Wernicke Encephalopathy and Korsakoff Syndrome (Clinical)

Overview

Definition^[1,3]

Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome and Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome are neurologic conditions that arise because of thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies (vitamin B₁) deficiency.

• Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome is an acute, reversible condition. 
• Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome is an irreversible syndrome that is caused by more severe or prolonged thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies deficiency and occurs after incomplete recovery from Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome.

Epidemiology^[1]

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of Wernicke lesions Wernicke Lesions Wernicke Encephalopathy and Korsakoff Syndrome: 0.8%–2.8% of autopsies in general population 
• Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome impacts up to 12.5% of individuals with chronic alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder.
• Men are more commonly affected than women.
• Average age at onset of Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome: 50 years

Etiology^[1,3]

Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome and Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome are caused by a severe deficiency of thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies. This deficiency is most commonly due to:

• Chronic alcohol use:
  • Inadequate intake
  • Poor absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
  • Decreased hepatic storage
  • Improper utilization 
• Inadequate intake of thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies:
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Starvation
  • Thiamine-deficient diets Thiamine-Deficient Diets Wernicke Encephalopathy and Korsakoff Syndrome 
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
• Increased loss of thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies:
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Hyperemesis
  • Dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis 

Pathophysiology

The pathologic sequelae of Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome and Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome stem from the downstream effects of thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies deficiency in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification.^[1,3]

• Thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies is converted into its more active form, thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies pyrophosphate ( TPP TPP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura).
• TPP TPP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura is an essential coenzyme involved in cerebral metabolism.
• TPP TPP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura deficiency leads to:
  • ↓ Cerebral glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance metabolism and depleted ATP 
  • ↑ Free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage 
  • ↓ Neurotransmitter production 
  • Impaired lipid metabolism Lipid Metabolism Lipid metabolism is the processing of lipids for energy use, energy storage, and structural component production. Lipid metabolism uses fats from dietary sources or from fat stores in the body. A complex series of processes involving digestion, absorption, and transport are required for the proper metabolism of lipids. Lipid Metabolism
• The deficiencies in TPP TPP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura injure neuronal elements, including myelin sheaths and the blood–brain barrier Blood–Brain Barrier Meningitis in Children, ultimately impairing neuronal conduction. 
• Wernicke lesions Wernicke Lesions Wernicke Encephalopathy and Korsakoff Syndrome are most often found in the:
  • Periventricular region
  • Diencephalon Diencephalon The paired caudal parts of the prosencephalon from which the thalamus; hypothalamus; epithalamus; and subthalamus are derived. Development of the Nervous System and Face ( thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus: Anatomy, hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus, epithalamus, subthalamus)
  • Midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem: Anatomy
• In Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome, long-term damage to components of the limbic system Limbic system The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli. Limbic System: Anatomy ( mammillary bodies Mammillary bodies A pair of nuclei and associated gray matter in the interpeduncular space rostral to the posterior perforated substance in the posterior hypothalamus. Limbic System: Anatomy, anterior thalamic nuclei Anterior thalamic nuclei Three nuclei located beneath the dorsal surface of the most rostral part of the thalamus. The group includes the anterodorsal nucleus, anteromedial nucleus, and anteroventral nucleus. All receive connections from the mamillary body and brain fornix, and project fibers to the cingulate body. Thalamus: Anatomy) leads to:
  • Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment loss
  • Apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome
  • Emotional upset
• The location of the lesions predicts the symptoms of disease:
  • Hypothalamic lesions → autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome
  • Medullary lesions → ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Mammillary body lesions → amnestic syndrome

Clinical Presentation

History^[1,3,4]

