Wernicke’s encephalopathy

 

Short description

Wernicke’s encephalopathy a pathological neurological disorder caused by thiamin deficiency, and characterized by nystagmus, partial ophthalmoplegia, ataxia, and confusion that shows up abruptly.

Overview

Wernicke’s encephalopathy (WE) a rare life threatening neurological disorder caused by Vitamin B deficiency and characterized by altered consciousness, ocular dysfunction, and ataxia (classic clinical triad) [1][2]. It is common in chronic alcohol addicts, as chronic alcoholism affects thiamine uptake and utilization, resulting in its deficiency. Chronic Thiamine deficiency affects the brain barrier and contributes to a possible intracellular swelling (narrowing of the intracellular space) leading to a decreased perfusion in the affected part of the brain (disruption of the vascular-brain barrier), because thiamine is an osmotic gradient regulator and an essential intermediate coenzyme in the metabolism of carbohydrates [5] [6].

Less commonly, Wernicke’s encephalopathy develop in nonalcoholic habituary or pathological conditions, such as hyperemesis gravidarum, prolonged starvation, bariatric surgery, HIV positive, and in healthy infants given the wrong formulas [7].

Diagnostic imaging studies are useful in the diagnosis and treatment procedures, as it is a frequently unrecognized life threatening medical emergency, especially that the specific symptoms “classic clinical triad” may be absent at clinical onset, standard treatment consists of intravenous administration of thiamine [1] [2].

Neuroradiologic findings show symmetric impulse alterations in the mamillary bodies, medial thalamic, tectal plate, and periaqueductal area [3].

Epidemics can occur in artificial unnatural circumstances exclusively, as evidenced by a report of Israeli infants fed by formula deficient in thiamine while suffering of infantile thiamine deficiency [8].

Etiology

Thiamine plays an essential role in the metabolism of carbohydrates being a cofactor of several essential enzymes in the Krebs cycle and the pentose phosphate pathway, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase [9].

In thiamine deficiency, thiamine dependent cellular system begins to fail, leading eventually to apoptosis (cellular death) that triggers a the localized vasogenic response. Aside of that thiamine dependent enzymes (Pyruvate dehydrogenase and alpha-ketoglutarate ) are essential key factors in cerebral metabolism and energy utilization, thus thiamine deficiency accelerates brain tissue injury by inhibiting metabolism in brain regions with high thiamine turnover and higher metabolic demands [9]. Moreover, the reduced production of succinate, a component of gamma-aminobutyric acid (GABA) metabolism and a key in the electrical stimulation of neurons, leads to further CNS injury (central nervous system injury).

Pyruvate dehydrogenase deficit leads to increased lactic acid production, as the reduced conversion of pyruvate to acetyl coenzyme A results in less efficient oxidative phosphorylation [11].

Thiamine pyrophosphate is also essential for the synthesis of nucleotide, nicotinamide adenine dinucleotide phosphate (NADPH), as well as it plays an enormous role in the regulation and restoration of reduced glutathione levels within erythrocytes [11].

Causes

Chronic alcoholism is regarded as the main cause of WE in the western world, as it affects thiamine uptake and utilization.[1] In chronic alcoholism, malnutrition can reduce the amount of thiamine absorbed in the intestines by 70%, decreasing serum thiamine levels between 30% and 98% below the lower level established in normal people.

Thiamine acts as a coenzyme in the metabolism of glucose and lipids, and because the depots of water soluble vitamins are limited in the body, deficiency can present within 2 to 3 weeks of intake cessation [14].

Chronic alcohol consumption may induce thiamine deficiency leading to WE through several possible mechanisms: malnutrition (thiamine deficiency in parenteral nutrition), bad life habits (replacement of essential nutrients with alcoholic drinks and fast food), genetic predisposition, malabsorption (from celiac sprue), hepatocellular diseases, thiamine transport problems, decreased phosphorylation to thiamine pyrophosphate and excessive requirements for the metabolism of alcohol [14]. Moreover, nonalcoholic conditions can lead to WE in cases such as chronic starvation, hyperemesis gravidarum, hemodialysis-induced thiamine deficiency in patients with end-stage renal disease and bariatric surgery (thiamine deficiency after obesity surgery) “bariatric beriberi” [12][7].

