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HISTORY: TOO MUCH FOR TOO LONG
Mrs. B, age 73, has been alcohol-dependent for 20 years. Since her husband’s death 5 years ago, she has been drinking 1 to 2 liters of vodka a week. At her family’s insistence, she checks into a tertiary-care hospital for worsening alcohol use, memory problems, and increasing confusion.
Mrs. B’s family removed her car because of her alcohol and cognitive problems, but she walks half a mile to buy alcohol. She lives alone in an assisted-living facility and has been hospitalized for detoxification 3 times within 2 years.
At intake, her judgment and abstract thinking are impaired. She has poor insight into her condition. Physical examination reveals fine hand tremors. Lab test results and vital signs are normal. Mrs. B was previously diagnosed with bipolar disorder and takes divalproex, 250 each morning and 500 mg at bedtime, and paroxetine, 20 mg/d.
Mrs. B’s Folstein Mini-Mental State Examination (MMSE) score 1 week after admission was 5/30, indicating severe cognitive deficits. Her mood was euthymic, speech and motor activity were normal, and thought process was logical with intact associations. She exhibited no delusions or hallucinations but was disoriented, with a short attention span and poor concentration.
The authors’ observations
Mrs. B’s confusion has increased in recent weeks. Hand tremors could signal a neurologic problem triggered by a vascular event or alcohol use. Include dementia in the differential diagnosis.
Distinguishing between vascular dementia and alcohol-induced persisting dementia requires a thorough history, neurologic exam, and lab testing.
Vascular dementia. Cognition deteriorates step by step. Patients with this dementia have multiple vascular risk factors and display evidence of cerebrovascular events on physical examination or imaging studies. Watch for high blood pressure, high cholesterol, or obesity; history of diabetes, cardiac arrythmias, or strokes; or other vascular changes in the brain.
Alcohol-induced persisting dementia. Patients usually have abused alcohol for years, and memory slowly deteriorates. Vascular events that would explain cognitive deficits are not found. Such patients usually do not have vascular and cerebrovascular risk factors, but may exhibit worsening cognition in the context of alcohol use. Watch for mean corpuscular volume >100 femtoliters, gamma glutamyl transferase >50 U/L, and elevated liver function tests.
For Mrs. B, both dementia types were ruled out. Her memory problems were mild, and she had been functioning independently at the assisted-living facility. Dementia is not characterized by clouding of consciousness, and her disorder’s progression was fast. Mrs. B’s bipolar disorder was not a factor because she did not have significant depressive or manic symptoms.
Amnestic disorder. Mrs. B’s worsening mental status and neurologic signs after admission suggest amnestic disorder. Patients with amnestic disorder have trouble learning or recalling new information and forming new memories, although they can talk coherently and appropriately.
Injury to the diencephalic and medial temporal lobe structures triggers amnestic disorder. Head trauma, cerebral infections, and infarctions can damage these structures, but alcoholism is the most common cause.
ADMISSION: INCREASING CONFUSION
Mrs. B was admitted to the dual diagnosis unit for patients with substance use and psychiatric disorders. Although confused, she could eat and walk.
For 2 days, Mrs. B received chlordiazepoxide, 200 mg/d, for detoxification; a multivitamin tablet; and oral vitamin B1 (thiamine), 100 mg once daily. She also continued her divalproex/paroxetine regimen. Chlordiazepoxide was tapered and discontinued over 4 days. Vital signs remained normal.
Two days after starting detox, Mrs. B’s condition began to worsen. She became incontinent of urine and feces, had trouble eating, and required extensive assistance with activities of daily living.
On examination by the geriatric psychiatry team, Mrs. B appeared very confused. She was confabulating, had hand tremors, and was ataxic, with nystagmus on lateral gaze. Coordination was poor. Because she reported visual hallucinations and appeared delirious, divalproex sodium and paroxetine—which can worsen delirium—were stopped.
Head MRI with contrast revealed sulcal space prominence in the cerebral and cerebellar hemispheres, suggesting minimal volume loss, and nonspecific bilateral periventricular punctuate flairs and T2 hypodensities, indicating small-vessel ischemic disease. EEG showed moderate rhythm slowing. Blood and urine tests showed no infectious disease or metabolic abnormalities.
