Review Article | Open Access
Wernicke Encephalopathy after Sleeve Gastrectomy. A Review of the Literature
Bariatric surgery has been established as the cornerstone of treatment of morbid obesity with good immediate and long-term results. Nutrient deficiencies though, can be an important long-term complication and may lead to hematological, metabolic and especially neurological disorders which are not always reversible. Thiamine (vitamin B1) deficiency has been reported both after restrictive and malabsorptive procedures. The aim of this study is to review all cases that presented with Wernicke Encephalopathy after sleeve gastrectomy.
A review of the literature was conducted to evaluate all sleeve gastrectomies performed till today and caused Wernicke encephalopathy to the patients. Demographic data, operative parameters, postoperative outcomes were collected and assessed.
A total of 13 studies, including 13 patients were analyzed. Patients ranged in age from 17 to 55 years. The onset of Wernicke encephalopathy occurred as early as 3 weeks after surgery to as late as 60 weeks after surgery. When symptoms of Wernicke encephalopathy developed, patients had lost from 19 kg up to 60 kg of body weight.
Bariatric surgery is currently the most effective treatment modality to induce weight loss and ameliorate the various comorbidities of obesity 1, 2. However, bariatric interventions induce major changes in the anatomy and physiology of the gastrointestinal tract thus can be responsible for quite a range of side-effects, including nutritional deficiencies. Bariatric operations traditionally are divided to restrictive, malabsorptive or combined according to the mechanism they induce weight-loss. Malabsorptive procedures have been reported as having more sustainable long-term results in terms of weight loss and amelioration of related comorbidities compared to restrictive procedures, in exchange for more common post-operative nutritional deficiencies 3. Restrictive procedures on the other hand are linked with a progressively attenuated weight-loss and metabolic result but have a more favorable long-term nutritional profile 4,5,6,7
Sleeve gastrectomy is currently the most commonly used bariatric procedure worldwide due to its very good immediate and quite promising long-term results 8, 9,10,4. Concerning its potential long-term nutritional disorders, it has been reported to have a safe profile, with Ferrum, calcium, and vitamin D deficiencies being the most commonly reported problems 7.
The aim of this study is to focus on the thiamine (vitamin B1) deficiency and the ensuing Wernicke encephalopathy which although a rare complication can have grave consequences.
We searched MEDLINE, Ovid, Embase, ISI (Science Citation Index), and Google Scholar independently and in duplicate, using the MeSH terms (Wernicke encephalopathy and bariatric surgery or obesity surgery or sleeve gastrectomy). We reviewed references of all reports for additional cases. We used the related articles link and searched the citations of reports in the ISI Science Citation Index to identify additional reports. We reviewed the full text and the abstracts of these articles and reviewed the data on age, sex, comorbidities, onset duration, weight loss, neurologic findings and outcomes. All of the included studies were case reports. In order to avoid missing data that could be pooled with other long-term deficiencies, we also searched for published reviews of long-term results after sleeve gastrectomy with special interest on nutritional deficiencies.
Included were case reports, case series, or cohort studies describing Wernicke encephalopathy after sleeve gastrectomy. Cases included were those that met the operational case definition of Wernicke encephalopathy, comprising two of the following four symptoms: 1) dietary deficiencies, 2) oculomotor abnormalities, 3) cerebellar dysfunction, and 4) altered mental state or mild memory impairment. We independently reviewed the full text of these articles and abstracted data on age, sex, duration of onset, type of surgery, severity of weight loss, predisposing factors, radiographic findings, unique neurologic features, and outcomes.
We identified 13 Figure 1 case reports. Patient’s demographics and clinical characteristics can be seen in Table 1, Table 2. Briefly, most patients were men (n=7) in their twenties and thirties.11, 12, 13, 14, 15, 16 The onset of Wernicke encephalopathy occurred as early as 2 weeks post-operatively, to as late as 60 weeks after surgery. When symptoms of Wernicke encephalopathy developed, patients had lost from 19 kg up to 60 kg of body weight. The respective data of percentage of excessive weight-loss for each patient were not universally reported.
