eMedicine Specialties > Neurology > Neurotoxicology

Methanol

Author: Kalyani Korabathina, MD, Consulting Physician, North County Neurology Associates, Inc., Oceanside, California
Coauthor(s): Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; David Likosky, MD, Clinical Instructor, Department of Neurology, University of Washington
Contributor Information and Disclosures

Updated: Nov 9, 2009

Introduction

Background

Methanol, also known as wood alcohol, is a commonly used organic solvent, the ingestion of which has severe potential ramifications. It is a constituent in many commercially available industrial solvents and in poorly adulterated alcoholic beverages. Toxicity usually occurs from intentional overdose or accidental ingestion and results in metabolic acidosis, neurologic sequelae, and even death. Methanol toxicity remains a common problem in many parts of the developing world, especially among members of lower socioeconomic classes.

Sophisticated imaging techniques have enabled a better understanding of the clinical manifestations of methanol toxicity. Additionally, with the improvement in medical therapy, neurological complications are recognized more frequently. This is possible because of early recognition of the toxicity and because of advances in supportive care. Hemodialysis and better management of acid-base disturbances remain the most important improvements.

Pathophysiology

Methanol has a relatively low toxicity. The adverse effects are thought to be from the accumulation of formic acid, a metabolite of methanol metabolism.

Upon ingestion, methanol is quickly absorbed in the gastrointestinal tract and metabolized in the liver. In the first step of degradation, methanol is transformed to formaldehyde via the enzyme alcohol dehydrogenase (ADH). This reaction is slower than the next step, the transformation of formaldehyde to formic acid via the enzyme aldehyde dehydrogenase. This may explain the reason for the latency of symptoms between ingestion and effect. The half-life of formaldehyde is estimated to be 1-2 minutes.1

Formic acid is further oxidized to carbon dioxide and water in the presence of tetrahydrofolate. The metabolism of formic acid is very slow; thus, it often accumulates in the body, which results in metabolic acidosis.1

The eye damage caused by methanol has been well described; however, the mechanism behind this phenomenon is not well understood. The major damage occurs at the retrolaminar optic nerve with intra-axonal swelling and organelle destruction. Little to no change is seen in the retina.2

Methanol also affects the basal ganglia. With severe intoxication, common problems are hemorrhagic and nonhemorrhagic damage of the putamen. This was described initially in 1953, although the clinical syndrome associated with this lesion was not described until more recently.3 As a result, patients can develop parkinsonism or other dystonic/hypokinetic clinical pictures.

The predilection for and mechanism of toxicity to the putamen is not understood. Some postulate that striatal neurons have a varying sensitivity to toxic metabolites of methanol. However, this remains to be proven.4

In addition, cases of axonal polyneuropathy in association with chronic exposure have been reported.5 Further, motor neuron disease resembling amyotrophic lateral sclerosis has been documented in 1 case report.6

Mortality/Morbidity

  • Exact rates of morbidity and mortality from intoxication are not available.
  • Prognosis is correlated with the degree of metabolic acidosis (and the quantity of methanol ingested); more severe acidosis confers a poorer prognosis.
  • Direct correlation exists between the formic acid concentration and the morbidity and mortality.

Clinical

History

  • Time course
    • Initial symptoms generally occur 12-24 hours after ingestion.
    • The interval between ingestion and the appearance of symptoms is correlated with the volume of methanol ingested and the amount of ethanol concomitantly ingested; competitive inhibition exists between the two.1 Methanol blood levels peak at 30-90 minutes following ingestion and are often not correlated with time to symptom appearance. The minimal lethal dose in adults is believed to be 1 mg/kg of body weight.
    • In cases of altered mental status and intentional overdose, the diagnosis may be difficult without a high clinical index of suspicion.
  • Neurologic manifestations
    • Initially, the symptoms from methanol intoxication are similar to those of ethanol intoxication, often with disinhibition and ataxia.
    • Following a latent period, patients may develop headache, nausea, vomiting, or epigastric pain.
    • In later stages, drowsiness may rapidly progress to obtundation and coma.
    • Seizures may occur, generally as a complication of the metabolic derangement or as a result of damage to the brain parenchyma.
    • Methanol appears to affect the basal ganglia, primarily the putamen. With advanced neuroimaging techniques, the putaminal damage is detected much earlier in current practice than in the past.
  • Vision loss
    • Blindness from methanol inhalation was described as early as 1910.
    • Formic acid accumulates within the optic nerve, which results in classic visual symptoms of flashes of light and blurring. Subsequently, this may progress to scotomas and scintillations.
    • Vision loss is thought to be caused by interruption of mitochondrial function in the optic nerve, resulting in hyperemia, edema, and optic nerve atrophy. Optic nerve demyelination has also been reported to be due to formic acid destruction of myelin.
    • Patients initially may present with diminished visual acuity, which can progress to scotomata and scintillations.
    • The frank blindness that develops sometimes responds to immediate therapy; however, complete loss of vision is a common sequela.

