Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management

Summary

Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. According to autopsy-based studies, the disorder is still greatly underdiagnosed in both adults and children. In this review, we provide an update on the factors and clinical settings that predispose to Wernicke's encephalopathy, and discuss the most recent insights into epidemiology, pathophysiology, genetics, diagnosis, and treatment. To facilitate the diagnosis, we classify the common and rare symptoms at presentation and the late-stage symptoms. We emphasise the optimum dose of parenteral thiamine required for prophylaxis and treatment of Wernicke's encephalopathy and prevention of Korsakoff's syndrome associated with alcohol misuse. A systematic approach helps to ensure that patients receive a prompt diagnosis and adequate treatment.

Introduction

Wernicke's encephalopathy is an acute, neuropsychiatric syndrome that is common relative to other neurological disorders. It is characterised by nystagmus and ophthalmoplegia, mental-status changes, and unsteadiness of stance and gait—although this triad is seen in only 16% of patients.1, 2 The disorder results from a deficiency in vitamin B1 (thiamine), which in its biologically active form, thiamine pyrophosphate, is an essential coenzyme in several biochemical pathways in the brain.³ Carl Wernicke described this distinctive entity in 1881 as acute superior haemorrhagic polioencephalitis in two alcohol-misusing men and a young woman who developed persistent vomiting due to pyloric stenosis after the ingestion of sulphuric acid.⁴ The classic triad and fundoscopic changes, consisting of swelling of the optic disks and retinal haemorrhages, were present in these patients.⁴ All of them died within 2 weeks of onset of neurological manifestations.

Campbell and Russell in the 1940s stressed the nutritional association of the encephalopathy and suggested thiamine deficiency as a causative factor.⁵ Thiamine requirement is directly related to both total caloric intake and the proportion of calories provided as carbohydrates.⁶ Thus, high caloric and high carbohydrate diets increase the demand for thiamine. The recommended dose of thiamine for an average, healthy adult is 1·4 mg per day or 0·5 mg of thiamine per 1000 kcal consumed. This dose is higher in children, in critically ill conditions, and during pregnancy and lactation.⁷ Because thiamine is absorbed in the duodenum by a rate-limited process, in healthy individuals, the calculated maximum amount of thiamine that can be absorbed from a single oral dose is about 4·5 mg.⁸ At the blood–brain barrier, transport occurs by both passive and active mechanisms,⁸ which allows a rapid correction of brain thiamine deficiency, mainly by passive diffusion, if a steep concentration gradient between plasma and the brain is established, as happens after parenteral administration of the vitamin.⁸

Although in recent years there has been an increase in the number of clinical settings in which Wernicke's encephalopathy is encountered, this potentially fatal disease is still greatly underdiagnosed in both adults and children. However, major advances have been made in our understanding of the pathophysiology, genetics, prophylaxis, and management of Wernicke's encephalopathy. In this review, we provide an update on these advances, emphasising the predisposing factors, including clinical settings, in which Wernicke's encephalopathy is encountered and offer some new insights into diagnostic and management procedures.