Methods
We searched MEDLINE, EMBASE, and Google Scholar, using MeSH terms (WE, Korsakoff syndrome, beriberi, restrictive weight loss surgery, gastrectomy). There were no language restrictions. Studies published from 1985 to 2017 on bariatric surgery with a diagnosis of WE were included. We reviewed the title and abstract of these articles, and indexed the data for year of publication, age, sex, BMI, onset duration and progression of symptoms, radiographic findings, treatment, and follow-up. All included studies were either case reports or case series, since information on the course of illness and symptomatology was often lacking in all group studies. The maximum number of represented case descriptions in one study was five [
10]. One study reviewed four cases [
11], three studies reviewed three cases [
12‐
14], and eight cases reviewed two cases [
15‐
23]. Cases were excluded if too little information was available to confirm a diagnosis of WE or no clinical characteristics regarding the patient or course of illness were available. Since the collected data is not a random sample of cases, and not likely to be normally distributed, nonparametric statistical procedures were applied (Mann-Whitney
U test for comparison of two independent means, chi-square test for multiple means). The recorded data are either number of patients (percentage) or median (range) as appropriate.
Discussion
Persistent vomiting is a common symptom suggesting a complication after bariatric surgery [
109]. Nausea, vomiting, and a loss of appetite are also common, non-specific symptoms of thiamine deficiency [
8]. Ultimately, vomiting and a loss of appetite are also a preventable cause of thiamine deficiency [
110], leading to Wernicke’s encephalopathy (WE) in the majority of bariatric case reports. Adequate, timely, prophylactic, and substantial thiamine treatment in all patients undergoing bariatric surgery is required to prevent the development of WE, which is a rare but severe complication. The present review highlights that current treatment was neither prophylactic, adequate, timely, nor substantial in the majority of cases, leading to worsening of WE symptoms, the development of additional WE symptoms, and ultimately chronic Korsakoff’s syndrome.
One of the most remarkable findings in the present review is that the initial symptoms of WE are often not recognized as such, leading to a prolonged state of emergent WE. In 31.6% of the cases, the initial symptoms progressed into more severe symptoms, ultimately leading to chronic Korsakoff’s syndrome. Prompt treatment of the first symptoms suggestive of WE with high doses of parenteral thiamine replacement therapy is necessary to prevent further damage [
110]. According to the European Federation of Neurological Societies and the Royal College of Physicians, 500 mg of parenteral thiamine should be given three times daily until symptoms of acute WE resolve [
107]. Interestingly, guidelines for treating WE suggest that patients suspected of WE should already be treated as such [
107,
111]. Additionally, prophylaxis of WE following early signs and symptoms is only achieved by use of parenteral vitamin supplements, since oral supplements are not absorbed in significant amounts [
111]. Moreover, in bariatric surgery, it is always relevant to give prophylactic vitamin therapy, according to international guidelines, to prevent patients from WE.
Of interest, newer methods for bariatric surgery such as sleeve gastrectomy and intragastric ballooning still can lead to WE, despite their relative benefits for the patient. Recently, Armstrong–Javors (2016) pointed out that new techniques lead to the primary risk factor of WE, namely vomiting, despite a theoretical advantage by reducing the stomach volume without bypassing the duodenum [
112]. Suspicion for WE should therefore be equally high in more traditional surgical procedures and newer procedures. Also, the risk of developing WE due to vitamin B
1 deficiency is not restricted to the first half year after surgery but appears to be lifelong, given other factors such as new infections, insufficient meals, or alcohol consumption [
110,
113,
114]. Preventive education on the necessity of sufficient vitamin intake should be given before bariatric surgery is performed and is relevant in long-term follow-up.
Bariatric patients in their teens or twenties are likely to be more protected for mental status change in the course of WE than patients in their thirties or older, as reflected in a younger age of non-mental status change patients. This finding is in line with earlier reports showing that age is the strongest predictor for postoperative delirium [
115,
116]. Importantly, pediatric patients and young adults undergoing bariatric surgery therefore require more attention for sensorimotor problems, such as ataxia and eye movement disorders, besides prophylactic parenteral thiamine treatment. In this specific group, more attention to lifestyle training should be an essential element of treatment, since non-compliance is relatively higher [
50]. Relatively more cognitive reserve in combination with non-compliance can leave symptoms of WE unnoticed for a longer period.
Although eye movement disorders such as nystagmus and ophthalmoplegia were much more common in bariatric cases than those in the general WE population [
113], a higher preoperational BMI was predictive for fewer eye movement disorders. Additionally, male subjects with longer post-bariatric onsets often had no eye movement disorders as a presenting characteristic of WE. It is likely that eye movement disorders represent the most severe form of thiamine deficiency, since it is also the least common phenomenon of the WE triad. Moreover, females are at greater risk for full thiamine depletion than males [
8]. A possible mechanism of action explaining the protective effect of higher weight is a greater storing reserve of thiamine in severely obese patients in comparison with less severely obese patients. This mechanism of action has been referred to as “preferential intracellular thiamine recycling” [
116], leading to relatively less thiamine depletion in patients with higher body weight. Often, cases with WE following anorexia nervosa present themselves first with eye movement disorders [
117], suggesting that this symptom is likely to be the result of full thiamine depletion. This suggests that both patients with lower body weight, and female patients are at greater risk for developing WE, and should guide clinicians in preventive thiamine therapy [
1‐
4,
118].
Radiologic imaging can be employed to support the diagnosis of WE, but is not always sensitive to WE symptomatology. Often, hyperintensities were visible in the thalamic region, the mammillary bodies, and the region around the third and fourth ventricle, in line with previous research on WE [
7]. Our results show that MRI alterations are frequently associated with mental status change, but not the motoric aspects of WE. This finding is relevant, because it suggests that specifically in bariatric patients with motoric problems, such as ataxia or eye movement disorders, WE should be treated despite the outcome of an MRI.
Non-compliance is common in WE patients following bariatric surgery (10.3%) and could be viewed as a more discrete symptom of the disorder. Patients with WE lack insight into their situation, due to the severity of the neurological problems [
108,
110]. Education on the direct adverse consequences of malnourishment should be incorporated into the provision of information before surgery. After surgery, more automated checks on vomiting are relevant.
A limitation of the present review is that we only reviewed case descriptions. Therefore, predictive information regarding prevalence rates and incidence rates is limited. Despite this limitation, the level of detail in the reviewed case studies leads to new insights into WE following bariatric surgery.
Recently published studies on treatment perspectives of WE in general and psychiatric hospitals are alarming: European as well as American studies demonstrated that most patients did not receive thiamine at all or only received it orally in low doses [
119,
120]. Both types of treatment lead to unnecessary cases of chronic Korsakoff’s syndrome characterized by severe amnesia, executive problems, and confabulations, leading to lifelong impairment [
108]. It is therefore important to highlight the clinical signs of symptoms in this specific condition.
In conclusion, there is a growing number of bariatric patients worldwide. Malnourishment-related WE is a rare but severe and preventable consequence of bariatric surgery that warrants attention given its rapid onset and detrimental course. All bariatric procedures can lead to deficiencies and therefore to WE. WE can be fully prevented by supplying prophylactic thiamine given either parenterally in vomiting patients or orally in non-vomiting patients. Mental confusion, eye movement disorders, and ataxia are often missed as crucial symptoms of WE. After the initial onset of symptoms, rapid treatment with high doses of thiamine is still a life-saving measure, directly ameliorating the core symptoms of WE. The large distribution of WE onsets suggests that bariatric patients remain more vulnerable to vitamin B1 deficiency for life, and therefore require lifelong routine follow-up on their B1 status.