• Suspected in individuals with a history of:
  • Chronic excessive alcohol consumption
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries/ malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion:
    • History of bowel resection
    • History of bariatric surgery Bariatric surgery Bariatric surgery refers to a group of invasive procedures used to surgically reduce the size of the stomach to produce early satiety, decrease food intake (restrictive type) and/or alter digestion, and artificially induce malabsorption of nutrients (malabsorptive type). The ultimate goal of bariatric surgery is drastic weight loss. Bariatric Surgery
    • History of inflammatory bowel disease
• History often provided by caregivers, family, first responders:
  • Amnesia, both anterograde and retrograde
  • Disorientation Disorientation St. Louis Encephalitis Virus 
  • Confabulation Confabulation Memory fabrication to make up for memory lapses Wernicke Encephalopathy and Korsakoff Syndrome ( memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment fabrication to make up for memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment lapses)
  • Personality changes, including apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome, indifference, and executive function 
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
• In cases of alcohol dependence, may present with acute withdrawal symptoms and/or delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium tremens

Examination

Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome (reversible):^[1,4]

• Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome presents with a classic triad of examination findings:
  • Encephalopathy Encephalopathy Hyper-IgM Syndrome:
    • Profound disorientation Disorientation St. Louis Encephalitis Virus
    • Indifference
    • Inattentiveness
  • Oculomotor dysfunction:
    • Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
    • Lateral rectus Lateral rectus Orbit and Extraocular Muscles: Anatomy palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies
    • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
  • Gait ataxia Gait ataxia Impairment of the ability to coordinate the movements required for normal ambulation (walking) which may result from impairments of motor function or sensory feedback. This condition may be associated with brain diseases (including cerebellar diseases and basal ganglia diseases); spinal cord diseases; or peripheral nervous system diseases. Friedreich Ataxia:
    • Wide-based, slow gait Gait Manner or style of walking. Neurological Examination
    • Short-spaced steps
    • In severe cases, inability to walk
• Other signs:
  • Autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension 
    • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope 
    • Hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia 
  • Peripheral neuropathy Neuropathy Leprosy (particularly of lower extremities)
    • Paresthesia 
    • Foot drop Foot Drop Leprosy 
    • Decreased deep tendon reflexes Deep Tendon Reflexes Neurological Examination 
  • Cardiovascular dysfunction
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children 
    • Exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea 

Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome (irreversible):^[3,8]

• Confabulation Confabulation Memory fabrication to make up for memory lapses Wernicke Encephalopathy and Korsakoff Syndrome (using fabricated memories to “fill in the gaps”)
• Anterograde and retrograde amnesia Retrograde amnesia Loss of the ability to recall information that had been previously encoded in memory prior to a specified or approximate point in time. This process may be organic or psychogenic in origin. Organic forms may be associated with craniocerebral trauma; cerebrovascular accidents; seizures; dementia; and a wide variety of other conditions that impair cerebral function. Wernicke Encephalopathy and Korsakoff Syndrome:
  • Anterograde = impaired capacity Impaired capacity Impaired capacity is the lack of decision-making capacity. Decision-making Capacity and Legal Competence for new learning 
  •  Retrograde = impaired access to previously held memories
• Personality changes (if frontal lobe Frontal lobe The part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus. Cerebral Cortex: Anatomy affected):
  • Apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome 
  • Indifference 
  • Decreased executive function 
• Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia 
• Disorientation Disorientation St. Louis Encephalitis Virus

Mnemonic

Mnemonic for the key symptoms of Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome: CAN OPEN 

• Confusion
• Ataxia
• Nystagmus
• Ophthalmoplegia
• PEripheral Neuropathy

Diagnosis

Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome and Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome are primarily clinical diagnoses.^[1,3,4]

• Hold a strong clinical suspicion if the aforementioned symptoms are present in individuals with excessive alcohol intake or malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries.
• Ambiguous cases can be supported by laboratory tests, but awaiting results should NOT delay treatment.
• Laboratory tests:
  • ↓ Serum thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies levels (measure prior to thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies supplementation)
  • ↓ Erythrocyte transketolase Erythrocyte Transketolase Wernicke Encephalopathy and Korsakoff Syndrome activity 
  • ↑ Serum lactate and pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis 
  • Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests (altered levels may indicate alcohol-related dysfunction)
• Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant:^[2]
  • CT has little value.
  • MRI findings are highly specific and may show:
    • ↑ Signal in mammillary bodies Mammillary bodies A pair of nuclei and associated gray matter in the interpeduncular space rostral to the posterior perforated substance in the posterior hypothalamus. Limbic System: Anatomy and thalami
    • Symmetrical Symmetrical Dermatologic Examination periventricular hemorrhage

Suggested diagnostic criteria^[4]

There are no sensitive and specific diagnostic criteria for Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome (WE). 

