Wernicke-Korsakoff Syndrome Treatment & Management
- Author: Glen L Xiong, MD; Chief Editor: David Bienenfeld, MD more...
Wernicke-Korsakoff syndrome (unlike acute Wernicke encephalopathy) is often a long-term condition. It should be treated aggressively as Wernicke encephalopathy in the acute setting, but with the understanding that it is rare for the Korsakoff amnestic state to fully reverse with treatment. After a course of treatment with high-dose parenteral thiamine and reversal of the acute effects of Wernicke encephalopathy, if there is no improvement in the Korsakoff amnestic state or other mental status abnormalities for 7 days, then a strategy of secondary harm prevention should be pursued. This includes maintenance with oral thiamine to prevent further insult, as well as consideration for rehabilitation, treatment of comorbid deficiencies and medical conditions, and consideration of the need for long-term residential care or supportive accommodation.
Traditional regimens in the United States have used 100 mg of parental (intravenous or intramuscular) thiamine for 3-7 days (treatment period), followed by oral thiamine indefinitely as long as the patient is consuming alcohol. Because of case reports suggesting that much higher doses are needed (up to 1 g of parental thiamine) to obtain resolution of symptoms, some authorities such as the Royal College of Physicians have suggested 500 mg intravenously 3 times a day for 2-3 days. If no response is noted, discontinue supplementation and assess for supportive care (unless the patient is comatose). If there is a partial response, continue at 250 mg parenterally for 5 days or as long as improvement continues in patients with neuropsychiatric symptoms.[34, 27]
Use of high-dose thiamine (500 mg TID intravenously) may be indicated given the detrimental consequence of untreated or undertreated WKS. A response to high-dose thiamine was reported as last as 30 days after initial recognition and treatment with thiamine at 100mg/day IV. Monitoring of thiamine levels after treatment may be useful in guiding both route of administration and dosing.
After the patient’s response has plateaued, supplement with oral thiamine indefinitely until the patient is no longer at risk (eg, as long as they are drinking alcohol).
Most recommendations for the initial use of parental thiamine are based on the poor bioavailability of oral thiamine, which is estimated to be between 3.7% and 5.3%. Studies have suggested that 8.3 mg is the maximum that can be absorbed from a single oral thiamine dose, suggesting an absorption pathway that is easily saturated. This seemed to be confirmed when another study showed very little thiamine is excreted in urine when oral doses greater than 2.5 mg are given.
The most prominent study was in 52 prisoners of war in a report published in 1947. All developed Wernicke-Korsakoff syndrome during a period of starvation and/or nutritional deficiency (eg, living on white rice). Fifteen patients were treated with oral thiamine only and 67% (10 patients) died. Of the 37 who received intramuscular thiamine, 11 died, a mortality rate of 30%.
Recent studies have challenged this and demonstrated that high-dose oral thiamine (500-1500 mg) can achieve correspondingly high blood levels in healthy subjects. However, these studies have generally been in healthy subjects without comorbidities and no measurement has been made of the biological effect or tissues absorption of thiamine, especially in the brain. Until clinical studies have been undertaken on high-dose oral thiamine, the strong recommendation is that parental thiamine be the first line for the initial treatment of Wernicke-Korsakoff syndrome.
Allergic/anaphylactic reactions to thiamine do occur, but it does not appear to be at a rate to justify specific concern, despite a case report in the nursing literature that appears to have impacted many hospital protocols for thiamine administration. One paper reported more than 300,000 patients treated with parental thiamine without anaphylaxis.
The Royal College of Physician guidelines recommend that intravenous thiamine be given over 30 minutes. This usually involves adding the thiamine to intravenous rehydration solutions, often with a parenteral multivitamin (banana bag). However, this is an empiric recommendation and is not followed at all institutions.
Administration of intravenous glucose to patients who are severely malnourished can exhaust their supply of thiamine and precipitate Wernicke-Korsakoff syndrome. Thus, good practice demands administration of thiamine prior to or simultaneously with glucose infusion in patients at high risk for Wernicke-Korsakoff syndrome. However, emergency care for life-threatening hypoglycemia should not be withheld for thiamine administration.
