Wernicke's encephalopathy: what is it, symptoms, treatment, prognosis

What is Wernicke's encephalopathy?

Wernicke's encephalopathy (EV) is an acute neurological disease characterized by the clinical triad of ophthalmoplegia with nystagmus, ataxia and confusion. It is a life-threatening disease caused by a deficiency of thiamine (vitamin B1), which primarily affects the peripheral and central nervous system. This disease must be differentiated from Korsakoff's syndrome, which is preventable and is usually suspected as a consequence of at least one episode of Wernicke's encephalopathy. Korsakov's syndrome is a neuropsychiatric disorder associated with memory impairment, in which there is a significant deficit in anterograde and retrograde memory. Immediate memory is preserved, but short-term memory is reduced while maintaining sensitivity. The disorder is associated with the fact that patients make up stories in a lucid environment. It happens that these syndromes occur simultaneously. When EV occurs concurrently with Korsakoff syndrome, the condition is called Wernicke – Korsakoff syndrome *.

*Wernicke-Korsakoff syndrome - an unusual form of amnesia that combines two disorders: acute confusion (i.e., Wernicke's encephalopathy) and a type of long-term amnesia (i.e. e. Korsakov's syndrome). Korsakoff syndrome occurs in 80% of untreated patients with Wernicke encephalopathy.

Signs and symptoms

Symptoms of Wernicke's encephalopathy include:

• confusion of consciousness;
• drowsiness;
• involuntary eye movements (nystagmus);
• partial paralysis of the eye muscles (ophthalmoplegia);
• ataxia (violation of the coordination of movements of various muscles, people walk with their legs wide apart, and take slow short steps).

Internal processes in the body can be disrupted, causing tremors, agitation, low body temperature, a sudden and excessive drop in blood pressure when standing (orthostatic hypotension) and fainting.

Causes and risk factors

Thiamine deficiency is commonly associated with severe alcohol use disorder. Although Wernicke encephalopathy mainly affects people with thiamine deficiency due to chronic alcohol addictions (alcoholism), various other causes can cause this disease, including:

• severe malnutrition;
• hyperemesis (vomiting) of pregnant women;
• long-term parenteral nutrition;
• malignant neoplasms;
• immunodeficiency syndromes;
• liver disease;
• hyperthyroidism;
• neurogenic anorexia.

Chronic alcohol use can cause thiamine deficiency due to impaired absorption of thiamine from the intestine, possibly genetic predisposition, inadequate nutrition, decreased accumulation of thiamine in the liver and other deficiencies nutrients.

A common triggering event causing EV is acute infection. Other triggers include prolonged carbohydrate or glucose load when thiamine is deficient. Typically, patients receiving glucose should be given thiamine at the same time.

Epidemiology

There are no convincing statistical studies on the prevalence of Wernicke's encephalopathy, all figures are based on partial research, and because of ethical concerns, controlled trials are unlikely to be able to get them into the future.

Wernicke's lesions were observed at autopsies (autopsies) from 0.8 to 2.8% of the total population and in 12.5% ​​of alcoholics. This figure rises to 35% in alcoholics when the damage to the cerebellum due to vitamin B1 deficiency is considered.

Most of the autopsies were done on alcoholics. A series of autopsies were performed in hospitals on available material that is unlikely to be representative of the general population. Given the minor lesions, the percentage should be higher before the observed lesions appear in necropsy. There is evidence of insufficient diagnosis of Wernicke's encephalopathy. For example, in one 1986 study, 80% of cases were diagnosed posthumously. It is estimated that only 5-14% of EV patients are diagnosed during their lifetime.

A series of autopsies conducted in Recife, Brazil, found that only 7 out of 36 were alcohol addicted and only a small minority were malnourished. A review of 53 published case reports from 2001 to 2011 found that alcohol association was also about 20% (10 out of 53 cases).

Wernicke's lesions are more common in men than in women. Among the diagnosed minority, the mortality rate can be as high as 17%. Infections and liver dysfunctions are believed to be the main factors causing mortality.

Pathophysiology

Thiamin, one of the first to be discovered B vitamins, also known as vitamin B1, is a coenzyme essential for complex organic pathways and plays a central role in brain metabolism. This vitamin acts as a cofactor for several enzymes of the Krebs cycle and the pentose phosphate pathway, including the oxidation of alpha-ketoglutamic acid and the decarboxylation of pyruvate. Thiamine-dependent enzymes act as a link between the glycolytic and citric acid cycles. Hence, thiamine deficiency will result in decreased levels of alpha-ketoglutarate, acetate, citrate, acetylcholine and accumulation of lactate and pyruvate. This deficiency can cause metabolic imbalances leading to neurological complications, including nerve cell death. The death of neurons in the mammillary bodies and thalamus has been implicated in many of the studied cases of Wernicke's encephalopathy. Studies that include computed tomography (CT) and magnetic resonance imaging (MRI) in patients with Wernicke encephalopathy, revealed lesions in the thalamus with dilated ventricles and volume loss in the mammillary bodies. Lesions are usually symmetrical in the midbrain, hypothalamus, and cerebellum.

