CHRONIC
LEAD
ENCEPHALOPATHY
A
Diagnostic
Consideration
in
Mental
Retardation
Harry H. White, M.D., and Fred D. Fowler, M.D.
Section of Neurology, Department of Interivil Medicine (H.H.W.), and Department of
Neurosurgery (F.D.F.), University of Kansas Medical Center
309
PEDIATRICS, February 1960 EAD POISONING is more commonly seen in
children than in adults in present day
medical practice. This is related to the fact that the ingestion of material from paint,
water pipes, sprays, toys and crayons is
most usually found in the younger age
group as well as careful safeguarding of adults from occupational sources of the
poison. The onset of symptoms may be
acute, but is most often insidious, and chronic intoxication is most commonly seen
(
except in tile case of inhalation of fumes from burning battery casings). Complaints of anorexia, vomiting, irritability, pallor, constipation and colicky abdominal painmay be present oven a bong period of time before attracting medical attention.12 These
symptoms may be so chronic and mild that
medical help is not sought until onset of an acute encephalopathy which may begin with convulsive seizures and signs of in-creased intracranial pressure.
It is the purpose of this communication
to report a case of chronic lead poisoning occurring in a child who presented, not with the classic signs and symptoms of lead
encephalopathy, but instead with the
pic-tune of a behavior disorder associated with progressive dementia.
First Admission
CASE REPORT
HISTORY: A 3-year-old Negro female was
ad-mitted to the Children’s Mercy Hospital on September 23, 1958 because the mother had
noted that the child cried very easily. The patient was born after a 9-month gestation and normal delivery. The birth weight was 3.1 kg.
There was no history of prenatal infection,
(Accepted July 18, 1959; submitted June 11.)
ADDRESS: (H.H.W.) Kansas City 12, Kansas.
paranatal asphyxia or postnatal encephalitis. The baby was breast-fed for 1 week, after which a homogenized milk formula was given, and solid foods were started at 3 months. She took feedings well. The physical milestones
were reached at appropriate ages : she sat
alone at 4 months; stood at 1 1 months; walked
at 13 months; was toilet-trained at 15 months; spoke simple sentences by 20 months. The parents were unrelated, living and vebl, ab-though the mother had diabetes. The patient had one brother, age 8 years, who was living
and well. One cousin had died at 13 ears of age from “cerebral palsy.” Immunizations in-eluded one dose of triple vaccine (diphtheria,
pertussis, tetanus), one injection of
poliomye-litis vaccine, and a small-pox vaccination, all
given at 2 years of age. The patient’s only
previous illness was measles at age 9 months. The patient had been perfectly well until 1
month prior to admission when she fell from a crib, a distance of 2 feet, striking hen head on the floor. Two episodes of vomiting occurred shortly after the fall, but consciousness was maintained. One week later she again vomited on two separate occasions, but was not both-ered by abdominal pain or constipation. Ap-proximately 2 weeks prior to admission the family noticed a rather abrupt change in her personality. While previously having a good
vocabulary, she now began to speak in single
words (“Mama,” “Cecil,” “cat”). She became withdrawn, displayed a complete lack of
in-terest in her environment and began to cry
almost constantly. Toys no longer interested
her, objects given to her were thrown aside, she would hit or kick those about her, and on occasions, would fall on the floor and lie
kick-ing as if “mad.” Formerly, she had been a
webb-mannered child; now she would
310
LEAD
ENCEPHALOPATHY
defecate or urinate on the floor. This
personal-ity pattern had remained essentially unchanged
from its onset to the time of admission.
PHYSICAL Fn’mINcS: Examination revealed a
well-developed, well-nourished child in no dis-tress, but who occupied herself by reaching
for objects in the bed, babbling incoherently, and occasionally rocking back and forth in the sitting position. She showed no response to
verbal commands. Temperature on admission was 37#{176}C, pulse rate 120, respirations 24/mm and systolic blood pressure measured 80 mm Hg. Weight was 12.8 kg, height 100 cm, and the head circumference measured 48 cm. The neck was supple. Except for a few small, soft, non-tender nodes in the posterior cervical chain,
and cryptic hypertrophy of the tonsils, the
general physical examination was not revealing. On neurobogic examination the station and gait were not remarkable. The cranial nerves showed no abnormalities. The optic fundi were not remarkable and there was no gross im-painment of the motor system in the form of
weakness, alteration of tone or abnormal
move-ments. The cerebeblar function tests and
sen-sony examinations, though difficult to elicit in this patient, seemed normal. The deep tendon reflexes were active and equal bilaterally and no abnormal reflexes were elicited.
