While there are known sequelae in these patients, they may initially present with nonspecific symptoms such as anorexia, abdominal discomfort, fatigue, irritability, and precordial pain. Other early signs may include memory loss and sleep changes.

Neurologic

There are two components of neurologic complications which include peripheral neurologic deficits as well as central impairment. The former manifests in a stocking-glove distribution especially in the lower extremities. Specifically, the clinical picture consists of toe paresthesias, burning in the feet, calf muscles cramping, leg pain, and plantar dysesthesias. Persistent thiamine insufficiency leads to the progression of these symptoms as well as upper extremity involvement.

Patients with Wernicke encephalopathy exhibit psychomotor trouble in addition to an altered mental status with an impaired consciousness that may proceed to coma and even death if not treated.

Korsakoff psychosis emerges as confusion, amnesia of recent events, trouble with speaking, and confabulation.

Cardiovascular

Patients with acute heart failure experience peripheral and pulmonary edema. Moreover, they present with signs and symptoms such as orthopnea, diaphoresis, and warm skin.

Infantile condition

In very young infants receiving low thiamine breast milk, the consequences include rapid onset of heart failure and aphonia. Furthermore, they characteristically exhibit a loss of deep tendon reflexes.

Physical exam

In terms of the neurologic exam, remarkable findings include calf muscle tenderness and decreased vibratory sense in the toes. Additionally, these patients may encounter trouble with changing positions between squatting and standing.

A mental status exam is crucial as it reveals evidence of Wernicke-Korsakoff syndrome in those affected with it.

Patients with cardiovascular involvement are notable for features such as tachycardia, wide pulse pressure, evidence of edema, and other related findings. Cases with severe vasodilation can result in shock.

• Fever

  […] leads to lactate production) CAUSES inadequate intake (alcoholics, diet, starvation) decreased absorption (intestinal disease, alcoholism, malnutrition, gastric bypass, folate deficiency) increased consumption (hyperthyroidism, pregnancy, lactation, fever [lifeinthefastlane.com]

  There was a massive number of deaths as a result of fevers such as malaria and beriberi. A decoction of the leaves were used for beriberi. [dictionary.cambridge.org]

  ‘The troops suffered from malaria, dengue fever, beriberi, hookworm and pellagra.’ ‘Diseases such as beriberi and malaria have become more common as problems with sanitation have increased.’ [en.oxforddictionaries.com]

  It is hardly necessary to speak of the success which the Japanese had in preventing the spread of the infectious diseases of known origin, such as typhoid fever and dysentery, for this is common knowledge, but it is perhaps not widely known that, at a [jamanetwork.com]

• Fatigue

  All three reported that they experienced a relief in their fatigue during the second survey—and two had a complete remission of their fatigue! [thyroidpharmacist.com]

  At first, people have vague symptoms such as fatigue and irritability, but a severe deficiency (beriberi) can affect the nerves, muscles, heart, and brain. The diagnosis is based on symptoms and a favorable response to thiamin supplements. [merckmanuals.com]

  They can include fatigue, irritability, sleep disturbances and even abdominal discomfort – all symptoms that can easily describe a host of other conditions and ailments. There are two types of beriberi. [livestrong.com]

  While there are known sequelae in these patients, they may initially present with nonspecific symptoms such as anorexia, abdominal discomfort, fatigue, irritability, and precordial pain. Other early signs may include memory loss and sleep changes. [symptoma.com]

• Anemia

  Individuals with thiamine-responsive megaloblastic anemia syndrome begin to show symptoms of megaloblastic anemia between infancy and adolescence; they also develop hearing loss caused by abnormalities of the inner ear during early childhood. [flipper.diff.org]

  […] man with a history of partial gastrectomy presented to the emergency department with subacute gait instability associated with painful dysesthesias and clumsiness in both hands. 10 years before presentation he had received a diagnosis of megaloblastic anemia [ncbi.nlm.nih.gov]

  Anemia is particularly prevalent among refugee children. [web.archive.org]

  One of a few follow-up original articles that investigates the mechanisms of salt and water retention in chronic severe anemia. PubMed Google Scholar 11. Fowler NO, Holmes JC: Blood viscosity and cardiac output in acute experimental anemia. [doi.org]

