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Clinical Pediatrics, Vol. 5, No. 5, May 1966, Pp. 292-298. Neurologic Sequelae of Plumbism in Children MEYER A. PERLSTEIN, M.D.,* RAMZY ATTALA, M.D.f From the Children's Neurology Service of the Cook County Hospital and The Hekioen Institute for Medical Research, Chicago Prevention is still the best treatment for lead poisoning and its sequelae. Here is a survey on the nature and in cidence of the neurologic sequelae of lead intoxication among 425 patients over a ten-year period. Jl _/EAD has become a prime cause of poisoning. among children in the United States, particularly in the lower socio-economic group. In and around Chicago, lead accounts for nearly 80 per cent of all deaths due to accidental poisoning.4 Intoxica tion from arsenic, thallium, salicylates, and other chemicals usually result in either death or com plete recovery, but plumbism is far more likely to leave permanent sequelae. Mortality rates and the incidence of sequelae from lead poisoning vary both with tire age of the patient and the clinical picture at the onset of the disease. They are greater among infants and among those presenting with severe encepha litic symptoms, than among older children and those who present with only gastrointestinal symptoms or general malaise without neurologic symptoms. Morbidity and the incidence of se quelae are not necessarily related to blood lead or urinary coproporphyrin levels, either, since some of the most severely involved patients may have only modest increases in blood lead and urinary coproporphyrins at the time of admission. The clinical aspects and mortality in lead poi soning in the Chicago area have been reviewed elsewhere.4-7 The purpose of this paper is to delineate and to describe the nature and inci dence of the neurologic sequelae in those patients Aided by a grant from United Cerebral Palsy, Chicago. * Associate Professor in Pediatrics, Northwestern University Medical School, Chicago. f United Cerebral Palsy Fellow in Neuropediatrics. 292 who survive. The sequelae of lead poisoning have been documented by Byers and Lord * '-* in 20 children, by Thurston ef a/.'42 in 11, by Smith 10 in 30, and by Chisolm and Harrison 8 in 36 chil dren. The most common sequelae reported include mental retardation, recurrent seizures, cerebral palsy, and optic atrophy'. Although others have reported sequelae involving kidney, liver, heart, and muscle, these are beyond the scope oF this present review. As in all retrospective studies, the condition of die children in this study before the onset of plumbism has to be surmised from the history. Thus, one cannot always be sure that some of the observed sequelae do not antedate the plumbism. Children who are mentally retarded are more likely to indulge in pica, and children who de velop plumbism from pica are more likely to become mentally retarded. Plan of Study and Materials Of 425 patients in this study, 389 were from tire Children's Neurology Clinic of the Cook County Hospital, and 36 from the private prac tice of the senior author. Most of the Cook County Hospital patients had been initially hos pitalized, and on discharge had been followed through the Out-Patient Clinic for periods rang ing from six months to ten years. Eighty-four per cent were Negro children from the slum areas in Chicago. There were 214 male and 211 female patients and their ages ranged from nine months to eight years at the time of the first admission, with the median age around two years--the age at which most accidental poisonings occur. The source of lead in 408 patients was from chewing or eating loose plaster with old leadcontaining paint on it in shim clearance projects; the burning of battery casings was responsible for intoxication by the inhalation of lead in 17 instances. In a pair of twins, tire lead source was from sucking on lead-containing toys, and in one case, from water in a tank contaminated by red Vol. 5 No. 5 CLINICAL PEDIATRICS N36959 NEUROLOGIC SEQUELAE OF PLUMBISM lend paint. Case distribution and sources of lead are summarized in Table 1. The histories were verified, when feasible, by social service interviews, and die prc-plumbism status of the patients was judged by detailed de velopmental histories or by school records when available. The incidence of each type of sequela was correlated with die mode of clinical onset and the source of lead exposure. Results of Study In 257 or 61 per cent of the 425 patients stud ied, there was complete recovery from lead in toxication; in 1S8 