Lead in a case of encephalopathy.

A 2-year-old boy with a history of pica was admitted with vomiting and treated overnight for viral tonsillitis. A week later, he presented with a prolonged afebrile seizure and required intubation and ventilation. Antibiotics and acyclovir were started. Despite extensive investigations including MRI head, no cause was identified. Four days later, he deteriorated with signs of raised intracranial pressure. On day 5, blood lead concentration in the sample collected at admission was reported as grossly elevated, consistent with a diagnosis of severe lead poisoning from ingesting lead-containing paint at the family home. Chelation therapy was started but, unfortunately, he did not make a neurological recovery, and care was withdrawn. A serious case review identified a lack of awareness of lead poisoning and its relation to pica as a root cause. We report this case to share our experience and the importance of considering lead poisoning in children with pica.

Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid.

OBJECTIVE: The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. METHODS: The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4) Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). RESULTS: In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. CONCLUSION: It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.

Role of chelation in the treatment of lead poisoning: discussion of the Treatment of Lead-Exposed Children Trial (TLC).

Lead exposure in children is one component leading to cognitive impairment. The Treatment of Lead-Exposed Children Trial (1994-2004) studied the effect of succimer in treating low levels of lead exposure (20-44 mcg/dL) in children 12 to 33 months old. While succimer was effective in reducing blood lead concentrations in the short term, treatment of blood lead levels did not result in any detectable improvement in a wide variety of measurements of cognitive or behavioral function. Furthermore, blood lead concentrations were not distinguishable between chelated and non-chelated individuals at 1 year. The most important treatment strategy is identification and termination of major sources of lead exposure.

Encephalopathy from lead poisoning masquerading as a flu-like syndrome in an autistic child.

Acute encephalopathy from childhood lead poisoning is fortunately rare. However, in pediatric patients with developmental disabilities and pica, there is a risk of lead exposure at a dose commensurate with encephalopathy, coupled with a risk of delayed diagnosis because of difficulty in distinguishing between baseline and altered behavior. We report here a 4-year old autistic boy who presented to the pediatrician's office with gastrointestinal symptoms and behavioral changes and was at first thought to have a viral syndrome. He returned 2 days later with a worsening illness; increasing pallor, vomiting, abdominal colic, and changes in consciousness were recognized in the emergency department as lead-induced anemia and encephalopathy, associated with a positive abdominal film for paint chips and a blood lead level equal to 216 microg/dL (10.43 micromol/L) (reference, <10 microg/dL or 0.483 micromol/L). As this case illustrates, prompt recognition is dependent on the skills and suspicions of an astute clinician, especially in the busy emergency department.

Does background postnatal methyl mercury exposure in toddlers affect cognition and behavior?

Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn 1 week before randomization and 1 week after treatment began when succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 microg/L and 0.52 microg/L and post-treatment concentrations were 0.51 microg/L and 0.48 microg/L for placebo and succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable.

The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels.

CONTEXT: Lead toxicity is an ongoing concern worldwide, and children, the most vulnerable to the long-lasting effects of lead exposure, are in urgent need of a safe and effective heavy metal chelating agent to overcome the heavy metals and lead exposure challenges they face day to day. OBJECTIVE: This clinical study was performed to determine if the oral administration of modified citrus pectin (MCP) is effective at lowering lead toxicity in the blood of children between the ages of 5 and 12 years. METHOD: Hospitalized children with a blood serum level greater than 20 microg/dL, as measured by graphite furnace atomic absorption spectrometry (GFAAS), who had not received any form of chelating and/or detoxification medication for 3 months prior were given 15 g of MCP (PectaSol) in 3 divided dosages a day. Blood serum and 24-hour urine excretion collection GFAAS analysis were performed on day 0, day 14, day 21, and day 28. RESULT: This study showed a dramatic decrease in blood serum levels of lead (P = .0016; 161% average change) and a dramatic increase in 24-hour urine collection (P = .0007; 132% average change). CONCLUSION: The need for a gentle, safe heavy metal-chelating agent, especially for children with high environmental chronic exposure, is great. The dramatic results and no observed adverse effects in this pilot study along with previous reports of the safe and effective use of MCP in adults indicate that MCP could be such an agent. Further studies to confirm its benefits are justified.