• Epilepsy

  CONCLUSIONS: Our findings indicate that severe infantile thiamine deficiency may result in epilepsy. [ncbi.nlm.nih.gov]

  There was a high incidence of epilepsy and four patients were hypothermic. The diagnosis of Wernicke's encephalopathy may be missed at necropsy unless the brain is examined histologically. [doi.org]

  Treatment initiated later in the disease course or lack of treatment may result in death or chronic neurologic sequelae including dystonia, quadriparesis, epilepsy, or mild intellectual disability may ensue. Prevalence Prevalence is unknown. [web.archive.org]

• Hypothermia

  Beriberi, also caused by thiamine deficiency, accounted for his tachycardia, polyneuropathy, areflexia, hypothermia and biochemical abnormalities. [casereports.bmj.com]

  […] impaired consciousness and problems of eye movement Korsakoff’s Psychosis – loss of memory for both new (anterograde) and past (retrograde) events together with confabulation, making up a version of events to cover for the loss of memory Other features – hypothermia [stewartnutrition.co.uk]

  ( 28733807 ) 2017 25 A patient with a 'typical presentation' of Wernicke encephalopathy was found to have sporadic Creutzfeldt-Jakob disease. ( 28653943 ) 2017 26 Fundus Findings in Wernicke Encephalopathy. ( 28924437 ) 2017 27 Hypothermia Presenting [malacards.org]

  At age 53 began an acute condition with intense hypothermia, hyperhidrosis and lethargy, without fever. Was initially mistaken with a respiratory infection. [enfermedad-de-wernicke.weebly.com]

  The differential diagnosis of lactic acidosis includes not only thiamine deficiency, but all causes of inadequate tissue perfusion (e.g., sepsis and hypovolemia), all causes of hypoxia (e.g., hypothermia and strenuous exercise), and several systemic disorders [cdc.gov]

• Dyspnea

  Symptoms: dyspnea, paresthesias and leg pain. Infant: sudden death at 30 days of age after 24 hours of crying, then dysphonia and unable to suck, dyspnea then cyanosis. He had liquid stools but no fever. [ncbi.nlm.nih.gov]

  Wet beriberi is characterized by: Increased heart rate Vasodilation leading to decreased systemic vascular resistance, and high output heart failure Elevated jugular venous pressure Dyspnea (shortness of breath) on exertion Paroxysmal nocturnal dyspnea [en.wikipedia.org]

  Design, Setting, and Participants The illness was defined as acute onset of lower limb edema, with dyspnea, chest pain, palpitations, nausea, vomiting, abdominal pain, or headache. [doi.org]

• Cough

  He has a cough that recently started. He is poorly kempt, unshaven, and wearing a bathrobe. He does not cooperate with a neurological exam. On physical exam you note the findings in Figure A. The patient's skin is dry and unwashed. [medbullets.com]

  The child was anuric, no liquid stools, no fever, no cough. File N°153. [ncbi.nlm.nih.gov]

  Weijing Tang with coix, persica, benincasa, and phragmites; used for cough with pulmonary abscess. [web.archive.org]

• Hypotension

  A 72-year-old woman became profoundly hypotensive and hypothermic 10 hours after undergoing a panniculectomy. [ncbi.nlm.nih.gov]

  […] consciousness and problems of eye movement Korsakoff’s Psychosis – loss of memory for both new (anterograde) and past (retrograde) events together with confabulation, making up a version of events to cover for the loss of memory Other features – hypothermia, hypotension [stewartnutrition.co.uk]

  Lactic acidosis, hypotension, and muscle wasting characterize dry beriberi. [todaysdietitian.com]

  Case Presentation A 4-year-old boy with a history of medulloblastoma status-post partial resection and port placement presented to the PICU with fever, hypotension, and tachycardia. His mentation was normal. [pediatrics.aappublications.org]

• Gallop Rhythm

  The apex of the heart is displaced to the left so hat it may reach the axilla and it is easily felt; there are usually systolic 'flow' murmurs and a third heart sound giving a 'galloping' rhythm that is accentuated when the patient lies on the left side [web.archive.org]

  rhythm on auscultation, hepatomegaly), associated with a positive squat test (unable to rise after squatting) [2]. [ncbi.nlm.nih.gov]

  rhythm on auscultation, hepatomegaly), associated with a positive squat test (unable to rise after squatting) [ 2 ]. [journals.plos.org]