or 39 per cent, neurologic se quelae remained, and these are summarized in Table 2. Sequelae of Lead Poisoning The sequelae were groupal into four main subdivisions: (1) Mental retardation was the most common sequela, occurring in 22 per cent of the total scries. Included in this group were some children who had had pre-existing mental retardation as judged from the developmental history or I.Q. records when available, but in whom die intellectual deficit was aggravated as a result of the plumbism. The degree of retardation was usually profound. In a few patients, the intellectual involvement was less marked, and I.Q. scores were in the low nor mal category. These were included only if their I.Q. had been average or above before the plum bism. In some, the brain damage was minimal with learning blocks, usually of a visual-perceptual type, being the only sign of impaired learning. Tabl e 1. Distribution of 4Z5 Coses oj Plumbism Area No. of Patients Source Coot County Hospital. Private Practice 389 36 Race Sex Negro White Male Female 3S7 68 214 211 Age Source oj Lead 9 mos, to 8 yrs. (Median age 2 yrs.) Enteric Pica for paint or plaster Lead toys Contaminated water supply Respiratory Burning of battery casings 405 2 1 17 (2) Recurrent seizures were almost as common, occurring in 20 per cent of the patients. Only those who had previously been seizure-free, or whose pre-existing seizures had been perceptibly aggravated by plumbism were included in this group. The most common type of seizure was grand mal, present in 85 per cent, although focal, Jacksonian, myoclinic, akinetic and vegetative spells often co-existed with the predominant grand mal seizures. Only 10 per cent of the patients with seizures had focal or Jacksonian convulsions without accompanying grand mal. In only three patients did myoclonic, akinetic, and Tabl e 2. Sequelae oj Plumbism by Mode of Onset in 4Z5 Patients Mode of Onset Sequelae None Mental retardation Seizures Cerebral palsy Optic atrophy Total Total (N = 425) N% 257 61 93 22 85 20 92 51 106%* Enceph. (N = 59) ,V % 11 18 23 38 32 54 8 13 46 123%* Seizures IS! = 43) -V % 14 33 14 33 Ataxia (N = 17) R% 7 41 5 29 17 39 00 6 35 16 00 105%* 16 U7%* G.I. <N = 232) N% 159 69 43 19 30 13 00 00 101%* * Percentages total more than 100% because of multiple sequelae in same patient. CLINICAL PEDIATRICS May 1966 Febrile (N = 16) N% 13 81 3 19 00 00 00 100% Asymp tomatic (N = 58) Ti % 53 91 59 00 00 00 100% 293 DUP050315202 PERLSTEIN AND ATTALA vegetative seizures, respectively, each occur as the only type of residual seizure. (3) Cerebral palsy was third in frequency as a sequela, occurring in only nine patients or 2 per cent. Spasticity was the most common type, present in six children, five hcmiplcgics and one triplegic Exirapyramidat forms of cerebral palsy occurred in three patients--one ataxic, one with combined athetosis and hemirigidity, and one with an unusual complication of progressive dys tonia musculorum deformans. Case reports of three of these patients arc appended. (4) Optic atrophy was die most common ocular sequela, occurring in five patients or 1 per cent. One of these also had retrobulbar neuritis, one had corneal opacities, and one had bilateral ptosis. Strabismus occurred in three other patients. Mode of Onset of Symptoms From a prognostic viewpoint, it is interesting to correlate the incidence and types of sequelae with die mode of onset of the disease. For pur poses of this study, the mode of onset was divided into six clinical types, three with neurologic symp toms, and three widiout. 1. Encephalopathic. These patients had the most severe neurologic involvement. There was usually an acute or subacute onset with signs of increased intracranial pressure--clouded sensorium, slowing of the pulse or respiration, choked discs, and increased cerebrospinal fluid pressure. Coma, fever, ataxia, convulsions, and cerebrospinal fluid pleocytosis and increased pro tein were also usually, but not always present on admission or a few days later. 2. Seizure. Here, the presenting symptom was a seizure in a child previously seizure-free. The seizure was generally a grand mal, focal, or vege tative spell, with or without the presence of fever. In some of these patients, ataxia of variable de gree did co-exist, but the signs of increased intra cranial pressure, characteristic of die encephalo pathic group, were absent. 