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Wernicke-Korsakoff Syndrome

Wernicke-Korsakoff syndrome is a brain disorder caused by deficiency of thiamine. This syndrome is also related to alcohol abuse. Symptoms depend on the part of the brain affected. 


Presentation

Classic symptoms of Wernicke encephalopathy, confusion, ataxia and ocular symptoms are present in about 38% of the patients [9]. Ocular abnormalities which include one or more of the following symptoms are reliable in diagnosing WKS.

Damage to different parts of the brain leads to impaired movement and coordination manifested by abnormal gait and posture. In severe form of the condition, patient may be unable to walk without proper support. Slow movement with short-steps, wobbling or unsteady, uncoordinated gait is also characteristic. Tremors can be noted in those with alcohol withdrawal symptoms. Those affected may generally be indifferent to the events taking place around and may lack of concentration.

Few weeks after the appearance of the ocular and ataxia symptoms, about 90% of the patients may develop slight changes in their consciousness. Hallucinations are common among patients and many have memory deficits. Both anterograde and retrograde amnesia is noted in the patients. Inability to recall or memorize the events after a few minutes is characteristic, and becomes  severe in patients with this syndrome. Some may have mood variations that range from calm presence to agitation or acute delirium. Alcoholics may present an unkempt look and may not be worried about their health condition.

When the thermoregulatory centers of the brain are affected, this may result in hypothermia. About 80% of the patients with WKS have peripheral neuropathy. Tachycardia, syncope and postural hypotension are also common. Vomiting and many conditions associated with vitamin B-12 deficiency like pellagra, amblyopia and iron-deficiency anemia may be noted as comorbid conditions.

Amnesia
  • Anterograde amnesia could therefore be the expression of damage to an extended hippocampal system, and the distinction between temporal lobe and diencephalic amnesia has limited value.[ncbi.nlm.nih.gov]
  • Wernicke's encephalopathy is characterised by eye and gait disorders and mental confusion, and can lead to the profound and permanent amnesia known as Korsakoff's psychosis.[ncbi.nlm.nih.gov]
  • Nystagmus and cerebellar ataxia quickly resolved when administered thiamine, although severe global amnesia consistent with Korsakoff's syndrome persisted.[ncbi.nlm.nih.gov]
  • Abstract The neural correlate of anterograde amnesia in Wernicke-Korsakoff syndrome (WKS) is still debated.[ncbi.nlm.nih.gov]
  • A neuropsychological evaluation at 14 months post-surgery revealed anterograde amnesia for verbal and visual-perceptual material. There was no clear period of temporally graded retrograde amnesia.[ncbi.nlm.nih.gov]
Memory Impairment
  • The pattern of both anterograde and retrograde memory impairment and frontal pathology is shown to be comparable with that observed in patients with Wernicke-Korsakoff Syndrome of an alcoholic etiology.[ncbi.nlm.nih.gov]
  • Memory impairment has been linked to dysfunction of neurons in the cholinergic system.[ncbi.nlm.nih.gov]
  • From a clinical perspective, neuropsychological evaluation of thiamine treated, bariatric surgery-related, Wernicke's encephalopathy cases is indicated if there is suspicion of residual memory impairment.[ncbi.nlm.nih.gov]
  • The operational diagnostic criteria (at least two of the following: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment), which are considered more reliable than the classical triad, were[ncbi.nlm.nih.gov]
Upbeat Nystagmus
  • Ophthalmologic examination showed decreased visual acuity, upbeat nystagmus, diplopia and retinal hemorrhage. We report a relatively rare case of Wernicke-Korsakoff syndrome with ophthalmic symptoms induced by hyperemesis gravidarum.[ncbi.nlm.nih.gov]

Workup

Even before a definitive diagnosis is made, treatment is started to prevent complications. If a confirmation is not obtained for the condition, empirical treatment can be started. A number of laboratory studies will help in differential diagnosis and serum thymine levels is one of them. This is particularly important in the case of patients who have an increased risk of thymine deficiency. Physical examination and a complete medical history play a major role in diagnosis of the condition.

Electrolyte levels will help in differentiating the symptom of WKS from that caused by metabolic alterations. Liver function test is beneficial in checking alcohol abuse and organ dysfunction, if any. Symptoms due to hypoxia and hypercarbia can be evaluated by measuring arterial blood gases. In most of the cases serum thymine levels remain low and often help in confirming the presence of the syndrome. Symptoms caused by infections in the central nervous system can be differentiated by a lumbar puncture.

CT imaging helps in diagnosing hemorrhage and edema. MRI is more sensitive in diagnosing the condition, particularly in those cases where medical history shows susceptibility but ocular and ataxia symptoms are absent. The sensitivity is better in diffusion-weighted MRI [10]. EEG is suggested to rule out the differential diagnosis for convulsive and non-convulsive epilepsy.

