research • Vol. 5, No. 1, 2005
83

---

Lidsky-vol5no1 3/5/05 6:18 PM Page 84
Figure 2. Blood lead levels of patient 2 as a function of age.
appropriate for gestational age. There
Clinic notes from his hospital admis-
was no maternal history of alcohol, drug
sion indicated that his intake examina-
or tobacco use during pregnancy.
tion was “unremarkable”. There were no
Prenatal vitamins and iron supplements
descriptions of behavioral or neurologi-
were taken during the pregnancy, which
cal problems, although the child’s moth-
was monitored with standard prenatal
er expressed concern about his high
care. Physical growth and development
level of activity. It was reported that
were normal; early developmental mile-
there was a “paucity of speech” and a
stones in all areas were met in an age
“decrease in following of commands”
appropriate fashion.
although it was thought that this might
The patient’s medical history is
be attributable to sleepiness. At dis-
remarkable for severe lead poisoning
charge the patient was described as
that was first detected at approximately
“alert, playful” and as a “cute, well-
3 years, 4 months of age and which last-
developed, well-nourished boy”. No
ed at least 5 years. Several months after
mention was made of any concerns
poisoning was detected, his blood lead
about the patient’s cognitive status.
levels increased to 110 µg/dL prompting
Problems concerning the patient’s
hospital admission for intravenous
cognitive abilities or behavior were not
chelation therapy. He was discharged
described until he began kindergarten.
home with a blood lead level of 52
A history taken at that time (age 5 years
µg/dL and received outpatient chelation
11 months) reported that his develop-
therapy. The patient’s history of lead
ment up that point was within normal
poisoning and blood lead levels are
limits. The school’s student support team
shown in Figure 2.
administered the WISC-III and the child
84
Vol. 5, No. 1, 2005 • The Journal of Applied Research

---

Lidsky-vol5no1 3/5/05 6:18 PM Page 85
attained a verbal IQ of 79 (8th per-
“...often stares blankly when others
centile), performance IQ of 79 (8th per-
attempt to communicate with him”, that
centile) and full scale IQ of 77 (6th
he “...makes squealing noises, lays on the
percentile), each in the borderline range.
floor and cries, and runs away from
Difficulties were noted in the “areas of
adults. A teacher noted an incident in
memory, processing information, and
which [the child] vomited and exhibited
spatial reasoning”. In addition, the
no interest in removing the vomit from
patient was described as being “aware of
his hands and clothing.” The CARS was
his academic difficulties in the classroom
used to evaluate the patient’s behavior
and he displays feelings such as insecuri-
and his score was in the clinically signifi-
ty in terms of his academic skills.”
cant range for mild to moderate autism.
Notably, with respect to his future
The child was placed in a small class-
“autistic like behaviors” (see below), the
room with one-on-one instruction and
patients “highest score was in the area
modeling prompts that emphasized the
of practical social judgment” and he was
use of language in functional settings.
also noted to respond well to praise and
A school-based evaluation several
positive reinforcement. The child was
years later, when the child was about 12
recommended for special educational
years old, indicated some progress in
services.
language and social skills. For example,
The patient’s cognitive functioning
although he did not initiate conversa-
progressively deteriorated over the next
tions, he would have conversations if
two years with most significant declines
approached, would interact with his
in speech and communication. A
peers, and he no longer exhibited any
speech/language evaluation performed
maladaptive behaviors. In contrast, his
at the age of 7 years 9 months indicated
cognitive impairments persisted, as did
that both receptive and expressive lan-
his attentional problems.
guage skills were at a 2 to 2 1/2 year-old
When the patient was about 13
age level. The Stanford-Binet Intelligence
years old, the authors of this paper eval-
Scale, Fourth Edition was administered
uated him. At the time of this assess-
and the patient’s composite score (54, <
ment he no longer met DSM-IV2 criteria
1st percentile) had decreased to the
for autistic disorder. He presented as a
mentally retarded range. Areas of
neatly dressed, well-groomed, well-nour-
impairment were verbal reasoning (< 1st
ished boy who was quiet but cooperative
percentile), quantitative reasoning (2nd
during the testing session. He sat with
percentile), and short-term memory (<
his head facing down for most of the
1st percentile); abstract/visual reasoning
time, making eye contact only briefly
was relatively preserved (19th per-
and, when the contact was reciprocated,
centile). In addition, the patient was
quickly averted his eyes. He showed no
unable to sustain attention. A psychoed-
emotion and exhibited few spontaneous
ucational review at this time indicated
movements. No unusual behaviors or
his teacher’s concern about the child’s
abnormal body use were observed. He
“autistic like” behaviors viz: “He does
showed an appropriate interest in and
not communicate or interact with peers
use of toys and other objects, such as a
and adults appropriately and efforts to
pencil. The patient always answered
communicate with him often produce
questions when asked, but typically
blank stares. (The child)...also runs out
replied with single words or a 2 to 3
of the room whenever possible, and he
word phrase. For example, when asked
frequently “twirls in the hall.” A subse-
what he did during the summer, he
quent report also noted that the child
responded “played”. When asked if he
The Journal of Applied Research • Vol. 5, No. 1, 2005
85