3. Ataxia. In these patients, ataxia was the only or primary presenting neurologic sign. The onset was generally less acute or less dramatic than in the two preceding groups. There was usually a gradually progressive ataxic gait plus incoordination iu hand function, with or without nystagmus. Of the three neurologic types of onset, the ataxic group was tlic most benign. 4. Gastro-intesthial. These patients presented not with neurologic symptoms, but with subacute or chronic complaints of nausea, vomiting, colic, constipation, or diarrhea. There might also have been some evidence of anemia, malnutrition or general malaise, but gastro intestinal complaints predominated. Children entering the Cook Comity Hospital with-such complaints are viewed with suspicion of lead poisoning unless proven other wise. 5. Febrile. The onset here was not suggestive of ptumbism. The presenting symptom was fever, with or without signs of infection. In many of these patients, the acidosis associated with the febrile episode with its mobilization of stored lead might have been responsible for the later superimposition of secondary gastro-intestinal or neurologic symptoms. 6. Asymptomatic or subclinical. In these childr.en, the diagnosis of plumbum was made either by our routine workup of asymptomatic siblings of children with known lead poisoning, or was ail inadvertent or accidental finding. Incidence of Sequelae Classified by Mode of Onset As expected, mortality, morbidity, and all types of sequelae were most frequent in patients with an encephalopathic onset of symptoms. In this group, tlie mortality varied from 28 per. cent to 45 per cent s depending upon the treatment em ployed and being greatest among those in whom extensive craniotomies were done. The incidence and nature of the sequelae, however, was not essentially different with both types of treatment. In 59 patients surviving encephalopathy and followed for six months to ten years, sequelae, summarized in Table 2, persisted in over four out of five or 82 per cent. The most common sequela was recurrent seizures. These occurred in over one-half or 54 per cent of the patients, were generally resistant to drug control, and were of a mixed type, such as a combination of grand mal, focal and myoclonic. Mental retardation was the next most common sequela, being present in 38. per cent. It was gen erally of a profound type and many of these pa tients remained vegetative. Cerebral palsy oc curred in only 13 per cent of these patients, but it is interesting that of the nine in the total series who were left with cerebral palsy, eight presented with encephalopathy. Mental retarda tion and seizures co-existed in many of these cases. Optic atrophy, the least common sequela, oc curred in only four or 6 per cent of the patients. However, of the five patients with this complica tion, four were encephalopathic on first presenta tion. This relatively low incidence of optic atrophy does, not necessarily reflect a decreased sensitivity of the optic nerves to lead, but, rather, that this sequela occurs only in severe cases, most of whom die. In the patients with optic atrophy, one had 294 Vol. 5 No. 5 CLINICAL PEDIATRICS DUP050315203 NEUROLOGIC SEQUELAE OF PLUMBISM a concomitant retrobulbar neuritis, another had corneal opacities, and a third had ptosis. In some patients there were multiple sequelae, so that a total of 67 sequelae were recorded in 59 patients. Of 43 patients presenting Erst with seizures, . but with no other evidence of encephalopathy, 14 or S3 per cent had no sequelae. Among the 29 with sequelae, recurrent seizures were most common and persisted in 17 patients or 39 per cent. These seizures, primarily of the grand mal type, were generally more amenable to drug ther apy than seizures following the encephalopathic onset of lead intoxication. Mental retardation occurred in 14 or 33 per cent of patients, two of them with recurrent seizures. The mental retardation teas generally less severe than in the encephalitic group. There was no cerebral palsy or optic atrophy in this category. Among 17 patients, the onset of symptoms was with ataxia alone. There were no seizures or in creased intracranial pressure. In. seven or 41 per cent, there were no sequelae. Six or 35 per cent developed recurrent seizures, five or 29 per cent were left with mental retardation, and one with optic atrophy and ptosis. One other patient who developed progressive dystonia musculorum de formans, and described in Case Report No. 3, had repeated exposures to lead and may have had an unrecognized encephalopathy. In three patients who presented with ataxia, combined sequelae existed; the patient with optic atrophy also had