LABORATORY FINDINGS: In the blood, the con-centration of hemoglobin was 9.0 gm/100 ml, hematocnit, 30%. Smear for basophilic stippling on both admissions was negative. Leukocyte count was 9,400/mm3 with a normal differen-tiab. The specific gravity of urine was 1.025; albumin, slight trace; microscopic, 6-8 beuko-cytes per high-power field; sugar, negative;
fernic chloride test for phenybpyruvic acid,
neg-ative.
The pressure in the cerebrospinal fluid was 180 mm H20. There were 6 leukocytes (3 poly-morphonuclear leukocytes and 3 lymphocytes) and 68 enythrocytes; protein was 44 mg/100 ml; sugar, 40-45 mg/100 ml. Culture of the fluid was negative. Serology was negative.
Skin tests for tuberculosis and histoplasmosis were both negative after 48 hours.
An electroencephalogram obtained on Sep-tember 25 was abnormal with diffuse slowing in all leads (Fig. 1A). Roentgenograms of the skull and chest were normal. Pneumoencephal-ognaphy was done on October 6 using 30 ml of air. This showed evidence of slight cortical atrophy but was otherwise within normal limits.
Psychobogic testing on October 10 revealed a mental age of 9 months, with an I.Q. score of
24, (Cattell Infant Intelligence Scale).
COURSE AND THERAPYI During the patient’s first hospital admission she remained irritable
and withdrawn. At times she acted afraid and cried almost constantly. On several occasions
she had episodes of destructive behavior and would tear up the bed, toys, or bite and scratch the attendants. She often would sit in the bed and mumble to herself and make unintelligible
humming sounds. The psychologist reported, “When she was first placed in the high chain in
the testing room, she held her left hand aloft and kept it in this position for a minute or two until I put her arm down on the tray of the chair.”
On the day of admission administration of 5 mg of methvphenidate HCI (Ritalin#{174}), three
times daily, was started. This dosage was sub-sequently increased to 15 mg three times daily without significant change in behavior.
On October 13, the child was noted to be chewing her toys. Subsequent observations in-dicated she would eat anything she could get
her hands on, including skin lotions, stuffing
from rag dolls, and even the soles of her shoes. A random urine specimen was collected on that
day and sent to the laboratory for determina-tion of coproporphyrins. However, the patient
was discharged the following day, before the result of this test was reported, with the tenta-tive diagnosis of “degenerative disease of the
central nervous system, type unknown,” to be followed in the Neurology Outpatient Clinic.
Second Admission
Subsequently, the urine specimen obtained before discharge was reported as strongly
posi-tive for coproporphyrins, and the patient was
re-admitted to the hospital on October 23.
The clinical condition had remained unchanged.
ADDITIONAL HISTORY: Further questioning of the mother as to possible sources of lead
re-vealed that the child was in the habit of eat-ing anything she could get her hands on. The
family lived in a three-story frame house, ap-proximately 25 years old, which had been
ne-painted many times. The paint was flaking off the front porch where the patient usually
played and her mother had often seen hen eat-ing small flecks of the old paint, but she was not aware of its toxic potentialities. It was
en-?JWOR TJMPOM
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‘ .
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Fic. 1. Electroencephalogram. (A) September 25, 1958, prior to therapy. Definitely abnormal tracing with diffuse high voltage slow wave activity. (B) December 12, 1958. Recording made after therapy
312 LEAD ENCEPHALOPATHY
FIG. 2. Hand and knee, demonstrating the deposition of lead beneath tile epiphyses of the bong bones.
joved eating crayons, and had eaten two to three boxes during the past year. The mother could not accurately date the onset of pica, but it had been noticeable to the family for at least 2 years prior to the onset of the present illness.
LABORATORY FINDINGS: Roentgenograms of
the bong bones confirmed the suspicion of heavy metal ingestion (Fig. 2) and the concentration of bead in the blood was found to be 0.18 mg//
100 ml.
THERAPY AND COURSE: On October 28
treatment was instituted with 800 mg of eda-thamib cabcium-disodium#{176} (CaEDTA) in a 20% solution with 0.5% procaine, given intramuscu-banly in five divided doses daily. This regimen was discontinued on November 2 after 6 days of treatment. On November 3 the
pa-tient was noted to be less irritable and more sociable than previously. On November 7, coproporphvrins in the urine were still positive,
so treatment was reinstituted for 7 days, from
0 Calcium Disodium Versenate#{174}, calcium
diso-dium ethylenediarninetetraacetic acid.
