Wernicke Encephalopathy Patricia F. Jenkins, C.O.
ABSTRACT Introduction and Purpose: This paper reviews the complaints and associated symptoms/ consequences of lacking essential nutrients and vitamins in our central and peripheral nervous systems. This has become important as there has been a rise in malnutrition following the increasing incidence of bariatric surgery for obesity. Methods: A case report example involving review of the clinical presentation and treatment. Results: A 30-year-old Caucasian woman who had gastric sleeve surgery did not take the recommended capsules as they were too large to swallow. She noted diplopia and oscillopsia 2 months later, which led her to have full orthoptic and neuro-ophthalmic evaluations. After being treated with chewable vitamins with thiamine, she noted a tremendous improvement in her symptoms. Conclusion: Wernicke encephalopathy is a disease that was seen more in the 1940s and 1950s, following war times and mostly in underdeveloped countries. However, with the increasing utilization of bariatric surgery for obesity, neurological offices are seeing more patients with neurological impairments. We recommend inquiring about any obesity surgery in one’s history and including Wernicke encephalopathy in possible differential diagnoses in those patients who have a recent onset of strabismus or nystagmus, altered mental status, and/or gait ataxia.
INTRODUCTION Proper nutrition is essential in maintaining our central and peripheral nervous systems. We know that malnutrition can lead to many problems, including neurological deficits. This has been seen primarily in underdeveloped countries.1 In 1881, Carl Wernicke first described two men with alcoholism and one woman
From the Neuro-Ophthalmology of Texas Medical Clinic, Houston, Texas. Requests for reprints should be addressed to: Patricia F. Jenkins, C.O., Neuro-Ophthalmology of Texas, 2726 Bissonnet, Suite 240-54, Houston, TX 77005.
with recurrent vomiting after pyloric stenosis from ingesting sulfuric acid who presented with acute superior hemorrhagic polioencephalitis. This is the pathological equivalent of Wernicke encephalopathy, which causes findings similar to polio.2 Low levels of Vitamin B1 or thiamine affect the central nervous system, the peripheral nervous system and the cardiovascular system. Thiamine is critical as it acts as a co-enzyme in metabolizing carbohydrates, lipids, and “branchchained” amino acids.1 B1 also aids in energy production of “adenosine triphosphate” synthesis, which is also known as ATP, the leading product to produce
© 2015 Board of Regents of the University of Wisconsin System, American Orthoptic Journal, Volume 65, 2015, ISSN 0065-955X, E-ISSN 1553-4448
104
JENKINS
energy in cells as well as helping to maintain myelin sheath. Thiamine aids in glucose metabolism and in neurotransmitter synthesis. 1,3 Wernicke encephalopathy occurs when the normal nutritional status is low and the proper absorption of thiamine is impaired, such as in alcoholism, AIDS, prolonged vomiting, infectious and noninfectious diseases, and chemotherapy.3 Certain disorders, such as anemia and inflammatory bowel disease, can also cause vitamin and mineral deficiencies. Unfortunately, there has been an epidemic of obesity in the United States and elsewhere. A common treatment for obesity is bariatric surgery and this has induced a new peak in this malabsorption entity.1, 4, 5, 6 Vitamin B1 is absorbed through our gastro-intestinal system, but because B1 has a short “half life” and there is low storage, there must be a continuous supply of B1 in our diet. A deficiency can develop in only a matter of days.1 The normal healthy person (depending on the carbohydrate intake) needs approximately 1-2 mg of thiamine daily; the body’s reserves are only 30-50 mg and would be completely depleted in 4-6 weeks without replenishing the thiamine vitamin. 3 Since this is difficult to diagnose until there is severe thiamine deficiency, most neurologists and clinicians feel subclinical symptoms are enough to initiate treatment.1, 3 The typical symptoms include headache, irritability, fatigue, and lethargy.7 Finally, there can be ataxia that indicates vestibular and cerebellar dysfunction, as well as loss of deep tendon reflexes, similar to Guillain Barre syndrome. If untreated, patients will lose the ability to concentrate, develop apathy, then eventually spatial disorientation, confusion, psychosis, and coma. Ocular abnormalities are acquired nystagmus, mostly horizontal, oscillopsia, diplopia, sixth cranial nerve pareses, skew deviation, sluggish pupils, anisocoria, miosis, light/near dissociation, retinal hemorrhage or papilledema, optic neuropathy, central
American Orthoptic Journal