seizures, and two of those with seizures also became mentally retarded. It is in teresting that in no patient presenting with ataxia alone did this symptom persist. The only patient in the total series in whom ataxia remained as a sequela had an encephalopathy associated with seizures and ataxia. The largest group of patients, 232, presented ivith gastro-intestinal symptoms, such as nausea, vomiting, constipation, diarrhea, and colic. In this group, sequelae were relatively infrequent, occur ring in only 31 per cent. In 30 or IS per cent of . these patients, seizures persisted. These were mainly of the grand mal type, and most were amenable to drug therapy. Mental retardation remained in 43 or 19 per cent. It was less pro found than that in the group with encephalo pathic or seizure onset. Four patients with a severe . degree of mental retardation actually had aggra vation of a pre-existing intellectual defect, one of them due to meningitis at one year of age. There was no cerebral palsy or optic atrophy as sequelae in this group. Of four patients with sickle cell anemia, none developed sequelae. The group which presented with fever was the smallest. It consisted of 16 patients who pre sented with fever only, with or without an asso ciated infection. As expected with this relatively benign type of onset, sequelae were less frequent, even though transitory neurologic symptoms may have appeared in the course of the febrile epi sode. The only sequela was mental retardation, and this was seen in only three or 19 of these patients. Among these three, intelligence was definitely less than before the febrile episode, but whether the mental retardation was attributable to plumbism or to some other infective factor is not certain. Among the asymptomatic patients, numbering 58, no symptoms referable to plumbism were pres ent. The diagnosis was made accidentally, or be cause a sibling was known to have plumbism. In one family where ten patients were examined because a sibling had lead encephalopathy from die burning of battery casings, no sequelae were found. In another where two children had died from lead encephalopathy, five siblings were fol lowed for two years. Of these, three were per fectly normal, one had an I.Q. of 85 not at tributable to die lead exposure, and one had seizures before the lead exposure which were not aggravated after it. In another family where five siblings were followed for 18 months, two chil dren were perfectly normal and three showed slightly retarded to low normal I.Q.'s, but were considered to have familial or socio-cultural type of retardation, rather than that due to plumbism. In only five patients or 9 per cent of those who were asymptomatic on first presentation was men tal retardation considered to be a possible se quela. Even in these, however, the reliability of the maternal histories was questionable. In only one of these had the onset of mental retardation been suddenly noted when a sibling developed lead encephalopathy. Sequelae Classified by Origin of Plumbism No significant differences in the incidence or nature of sequelae were found among children in whom the disease followed pica and among those from lead vapor inhalation. Re-exposure or multiple exposures to lead, however, did tend to result in greater mortality, morbidity and sequelae. Significant Case Reports In an attempt to better describe the treatment and outcome of our cases of lead intoxication, we have included here three of our most interesting cases in detail. 1. f.ead encephalopathy with left spastic hemiplegia, focal seizures, mental retardation, and optic atrophy as sequelae. CLINICAL PEDIATRICS May 1966 295 PERLSTEIN AND ATTALA S. 13. was a two-year-old Negro girl who was admit* led on July 28. 1962 with history of anorexia For six months, vomiting for two weeks, ami sore throat, and iistlcssncss for two days. The patient had been pick* Ing paint off the window sills. She lived with two older siblings and a 2-4-ycar-old unmarried mother on re lief in a two*room dilapidated apartment. Except for a birthweight of 3 lb., the pregnancy, delivery, neo natal period and development were normal. The pa tient had walked at 11 niontlis and spoken sentences at two years. On admission, she was lethargic, undernourished, pale, and dehydrated. Except for slight nuchal rigid ity and mild papilledema, the physical examination was normal. Cerebrospinal fluid was clear, but under increased pressure--COO mm. of water opening and 300 mm. closing pressure; there were 0 lymphocytes, 90 mg. glucose, 78 