WASHINGTON: A toxin in litchi fruits may be linked to a mysterious and sometimes fatal brain disease that has afflicted children in Muzaffarpur, Bihar, and neighbouring districts since 1995, US researchers claim.An association between the illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit producing region, according to a report by the US Centres for Disease Control and Prevention.The Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks of the illness in 2013 and 2014."Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin," the report said.A common laboratory finding was low blood glucose on admission, a finding associated with a poorer outcome; 44 per cent of all cases were fatal.A 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause, the report said.The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur.The 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies.During May 17 - July 22, 2013, a total of 133 children were admitted to the two main referral hospitals in Muzaffarpur with illnesses that met the investigation case definition of acute onset seizures or altered mental status within 7 days of admission in a child aged 15 years.Of these, 71 per cent patients were from Muzaffarpur; other patients were from six neighbouring districts.Analysis of risk factors for death among 94 affected children showed that low blood glucose at admission was more common among those who died.Data collected during the 2013 investigation suggested that the illness was more likely to be a noninflammatory encephalopathy than an infectious encephalitis, and raised concern for the possibility of a toxin-mediated illness.Building on the 2013 findings, NCDC and CDC again investigated this syndrome in 2014.During May 26 - July 17, 2014, a total of 390 patients admitted to the two referral hospitals in Muzaffarpur with illnesses that met the same case definition used in 2013.Detailed clinical evaluation of 52 patients within 12 hours of admission elicited a history of generalised tonic or tonic-clonic seizures in 100 per cent, researchers said."The 2013 and 2014 Muzaffarpur investigations indicate that this outbreak illness is an acute noninflammatory encephalopathy," the CDC said.The consistent finding of hypoglycemia among affected children underscores the importance of examining the possible role of compounds that might acutely result in low blood sugar, seizures, and encephalopathy, including the possible role of MCPG in litchis.