---

Lidsky-vol5no1 3/5/05 6:18 PM Page 86
played sports, he responded “yes”. When
ment following poisoning, presented
asked which sport, he responded “bas-
with the symptoms of autism. The first
ketball”. The child also clearly had an
case met each of the diagnostic criteria
appreciation for his level of perform-
for autistic disorder while the second
ance on at least some tasks. While per-
case, due to the age at which symptoms
forming the computer based Wisconsin
emerged, would be identified as perva-
Card Sorting Test, he quickly learned the
sive developmental disorder, NOS.2
rule needed to perform the task correct-
However, in addition to the late onset of
ly. Once the rule was changed, he per-
symptoms in the second patient, both
sisted in using the old rule and had
cases differed from idiopathic autism in
difficulty in learning the new rule. After
another important respect; each child
several wrong answers, he shrugged his
emerged from the autistic phase.
shoulders and, gestured toward the com-
Although there have been several cases
puter and said, “something wrong with
reported in which autistic individuals
it”.
were able to emerge from autism,8 those
The WISC-III was administered and
patients had a high level of cognitive
the patient’s verbal IQ (46, < 1st per-
functioning and underwent specialized
centile), performance IQ (65, 1st per-
cognitive rehabilitation. In contrast, both
centile) and full scale IQ (53, < 1st
of the children described in this report
percentile) were in the intellectually
had very low levels of cognitive func-
deficient range. Neuropsychological
tioning and neither was exposed to spe-
testing indicated impairments affecting
cialized treatment.
expressive language, visual attention,
Certain cases of autism have been
visuospatial constructional ability and
reported to be caused by disorders that
visuospatial memory, fine motor func-
produce structural abnormalities in the
tioning, auditory working memory, ver-
brain or space occupying lesions as well
bal concept formation, planning ability
as by brain infections. Herpes
and cognitive flexibility.
encephalopathy can produce all of the
The patient’s mother was inter-
core symptoms of autism and, similar to
viewed by J. Schneider to complete the
the second patient, appear well after the
Vineland Adaptive Behavior Scales. The
age typically associated with the onset of
child was severely delayed in all
idiopathic autism. Indeed, there are case
domains (communication, daily living
reports of herpes-induced autism in pre-
skills, socialization, low adaptive level;
viously healthy adolescents9,10 and in an
percentile rank < 0.1). However, the pat-
adult of 31 years11. Herpes-induced
tern of standard scores typical of autism,
autism, like the lead poisoning-induced
wherein the daily living score is signifi-
cases described in the present paper, is
cantly superior to both communication
sometimes reversible.4
and socialization scores, was not
The two case histories presented
observed in this child. The CARS was
here, as well as the reports of autistic
again used to evaluate his behavior and
symptoms in children with disorders that
unlike the previous rating, the patient’s
produce brain lesions or encephalopa-
overall score was incompatible with a
thy, indicate that there are multiple
diagnosis of autism.
causes of autism. Further, the ability of
brain infections and lead poisoning to
DISCUSSION
produce such symptoms highlights the
This paper described the case histories
importance of environmental factors in
of two children with severe lead poison-
the etiology of autism.
ing that, for a period during develop-
The ability of lead poisoning to
86
Vol. 5, No. 1, 2005 • The Journal of Applied Research

