Toxic leukoencephalopathy is a rare condition that is characterized by progressive damage (-pathy) to white matter (-leuko-) in the brain (-encephalo-), particularly myelin, due to causes such as exposure to substance use, environmental toxins, or chemotherapeutic drugs. The prevalence of this disease is infrequent and often goes unreported, especially in cases resulting from substance use. Magnetic resonance imaging (MRI) is a popular method to study and diagnose the disease. However, even with technological advances, the exact mechanism and underlying pathophysiology of toxic leukoencephalopathy remains unknown and is thought to vary between sources of toxicity. The clinical severity of toxic leukoencephalopathy also varies among patients, exposure time, concentration, and purity of the toxic agent. Some reversibility of the condition has been seen in many cases when the toxic agent is removed. Signs and symptoms Symptoms vary widely between sources of toxicity, dosage, length of time patient was exposed to the toxic substance, patient history, and patient genetics. Especially in the case of leukoencephalopathy developing due to substance use or environmental toxins, symptoms typically do not develop until several days to months after exposure to the pharmacological agent. Clinical features range from inattention, forgetfulness, and changes in personality to dementia, coma, and even death. Obvious signs of the condition are difficulty with cognitive function and equilibrioception. Common initial symptoms include confusion, somnolence, generalized seizures, headaches, and vision impairment. Young acute lymphoblastic leukemia patients with methotrexate-induced leukoencephalopathy appear asymptomatic. However, toxic leukoencephalopathy induced by substance use or environmental toxins have had more damaging side effects. Heroin-induced leukoencephalopathy has had three stages described. The first stage features soft (pseudobulbar) speech, cerebellar ataxia, motor restlessness, and apathy/bradyphrenia. The intermediate stage includes pyramidal tract and pseudobulbar signs, spastic paresis, myoclonic jerks, and choreoathetoid movements. The final or terminal stage is characterized by stretching spasms, akinetic mutism, hypotonic paresis, central pyrexia, and death. Similarly, leukoencephalopathy induced by orally administered methotrexate for arthritis patients presents similar symptoms including ataxia, dysarthria, and seizures; however, long-term cognitive effects remain unknown. Symptoms of leukoencephalopathy caused by overdose of metronidazole medication include dysarthria, gait disturbance, weakness of extremities, and mental confusion. Despite the pharmacological agent or source of toxicity, some patients completely recover from toxic leukoencephalopathy. Related disorders Posterior reversible encephalopathy syndrome (PRES) can also result from medication toxicity. Symptoms similar to those of leukoencephalopathy patients have been seen in PRES patients. However, the prognosis of toxic leukoencephalopathy is typically slightly worse