Lesions associated with Wernicke’s encephalopathy (WE) usually are found in the third ventricle, cerebral aqueduct, fourth ventricle, mamillary bodies, periaqueductal gray matter, dorsomedial thalamus, septal region, and oculomotor nuclei.
In approximately 50% of cases, damage to the cerebellum also occurs. Such damage is usually symmetrical and shows diffuse, patchy endothelial prominence, proliferation of microglia, and petechial hemorrhage.
In chronic cases, demyelination and gliosis occur. Neuronal loss is prominent in the medial thalamus. Atrophy of the mamillary bodies indicates chronic WE.
Source: References 8-10.
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.
Table 1
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.
Parenteral thiamine, 100 mg/d for 5 to 7 days, is given for acute WE. Some patients who are genetically predisposed to thiamine deficiency may need up to 1,000 mg/d. Continue oral thiamine, 100 mg/d, after parenteral dosing.
Although anaphylaxis risk during a 10-minute thiamine infusion is less than 1 in 1 million, make sure cardiopulmonary resuscitation is available during treatment. Glucose load can precipitate or worsen WE in a thiamine-deficient patient, so give thiamine before giving glucose in any form, including everyday foods.
Watch for other vitamin and magnesium deficiencies common to patients with alcoholism, as these might compromise response to IV/IM thiamine.15 Also rule out stroke in men age >65 who present with signs of hemiparesis.
Related resources
- Stern Y, Sackheim HA. Neuropsychiatric aspects of memory and amnesia. In: Yudofsky SC, Hales RE, (eds). Essentials of neuropsychiatry and clinical neurosciences. Washington, DC: American Psychiatric Publishing, 2004:201-38.
- National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/health_and_medical/disorders/wernicke-korsakoff.htm
Drug brand names
- Chlordiazepoxide • Libritabs, Lithium
- Divalproex sodium • Depakote
- Paroxetine • Paxil
- Risperidone • Risperdal
- Trazodone • Desyrel
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgment
Dr. Tampi’s efforts were supported by funds from the Division of State, Community, and Public Health, Bureau of Health Professions, Health Resources and Services Administration, Department of Health and Human Services, under grant number 1 K01 HP 00071-01, and the Geriatric Academic Career Award ($57,007). The information is that of Dr. Tampi and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the aforementioned departments or the United States government.
1. Torvik A, Lindboe CF, Rodge S. Brain lesions in alcoholics. A neuropathological study with clinical correlations. J Neurol Sci 1982;56:233-48.
2. Grant BF. Prevalence and correlates of alcohol use and DSM IV dependence in the United States: results of the National Longitudinal Alcohol Epidemiological Survey. J Stud Alcohol 1997;58:464-73.
3. Lindboe CF, Loberg EM. Wernicke’s encephalopathy in non-alcoholics. An autopsy study. J Neurol Sci 1989;90:125-9
4. 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;49:341-5.
5. Thompson AD, Cook CCH, Touquet R, Henry JA. The Royal College of Physicians Report on Alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department. Alcohol Alcohol 2002;37(6):513-21.
6. Blansjaar BA, Van Dijk JG. Korsakoff minus Wernicke syndrome. Alcohol Alcohol 1992;27:435-7.
7. Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. AJR Am J Roentgenol 1998;171:1131-7.
8. Charness ME. Intracranial voyeurism: revealing the mamillary bodies in alcoholism. Alcohol Clin Exp Res 1999;23:1941-4.
9. 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.
10. Weidauer S, Nichtweiss M, Lanfermann H, Zanella FE. Wernicke encephalopathy. MR findings and clinical presentation. Eur Radiol 2003;13(5):1001-9.
11. Hazell AS, Todd KG, Butterworth RF. Mechanism of neuronal cell death in Wernicke’s encephalopathy. Metab Brain Dis 1998;13(2):97-122.
12. Cook CC, Hallwood PM, Thomson AD. B vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol 1998;33:317-36.
13. Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol 2000;35(suppl 1):2-7.
14. Victor M, Adams RA, Collins GH. The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition. Philadelphia: FA Davis, 1989.
