A 54-year-old woman was admitted to the hospital with a chief complaint of altered mental status and confusion of 2 days’ duration. Family members reported that she had a 2-week history of increased swelling in both legs and difficulty in walking. There was no reported vomiting, dyspnea, or increasing pain.
The patient lived with her parents who said that she had been receiving chemotherapy for 5 months to treat metastatic pancreatic adenocarcinoma. Other relevant medical history included deep venous thrombosis, anemia, chronic hyponatremia, osteoporosis, irritable bowel syndrome, and seasonal allergies. An extensive surgical history included cholecystectomy with choledochojejunostomy, hysterectomy, and benign breast mass removal. Her parents said she did not use tobacco, alcohol, or illicit substances.
On presentation, the patient was not in distress. Physical examination revealed the following: temperature, 36.2°C (97.2°F); pulse, 80 beats/min; respiratory rate,18 breaths/min; oxygen saturation, 97% on room air; blood pressure, 129/57 mm Hg; and weight, 154 lb (reflecting a 17-lb weight loss over the previous 5 months). HEENT, respiratory, and dermatologic examinations were normal. Abdominal examination revealed chronic pain that was nonspecific and diffuse. Cardiovascular examination found chronic left upper extremity 3+ pitting edema associated with chronic deep venous thrombosis, and worsening bilateral lower extremity 3+ pitting edema. The patient was pleasant and cooperative but disoriented to place and had trouble answering basic questions. Cranial nerve function was intact but ocular examination revealed bilateral horizontal nystagmus. Neuromuscular examination revealed bilateral lower extremity 4/5 strength with inability to stand or walk.
Results of a brain CT scan were normal. A complete blood cell count revealed chronic anemia (hemoglobin, 9.8 g/dL). Initial serum chemistries revealed the following: sodium, chronically low at 125 mEq/L (normal, 132 to 146 mEq/L); creatinine, 1.1 mg/dL (normal, 0.4 to 1.1 mg/dL). Urinalysis revealed the following: osmolality, 397 mOs/kg (normal, 50 to 800 mOs/kg); sodium, 125 mEq/L (normal, 132 to 146 mEq/L); magnesium, 1.4 mg/dL (normal, 1.6 to 2.2 mg/dL); total protein, 4.6 g/dL (normal, 5.9 to 8.4 g/dL); albumin, 2.1 g/dL (normal, 3.2 to 5.2 g/dL); and vitamin B12, 1530 pg/dL (normal, 211 to 946 pg/dL). Findings of a lumbar puncture were unremarkable. MRI study of the brain revealed abnormal signaling in the periaqueductal gray matter (Figure), which raised suspicion for Wernicke encephalopathy. Intravenous thiamine replacement was promptly initiated. A baseline serum thiamine level was extremely low—2 nmol/L (normal, 8 to 30 nmol/L).
The patient’s symptoms improved dramatically after the first dose of thiamine, and improvement continued over the next 3 days at which point she was discharged. The metastatic burden of her pancreatic cancer had decreased in response to chemotherapy. The patient’s hyponatremia was assessed as chronic and attributed to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) with acute volume depletion. After intravenous volume replacement, her sodium level rose to 130 mEq/L from 125 mEq/L. She was placed on free-water restriction as first-line treatment for SIADH. Wernicke encephalopathy was unrelated to the SIADH and was attributed to the pancreatic cancer and severe malnutrition. Nutrition supplementation was initiated in the hospital and continuation was prescribed on discharge.
Wernicke encephalopathy (WE) is a preventable acute neurologic complication of thiamine (vitamin B1) deficiency. WE is most often associated with chronic alcoholism but is also seen in patients who are malnourished as a result of poor dietary intake (eg, anorexia, extreme dieting), hyperemesis, increased metabolic requirement (eg, systemic illness or malignancy), renal dialysis, AIDS, prolonged parenteral feeding without proper supplementation, GI surgery, and transplantation.1
Thiamine is a cofactor of several enzymes important in energy metabolism.2Thiamine deficiency causes decreased cerebral glucose utilization which, in turn, causes mitochondrial damage, glutamate accumulation, and possible cell damage.2 Thiamine deficiency can result from inadequate dietary intake, as was the case with this patient, reduced GI absorption, decreased hepatic storage, and impaired utilization.2 There may be some genetic predisposition.3
WE is primarily a clinical diagnosis. It should be included in the differential diagnosis of all patients who present with acute delirium or acute ataxia. The classic clinical triad of WE includes encephalopathy, oculomotor dysfunction, and gait ataxia. These elements may appear alone or in combination.4 Other findings characteristic of WE include protein-calorie malnutrition, hypothermia, hypotension, syncope, lower extremity peripheral neuropathy, tachycardia, exertional dyspnea, elevated cardiac output, magnesium deficiency, and ECG abnormalities.5 Left untreated, WE can cause Korsakoff syndrome with permanent debility, stupor, coma, and/or death.
If clinical findings create a high index of suspicion for WE, thiamine replacement should begin immediately and takes precedence over ordering a thiamine level1 and obtaining brain imaging studies (MRI). The recommended thiamine regimen is 500 mg intravenously infused over 30 minutes, 3 times daily for 2 days, then 500 mg intravenously or intramuscularly once daily for 5 days. Then an oral regimen of thiamine 100 mg daily, magnesium, multivitamins, and improved nutrition should be established.2 Prompt treatment leads to rapid improvement in most cases.2
• Wernicke encephalopathy is not a diagnosis exclusive to individuals with chronic alcoholism.
• Thiamine deficiency should be included in the differential diagnosis of all patients who present with altered mental status and abnormal gait.
• Thiamine deficiency, along with potential deficits in levels of other essential vitamins, should be considered in all patients who have anorexia, have experienced dramatic weight loss, or are malnourished, regardless of etiology.
1. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry. 1986;49:341-345.
2. Martin PR, Singleton CK, Hiller-Sturmhofel S. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003;27:134-142.
3. Kono, S, Miyajima H, Yoshida K, et al. Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. N Engl J Med. 2009;360:1792-1794.
4. Torvik A, Lindboe CF, Rogde F. Brain lesions in alcoholics: a neuropathological study with clinical correlations. J Neurol Sci. 1982;56:233-248.
5. Victor, M, Adams, RA, Collins, GH. The Wernicke-Korsakoff Syndrome and Related Disorders Due to Alcoholism and Malnutrition. Philadelphia: FA Davis; 1989.