Epidemiology

The incidence of WE in developing nations is higher than that found in advanced modern nations, because in these developing countries the incidence of malnutrition is higher, as well as the poor people in these countries are less likely to get proper vitamin supplementation to correct the deficit. Additionally, cases of WE in men outnumber those in women, and women appear to be more susceptible to developing WE than men, because alcoholism is 3-4 times more frequent in men than in women and the male-to-female ratio for WE is 1.7:1. Moreover, the prevalence of WE lesions seen on autopsy of alcohol abusers in one report was 12.5 percent [18]. Additionally, autopsy revealed WE lesions in nearly one third of those alcohol-related deaths [19] [20].

Pathophysiology

Normally, a healthy individual needs about 1–2 mg of thiamine daily. Moreover, the deposited amount of thiamine in the body in case of deprivation is enough for a period of four-to-six weeks at most, as the body can only store an amount between 30–50 mg of thiamine.

During the initial phases of deprivation, the deficit can be corrected by prescribing thiamine supplementation orally. alcohol addicts commonly suffer of alcohol-related liver damage, and the ability to store thiamine in the liver is progressively reduced. Also alcoholics usually drink alcohol instead of properly eating, whereas alcoholic drinks are highly saturated in carbohydrates and often include very low amounts of thiamine (commonly thiamine is absent), additionally a state with an already compromised nutritional and physiological factors may be further exacerbated by vomiting, diarrhea, and steatorrhea that in turn promote malnutrition [24].

Dietary thiamine undergo at least four transport steps before being activated in brain cells, in the 1st step dietary thiamine is absorbed from the intestines through an active, saturable, stereospecific and sodium-dependent transport mechanism, and then it is exported by the enterocytes into the blood. This transport mechanism limits thiamine absorption in healthy individuals to less than 4.5 mg–5.6 mg per oral dose greater than 15 mg. In malnourished, alcoholic or intoxicated individuals absorption can decrease to less than 1.5 mg per the same oral dose [22]. Following Thiamine must then cross the vascular-brain barrier to reach the neurons before it is finally transported into the mitochondria and nuclei of the neurons.

Prognosis

Administration of thiamine improves the outcome of this life threatening condition to a degree and fastens the recovery rate in many patients; however, neurologic dysfunction can persist even after treatment [9]. Ataxia and confusion may persist for months thereafter. If untreated, WE progresses with mortality rate of 10 to 20%. Of those surviving 80% develop Korsakoff psychosis, a combination called Wernicke’s-Korsakoff syndrome.

Presentation

The classic triad of WE include encephalopathy, ataxic gait, and to an extinct a form of oculomotor dysfunction. However, 90% of patients present with symptoms and signs that may not be associated with the classical clinical triad. Chronic alcohol addicts presenting with any of the following symptoms or signs like acute confusion, ataxia, memory disturbance, delirium tremens, stupor, seizures, ophthalmoplegia, bilateral visual disturbances and papilledema, hypotension and tachycardia, hypothermia with hypotension,  hearing loss, hallucinations and behavioral disturbances should be considered for WE. Late disease may present with symptoms like increased muscular tone and spastic paresis, hyperthermia, choreic dyskinesias and coma.

Wernicke’s encephalopathy is usually accompanied or followed by Korsakoff’s syndrome, a situation that is characterized by Korsakoff’s dementia, severe memory loss, ataxia, apathy, disorientation, confabulations, hallucinations, paralysis of muscles controlling the eye and coma.

A key point in the diagnosis and treatment process is that Wernicke’s encephalopathy may respond to vitamin B1 therapy, while Korsakoff’s syndrome does not.

Symptoms

Wernicke’s encephalopathy cause specific and nonspecific symptoms; classic symptoms termed as the classical clinical triad include confusion, drowsiness, involuntary eye movements (nystagmus), partial paralysis of the eyes (ophthalmoplegia), and loss of balance.

To maintain balance, people take slow, short steps while walking with their feet far apart.