Emergency psychiatric hospitalization and evaluation are indicated when the patient is having active psychotic symptoms that pose a danger to himself or herself or to others. Many such patients also meet the criteria of grave disability (ie, inability to provide basic needs, such as food and shelter). In such cases, however, the patient should generally be medically and neurologically stable prior to transfer to a psychiatric facility, where acute medical work-up and monitoring may be available (eg, IV access, neuroimaging, nutritionist, neurology consultation).
In most cases, patients with psychotic symptoms may require inpatient medical hospitalization and psychiatric consultation. Once medically stabilized, patients may need continued psychiatric care if severe psychotic symptoms persist.
In patients with comorbid acute alcohol withdrawal, treatment with IV/IM thiamine occurs concurrently with the indicated alcohol withdrawal procedures.
Supplementation of electrolytes, particularly magnesium and potassium (often low in people with alcoholism), may be required in addition to thiamine. Magnesium acts as a cofactor for many enzymes (eg, transketolase for the conversion of thiamine to thiamine pyrophosphate), and, therefore, its deficiency may lead to a refractory response to thiamine supplementation. In patients who are chronically malnourished, the remainder of the B vitamins also should be supplemented with an intravenous or oral multivitamin supplement. In patients with clinical evidence of Wernicke-Korsakoff syndrome, vitamin B-12 levels should be measured.
Further inpatient care
Evaluation for progression or recovery from Wernicke-Korsakoff syndrome symptom complex is the primary reason for further inpatient care. Patients also require monitoring for alcohol withdrawal and the potential cardiac manifestations of Wernicke-Korsakoff syndrome (eg, congestive heart failure). Owing to the acuity of the confessional state and continued neuronal damage, inpatient treatment may be needed to ensure sufficient thiamine supplementation via either oral and parenteral routes.
Diet and Activity
A balanced diet should be resumed as early as possible. Vitamin and electrolyte supplementation should be adhered to in addition to a well-balanced diet initially. Supplementation can be tapered as the patient resumes normal intake and demonstrates symptomatic improvement.
Due to gait abnormalities, unassisted ambulation is discouraged during the initial phase of treatment. Patients may require physical therapy evaluation for gait assistance. Gait abnormalities may be permanent, depending on the severity at initial presentation and the timeliness of therapy.
Referral and Follow-Up Care
Long-term alcohol use is the most common etiology for Wernicke-Korsakoff syndrome, and abstinence provides the best chance for recovery. Referral to an alcohol recovery program should be part of the treatment regimen. Inpatient treatment versus outpatient rehabilitation depends on the needs of the individual and risks of relapse.
Recovering patients will require outpatient follow-up care to evaluate for continued progress or relapse. Patients with long-term alcoholism may benefit from further inpatient or outpatient rehabilitation, depending on the likelihood of compliance.
Patients should continue taking thiamine supplementation, as well as other vitamins and electrolytes, until a well-balanced diet can be maintained. Long-term supplementation may be required in patients who cannot maintain adequate nutritional intake, whether from noncompliance or the underlying disorder.
Deterrence and Prevention
Long-term alcohol use is the most common etiology for the development of Wernicke-Korsakoff syndrome. Abstinence from alcohol, in conjunction with thiamine replacement, provides the best chance for recovery. Refer patients for alcohol abuse counseling, community alcohol abuse treatment programs (eg, Alcoholics Anonymous and other consumer support programs), and couples/family therapy on an individual basis to deter future alcohol use and prevent future episodes of Wernicke-Korsakoff syndrome.
In patients at risk for malnutrition (eg, after gastric bypass surgery), appropriate thiamine and other B-vitamin supplementation should be taken in accordance with a nutritionist’s advice.
In emergency management of patients with acute confusion and concurrent risk factors (eg, alcohol dependence and malnutrition), thiamine administration should be strongly considered, especially prior to glucose administration. Generally, high-carbohydrate diets increase the demand for thiamine. Immediate intravenous thiamine supplementation is the standard of care in ER patients with alcohol use disorders and withdrawal, and should be strongly considered in anyone with malnutrition.
In a large, prospective study, the introduction of thiamine-enriched bread flour was shown to reduce the prevalence of Wernicke-Korsakoff syndrome in Australia. However, whether thiamine fortification in general or additional supplementation in alcoholic beverages could reduce Wernicke-Korsakoff syndrome has not been systematically studied.