Human Herpesvirus 6
  • We found human herpesvirus 6 (HHV-6) DNA in CSF and cytomegalovirus in bronchoalveolar lavage using polymerase chain reaction techniques. Treatment with ganciclovir and foscarnet was effective, with total resolution of symptoms.[ncbi.nlm.nih.gov]

Treatment

This disease spectrum is a progressive, long-term condition which requires immediate treatment to prevent advancement. To start with, high-dose of vitamin B1 is administered parenterally and this will help in improving the symptoms of Wernicke syndrome. In most of the cases, the mental state also improves, and if it does not secondary steps like oral thiamine should be taken. Patients whose symptoms of Korsakoff syndrome does not improve, rehabilitation and long-term treatment is suggested. It is equally important to control the different comorbid conditions and deficiencies, if present. The recommended thiamine dosage is 500mg administered intravenously for 2-3 days followed by oral thiamine to resolve the symptoms [11]. Serum thiamine levels should be monitored to decide further dosage and route of administration. Oral thiamine should be continued till the person is no longer under the risk of the disease spectrum. In addition to thiamine, other electrolytes including magnesium and potassium might be needed for the patient to avoid a refractory response to the administration of the vitamin. And if the patient is severely malnourished, entire set of vitamin B complex needs to be supplemented.

Patient who have acute psychosis require hospitalization for evaluation and treatment. When symptoms of psychosis persist psychiatric care should be continued. In case of dementia, acetylcholinsterase inhibitors and memantine might be helpful in enhancing the cognitive state of the patient.

Prognosis

When timely and adequate treatment is not given for patients with Wernicke’s encephalopathy, about 85% of the survivors develop Korsakoff’s syndrome. A study conducted on 245 patients with WKS reported that about 25% of the patients need long-term care for management. Most of the abnormalities in the eye (nystagmus) improve with thiamine replenishment. Symptoms of ataxia also resolve in about 40% of the patients with this syndrome. Changes in the mental state like confusion may also resolve gradually with thiamine treatment. Amnesia may persist for some more time even when confusion is resolved. Some patients may have learning and memory defects. Recovery is easier and earlier when alcohol consumption is controlled or zero. If secondary complications like infections and liver failure result, they may be life-threatening.

Etiology

Thiamine deficiency is the main cause WKS and thus, malnourishment increases the risk of this syndrome considerably. It is also linked to alcohol abuse but can also be seen in people who do not have alcohol-dependency. A number of factors are associated with WKS including:

  • Disorders like anorexia nervosa, terminal cancer and schizophrenia as all these conditions may lead to starvation and malnourishment [2] [3]
  • Alcohol abuse, which when present along with thiamine deficiency has a synergistic effect leading to WKS syndrome. Alcoholism affects the absorption, transport and storage of thiamine
  • Malignant or benign tumors in the gastric or intestinal region
  • Obstruction in the intestine [4]
  • AIDS and diseases like disseminated tuberculosis
  • Chronic dialysis which affects the absorption of thiamine [5]
  • Bariatric surgery may lead to Wernicke’s encephalopathy in the first few weeks after surgery. If this condition is not treated adequately, it may lead to Korsakoff’s syndrome

Epidemiology

Alcohol abuse and malnourishment are two most important factors in the development of this syndrome. About 0-3% of the people in different countries are found to have WKS [6]. About 85% of the patients who survive acute form of Wernicke encephalopathy without adequate treatment go on to develop WKS. The prevalence of this syndrome is found to be higher in socially and economically backward sections of society. This is especially true for people who live alone, or are homeless and alcoholics. The symptoms of this syndrome are rare in children but may develop at any age from 30 years and over. WKS is found to be more common among males than females. Rate of alcohol abuse is related to the development of this disease spectrum. But age-related changes or Alzheimer disease are not known to increase or influence the risk of WKS. This syndrome is not known to have genetic susceptibility that raises the risk of its occurrence in certain races.

Sex distribution
Age distribution

Pathophysiology

Thiamine or vitamin B1 is absorbed from the anterior part of the gastrointestinal tract and stored in the body for approximately 18 days. The active form of this vitamin is thiamine pyrophoshphate which is important in the action of enzymes including pyruvate dehydrogenase and transketolase. These enzymes play an important role in the synthesis of amino acids and neurotransmitters. When the intake of thiamine is inadequate or when the store of this vitamin is depleted, some areas of the brain start showing signs of injury and impaired functioning [7]. Damage in the neurons of the brain results in altered ocular movements. But thiamine supplementation is found to reverse the condition, suggesting that the damage is not considerable.

When the lesions appear in the cerebellum, WKS affects movement and coordination resulting in ataxia. Ataxia of gait is a very common symptom of cerebellar damage due to thiamine deficiency. Damages to diencephalon including the connector to amygdala result in memory defects. This structural damage seems to be persistent as the symptoms are irreversible even with thiamine replenishment. Prolonged subdural hematoma brings about structural changes in the frontal and temporal lobes resulting in symptoms of WKS [8]. These symptoms are also irreversible as the damage is persistent.