15. Traviesa DC. Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy. J Neurol Neurosurg Psychiatry 1974;37:959-62.
HISTORY: TOO MUCH FOR TOO LONG
Mrs. B, age 73, has been alcohol-dependent for 20 years. Since her husband’s death 5 years ago, she has been drinking 1 to 2 liters of vodka a week. At her family’s insistence, she checks into a tertiary-care hospital for worsening alcohol use, memory problems, and increasing confusion.
Mrs. B’s family removed her car because of her alcohol and cognitive problems, but she walks half a mile to buy alcohol. She lives alone in an assisted-living facility and has been hospitalized for detoxification 3 times within 2 years.
At intake, her judgment and abstract thinking are impaired. She has poor insight into her condition. Physical examination reveals fine hand tremors. Lab test results and vital signs are normal. Mrs. B was previously diagnosed with bipolar disorder and takes divalproex, 250 each morning and 500 mg at bedtime, and paroxetine, 20 mg/d.
Mrs. B’s Folstein Mini-Mental State Examination (MMSE) score 1 week after admission was 5/30, indicating severe cognitive deficits. Her mood was euthymic, speech and motor activity were normal, and thought process was logical with intact associations. She exhibited no delusions or hallucinations but was disoriented, with a short attention span and poor concentration.
The authors’ observations
Mrs. B’s confusion has increased in recent weeks. Hand tremors could signal a neurologic problem triggered by a vascular event or alcohol use. Include dementia in the differential diagnosis.
Distinguishing between vascular dementia and alcohol-induced persisting dementia requires a thorough history, neurologic exam, and lab testing.
Vascular dementia. Cognition deteriorates step by step. Patients with this dementia have multiple vascular risk factors and display evidence of cerebrovascular events on physical examination or imaging studies. Watch for high blood pressure, high cholesterol, or obesity; history of diabetes, cardiac arrythmias, or strokes; or other vascular changes in the brain.
Alcohol-induced persisting dementia. Patients usually have abused alcohol for years, and memory slowly deteriorates. Vascular events that would explain cognitive deficits are not found. Such patients usually do not have vascular and cerebrovascular risk factors, but may exhibit worsening cognition in the context of alcohol use. Watch for mean corpuscular volume >100 femtoliters, gamma glutamyl transferase >50 U/L, and elevated liver function tests.
For Mrs. B, both dementia types were ruled out. Her memory problems were mild, and she had been functioning independently at the assisted-living facility. Dementia is not characterized by clouding of consciousness, and her disorder’s progression was fast. Mrs. B’s bipolar disorder was not a factor because she did not have significant depressive or manic symptoms.
Amnestic disorder. Mrs. B’s worsening mental status and neurologic signs after admission suggest amnestic disorder. Patients with amnestic disorder have trouble learning or recalling new information and forming new memories, although they can talk coherently and appropriately.
Injury to the diencephalic and medial temporal lobe structures triggers amnestic disorder. Head trauma, cerebral infections, and infarctions can damage these structures, but alcoholism is the most common cause.
ADMISSION: INCREASING CONFUSION
Mrs. B was admitted to the dual diagnosis unit for patients with substance use and psychiatric disorders. Although confused, she could eat and walk.
For 2 days, Mrs. B received chlordiazepoxide, 200 mg/d, for detoxification; a multivitamin tablet; and oral vitamin B1 (thiamine), 100 mg once daily. She also continued her divalproex/paroxetine regimen. Chlordiazepoxide was tapered and discontinued over 4 days. Vital signs remained normal.
Two days after starting detox, Mrs. B’s condition began to worsen. She became incontinent of urine and feces, had trouble eating, and required extensive assistance with activities of daily living.
On examination by the geriatric psychiatry team, Mrs. B appeared very confused. She was confabulating, had hand tremors, and was ataxic, with nystagmus on lateral gaze. Coordination was poor. Because she reported visual hallucinations and appeared delirious, divalproex sodium and paroxetine—which can worsen delirium—were stopped.
Head MRI with contrast revealed sulcal space prominence in the cerebral and cerebellar hemispheres, suggesting minimal volume loss, and nonspecific bilateral periventricular punctuate flairs and T2 hypodensities, indicating small-vessel ischemic disease. EEG showed moderate rhythm slowing. Blood and urine tests showed no infectious disease or metabolic abnormalities.