November 10 to November 17. From Novem-ber 10 to November 23 there was a steady and noticeable improvement in the patient’s be-havior. She began to react to verbal stimuli and to play with the other children on the ward. B November 25 she was active and
co-operative; she began to talk, regain her previ-ousby lost toilet-training and became affection-ate with her parents and attendants. On De-cember 4 the parents stated that she didn’t eat things as she had previously. A second
electro-encephalogram on December 12 was normal (Fig. 1B).
The Kansas City Board of Health was helpful
ill aiding the family in the location of new living quarters free from any sources of lead. The patient was discharged on December 19 to be followed ill the Neurology Outpatient
The patient was seen in the clinic Ofl January 9, 1959 at which time psychologic evaluation revealed a mental age of 2 years, 4 months, with an I.Q. score of 68 (Revised Stanford-Binet Scale Form). A determination of lead in blood obtained at that time was 0.135 mg/100 ml. For this reason the patient was re-admitted to the hospital on January 12 for further treat-ment. During the interim since her previous discharge the patient had been well and
asymp-tomatic. Laboratory studies showed that the
concentration of hemoglobin had risen to 11.4 gm/100 ml. Treatment consisted of 800 mg of
CaEDTA daily, in the manner previously
de-scribed, for a total of 5 days. The concentration of bead in the blood at the time of discharge
was reported as 0.059 mg/100 ml.
On exammation in the clinic on February 2, the patient was noted to be doing well and car-rving on normal activities.
DISCUSSION
Symptoms referable to the central nerv-ous system in lead intoxication are rarely
seen in adults and usually occur as a con-sequence of rapid absorption of barge
quan-tities of lead.3 In the younger age groups neunopathy is rare, encephabopathy being the most outstanding evidence for
involve-ment of the nervous system. The dramatic
signs of coma, severe and repeated
convul-sions with evidence of increased intracranial pressure are well known accompaniments to acute lead encephalopathy. Results of
treat-ment at this stage, however, have been
dis-appointing and many of the surviving pa-tients become hopelessly mentally deficient.
Therefore, it would seem that early diag-nosis is essential if the outcome is to be favorable. The early systemic manifestations
of anemia, basophilic stippling of the eryth-rocytes, anorexia, vomiting, constipation
and abdominal pain have been emphasized in the textbooks. Less emphasis, however,
has been placed on the early signs and symptoms of involvement of the nervous system.
McKhann and Karpinski4 mention that
frequently the child may have been
con-sidered to present a problem in behavior.
Mellins and Jenkins5 found a characteristic
pattern of behavior in 15 of 21 cases studied. Extreme irritability, fearfulness, weakness, withdrawal and frequent crying for no ap-parent reason antedated the acute onset of
the disease by 1 or 2 weeks. Gibb and
Mac-Mahon6 have reported a child with mental
deficiency whose early manifestations
in-eluded mutism, withdrawal, irritability, loss
of affection, and incontinence of urine and
feces. These authors suggest that particular
attention should be given to bead poisoning in patients with signs and symptoms
sugges-tive of schizophrenia, infantile autism, amentia, educational subnormality,
hyper-kinetic behavior and other behavior dis-orders. Feldman,7 in an excellent review of the subject, states that in many cases con-vulsions were preceded by behavior changes
such as nervousness, irritability, listlessness,
disobedience and crying spells. He further emphasized that not infrequently cases are
incorrectly diagnosed as having primary
be-havior disorders, brain tumors or epilepsy.
Williams et al.,8 in a survey of 295 cases during a 20-year period in Baltimore, point out that plumbism may be the cause of
many obscure nervous conditions and early manifestations are frequently irritability and
fretfulness. Tanis9 found irritability as a symptom in 67% of cases, listlessness in 61% and behavioral on mental symptoms in 21%.
Other signs and symptoms of abnormal
be-havior included dullness, inactivity, with-drawal, refusal to play, inattention, disobedi-ence and temper tantrums. Thurston et al.b0
reported irritability as a symptom in 72% of cases. The present case report exhibited all of the characteristics described as
“be-havioral and mental symptoms” but vomit-ing was the only systemic manifestation
noted.
Lead poisoning in children becomes
symptomatic most frequently between the months of May and September. Of 105 cases reviewed by Chisolm and Harrison1’ 88 had
the onset during this 5-month period.
