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Methanol Toxicity

  • Author: Kalyani Korabathina, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
 
Updated: Mar 30, 2016
 

Background

Methanol, also known as wood alcohol, is a commonly used organic solvent that, because of its toxicity, can cause metabolic acidosis, neurologic sequelae, and even death, when ingested. It is a constituent of many commercially available industrial solvents and of poorly adulterated alcoholic beverages. Methanol toxicity remains a common problem in many parts of the developing world, especially among members of lower socioeconomic classes. (See Etiology and Pathophysiology and Presentation.)

Sophisticated imaging techniques have enabled a better understanding of the clinical manifestations of methanol intoxication. Additionally, neurologic 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 therapeutic improvements. (See Workup, Treatment, and Medication.)

According to a study by Jaff et al, methanol intoxication can lead to several ECG changes, with sinus tachycardia and non-specific T-wave changes being the most common. In the study, the changes were more prominent in cases of severe acidosis. A retrospective chart review of 9 patients between 2006 and 2011 revealed that lower pH and higher plasma methanol concentration were associated with multiple ECG changes. On admission, ECG changes included sinus tachycardia (44%), PR prolongation (11%), QTc prolongation (22%), and non-specific T-wave changes (66%). One patient developed a type-1 Brugada ECG pattern.[1]

According to Zakharov et al, S-formate measurement can help in the laboratory diagnosis and clinical management of acute methanol poisoning. In their study of 38 patients from a Czech methanol mass poisoning in 2012, S-formate levels ≥3.7 mmol/L were seen to lead to the first clinical signs of visual toxicity, indicating hemodialysis. S-formate ≥11-12 mmol/L was associated with visual/CNS sequelae and a lethal outcome. The probability of a poor outcome (death or survival with sequelae) was higher than 90% in patients with S-formate levels ≥17.5 mmol/L, S-lactate levels ≥7.0 mmol/L, and/or pH < 6.87.[2]

Complications

Vision loss

The mechanism by which the methanol causes toxicity to the visual system is not well understood. Formic acid, the toxic metabolite of methanol, is responsible for ocular toxicity in animal models and is rightly presumed to be responsible in human studies. (See Etiology and Pathophysiology.)

Serum methanol levels of greater than 20 mg/dL correlate with ocular injury. Funduscopic changes are notable within only a few hours after methanol ingestion and range from retinal edema in the perimacular region to the entire fundus. Optic disc edema and hyperemia are observed within 48 hours.

Visual injury may be prevented with prompt antidote therapy or via elimination of the metabolites from the system with hemodialysis; however, this is not always the case. (See Treatment and Medication.)

Movement disorders

Parkinsonian motor impairment has been described in some long-term survivors of methanol poisoning. This is thought to be due to formic acid’s predilection for accumulating in high concentrations within the putamen, but the reasons for this phenomenon are unclear. One proposed reason is that formic acid has the ability to impair dopaminergic pathways and increase enzymatic activity of dopa-B-hydroxylase. (See Etiology and Pathophysiology.)[3]

Symptom onset is usually delayed several weeks after methanol exposure. Common parkinsonian symptoms, such as tremor, cogwheel rigidity, stooped posture, shuffling gait, and hypokinesis, have been well described. In addition, the development of dystonia and corticospinal tract signs has been established.

Several case reports have indicated symptom response to standard antiparkinsonian agents, particularly levodopa, amantadine, and bromocriptine.[4]

Muscle spasms have also been reported in methanol poisoning. As expected, this symptom responds poorly to traditional therapy.[5]

Rarely, lesions in the lobar regions of the cerebrum and cerebellum have been observed.[6]

Prognosis

The prognosis in methanol poisoning correlates with the amount of methanol consumed and the subsequent degree of metabolic acidosis; more severe acidosis confers a poorer prognosis. The prognosis is further dependent on the amount of formic acid that has accumulated in the blood, with a direct correlation existing between the formic acid concentration and morbidity and mortality. Little long-term improvement can be expected in patients with neurologic complications. (See Treatment and Medication.)[7]

The minimal lethal dose of methanol in adults is believed to be 1mg/kg of body weight. The exact rates of morbidity and mortality from methanol intoxication are not available.

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Etiology and 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 into formaldehyde via the enzyme alcohol dehydrogenase (ADH). This reaction is slower than the next step, the transformation of formaldehyde into 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.[8]

Formic acid is further oxidized to carbon dioxide and water in the presence of tetrahydrofolate. The metabolism of formic acid is very slow; thus, formic acid often accumulates in the body, which results in metabolic acidosis.[8]

The eye damage caused by methanol has been well described; however, the mechanism behind this phenomenon is not well understood. 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 been reported to be due to formic acid destruction of myelin. 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.[9]

Methanol also affects the basal ganglia. Hemorrhagic and nonhemorrhagic damage to the putamen are common problems in cases of severe intoxication. As a result of this damage, patients can develop parkinsonism or other dystonic/hypokinetic clinical pictures.[10]

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.[5]

At-risk populations

Suicide attempts using methanol are uncommon.[11] However, unintentional methanol poisoning occurs under a variety of circumstances in several discrete populations, including the following:

  • Children - 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
  • Persons with alcoholism - These individuals commonly consume methanol as a substitute for ethanol
  • Populations of developing countries - 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 members of lower socioeconomic classes
  • Industrial workers - In the industrial setting, the inhalation of methanol fumes poses a health risk; methanol is used in the production of formaldehyde and in shellac processing; in addition, it is used as an extractant in chemical processes and as a denaturant in ethanol [12]
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Contributor Information and Disclosures
Author

Kalyani Korabathina, MD Consulting Physician, North County Neurology Associates, Inc

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

Disclosure: Nothing to disclose.

Coauthor(s)

David Likosky, MD Director of Stroke Program, President of Medical Staff, Evergreen Hospital Medical Center

David Likosky, MD is a member of the following medical societies: American Academy of Neurology, American College of Physicians-American Society of Internal Medicine, American Heart Association

Disclosure: Nothing to disclose.

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

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.

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.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
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