The authors’ observations
Mrs. B’s presentation suggests Wernicke’s encephalopathy (WE), an acute amnestic disorder caused by thiamine deficiency.
WE lesions are seen on autopsy in approximately 12.5% of alcohol abusers.1 Although alcoholism is more prevalent in men age 65, women are more likely to develop WE and cognitive dysfunction secondary to alcohol use.2
Alcoholism accounts for 77% of WE cases,3 although malnutrition caused by infection, cancer, gastric surgery, hemodialysis, hyperemesis, or starvation is another cause.
Clinical features of WE include confusion and disorientation (80% of cases, with stupor in 5%), ataxia (23%), and ocular abnormalities (29%). Nystagmus, especially to lateral gaze but also in vertical and other forms, is most common.4 Because less than one-third of patients with WE exhibit all 3 symptoms,5 the diagnosis is often missed. In studies, 15% of WE cases were diagnosed antemortem.1,6
Imaging studies. Brain MRI is more sensitive than computed tomography (CT) in detecting diencephalic, periventricular, and periaqueductal lesions (Box).7 Because of costs, physicians tend to order CT more often than MRI. CT can help rule out gross structural and vascular defects but is less adequate for evaluating specific lesions. In detecting WE lesions, MRI’s sensitivity is 53% and its specificity is 93%.7
Thiamine deficiency can occur when the liver can no longer absorb or store thiamine. Enzyme systems involved in the citric acid cycle and pentose phosphate pathway malfunction, and lactic acid production is increased. The associated pH change damages the apoenzymes. Glutamate accumulates, leading to production of free radicals, which cause cellular damage.11
Circulating thiamine levels are low (<50 ng/mL) in 30% to 80% of persons with alcoholism, putting them at risk for WE.12 Malnutrition secondary to alcoholism reduces thiamine absorption from the gut by 70%. Alcohol alone can reduce thiamine absorption by nearly 50%.13
WE lesions usually shrink within 48 to 72 hours of treatment with parenteral thiamine. Lactate <3.3 mg/dL or >14.9 mg/dL, and pyruvate <0.37 mg/dL or >0.75 mg/dL, indicate abnormal thiamine levels.14
Mrs. B’s confusion, hallucinations, and clouding of consciousness suggested DT, but this was ruled out because she had normal vital signs, classic eye signs of WE, no autonomic instability, and had been adequately tapered off alcohol.
TREATMENT: SHAKING ALCOHOL’S GRIP
A consulting neurologist confirmed a tentative diagnosis of WE.
Mrs. B’s oral thiamine was increased to 100 mg tid. She also received IM thiamine, 100 mg once daily for 5 days; risperidone, 0.5 mg every 4 hours as needed; and trazodone, 50 mg at bedtime as needed for irritability, agitation, and poor sleep. Multivitamins and folic acid were continued.
One week after starting IM thiamine, Mrs. B’s gait steadied, her coordination improved, and tremors and nystagmus stopped. She became more adept at eating. Cognitive impairment continued, but she confabulated less frequently. Her insight into her condition was improving.
Over the next 10 days, Mrs. B continued to improve, although neuropsychological assessment revealed major deficits in visuospatial function, attention, concentration, and memory. Repeat EEG showed diffuse slowing with frontal intermittent rhythmic delta activity, consistent with diffuse toxic metabolic encephalopathy.
Three weeks after admission, Mrs. B was discharged to her assisted-living facility, where she receives follow-up medical and psychiatric care. Her MMSE score at discharge was 12/30, indicating moderately severe cognitive impairment. Motor function has improved, although Mrs. B remains confused and needs help with daily living.
One month after discharge, Mrs. B’s diet was much improved; thiamine was reduced to 100 mg once daily. She has stayed sober but has repeatedly tried to drink. She was referred to a 12-step program but has not complied.
Clinical features of WE, Korsakoff’s psychosis
|Wernicke’s encephalopathy||Korsakoff’s psychosis|
|Acute onset||Subacute or chronic onset|
|Clouding of conciousness common||Consciousness usually clear|
|Ataxia, nystagmus, ophthalmoplegiao usually present||Ataxia, nystagmus, ophthalmoplegia not common|
|Impaired anterograde, retrograde memory; confabulation is rare||Impaired anterograde, retrograde memory with prominent confabulation|
|Without adequate treatment, >80% progress to Korsakoff’s psychosis; death rate is 20%||>80% progress to alcohol induced persisting dementia; nursing home admission rate is 25%|
|Source: Reference 14.|
The authors’ observations
Suspect WE in all patients with alcohol abuse disorder who are malnourished and/or elderly and whose dietary history is unclear. Early detection and treatment are crucial to preventing WE from becoming chronic. WE progresses to Korsakoff’s psychosis—a form of permanent short-term memory loss—in up to 80% of patients.5
Because Korsakoff’s psychosis carries an 8% death rate, consider the disorder in the differential diagnosis (Table). The disorder was ruled out in Mrs. B because of clouding of consciousness, ataxia, nystagmus, and shorter symptom duration.
Thiamine should be given IV, but can be given IM if unit nurses are not certified to give IV injections. Oral thiamine cannot generate the high thiamine blood concentrations (>50 ng/mL within the first 12 hours of treatment) needed to prevent irreversible damage.