5ev-enty-nine percent of the cases reported by Tanis9 occurred from June to August. This striking seasonal incidence has been noted
314
LEAD
ENCEPHALOPATHY
derstood, the experimental evidence of Ra-poport and Rubin12 seems to indicate that increased amounts of vitamin D, incident to tile exposure to sunlight during the sum-men months, increases the absorption of lead from the gastrointestinal tract.
Occa-sionally a febnile episode may mobilize bead stored in the body and produce acute onset
of symptoms.
From 6 months to 1 year of age the nor-mab behavior of children includes chewing on on the ingestion of any object placed
within reach/s but after this age such
actions may be considered perversions of appetite. Pica is observed in defective and
neurotic children although most authors
consider it a pernicious habit in the
ma-jonity of cases unrelated to any underlying
abnormal
Bradley et al.15 report a history of pica in 124 of 197 cases. This single finding gave a
higher correlation with increased levels of lead in blood than any other test on mani-festation (i.e., noentgenograms of long bones, anemia, basophibic stippling, gastrointestinal or nervous system symptomatology). Tanis9 reports an incidence of 94% of cases with a history of pica. The existence of a perverted
appetite may be overlooked, as in the
pres-ent case report, unless specifically asked for
by the examiner.
The chemical diagnosis of lead poisoning
is made by demonstrating increased
amounts of lead in the serum or blood on in a 24-hour urine specimen. Lead-free con-tainers must be used for collection of the samples, and the determination requires careful analytic techniques and accurate control studies. Because of expense and in-convenient access to proper laboratory facil-ities, such tests have little value as a screen-ing procedure in most office situations.
It is known that the type III isomer of copnoporphyrin is excreted in excess in bead
poisoning.1#{176} A semi-quantitative method for
estimating urinary ponphyrins has been de-scribed17 which can be done quickly and easily in any office laboratory with a mini-mum of equipment. McCord18 in an excel-lent review of
the
biochemistry
of
por-phynins states, “Porphyrinuria is not
diag-nostic of lead intoxication but as a screen-ing procedure constitutes a measure con-tnibutory to diagnosis.”
Treatment of lead poisoning consists of
two main objectives: 1) cessation of ex-posune, and 2) removal of bead from the
body. The former can usually be accom-plished by combined efforts of the local
public health department, social workers and physicians. The safe removal of lead from the soft tissues by sodium citrate and
2,3-dimencaptopropanol (BAL) has in the
past produced varying degrees of success.4
More recently attention has been focused on the organic chelating agent, CaEDTA. The chemical and pharmacologic actions of this drug have been outlined in the comprehen-sive summary of Bessman et al.19 Evidence at present seems to indicate that in the pnes-ence of adequate renal function, CaEDTA is the drug of choice in both acute and
chronic lead poisoning.
A long-term
follow-up
of
patients treated with CaEDTA has not yet been reported, but with previous forms of therapy for acute lead encephalopathy, the end results in sun-viving cases have been 20Gibb and MacMahon6 state “There can, in-deed, be no doubt about the gravity of the
aftermath of plumbism in children, and in
the few instances in which adequate follow-UP techniques have been applied, its conse-quences have been, even in so-called ‘cured
cases,’ deleterious to tile progress of mental
growth.”
The prognosis in this patient must be guarded until time has permitted an ade-quate evaluation of intellectual develop-ment, but the dramatic clinical improve-ment offers hope for a relatively favorable outcome.
Because of the disastrous results of acute
lead encephabopathy the need for early
diagnosis and prompt treatment cannot be
CONCLUSION
Chronic bead encephalopathy must be considered in the differential diagnosis of pediatric patients who present with mani-festations of schizophrenia, behavior dis-orders or degenerative diseases of the cen-tral nervous system. Determination of
un-nary coproporphynin is a simple, fast
screen-ing procedure applicable to office practice. The prognosis for normal mental develop-ment following encephabopathy is poor. It is hoped that early recognition of the more subtle signs of central nervous system in-volvement will allow treatment to be insti-tuted soon enough to prevent the crippling mental deterioration which is so often a sequela of lead poisoning.
Acknowledgment
The authors wish to express their thanks to Dr. Wayne Hart for permission to publish this case, and to Dr. Rachel Driver who managed
the patient’s hospital care.
REFERENCES
1. Nelson, W. E., ed. : Textbook of Pediatrics,
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2. Ford, F. R. : Diseases of the Nervous
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18. McCord, C. P. : The porphyrins. Indust. Med., 20:185, 1951.
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20. Bvers, R. K., and Lord, E. E. : Late effect