Other symptoms include tremor, agitation, a cold body temperature, Orthostatic hypotension (a sudden and excessive decrease in blood pressure when people stand), and fainting all of which are caused by Internal corpuscular malfunctions.

If untreated, Wernicke’s encephalopathy progress and can lead to Korsakoff’s syndrome, coma, or death.

The combination of WE with Korsakoff’s syndrome is called Wernicke-Korsakoff syndrome.

Workup

Wernicke’s encephalopathy Patients commonly present with altered mental status and other neurologic abnormalities. Obtaining a detailed patient history, while performing a detailed physical / neurological examination, radiographic evaluation and laboratory workup, are the golden standard maneuvers used to rule out other possible causes of central nervous system (CNS) dysfunction.

Clinical interview and history disease, case study to identify malnutrition or vitamin deficiency, while seeking any related neurological abnormalities.

Imaging studies, such as CT of the brain or EEG.

Laboratory tests to rule out other etiologies and disorders, as no specific laboratory tests are available for diagnosing WE, standard management include blood tests, glucose, CBC, liver function tests, ABG measurements, toxicology screening.

Thiamin levels are not routinely measured. Nevertheless, thiamine administration is mandatory and recommended while tests are being processed, the all time motto should be “If in doubt, treat,” as administration of thiamine have no side effects. Moreover, the diagnosis of Wernicke’s encephalopathy is a clinical diagnosis, and normal electrolyte levels may give only false reassurance and delay therapy. In addition, neither a normal CT (computed tomography) scan nor a normal MRI (magnetic resonance imaging) of the brain rule out the presence of acute WE or chronic WKS [26].

The use of laboratory and radiographic tests remains important to exclude other underlying conditions.

Treatment

Onset of the disease may be acute, subacute, or chronic, but regardless of the form WE must be always managed as a medical emergency, an immediate administration of thiamin 100 mg IV or IM, is highly recommended and should be continued daily for at least 3 to 5 days even if other competing diagnoses of CNS processes are being considered. Because the condition is potentially reversible, and thiamine improves the patient’s condition to some degree in almost all cases. However, persistent neurologic dysfunction is common [9].

Treatment is indicated in patients exhibiting any combination of symptoms and signs, particularly if the patient is in a high-risk population.

Treatment consists of parenteral administration of thiamin (typically 100 mg IM followed by 50 mg po once/day), hypomagnesemia should be corrected by administering Magnesium sulfate 1 to 2 g IM or IV q 6 to 8 h or Magnesium oxide 400 to 800 mg po once/day, Magnesium is a necessary cofactor in thiamin-dependent metabolism.

Supportive treatment includes rehydration, correction of electrolyte abnormalities, and general nutritional therapy, including multivitamins especially vitamin B12 and folate (1 mg po once/day for both), to be considered if IV dextrose is necessary. Alcohol cessation is mandatory.

Patients with advanced disease require hospitalization.

Prevention

Daily administration of oral thiamine (100 mg) is the only available long-term therapy with proven efficacy for prevention or treatment of WE in most alcoholic patients (outpatient basis).

Patient Information

Thiamin deficiency is the basic cause behind Wernicke’s encephalopathy, a disease characterized by a triad of specific symptoms including confusion, eye problems, and loss of balance.

Wernicke’s encephalopathy commonly develops in alcoholic people because the chronic extreme use of alcohol decreases the absorption of thiamin in the intestines. In addition, alcohol addicts often fail to get an adequate diet leading to long-term deficit of thiamin (a B vitamin). Rarely, Wernicke’s encephalopathy may result from other conditions such as dialysis, severe vomiting, cancer, AIDS, and starvation (forced or self-imposed starvation) that cause prolonged malnutrition or vitamin B deficiencies.