mg. protein, and 109 mg. chloride per cc. Urine coproporphyria was 4*f. X-rays showed dense epiphyseal lines in the long bones and radio opaque material in the bowel. There was a mild ane mia with hypochromia and basophilic stippling of the red blood cells. The blood lead was MO micrograms per 100 ml. A diagnosis of early lead encephalopathy was made. * After cleansing enemas to remove rectal and colonic lead, intravenous urea, 8 Cm., and mcthylprednisoldnc succinate, 6 mg. q 8 hr., were started. On the third day, the patient became irritable, and began to have generalized seizures controlled by. intravenous pento barbital sodium, ether inhalation, and rectal paralde hyde. Aspiration of vomitus on one occasion was fol lowed by respiratory^ arrest; this was relieved by trache ostomy and positive pressure respirator. The patient remained comatose and pupils reacted sluggishly to light. On the fourth day, Calcium Versenate, 300 mg. b.i.d,, was started intravenously and given for five days. On the Filth hospital day, because oF rising tem perature and poor condition, hypothermia was induced to 94 F. rectally. From (he fifth to eighth days, twitching of the left side, generalized seizures, and multiple premature heart beats with sinus arrhythmia were observed, but the blood pressure, urinary output, and serum elec trolytes remained normal. On the ninth day, the pa tient was more responsive and opened her eyes; by the 11th day. the tracheostomy was removed. It was now noted that the left arm was flaccid and the left knee jerk exaggerated. Urine coproporphyrin was still 3-f on the 20th day. On the 30th day, after four more five-day courses of Versenate and eight courses of urea, she was walking with help, but with an unsteady gait. She was discharged and referred to the clinic where she was followed for the next 18 months. The ataxia disappeared within two months, but focal and generalized seizures persisted; there was a nifld residual left spastic hemiplegia.' When last seen bilat eral optic atrophy and profound mental retardation to the idiot level were present. Speech had not been re gained, and patient still needed minimal support for walking. Commit/; The encephalopathy in this child, was not aborted by urea, steroids, hypothermia, or Versenate. The brain damage may have been compounded in some measure by the respiratory arrest. The long ex posure to lead and the relative youth oF the patient were probably (he most important factors. 2. Lead encephalopathy aiul duodenal ulcer from pica with residual ataxia, seizures, mental retarda tion, and optic atrophy. W. G., a 29-xnoiuh-olcl Negro boy, was admitted on August 5, 1962 with a history of plaster pica for sev eral weeks, vomiting, constipation and lethargy for nine days, and fever for five days. He had previously been normal; he walked at 1! montlis, spoke words at nine months, and used sentences at 14 months. On admission, except for lethargy and hyperirritabil ity, the physical and neurologic findings, including fuudoscopfc, were normal. Spinal tap allowed 600 min. of water opening, and 5G0 min. closing pressure. A Pandy test for spinal fluid globulin was positive, and there were 60 lymphocytes, 9S mg.% glucose, ami 204 mg.% protein per cc, Urine coproporphyria was 4 +. X-rays showed typical heavy epiphyseal lines in the long bones, radio-opaque material in tire colon and rectum, and some separation of the skull sutures. There was a secondary anemia, but no basophilic stip pling. The blood lead was later reported as 110 mi* crograms per 100 ml. A diagnosis of early lead en cephalopathy was made. Cleansing enemas were given, followed by intra venous urea, 1-1.2 Gm. q 8 hr., and raethylprcduisolouc succinate, 8 mg. q 6 hr. There was slight improvement after the second course of urea, but on the second day. the patient became more irritable mid apprehensive, Ills neck became rigid, and by the third day, he started to convulse. Convulsions became progressively worse and were only partially controlled with sodium amytal. Papilledema and deepening coma were now noted. Vital signs remained stable. Urea was continued and temperature was reduced to 94 F. rectally by tee-water mattress. On the sixth day, while still convulsing, he had a tarry stool and stopped breathing. Tracheostomy was performed and a positive pressure respirator at tached after resuscitation. Calcium Versenate was started intramuscularly on the seventh day, 540 mg. b.i.d., and given for five days. This was repeated until three courses were given. Bleeding from the bowel