Non-alcoholic Wernicke encephalopathy: great masquerader

Abstract

Thiamine is an important coenzyme, which is essential for metabolism and maintaining cellular osmotic gradient. Thiamine deficiency can cause focal lactic acidosis, alteration of the blood–brain barrier and the production of free radicals through cell death by necrosis and apoptosis. Wernicke encephalopathy (WE) is a clinical diagnosis. Cytotoxic and vasogenic oedema are the most typical neuroimaging findings of WE, presenting as bilateral symmetrical hyperintense signals on T2-weighted MR images. MRI is not necessary for the diagnosis of WE, but it can be helpful in ruling out alternative diagnosis. We present the case of an 61-year-old man with the history of class II obesity presenting with diplopia, dysarthria and vertigo, confirmed to be non-alcoholic WE. We aim to highlight the occurrence of WE in patients with large bowel resection though. Delay in diagnosis, particularly in obese individuals due to lack of suspicion, can lead to grim prognosis.

Background

Alcoholics account for most cases of Wernicke encephalopathy (WE) but patients with malnutrition due to hyperemesis, starvation, dialysis, cancer or gastric surgery are also at high risk and they are diagnosed with non-alcoholic WE. The challenge with non-alcoholic WE is low level of suspicion associated with its presentation. In one autopsy series, non-alcohol abusers accounted for 23% of WE.¹ WE classically presents as a triad of ataxia, ophthalmoplegia and global confusion, but this is only seen in 16%–20% of cases. Other neurological manifestations such as decrease in deep tendon reflexes, peripheral neuropathy and decreased tone or dysarthria have been documented as possible rare but atypical presentations of WE.² Atypical presentation is more common in non-alcoholic WE.

Case presentation

A 61-year-old man with medical history of diabetes mellitus type 2 with peripheral neuropathy and class II obesity was admitted to the general medical unit with intractable nausea, vomiting and 78-pound weight loss over 2 months. He had recent laparotomy and right hemicolectomy for a ruptured appendix. He had no history of alcohol or illicit drug use. An upper gastrointestinal X-ray with small bowel follow through showed redundant gastric mucosa prolapsing into the pyloric channel. Gastric emptying study was unremarkable. Oesophagogastroduodenoscopy showed mild gastritis; CT abdomen and pelvis and hepatobiliary iminodiacetic acid scan were suggestive of acute cholecystitis. He underwent laparoscopic cholecystectomy. Post procedure, he continued to have nausea with no vomiting but was tolerating general diet. On postoperative day 2, he developed diplopia, dysarthria and vertigo.

His vital signs were blood pressure 162/87 mm Hg, heart rate 79/min, respiratory rate 18/min, temperature 37.3 °C, saturating 95% on room air and body mass index 37. (table 1) His physical examination was significant for abnormal eye movements bilaterally with weak abduction of the left eye. He had significant horizontal nystagmus bilaterally. Looking to the right, he had very slow and high amplitude nystagmus with slow phase moving left, fast to the right. When his eyes were tested separately, the right eye moved better and could go in all directions. The left could not move outward. Upgaze and downgaze were without nystagmus and he had mild dysarthria and trouble clearing secretions. The rest of the examination was unremarkable, reflexes were intact, but he had vertigo unrelated to position. Gait assessment for ataxia was deferred as patient could not tolerate testing.

Table 1.

Biochemical analysis during patient’s admission

	8 weeks preadmission	Admission	1 week	3 weeks	4 weeks postdischarge
Total protein (g/dL)		7.1	5.9	6.8	7.4
Albumin (g/dL)		3.4	2.8	2.3	3.6
AST (IU/L)		15	9	81	13
ALT (IU/L)		6	6	53	14
Vitamin B12 (pg/mL) (range>140)				1178
Thiamine (nmol/L) (range 74–222)				<7
Body mass index (kg/m2)	51.4	37

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Brainstem stroke was considered, so MRI brain was done which was unremarkable. The patient became lethargic and developed global encephalopathy. His labs were unremarkable, and all sedating medications were discontinued. A repeat MRI was done which was unremarkable and arterial blood gas analysis ruled out carbon dioxide narcosis as a cause of his encephalopathy. He continued to deteriorate, developed generalised weakness, dysarthria worsened and was areflexic on neurological examination. He was started on dobhoff-tube feeds and was transferred to intensive care unit for desaturation secondary to aspiration and was intubated. Electroencephalogram EEG showed generalised encephalopathy without epileptiform activity.