Very low lead exposures and children's neurodevelopment.

PURPOSE OF REVIEW: We remain far from achieving the goal of eliminating lead-associated neurodevelopmental morbidities in children. New evidence regarding the blood lead levels at which morbidities occur have led to calls for the Centers for Disease Control and Prevention to reduce the current screening guideline of 10 microg/dl. The review evaluates the basis for these calls. RECENT FINDINGS: Adverse outcomes, such as reduced intelligence quotient and academic deficits, occur at levels below 10 microg/dl. Some studies suggest that the rate of decline in performance is greater at levels below 10 microg/dl than above 10 microg/dl, although a plausible mechanism has not been identified. Increased exposure is also associated with neuropsychiatric disorders such as attention deficit hyperactivity disorder and antisocial behavior. Functional imaging studies are beginning to provide insight into the neural substrate of lead's neurodevelopmental effects. Current protocols for chelation therapy appear ineffective in preventing such effects, although environmental enrichment might do so. SUMMARY: No level of lead exposure appears to be 'safe' and even the current 'low' levels of exposure in children are associated with neurodevelopmental deficits. Primary prevention of exposure provides the best hope of mitigating the impact of this preventable disease.

Effect of succimer chelation therapy on postural balance and gait outcomes in children with early exposure to environmental lead.

This study investigated the influence of succimer chelation therapy in eliminating and/or minimizing lead-associated impairments of motor functions such as postural balance and locomotion or gait activities. In this study, postural balance and functional locomotion or gait were quantitated in 161 children in Cincinnati enrolled in a randomized, placebo-controlled, double blind clinical trial. In comparison to the placebo group, the succimer therapy group showed significantly decreased postural sway during dynamic task performance implying improved postural balance. The results from locomotion tests demonstrated significant improvements in functional tasks of obstacle crossing and normal walking in the succimer treated group. While some beneficial neuromotor effects of succimer therapy were observed in the present study there remains several unanswered questions such as how long these effects will persist and how succimer therapy modifies lead-associated cerebellar deficits manifesting as perturbations in vestibular and/or proprioception systems for postural balance and functional locomotion.

Lead exposure, IQ, and behavior in urban 5- to 7-year-olds: does lead affect behavior only by lowering IQ?

BACKGROUND: Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information. OBJECTIVES: The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration. METHODS: Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33-month-olds with blood lead concentrations of 20 to 44 microg/dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study. RESULTS: Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale-Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7. CONCLUSIONS: Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ.

Succimer therapy for congenital lead poisoning from maternal petrol sniffing.

An infant, born at 35 weeks' gestation to a woman who sniffed petrol, had a cord blood lead level eight times the accepted limit. Treatment with oral dimercaptosuccinic acid promptly reduced his blood lead levels. To our knowledge, this is the first reported case of congenital lead poisoning secondary to maternal petrol sniffing. We suggest that at-risk pregnancies should be identified, cord blood lead levels tested, and chelation therapy and developmental follow-up offered to affected infants.

Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure.

Maternally lead (Pb)-exposed, juvenile rats exhibit significant deficits in spatial reference memory acquisition and working memory performance in the Morris water maze (MWM). Acute systemic application of nicotine reverses these deficits without affecting behavioral performance of the age-matched, lead-unexposed control animals. These results suggest that nicotinic agonist treatments can ameliorate learning and memory impairments, presumably by compensating for deficient nicotinic function in developmentally lead-exposed animals.

Succimer (meso-2,3-dimercaptosuccinic acid (DMSA)) treatment of Andean children with environmental lead exposure.

The authors studied children in Andean villages contaminated by a lead-glazing cottage industry. Mean blood lead (PbB) level in 35 exposed children, aged 3-14 years, a year before treatment, at the time of initiation of a comprehensive lead education and prevention program, was 53.4 microg/dL. PbB levels immediately before and three weeks after a ten-day regimen of succimer treatment of the 35 children were 43.4 microg/dL and 34.3 microg/dL, respectively, showing a 21% reduction and a significant difference between means (t = 5.09, p = 0.0001). PbB levels of the same children a year before treatment and immediately pre-treatment were also significantly different (t = 10.59, p = 0.0001). Thus, a ten-day course of succimer chelation effectively reduced PbB in children with moderate to severe Pb intoxication, and the education and prevention program, initiated with parents, health care providers, and educators, also contributed significantly to reducing PbB.