continued, and the hemato crit dropped from 32 to 16. A whole blood transfusion was given and repeated on the eighth day. Urinary coproporphyrin was still 3-1- after die Versenate. On the lGtli clay, tarry stools still continued and the hematocrit again dropped to 15. Another transfusion was given and steroids were decreased. Emesis and melcna failed to respond to medical treatment, including gastric balloon insertion, and on the 25tli day, a laparotomy was performed. A 1 cm. indurated chronic posterior duodenal ulcer was found, plus' a small intestinal tear 4 inches distal to the liga* ment of Tvietz, probably due to the balloon. A pyloro plasty, small bowel resection, and bilateral vagotomy were done. The procedure was well tolerated, bleeding stopped, and the patient began to improve. By' Oc tober 4, 1962, two mouths after admission, the palicut had developed corneal opacities, poor vision, loss of speech, mental retardation, and an inability to walk. He was discharged and referred to the clinic. ' First clinic visit was three months later. At this time, he had mild recurrent right focal seizures lasting two to three minutes, becoming generalized. These were eventually controlled with Dilantin and Mysolinc. Abil ity to walk alone returned six months after discharge, but still with ataxia. There was a bilateral severe optic atrophy, bilateral corneal opacities, ami almost no re action to visual stimuli. In April 1965, two and onehalf years later, the patient still did not talk, was incontinent, could not feed himself, and was pro foundly retarded. He was still walking with an ataxic gait. No involvement of the eighth nerve could be demonstrated. 296 Voi. 5 No. 5 CLINICAL PEDIATRICS DUP050315205 NEUROLOGIC SEQUELAE OF PLUMBISM Comment: The severe neurologic sequelae may have hecn due in part to the anemia, respiratory arrest, and surgery. Ataxia of central {presumably cerebellar) ori gin is one of the less common permanent sequelae of plumbism. The complication of a bleeding duodenal ulcer is of interest, and not too uncommon. 3. Onset of plumbism with ataxia, tremors, and later exlrapyramtdal rigidity, but without signs of increased intracranial pressure. The course continued at a progressive dystonia musculorum deformans, a rare complication. A three-year-old Negro bdy, previously well, was ad mitted on June 5, 1958 with a history of vomiting and ivcight loss for five weeks, unsteady gait for three , weeks, and fever for one clay. A two-year history of pica was elicited. The patient was a full-term normal infant of birthwciglu 8 lb. 5 or. He had walked at 11 months and spoken sentences at 18 months. On admission, there was exudative tonsiiitis for which penicillin was given. Pulse, respiration, tem perature, and blood pressure were normal. The only abnormal neurologic finding was an ataxic gait plus coarse tremors of the hands, especially on intention. There was no increased intracranial pressure; spinal tap and fundoscopy were normal. X-rays of the bones showed typical lead lines, and urine coproporphyrin was 4 +. The blood count showed a moderate anemia. Blood lead level was 85 micrograms per 100 ml. The patient was given two five-day courses of intra muscular Calcium Verscnatc, 400 mg. b.i.d. He also received oral Calcium Verscnatc, 500 mg. q.i.d. for ten days. By the 12th day, the urine coproporphyria had disappeared, and the gait had improved. He still had some ataxia and tremors, however, when discharged three weeks after admission. Four weeks later, August 2, 1958, he was readmitted because of vomiting for four days and a gait which was becoming more un steady since discharge from tire hospital. Pica tor plaster had persisted since discharge. On this second admission, the patient was still am bulatory. General examination was normal except for slight pallor. Neurologic examination revealed a pro pulsion gait, with tendency to fall to the left. Tremors and cogwheel rigidity were present bilaterally, more on the left. Urinalysis showed 4 + coproporphyrin. The hemoglobin was 6.9 g. per 100 ml. (45%); RBC's numbered 2.38 millions; Turk irritation cells were seen in the differential, but there was no basophilic stippling of the red blood cells. There was no evi dence of increased intracranial pressure or cerebro spinal fluid change noted on lumbar purieture. . The patient was treated again with Calcium Vcrsenate for five days, 250 mg. b.i.d,, and was placed ou iron supplements. A therapeutic trial with Artanc for two weeks to control tremors and rigidity was without benefit. The