Differential diagnosis

Myasthenia gravis and Miller-Fisher variant of Guillain-Barre syndrome (GBS) were considered. He was treated empirically with pyridostigmine and high-dose steroids, but he became bradycardic with pyridostigmine, so this therapy was discontinued. Voltage-gated calcium channels, Ach-R and GQ1b antibodies, were negative.

Treatment

On postoperative day 14, MRI brain with fluid attenuated inversion recovery (FLAIR) sequences showed hyperintensity along the medial aspect of both thalami and periaqueductal region (figure 1). He was diagnosed with WE and treated with high-dose intravenous thiamine.

Figure 1.

MRI brain with FLAIR sequences showing hyperintensity of the periaqueductal region.

Outcome and follow-up

On postoperative day 23, patient was able to follow some commands, and could move his extremities; he was eventually discharged to long-term acute care facility with a percutaneous endoscopic gastrostomy tube. On postoperative day 55 of his cholecystectomy, patient’s mental status significantly improved. On neurological examination, his extraocular muscles were intact, and no nystagmus could be appreciated; his voice was clear with symmetrical palatal elevation. Although light touch and pinprick discrimination was still difficult to assess in his lower extremities, his reflexes were intact in all extremities.

Discussion

WE is a neurological disorder caused by thiamine deficiency.³ It is a medical emergency and the classic triad of ataxia, ophthalmoplegia and global confusion at presentation, is only seen in 16%–20% of cases.^{4 5} Atypical neurological manifestations such as decrease in deep tendon reflexes, peripheral neuropathy and decreased tone or dysarthria have been observed in patients with WE, especially those with non-alcoholic WE.^{6 7} Clinical diagnosis of WE are missed in 75%–80% of cases. Our patient had significant weight loss, with 2 months of intractable nausea and vomiting which increased his risk for WE. He had vertigo and diplopia and was found to have ophthalmoplegia and dysarthria on examination. He eventually developed global encephalopathy, generalised weakness and areflexia. These neurological manifestations and its progression led us to investigate alternate diagnoses like Miller-Fisher variant of GBS, myasthenia gravis and acute brainstem stroke delaying the diagnosis of WE and the initiation of appropriate therapy. There was not a strong suspicion for WE, so the initiation of parenteral thiamine was delayed until his repeat MRI with FLAIR sequences showed hyperintensity along the medial aspect of both thalami and periaqueductal region and provided the diagnosis of WE. While MRI can be helpful in confirming the diagnosis, it is only 53% sensitive and findings may only manifest late in the clinical spectrum of thiamine deficiency.⁸ Our patient had three MRIs before the diagnosis was reached, at which point he already had severe neurological deficits and had endured several other expensive investigations.

Early detection of subclinical thiamine deficiency can be very challenging, however, because symptoms are usually non-specific, including loss of appetite, headaches, fatigue, difficulty in concentration, irritability and abdominal discomfort. Intractable nausea, vomiting and severe dysphagia have also been reported as rare presenting symptoms of thiamine deficiency.^{9 10} Missing the early clinical signs of WE may lead to delay in treatment with debilitating consequences including progression to Korsakoff’s psychosis, which has a mortality rate as high as 20%.^{11 12} Thiamine supplementation has a low adverse effect profile, and it is an important coenzyme for metabolism, so we should have a low threshold for replacing thiamine in patients with risk factors. Also, having a high index of suspicion for the diagnosis of WE in patients with neurological symptoms in the setting of malnutrition and a very low threshold for the initiation of treatment even prior to obtaining imaging confirmation is important for early intervention, which can potentially prevent devastating outcomes.

Learning points.

• Untreated Wernicke encephalopathy’s mortality can be as high as 20%.

• Delayed diagnoses and treatment are associated with residual deficits, as motor recovery that occurs memory and learning deficits can become more apparent.

• MRI is not necessary for the diagnosis; as seen in our patient, the initial two MRIs were not suggestive of Wernicke encephalopathy.