Wernicke's encephalopathy

Nervous System & Special Senses


Clinicals - History

Fact Explanation
{"ops":[{"insert":"Introduction\n"}]}
{"ops":[{"insert":"Wernicke\u0027s encephalopathy (WE) is a neurological disorder caused by thiamine (vitamin B1) deficiency. Thiamine deficiency can occur in individuals with compromised absorption (e.g., hyperemesis), increased metabolism (e.g., sepsis), or increased carbohydrate intake (e.g., following IV dextrose administration). Chronic alcohol abuse is the most common etiology. The underlying pathophysiology involves lactic acid accumulation secondary to altered glucose metabolization in the absence of thiamine. This results in neurotoxic edema and oxidative stress that affects multiple brain structures.\n"}]}
{"ops":[{"insert":"Altered mentation\n"}]}
{"ops":[{"insert":"Altered mentation is the most frequent symptom. This can manifest as: "},{"insert":"cognitive ","attributes":{"color":"#212529"}},{"insert":"impairment, including impairment of memory and an inability to concentrate; delirium; spatial disorientation; dizziness; drowsiness; apathy; coma; or, death. Altered mentation is believed to occur due to lesions affecting the dorsomedial thalamus, mammillary bodies, and cerebral cortex.\n"}]}
{"ops":[{"insert":"Visual disturbances\n"}]}
{"ops":[{"insert":"Diplopia is a classic symptom. This is "},{"insert":"thought ","attributes":{"color":"#212529"}},{"insert":"to be due to lesions of cranial nerves III and IV.\n"}]}
{"ops":[{"insert":"Poor nutrition\n"}]}
{"ops":[{"insert":"Patients should be asked about their diet, and if they have any conditions that might impact nutrition, including: alcoholism, malignancies, gastrointestinal disease, gastrointestinal surgery. This is because an inadequate diet may cause thiamine deficiency. \n"}]}
{"ops":[{"insert":"Alcoholism\n"}]}
{"ops":[{"insert":"WE is more frequent in alcoholic patients, in whom it often presents as a subclinical syndrome.\n"}]}
{"ops":[{"insert":"Loss of balance\n"}]}
{"ops":[{"insert":"Patients may present with loss of balance and falls. This is due to ataxia.\n"}]}
{"ops":[{"insert":"Introduction\n"}]}
{"ops":[{"insert":"Wernicke\u0027s encephalopathy (WE) is a neurological disorder caused by thiamine (vitamin B1) deficiency. Thiamine deficiency can occur in individuals with compromised absorption (e.g., hyperemesis), increased metabolism (e.g., sepsis), or increased carbohydrate intake (e.g., following IV dextrose administration). Chronic alcohol abuse is the most common etiology. The underlying pathophysiology involves lactic acid accumulation secondary to altered glucose metabolization in the absence of thiamine. This results in neurotoxic edema and oxidative stress that affects multiple brain structures.\n"}]}
{"ops":[{"insert":"Altered mentation\n"}]}
{"ops":[{"insert":"Altered mentation is the most frequent symptom. This can manifest as: "},{"insert":"cognitive ","attributes":{"color":"#212529"}},{"insert":"impairment, including impairment of memory and an inability to concentrate; delirium; spatial disorientation; dizziness; drowsiness; apathy; coma; or, death. Altered mentation is believed to occur due to lesions affecting the dorsomedial thalamus, mammillary bodies, and cerebral cortex.\n"}]}
{"ops":[{"insert":"Visual disturbances\n"}]}
{"ops":[{"insert":"Diplopia is a classic symptom. This is "},{"insert":"thought ","attributes":{"color":"#212529"}},{"insert":"to be due to lesions of cranial nerves III and IV.\n"}]}
{"ops":[{"insert":"Poor nutrition\n"}]}
{"ops":[{"insert":"Patients should be asked about their diet, and if they have any conditions that might impact nutrition, including: alcoholism, malignancies, gastrointestinal disease, gastrointestinal surgery. This is because an inadequate diet may cause thiamine deficiency. \n"}]}
{"ops":[{"insert":"Alcoholism\n"}]}
{"ops":[{"insert":"WE is more frequent in alcoholic patients, in whom it often presents as a subclinical syndrome.\n"}]}
{"ops":[{"insert":"Loss of balance\n"}]}
{"ops":[{"insert":"Patients may present with loss of balance and falls. This is due to ataxia.\n"}]}

