Diagnosis of Wernicke's encephalopathy or disease is made clinically. Caine et al. in 1997 established criteria that Wernicke's encephalopathy can be diagnosed in any patient with just two or more of the main symptoms noted above. The sensitivity of the diagnosis by the classic triad was 23% but increased to 85% taking two or more of the four classic features. This criteria is challenged because all the cases he studied were alcoholics.

Some consider it sufficient to suspect the presence of the disease with only one of the principal symptoms. Some British hospital protocols suspect WE with any one of these symptoms: confusion, decreased consciousness level (or unconsciousness, stupor or coma), memory loss, ataxia or unsteadiness, ophthalmoplegia or nystagmus, and unexplained hypotension with hypothermia. The presence of only one sign should be sufficient for treatment.

As a much more diverse range of symptoms has been found frequently in patients it is necessary to search for new diagnostic criteria, however Wernicke's encephalopathy remains a clinically-diagnosed condition. Neither the MR, nor serum measurements related to thiamine are sufficient diagnostic markers in all cases. Non-recovery upon supplementation with thiamine is inconclusive.

The sensitivity of MR was 53% and the specificity was 93%. The reversible cytotoxic edema was considered the most characteristic lesion of WE. The location of the lesions were more frequently atypical among non-alcoholics, while typical contrast enhancement in the thalamus and the mammillary bodies was observed frequently associated with alcohol abuse. These abnormalities may include:

- Medial thalami, periaqueductal gray matter, mamillary bodies, and brainstem nuclei edema (Zuccoli G.). Involvement is always bilateral symmetrical. Value of DWI in the diagnosis of WE is minimal. Axial FLAIR MRI images represent the best diagnostic MRI sequence. Contrast material may highlight involvement of the mamillary bodies.

There appears to be very little value for CT scans.

Thiamine can be measured using an erythrocyte transketolase activity assay, or by activation by measurement of in vitro thiamine diphosphate levels. Normal thiamine levels do not necessarily rule out the presence of WE, as this may be a patient with difficulties in intracellular transport.

There are hospital protocols for prevention, supplementing with thiamine in the presence of: history of alcohol misuse or related seizures, requirement for IV glucose, signs of malnutrition, poor diet, recent diarrhea or vomiting, peripheral neuropathy, intercurrent illness, delirium tremens or treatment for DTs, and others. Some experts advise parenteral thiamine should be given to all at-risk patients in the emergency room.

In the clinical diagnosis should be remembered that early symptoms are nonspecific, and it has been stated that WE may present nonspecific findings. There is consensus to provide water-soluble vitamins and minerals after gastric operations.

In some countries certain foods have been supplemented with thiamine, and have reduced WE cases. Improvement is difficult to quantify because they applied several different actions. Avoiding alcohol and having adequate nutrition reduces one of the main risk factors in developing Wernicke-Korsakoff syndrome.

Blood tests, cerebrospinal fluid examination by lumbar puncture (also known as spinal tap), brain imaging studies, electroencephalography (EEG), and similar diagnostic studies may be used to differentiate the various causes of encephalopathy.

Diagnosis is frequently clinical. That is, no set of tests give the diagnosis, but the entire presentation of the illness with nonspecific test results informs the experienced clinician of the diagnosis.

Rapid diagnosis is important to attempt to prevent further damage to the brain and further neurologic deficits. It is a diagnosis of exclusion, so a full work up for other possible etiologies (hepatic, uremic, infectious, oncologic) should be performed. Screening for heavy metals, as well as other toxins, should be done immediately as those are some of the most common causes and the patient can then remove themselves from the dangerous environment. In addition, a full examination of blood (CBC) and metabolites (CMP) should be done.

The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease (types A and C) or a portosystemic shunt (type B), as its symptoms are similar to those encountered in other encephalopathies. To make the distinction, abnormal liver function tests and/or ultrasound suggesting liver disease are required, and ideally liver biopsy. The symptoms of hepatic encephalopathy may also arise from other conditions, such as cerebral haemorrhage and seizures (both of which are more common in chronic liver disease). A CT scan of the brain may be required to exclude haemorrhage, and if seizure activity is suspected an electroencephalograph (EEG) study may be performed. Rarer mimics of encephalopathy are meningitis, encephalitis, Wernicke's encephalopathy and Wilson's disease; these may be suspected on clinical grounds and confirmed with investigations.