scotoma, horizontal gaze palsy, and Miller Fisher type symptoms including ocularmotor abnormalities.1 Recently, a sharp increase in thiamine deficits has been noted that has not been seen in the United States for a very long time. This increase is mostly from bariatric surgery for obesity. There are many procedures and some are not performed any longer because of the association with severe malnutrition. Some surgical modalities include gastric restriction, gastric partitioning, gastroplasty, and vertical-banded gastroplasty. There are also other procedures such as adjustable gastric band, biliopancreatic diversion, and duodenal switch modifier.1, 4, 5, 6 Gastric bypass seems to work better as it restricts the volume eaten. However, Wernicke encephalopathy has been noted in something as benign as persistent vomiting with migraines. CASE A 30-year-old Caucasian woman presented with complaints of sudden onset diplopia and “bouncing” vision. She saw an otolaryngologist and tested for a central vestibular anomaly, where it was found when the patient tilted her head to the right, she developed a vertical type of oscillopsia. She was referred for a complete neuro-ophthalmological evaluation, which included an orthoptic evaluation. There was a history of gastric bypass surgery. She had a small, comitant right hyperphoria, with intermittent complaints of vertical diplopia and a small esophoria in right gaze, normal ductions, and versions and fair stereopsis. It was noted she had asymmetric, nystagmoid movements that increased in right gaze as well as complaints of increased oscillopsia. There was gaze-evoked nystagmus that was left beating in left gaze and down-beating with a right beating component in right gaze. All other tests were normal including visual field, visual-evoked potential, pupils, color vision, and fundus photos. This patient’s MRI demonstrated abnormal peri-
105
WERNICKE ENCEPHALOPATHY
ventricular and subcortical changes, with one enhancing lesion. The report stated it was difficult to determine any abnormality in the mamillary bodies.8 There was known low Vitamin A and low Vitamin D, but it was not ascertained if a B1 level was drawn. Since her symptoms were suggestive of Wernicke encephalopathy, she was started on thiamine 100 mg every day in addition to a multivitamin.8 At her follow-up appointment, she had dramatically reduced complaints of double and bouncing vision. She was told to continue the B1 and multivitamins and will be followed by the neurologist and ophthalmologist/orthoptist team.
FIGURE 1: The arrow shows the periventricular area and the white enhancement revealing cytotoxic edema.
DISCUSSION In general, Wernicke encephalopathy is most commonly associated with alcohol abuse in men and bariatric surgery in women. Iron and B12 deficiencies are the most common following the gastric bypass procedure. Other vitamin deficits are common; however, it is the deficient B1 that causes Wernicke encephalopathy, which is found more frequently on autopsies than expected from clinical studies, even with alerts following obesity surgery. There are most likely two main reasons for this: dietary supplements and certain foods containing bacteria. Occasionally, diet pills have herbal supplements that can interfere with thiamine absorption in our bodies. These actually act as thiamine antagonists. Raw fish and some shellfish contain bacteria with thiaminases, inactivating what thiamine is present. This inactivation can happen with baking bread, cooking long periods of time, pasteurization of milk, and even excessive antacid use can interfere with the absorption of thiamine. Anti-thiamine agents can be found in Betel nuts, tea, and coffee.1 THIAMINE Red blood cell count, in a simple blood test, is a good indicator of body thiamine
106
stores (approximately 30 mg). Thiamine levels must be specifically requested on the blood test, since it is not part of the complete blood count (CBC).8 MRI of the brain is the choice diagnostic tool for Wernicke encephalopathy. Even with this technology, around one half of patients have normal findings. According to Zuccoli, the most common distinctive finding of Wernicke encephalopathy on the MRI is “reversible cytotoxic edema.”3 The most common anatomic regions with this edema are the medial thalami and periventricular region of the third ventricle. There are high levels of thiamine specifically needed in these particular areas and any deficiency or lack of B1 will cause an imbalance in the fluid shift, thereby producing cytotoxic edema.3 The brain MRI of the Wernicke encephalopathy patient closely resembles the brain MRI of the multiple sclerosis patient where they both have periventricular lesions that often enhance on the MRI.10 These findings and symptoms may be reversed with thiamine treatment. See Figure 1, where the arrow shows the periventricular area and the white enhancement revealing cytotoxic edema. Figure 2 is the same patient following thiamine
Volume 65, 2015
JENKINS
tients, those partaking in certain food fads, and those with eating disorders such as anorexia and bulimia. Persistent vomiting following bariatric surgery for obesity can also lead to this entity. Many patients may have multiple deficits. Complete vitamin nourishment, including the addition of thiamine, should help prevent Wernicke encephalopathy, but the patient must be well informed and monitored closely. CONCLUSION
FIGURE 2: The same patient following thiamine treatment, but without enhancement or edema.
