Episode 118: Wernicke’s Encephalopathy 

Dr. Malave explains the diagnosis and treatment of Wernicke’s encephalopathy. Editing and comments by Hector Arreaza.  

Written by Maria Fernanda Malave, edited by Hector Arreaza, MD.

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Definition.

As a reminder for everyone, vitamin B1 and thiamine are the same substance with different names. Wernicke’s encephalopathy (WE) is a neurological syndrome secondary to severe, short-term B1 deficiency. In the past, but less frequently nowadays, it was more commonly associated with alcohol use disorder. However, today we know that any condition that decreases dietary intake and increases thiamine use, or its elimination, puts patients at risk of developing this encephalopathy. 

Causes:

Chronic alcoholism is the most important cause of WE. Around 70-80% of the causes are associated with chronic alcohol consumption. 

Non-alcoholic WE may be caused by 

• Decreased intake: Some types of WE may be caused by a psychiatric illness that decreases the dietary intake of B1, such as anorexia nervosa, schizophrenia, or dementia. Arreaza: Also, prolonged fasting or starvation.
• Lack of absorption of B1: Other causes might be related to malabsorptive syndromes, bariatric surgeries, or hyperemesis gravidarum
• Increased use of B1: Any disease that increases the use of B1 and, therefore, low levels of thiamine, such as cancer, thyrotoxicosis, and systemic illnesses like infections. High-carb diets are associated with high thiamine use. Also, patients who receive IV glucose w/o supplements are at risk of developing Wernicke’s encephalopathy.
• Increased elimination of B1: Other causes are related to increased elimination of B1, such as dialysis.
• Immunodeficiencies: Immunodeficiency syndromes and transplantation also cause WE.

Why is thiamine important?

Thiamine is one of the main cofactors in three key enzymes for energy metabolism: alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase. If we go back to biochemistry in med school, we can remember these enzymes play a significant role in the Krebs cycle and pentose phosphate pathways. Thiamine uses Mg+2 as a cofactor, so a magnesium deficiency can mimic WE.

Pathophysiology.

B1 deficiency causes lactic acid accumulation due to anaerobic glycolysis, leading to neuronal cytotoxic edema and vasogenic edema with petechial hemorrhages. MRI of the brain shows symmetrical hyperintensities, most commonly in the thalamus, mammillary bodies, cerebellum, and the periaqueductal area surrounding the third and fourth ventricles. The diagnosis of WE is made clinically, even though the MRI is a useful complementary tool to the clinical diagnosis. 

Diagnosis.

WE presentation has always been described as the classic triad of ophthalmoplegia (or nystagmus), encephalopathy (confusion or memory impairment), and gait ataxia. However, this presentation is present only in less than 20% of patients, and most of the patients present with a neurologic syndrome that includes 2 out of the classic triad plus nonspecific symptoms such as hallucinations, hypothermia, hypotension, indifference or inattentiveness, seizures, behavioral disturbances, and bilateral lower extremity weakness. 

In 1997, Caine et al. suggested that a diagnosis of WE can be made if 2 out of 4 of these criteria were present in a patient with ophthalmoplegia/nystagmus + ataxia + memory impairment or confusion and clinical evidence of malnutrition or from laboratory data. Thiamine levels can be normal in patients with WE, so thiamine level is not a requirement for diagnosis.

Almost 80% of WE cases are diagnosed on autopsy, which means this disease goes undiagnosed most of the time. The diagnosis is clinical, and MRI can assist in cases that are uncertain. 

Treatment.

Thiamine supplementation is inexpensive, accessible, and easy to administer, so if we have a patient with a suspicious neurologic syndrome that could be WE, B1 must be given as soon as possible. Treatment should not be delayed while waiting for MRI results, 

The treatment consists of IV thiamine 500mg TID for 2-3 days, followed by 250 IM or IV for additional 5 days, in combination with other B vitamins. Because GI absorption of thiamine is impaired in alcoholics and malnourished patients, oral administration is contraindicated during initial treatment for WE. Thiamine 100 mg PO should be continued after the completion of parenteral treatment and after discharge from the hospital until patients are no longer considered at risk. Magnesium and other vitamins are replaced as well, along with other nutritional deficits if present.

B1 blood levels or erythrocyte transketolase activity (which is a way to evaluate thiamine deficiency) are measured before and after thiamine pyrophosphate supplementation. A low transketolase and a more than 25 percent stimulation are positive for thiamine deficiency. This test is often not readily available, especially at the ED. High-quality liquid chromatography can also measure serum thiamine or TPP level in serum or whole blood.

For practical purposes, and given high undiagnosed rates and mortality, IV thiamine should be given to all patients with malnutrition admitted to the hospital or seen in clinic. 

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Conclusion: Now we conclude episode number 117 “Wernicke’s Encephalopathy.” Dr. Malave explained that a low thiamine level is not required for the diagnosis of Wernicke’s encephalopathy. Start supplementation if you have a high suspicion of thiamine deficiency, especially before giving IV glucose to a malnourished patient. We were reminded that GI absorption of thiamine is impaired in patients with chronic alcohol use, so make sure you give thiamine IV or IM. 

This week we thank Hector Arreaza and Maria Fernanda Malave. Audio edition by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! 

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Links:

1. He Jingqi, Li Jinguang, Li Zhijun, Ren Honghong, Chen Xiaogang, Tang Jinsong. A Case Report of Wernicke's Encephalopathy Associated with Schizophrenia. Frontiers in Psychiatry. Vol 12. Year 2021. DOI=10.3389/fpsyt.2021.657649. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.657649/full
2. Ota, Y., Capizzano, A.A., Moritani, T. et al. Comprehensive review of Wernicke encephalopathy: pathophysiology, clinical symptoms and imaging findings. Jpn J Radiol 38, 809–820 (2020). https://doi.org/10.1007/s11604-020-00989-3.
3. Yuen T So, MD, PhD, Wernicke encephalopathy, last updated: Feb 11, 2020, UpToDate. Retrieved October 25, 2022.https://www.uptodate.com/contents/wernicke-encephalopathy.
4. Patel S, Topiwala K, Hudson L. Wernicke's Encephalopathy. Cureus. 2018 Aug 22;10(8):e3187. doi: 10.7759/cureus.3187. PMID: 30364782; PMCID: PMC6199146. https://pubmed.ncbi.nlm.nih.gov/30364782/
5. Royalty-free music used for this episode: Simon Pettersson – good vibes_ Fashionista, downloaded on October 1, 2022, from https://www.videvo.net 

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