Safety and efficacy of succimer in toddlers with blood lead levels of 20-44 microg/dL. Treatment of Lead-Exposed Children (TLC) Trial Group.

Although lead encephalopathy has virtually disappeared from the United States, thousands of children still have sufficient lead exposure to produce cognitive impairment. It is not known whether treating children with blood lead levels < 45 microg/dL (2.2 microM) is beneficial and can be done with acceptable safety. We conducted a 780-child, placebo-controlled, randomized trial of up to three courses of succimer in children with blood lead levels of 20-44 microg/dL (1.0-2.1 microM). Children were aged 12-33 mo, 77% were African-American, 7% were Hispanic, and they lived in deteriorating inner city housing. Placebo-treated children had a gradual decrease in blood lead level. Succimer-treated children had an abrupt drop in blood lead level, followed by rebound. The mean blood lead level of the succimer-treated children during the 6 mo after initiation of treatment was 4.5 microg/dL (95% confidence intervals, 3.7 to 5.3 microg/dL; 0.22 microM, 0.18 to 0.26 microM) lower than that of placebo-treated children. There were more scalp rashes in succimer-treated children (3.5% versus 1.3%) and an unanticipated excess of trauma. Succimer lowers blood lead level with few side effects. The unanticipated excess of trauma requires confirmation.

Developmental stage-dependent protective effect of NGF against lead cholinotoxicity in the rat septum.

The ability of nerve growth factor (NGF) to ameliorate developmental cholinotoxicity of inorganic lead (Pb) for the septal neurons was investigated by making intracerebroventricular injections of single doses of 30 microg 2.5S NGF into maternally lead-exposed suckling rats on postnatal days P2, P4, P11, or P18. Administration of NGF on P4 or later induced septal choline acetyltransferase (ChAT) activity to the same relative extent in both Pb-exposed as in control rats but failed to reverse the net reductions of ChAT activity induced by Pb. In contrast, injection of NGF at P2 completely restored ChAT activity in Pb-exposed pups to control levels by preventing the loss of ChAT-immunoreactive cells in the septum. It is concluded that although NGF retains the capacity to upregulate ChAT throughout the period of Pb exposure, it protects against the Pb-induced loss of septal cholinergic neurons only when applied within the critical period of Pb-vulnerability between postnatal days 2 and 4.

An unusual case of lead poisoning in an infant: nursing-associated plumbism.

Lead poisoning remains a common environmental threat for children today. The majority of cases of lead poisoning are caused by oral intake of lead dust or lead-containing paint flakes and thus occur during the second and third years of life. An unusual case of severe lead poisoning in a breast-feeding infant girl is here presented; the source proved to be a nipple shield made of a lead-containing metal. Despite the severity of the intoxication, by the end of treatment and for a year afterwards the infant has been well and her psychokinetic development has been normal.

A comparison of two dosing regimens of succimer in children with chronic lead poisoning.

There is limited information defining the optimal dosing regimen of succimer in the treatment of children with chronic lead poisoning. It is typically administered as a five day course of high dose therapy (1,050 mg/m2/day) followed by 14 days of low dose therapy (700 mg/m2/day). This study compared the effect on blood lead concentrations (BPb) of treatment with this standard regimen and an alternate regimen consisting of two courses of high dose therapy separated by one week. There were significant reductions in the mean BPb in both the standard (n = 7) and alternate (n = 4) treatment groups but there was not a significant difference between the groups. In the standard group, the BPb decreased from 33 +/- 4 to 27 +/- 6 mcg/dL. The BPb decreased from 33 +/- 6 to 23 +/- 4 mcg/dL in those treated with alternate therapy. This study suggests that two short courses of high dose therapy may be an acceptable alternative to standard succimer therapy. Because of the small size of this study, other studies are warranted.