Encephalopathy, lead

Full Fanconi syndrome has been reported to be present in some children with lead encephalopathy (Chisolm 1968 Chisolm et al. 1955). According to the National Academy of Sciences (NAS 1972), the Fanconi syndrome is estimated to occur in approximately one out of three children with encephalopathy and PbB levels of approximately 150 pg/dL. Aminoaciduria occurs at PbB levels >80 pg/dL in children with acute symptomatic lead poisoning (Chisolm 1962). The aminoaciduria and symptoms of lead toxicity disappeared after treatment with chelating agents (Chisolm 1962). 

Neurological Signs and Symptoms in Adults. The most severe neurological effect of lead in adults is lead encephalopathy, which is a general term to describe various diseases that affect brain function. Early symptoms that may develop within weeks of initial exposure include dullness, irritability, poor attention span, headache, muscular tremor, loss of memory, and hallucinations. The condition may then worsen, sometimes abruptly, to delirium, convulsions, paralysis, coma, and death (Kumar et al. 1987). Histopathological findings in fatal cases of lead encephalopathy in adults are similar to those in children (see discussion below). 

Histopathological findings in fatal cases of lead encephalopathy in children include cerebral edema, altered capillaries, and perivascular glial proliferation. Neuronal damage is variable and may be caused by anoxia (EPA 1986a). 

Death. Death can be the end result in cases of severe lead encephalopathy in both adults and children. The National Academy of Sciences (NAS 1972) analyzed unpublished data obtained from the patient populations reported in Chisolm (1962, 1965) and Chisolm and Harrison (1956) and concluded that the range of blood lead levels associated with death from lead encephalopathy in children was approximately 125-750 pg/dL (mean, 327 pg/dL). A case report described a 70-year-old female nursing home resident... 

In cases of lead encephalopathy with cerebral edema, edema can be treated with mannitol, corticosteroids, and hypothermia. Convulsions can be treated with diazepam, phenytoin, and/or phenobarbital (Garrettson 1990). 

Accidental or intentional ingestion of folk remedies containing lead (discussed in Section 5.5) represents another source for potential lead-poisoning in children. Acute lead encephalopathy in early infancy has been reported in a Middle Eastern study for 14 infants following the use of Bint al Thahab, a traditional... 

A1 Khayat A, Menon NS, Alidina MR. 1997a. Acute lead encephalopathy in early infancy-clinical presentation and outcome. Annals of Tropical Paediatrics 17(l) 39-44. 

Bradley JE, Baumgartner RJ. 1958. Subsequent mental development of children with lead encephalopathy, as related to type of treatment. J Pediatr 53 311-315. 

Habashi N, Kruszewski S. 1987. Lead encephalopathy from inhalation of leaded gasoline in an adult. Meeting of the Society for Research and Education in Primary Care Internal Medicine, San Diego, CA, April 30-May 1. Clin Res 35 743A. 

Holtzman D, DeVries C, Nguyen H, et al. 1984. Maturation of resistance to lead encephalopathy Cellular and subcellular mechanisms. Neurotoxicology 5 97-124. 

Sundstrom, R., K. Muntzing, H. Kalimo, and R Sourander. 1985. Changes in the integrity of the blood-brain barrier in suckling rats with low dose lead encephalopathy. Acta Neuropathol. 68 1-9. 

Higher concentrations of a chemical entity may cause a pharmacological response whereas lower concentrations are incapable of doing so. For example, edetate calcium disodium (9) at a formulated concentration of 20% is indicated as a drug for the treatment of lead poisoning and lead encephalopathy while it can be found commonly present as an excipient in concentrations ranging from 0.01% to 0.1% in parenteral formulations to prevent oxidation of the active ingredient. 

Injection of calcium disodium EDTA does not affect blood calcium levels but heavy metal ions in the body have a higher affinity for EDTA than does calcium, and hence these metals readily exchange in vivo to form soluble EDT A-heavy-metal complexes that are excreted in the urine. Because of its poor absorption from the alimentary tract, calcium disodium EDTA is usually injected intramuscularly or intravenously. These considerations led to its being used, initially in 195270), to treat lead encephalopathy. 

SAFETY PROFILE Poison by ingestion. Moderately toxic by intraperitoneal route. Questionable carcinogen. Human systemic effects by ingestion and inhalation loss of appetite, anemia, malaise, insomnia, headache, irritability, muscle and joint pains, tremors, flaccid paralysis without anesthesia, hallucinations and distorted perceptions, muscle weakness, gastritis, and liver changes. The major organ systems affected are the nervous system, blood system, and kidneys. Lead encephalopathy is accompanied by severe cerebral edema, increase in cerebral spinal fluid pressure, proliferation and swelling of endothelial cells in capillaries and... 

In children with lead encephalopathy, proximal tubule reabsorptive defects characterized by the Fanconi syndrome have been observed [13]. The Fanconi syndrome appears when blood lead levels approach 150 //g/ dL. It is rapidly reversed by chelation therapy designed to treat the far more dangerous lead encephalopathy. The proximal tubule reabsorptive defect can regularly be induced experimentally in rats fed dietary lead [14]. In both children and experimental animals, acute lead nephropathy is consistently associated with acid-fast intranuclear inclusions in proximal tubule... 

Goldings AS, Stewart RM. 1982. Organic lead encephalopathy Behavioral change and movement disorder following gasoline inhalation. J Clin Psychiatry 43 70-72. 

Ross CA. 1982. Gasoline sniffing and lead encephalopathy. Can Med Assoc J 127 1195-1197. 

Hay W Lead encephalopathy in a cooperage. British Journal of Industrial Medicine 7 177-186, 1950... 

---