Toxic leukoencephalopathy

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.[1] Clinical features range from inattention, forgetfulness, and changes in personality to dementia, coma, and even death.[2] Obvious signs of the condition are difficulty with cognitive function[3] and equilibrioception. Common initial symptoms include confusion, somnolence, generalized seizures, headaches, and vision impairment.[4]

Young acute lymphoblastic leukemia patients with methotrexate-induced leukoencephalopathy appear asymptomatic.[5] However, toxic leukoencephalopathy induced by substance use or environmental toxins have had more damaging side effects. Heroin-induced leukoencephalopathy has had three stages described.[6] The first stage features soft (pseudobulbar) speech, cerebellar ataxia, motor restlessness, and apathy/bradyphrenia.[1] 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;[4] however, long-term cognitive effects remain unknown.[7] Symptoms of leukoencephalopathy caused by overdose of metronidazole medication include dysarthria, gait disturbance, weakness of extremities, and mental confusion.[8] Despite the pharmacological agent or source of toxicity, some patients completely recover from toxic leukoencephalopathy.[9][5][10][11][1]

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.

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.[8] Toxic leukoencephalopathy encompasses the degeneration of white matter tracts devoted to higher cerebral function;[2] however, white matter can appear normal until the disease has progressed more intensely.[1] 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. Heroin-induced leukoencephalopathy often involves damage to cerebellar white matter, posterior cerebral white matter, posterior limb of internal capsule, and cerebellar peduncles.[1] The occipital lobe is typically most affected though the frontal, parietal, and temporal lobes have shown involvement as well. Other toxins have been shown to extend damage to other structures of the brain, including the hippocampus, dorsal medulla, and brainstem.[8]

With such a wide array of causes and unclear understanding of the pathophysiology, there is no known cure or treatment for the disease. In some cases of leukoencephalopathy induced by medications, such as methotrexate and metronidazole, the disease will reduce gradually once the medication is no longer distributed to the patient.[4][5][8] Depending on the source of toxicity or pharmacological substance and severity of the white matter damage, many patients can have complete clinical recovery.

Coenzyme Q and vitamin supplements, typically vitamin C and vitamin E, and other antioxidant therapies have been suggested to treat heroin-induced leukoencephalopathy patients. However, such treatments have rarely been trialed.[6]

• Leukoencephalopathy

• Hill MD, Cooper PW, Perry JR (January 2000). "Chasing the dragon – neurological toxicity associated with inhalation of heroin vapour: case report". CMAJ. 162 (2): 236–8. PMC 1232277. PMID 10674060.