• Sweating

  The first effects are vasodilation, tachycardia, a wide pulse pressure, sweating, warm skin, and lactic acidosis. Later, heart failure develops, causing orthopnea and pulmonary and peripheral edema. [merckmanuals.com]

• Pruritus

  There was no history of fever, pruritus of hand and feet, headache, hypertension, oliguria, edema, and visual disturbances. [ijnpnd.com]

• Hyperhidrosis

  At age 53 began an acute condition with intense hypothermia, hyperhidrosis and lethargy, without fever. Was initially mistaken with a respiratory infection. [enfermedad-de-wernicke.weebly.com]

• Muscle Weakness

  Symptoms include vomiting, seizures, muscle weakness, loss of muscle function in the legs, and mental confusion. Wet beriberi, which affects the cardiovascular system. [kidshealth.org]

  weakness, paralysis, and death. [thiamine.dnr.cornell.edu]

  Thiamin deficiency can cause loss of weight and appetite, confusion, memory loss, muscle weakness, and heart problems. [web.archive.org]

• Confusion

  It is characterized by a classical clinical triad of symptoms: ocular impairment, cerebellar dysfunction, and confusion. [ncbi.nlm.nih.gov]

  Classically, Wernicke encephalopathy is characterized by confusion (encephalopathy), ataxia, and nystagmus. Korsakoff syndrome is a more severe finding that includes confabulations. [pixorize.com]

  Typhoid, malaria, pneumonia and septicaemia are commonly confused with this form of beriberi. Aphonic beriberi The peak prevalence is in 4-6 month old children. [web.archive.org]

  Symptoms Wet beriberi: •Shortness of breath with activity •Mental confusion •Awakening at night short of breath •Increased heart rate (tachycardia) •Swelling of the legs •Muscolar atrophy •Edema •Peripheral neuropathy Dry beriberi: •Mental confusion and [flipper.diff.org]

  Neurologically, she had mild confusion, with almost complete ophthalmoplegia and vertical nystagmus, normosthenia, normoreflexia, distal apallesthesia and abatesthesia, and truncal ataxia. [n.neurology.org]

• Ataxia

  We report four cases of childhood ataxia with and without encephalopathies which were successfully managed with thiamine supplementation and diagnosed in retrospect as being caused by thiamine deficiency. [ncbi.nlm.nih.gov]

  Syndromes such as beriberi, Wernicke’s disease, Leigh’s disease, African Seasonal Ataxia, and various inherited ataxias, have all benefited from improved scientific approaches. [books.google.com]

• Nystagmus

  Moreover, quantitative data has shown decreased horizontal vestibulo-ocular reflex (VOR) gain and nystagmus, with a favorable response to timely treatment. [ncbi.nlm.nih.gov]

  Classically, Wernicke encephalopathy is characterized by confusion (encephalopathy), ataxia, and nystagmus. Korsakoff syndrome is a more severe finding that includes confabulations. [pixorize.com]

  […] to have enough dihydrofolate reductase to regenerate NADH) CLINICAL FEATURES Dry Beri-Beri bilateral, peripheral sensory and motor neuropathy with weakness and hyporeflexia Wernicke encephalopathy altered mental state ophthalmoplegia with horizontal nystagmus [lifeinthefastlane.com]

  Thiamine deficiency as a possible diagnosis with just documentation of Alcohol dependence/withdrawal and the initiation of CIWA/thiamine administration or would you wait to query until documentation of other clinical indicators (irritability, depression, nystagmus [forums.acdis.org]

• Peripheral Neuropathy

  In addition to WKS, thiamine deficiency may also result in beriberi, a cardiac and peripheral nervous system disease, and it has been implicated in the pathogenesis of cerebellar degeneration and peripheral neuropathy. [ncbi.nlm.nih.gov]

  Later, patients experience weakness, peripheral neuropathy, headache, and tachycardia. [fpnotebook.com]

  However, several months are required for peripheral neuropathy. [flipper.diff.org]