The diagnosis of hepatic encephalopathy is a clinical one, once other causes for confusion or coma have been excluded; no test fully diagnoses or excludes it. Serum ammonia levels are elevated in 90% of people, but not all hyperammonaemia (high ammonia levels) is associated with encephalopathy. A CT scan of the brain usually shows no abnormality except in stage IV encephalopathy, when cerebral oedema may be visible. Other neuroimaging modalities, such as magnetic resonance imaging (MRI), are not currently regarded as useful, although they may show abnormalities. Electroencephalography shows no clear abnormalities in stage 0, even if minimal HE is present; in stages I, II and III there are triphasic waves over the frontal lobes that oscillate at 5 Hz, and in stage IV there is slow delta wave activity. However, the changes in EEG are not typical enough to be useful in distinguishing hepatic encephalopathy from other conditions.

Once the diagnosis of encephalopathy has been made, efforts are made to exclude underlying causes (such as listed above in "causes"). This requires blood tests (urea and electrolytes, full blood count, liver function tests), usually a chest X-ray, and urinalysis. If there is ascites, diagnostic paracentesis (removal of a fluid sample with a needle) may be required to identify spontaneous bacterial peritonitis (SBP).

Treatment varies according to the type and severity of the encephalopathy. Anticonvulsants may be prescribed to reduce or halt any seizures. Changes to diet and nutritional supplements may help some patients. In severe cases, dialysis or organ replacement surgery may be needed.

Sympathomimetic drugs can increase motivation, cognition, motor performance and alertness in patients with encephalopathy caused by brain injury, chronic infections, strokes, brain tumors.

The diagnosis of minimal hepatic encephalopathy requires neuropsychological testing by definition. Older tests include the "numbers connecting test" A and B (measuring the speed at which one could connect randomly dispersed numbers 1–20), the "block design test" and the "digit-symbol test". In 2009 an expert panel concluded that neuropsychological test batteries aimed at measuring multiple domains of cognitive function are generally more reliable than single tests, and tend to be more strongly correlated with functional status. Both the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and PSE-Syndrom-Test may be used for this purpose. The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test.

Treatment is mainly for the symptoms that toxic encephalopathy brings upon victims, varying depending on how severe the case is. Diet changes and nutritional supplements may help some patients. To reduce or halt seizures, anticonvulsants may be prescribed. Dialysis or organ replacement surgery may be needed in some severe cases.

Management of affected individuals consists of immediate removal from exposure to the toxic substance(s), treatment of the common clinical manifestation of depression if present, and counselling for the provision of life strategies to help cope with the potentially debilitating condition.

Diagnosis of Wernicke–Korsakoff syndrome is by clinical impression and can sometimes be confirmed by a formal neuropsychological assessment. Wernicke's encephalopathy typically presents with ataxia and nystagmus, and Korsakoff's psychosis with anterograde and retrograde amnesia and confabulation upon relevant lines of questioning.

Frequently, secondary to thiamine deficiency and subsequent cytotoxic edema in Wernicke's encephalopathy, patients will have marked degeneration of the mamillary bodies. Thiamine (vitamin B) is an essential coenzyme in carbohydrate metabolism and is also a regulator of osmotic gradient. Its deficiency may cause swelling of the intracellular space and local disruption of the blood-brain barrier. Brain tissue is very sensitive to changes in electrolytes and pressure and edema can be cytotoxic. In Wernicke's this occurs specifically in the mammillary bodies, medial thalami, tectal plate, and periaqueductal areas. Sufferers may also exhibit a dislike for sunlight and so may wish to stay indoors with the lights off. The mechanism of this degeneration is unknown, but it supports the current neurological theory that the mammillary bodies play a role in various "memory circuits" within the brain. An example of a memory circuit is the Papez circuit.

It can be diagnosed clinically in the appropriate context, but may be difficult to confirm radiologically using conventional imaging techniques. Changes are more prominent on MRI than on CT, but often take days or weeks after acute symptom onset to develop. Imaging by MRI typically demonstrates areas of hyperintensity on T2-weighted images.

As described, Korsakoff 's syndrome usually follows or accompanies Wernicke's encephalopathy. If treated quickly, it may be possible to prevent the development of Korsakoff's syndrome with thiamine treatments. This treatment is not guaranteed to be effective and the thiamine needs to be administered adequately in both dose and duration. A study on Wernicke-Korsakoff's syndrome showed that with consistent thiamine treatment there were noticeable improvements in mental status after only 2–3 weeks of therapy. Thus, there is hope that with treatment Wernicke's encephalopathy will not necessarily progress to WKS.