Clinicals - Examination

Fact Explanation
{"ops":[{"insert":"Altered mentation\n"}]}
{"ops":[{"insert":"Patients can present with "},{"insert":"cognitive ","attributes":{"color":"#212529"}},{"insert":"impairment, memory impairment, delirium, disorientation, dizziness, drowsiness, apathy, or coma. This is thought to be due to lesions affecting the dorsomedial thalamus, mamillary bodies, and cerebral cortex. This may persist for several weeks, even after prompt treatment.\n"}]}
{"ops":[{"insert":"Ocular signs\n"}]}
{"ops":[{"insert":"Patients can present with various ocular signs: nystagmus, papilledema, or gaze palsies. Pupillary sluggishness, ptosis, and anisocoria are also common. This is thought to be due to lesions affecting the cranial nerves III and IV, the locus ceruleus, and periaqueductal gray area.\n"}]}
{"ops":[{"insert":"Gait disturbances\n"}]}
{"ops":[{"insert":"Patients can present with various gait disturbances that can vary from mild gait impairment to a complete inability to stand. This is thought to be due to lesions in the superior cerebellar vermis, cerebellar cortex, and vestibular dysfunction.\n"}]}
{"ops":[{"insert":"Peripheral neuropathy\n"}]}
{"ops":[{"insert":"Patients can present with peripheral, ascending motor and sensory neuropathy (also called dry beriberi). This is thought to be due to axonal degeneration caused by thiamine deficiency. This can latter progress to demyelination in end-stage disease.\n"}]}
{"ops":[{"insert":"Hearing impairment\n"}]}
{"ops":[{"insert":"Patients can present with hearing impairment. This is thought to be due to thalamic involvement.\n"}]}
{"ops":[{"insert":"Seizures\n"}]}
{"ops":[{"insert":"Patients can present with seizures. This is thought to be due to glutamatergic hyperactivity.\n"}]}
{"ops":[{"insert":"Abnormal regulation of body temperature\n"}]}
{"ops":[{"insert":"Patients can present with hypothermia. This is thought to be due to hypothalamic involvement.\n"}]}
{"ops":[{"insert":"Cardiac examination\n"}]}
{"ops":[{"insert":"Patients can present with hypotension, tachycardia, and peripheral edema. This is thought to be due to decreased cardiac function resulting from decreased cellular energy production. Thiamine deficiency affects production of adenosine triphosphate (ATP), causing the accumulation of adenosine. This causes reduction of systemic vascular resistance and a compensatory high-output heart failure (called \u201ccardiac\u201d or \u201cwet\u201d beriberi). Ultimately, myocardial weakness develops, resulting in systolic dysfunction and a low-output heart failure.\n"}]}
{"ops":[{"insert":"Altered mentation\n"}]}
{"ops":[{"insert":"Patients can present with "},{"insert":"cognitive ","attributes":{"color":"#212529"}},{"insert":"impairment, memory impairment, delirium, disorientation, dizziness, drowsiness, apathy, or coma. This is thought to be due to lesions affecting the dorsomedial thalamus, mamillary bodies, and cerebral cortex. This may persist for several weeks, even after prompt treatment.\n"}]}
{"ops":[{"insert":"Ocular signs\n"}]}
{"ops":[{"insert":"Patients can present with various ocular signs: nystagmus, papilledema, or gaze palsies. Pupillary sluggishness, ptosis, and anisocoria are also common. This is thought to be due to lesions affecting the cranial nerves III and IV, the locus ceruleus, and periaqueductal gray area.\n"}]}
{"ops":[{"insert":"Gait disturbances\n"}]}
{"ops":[{"insert":"Patients can present with various gait disturbances that can vary from mild gait impairment to a complete inability to stand. This is thought to be due to lesions in the superior cerebellar vermis, cerebellar cortex, and vestibular dysfunction.\n"}]}
{"ops":[{"insert":"Peripheral neuropathy\n"}]}
{"ops":[{"insert":"Patients can present with peripheral, ascending motor and sensory neuropathy (also called dry beriberi). This is thought to be due to axonal degeneration caused by thiamine deficiency. This can latter progress to demyelination in end-stage disease.\n"}]}
{"ops":[{"insert":"Hearing impairment\n"}]}
{"ops":[{"insert":"Patients can present with hearing impairment. This is thought to be due to thalamic involvement.\n"}]}
{"ops":[{"insert":"Seizures\n"}]}
{"ops":[{"insert":"Patients can present with seizures. This is thought to be due to glutamatergic hyperactivity.\n"}]}
{"ops":[{"insert":"Abnormal regulation of body temperature\n"}]}
{"ops":[{"insert":"Patients can present with hypothermia. This is thought to be due to hypothalamic involvement.\n"}]}
{"ops":[{"insert":"Cardiac examination\n"}]}
{"ops":[{"insert":"Patients can present with hypotension, tachycardia, and peripheral edema. This is thought to be due to decreased cardiac function resulting from decreased cellular energy production. Thiamine deficiency affects production of adenosine triphosphate (ATP), causing the accumulation of adenosine. This causes reduction of systemic vascular resistance and a compensatory high-output heart failure (called \u201ccardiac\u201d or \u201cwet\u201d beriberi). Ultimately, myocardial weakness develops, resulting in systolic dysfunction and a low-output heart failure.\n"}]}