Neuropsychological Testing and Rehabilitation
After the acute clinical symptoms stabilize and adequate thiamine supplementation is established, persistent cognitive symptoms will likely stabilize and plateau. Neuropsychological testing should be considered in patients with persistent cognitive symptoms to delineate the various cognitive domains that are impaired. Most commonly, declarative memory, immediate recall, attention and concentration, and executive function are impaired. Procedural learning and memory rehabilitation can be employed to help the patient compensate for certain cognitive deficits to improve quality of life and overall functional improvement.
Thomson AD, Cook CC, Guerrini I, Sheedy D, Harper C, Marshall EJ. Wernicke's encephalopathy: 'Plus ça change, plus c'est la même chose'. Alcohol Alcohol. 2008 Mar-Apr. 43(2):180-6. [Medline].
Thomson AD, Marshall EJ. The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol. 2006 Mar-Apr. 41(2):151-8. [Medline].
Wijnia JW, van de Wetering BJ, Zwart E, Nieuwenhuis KG, Goossensen MA. Evolution of Wernicke-Korsakoff syndrome in self-neglecting alcoholics: preliminary results of relation with Wernicke-delirium and diabetes mellitus. Am J Addict. 2012 Mar-Apr. 21(2):104-10. [Medline].
Thomson AD, Marshall EJ, Bell D. Time to act on the inadequate management of Wernicke's encephalopathy in the UK. Alcohol Alcohol. 2013 Jan-Feb. 48(1):4-8. [Medline].
Singh S, Kumar A. Wernicke encephalopathy after obesity surgery: a systematic review. Neurology. 2007 Mar 13. 68(11):807-11. [Medline].
Van Stavern G, Kumar G, Thuruthumaly C. Visual disturbance after bariatric surgery. JAMA Ophthalmol. 2015 Mar. 133 (3):345-6. [Medline].
Hutcheon DA. Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet. Nutr Clin Pract. 2015 Feb. 30 (1):92-9. [Medline].
Yae S, Okuno S, Onishi H, Kawanishi C. Development of Wernicke encephalopathy in a terminally ill cancer patient consuming an adequate diet: a case report and review of the literature. Palliat Support Care. 2005 Dec. 3(4):333-5. [Medline].
Kesler A, Stolovitch C, Hoffmann C, Avni I, Morad Y. Acute ophthalmoplegia and nystagmus in infants fed a thiamine-deficient formula: an epidemic of Wernicke encephalopathy. J Neuroophthalmol. 2005 Sep. 25(3):169-72. [Medline].
Chiossi G, Neri I, Cavazzuti M, Basso G, Facchinetti F. Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature. Obstet Gynecol Surv. 2006 Apr. 61(4):255-68. [Medline].
Restivo A, Carta MG, Farci AM, Saiu L, Gessa GL, Agabio R. Risk of thiamine deficiency and Wernicke's encephalopathy after gastrointestinal surgery for cancer. Support Care Cancer. 2015 May 2. [Medline].
Rakici SY, Erdemli SD, Yazici ZA, Cengiz E, Acar OG, Tufan G. Wernicke's encephalopathy in a patient with unresectable gastric carcinoma and literature review. Int J Clin Exp Med. 2015. 8 (1):1453-9. [Medline].
Welsh A, Rogers P, Clift F. Nonalcoholic Wernicke's encephalopathy. CJEM. 2015 May 19. 1-4. [Medline].
Schattner A, Kedar A. An unlikely culprit--the many guises of thiamine deficiency. Am J Emerg Med. 2013 Mar. 31(3):635.e5-6. [Medline].
Gardiner S, Hartzell T. Thiamine Deficiency: A Cause of Profound Hypotension and Hypothermia After Plastic Surgery. Aesthet Surg J. 2014 Aug 13. [Medline].
Han JW, Lim S, Shin HS, Park HJ, Jung WJ, Kwon SY, et al. Two cases of Wernicke's encephalopathy in young age patients receiving allogeneic hematopoietic stem cell transplantation. Yonsei Med J. 2012 Sep. 53(5):1049-53. [Medline]. [Full Text].
Cefalo MG, De Ioris MA, Cacchione A, Longo D, Staccioli S, Arcioni F, et al. Wernicke Encephalopathy in Pediatric Neuro-oncology: Presentation of 2 Cases and Review of Literature. J Child Neurol. 2014 Dec. 29(12):NP181-5. [Medline].
Alcaide ML, Jayaweera D, Espinoza L, Kolber M. Wernicke's encephalopathy in AIDS: a preventable cause of fatal neurological deficit. Int J STD AIDS. 2003 Oct. 14(10):712-3. [Medline].