Prevention

One of the most common causes for the development of WKS is alcohol abuse and hence abstaining from alcohol is the best way to avoid this syndrome. Thiamine supplementation is a must for those patients who are alcoholic. Socioeconomic and nutritional status of the patient will help in understanding whether a person is under the risk of developing WKS. To prevent any complications, thiamine supplementation should be diligently continued.

Summary

Wernicke-Korsakoff syndrome (WKS) is a disease spectrum characterized by the presence of symptoms of both Wernicke encephalopathy and Korsakoff syndrome [1]. Wernicke’s encephalopathy, also known as Wernicke syndrome, manifests itself in the form of a characteristic clinical triad – confusion, ataxia and ocular abnormalities. Korsakoff syndrome, on the other hand, is a psychiatric disorder characterized by memory loss and psychosis. In WKS, confusion is acute or subacute in nature and is often reversible, while dementia is more or less persistent. Symptoms of Korsakoff syndrome are manifested late, particularly when the Wernicke’s syndrome is not treated appropriately. This syndrome is mostly seen in people belonging to socially and economically deprived background who are prone to alcohol abuse.

Patient Information

Wernicke-Korsakoff syndrome (WKS) is a brain disorder caused by deficiency of vitamin B1 and is associated with alcohol abuse. But in some cases this syndrome may be noted in patients who are not alcoholic. In this disease spectrum, two separate conditions are present – Wernicke encephalopathy and Korsakoff syndrome. Symptoms of Korsakoff psychosis often appear few weeks after the symptoms of Wernicke syndrome. Conditions that affect the absorption of vitamin B1 also result in this syndrome. The major risk factors of this disease spectrum include poor socioeconomic conditions, prolonged dialysis, AIDS, bariatric surgery, and malignant conditions in the gastrointestinal track.

The most common symptoms of Wernicke encephalopathy include abnormalities in vision like double vision, drooping eyelid, abnormal movements, and loss of muscle coordination. When left untreated, Wernicke syndrome may lead to psychosis and dementia, two most common symptoms of Korsakoff syndrome. The person might have severe memory loss, confusion and hallucinations.

Diagnosis of this syndrome is a little bit hard as the patient is confused and may not be able to give all the physical details to the doctor. The doctor will check for signs of alcohol addiction and prescribe a liver function test to assess the damage to the organ. Symptoms of malnourishment are also noted as they may suggest thiamine deficiency. Doctor may opt for imaging techniques like CT scan and MRI to look for damages in different parts of the brain. Mental defects of the patient are also checked using neurophysiological tests.

Treatment for the disease is started almost immediately to prevent its progression and avoid complications. Vitamin B1 will be given intravenously followed by oral vitamin to resolve vitamin B1 deficiency. If the patient is an alcoholic, rehabilitation might be suggested. Early treatment will help in preventing irreversible damage and avoiding eye and muscle abnormalities. Patients should remember to have a well-balanced diet to prevent deficiencies of any kind.

References

Article

  1. Thomson A. The natural history and pathophysiology of Wernicke's encephalopathy and Korsakoff's psychosis. Alcohol and Alcoholism. 2006;41(2):151-158. 
  2. Saad L, Silva L, Banzato C, Dantas C, Garcia C. Anorexia nervosa and Wernicke-Korsakoff syndrome: a case report. J Med Case Rep. 2010;4(1):217. 
  3. Harrison R, Vu T, Hunter A. Wernicke's Encephalopathy in a Patient with Schizophrenia. J Gen Intern Med. 2006;21(12):C8-C11. 
  4. Schattner A, Kedar A. An unlikely culprit—the many guises of thiamine deficiency. The American Journal of Emergency Medicine. 2013;31(3):635.e5-635.e6. 
  5. Ueda K, Takada D, Mii A et al. Severe thiamine deficiency resulted in Wernicke's encephalopathy in a chronic dialysis patient. Clinical and Experimental Nephrology. 2006;10(4):290-293. 
  6. Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw J. An international perspective on the prevalence of the Wernicke-Korsakoff syndrome. Metab Brain Dis. 1995;10(1):17-24. 
  7. Abdou E, Hazell A. Thiamine Deficiency: An Update of Pathophysiologic Mechanisms and Future Therapeutic Considerations. Neurochem Res. 2014;40(2):353-361. 
  8. Inagaki T, Shimitzu Y, Tsubouchi K et al. Korsakoff syndrome following chronic subdural hematoma. General Hospital Psychiatry. 2003;25(5):364-366. 
  9. Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. The Lancet Neurology. 2007;6(5):442-455. 
  10. Cagli B, Tekatas A, Tuncel S, Celik Y. Diffusion-weighted cranial MR imaging in Wernicke'/INS;s encephalopathy associated with enterocutaneous fistula/INS;. Journal of the Neurological Sciences. 2013;333:e592. 
  11. Thomson A. The royal college of physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and emergency department. Alcohol and Alcoholism. 2002;37(6):513-521. 

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Last updated: 2019-07-11 20:21