Differential diagnoses

Fact Explanation
{"ops":[{"insert":"Korsakoff syndrome\n"}]}
{"ops":[{"insert":"Korsakoff syndrome can also present with memory impairment. This can be differentiated from WE by the presence of provoked confabulation. If left untreated, WE may lead to Korsakoff syndrome.\n"}]}
{"ops":[{"insert":"Hepatic encephalopathy\n"}]}
{"ops":[{"insert":"Hepatic encephalopathy can also present with altered mental status. This can be differentiated from WE by the presence of history of hepatic disease, asterixis and extrapyramidal dysfunction, and the absence of ocular signs.\n"}]}
{"ops":[{"insert":"Stroke\n"}]}
{"ops":[{"insert":"Stroke can also present with gait abnormalities and ocular disturbances. This can be differentiated from WE by the presence of hemorrhage or ischemia on brain imaging. Brain ischemia be apparent on MRI of the brain or several days afterwards, on CT brain images.\n"}]}
{"ops":[{"insert":"Alcohol withdrawal syndrome\n"}]}
{"ops":[{"insert":"Alcohol withdrawal syndrome can also present with altered mental status, gait abnormalities, ocular disturbances, and seizures. This can be differentiated from WE by a history of alcohol abuse with recent reduction or abrupt cessation in alcohol consumption.\n"}]}
{"ops":[{"insert":"Normal pressure hydrocephalus\n"}]}
{"ops":[{"insert":"Normal pressure hydrocephalus can also present with gait and cognitive disturbances. This can be differentiated from WE by the presence of urinary incontinence and suggestive signs on brain MRI, such as ventricular enlargement and dilated Sylvian fissures.\n"}]}
{"ops":[{"insert":"Central nervous system infection\n"}]}
{"ops":[{"insert":"Central nervous system infection can present with hypotension, gait abnormalities and ocular disturbances. This can be differentiated from WE by the presence of abnormalities in cerebrospinal fluid (decreased glucose, increased proteins and white blood cells), elevated inflammatory markers, and clinical signs of sepsis and meningism.\n"}]}
{"ops":[{"insert":"Brain tumors\n"}]}
{"ops":[{"insert":"Brain tumors can also present with gait abnormalities and ocular disturbances. This can be differentiated from WE by the presence of space occupying lesions on neuroimaging.\n"}]}
{"ops":[{"insert":"Guillain-Barr\u00e9 syndrome\n"}]}
{"ops":[{"insert":"Guillain-Barr\u00e9 syndrome can present with a peripheral ascending motor and sensory neuropathy. Miller-Fisher syndrome, a rare variant of Guillain-Barr\u00e9 syndrome, "},{"insert":"can be even more similar, with ophthalmoplegia and ataxia. ","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"These syndromes can be differentiated from WE by the presence of"},{"insert":" areflexia or bulbar symptoms, and the ","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"absence of abnormalities in the basal ganglia on MRI of the brain.\n"}]}
{"ops":[{"insert":"Korsakoff syndrome\n"}]}
{"ops":[{"insert":"Korsakoff syndrome can also present with memory impairment. This can be differentiated from WE by the presence of provoked confabulation. If left untreated, WE may lead to Korsakoff syndrome.\n"}]}
{"ops":[{"insert":"Hepatic encephalopathy\n"}]}
{"ops":[{"insert":"Hepatic encephalopathy can also present with altered mental status. This can be differentiated from WE by the presence of history of hepatic disease, asterixis and extrapyramidal dysfunction, and the absence of ocular signs.\n"}]}
{"ops":[{"insert":"Stroke\n"}]}
{"ops":[{"insert":"Stroke can also present with gait abnormalities and ocular disturbances. This can be differentiated from WE by the presence of hemorrhage or ischemia on brain imaging. Brain ischemia be apparent on MRI of the brain or several days afterwards, on CT brain images.\n"}]}
{"ops":[{"insert":"Alcohol withdrawal syndrome\n"}]}
{"ops":[{"insert":"Alcohol withdrawal syndrome can also present with altered mental status, gait abnormalities, ocular disturbances, and seizures. This can be differentiated from WE by a history of alcohol abuse with recent reduction or abrupt cessation in alcohol consumption.\n"}]}
{"ops":[{"insert":"Normal pressure hydrocephalus\n"}]}
{"ops":[{"insert":"Normal pressure hydrocephalus can also present with gait and cognitive disturbances. This can be differentiated from WE by the presence of urinary incontinence and suggestive signs on brain MRI, such as ventricular enlargement and dilated Sylvian fissures.\n"}]}
{"ops":[{"insert":"Central nervous system infection\n"}]}
{"ops":[{"insert":"Central nervous system infection can present with hypotension, gait abnormalities and ocular disturbances. This can be differentiated from WE by the presence of abnormalities in cerebrospinal fluid (decreased glucose, increased proteins and white blood cells), elevated inflammatory markers, and clinical signs of sepsis and meningism.\n"}]}
{"ops":[{"insert":"Brain tumors\n"}]}
{"ops":[{"insert":"Brain tumors can also present with gait abnormalities and ocular disturbances. This can be differentiated from WE by the presence of space occupying lesions on neuroimaging.\n"}]}
{"ops":[{"insert":"Guillain-Barr\u00e9 syndrome\n"}]}
{"ops":[{"insert":"Guillain-Barr\u00e9 syndrome can present with a peripheral ascending motor and sensory neuropathy. Miller-Fisher syndrome, a rare variant of Guillain-Barr\u00e9 syndrome, "},{"insert":"can be even more similar, with ophthalmoplegia and ataxia. ","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"These syndromes can be differentiated from WE by the presence of"},{"insert":" areflexia or bulbar symptoms, and the ","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"absence of abnormalities in the basal ganglia on MRI of the brain.\n"}]}

