than that of PRES because toxic leukoencephalopathy is more likely to lead to ataxia, dementia, or coma. Hypoglycemic encephalopathy is often seen in diabetics as a result to accidental overdose with the long-acting sulfonylurea drug group. Brain regions affected by toxic leukoencephalopathy have been seen to be affected by this disease as well; however, hypoglycaemic encephalopathy has been known to involve both white and grey matter abnormalities. Causes Various pharmacological agents have been known to cause toxic leukoencephalopathy. The most common causes are substance use and chemotherapy; however, the disease has also occurred on the rare occasion as a side effect of certain medications and environmental toxins. Substance use Leukoencephalopathy may result from the inhalation, intravenous injection, or ingestion of addictive substances. However, such occurrences are rare, sporadic, and often go undocumented. Leukoencephalopathy caused by inhalation of heroin, also known as "chasing the dragon" syndrome, is one of the most studied of these rare occurrences and has even been recognized for over twenty five years. It is believed by some researchers that heroin-induced leukoencephalopathy may be caused by a contaminant, or “cutting agent,” in the heroin. However, no such agent has been identified; and indeed, toxic leukoencephalopathy has been observed as a result of intoxication with contaminant-free opiates. Cases include a 65-year-old woman who had mistakenly been taking three times the dose of methadone that had been prescribed for pain management, and a young girl intoxicated with pure morphine sulfate tablets. Other drugs that have been associated with toxic leukoencephalopathy in much more rare occurrences include psychoactive drug 2C-E ("Europa"), oxycodone, cocaine, and methadone. The dose–response relationship for these substances remains unclear. Chemotherapy Various chemotherapy drugs have shown increased risk of cancer patients developing leukoencephalopathy. High doses of intravenous methotrexate, or intrathecal (injection into the spinal fluid) methotrexate are both necessary components of chemotherapy for acute lymphoblastic leukemia. However, these are known to cause asymptomatic leukoencephalopathy in children and young adults. Methotrexate-related leukoencephalopathy prevalence has been reported to decline with time and dosage. Other chemotherapeutic agents that have induced neurotoxicity include 5-fluorouracil and fludarabine. Medication neurotoxicity Besides its role in chemotherapy, methotrexate is also used as an orally administered treatment for rheumatoid arthritis. Leukoencephalopathy can develop from long-term treatment of methotrexate even at low doses. In contrast to intravenous methotrexate for cancer patients, leukoencephalopathy induced by orally taken methotrexate may be associated with cognitive dysfunction and even death. Oxycodone is