The triad of WE includes encephalopathy, oculomotor abnormalities and gait ataxia. This triad was reported in five of identified SG cases.14, 15, 16, 17, 18 The most common sign was altered mental status.14, 15, 16, 18, 19 However, WE can be underestimated because not all of the elements are present at the onset of the disease. The symptoms of subclinical thiamine deficiency include fatigue and lethargy as reported in most cases. Other atypical clinical signs and symptoms are peripheral neuropathy, vestibular dysfunction, dysphagia and depression.Table 1. Obese patients’ demographics
|Author||Sex/age||Onset ( wk )||Neurologic deficits||Thiamine levels||BMI * (weight loss-kg)||Comorbidities|
|Cerruti et al. 11||M 33||18||Paresthesia, dysarthria||-||47(60)||-|
|Jeong et al. 12||M 24||60||dysarthria||15nmol/L (20-50)||47,1( 60)||DM**, HTN±|
|Makarewicz et al. 17||F 38||4||Paresis of left tibial nerve, loss of sensation||-||62||DM, HTN|
|Moize et al. 33||F 35||8||-||11ng(35-91)||49,8 (19,5)||DM, HTN|
|Scarano et al. 34||F 27||12||Lower limb paresthesia||Urine 22mg (40-90)||43,7||-|
|Sharabi et al. 35||F43||8||-||17 ng(28-85)||-||-|
|Saab et al. 36||F 27||3||-||43(70-180)||-||-|
|Samanta 19||F17||3||Paresthesia, nystagmus||<2 nmol/L (8-15)||51.6 kg/m2||-|
|Serlin et al.18||F37||10||confusion, postural imbalance and visual impairment||13.9 ng/mL(32-95 ng/mL)||43 (25.8)||-|
|Dirani et al.13||M20||3||visual impairment,nystagmus||-||45||-|
|Landais et al.14||M31||4||nystagmus, ataxia, confusion||55,9 nmol/L( 66,5–200)||47|
|Pardo-Aranda et al.15||M20||5||confusion, motor ataxia, diplopy and nystagmus||12.2 ng/mL(35–91 ng/mL)||50.17||-|
|Kröll et al.16||M55||8||confusion, motor ataxia and nystagmus||67 kg/m2||arterial hypertension, type 2diabetes mellitus, dyslipidemia,NASH, GERD, obstructive sleep apnea|
|Author||Sleeve complication||Therapy B1||Glycemic status|
|Cerruti et al.11||-||1500mg/iv-500mg orally||-|
|Jeong et al. 12||Staple- line leakage||Iv 100mg for 10d then orally||DM**|
|Makarewicz et al. 17||Edema of gastric wall, functional stenosis of the stomach||Iv 50mg per day||-|
|Moize et al. 33||Laceration of the mucosa of GEJ±±||100mgx3 +5mg folic orally||DM|
|Scarano et al. 34||-||1800mcg im/w, iv 500 mg x3 then orally 100mg x1||Eyglucemic|
|Sharabi et al. 35||Inguinal abscess- paralytic ileus||Iv 600 mg x1||-|
|Saab et al. 36||-||Iv 100 mg-orally 100 x3||-|
|Samanta 19||-||Iv 500 mg x3||Eyglucemic|
|Serlin et al.18Dirani et al.13||-Fistulawith thoraco-abdominal abscess||Iv 500 mg x3Iv 500 mg x3 and IM 500mgx1 for 5 days||Eyglycemic|
|Landais et al.14||-||Iv 1g/d||Eyglycemic|
|Pardo-Aranda et al.15||-||IV 100MG/d and orally 600 mg per day||Eyglycemic|
|Kroll et al.16||-||i.v 300 mg three times daily||DM|
In most of the reported cases, serum thiamine levels were reduced. But the serum and urinary tests in symptomatic patients are not sensitive and remain technically difficult and time-consuming. MRI is the diagnostic tool of choice, with a high sensitivity and specificity for WE.20
All patients were treated with parenteral thiamine administration. Four patients had a complete recovery. Eight patients had residual neurologic defects, including Korsakoff psychosis, persistent amnestic state with antegrade amnesia and retrograde memory loss, memory problems, persistent ataxia, nystagmus, and neuropathy. One patient died from an unrelated cause (septic shock).