Steinberg A, Gorman E, Tannenbaum J. Thiamine deficiency in stem cell transplant patients: a case series with an accompanying review of the literature. Clin Lymphoma Myeloma Leuk. 2014 Sep. 14 Suppl:S111-3. [Medline].
Ueda K, Takada D, Mii A, et al. Severe thiamine deficiency resulted in Wernicke's encephalopathy in a chronic dialysis patient. Clin Exp Nephrol. 2006 Dec. 10(4):290-3. [Medline].
Rahme R, Moussa R, Awada A, et al. Acute Korsakoff-like amnestic syndrome resulting from left thalamic infarction following a right hippocampal hemorrhage. AJNR Am J Neuroradiol. 2007 Apr. 28(4):759-60. [Medline].
Barennes H, Sengkhamyong K, René JP, Phimmasane M. Beriberi (thiamine deficiency) and high infant mortality in northern Laos. PLoS Negl Trop Dis. 2015 Mar. 9 (3):e0003581. [Medline].
Abdou E, Hazell AS. Thiamine Deficiency: An Update of Pathophysiologic Mechanisms and Future Therapeutic Considerations. Neurochem Res. 2014 Oct 9. [Medline].
McEntee WJ, Mair RG. Memory enhancement in Korsakoff's psychosis by clonidine: further evidence for a noradrenergic deficit. Ann Neurol. 1980 May. 7(5):466-70. [Medline].
Day E, Bentham P, Callaghan R, Kuruvilla T, George S. Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse. Cochrane Database Syst Rev. 2004. CD004033. [Medline].
Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw JJ. An international perspective on the prevalence of the Wernicke-Korsakoff syndrome. Metab Brain Dis. 1995 Mar. 10(1):17-24. [Medline].
Carvajal E, Verdeguer A, Fernández JM, Cañete A, Castel V. Herpesvirus-6 encephalitis complicated by Wernicke-Korsakoff syndrome in a pediatric recipient of unrelated cord blood transplantation. J Pediatr Hematol Oncol. 2001 Dec. 23(9):626-8. [Medline].
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. [Medline].
Gerridzen IJ, Goossensen MA. Patients with Korsakoff syndrome in nursing homes: characteristics, comorbidity, and use of psychotropic drugs. Int Psychogeriatr. 2014 Jan. 26(1):115-21. [Medline].
Victor M, Adams R, Collins G, eds. The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition. Philadelphia, Pa: FA Davis; 1989. 142-5.
Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007 May. 6(5):442-55. [Medline].
Kim J, Park S, Kim JH, Kim SW, Kang WC, Kim SJ. A case of shoshin beriberi presenting as cardiogenic shock with diffuse ST-segment elevation, which dramatically improved after a single dose of thiamine. Cardiovasc J Afr. 2014 Nov 23. 25 (6):e1-5. [Medline].
Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics. 2012 Nov-Dec. 53(6):507-16. [Medline].
Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry. 1997 Jan. 62(1):51-60. [Medline]. [Full Text].
Duca J, Lum CJ, Lo AM. Elevated Lactate Secondary to Gastrointestinal Beriberi. J Gen Intern Med. 2015 Apr 16. [Medline].
Giacalone M, Martinelli R, Abramo A, Rubino A, Pavoni V, Iacconi P, et al. Rapid reversal of severe lactic acidosis after thiamine administration in critically ill adults: a report of 3 cases. Nutr Clin Pract. 2015 Feb. 30 (1):104-10. [Medline].
Dingwall KM, Delima JF, Gent D, Batey RG. Hypomagnesaemia and its potential impact on thiamine utilisation in patients with alcohol misuse at the Alice Springs Hospital. Drug Alcohol Rev. 2015 May. 34 (3):323-8. [Medline].
Maschke M, Weber J, Bonnet U, et al. Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI. J Neurol. 2005 Jun. 252(6):704-11. [Medline].
Antunez E, Estruch R, Cardenal C, Nicolas JM, Fernandez-Sola J, Urbano-Marquez A. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke's encephalopathy. AJR Am J Roentgenol. 1998 Oct. 171(4):1131-7. [Medline].