treatment, but without enhancement or edema. As for management, Kumar suggests a regiment of 100-300 mg for 8 hours, either IV, intramuscular (IM), or orally. At risk patients should receive IV thiamine prior to glucose or IV nutrition and possibly prior to gastric bypass.1 There has been a sharp rise in concern over health issues, and an increase in the availability of healthy foods as well as fad diets. Those specifically at risk from malnutrition, including in the United States and other developed countries, are at risk for dangerously low vital nutrients and vitamins, especially B1. This particular Bvitamin does not have a long storage value, so there can be a life and death situation quickly. At risk patients should be given B1 prior to glucose and possibly prior to gastric bypass. Some authors feel Wernicke encephalopathy is under-diagnosed especially when the clinical presentation is atypical and there is not a history of alcohol abuse.3 SUMMARY Thiamine deficiency is a major health concern for alcoholics, the elderly, the homeless, the poor, chemotherapy pa-
American Orthoptic Journal
Wernicke encephalopathy has a triad of abnormalities: nystagmus, gait ataxia, and altered mental status, usually confusion. Diplopia and oscillopsia are common complaints as well. If detected early, these symptoms can be reversed by replacing thiamine stores. Diagnosis relies on clinical symptoms since only 40-50% of patients have findings on the MRI. B-group vitamins are particularly important for a well functioning nervous system. There may be sufficient suspicions to warrant adding a question about lap band, gastric bypass, or other bariatric surgery to your complete history of the patient. ACKNOWLEDGEMENTS Many thanks to Rosa A. Tang, M.D., and Jade Schiffman, M.D., for their help with this paper. REFERENCES 1. Kumar N: Neurologic presentations of nutritional deficiencies. Neurol Clin 2010; 28:107-170. 2. Wernicke C: Die akute haemorrhagische polioencephalitis superior. In: Lehrbuch der Gehirnkrankheiten für Ärzte und Studierende, Bd. II. Kassel: Fischer Verlag, 1881, pp. 229-242. 3. Zuccoli G, Pipitone N: Neuroimaging findings in acute Wernicke’s encephalopathy: Review of the literature. Am J Rad 2009; 192:501-507. 4. Halverson JD: Micronutrient deficiencies after gastric bypass for morbid obesity. Am Surg 1986; 52:594-598.
107
WERNICKE ENCEPHALOPATHY
5. Buchwald H, Buchwald JN: Evolution of operative procedures for the management of morbid obesity, 1950-2000. Obes Surg 2002; 12:705-717. 6. Sanchez-Crespo NE, Parker M: Wernicke’s encephalopathy: A tragic complication of gastric bypass. J Hosp Med 2006; 1:72. 7. Sechi G, Serra A: New clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007; 6:442-455. 8. Tang RA: Personal communication, 2014-15, Houston, TX. 9. Reuler JB, Girard DE, Cooney TG: Current concepts: Wernicke’s encephalopathy. New Engl Jr Med 1985; 312:1035-1039.
108
10. Schiffman J: Personal communication, 2014, Houston, TX. 11. Campbell ACP, Russell WR: Wernicke’s encephalopathy: The clinical features and their probable relationship to vitamin B deficiency. Q J Med 1941; 10:41-64. 12. Butterworth RF. Modern Nutrition in Health and Disease. Baltimore: Lippincott, Williams, and Wilkins; 2006, pp. 426-433.
Key words: Wernicke encephalopathy, obesity surgery, diplopia, oscillopsia, ataxia, mental confusion.