  Both types cause peripheral neuropathy (numbness and tingling of the hands and feet). Dry beriberi also has the symptoms of weakness, nerve degeneration, irritability, poor arm/leg coordination, and loss of nerve transmission. [sharecare.com]

• Paresthesia

  This patient illustrates that eating disorders can be an uncommon cause of rapidly progressive paresthesias, weakness, and neurological decline due to thiamine deficiency. [ncbi.nlm.nih.gov]

  Pregnancy: pain and paresthesia of upper and lower extremities. The symptoms increased after delivery. [journals.plos.org]

The clinical assessment consists of retrieving the medical and social history (including dietary and alcoholic intake) of the patient, performing a physical exam with a focus on cardiovascular and neurologic systems, and observing a therapeutic response to thiamine. It is important for a clinician to develop a high index of suspicion based on the understanding of the risk factors as well as the patient's history and physical exam.

The confirmatory method for diagnosis of this nutritional disorder is the successful response to thiamine correction. Note that this observation along with electrolyte measurements will help exclude differential diagnoses that present similarly to thiamine deficiency such as diabetes, vitamin B12 deficiency, and metal toxicities.

In cases with uncertainty, levels of serum thiamine, pyruvate lactate, alpha-ketoglutarate, and glyoxylate, as well as urinary thiamine can be obtained.

• Thiamine Decreased

  Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure. Liver thiamine stores are reduced due to hepatic steatosis or fibrosis. [en.wikipedia.org]

The therapeutic approach is to replace thiamine. Generally, it is crucial to administer 100mg thiamine in alcoholics and malnourished patients prior to providing intravenous glucose therapy.

With regards to Wernicke-Korsakoff syndrome, the recommended regimen is treatment with 50 to 100mg thiamine intravenous (IV) or intramuscular (IM) to be administered twice a day for several days. This is followed by 10mg to 20mg daily until a successful response is achieved. Korsakoff psychosis may take up to 3 months for recovery.

Other

Intake of the offending substance, alcohol, should be discontinued while the clinician monitors for alcohol withdrawal syndrome in these patients. Also, since alcohol cessation is difficult, the clinician should provide alcoholic patients with educational and community resources to help tackle this challenge.

Cardiovascular disease should also be addressed promptly in order to control the current manifestations and prevent further deterioration.

Finally, patients should consume a well-balanced diet with adequate levels of vitamins including thiamine. Furthermore, other B vitamins and water-soluble vitamins should be supplemented since deficiencies of these vitamins often coexist with thiamine deficiency.

While this easily treatable vitamin abnormality can be life-threatening, it is associated with a good prognosis if therapy is initiated in the early stage of the disease. Once Wernicke-Korsakoff syndrome manifests, this severe degree of damage can be irreversible. Although improvement can occur with thiamine administration. Specifically, Korsakoff psychosis is improved in 1 to 3 months although the neurologic features do not typically completely recover. Furthermore, ophthalmoplegia resolves within a day of treatment.

With regards to cardiovascular complications, thiamine replacement produces symptomatic improvement of acute cardiac failure within 12 hours of therapy while function and size are usually restored in 24 to 48 hours.

This nutritional disorder has an impact on the quality of life since it produces a state of low energy. Therefore, patients struggle with accomplishing normal daily activities.

Thiamine deficiency is more common in geographical areas with high consumption of food sources that are lacking in thiamine. Examples include highly processed foods, white cereals, polished white rice, white sugar and wheat flour. Additionally, foods that contain thiaminase such as raw shellfish, raw freshwater fish, and milled rice can lead to a significant deficiency in this vitamin. Furthermore, food with anti-thiamine factors like betel nuts, coffee, and tea can destroy thiamine. In contrast, poor intake of food rich in thiamine such as meat, fish,and vegetables also contribute to this nutritional disorder [3].

There are patient profiles that increase the risk for this condition, which tends to be those with a history of alcoholism, starvation, or gastric bypass surgery, with the latter resulting from diets restricted to reduced calories (600 to 900 kcal/day) [4] [5] [6]. Furthermore, patients receiving parenteral nutrition lacking thiamine replacement are at risk for developing this nutritional abnormality [7]. as well as persons receiving peritoneal dialysis without thiamine correction, and patients treated with intravenous fluids containing high levels of glucose.