• However, ≥ 2 of the following suggest WE in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with alcohol dependence/abuse (Caine criteria):
  • Nutritional deficiencies
  • Oculomotor dysfunction
  • Cerebellar dysfunction
  • Altered mental status Altered Mental Status Sepsis in Children or memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment impairment
• Note:
  • These criteria are not intended to be applied to patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without alcohol dependence/abuse.
  • Sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests is low.

Additional evaluation^[1,6]

The following should be considered based on the individual’s history and presentation. These tests are not required for the diagnosis of WE, but they are often used to rule out other conditions, particularly if the diagnosis is unclear.

• Serum alcohol level → alcohol intoxication Alcohol intoxication An acute brain syndrome which results from the excessive ingestion of ethanol or alcoholic beverages. Alcohol Use Disorder
• CBC, liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests, and measurement of serum chemistry levels to evaluate for stigmata of chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease.
• Ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance level → hepatic encephalopathy Encephalopathy Hyper-IgM Syndrome
• Urine/blood toxicity Toxicity Dosage Calculation screen
• Drug levels of selected prescribed medications
• Thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy → hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism/ myxedema coma Myxedema Coma Hypothyroidism
• Vitamin B₁₂ level
• Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children/ urine culture Urine culture Urinary tract infections (UTIs) → infection
• Blood gas → acid–base disturbances
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests → infection
• EEG EEG Seizures → if there is concern for seizure
• Lumbar puncture Lumbar Puncture Febrile Infant → if there is concern for meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis

Management

In addition to treatment of the presenting encephalopathy Encephalopathy Hyper-IgM Syndrome, the clinician Clinician A physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients. Clinician–Patient Relationship should also have a high clinical suspicion for acute alcohol intoxication Alcohol intoxication An acute brain syndrome which results from the excessive ingestion of ethanol or alcoholic beverages. Alcohol Use Disorder, hepatic encephalopathy Encephalopathy Hyper-IgM Syndrome, alcohol withdrawal Alcohol withdrawal With chronic alcohol use, body increases activity of excitatory receptors (e.g., glutamate) while decreasing activation of inhibitory receptors (e.g., GABA). Cessation of alcohol use leads to unchecked glutamate activation, presenting as withdrawal. Alcohol Use Disorder syndrome, and alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis and treat these accordingly.

Initial management of Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome^[1,4,5]

Treatment should be prompt to prevent progression to permanent memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment deficits.

• Immediate thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies supplementation:
  • Route: IV or IM
  • Duration: Continue treatment until symptoms resolve (or minimum of 5 days, whichever is longer).
  • Dose:
    • 500 mg 3x daily for 2–3 days, then 250 mg daily for the next 3–5 days
    • Given over 30 minutes
    • Dilute in 50–100 mL of normal saline Normal saline A crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy. Intravenous Fluids
    • Should be followed by oral dosage Dosage Dosage Calculation of 100 mg 3x daily
• Laboratory studies evaluating thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies level and other vitamin/mineral levels (e.g., magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes)
• Provide multivitamin and electrolyte supplementation, as appropriate
• Hypoglycemic individuals should be given glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance AFTER thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies because glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance will deplete remaining stores of thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies and worsen encephalopathy Encephalopathy Hyper-IgM Syndrome

Initial management of Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome^[3,8]

Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome may require lifelong care, as memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment deficits are often permanent.

• Thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies (IV or IM)
  • There is little consensus on the correct dosing regimen.
  • High-dose therapy (500 mg 3x daily for at least 3 days) is often recommended. 
  • Consult your local guidelines or a neurologist for up-to-date treatment regimens.
• Psychiatric evaluation and therapy
• Administration of acetylcholinesterase inhibitors may be considered to improve cognitive functioning.

Long-term management of Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome and Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome^[1,5,8]

• Referral for community social support:
  • Psychiatrist
  • Substance use disorder counselor
  • Provide a list of local Alcoholics Anonymous Alcoholics Anonymous An organization of self-proclaimed alcoholics who meet frequently to reinforce their practice of abstinence. Alcoholic Liver Disease meetings and/or contact info.
• Patient education:
  • Abstinence from alcohol (absolute in Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome) 
  • Diet (may require referral to a dietitian)
• Oral vitamin supplementation:
  • Long-term thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies supplementation (100 mg 3x daily) 
  • Multivitamin supplements, depending on diet
• Rehabilitation services:
  • Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment 
  • Walking

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Wernicke encephalopathy Encephalopathy Hyper-IgM Syndrome:^[1,6]
  • Generally reversible if treatment is initiated promptly 
  • Oculomotor function resolves. 
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia and confusion may persist for days to months. 
• Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome:^[6–8]
  • Symptoms may be irreversible. 
  • Research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest has shown promise for memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment rehabilitation.

Differential Diagnosis

• Cerebellar stroke: cerebrovascular event leading to impaired perfusion of O₂ to the posterior fossa of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification. Cerebellar strokes account for 1%–4% of all strokes and can be thromboembolic or hemorrhagic in nature. Symptoms include headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo, unilateral hearing loss Unilateral hearing loss Partial or complete hearing loss in one ear. Hearing Loss, and contralateral sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology loss ( pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and temperature). Diagnosis is clinical and confirmed by neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant. Acute thrombolytic therapy can be used in selected acute cases. Long-term management consists of risk factor modification of further ischemic events. 
• Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium tremens: severe form of ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism withdrawal characterized by tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, auditory hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia, diaphoresis, and severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension. Diagnosis is clinical but supported by laboratory evaluation and neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant. Treatment includes IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids for rehydration Rehydration Dengue Virus, thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies and magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes supplementation, and benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus and seizure prophylaxis Prophylaxis Cephalosporins. 
• Hepatic encephalopathy Encephalopathy Hyper-IgM Syndrome: altered mental status Altered Mental Status Sepsis in Children in the setting of chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease due to elevated ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance levels. May be associated with ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, personality changes, and altered level of consciousness Altered Level of Consciousness Intracerebral Hemorrhage. Diagnosis is clinical but supported by evidence of hepatic decompensation and elevated serum ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance. Lactulose Lactulose A synthetic disaccharide used in the treatment of constipation and hepatic encephalopathy. It has also been used in the diagnosis of gastrointestinal disorders. Laxatives is the mainstay of acute management for lowering ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance levels. Long-term management consists of efforts to stabilize hepatic function and hepatic transplantation. 
• Lewy body dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders: condition associated with deposition of Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease (clumps of protein) in the cortical region of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification. Lewy body dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders is a progressive disease that presents with dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, cognitive decline, and visual hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia. Diagnosis is based on the clinical presentation. The time frame of symptom onset is an important piece of the history, as this entity presents more gradually than Wernicke/ Korsakoff syndrome Korsakoff syndrome An acquired cognitive disorder characterized by inattentiveness and the inability to form short term memories. This disorder is frequently associated with chronic alcoholism; but it may also result from dietary deficiencies; craniocerebral trauma; neoplasms; cerebrovascular disorders; encephalitis; epilepsy; and other conditions. Wernicke Encephalopathy and Korsakoff Syndrome. There is no cure for Lewy body dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders. Treatment is supportive and aimed at reducing behavioral changes.