Investigations - Diagnosis

Fact Explanation
{"ops":[{"insert":"MRI brain\n"}]}
{"ops":[{"insert":" MRI can be used to support the diagnosis of acute WE, and to monitor recovery; it cannot be used to exclude WE. Typical imaging findings include symmetric lesions in the thalami, mamillary bodies, tectal plate and periaqueductal region. Lesions may also be seen in the cerebellum, cranial nerve nuclei, and cerebral cortex. The appearance of these lesions differs based on disease severity, acuteness of the disease, and timing of imaging. Note that contrast enhancement of the thalamus and mamillary bodies is generally associated with alcoholism.\n"}]}
{"ops":[{"insert":"CT brain\n"}]}
{"ops":[{"insert":"CT imaging of the brain may show areas of reduced attenuation in the periaqueductal grey matter and medial portion of the thalami. That said, CT is often normal in the acute phase.\n"}]}
{"ops":[{"insert":"Metabolic panel\n"}]}
{"ops":[{"insert":"A comprehensive metabolic panel is important to exclude other causes of central nervous system abnormalities.\n"}]}
{"ops":[{"insert":"Thiamine levels\n"}]}
{"ops":[{"insert":"Thiamine levels may be measured by high-performance liquid chromatography (HPLC). This should be performed before the administration of thiamine. It is important to appreciate that rarely, WE can occur in the presence of normal thiamine levels\u2014 for example, when the thiamine transporter gene mutation is present.\n"}]}
{"ops":[{"insert":"MRI brain\n"}]}
{"ops":[{"insert":" MRI can be used to support the diagnosis of acute WE, and to monitor recovery; it cannot be used to exclude WE. Typical imaging findings include symmetric lesions in the thalami, mamillary bodies, tectal plate and periaqueductal region. Lesions may also be seen in the cerebellum, cranial nerve nuclei, and cerebral cortex. The appearance of these lesions differs based on disease severity, acuteness of the disease, and timing of imaging. Note that contrast enhancement of the thalamus and mamillary bodies is generally associated with alcoholism.\n"}]}
{"ops":[{"insert":"CT brain\n"}]}
{"ops":[{"insert":"CT imaging of the brain may show areas of reduced attenuation in the periaqueductal grey matter and medial portion of the thalami. That said, CT is often normal in the acute phase.\n"}]}
{"ops":[{"insert":"Metabolic panel\n"}]}
{"ops":[{"insert":"A comprehensive metabolic panel is important to exclude other causes of central nervous system abnormalities.\n"}]}
{"ops":[{"insert":"Thiamine levels\n"}]}
{"ops":[{"insert":"Thiamine levels may be measured by high-performance liquid chromatography (HPLC). This should be performed before the administration of thiamine. It is important to appreciate that rarely, WE can occur in the presence of normal thiamine levels\u2014 for example, when the thiamine transporter gene mutation is present.\n"}]}