In order to reduce the risk of developing WKS it is important to limit the intake of alcohol or drink in order to ensure that proper nutrition needs are met. A healthy diet is imperative for proper nutrition which, in combination with thiamine supplements, may reduce the chance of developing WKS. This prevention method may specifically help heavy drinkers who refuse to or are unable to quit.

Alcoholic polyneuropathy is very similar to other axonal degenerative polyneuropathies and therefore can be difficult to diagnose. When alcoholics have sensorimotor polyneuropathy as well as a nutritional deficiency, a diagnosis of alcoholic polyneuropathy is often reached.

To confirm the diagnosis, a physician must rule out other causes of similar clinical syndromes. Other neuropathies can be differentiated on the basis of typical clinical or laboratory features. Differential diagnoses to alcoholic polyneuropathy include amyotrophic lateral sclerosis, beriberi, Charcot-Marie-Tooth disease, diabetic lumbosacral plexopathy, Guillain Barre Syndrome, diabetic neuropathy, mononeuritis multiplex and post-polio syndrome.

To clarify the diagnosis, medical workup most commonly involves laboratory tests, though, in some cases, imaging, nerve conduction studies, electromyography, and vibrometer testing may also be used.

A number of tests may be used to rule out other causes of peripheral neuropathy. One of the first presenting symptoms of diabetes mellitus may be peripheral neuropathy, and hemoglobin A1C can be used to estimate average blood glucose levels. Elevated blood creatinine levels may indicate renal insufficiency and may also be a cause of peripheral neuropathy. A heavy metal toxicity screen should also be used to exclude lead toxicity as a cause of neuropathy.

Alcoholism is normally associated with nutritional deficiencies, which may contribute to the development of alcoholic polyneuropathy. Thiamine, vitamin B-12, and folic acid are vitamins that play an essential role in the peripheral and central nervous system and should be among the first analyzed in laboratory tests. It has been difficult to assess thiamine status in individuals due to difficulties in developing a method to directly assay thiamine in the blood and urine. A liver function test may also be ordered, as alcoholic consumption may cause an increase in liver enzyme levels.

There are several different forms of glycine encephalopathy, which can be distinguished by the age of onset, as well as the types and severity of symptoms. All forms of glycine encephalopathy present with only neurological symptoms, including mental retardation (IQ scores below 20 are common), hypotonia, apneic seizures, and brain malformations.

With the classical, or neonatal presentation of glycine encephalopathy, the infant is born after an unremarkable pregnancy, but presents with lethargy, hypotonia, apneic seizures and myoclonic jerks, which can progress to apnea requiring artificial ventilation, and often death. Apneic patients can regain spontaneous respiration in their second to third week of life. After recovery from the initial episode, patients have intractable seizures and profound mental retardation, remaining developmentally delayed. Some mothers comment retrospectively that they noticed fetal rhythmic "hiccuping" episodes during pregnancy, most likely reflecting seizure episodes in utero. Patients with the infantile form of glycine encephalopathy do not show lethargy and coma in the neonatal period, but often have a history of hypotonia. They often have seizures, which can range in severity and responsiveness to treatment, and they are typically developmentally delayed. Glycine encephalopathy can also present as a milder form with episodic seizures, ataxia, movement disorders, and gaze palsy during febrile illness. These patients are also developmentally delayed, to varying degrees. In the later onset form, patients typically have normal intellectual function, but present with spastic diplegia and optic atrophy.

Transient neonatal hyperglycinemia has been described in a very small number of cases. Initially, these patients present with the same symptoms and laboratory results that are seen in the classical presentation. However, levels of glycine in plasma and cerebrospinal fluid typically normalize within eight weeks, and in five of six cases there were no neurological issues detected at follow-up times up to thirteen years. A single patient was severely retarded at nine months. The suspected cause of transient neonatal hyperglicinemia is attributed to low activity of the glycine cleavage system in the immature brain and liver of the neonate.

Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte Transketolase Activation Assay). Thiamine, as well as its phosphate derivatives, can also be detected directly in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent thiochrome derivatives (Thiochrome Assay) and separation by high-performance liquid chromatography (HPLC). In recent reports, a number of Capillary Electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as potential alternative techniques for the determination and monitoring of thiamine in samples.

The normal thiamine concentration in EDTA-blood is about 20-100 µg/l.

Due to its non-specific nature, diagnosing CSE requires a multidisciplinary "Solvent Team" typically consisting of a neurologist, occupational physician, occupational hygienist, neuropsychologist, and sometimes a psychiatrist or toxicologist. Together, the team of specialists together assesses the patient's history of exposure, symptoms, and course of symptom development relative to the amount and duration of exposure, presence of neurological signs, and any existing neuropsychological impairment.