Volume 65, 2015
ABSTRACT Introduction and Purpose: This paper reviews the complaints and associated symptoms/ consequences of lacking essential nutrients and vitamins in our central and peripheral nervous systems. This has become important as there has been a rise in malnutrition following the increasing incidence of bariatric surgery for obesity. Methods: A case report example involving review of the clinical presentation and treatment. Results: A 30-year-old Caucasian woman who had gastric sleeve surgery did not take the recommended capsules as they were too large to swallow. She noted diplopia and oscillopsia 2 months later, which led her to have full orthoptic and neuro-ophthalmic evaluations. After being treated with chewable vitamins with thiamine, she noted a tremendous improvement in her symptoms. Conclusion: Wernicke encephalopathy is a disease that was seen more in the 1940s and 1950s, following war times and mostly in underdeveloped countries. However, with the increasing utilization of bariatric surgery for obesity, neurological offices are seeing more patients with neurological impairments. We recommend inquiring about any obesity surgery in one’s history and including Wernicke encephalopathy in possible differential diagnoses in those patients who have a recent onset of strabismus or nystagmus, altered mental status, and/or gait ataxia.
INTRODUCTION Proper nutrition is essential in maintaining our central and peripheral nervous systems. We know that malnutrition can lead to many problems, including neurological deficits. This has been seen primarily in underdeveloped countries.1 In 1881, Carl Wernicke first described two men with alcoholism and one woman
From the Neuro-Ophthalmology of Texas Medical Clinic, Houston, Texas. Requests for reprints should be addressed to: Patricia F. Jenkins, C.O., Neuro-Ophthalmology of Texas, 2726 Bissonnet, Suite 240-54, Houston, TX 77005.
with recurrent vomiting after pyloric stenosis from ingesting sulfuric acid who presented with acute superior hemorrhagic polioencephalitis. This is the pathological equivalent of Wernicke encephalopathy, which causes findings similar to polio.2 Low levels of Vitamin B1 or thiamine affect the central nervous system, the peripheral nervous system and the cardiovascular system. Thiamine is critical as it acts as a co-enzyme in metabolizing carbohydrates, lipids, and “branchchained” amino acids.1 B1 also aids in energy production of “adenosine triphosphate” synthesis, which is also known as ATP, the leading product to produce
© 2015 Board of Regents of the University of Wisconsin System, American Orthoptic Journal, Volume 65, 2015, ISSN 0065-955X, E-ISSN 1553-4448
104
JENKINS
energy in cells as well as helping to maintain myelin sheath. Thiamine aids in glucose metabolism and in neurotransmitter synthesis. 1,3 Wernicke encephalopathy occurs when the normal nutritional status is low and the proper absorption of thiamine is impaired, such as in alcoholism, AIDS, prolonged vomiting, infectious and noninfectious diseases, and chemotherapy.3 Certain disorders, such as anemia and inflammatory bowel disease, can also cause vitamin and mineral deficiencies. Unfortunately, there has been an epidemic of obesity in the United States and elsewhere. A common treatment for obesity is bariatric surgery and this has induced a new peak in this malabsorption entity.1, 4, 5, 6 Vitamin B1 is absorbed through our gastro-intestinal system, but because B1 has a short “half life” and there is low storage, there must be a continuous supply of B1 in our diet. A deficiency can develop in only a matter of days.1 The normal healthy person (depending on the carbohydrate intake) needs approximately 1-2 mg of thiamine daily; the body’s reserves are only 30-50 mg and would be completely depleted in 4-6 weeks without replenishing the thiamine vitamin. 3 Since this is difficult to diagnose until there is severe thiamine deficiency, most neurologists and clinicians feel subclinical symptoms are enough to initiate treatment.1, 3 The typical symptoms include headache, irritability, fatigue, and lethargy.7 Finally, there can be ataxia that indicates vestibular and cerebellar dysfunction, as well as loss of deep tendon reflexes, similar to Guillain Barre syndrome. If untreated, patients will lose the ability to concentrate, develop apathy, then eventually spatial disorientation, confusion, psychosis, and coma. Ocular abnormalities are acquired nystagmus, mostly horizontal, oscillopsia, diplopia, sixth cranial nerve pareses, skew deviation, sluggish pupils, anisocoria, miosis, light/near dissociation, retinal hemorrhage or papilledema, optic neuropathy, central
American Orthoptic Journal
