Diagnosis, Workup and Treatment

A broad differential diagnosis for new-onset motility abnormalities, nystagmus, altered mental status and ataxia was considered. Possible etiologies included metabolic abnormalities, intoxication, stroke, encephalitis, meningitis and demyelinating disease.

The brain MRI showed numerous, symmetric, abnormal T2 FLAIR signal intensities within the bilateral thalami, symmetric regions surrounding the third ventricle, the aqueduct of Sylvius and within the region of the trochlear nerve nucleus. From the clinical history and exam, these symmetric T2 signal intensities were highly suggestive of Wernicke’s encephalopathy.

Complete blood count, chemistry panel and coagulation studies were normal other than hemoglobin of 12.5 g/dL. Blood ethanol level and urine toxicology were normal, which ruled out acute intoxication. Serum vitamin B12 was also within normal limits. Given the patient’s history of alcohol abuse, a serum B1 (thiamine) level was obtained and found to be 1.9 µg/dL (normal 2.5 to 7.5µg/dL).

The patient was started on parenteral thiamine in addition to nutritional support and measures to prevent alcohol withdrawal. Improvement in ophthalmoplegia and nystagmus was seen within three days of treatment and improvement in ataxia within two weeks. The delirium began to resolve within three days of treatment, but the patient continued to have significant memory difficulties. At three months follow-up, there was some further improvement, but the patient remains in a long-term care facility.

Discussion

Wernicke’s encephalopathy is a life-threatening neurological disease caused by a deficiency in vitamin B1 (thiamine). It is characterized by the triad of ophthalmoplegia, altered mental status and ataxia, but this triad is seen in only 16 percent of patients.^1,2 Within approximately two to three weeks of deficient thiamine intake or absorption, brain lesions develop in regions with high thiamine content and turnover.^3,4

While classically associated with chronic alcohol abuse, Wernicke’s encephalopathy may also be secondary to malnutrition, gastrointestinal surgical procedures, chronic vomiting or diarrhea and complications related to systemic diseases like AIDS.⁷ The condition is a medical emergency as it carries an estimated mortality of 17 percent.⁵ Eighty-five percent of survivors develop a memory disorder or Korsakoff syndrome, and 25 percent require long-term institutionalization.⁵

Twenty-nine percent of patients with Wernicke’s encephalopathy show some ocular abnormality. Findings can include nystagmus, unilateral or bilateral palsy of any extraocular muscles and conjugate-gaze palsies. Ophthalmoplegia results from insults to the pontine tegmentum, abducens or oculomotor nuclei.¹ Optic disc edema and retinal hemorrhages have also been reported in patients presenting with Wernicke’s encephalopathy.⁶

Magnetic resonance imaging is currently regarded as the most valuable modality to diagnose Wernicke’s encephalopathy. Despite a sensitivity of only 53 percent, a specificity of 93 percent makes MRI a valuable tool if typical findings are present. These findings include a bilateral increased T2 signal in the hypothalamus, mammillary bodies, paraventricular regions of the thalamus, periaqueductal grey matter, the floor of the fourth ventricle and midline cerebellum.⁷

Ultimately, improvement of neurological deficits after thiamine administration is the best method of confirming the diagnosis. Ocular abnormalities usually improve within days to weeks but ataxia and global confusion may require at least three months to significantly improve.^1,2 Blood thiamine concentrations and red blood cell transketolase activity can also be helpful in supporting clinical suspicion; however, they may be abnormal in patients who do not have encephalopathy.^8,9

The differential diagnosis of Wernicke’s encephalopathy includes encephalitis; paramedian thalamic infarction; Miller-Fisher variant of Guillain-Barre syndrome; multiple sclerosis; primary cerebral lymphoma; Behçet’s disease; and variant Creutzfeldt-Jakob disease.¹⁰ A carefully obtained history evaluating risk factors for Wernicke’s encephalopathy may be the most beneficial tool for the consulting ophthalmologist.  


The author thanks Mark Moster, MD, Wills Eye Hospital Neuro-ophthalmology Service, for his time and assistance in preparing this case report.



<sup>1. Victor M. The Wernicke-Korsakoff syndrome, Handbook of Clinical Neurology, vol 28, part II. Amsterdam: North-Holland Publishing Co., 1976:243–270.
2. 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
3. Manzo L, Locatelli C, Candura SM, Costa LG. Nutrition and alcohol neurotoxicity. Neurotoxicology 1994;15:555-565.
4. Schenker S, et al. Hepatic and Wernicke’s encephalopathies: Current concepts of pathogenesis. Am J Clin Nutr 1980;33:2719-2726.
5. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff syndrome: A clinical and pathological study of 245 patients, 82 with post-mortem examinations. Contemp Neurol Ser 1971;7:1-206.
6. Cooke CA, et al. An atypical presentation of Wernicke’s encephalopathy in an 11-year-old child. Eye 2006;20:1418-1420.
7. Antunez E, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. Am J Roentgenol 1998;171:1131-1137.
8. Baker H, et al. A method for assaying thiamine status in man and animals. Am J Clin Nutr 1964;14:197-201.
9. Dreyfus PM. Clinical application of blood transketolase determinations. N Engl J Med 1962;267:596-598.
10. Brechtelsbauer DL. Cytomegalovirus encephalitis and primary cerebral lymphoma mimicking Wernicke’s encephalopathy. Neuroradiology 1997;39:19-22.</sup>