patient was discharged after eight days still walking with ail unsteady gait to be followed in the Pediatric Neurology Clinic. His urine coproporphyria and blood lead nor malized, and the lead lines decreased over the course of six months. On the Stanford Billet, his I.Q. in 1959, at a chronologic age of four years two months was 74, ami in 1961, at a chronologic age of six years four months, it was 79. This was considered to be an inlelligcnce loss from his presumably average preplumbism intelligence, as judged from his develop mental history. Speech was distinct and hearing ade quate for ordinary conversation. In spite of no further lead ingestion, however, the hoy's motor condition became gradually worse. He developed extraneous involuntary movements which began in the left leg and then spread after a few months to all four extremities. These movements were tlysconic and more marked in proximal -and trunk muscles. While walking, his back would suddenly arch and his leg become forcibly flexed at the hip and knee, and he would frequently fall. He gradually be gan to assume the bizarre dystonic postures seen in typical dystonia musculorum deformans. The child finally became wheelchair and bedridden. During all this period, his speech and mentality, although reduced from his presumably pre-lead av erage levels, seemed to be adequate for normal use. When last seen, in April,-1966, nearly eight years after his first admission, a trial on Valium was given with moderate improvement in his muscle tension. A chemopaliidcctomy was being considered as the next possible procedure to relieve his deforming postural move ments. Comments: A double exposure to lead is seen here, the first being followed by cerebellar ataxia, and the second by extrapyramidal rigidity becoming progres sively worse and developing dystonic athetosis. To our knowledge, the clinical syndrome of a progressive dys tonia musculorum deformans as a sequela of plumbism is unique. The absence of signs of increased intracranial pres sure is of interest. It may be speculated that the first episode of plumbism caused a "locus rcsistentia minoris" in the central nervous system, so that the brain was more vulnerable to the continued exposure to lead. Comments and Discussion Mortality and sequelae of lead poisoning in children are still very high. The more fulminant the onset of plumbism and the younger the child at onset, the greater are the mortality and the incidence of sequelae. In adults, the neurologic sequelae are primarily of a peripheral neuropathic nature, characteristically with wrist drop due to radial palsy. In children, the central nervous sys tem is more likely to be involved, since the younger the child, the more vulnerable the brain to lead intoxication. The greater central nervous system involvement may also be due in part, as sugested by Chisolm and Harrison, to the more massive and acute exposure that occurs in childhood. Since lead encephalopathy is more common in children than in adults and since more vital centers are in volved in youngsters, it is understandable that mortality and morbidity from plumbism is higher in children. In childhood leatl encephalopathy, the mortal ity is between 28 per cent and 45 per cent, and four out of five who survive have sequelae. The mortality and sequelae are decreased when the onset is less acute, even though die presenting symptom may be a neurologic one, such as seizures or ataxia. In the most commonly seen form of plumbism, that which presents with gastrointes tinal symptoms, the mortality is negligible, and only three out of ten patients have sequelae. CLINICAL PEDIATRICS May 1966 297 DUP050315206 PERLSTEIN AND ATTALA Mental retardation and recurring seizures, die most common sequelae seen in. lead poisoning, reflect the diffuse severe cortical involvement.8-11 The degree of mental retardation is variable and dependent upon the severity of the disease. In die mildly involved, there are often only per ceptual problems, primarily of a visual type. Sei zures caused' by plumbism, as is true of most seizures due to organic brain involvement, are more refactory to anticonvulsant therapy than idiopathic epilepsy. The cerebral palsies were most commonly seen in children presenting with encephalopathies. As in most acquired cerebral palsies,8 these tend to be primarily of the spastic variety. The greater susceptibility of the "pyramidal tract system" in infancy may be due to its relatively incomplete myelinization and development, as compared to the basal nuclear or extrapyramidal