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.
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 the main active ingredient in various oral pain relief medications. High doses of opiates such as oxycodone can lead to leukoencephalopathy. The activity of various opioid and nociceptive receptors appear to play a role in the disease; however, the exact mechanism remains unknown.Metronidazole, an antibiotic used to treat anaerobic and protozoal infections, has been known at high doses to produce neurologic symptoms associated with toxic leukoencephalopathy. Other
Toxic leukoencephalopathy may also result from carbon monoxide poisoning, ingestion of methanol, ingestion of ethylene, toluene toxicity, ethanol poisoning, ingestion of methylenedioxymethamphetamine (MDMA or "ecstasy"), or ingestion of paradichlorobenzene, which is a toxic agent in mothballs. Diagnosis
Due to advances in MRI, this neurological disorder has been characterized more successfully in more recent years. MRI can aid in the detection of injured brain tissue; however, the severity and extent of the damage demonstrated by imaging does not always reflect patient clinical status. Toxic leukoencephalopathy encompasses the degeneration of white matter tracts devoted to higher cerebral function; however, white matter can appear normal until the disease has progressed more intensely. Toxic leukoencephalopathy-related damage to central nervous system (CNS) white matter, typically of the periventricular nucleus, and other structures in the brain is often bilateral and symmetric.