Lesions associated with Wernicke’s encephalopathy (WE) usually are found in the third ventricle, cerebral aqueduct, fourth ventricle, mamillary bodies, periaqueductal gray matter, dorsomedial thalamus, septal region, and oculomotor nuclei.
In approximately 50% of cases, damage to the cerebellum also occurs. Such damage is usually symmetrical and shows diffuse, patchy endothelial prominence, proliferation of microglia, and petechial hemorrhage.
In chronic cases, demyelination and gliosis occur. Neuronal loss is prominent in the medial thalamus. Atrophy of the mamillary bodies indicates chronic WE.
Source: References 8-10.
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.
Table 1
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.
Parenteral thiamine, 100 mg/d for 5 to 7 days, is given for acute WE. Some patients who are genetically predisposed to thiamine deficiency may need up to 1,000 mg/d. Continue oral thiamine, 100 mg/d, after parenteral dosing.
Although anaphylaxis risk during a 10-minute thiamine infusion is less than 1 in 1 million, make sure cardiopulmonary resuscitation is available during treatment. Glucose load can precipitate or worsen WE in a thiamine-deficient patient, so give thiamine before giving glucose in any form, including everyday foods.
Watch for other vitamin and magnesium deficiencies common to patients with alcoholism, as these might compromise response to IV/IM thiamine.15 Also rule out stroke in men age >65 who present with signs of hemiparesis.
Related resources
- Stern Y, Sackheim HA. Neuropsychiatric aspects of memory and amnesia. In: Yudofsky SC, Hales RE, (eds). Essentials of neuropsychiatry and clinical neurosciences. Washington, DC: American Psychiatric Publishing, 2004:201-38.
- National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/health_and_medical/disorders/wernicke-korsakoff.htm
Drug brand names
- Chlordiazepoxide • Libritabs, Lithium
- Divalproex sodium • Depakote
- Paroxetine • Paxil
- Risperidone • Risperdal
- Trazodone • Desyrel
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgment
Dr. Tampi’s efforts were supported by funds from the Division of State, Community, and Public Health, Bureau of Health Professions, Health Resources and Services Administration, Department of Health and Human Services, under grant number 1 K01 HP 00071-01, and the Geriatric Academic Career Award ($57,007). The information is that of Dr. Tampi and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the aforementioned departments or the United States government.
HISTORY: TOO MUCH FOR TOO LONG
Mrs. B, age 73, has been alcohol-dependent for 20 years. Since her husband’s death 5 years ago, she has been drinking 1 to 2 liters of vodka a week. At her family’s insistence, she checks into a tertiary-care hospital for worsening alcohol use, memory problems, and increasing confusion.
Mrs. B’s family removed her car because of her alcohol and cognitive problems, but she walks half a mile to buy alcohol. She lives alone in an assisted-living facility and has been hospitalized for detoxification 3 times within 2 years.
At intake, her judgment and abstract thinking are impaired. She has poor insight into her condition. Physical examination reveals fine hand tremors. Lab test results and vital signs are normal. Mrs. B was previously diagnosed with bipolar disorder and takes divalproex, 250 each morning and 500 mg at bedtime, and paroxetine, 20 mg/d.
Mrs. B’s Folstein Mini-Mental State Examination (MMSE) score 1 week after admission was 5/30, indicating severe cognitive deficits. Her mood was euthymic, speech and motor activity were normal, and thought process was logical with intact associations. She exhibited no delusions or hallucinations but was disoriented, with a short attention span and poor concentration.
The authors’ observations
Mrs. B’s confusion has increased in recent weeks. Hand tremors could signal a neurologic problem triggered by a vascular event or alcohol use. Include dementia in the differential diagnosis.
Distinguishing between vascular dementia and alcohol-induced persisting dementia requires a thorough history, neurologic exam, and lab testing.
Vascular dementia. Cognition deteriorates step by step. Patients with this dementia have multiple vascular risk factors and display evidence of cerebrovascular events on physical examination or imaging studies. Watch for high blood pressure, high cholesterol, or obesity; history of diabetes, cardiac arrythmias, or strokes; or other vascular changes in the brain.