areas, whose injury might result in dyskinetic syndromes. In only one instance was the ataxic form of cerebral palsy a sequel, in spite of the fact that ataxia was not uncommon as a presenting symp tom. The occurrence in one patient of dystonia musculorum deformans progressiva, described in Case Report 3, after repeated exposures is unique in our experience. Optic atrophy widi or without neuritis was the most common cranial nerve symptom. Ptosis, corneal opacities, and strabismus occasionally occurred. In our experience, deafness due to involvement of die eighth nerve did not occur. Although die fatality rate was greatest in those treated by cranial decompressions, the incidence and nature of sequelae was not related to die type of u-eatment of die encephalopathy, or to the portal of lead entry, whether by ingestion or by inhalation. Re-exposure and continuing ex posure to lead, however, increases mortality and morbidity. As a result of re-exposure, the subclinical case may begin to develop gastro-intestinal and then neurological symptoms. The mild case may develop ataxia, then seizures, and finally, a fulminant encephalopathy. Other factors which may trigger a latent plum bism into an active form may be of a metabolic or seasonal nature. Acidosis, incident to infections, malnutrition or to increased ultraviolet radiation as occurs in summer, may precipitate an acute episode of plumbism. Thus, it becomes impor tant to detect plumbism in the early stages, before irreversible neurologic damage can occur. Once neurologic systems have become involved, they may become sensitized target organs vulnerable to repeated or continuing lead ingestion. At the present time, the best treatment for lead poison ing and its sequelae is its prevention. Summary of Findings Among 425 children with plumbism, 39 per cent had neurologic sequelae. Mental retardation and recurrent seizures arc most common and per sist in approximately one out of five patients. Cerebral palsy and optic atrophy occur less fre quently and are limited to those who present with either encephalopathic or ataxic syndromes. Cerebral palsy is usually of the spastic hemi plegic type. A patient who developed dystonia musculorum deformans is unique in our experi ence. Hie younger the child and the more ful minating the onset, the greater the incidence of sequelae. , In children presenting with severe encephalopa thy, sequelae persist in over four out of five. In those who present with seizures without increased intracranial pressure, sequelae occur in two out of three. When ataxia is the only neurologic pre senting symptom, sequelae occur in three out of five. In those in whom the presen ting symptoms are gastro-intestinal, sequelae occur in less than one out of three. When the onset is with a fever only, or asymptomatic, die incidence of sequelae is one out of five to ten. The nature and incidence of sequelae seems to be unrelated to die type of treatment employed. References 1. Byer, R. K. and Lord. E. E.: Late effects of lead poisoning on mental development. Azner. J. Dis. Child. 66: 471,1943. 2. Byers, R. K.: Lead poisoning. Pediatrics 23: 585, (Mar.) 1959. 3. Chisolm, J. J., Jr. and Harrison, H. E.: (a) The ex posure of children to lead. Pediatrics 18: 943, (Dec.) 1956. (b) The treatment of acute lead encephalopathy in children. Pediatrics 19(1): 2-20, (Jan.) 1957. 4. Christian, J. R., Celewycz, B. S. and Andclman, S. H.: A three year study of lead poisoning in Chi cago. Atner. J. Pub. Health 54: 1241, (Aug.) 1964. 5. Greengard, J., Adams. B. and Benuan, E.: Acute lead encephalopathy in young children. J. Pediat. 66(4): 707, (April) 1965. 6. Greengard, J. J., Rowley, W., Elam, H. and Perlstein, M. A.: Lead encephalopathy in children: intravenous use of urea in its management. New Eng. J. Med. 264: 1027, (May) 1961. 7. Greengard, J.: Symposium on lead intoxication--I. Clinical features. (This issue.) 8. Hass, G., Brown, D. V. L., Eisenstein, R. and Hemmens, A.: Relations between lead poisoning in rabbit and man. Amer. J. Path. 45(5): (Nov.) 1964. 9. Perlstein, M. A. and Hood, P.: Etiology of postnconatally acquired cerebral palsy. J. A. M. A. 188: 850, (June 8) 196-1.' 10. Smith, H. D-, Baelmcr, R. L., Carney. T. and Ma jors, W. J.: Sequela of pica with and without lead poisoning. Amer. J. Dis. Child. 105: 609. (June) 1963. 11. Szanto, P-: Symposium on lead intoxication--V. Pathology. (This issue.) 12. Thurston el al.: The late effects of lead poisoning. J. Pediat. 47: 413, 1955. 298 Vol. 5 No. 5 CLINICAL PEDIATRICS DUP050315207