Furthermore, CSE must be diagnosed "by exclusion". This means that all other possible causes of the patient’s symptoms must first be ruled out beforehand. Because screening and assessing for CSE is a complex and time-consuming procedure requiring several specialists of multiple fields, few cases of CSE are formally diagnosed in the medical field. This may, in part, be a reason for the syndrome’s lack of recognition. The solvents responsible for neurological effects dissipate quickly after an exposure, leaving only indirect evidence of their presence, in the form of temporary or permanent impairments.

Brain imaging techniques that have been explored in research have shown little promise as alternative methods to diagnose CSE. Neuroradiology and functional imaging have shown mild cortical atrophy, and effects in dopamine-mediated frontostriatal circuits in some cases. Examinations of regional cerebral blood flow in some imaging techniques have also shown some cerebrovascular abnormalities in patients with CSE, but the data were not different enough from healthy patients to be considered significant. The most promising brain imaging technique being studied currently is functional magnetic resonance imaging (fMRI) but as of now, no specific brain imaging techniques are available to reliably diagnose CSE.

To minimise the risk of this condition developing from its most common cause, overly rapid reversal of hyponatremia, the hyponatremia should be corrected at a rate not exceeding 10 mmol/L/24 h or 0.5 mEq/L/h; or 18 m/Eq/L/48hrs; thus avoiding demyelination. No large clinical trials have been performed to examine the efficacy of therapeutic re-lowering of serum sodium, or other interventions sometimes advocated such as steroids or plasma exchange.

Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.

Once osmotic demyelination has begun, there is no cure or specific treatment. Care is mainly supportive. Alcoholics are usually given vitamins to correct for other deficiencies. The favourable factors contributing to the good outcome in CPM without hyponatremia were: concurrent treatment of all electrolyte disturbances, early Intensive Care Unit involvement at the advent of respiratory complications, early introduction of feeding including thiamine supplements with close monitoring of the electrolyte changes and input.

Research has led to improved outcomes. Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia. Further study is required before using inositol in humans for this purpose.

It was once assumed that anyone suffering from Korsakoff's syndrome would eventually need full-time care. This is still often the case, but rehabilitation can help regain some, albeit often limited, level of independence. Treatment involves the replacement or supplementation of thiamine by intravenous (IV) or intramuscular (IM) injection, together with proper nutrition and hydration. However, the amnesia and brain damage caused by the disease does not always respond to thiamine replacement therapy. In some cases, drug therapy is recommended. Treatment of the patient typically requires taking thiamine orally for 3 to 12 months, though only about 20 percent of cases are reversible. If treatment is successful, improvement will become apparent within two years, although recovery is slow and often incomplete.

As an immediate form of treatment, a pairing of IV or IM thiamine with a high concentration of B-complex vitamins can be administered three times daily for period of 2–3 days. In most cases, an effective response from patients will be observed. A dose of 1 gram of thiamine can also be administered to achieve a clinical response. In patients who are seriously malnourished, the sudden availability of glucose without proper bodily levels of thiamine to metabolize is thought to cause damage to cells. Thus, the administration of thiamine along with an intravenous form of glucose is often good practice.

Treatment for the memory aspect of Korsakoff's syndrome can also include domain-specific learning, which when used for rehabilitation is called the method of vanishing cues. Such treatments aim to use patients' intact memory processes as the basis for rehabilitation. Patients who used the method of vanishing cues in therapy were found to learn and retain information more easily.

People diagnosed with Korsakoff's are reported to have a normal life expectancy, presuming that they abstain from alcohol and follow a balanced diet. Empirical research has suggested that good health practices have beneficial effects in Korsakoff's syndrome.

The most effective method of preventing Korsakoff's syndrome is to avoid B vitamin/thiamine deficiency. In Western nations, the most common causes of such a deficiency are alcoholism and eating disorders. Because these are behavioral-induced causes, Korsakoff's syndrome is essentially considered a preventable disease. Thus, fortifying foods with thiamine, or requiring companies that sell alcoholic beverages to supplement them with B vitamins in general or thiamine in particular, could avert many cases of Korsakoff's Syndrome.