Alcohol-induced persisting dementia. Patients usually have abused alcohol for years, and memory slowly deteriorates. Vascular events that would explain cognitive deficits are not found. Such patients usually do not have vascular and cerebrovascular risk factors, but may exhibit worsening cognition in the context of alcohol use. Watch for mean corpuscular volume >100 femtoliters, gamma glutamyl transferase >50 U/L, and elevated liver function tests.
For Mrs. B, both dementia types were ruled out. Her memory problems were mild, and she had been functioning independently at the assisted-living facility. Dementia is not characterized by clouding of consciousness, and her disorder’s progression was fast. Mrs. B’s bipolar disorder was not a factor because she did not have significant depressive or manic symptoms.
Amnestic disorder. Mrs. B’s worsening mental status and neurologic signs after admission suggest amnestic disorder. Patients with amnestic disorder have trouble learning or recalling new information and forming new memories, although they can talk coherently and appropriately.
Injury to the diencephalic and medial temporal lobe structures triggers amnestic disorder. Head trauma, cerebral infections, and infarctions can damage these structures, but alcoholism is the most common cause.
ADMISSION: INCREASING CONFUSION
Mrs. B was admitted to the dual diagnosis unit for patients with substance use and psychiatric disorders. Although confused, she could eat and walk.
For 2 days, Mrs. B received chlordiazepoxide, 200 mg/d, for detoxification; a multivitamin tablet; and oral vitamin B1 (thiamine), 100 mg once daily. She also continued her divalproex/paroxetine regimen. Chlordiazepoxide was tapered and discontinued over 4 days. Vital signs remained normal.
Two days after starting detox, Mrs. B’s condition began to worsen. She became incontinent of urine and feces, had trouble eating, and required extensive assistance with activities of daily living.
On examination by the geriatric psychiatry team, Mrs. B appeared very confused. She was confabulating, had hand tremors, and was ataxic, with nystagmus on lateral gaze. Coordination was poor. Because she reported visual hallucinations and appeared delirious, divalproex sodium and paroxetine—which can worsen delirium—were stopped.
Head MRI with contrast revealed sulcal space prominence in the cerebral and cerebellar hemispheres, suggesting minimal volume loss, and nonspecific bilateral periventricular punctuate flairs and T2 hypodensities, indicating small-vessel ischemic disease. EEG showed moderate rhythm slowing. Blood and urine tests showed no infectious disease or metabolic abnormalities.
Lesions associated with Wernicke’s encephalopathy (WE) usually are found in the third ventricle, cerebral aqueduct, fourth ventricle, mamillary bodies, periaqueductal gray matter, dorsomedial thalamus, septal region, and oculomotor nuclei.
In approximately 50% of cases, damage to the cerebellum also occurs. Such damage is usually symmetrical and shows diffuse, patchy endothelial prominence, proliferation of microglia, and petechial hemorrhage.
In chronic cases, demyelination and gliosis occur. Neuronal loss is prominent in the medial thalamus. Atrophy of the mamillary bodies indicates chronic WE.
Source: References 8-10.
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.
Table 1
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.
Parenteral thiamine, 100 mg/d for 5 to 7 days, is given for acute WE. Some patients who are genetically predisposed to thiamine deficiency may need up to 1,000 mg/d. Continue oral thiamine, 100 mg/d, after parenteral dosing.
Although anaphylaxis risk during a 10-minute thiamine infusion is less than 1 in 1 million, make sure cardiopulmonary resuscitation is available during treatment. Glucose load can precipitate or worsen WE in a thiamine-deficient patient, so give thiamine before giving glucose in any form, including everyday foods.
Watch for other vitamin and magnesium deficiencies common to patients with alcoholism, as these might compromise response to IV/IM thiamine.15 Also rule out stroke in men age >65 who present with signs of hemiparesis.
Related resources
- Stern Y, Sackheim HA. Neuropsychiatric aspects of memory and amnesia. In: Yudofsky SC, Hales RE, (eds). Essentials of neuropsychiatry and clinical neurosciences. Washington, DC: American Psychiatric Publishing, 2004:201-38.