Physical

Physical examination helps to rule out other causes of altered mental status and visual dysfunction, the 2 most common presenting signs of methanol intoxication.

  • General physical examination
    • During the initial phase, individuals may experience effects similar to inebriation with alcohol and thus do not seek medical attention. As symptoms develop, most signs are related to metabolic acidosis manifested as tachycardia, tachypnea, hypertension, and altered mental status.
    • Pulmonary edema and acute respiratory distress may ensue, requiring intubation.
    • With large ingestions, depressed cardiac contractility heralds circulatory collapse and leads to signs of heart failure, cardiac arrhythmias, or both.
  • Neurologic examination
    • In addition to the progression from drowsiness to stupor to coma, ocular findings are prominent during a careful neurologic examination.
    • Visual symptoms necessitate a thorough examination of the fundi.
    • Optic disc hyperemia occurs early in the course of the methanol intoxication.
    • Pupillary response to light is compromised and, subsequently, is lost. Little to no retinal damage is observed.

Causes

Methanol intoxication occurs in several discrete populations.

  • Accidental overdose can be seen in children. Methanol is found commonly in antifreeze, perfumes, paint solvents, photocopying fluid, and windshield washing fluid, all of which are readily available.
  • Alcoholic persons commonly consume methanol as a substitute for ethanol. The excessive consumption of methanol then leads to intoxication.
  • In many parts of the developing world, methanol is often a component of "bootlegged alcohol," which is made in rural regions. Because of its low cost, it is often consumed by those in lower socioeconomic classes.
  • In the industrial setting, inhalation of methanol fumes is a risk. It is used in the production of formaldehyde and shellac processing. In addition, it is used as an extractant in chemical processes and as a denaturant in ethanol.7
  • Suicide attempts using methanol are uncommon.8

More on Methanol

Overview: Methanol
Differential Diagnoses & Workup: Methanol
Treatment & Medication: Methanol
Follow-up: Methanol
References
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References

  1. Rathi M, Sakhuja V, Jha V. Visual blurring and metabolic acidosis after ingestion of bootlegged alcohol. Hemodial Int. Jan 2006;10(1):8-14. [Medline].

  2. Casarett LJ, Doull J, Klaassen CD, eds. Casarett and Doull's Toxicology: The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill; 1996:604-5, 756-7.

  3. Phang PT, Passerini L, Mielke B, et al. Brain hemorrhage associated with methanol poisoning. Crit Care Med. Feb 1988;16(2):137-40. [Medline].

  4. LeWitt PA, Martin SD. Dystonia and hypokinesis with putaminal necrosis after methanol intoxication. Clin Neuropharmacol. Apr 1988;11(2):161-7. [Medline].

  5. Hageman G, van der Hoek J, van Hout M, et al. Parkinsonism, pyramidal signs, polyneuropathy, and cognitive decline after long-term occupational solvent exposure. J Neurol. Mar 1999;246(3):198-206. [Medline].

  6. Chio A, Herrero Hernandez E, Mora G, et al. Motor neuron disease and optic neuropathy after acute exposure to a methanol-containing solvent mixture. Amyotroph Lateral Scler Other Motor Neuron Disord. Sep 2004;5(3):188-91. [Medline].

  7. Rosenstock L, Cullen MR, eds. Textbook of Clinical Occupational and Environmental Medicine. Philadelphia, Pa: WB Saunders; 1994:768.

  8. Jacobsen D, McMartin KE. Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol. 1997;35(2):127-43. [Medline].

  9. Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol. Sep-Oct 1986;1(5):309-34. [Medline].

