Presence of symptoms of encephalopathy, the clinical etiology of encephalopathy namely infectious or non infectious, the modified Glasgow coma scale (GCS) score on admission, the worst GCS score during the illness, and the outcome of the illness i.e. complete recovery, death or recovery with some neurological sequel (presence of speech, behavior or mood disorders, reduction in intellectual performance, motor deficits, movement disorders at discharge) were recorded. Cerebrospinal fluid studies, serum electrolytes, blood sugar and computerized tomographic scans of head were done for clinical etiology of encephalopathy. Baseline hemoglobin and lead was estimated in venous blood obtained in lead free EDTA vacutainers (Becton Dickinson) and analyzed by flameless atomic absorption spectrophotometry (HitachiZ-8000) in parts per billion at a wavelength of 283.3 nm with a slit width of 1.3 nm using the method described by Lagesson, et al.(6). The detection rate of lead for the instrument was 1 µg/L, with an average error rate of 5% for reproducibility of results. Result of lead levels was obtained two weeks after the admissions, so none of the children were offered lead chelation.

Data analysis: We estimated the overall prevalence of elevated blood lead levels (EBLL) and the proportion of children in each Center for Disease Control (CDC) risk classes I [(10-14 µg/dL), IIA(15-19µg/dL), IIB(20-44 µg/dL), III(45-69 µg/dL) and IV(>70 µg/dL)] in all participants(4). EBLL as a predictor of residual neurological sequel or death, after adjusting for other baseline variables was assessed using logistic regression. Using student’s t test for continuous variables, chi-squared test for categorical variables and multivariate linear regression, we assessed predictors of EBLL.

Of the 100 patients studied (49 with encephalopathy and 51 with no encephalopathy) blood lead levels were available for 42 and 49, respectively. Their baseline characteristics are presented in Table I. The overall mean blood lead was 7.9±10.4 µg/dL (range 0.07 to 67.7 µg/dL). EBLL was observed in 19 children (20.9%) of whom 8 were in class I (8.8%), 3 in class IIA (3.3%) and 8 children were in class IIB (8.8%). Mean blood lead levels were significantly higher in patients of encephalopathy (12.2±13.9 µg/dL) than in controls (4.2±2.8 µg/dL) (P<0.01). Of 42 children with encephalopathy, 17 had blood lead levels more than 10 µg/dL as compared to only 2 amongst the controls (P<0.01). Patients with encephalopathy were more likely (P<0.01) to be in higher CDC class.

Table I



Baseline Characteristics of the Study Population

On admission, 16 patients had infectious encephalopathy (8 of acute pyogenic, 4 of tuberculosis, 3 of viral encepholpathy and 1 of cerebral abscess) and 26 were of non infectious etiology (1 of Reye, 8 of anoxic, 7 of febrile and 10 of metabolic encephalopathy). EBLL was present in 3/17 (17.6%) patients with infective encephalopathy as compared to 18/25 (72%) patients with non-infective encephalopathy. Among patients of encephalopathy, 10/49 (23.8%) children had residual neurological sequel and 5 (11.9%) children died; rest 26(61.9%) children recovered completely on discharge. The mean blood lead levels were higher in children with residual neurologic sequel or death (13.61±14.72 µg/dL) as compared to those who recovered completely (11.69±13.83 µg/dL), but this difference was not statistically significant. Infective encephalopathy (OR 33.3; 95% CI 2.8, 100) was most predictive of poor recovery, after adjusting for age, wasting, the worst GCS and BLL. Residual neurological sequel and death in patients with infective encephalopathy was 9/13(69%) and rose to 100% (all three children died) when associated EBLL. In non infective encephalopathy residual neurological sequel or death was absent without EBLL and rose to 3/14 (21%) with EBLL.

The predictors of EBLL were presence of wasting (P=0.03), anemia (P=0.04), recent removal of house-pain (P=0.009), recent repainting (P= 0.003) and use of surma (P=0.02). There was no association of EBLL with the use of ayurvedic or homeopathic medicines, sindur (vermilion), pica, fathers’ occupational exposure, caste or income.

The overall prevalence of EBLL was 20.9% in hospitlalized children, 40.5% in children who presented with encephalopathy as compared to 4.1% in controls. Of the patients with encephalopathy, those with non-infective encephalo-pathy were more likely to have EBLL than those with infective encephalopathy. In children with non-infective as well as with infective encephalopathy, the proportion of children with residual neurological sequel or death increased when associated with EBLL (0 to 21%, and 69% to 100%, respectively). The lead levels most likely to result in neurotoxicity are still debated and has been observed at lower levels(7). This study is only the third in India to report BLL in children with encephalopathy. The mean blood lead level in children with encephalopathy (12.18±13.90 mg/dL) was significantly higher as compared to controls and consistent to the observations made in the previous two studies(8,9). So EBLL (even Class II or III poisoning) may exacerbate the neurological damage of coexisting non infective or infective pathology of the nervous system. Oxidative stress and free radical generation was reported to be the mode of neurological lead toxicity. Studies done in animals suggest that EBLL predisposes and aggravates infections by enhancing B cell activities and Th2 proliferation, and inhibits Th1 prolife-ration(10). In rodents, it enhanced susceptibility to endotoxin shock and lipopolysaccharide (LPS) lethality in gram-negative infections by increasing the secretion and uptake of tumor necrosis factor-alpha (TNF-alpha) and increasing other proinflam-matory cytokines(11). This increased concentration of proinflammatory cytokines (IL-1 beta and TNF-alpha IL-6) in the cerebrospinal fluid correlates well with presence of neurologic sequel or death in patients of infectious meningoencephalitis(12,13). The limitation of this study is that we did not assess levels of proinflammatory cytokines and markers of oxidative stress predictive of poor outcome. Children with EBLL would not only have an increased susceptibility to infections but also be at a greater risk of encephalopathy at lower levels of blood lead during infective and febrile episodes. However this causal relationship could not be studied in this cross-section of patients.

Predictors of EBLL were nutritional wasting, anemia and environmental exposures such as use of surma and recent removal of house paint or repainting, which were similar to those reported previously and indicate the need for implementing guidelines for preventing the use of lead based paints and eye cosmetics like surma(5).

In conclusion, developing countries like India where malnutrition, anemia and the incidence of infections is high, universal screening and early chelation especially in co-morbid neurological illness could prevent morbidity and mortality. The therapeutic benefits of investigating for EBLL and lead chelation in children of any encephalopathy, even in lower CDC classes, need further exploration. Additionally, public health regulations are also needed to reduce environmental exposures through paint and cosmetics.

We are thankful to INCLEN for funding and NEERI for analyzing the blood lead samples. We thank Dr H R Belsare for assisting in data collection and Smita Puppulwar for secretarial help.

Contributors: ABP designed the study, collected and analyzed the data and wrote the manuscript. AA assisted in data analysis, reviewing literature and manuscript writing.

Competing interests: None.

Funding: INCLEN Grant Number 1004-94-6305.

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