Introduced by a working group from the World Health Organization (WHO) in 1985, WHO diagnostic criteria states that CSE can occur in three stages, organic affective syndrome (type I), mild chronic toxic encephalopathy (type II), and severe chronic toxic encephalopathy (type III). Shortly after, a workshop in Raleigh-Durham, NC (United States) released a second diagnostic criterion which recognizes four stages as symptoms only (type 1), sustained personality or mood swings (type 2A), impairment of intellectual function (type 2B), and dementia (type 3). Though not identical, the WHO and Raleigh criteria are relatively comparable. WHO type I and Raleigh types 1 and 2A are believed to encompass the same stages of CSE, and WHO type II and Raleigh type 2B both involve deficiencies in memory and attention. No other international classifications for CSE have been proposed, and neither the WHO nor Raleigh criteria have been uniformly accepted for epidemiological studies.

The rate of incidence of alcoholic polyneuropathy involving sensory and motor polyneuropathy varies from 10% to 50% of alcoholics depending on the subject selection and diagnostic criteria. If electrodiagnostic criteria is used, alcoholic polyneuropathy may be found in up to 90% of individuals being assessed. The distribution and severity the disease depends on regional dietary habits, individual drinking habits, as well as an individual’s genetics. Large studies have been conducted and show that alcoholic polyneuropathy severity and incidence correlates best with the total lifetime consumption of alcohol. Factors such as nutritional intake, age, or other medical conditions are correlate in lesser degrees. For unknown reasons, alcoholic polyneuropathy has a high incidence in women.

Certain alcoholic beverages can also contain congeners that may also be bioactive; therefore, the consumption of varying alcoholic beverages may result in different health consequences. An individual’s nutritional intake also plays a role in the development of this disease. Depending on the specific dietary habits, they may have a deficiency of one or more of the following: thiamine (vitamin B1), pyridoxine (vitamin B6), pantothenic acid and biotin, vitamin B12, folic acid, niacin (vitamin B3), and vitamin A.

The existence of alcohol-related dementia is widely acknowledged but not often used as a diagnosis, due to a lack of widely accepted, non-subjective diagnostic criteria; more research is needed. Criteria for alcohol-induced persistent dementia in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) include the following:

There are problems with DSM diagnostic criteria, however. Firstly, they are vague and subjective. Furthermore, the criteria for diagnosis of dementia were inspired by the clinical presentation of Alzheimer's disease and are poorly adapted to the diagnosis of other dementias. This has led to efforts to develop better diagnostic models.

Oslin (Int J Geriatr Psychiatry 1998) proposed alternative clinical diagnostic criteria which were validated. The criteria include a clinical diagnosis of dementia at least 60 days after last exposure to alcohol, significant alcohol use (i.e. minimum 35 standard drinks/week for males and 28 for women) for more than 5 years, and significant alcohol use occurring within 3 years of the initial onset of cognitive deficits. Oslin proposed the new and refined diagnostic criteria for Alcohol Related Dementia because he hoped that the redefined classification system would bring more awareness and clarity to the relationship between alcohol use and dementia.

Oslin's proposed classification of ARD:

- "Definite" Alcohol Related Dementia

At the current time there are no acceptable criteria to definitively define Alcohol Related Dementia.

- "Probable" Alcohol Related Dementia

If the symptoms of alcohol dementia are caught early enough, the effects may be reversed. The person must stop drinking and start on a healthy diet, replacing the lost vitamins, including, but not limited to, thiamine. Recovery is more easily achievable for women than men, but in all cases it is necessary that they have the support of family and friends and abstain from alcohol.

Marchiafava-Bignami disease is routinely diagnosed with the use of an MRI due to the fact that the majority of clinical symptoms are non-specific. Before the use of such imaging equipment, it was unable to be diagnosed until autopsy. The patient usually has a history of alcoholism or malnutrition and neurological symptoms are sometimes present and can help lead to a diagnosis. MBD can be told apart from other neural diseases due to the symmetry of the lesions in the corpus callosum as well as the fact that these lesions don’t affect the upper and lower edges.

There are two clinical subtypes of MBD

Type A- Stupor and coma predominate. Radiological imaging shows involvement of the entire corpus callosum. This type is also associated with symptoms of the upper motor neurons.

Type B- This type has normal or only mildly impair mental status and radiological imaging shows partial lesions in the corpus callosum.

Polioencephalomalacia (PEM), also referred to as cerebrocortical necrosis (CCN), is a neurological disease seen in ruminants that is caused by disrupted thiamine production in the body. Thiamine is a key chemical in glucose metabolism that, when definicient, is most threatening to neurological activity. Cattles, sheep, goat, and other ruminants that are diagnosed with PEM or pre-PEM suffer opishotonus, cortical blindness, disoriented movement, and eventually fatality, if left untreated. Current data shows that the onset of PEM can range from birth to late adulthood.