scotoma, horizontal gaze palsy, and Miller Fisher type symptoms including ocularmotor abnormalities.1 Recently, a sharp increase in thiamine deficits has been noted that has not been seen in the United States for a very long time. This increase is mostly from bariatric surgery for obesity. There are many procedures and some are not performed any longer because of the association with severe malnutrition. Some surgical modalities include gastric restriction, gastric partitioning, gastroplasty, and vertical-banded gastroplasty. There are also other procedures such as adjustable gastric band, biliopancreatic diversion, and duodenal switch modifier.1, 4, 5, 6 Gastric bypass seems to work better as it restricts the volume eaten. However, Wernicke encephalopathy has been noted in something as benign as persistent vomiting with migraines. CASE A 30-year-old Caucasian woman presented with complaints of sudden onset diplopia and “bouncing” vision. She saw an otolaryngologist and tested for a central vestibular anomaly, where it was found when the patient tilted her head to the right, she developed a vertical type of oscillopsia. She was referred for a complete neuro-ophthalmological evaluation, which included an orthoptic evaluation. There was a history of gastric bypass surgery. She had a small, comitant right hyperphoria, with intermittent complaints of vertical diplopia and a small esophoria in right gaze, normal ductions, and versions and fair stereopsis. It was noted she had asymmetric, nystagmoid movements that increased in right gaze as well as complaints of increased oscillopsia. There was gaze-evoked nystagmus that was left beating in left gaze and down-beating with a right beating component in right gaze. All other tests were normal including visual field, visual-evoked potential, pupils, color vision, and fundus photos. This patient’s MRI demonstrated abnormal peri-
105
WERNICKE ENCEPHALOPATHY
ventricular and subcortical changes, with one enhancing lesion. The report stated it was difficult to determine any abnormality in the mamillary bodies.8 There was known low Vitamin A and low Vitamin D, but it was not ascertained if a B1 level was drawn. Since her symptoms were suggestive of Wernicke encephalopathy, she was started on thiamine 100 mg every day in addition to a multivitamin.8 At her follow-up appointment, she had dramatically reduced complaints of double and bouncing vision. She was told to continue the B1 and multivitamins and will be followed by the neurologist and ophthalmologist/orthoptist team.
FIGURE 1: The arrow shows the periventricular area and the white enhancement revealing cytotoxic edema.
DISCUSSION In general, Wernicke encephalopathy is most commonly associated with alcohol abuse in men and bariatric surgery in women. Iron and B12 deficiencies are the most common following the gastric bypass procedure. Other vitamin deficits are common; however, it is the deficient B1 that causes Wernicke encephalopathy, which is found more frequently on autopsies than expected from clinical studies, even with alerts following obesity surgery. There are most likely two main reasons for this: dietary supplements and certain foods containing bacteria. Occasionally, diet pills have herbal supplements that can interfere with thiamine absorption in our bodies. These actually act as thiamine antagonists. Raw fish and some shellfish contain bacteria with thiaminases, inactivating what thiamine is present. This inactivation can happen with baking bread, cooking long periods of time, pasteurization of milk, and even excessive antacid use can interfere with the absorption of thiamine. Anti-thiamine agents can be found in Betel nuts, tea, and coffee.1 THIAMINE Red blood cell count, in a simple blood test, is a good indicator of body thiamine
106
stores (approximately 30 mg). Thiamine levels must be specifically requested on the blood test, since it is not part of the complete blood count (CBC).8 MRI of the brain is the choice diagnostic tool for Wernicke encephalopathy. Even with this technology, around one half of patients have normal findings. According to Zuccoli, the most common distinctive finding of Wernicke encephalopathy on the MRI is “reversible cytotoxic edema.”3 The most common anatomic regions with this edema are the medial thalami and periventricular region of the third ventricle. There are high levels of thiamine specifically needed in these particular areas and any deficiency or lack of B1 will cause an imbalance in the fluid shift, thereby producing cytotoxic edema.3 The brain MRI of the Wernicke encephalopathy patient closely resembles the brain MRI of the multiple sclerosis patient where they both have periventricular lesions that often enhance on the MRI.10 These findings and symptoms may be reversed with thiamine treatment. See Figure 1, where the arrow shows the periventricular area and the white enhancement revealing cytotoxic edema. Figure 2 is the same patient following thiamine
Volume 65, 2015
JENKINS
tients, those partaking in certain food fads, and those with eating disorders such as anorexia and bulimia. Persistent vomiting following bariatric surgery for obesity can also lead to this entity. Many patients may have multiple deficits. Complete vitamin nourishment, including the addition of thiamine, should help prevent Wernicke encephalopathy, but the patient must be well informed and monitored closely. CONCLUSION
FIGURE 2: The same patient following thiamine treatment, but without enhancement or edema.