- National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/health_and_medical/disorders/wernicke-korsakoff.htm
Drug brand names
- Chlordiazepoxide • Libritabs, Lithium
- Divalproex sodium • Depakote
- Paroxetine • Paxil
- Risperidone • Risperdal
- Trazodone • Desyrel
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgment
Dr. Tampi’s efforts were supported by funds from the Division of State, Community, and Public Health, Bureau of Health Professions, Health Resources and Services Administration, Department of Health and Human Services, under grant number 1 K01 HP 00071-01, and the Geriatric Academic Career Award ($57,007). The information is that of Dr. Tampi and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the aforementioned departments or the United States government.
1. Torvik A, Lindboe CF, Rodge S. Brain lesions in alcoholics. A neuropathological study with clinical correlations. J Neurol Sci 1982;56:233-48.
2. Grant BF. Prevalence and correlates of alcohol use and DSM IV dependence in the United States: results of the National Longitudinal Alcohol Epidemiological Survey. J Stud Alcohol 1997;58:464-73.
3. Lindboe CF, Loberg EM. Wernicke’s encephalopathy in non-alcoholics. An autopsy study. J Neurol Sci 1989;90:125-9
4. 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;49:341-5.
5. Thompson AD, Cook CCH, Touquet R, Henry JA. The Royal College of Physicians Report on Alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department. Alcohol Alcohol 2002;37(6):513-21.
6. Blansjaar BA, Van Dijk JG. Korsakoff minus Wernicke syndrome. Alcohol Alcohol 1992;27:435-7.
7. Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. AJR Am J Roentgenol 1998;171:1131-7.
8. Charness ME. Intracranial voyeurism: revealing the mamillary bodies in alcoholism. Alcohol Clin Exp Res 1999;23:1941-4.
9. 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.
10. Weidauer S, Nichtweiss M, Lanfermann H, Zanella FE. Wernicke encephalopathy. MR findings and clinical presentation. Eur Radiol 2003;13(5):1001-9.
11. Hazell AS, Todd KG, Butterworth RF. Mechanism of neuronal cell death in Wernicke’s encephalopathy. Metab Brain Dis 1998;13(2):97-122.
12. Cook CC, Hallwood PM, Thomson AD. B vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol 1998;33:317-36.
13. Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol 2000;35(suppl 1):2-7.
14. Victor M, Adams RA, Collins GH. The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition. Philadelphia: FA Davis, 1989.
15. Traviesa DC. Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy. J Neurol Neurosurg Psychiatry 1974;37:959-62.
1. Torvik A, Lindboe CF, Rodge S. Brain lesions in alcoholics. A neuropathological study with clinical correlations. J Neurol Sci 1982;56:233-48.
2. Grant BF. Prevalence and correlates of alcohol use and DSM IV dependence in the United States: results of the National Longitudinal Alcohol Epidemiological Survey. J Stud Alcohol 1997;58:464-73.
3. Lindboe CF, Loberg EM. Wernicke’s encephalopathy in non-alcoholics. An autopsy study. J Neurol Sci 1989;90:125-9
4. 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;49:341-5.
5. Thompson AD, Cook CCH, Touquet R, Henry JA. The Royal College of Physicians Report on Alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department. Alcohol Alcohol 2002;37(6):513-21.
6. Blansjaar BA, Van Dijk JG. Korsakoff minus Wernicke syndrome. Alcohol Alcohol 1992;27:435-7.
7. Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. AJR Am J Roentgenol 1998;171:1131-7.
8. Charness ME. Intracranial voyeurism: revealing the mamillary bodies in alcoholism. Alcohol Clin Exp Res 1999;23:1941-4.
9. 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.
10. Weidauer S, Nichtweiss M, Lanfermann H, Zanella FE. Wernicke encephalopathy. MR findings and clinical presentation. Eur Radiol 2003;13(5):1001-9.
11. Hazell AS, Todd KG, Butterworth RF. Mechanism of neuronal cell death in Wernicke’s encephalopathy. Metab Brain Dis 1998;13(2):97-122.
12. Cook CC, Hallwood PM, Thomson AD. B vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol 1998;33:317-36.
13. Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol 2000;35(suppl 1):2-7.
14. Victor M, Adams RA, Collins GH. The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition. Philadelphia: FA Davis, 1989.
15. Traviesa DC. Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy. J Neurol Neurosurg Psychiatry 1974;37:959-62.