Investigations - Management

Fact Explanation
{"ops":[{"insert":"Magnesium\n"}]}
{"ops":[{"insert":"Magnesium deficiency can impair recovery, especially in alcoholics.\n"}]}
{"ops":[{"insert":"Echocardiography\n"}]}
{"ops":[{"insert":"Echocardiography may show a reduced ejection fraction. This indicates \u201cwet\u201d beriberi.\n"}]}
{"ops":[{"insert":"Magnesium\n"}]}
{"ops":[{"insert":"Magnesium deficiency can impair recovery, especially in alcoholics.\n"}]}
{"ops":[{"insert":"Echocardiography\n"}]}
{"ops":[{"insert":"Echocardiography may show a reduced ejection fraction. This indicates \u201cwet\u201d beriberi.\n"}]}

Management - Supportive

Fact Explanation
{"ops":[{"insert":"Magnesium\n"}]}
{"ops":[{"insert":"If present, magnesium deficiency should be treated. Not doing so will impair recovery.\n"}]}
{"ops":[{"insert":"Dietary consult\n"}]}
{"ops":[{"insert":"Most patients are usually frail and malnourished. A dietician should assess calorie needs and provide a dietary plan that correctly supplies food and thiamine.\n"}]}
{"ops":[{"insert":"Magnesium\n"}]}
{"ops":[{"insert":"If present, magnesium deficiency should be treated. Not doing so will impair recovery.\n"}]}
{"ops":[{"insert":"Dietary consult\n"}]}
{"ops":[{"insert":"Most patients are usually frail and malnourished. A dietician should assess calorie needs and provide a dietary plan that correctly supplies food and thiamine.\n"}]}

Management - Specific

Fact Explanation
{"ops":[{"insert":"Thiamine\n"}]}
{"ops":[{"insert":"Once the diagnosis of WE is suspected, thiamine should be administered intravenously (IV) over 30 minutes, diluted in 50-100 mL of normal saline. The optimal dosage regimen is unclear, but many authors recommend 500 mg three times daily. Note that thiamine should be given before any carbohydrates are administered. Treatment should be continued until there is no further clinical improvement. Oral thiamine is not"},{"insert":" ","attributes":{"color":"#212529"}},{"insert":"absorbed "},{"insert":"adequately ","attributes":{"color":"#212529"}},{"insert":"and should not be used in the treatment of these patients.\n"}]}
{"ops":[{"insert":"Normal diet\n"}]}
{"ops":[{"insert":"A normal diet (without nutrient restrictions) should be instituted immediately after thiamine therapy. It may be necessary to progressively increase nutrient and calorie intake due to the risk of refeeding syndrome in malnourished patients. \n"}]}
{"ops":[{"insert":"Alcohol cessation\n"}]}
{"ops":[{"insert":"Patients should be advised to stop consuming alcohol. Professional help may aid in alcohol cessation.\n"}]}
{"ops":[{"insert":"Thiamine\n"}]}
{"ops":[{"insert":"Once the diagnosis of WE is suspected, thiamine should be administered intravenously (IV) over 30 minutes, diluted in 50-100 mL of normal saline. The optimal dosage regimen is unclear, but many authors recommend 500 mg three times daily. Note that thiamine should be given before any carbohydrates are administered. Treatment should be continued until there is no further clinical improvement. Oral thiamine is not"},{"insert":" ","attributes":{"color":"#212529"}},{"insert":"absorbed "},{"insert":"adequately ","attributes":{"color":"#212529"}},{"insert":"and should not be used in the treatment of these patients.\n"}]}
{"ops":[{"insert":"Normal diet\n"}]}
{"ops":[{"insert":"A normal diet (without nutrient restrictions) should be instituted immediately after thiamine therapy. It may be necessary to progressively increase nutrient and calorie intake due to the risk of refeeding syndrome in malnourished patients. \n"}]}
{"ops":[{"insert":"Alcohol cessation\n"}]}
{"ops":[{"insert":"Patients should be advised to stop consuming alcohol. Professional help may aid in alcohol cessation.\n"}]}

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