Manzo G, De Gennaro A, Cozzolino A, Serino A, Fenza G, Manto A. MR imaging findings in alcoholic and nonalcoholic acute Wernicke's encephalopathy: a review. Biomed Res Int. 2014. 2014:503596. [Medline]. [Full Text].
Charness ME, DeLaPaz RL. Mamillary body atrophy in Wernicke's encephalopathy: antemortem identification using magnetic resonance imaging. Ann Neurol. 1987 Nov. 22(5):595-600. [Medline].
Thomson AD, Cook CC, 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 Nov-Dec. 37(6):513-21. [Medline].
Isenberg-Grzeda E, Hsu AJ, Hatzoglou V, Nelso C, Breitbart W. Palliative treatment of thiamine-related encephalopathy (Wernicke's encephalopathy) in cancer: A case series and review of the literature. Palliat Support Care. 2014 Oct 23. 1-9. [Medline].
Weber W, Kewitz H. Determination of thiamine in human plasma and its pharmacokinetics. Eur J Clin Pharmacol. 1985. 28(2):213-9. [Medline].
Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol Suppl. 2000 May-Jun. 35(1):2-7. [Medline].
Morrison AB, Campbell JA. Vitamin absorption studies. I. Factors influencing the excretion of oral test doses of thiamine and riboflavin by human subjects. J Nutr. 1960 Dec. 72:435-40. [Medline].
DeWardener HE, Lennox B. Cerebral beriberi (Wernicke's encephalopathy); review of 52 cases in a Singapore prisoner-of-war hospital. Lancet. 1947 Jan 4. 1(6436):11-7. [Medline].
Wrenn KD, Slovis CM. Is intravenous thiamine safe?. Am J Emerg Med. 1992 Mar. 10(2):165. [Medline].
Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA. 1998 Feb 25. 279(8):583-4. [Medline].
Harper CG, Sheedy DL, Lara AI, Garrick TM, Hilton JM, Raisanen J. Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference?. Med J Aust. 1998 Jun 1. 168(11):542-5. [Medline]. [Full Text].
Behura SS, Swain SP. Neuropsychological functioning in Wernicke's encephalopathy. Ind Psychiatry J. 2015 Jan-Jun. 24 (1):99-103. [Medline].
Oudman E, Nijboer TC, Postma A, Wijnia JW, Van der Stigchel S. Procedural Learning and Memory Rehabilitation in Korsakoff's Syndrome - a Review of the Literature. Neuropsychol Rev. 2015 Jun. 25 (2):134-48. [Medline].
Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec. 17(12):1408-18. [Medline].
Caso F, Fiorino A, Falautano M, et al. Treatment of Wernicke's encephalopathy with high dose of thiamine in a patient with pyloric sub-stenosis: description of a case. Neurol Sci. 2010 Dec. 31(6):859-61. [Medline].
Kishimoto Y, Ikeda K, Murata K, Kawabe K, Hirayama T, Iwasaki Y. Rapid development of central pontine myelinolysis after recovery from Wernicke encephalopathy: a non-alcoholic case without hyponatremia. Intern Med. 2012. 51(12):1599-603. [Medline].
Cochrane M, Cochrane A, Jauhar P, Ashton E. Acetylcholinesterase inhibitors for the treatment of Wernicke-Korsakoff syndrome--three further cases show response to donepezil. Alcohol Alcohol. 2005 Mar-Apr. 40(2):151-4. [Medline].
Rustembegovic A, Kundurovic Z, Sapcanin A, Sofic E. A placebo-controlled study of memantine (Ebixa) in dementia of Wernicke-Korsakoff syndrome. Med Arh. 2003. 57(3):149-50. [Medline].
Luykx HJ, Dorresteijn LD, Haffmans PM, Bonebakker A, Kerkmeer M, Hendriks VM. Rivastigmine in Wernicke-Korsakoff's syndrome: five patients with rivastigmine showed no more improvement than five patients without rivastigmine. Alcohol Alcohol. 2008 Jan-Feb. 43(1):70-2. [Medline].
Chen G, Luo J. Anthocyanins: are they beneficial in treating ethanol neurotoxicity?. Neurotox Res. 2010 Jan. 17(1):91-101. [Medline].
Scalzo SJ, Bowden SC, Ambrose ML, Whelan G, Cook MJ. Wernicke-Korsakoff syndrome not related to alcohol use: a systematic review. J Neurol Neurosurg Psychiatry. 2015 Jan 14. [Medline].