Methanol Side Effects
Which toxic alcohol can cause a basal ganglia hemorrhage?

  1. Ethanol
  2. Isopropanol
  3. Methanol
  4. Propylene glycol

[Left image from Wikimedia Commons]

3. Methanol

Methanol can cause basal ganglia necrosis with or without hemorrhage [1]. There are several proposed mechanisms, including direct toxic effects of methanol metabolites, decreased blood flow through the veins of Rosenthal, higher metabolic demands present at the putamen compared to other brain structures, and increased anoxia in vascular watershed areas present in the basal ganglia [1-4]. Although basal ganglia necrosis is a characteristic finding in methanol toxicity, it is not specific. It can be found in a variety of conditions including ethylene glycol poisoning, Wilson and Leigh disease, carbon monoxide poisoning, and cyanide poisoning [4,5].

What is methanol, and how does it cause poisoning?

  • Methanol is found in windshield washing fluid, paint strippers, gas line antifreeze, solid cooking fuel (SternoTM), shellac, de-icers, and many other agents.
  • The lethal dose of methanol is reported to be 1-2 ml/kg, though ingestion of as little as 0.1 ml/kg has resulted in permanent blindness [6,7].
  • Methanol is metabolized via alcohol dehydrogenase to formaldehyde, which is then metabolized by aldehyde dehydrogenase to formic acid. Formic acid inhibits cytochrome c in the mitochondria shifting cells to anaerobic glycolysis, leading to lactic acid formation, and anion gap metabolic acidosis [8].
  • Formic acid can cause retinal and neural damage.

What is the treatment for methanol poisoning? [8-10]

  • Fomepizole (4-methylpyrazole, 4-MP) is a potent inhibitor of alcohol dehydrogenase. It is the preferred antidote in treating methanol and ethylene glycol poisoning, although ethanol can be used if fomepizole is unavailable.
  • Fomepizole inhibits the production of toxic metabolites and, when administered early, prevents the development of metabolic acidosis.
  • This allows the parent compound to be excreted by non-toxic routes.
  • Fomepizole was first approved for use in ethylene glycol toxicity in 1997 and for the treatment of methanol toxicity in 2000.
  • Hemodialysis can remove methanol and metabolites, with recommended criteria as follows: [10]
    • Coma, seizures, or new visual deficits from methanol poisoning
    • pH < 7.15
    • Persistent metabolic acidosis despite adequate supportive measures
    • Serum anion gap higher than 24 mmol/L
    • Serum methanol concentration greater than 70 mg/dL with fomepizole, greater than 60 mg/dL with ethanol therapy, and greater than 50 mg/dL without an alcohol dehydrogenase blocker
    • Impaired kidney function
  • Adjunctive therapy with folate and serum alkalinization may also be used to enhance the clearance of toxic metabolites.

Bedside Pearls

  • Basal ganglia necrosis and hemorrhage can result from methanol poisoning, as well as other exposures.
  • Methanol poisoning can also result in severe metabolic acidosis and blindness.
  • The treatment for methanol poisoning includes inhibition of alcohol dehydrogenase with fomepizole or ethanol, and in selected cases, hemodialysis.

The American College of Medical Toxicology hosts this Toxicology Visual Pearls series. The post was peer reviewed on behalf of ACMT by Drs. Howard Greller, Louise Kao, and Sage Wiener.

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References

  1. Blanco M, Casado R, Vázquez F, Pumar JM. CT and MR imaging findings in methanol intoxication. AJNR Am J Neuroradiol. 2006;27(2):452-454. PMID: 16484428.
  2. Yang CS, Tsai WJ, Lirng JF. Ocular manifestations and MRI findings in a case of methanol poisoning. Eye (Lond). 2005;19(7):806-809. PMID: 15389282.
  3. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med. 2018;378(3):270-280. PMID: 29342392.
  4. Sharma R, Carroll D, Knipe H, et al. Methanol poisoning. Reference article, Radiopaedia.org (Accessed on 29 July 2023) https://doi.org/10.53347/rID-51680
  5. Caparros-Lefebvre D, Policard J, Sengler C, et al. Bipallidal haemorrhage after ethylene glycol intoxication. Neuroradiology. 2005 Feb;47(2):105-7. doi: 10.1007/s00234-005-1347-y. PMID: 15714272.
  6. Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol. 1986;1(5):309-334. PMID: 3537623.
  7. Röe O. Species differences in methanol poisoning. Crit Rev Toxicol. 1982;10(4):275-286. PMID: 6756793.
  8. Beauchamp GA, Valento M. Toxic Alcohol Ingestion: Prompt Recognition And Management In The Emergency Department. Emerg Med Pract. 2016;18(9):1-20. PMID: 27538060.
  9. Wiener S. Toxic Alcohols. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill Education; 2019.
  10. Roberts DM et al. (2015)  Recommendations for the Role of Extracorporeal Treatments in the Management of Acute Methanol Poisoning: A Systematic Review and Consensus Statement. Critical Care Medicine 43(2): 461-472. PMID: 25493973.
Fernanda Calienes-Cerpa, MD

Fernanda Calienes-Cerpa, MD

Emergency Medicine Faculty
Wake Forest Emergency Providers
Fernanda Calienes-Cerpa, MD

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Erik Fisher, MD

Erik Fisher, MD

Associate Program Director, Medical Toxicology Fellowship
Atrium Health Carolinas Medical Center and Levine Children's Hospital
Clinical Assistant Professor of Emergency Medicine
Wake Forest School of Medicine