Wernicke Encephalopathy Workup

Patients with Wernicke encephalopathy present with altered mental status and other neurologic abnormalities. Careful history, physical examination, laboratory workup, and radiographic evaluation are essential to exclude other causes of central nervous system (CNS) dysfunction.

No specific laboratory test is available for diagnosing Wernicke encephalopathy. Wernicke encephalopathy is a clinical diagnosis, and normal electrolyte levels may give only false reassurance and delay therapy. This is particularly the case when malnutrition is likely to be present. The motto should be "If in doubt, treat," as administration of thiamine does not pose potential harm.

Moreover, neither a normal computed tomography (CT) scan of the brain nor a normal magnetic resonance imaging (MRI) scan rule out the presence of acute or chronic Wernicke-Korsakoff syndrome.^[11]

Although Wernicke encephalopathy remains a clinical diagnosis with no characteristic abnormalities in diagnostic studies, the use of laboratory and radiographic tests remains important to exclude alternate or coexisting medical conditions. The patient’s history and initial evaluation guide the selection of these tests.

Tests to perform include the following:

• Complete blood count (CBC) - Rules out severe anemias and leukemias as causes of altered mental status
• Serum glucose levels - Exclude hypoglycemia and hyperglycemia
• Pulse oximetry and/or arterial blood gas (ABG) measurement - Exclude hypoxia and hypercarbia
• Toxic drug screening - Excludes some causes of drug-induced altered mental status.
• Consider lumbar puncture (LP) - Consider LP to exclude CNS infections, if indicated

Erythrocyte transketolase levels

Erythrocyte transketolase levels reliably detect thiamine deficiency but are not necessary for the diagnosis of Wernicke encephalopathy. In the erythrocyte transketolase activity assay, the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline levels (the thiamine pyrophosphate effect). Normal values range from 0-15%; a value of 15-25% indicates thiamine deficiency, and a value of greater than 25% indicates severe deficiency.^[2]

Blood pyruvate and lactate measurements

Blood pyruvate and lactate measurements, although not specific for thiamine deficiency illnesses, are sensitive and helpful, as thiamine is a cofactor of the pyruvate dehydrogenase enzyme, an important enzyme in aerobic metabolism.^[2]

Electroencephalogram

Consider an electroencephalogram (EEG) if nonconvulsive status epilepticus is suspected as a potential cause of coma and altered mental status.

Biomarkers, including an assay for thiamine, are not typically available for timely diagnostic purposes. In addition, no study has clearly described the sensitivity, specificity, and accuracy of thiamine levels in relation to active disease.^[4] However, the thiamine levels can help the clinician assuming care of the patient in ambiguous cases, and obtaining a thiamine level can be considered for diagnostic dilemmas.^[5]

Complete discrimination of Wernicke encephalopathy patients and controls has been reported for thiamine monophosphate, a dephosphorylation product of the coenzyme thiamine pyrophosphate. However, evidence is sparse, and thiamine assays have limited availability and usually do not allow for an immediate diagnosis.^[8]

Alterations in serum electrolyte levels, such as hypernatremia or hypercalcemia, can cause altered mental status and must be excluded.

One case series suggested that patients with Wernicke encephalopathy may exhibit a distinctive acid-base pattern consisting of a primary metabolic acidosis in conjunction with a primary respiratory alkalosis. The primary metabolic acidosis is secondary to thiamine's role in aerobic metabolism and the Krebs cycle; without thiamine, aerobic metabolism cannot progress and metabolic products, including lactate and pyruvate, are produced, which result in an anion gap acidosis. The role of thiamine in causing a primary respiratory alkalosis is unclear.^[4]

CT scanning

A head CT scan is an essential initial test for emergency diagnosis of focal neurologic disease, such as intracerebral hemorrhage. In patients who are comatose, CT scan can detect not only intracranial lesions but also fractures of the skull and minute amounts of blood. However, with a reported 13% sensitivity for Wernicke encephalopathy, CT of the head does not appear to be useful in screening for this syndrome.^[11]

MRI

Thiamine is a cofactor of several enzymes involved in glucose metabolism and cerebral energy utilization, and its depletion results in the neuronal damage as seen on MRI, including T2 and fluid-attenuated inversion recovery hyperintense signaling in the mamillary bodies, periventricular thalamus, and periaqueductal gray matter, as well as diffusion-weighted imaging to differentiate vasogenic from cytotoxic edema.^[1]

MRI offers a technique to make a definitive diagnosis antemortem, but the sensitivity is poor, and obtaining an MRI for this indication is typically impractical and unnecessary in the emergency department (ED).^[5]

Although the clinical evidence for the utility of MRI is based on a study in which the sample size was small, the reported sensitivity of MRI was 53% and the reported specificity was 93%, for acute and chronic Wernicke-Korsakoff syndrome. Because of the low sensitivity of MRI for Wernicke encephalopathy, particularly an acute presentation, and because many patients with Wernicke encephalopathy may not exhibit diagnostic features on MRI, normal MRI results should not be used to exclude the diagnosis of acute illness.^[11]

The appearance of acute Wernicke encephalopathy on MRI demonstrates abnormal hyperdensity of the mammillary bodies and periaqueductal gray matter with associated abnormal enhancement on T1-weighted images.^[12] In chronic Wernicke encephalopathy and Korsakoff syndrome, radiographic imaging, especially MRI, may be normal or may show mamillary body, cerebellar, and cerebral shrinkage, as well as symmetrical, low-density abnormalities in periventricular areas, the diencephalon, and the midbrain.^[11] Such symmetrical lesions are uncommon in other cerebral encephalopathic disorders and are suggestive of Wernicke-Korsakoff syndrome.^[11]

Morphometric studies of MRI imaging confirm that patients with Wernicke-Korsakoff syndrome show excessive mamillary body and cerebellar shrinkage, indicating that these are highly specific MRI findings for this kind of encephalopathy.^[11]

The image below shows brain morphologic studies as demonstrated on MRI. A 60-year-old man presented with bilateral gaze-evoked nystagmus, severe ataxia, and memory impairment. Brain fluid-attenuated inversion recovery (FLAIR)–weighted MRI shows concurrent cytotoxic and vasogenic edema patterns. This case demonstrates cytotoxic and vasogenic edema that may occur at the same time in Wernicke encephalopathy. These findings may result from different vulnerability of brain regions to thiamine deprivation and the corresponding time delay between the development of lesions.^[13]

Media file 1: This MRI shows typical high signal intensities (SIs) in the medial thalamus (A), periaqueductal gray (B), mamillary bodies (C), cerebellar vermis (B, C, D), and paravermian superior cerebellum (D). All the lesions represent high SIs on the DWI (E–H). The ADC images of the cerebellar vermis (K, L) and paravermian superior cerebellum (L) show low SIs (arrowheads), whereas other described areas (I, J) show iso-SIs (arrows). Image courtesy of Neurology. Apr 8 2008;70(15):e48.