Methanol Toxicity

Methanol toxicity can be very dangerous with high morbidity and mortality rates, and outcomes typically worsen with increasing acidemia, hyperglycemia, or acute kidney injury. Delayed treatment can result in irreversible injury, such as vision loss, or even death. The harmful effects of methanol come from its toxic metabolites, formaldehyde, and formic acid, as it is metabolized by alcohol dehydrogenase in the liver. Formic acid itself contributes to an anion-gap metabolic acidosis, but after it is deprotonated, formate also inhibits the cytochrome c oxidase pathway in oxidative phosphorylation, contributing further to acidosis and oxidative damage. This damage leads to methanol-induced toxic optic neuropathy, leukotriene-mediated neuroinflammation, acute kidney injury, and liver damage. Patients may experience CNS and GI effects such as confusion, drowsiness, nausea, vomiting, and abdominal pain in the first 4 hours after methanol poisoning, followed by acute kidney injury and ophthalmic manifestations from 6-24 hours after poisoning. In the neuro-ophthalmology clinic, there are several important clues that could lead to diagnosing methanol-induced toxic optic neuropathy. In the history, a patient may complain of photophobia or vision loss and may have a history of ingestion from a suicide attempt, consumption of homemade alcohol, or accidental poisoning. On examination, they may have several findings including reduced visual acuity, dilated pupils with decreased reactivity to light, nystagmus, normal intraocular pressure, normal anterior segment findings, bilateral optic disc edema, and hyperemia. Visual field testing may show a central or cecocentral scotoma. OCT RNFL testing may show optic nerve edema in the acute phase and thinning later on. OCT ganglion cell analysis may also show atrophy. Neuroimaging may reveal bilateral lesions in the basal ganglia, necrosis of the putamen, or abnormal changes to the caudate nucleus. Patients may develop Parkinsonian symptoms as a result of these types of injuries. Patients with methanol toxicity are treated acutely with ethanol or fomepizole +/- hemodialysis. Ethanol and fomepizole act as competitive inhibitors of alcohol dehydrogenase, thus slowing down the formation of toxic intermediates from methanol metabolism.[1] Fein DM, Sue YJ. Methanol ingestion. Pediatr Rev. Dec 2011;32(12):549-50. doi:10.1542/pir.32-12-549; [2] Liberski S, Kaluzny BJ, Kocięcki J. Methanol-induced optic neuropathy: a still-present problem. Arch Toxicol. Feb 2022;96(2):431-451. doi:10.1007/s00204-021-03202-0; [3] Md Noor J, Hawari R, Mokhtar MF, et al. Methanol outbreak: a Malaysian tertiary hospital experience. Int J Emerg Med. 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