While the epidemiologic data on thiamine deficiency is not established, it is known that vitamin insufficiency is more predominant in developing countries.

Additionally, this disorder occurs in individuals with chronic alcohol consumption, those who are severely malnourished, as well as persons with health states conducive to low-calorie intake and special diets.

Neurologic effects

Thiamine, an essential co-factor in key metabolic pathways, is found in all cells. Physiologically diminished levels of this vitamin result in the impairment of thiamine-dependent enzymes and mitochondrial function. Hence, the effects of thiamine shortage are devastating on all organs, especially that of the brain [8]. as neuronal death is a consequence of energy compromise at sites of increased metabolic requirements and thiamine turnover [9]. Specifically, this insufficiency leads to the degeneration of the mammillary bodies, thalamic nucleus, periaqueductal gray matter [10]., cerebral cortex, hippocampus, the fornices, and the areas surrounding the third ventricle [11]. This disorder also affects the structures on the floor of the fourth ventricle including the cerebellar vermis, vestibular nuclei, and the ocular motor nuclei [10].

Since the memory circuits are affected [12]., alcoholics are predisposed to develop Wernicke-Korsakoff syndrome. Specifically, this complication is a combination of Wernicke encephalopathy and Korsakoff psychosis. The former likely occurs in response to an acute deficiency of thiamine superimposed on the long-term deficit of the vitamin while the latter stems from chronic deprivation. Frequently, Korsakoff syndrome is preceded by Wernicke encephalopathy.

Additionally, there is a decline in cerebral perfusion as thiamine is a key factor in cerebral metabolism.

Cardiovascular effects

The cardiac structure and function can undergo serious alterations as a result of fluid entering the interstitial spaces resulting in the swelling of the muscle fibers and the dilation of the heart. Furthermore, peripheral edema secondary to vasodilation is likely to occur as well as increased arteriovenous blood shunting. These events culminate into high output cardiac failure.

Education is available to guide the public about adequate nutrition. It is imperative that people consume nutritionally balanced meals including the daily requirements of vitamins.

Those at risk for this condition such as alcoholics and anorexic individuals should be encouraged to address these serious issues to prevent thiamine deficiency and the many other serious health risks associated with these starved states.

Additionally, since patients post-gastric bypass typically consume low-calorie diets, they should be receiving thiamine supplementation. Furthermore, patients receiving parenteral nutrition also warrant thiamine therapy.

Finally, since this disorder can cause infant death, pregnant and lactating mothers should be educated about thiamine-rich diets and their effects on their infants.

Thiamine deficiency emerges primarily from the lack of thiamine, which is attributed to either the scarcity of this vitamin in available food or inadequate intake of thiamine-enriched foods. Additionally, states such as chronic alcoholism, starvation and other health related conditions are chief risk factors for developing this vitamin deficiency.

Since thiamine is critical for metabolism, its insufficiency is detrimental to the normal function of the brain, heart, and nerves. Severe complications include Wernicke encephalopathy and Korsakoff psychosis, which arise particularly in alcoholics [1] [2]. that manifest as cerebral impairment. Further sequelae of thiamine deficiency include peripheral nerve deficits, acute heart failure, and infantile death.

Diagnosis is achieved through careful assessment of the patient's history and risk factors, clinical picture (which should raise suspicion for this condition), and physical exam. Furthermore, the diagnosis is confirmed by the patient's successful therapeutic response to thiamine replacement. In cases where the diagnosis is inconclusive, there are blood and urine tests that can confirm the diagnosis.

Thiamine supplementation is the key treatment for these patients. It is initially administered in high doses and then tapered after a few days. Since it is highly likely that other vitamins abnormalities are also present, these should be corrected as well. Finally, another component in the management plan is alcohol cessation among alcoholics.

What is thiamine?

Thiamine is another name for vitamin B1, which is found in many foods. Thiamine is used in all cells and is required for the metabolism of carbohydrates and the production of energy. It is necessary for normal functioning of the brain, heart, muscle and the nerves.

Thiamine is found in meat, fish, vegetables, etc.

Who develops thiamine deficiency?