 

References

 

1.        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;49:341–45
2.        Ogershok PR, Rahman A, Nestor S, et al. Wernicke encephalopathy in nonalcoholic patients. Am J Med Sci 2002;323:107–11
3.        Gallucci M, Bozzao A, Splendiani A, et al. Wernicke encephalopathy: MR findings in five patients. AJNR Am J Neuroradiol 1990;11:887–92
4.        Victor M. The Wernicke-Korsakoff syndrome. In: Vinken PJ, Bruyn GW, eds. Handbook of Clinical Neurology.Vol 28 . Amsterdam: North Holland;1976 :243–70
5.        Harper C, Butterworth R. Nutritional and metabolic disorders. In: Graham DI, Lantos PL, eds. Greenfield’s Neuropathology,vol 1 , 6th ed. London: Hodder Arnold;1997:601–52
6.        Schroth G, Wichmann W, Valavanis A. Blood-brain-barrier disruption in acute Wernicke encephalopathy: MR findings. J Comput Assist Tomogr 1991;15:1059–61
7.        Attard O, Dietemann JL, Diemunsch P, Pottecher T, Meyer A, Calon BL. Wernicke encephalopathy: a complication of parenteral nutrition diagnosed by magnetic resonance imaging. Anesthesiology. 2006 Oct. 105(4):847-8.
8.        Fattal-Valevski A, Kesler A, Sela BA, et al. Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. Pediatrics. 2005 Feb. 115(2):e233-8.
9.        Donnino MW, Vega J, Miller J, et al. Myths and misconceptions of Wernicke’s encephalopathy: what every emergency physician should know. Ann Emerg Med.2007 Dec. 50(6):715-21.
10.     Buscaglia J, Faris J. Unsteady, unfocused, and unable to hear. Am J Med. 2005Nov. 118(11):1215-7.
11.     Decker MJ, Isaacman DJ. A common cause of altered mental status occurring at an uncommon age. Pediatr Emerg Care. 2000 Apr. 16(2):94-6.
12.     Aasheim ET. Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg. 2008 Nov. 248(5):714-20.
13.     Hung SC, Hung SH, Tarng DC, Yang WC, Chen TW, Huang TP. Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis. 2001 Nov. 38(5):941-7.
14.     Day E, Bentham PW, Callaghan R, Kuruvilla T, George S. Thiamine for prevention and treatment of Wernicke- Korsakoff Syndrome in people who abuse alcohol (Cochrane Review ). The Cochrane Library. 2013. 7:1-20.
15.     Victor, M, Adams, RA, Collins, GH. The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition. FA Davis, Philadelphia 1989.
16.     Harper C, Fornes P, Duyckaerts C, et al. An international perspective on the prevalence of the Wernicke-Korsakoff syndrome. Metab Brain Dis 1995; 10:17.
17.     Galvin R, Bråthen G, Ivashynka A, et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol 2010; 17:1408.
18.     Torvik A, Lindboe CF, Rogde S. Brain lesions in alcoholics. A neuropathological study with clinical correlations. J Neurol Sci 1982; 56:233.
19.     Naidoo DP, Bramdev A, Cooper K. Autopsy prevalence of Wernicke’s encephalopathy in alcohol-related disease. S Afr Med J 1996; 86:1110.
20.     Skullerud K, Andersen SN, Lundevall J. Cerebral lesions and causes of death in male alcoholics. A forensic autopsy study. Int J Legal Med 1991; 104:209.
21.     Harper C. The incidence of Wernicke’s encephalopathy in Australia—a neuropathological study of 131 cases. J Neurol Neurosurg Psychiatry 1983; 46:593.
22.     Cook CC, Hallwood PM, Thomson AD. B-vitamin deficiency and neuro-psychiatric syndromes in alcohol misuse. Alcohol, 1998:33:317-336.
23.     Thomson AD, Marshall EJ. The natural history of Wernicke’s encephalopathy and Korsakoff’s Psychosis. Alcohol, 2006;41:151-158.
24.     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.
25.     Thomson AD, Frank O, Baker H, et al. Thiamine propyl disulfide: absorption and utilization. Ann Intern Med, 1971;74:529–534.
26.     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 Oct.171(4):1131-7.

Verified by: Dr.Diab (January 7, 2017)

Citation: Dr.Diab. (January 7, 2017). Wernicke’s encephalopathy. Medcoi Journal of Medicine, 2(2). urn:medcoi:article15970.