Diagnostics

- History and physical examination.

EV should be suspected in any patient with chronic alcohol abuse or any form of malnutrition, and also anyone who has the following: acute change in mental status, ophthalmoplegia, ataxic gait, delirium and hypotension. The classic triad of Wernicke's encephalopathy is mental status change, ataxic gait, and ophthalmoplegia. Diagnosis is based on clinical presentation, but definitive diagnosis is often difficult because the clinical triad may be absent in up to 90% of patients.

A hallmark of Wernicke's encephalopathy is ocular abnormalities, especially nystagmus. Other oculomotor symptoms include damage to the oculomotor nerves, abducens, and vestibular nuclei, causing paralysis of the conjugate gaze. Sluggishness of the pupils, ptosis, and anisocoria.

Ataxia is also an important finding in Wernick's disease, when patients have a wide gait. Gait may also deteriorate, and in many cases, patients are unable to walk. The physical examination may include a complete neurologic examination with examination of the cerebellum. Encephalopathy characterized by disorientation and changes in the sensory system. Some patients may develop hyperactive delirium along with Wernicke's encephalopathy secondary to possible alcohol withdrawal symptoms. Less than 5% of patients with Wernicke's disease may have a severely suppressed level of consciousness, which ultimately leads to coma and death. Some other warning signs may include hyperthermia and hypotension. The patient may also have peripheral neuropathyaffecting the lower limb and examination reveals distal sensory loss.

The disease should be considered in a patient with prolonged malnutrition, episodes of confusion, and altered mental status. Over the past several decades, bariatric surgery has been associated with EV and malnutrition; The main reason is that food intake is limited after surgery and thiamine is quickly depleted.

- Analyzes and imaging studies.

There are no specific laboratory tests to diagnose Wernicke's encephalopathy as it is a clinical diagnosis with the aforementioned classic signs and symptoms.

A clinical diagnosis of EV is present if the patient has two of the following:

• eye signs;
• thiamine deficiency;
• changes in mental state;
• dysfunction of the cerebellum.

However, a complete blood count and a comprehensive metabolic panel can be done to rule out other causes of central nervous system abnormalities. Moreover, normal brain imaging cannot rule out Wernicke's encephalopathy and therefore is not very helpful either. In 1997 g. criteria have been established that are currently 85% sensitive if patients have two or more of the classic features, including ataxia, confusion, and ophthalmoplegia. In addition, the search for risk factors helps in patient assessment, since classical Wernicke encephalopathy was considered a disease caused exclusively by alcoholism. However, in recent years, Wernicke encephalopathy has also been observed in patients with chronic malnutrition, after bariatric surgery, hyperemesis of pregnant women, liver disease, hyperthyroidism and severe nervous anorexia.

MRI can reveal hyperintense signaling in the periventricular thalamus, mammillary bodies, and periaqueductal gray matter.

Erythrocyte transketolase levels can indicate thiamine deficiency. Lactate and pyruvate levels are often measured because thiamine is a cofactor for the enzyme pyruvate dehydrogenase.

Treatment

The goal of treatment is to quickly eliminate the thiamine deficiency in the brain. Wernicke's encephalopathy is a medical emergency and is considered a reversible disease. therefore requires immediate emergency care, although the onset of the disease may be acute or chronic. Parenteral administration of thiamine is most effective and provides rapid administration, but in some cases there is a persistent neurological deficit, and the acute condition can progress to a chronic syndrome Korsakov. The preferred dose of thiamine for the treatment of Wernicke's encephalopathy can be up to 500 mg when administered parenterally one to three times a day. All malnourished patients may require higher doses of thiamine. Oral thiamine is not reliable and is not recommended.

There is some evidence that thiamine treatment can improve confusion and rapidly resolve ataxia, ophthalmoplegia, and nystagmus. Thiamine is usually administered before or with glucose solutions because glucose oxidation can lower thiamine levels, thereby exacerbating the neurological symptoms of Wernicke's encephalopathy. Patients with magnesium deficiency should also be treated as this can slow down recovery due to Wernicke's disease, especially in patients with alcoholism.

Most patients need hospitalization to receive IV thiamine and magnesium.

Forecast

Wernicke's encephalopathy is a serious life-threatening disease with severe disability. Although thiamine can cause partial improvement, neuropsychological deficits persist in many cases. Confusion is usually ameliorated by intravenous thiamine through learning, and memory deficits are only partially improved. A small number of patients show no improvement and may develop Korsakov's psychosis, which often requires hospitalization. Very few people have recovered by this time.

Complications

EV causes the following complications:

• neurological injury;
• ataxia;
• Korsakov's psychosis;
• ophthalmoplegia;
• heart failure;
• lactic acidosis.