Individuals with low thiamine diets tend to develop this condition. The following foods have low amounts of thiamine:

• White cereals
• Polished rice
• White flour
• White sugar
• Highly processed foods

Foods that contain enzymes and factors that degrade thiamine can cause this as well. Examples include:

• Raw shellfish
• Raw freshwater fish
• Milled rice
• Betel nuts
• Coffee
• Tea

Individuals with the following conditions can develop thiamine deficiency:

• Alcoholism
• Starvation
• Gastric bypass surgery

What are the signs and symptoms of thiamine deficiency?

Early symptoms may include:

• Anorexia
• Abdominal discomfort
• Fatigue
• Irritability
• Memory loss
• Sleep disturbance

The main complications of thiamine deficiency include peripheral nerve deficits, Wernecke-Korsakoff syndrome, and heart failure.

Symptoms of peripheral nerve include:

• Toe numbness and tingling
• Burning in the feet
• Cramping of the calf muscles
• Leg pain
• Possible arm involvement as well

Signs of Wernicke-Korsakoff syndrome include:

• Changes in the mental status such as loss of consciousness
• Loss of memory of recent events
• Difficulty with speaking
• Difficulty with balance
• Coma that may progress to death

Signs of heart failure include:

• Fluid build-up in the legs
• Fluid build-up the lungs
• Difficulty breathing
• Shortness of breath

How is this diagnosed?

The clinician will obtain a full history of the patient including details about the alcohol and food consumption. Also, the clinician will examine the patient thoroughly. The clinical picture will be indicative of the thiamine deficiency.

The best method to confirm this condition is by treating it with thiamine and achieving improvement.

There are blood and urine tests that can be performed to confirm the condition if necessary.

How is this treated?

Replacing thiamine is the main treatment of this deficiency. The first few days will require high amounts of thiamine which can then be decreased to lower doses. Also, since these patients may lack other vitamins, those should be corrected as well.

Note that alcohol should be stopped altogether. Furthermore, since quitting alcohol intake is difficult and challenging, these individuals should be receiving resources to help them through their journey.

How can this be prevented?

Public health education should include information on healthy diets and nutritious meals. Pregnant and breastfeeding women should also receive education on what constitutes a thiamine-rich diet and how this impacts their infants.

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2. Kopelman MD, Thomson AD, Guerrini I, et al. The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol Alcohol. 2009; 44(2):148-54.
3. McGready R, Simpson JA, Cho T, et al. Postpartum thiamine deficiency in a Karen displaced population. American Journal of Clinical Nutrition. 2001;74(6):808-13.
4. Masumoto K, Esumi G, Teshiba R, et al. Need for thiamine in peripheral parenteral nutrition after abdominal surgery in children. Journal of Parenteral and Enteral Nutrition. 2009; 33(4):417-22.
5. Matrana MR, Davis WE. Vitamin deficiency after gastric bypass surgery: a review. Southern Medical Journal. 2009; 102(10):1025-31.
6. Ahmed A, Daida Y, Novotny R. PS2-02: Micronutrient Deficiencies After Bariatric Surgery: Does Ethnicity Matter?. Clinical Medicine and Research. 2001; 9(3-4):165.
7. Francini-Pesenti F, Brocadello F, Manara R, et al. Wernicke's syndrome during parenteral feeding: not an unusual complication. Nutrition. 2009; 25(2):142-6.
8. Hoffman-LaRoche F. Vitamins (Basics). New York: Seaboard Lithographers; 1994.
9. Hazell AS, Todd KG, Butterworth RF. Mechanisms of neuronal cell death in Wernicke's encephalopathy. Metabolic Brain Disease. 1998;13(2):97-122.
10. Baker KG, Harding AJ, Halliday GM, et ak. Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy. Neuroscience. 1999;91(2):429-38.
11. Torvik A. Brain lesions in alcoholics: neuropathological observations. Acta Medica Scandinavica Supplementum. 1987;717:47-54.

12. Kessels RP, Kortrijk HE, Wester AJ, et al. Confabulation behavior and false memories in Korsakoff's syndrome: role of source memory and executive functioning. Psychiatry and Clinical Neurosciences. 2008; 62(2):220-5.