  10. Blanco M, Casado R, Vazquez F, Pumar JM. CT and MR imaging findings in methanol intoxication. AJNR Am J Neuroradiol. Feb 2006;27(2):452-4. [Medline].

  11. Hantson P, Duprez T, Mahieu P. Neurotoxicity to the basal ganglia shown by magnetic resonance imaging (MRI) following poisoning by methanol and other substances. J Toxicol Clin Toxicol. 1997;35(2):151-61. [Medline].

  12. McKellar MJ, Hidajat RR, Elder MJ. Acute ocular methanol toxicity: clinical and electrophysiological features. Aust N Z J Ophthalmol. Aug 1997;25(3):225-30. [Medline].

  13. Finkelstein Y, Vardi J. Progressive parkinsonism in a young experimental physicist following long-term exposure to methanol. Neurotoxicology. Oct 2002;23(4-5):521-5. [Medline].

  14. Bitar ZI, Ashebu SD, Ahmed S. Methanol poisoning: diagnosis and management. A case report. Int J Clin Pract. Nov 2004;58(11):1042-4. [Medline].

  15. Aquilonius SM, Bergstrom K, Enoksson P, et al. Cerebral computed tomography in methanol intoxication. J Comput Assist Tomogr. Aug 1980;4(4):425-8. [Medline].

  16. Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415-46. [Medline].

  17. Batterman SA, Franzblau A, D'Arcy JB, et al. Breath, urine, and blood measurements as biological exposure indices of short-term inhalation exposure to methanol. Int Arch Occup Environ Health. Jul 1998;71(5):325-35. [Medline].

  18. Brown MJ, Shannon MW, Woolf A, Boyer EW. Childhood methanol ingestion treated with fomepizole and hemodialysis. Pediatrics. Oct 2001;108(4):E77. [Medline].

  19. Fujita M, Tsuruta R, Wakatsuki J, et al. Methanol intoxication: differential diagnosis from anion gap-increased acidosis. Intern Med. Aug 2004;43(8):750-4. [Medline].

  20. Hantson P, de Tourtchaninoff M, Simoens G, et al. Evoked potentials investigation of visual dysfunction after methanol poisoning. Crit Care Med. 1999;27(12):2707-15. [Medline].

  21. Ikeda M. Public health problems of organic solvents. Toxicol Lett. Dec 1992;64-65 Spec No:191-201. [Medline].

  22. Katz KD, Ruha AM, Curry SC. Aniline and methanol toxicity after shoe dye ingestion. J Emerg Med. Nov 2004;27(4):367-9. [Medline].

  23. LoVecchio F, Sawyers B, Thole D, et al. Outcomes following abuse of methanol-containing carburetor cleaners. Hum Exp Toxicol. Oct 2004;23(10):473-5. [Medline].

  24. Lushine KA, Harris CR, Holger JS. Methanol ingestion: prevention of toxic sequelae after massive ingestion. J Emerg Med. May 2003;24(4):433-6. [Medline].

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Further Reading

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Keywords

organic solvent, formaldehyde, alcohol dehydrogenase, methanol ingestion, methanol toxicity, methanol intoxication, antifreeze ingestion, perfume ingestion, paint solvent ingestion, inhalation of methanol, methanol fumes, methanol poisoning

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Contributor Information and Disclosures

Author

Kalyani Korabathina, MD, Consulting Physician, North County Neurology Associates, Inc., Oceanside, California
Kalyani Korabathina is a member of the following medical societies: American Academy of Neurology and American Epilepsy Society
Disclosure: Nothing to disclose.

Coauthor(s)

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

David Likosky, MD, Clinical Instructor, Department of Neurology, University of Washington
David Likosky, MD is a member of the following medical societies: American Academy of Neurology, American College of Physicians-American Society of Internal Medicine, and American Heart Association
Disclosure: Nothing to disclose.

Medical Editor

Jonathan S Rutchik, MD, MPH, Assistant Professor, Department of Occupational and Environmental Medicine, University of California at San Francisco
Jonathan S Rutchik, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Occupational and Environmental Medicine, and Society of Toxicology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Nestor Galvez-Jimenez, MD, MSc, MHA, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida
Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society
Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart Association, American Stroke Association, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine
Disclosure: Abbott Labs  Honoraria Consulting; Teva Marion Honoraria Consulting; Boeringer-Ingelheim Honoraria Speaking and teaching

 
 
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