History and exam
Key diagnostic factors
common
history of gastrointestinal (GI) surgery
Bariatric surgery for class 3 (BMI ≥40 kg/m²) obesity can result in thiamine deficiency. Any type of GI surgery may precipitate thiamine deficiency if it results in a reduced mucosal absorptive surface area in the small intestine, as well as sustained post-operative vomiting and reduced dietary intake.[31][34][35][61][62][63]
mental slowing, confusion, impaired concentration, and apathy
Up to 82% of patients with Wernicke's encephalopathy will develop mental status changes.[16] May be erroneously misattributed to alcohol intoxication or withdrawal.
oculomotor signs
Nystagmus is the most common finding in patients with Wernicke's encephalopathy.[71] Other oculomotor findings include gaze palsies, sixth nerve palsies, and impaired horizontal vestibulo-ocular reflexes.
history of alcohol-use disorder
Patients with alcohol-use disorder are at a high risk for developing thiamine deficiency as a result of a combination of factors: poor intake, low content of vitamins in alcohol, low storage capacity of the liver, decreased intestinal absorption, impaired conversion of thiamine to its active form (thiamine pyrophosphate), and increased demand to metabolise the carbohydrates in alcohol.[27]
pre-existing conditions that predispose to malnutrition: for example, HIV/AIDS, cancer, anorexia/bulimia, prolonged vomiting, or diarrhoea
Any medical illness that causes reduced oral intake compounded by inadequate parenteral supplementation or increased metabolic demand can predispose to thiamine deficiency.
uncommon
classic triad: mental status changes, ophthalmoplegia, and gait dysfunction
This classic triad may only be present in up to 16% of patients with Wernicke's encephalopathy; around 19% of patients may present without any classic signs.[16]
Other diagnostic factors
common
uncommon
coma
Seen if untreated or when there are coexistent conditions such as meningitis, head trauma, subdural haemorrhage, or alcohol toxicity.[73]
miosis, anisocoria, light-near dissociation
Rare manifestations, seen in advanced untreated cases.[71]
papilloedema, retinal haemorrhages
May occasionally be a presenting manifestation.[71]
hypothermia or hyperthermia
hearing loss, epileptic seizures, and spastic paraparesis
Risk factors
strong
alcohol-use disorder
In people with alcohol-use disorder, thiamine deficiency is a result of a combination of factors: poor intake, low content of vitamins in alcohol, low storage capacity of the liver, decreased intestinal absorption, impaired conversion of thiamine to its active form (thiamine pyrophosphate), and increased demand to metabolise the carbohydrates in alcohol.[27]
HIV infection and AIDS
Thiamine deficiency has been observed in patients with HIV infection and AIDS.[39][40][41][42] Deficiency has been reported in up to 23% of patients with AIDS, and may also be present in clinically asymptomatic patients with HIV.[39][41] Pathologically confirmed findings suggestive of Wernicke's encephalopathy were seen in 10% of 380 patients with AIDS in one autopsy series.[19]
Thiamine deficiency in these patients most probably results from the cachexia and catabolic state associated with these conditions.[41]
cancer and treatment with chemotherapeutic agents
Thiamine deficiency in the course of cancers and their treatment with chemotherapeutic agents is likely to be caused by a combination of reduced intake due to nausea and a lack of appetite, inadequate parenteral nutrition, significant malabsorption, and increased metabolic demand by cancerous cells.[23]
In a single-centre prevalence study, 55% of patients with cancer referred for psychiatric consultation were found to be thiamine deficient.[59] Gastrointestinal and haematological malignancies are particularly implicated due to means by which they induce inadequate supply of the thiamine (e.g., mucositis, gastrointestinal obstruction, gastrointestinal tract resection) and the increased thiamine consumption of fast-growing cancer cells.[43][44]
Ifosfamide - a chemotherapeutic agent - may interfere with the conversion of thiamine to its active metabolite (thiamine pyrophosphate) or compete with it to cause a functional deficiency mimicking Wernicke's encephalopathy.[45]
malnutrition
Any medical illness that causes reduced dietary intake, or recurrent vomiting and diarrhoea, can cause thiamine deficiency. This may be further compounded by inadequate parenteral nutrition.[9][10][60] The susceptible population includes patients with hyperemesis gravidarum, restrictive eating patterns (e.g., due to anorexia nervosa or bulimia nervosa), and a restricted or unbalanced diet (e.g., secondary to fasting, starvation, or a diet rich in thiaminases or thiamine antagonists).[12][23]
history of gastrointestinal (GI) surgery
Bariatric surgery for class 3 (BMI ≥40 kg/m²) obesity can result in thiamine deficiency. Any type of GI surgery may precipitate thiamine deficiency if it results in a reduced mucosal absorptive surface area in the small intestine, as well as sustained post-operative vomiting and reduced dietary intake.[31][34][35][61][62][63]
weak
genetic variants associated with altered thiamine metabolism and transport
Genetic variants in enzymes and transporters involved in thiamine metabolism have been shown to increase susceptibility to Wernicke's encephalopathy in small case series.[51]
Mutations in four genes are known to cause impairment of thiamine transport and metabolism: SLC19A2 (thiamine transporter-1), SLC19A3 (thiamine transporter-2), SLC25A19 (mitochondrial thiamine pyrophosphate carrier), and TPK1 (thiamine pyrophosphokinase).[52]
bone marrow transplantation
Wernicke's encephalopathy is a rare adverse effect of bone marrow transplantation.[21] This may occur secondary to long-term use of total parenteral nutrition as a result of reduced oral intake. Wernicke's encephalopathy has been reported in 6% of autopsy studies in patients who had undergone bone marrow transplantation.[20]
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