---

Lidsky-vol5no1 3/5/05 6:18 PM Page 87
induce symptoms of autism is also rele-
4.
DeLong GR, Bean SC, Brown FR. Acquired
vant to cases of preexisting pervasive
reversible autistic syndrome in acute
encephalopathic illness in children. Arch
developmental disorders irrespective of
Neurol. 1981;38:191-194.
etiology. Such individuals have a greater
5.
Lidsky TI, Schneider JS. Lead neurotoxicity
propensity to engage in pica and, as a
in children: basic mechanisms and clinical
result, are more likely to become lead
correlates. Brain. 2003;126:5-19.
poisoned.12,13 In such cases, lead poison-
6.
Eppright TD, Sanfacon JA, Horwitz EA.
ing can be expected not only to nega-
Attention deficit hyperactivity disorder,
infantile autism, and elevated blood-lead: a
tively impact neurocognitive
possible relationship. Mol Med. 1996;93:136-
functioning,5 but also to potentially
138.
exacerbate the preexisting symptoms of
7.
Accardo P, Whitman B, Caul J, Rolfe U.
autism. Indeed, one case report
Autism and plumbism: a possible association.
describes a decrease in hyperactivity and
Clin Ped. 1988;27:41-44.
stereotypies in an autistic child with a
8.
Perry R, Cohen I, DeCarlo R. Deterioration,
autism and recovery in two siblings. J Am
blood lead of 42 µg/dL once this level
Acad Child Adolesc Psychiatry. 1995;34:232-
was reduced by chelation with succimer. 6
237.
9.
Ghaziuddin M, Al-Khouri I, Ghaziuddin N.
ACKNOWLEDGMENTS
Autistic symptoms following herpes
The authors thank Drs. J.F. Rosen and V.
encephalitis. Eur Child Adolesc Psychiatry.
2002;11:142-146.
Sudhalter for helpful suggestions on pre-
vious drafts of this paper. Supported in
10.
Gilberg IC. Onset at age 14 of a typical autis-
tic syndrome: A case report of a girl with her-
part by the Office of Mental
pes simplex encephalitis. J Autism Dev
Retardation and Developmental
Disord. 1986;16:369-375.
Disabilities of the N.Y.S. Department of
11.
Gilberg IC. Autistic syndrome with onset at
Mental Hygiene.
age 31 years: herpes encephalitis as a possible
model for childhood autism. Devel Med
Child. 1991;33:920-924.
REFERENCES
12.
Cohen DJ, Johnson WT, Caparulo BK. Pica
1.
Kanner L. Autistic disturbances of affective
and elevated blood lead level in autistic and
contact. Nervous Child. 1943;2:217-250.
atypical children. Am J Dis Child.
1976;130:47-48.
2.
Diagnostic and Statistical Manual of Mental
Disorders. 4th ed. Washington, DC: American
13.
Shannon M, Graef JW. Lead intoxication in
Psychiatric Association; 2000.
children with pervasive developmental disor-
ders. J Toxicol Clin Toxicol. 1996;34:177-181.
3.
Harris JC. Developmental Neuropsychiatry.
Vol 2. New York, NY: Oxford University
Press; 1998.
The Journal of Applied Research • Vol. 5, No. 1, 2005
87

---