treatment, but without enhancement or edema. As for management, Kumar suggests a regiment of 100-300 mg for 8 hours, either IV, intramuscular (IM), or orally. At risk patients should receive IV thiamine prior to glucose or IV nutrition and possibly prior to gastric bypass.1 There has been a sharp rise in concern over health issues, and an increase in the availability of healthy foods as well as fad diets. Those specifically at risk from malnutrition, including in the United States and other developed countries, are at risk for dangerously low vital nutrients and vitamins, especially B1. This particular Bvitamin does not have a long storage value, so there can be a life and death situation quickly. At risk patients should be given B1 prior to glucose and possibly prior to gastric bypass. Some authors feel Wernicke encephalopathy is under-diagnosed especially when the clinical presentation is atypical and there is not a history of alcohol abuse.3 SUMMARY Thiamine deficiency is a major health concern for alcoholics, the elderly, the homeless, the poor, chemotherapy pa-
American Orthoptic Journal
Wernicke encephalopathy has a triad of abnormalities: nystagmus, gait ataxia, and altered mental status, usually confusion. Diplopia and oscillopsia are common complaints as well. If detected early, these symptoms can be reversed by replacing thiamine stores. Diagnosis relies on clinical symptoms since only 40-50% of patients have findings on the MRI. B-group vitamins are particularly important for a well functioning nervous system. There may be sufficient suspicions to warrant adding a question about lap band, gastric bypass, or other bariatric surgery to your complete history of the patient. ACKNOWLEDGEMENTS Many thanks to Rosa A. Tang, M.D., and Jade Schiffman, M.D., for their help with this paper. REFERENCES 1. Kumar N: Neurologic presentations of nutritional deficiencies. Neurol Clin 2010; 28:107-170. 2. Wernicke C: Die akute haemorrhagische polioencephalitis superior. In: Lehrbuch der Gehirnkrankheiten für Ärzte und Studierende, Bd. II. Kassel: Fischer Verlag, 1881, pp. 229-242. 3. Zuccoli G, Pipitone N: Neuroimaging findings in acute Wernicke’s encephalopathy: Review of the literature. Am J Rad 2009; 192:501-507. 4. Halverson JD: Micronutrient deficiencies after gastric bypass for morbid obesity. Am Surg 1986; 52:594-598.
107
WERNICKE ENCEPHALOPATHY
5. Buchwald H, Buchwald JN: Evolution of operative procedures for the management of morbid obesity, 1950-2000. Obes Surg 2002; 12:705-717. 6. Sanchez-Crespo NE, Parker M: Wernicke’s encephalopathy: A tragic complication of gastric bypass. J Hosp Med 2006; 1:72. 7. Sechi G, Serra A: New clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007; 6:442-455. 8. Tang RA: Personal communication, 2014-15, Houston, TX. 9. Reuler JB, Girard DE, Cooney TG: Current concepts: Wernicke’s encephalopathy. New Engl Jr Med 1985; 312:1035-1039.
108
10. Schiffman J: Personal communication, 2014, Houston, TX. 11. Campbell ACP, Russell WR: Wernicke’s encephalopathy: The clinical features and their probable relationship to vitamin B deficiency. Q J Med 1941; 10:41-64. 12. Butterworth RF. Modern Nutrition in Health and Disease. Baltimore: Lippincott, Williams, and Wilkins; 2006, pp. 426-433.
Key words: Wernicke encephalopathy, obesity surgery, diplopia, oscillopsia, ataxia, mental confusion.
Volume 65, 2015