Wernicke Encephalopathy (WE) was first described by Carl Wernicke in 1881 as “superior acute hemorrhagic poliencephalitis”. Despite the fact that WE was described so early, it took more than half a century to recognize the relation between the disease and the thiamine deficiency. Thiamine is a water-soluble vitamin of the B complex. It is involved with several other enzymes and co-enzymes in the Krebs cycle and the pentose phosphate pathway and plays a central role in cerebral metabolism. Thiamine deficiency in turn instigates brain injury by inhibiting metabolism in regions of the brain with high metabolic demand. The most frequently affected regions are the medial thalamus and periventricular region of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectum (superior and inferior colliculi). Often, there is a selective loss of the Purkinje cells in the cerebellum. Although alcoholic patients account for more than 90% of both acute and chronic WE in developed countries, acute WE can also occur in cases of malnutrition (prolonged fasting, parenteral nutrition without the addition of thiamine) or even in cases of prolonged vomiting 21, 22. Suddenly occurring in its most common form, WE is classically characterized by a clinical triad including reduced consciousness, a cerebellar syndrome (in particular ataxia and dysarthria) as well as oculomotor disorders (ophthaloplegia, nystagmus). The classic triad of WΕ was present in only 16% of patients in a retrospective autopsy review 23. According to the Caine criteria 22, the diagnostic criteria for Wernicke encephalopathy require 2 of the following 4 features: (1) dietary deficiency, (2) oculomotor abnormality, (3) cerebellar dysfunction, and (4) confusion or mild memory impairment. These criteria have a very high inter-observer reliability for the diagnosis.
Bariatric surgery can imitate or be complicated by all the above mentioned conditions. The risk of WE evolvement is highly dependent on the type of bariatric surgery performed. Purely restrictive operations, such as laparoscopic adjustable gastric banding, sleeve gastrectomy and vertical banded gastroplasty, tend to cause fewer deficiencies than do malabsorptive procedures such as laparoscopic Roux-en-Y gastric bypass and biliopancreatic diversion. Thiamine deficiency is reported to occur more often after RYGB. The possible reason is that maximal absorption of thiamine takes place in the jejunum, which can be affected by anatomical changes after a RYGB. Clements et al. noted a significant incidence rate up to 18 % 2 years after a RYGB. 24, 25, 26, 27, 28, 29, 13. Following SG for morbid obesity more particularly, several factors, including the restriction in energy intake, prolonged vomiting, rapid and excessive weight loss, and medication non-compliance, have been associated to the development of WE 30, 31. In particular, vomiting represents a well-known complication of SG, which may be due to surgery-related complications such as the presence of an anatomical or functional gastric stricture, a leak or a staple-line bleeding.
Despite the availability of different diagnostic modalities, including laboratory evaluation, electroencephalography, and brain imaging, WE remains a clinical diagnosis, requiring a high index of suspicion. The presumptive diagnosis may be confirmed by the measurement of thiamine and its phosphate esters in the human blood by high-performance liquid chromatography (HPLC) or by measuring the activity of the enzyme transketolase in the erythrocytes 32. However, because of the technical difficulty and lack of specificity of these tests, which additionally require several days to perform, their aid in the process of decision-making is limited. Neuroimaging studies are powerful tools in supporting the diagnosis of WE. Brain MRI offers the best means to establish a definitive diagnosis of WE, having a low sensitivity of 53%, but a high (93%) specificity rate 20. Common brain MRI findings are hyper-intense signals in the dorsal medial thalamic nuclei, the peri-aqueductal gray area, and the third and fourth ventricle 31. In the acute setting a mammillary body enhancement may be revealed, whereas in a more chronic stage a mammillary body atrophy may be shown 20.
The mainstay of treatment of WE is the administration of thiamine. The standard recommendation is 200 mg, 3 times per day. The intravenous route is preferred instead of the intramuscular one, while the oral route in the acute setting is not recommended due to decreased gastrointestinal absorption or even not applicable due to circumstances precluding normal oral diet. However, several authors state that the dose should be increased to 500 mg thiamine 3 times per day 22. With these thiamine administration schemes, WE has been reported to be treated with very good results, since it seems that the majority of patients can be totally cured while in a minority some minor residual neurological defects may ensue.
This study has of course some limitations. It is retrospective, the number of the reported cases is low, and it can always happen that despite the exhaustive search some cases may be missed. Despite these, this study tries to address the problem of a rare cause of severe morbidity after a rather commonly used operation like SG and as such, it can be helpful for the clinician, who although rarely, may encounter such a patient.
In summary, this study reaffirms that only a small number of patients have been reported as having suffered from clinically significant B1 deficiency after SG for morbid obesity. Physicians should be highly suspicious for the diagnosis of Wernicke’s encephalopathy in cases of rapidly altered mental status occurring in patients with malnutrition or malabsorption as a consequence of prolonged vomiting after SG. Since B1 levels are not included either in the pre-operative nutritional assessment or in any rigorous postoperative follow-up plan, the parenteral administration of high doses of B1 in all suspicious cases is imperative and usually results in the resolution of the symptoms.