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[Ed. For every molecule of aspartame - there is a molecule of methanol released. Aspartame is 10% methanol by weight. A diet soda sweetened with aspartame contains 225 mg aspartame - 22.5 mg methanol. ]

Last Updated: March 15, 2007
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Synonyms and related keywords: organic solvent, formaldehyde, formate, alcohol dehydrogenase, ADH, methanol ingestion, methanol toxicity, methanol intoxication, antifreeze ingestion, perfume ingestion, paint solvent ingestion, photocopying fluid ingestion, windshield washing fluid ingestion, shellac ingestion, inhalation of methanol, methanol fumes, methanol poisoning

Section 1 of 10     
Author Information  Introduction  Clinical  Differentials  Workup  Treatment  Medication  Follow-up  Miscellaneous  Bibliography

 Author: Kalyani Korabathina, MD, Department of Neurology, University of South Florida College of Medicine

 Coauthor(s): Selim R Benbadis, MD, Professor of Neurology, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida College of Medicine, Tampa General Hospital; David Likosky, MD, Clinical Instructor, Department of Neurology, University of Washington

 Kalyani Korabathina, MD, is a member of the following medical societies: American Academy of Neurology

 Editor(s): Jonathan S Rutchik, MD, MPH, Assistant Professor, Department of Occupational and Environmental Medicine, University of California at San Francisco; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;  Nestor Galvez-Jimenez, MD, Program Director of Movement Disorders, Director of Neurology Residency Training Program, Department of Neurology, Division of Medicine, Cleveland Clinic Florida;  Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; and  Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants

 Disclosure Author Information  Introduction  Clinical  Differentials  Workup  Treatment  Medication  Follow-up  Miscellaneous  Bibliography

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 (Rathi, 2006).

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 (Rathi, 2006).

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 (Casarett, 1996).

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 (Phang, 1988). 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 (LeWitt, 1988).

In addition, cases of axonal polyneuropathy in association with chronic exposure have been reported (Hageman, 1999). Further, motor neuron disease resembling amyotrophic lateral sclerosis has been documented in 1 case report (Chio, 2004).

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.

Section 3 of 10     
Author Information  Introduction  Clinical  Differentials  Workup  Treatment  Medication  Follow-up  Miscellaneous  Bibliography

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 (Rathi, 2006). 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.
Neurological 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 (Rosenstock, 1994).
Suicide attempts using methanol are uncommon (Jacobsen, 1997).