Ataxia in the context of Orthostatic hypotension

Alcohol intoxication, commonly described in higher doses as drunkenness or inebriation, and known in overdose as alcohol poisoning, is the behavior and physical effects caused by recent consumption of alcohol. The technical term intoxication in common speech may suggest that a large amount of alcohol has been consumed, leading to accompanying physical symptoms and deleterious health effects. Mild intoxication is mostly referred to by slang terms such as tipsy or buzzed. In addition to the toxicity of ethanol, the main psychoactive component of alcoholic beverages, other physiological symptoms may arise from the activity of acetaldehyde, a metabolite of alcohol. These effects may not arise until hours after ingestion and may contribute to a condition colloquially known as a hangover.

Symptoms of intoxication at lower doses may include mild sedation and poor coordination. At higher doses, there may be slurred speech, trouble walking, impaired vision, mood swings and vomiting. Extreme doses may result in a respiratory depression, coma, or death. Complications may include seizures, aspiration pneumonia, low blood sugar, and injuries or self-harm such as suicide. Alcohol intoxication can lead to alcohol-related crime, with perpetrators more likely to be intoxicated than victims.

Wernicke–Korsakoff syndrome (WKS), colloquially referred to as wet brain syndrome, is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome. It mainly causes vision changes, ataxia and impaired memory.

The cause of the disorder is thiamine (vitamin B₁) deficiency. This can occur due to eating disorders, malnutrition, and alcohol abuse. These disorders may manifest together or separately. WKS is usually secondary to prolonged alcohol abuse.

Huntington's disease (HD), also known as Huntington's chorea, is a fatal neurodegenerative disease that is mostly inherited. It typically presents as a triad of progressive psychiatric, cognitive, and motor symptoms. The earliest symptoms are often subtle problems with mood or mental/psychiatric abilities, which precede the motor symptoms for many people. The definitive physical symptoms, including a general lack of coordination and an unsteady gait, eventually follow. Over time, the basal ganglia region of the brain gradually becomes damaged. The disease is primarily characterized by a distinctive hyperkinetic movement disorder known as chorea. Chorea classically presents as uncoordinated, involuntary, "dance-like" body movements that become more apparent as the disease advances. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia, depression, apathy, and impulsivity at times. The specific symptoms vary somewhat between people. Symptoms can start at any age, but are usually seen around the age of 40. The disease may develop earlier in each successive generation. About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinson's disease rather than those of chorea.

HD is typically inherited from an affected parent, who carries a mutation in the huntingtin gene (HTT). However, up to 10% of cases are due to a new mutation. The huntingtin gene provides the genetic information for huntingtin protein (Htt). Expansion of CAG repeats of cytosine-adenine-guanine (known as a trinucleotide repeat expansion) in the gene coding for the huntingtin protein results in an abnormal mutant protein (mHtt), which gradually damages brain cells through a number of possible mechanisms. The mutant protein is dominant, so having one parent who is a carrier of the trait is sufficient to trigger the disease in their children. Diagnosis is by genetic testing, which can be carried out at any time, regardless of whether or not symptoms are present. This fact raises several ethical debates: the age at which an individual is considered mature enough to choose testing; whether parents have the right to have their children tested; and managing confidentiality and disclosure of test results.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, postural instability (collectively known as parkinsonism), autonomic dysfunction and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum. MSA was first described in 1960 by Milton Shy and Glen Drager and was then known as Shy–Drager syndrome.

Many people affected by MSA experience dysfunction of the autonomic nervous system, which commonly manifests as orthostatic hypotension, impotence, loss of sweating, dry mouth and urinary retention and incontinence. Palsy of the vocal cords is an important and sometimes initial clinical manifestation of the disorder.

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of progressive, incurable, and invariably fatal conditions that are associated with the degeneration of the nervous system in many animals, including humans, cattle, and sheep. Strong evidence supports the once unorthodox hypothesis that prion diseases are transmitted by abnormally shaped protein molecules known as prions. Prions consist of a protein called the prion protein (PrP). Misshapen PrP (often referred to as PrP) conveys its abnormal structure to naive PrP molecules by a crystallization-like seeding process. Because the abnormal proteins stick to each other, and because PrP is continuously produced by cells, PrP accumulates in the brain, harming neurons and eventually causing clinical disease.

Prion diseases are marked by mental and physical deterioration that worsens over time. A defining pathologic characteristic of prion diseases is the appearance of small vacuoles in various parts of the central nervous system that create a sponge-like appearance when brain tissue obtained at autopsy is examined under a microscope. Other changes in affected regions include the buildup of PrP, gliosis, and the loss of neurons.

Minamata disease (Japanese: 水俣病, Hepburn: Minamata-byō) is a neurological disease caused by severe mercury poisoning. Signs and symptoms include ataxia, numbness in the hands and feet, general muscle weakness, loss of peripheral vision, and damage to hearing and speech. In extreme cases, insanity, paralysis, coma, and death follow within weeks of the onset of symptoms. A congenital form of the disease affects fetuses, causing microcephaly, extensive cerebral damage, and symptoms similar to those seen in cerebral palsy.

Minamata disease was first discovered in the city of Minamata, Kumamoto Prefecture, Japan, in 1956. It was caused by the release of methylmercury in the industrial wastewater from a chemical factory owned by the Chisso Corporation, which continued from 1932 to 1968. It has also been suggested that some of the mercury sulfate in the wastewater was also metabolized to methylmercury by bacteria in the sediment. This highly toxic chemical bioaccumulated and biomagnified in shellfish and fish in Minamata Bay and the Shiranui Sea, which, when eaten by the local population, resulted in mercury poisoning. The poisoning and resulting deaths of both humans and animals continued for 36 years, while Chisso and the Kumamoto prefectural government did little to prevent the epidemic. The animal effects were severe enough in cats that they came to be named as having "dancing cat fever."

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of progressive, incurable, and invariably fatal conditions that are associated with the degeneration of the nervous system in many animals, including humans, cattle, and sheep. Strong evidence supports the once unorthodox hypothesis that prion diseases are transmitted by abnormally shaped protein molecules known as prions. Prions consist of a protein called the prion protein (PrP). Misshapen PrP (often referred to as PrP) conveys its abnormal structure to native PrP molecules by a crystallization-like seeding process. Because the abnormal proteins stick to each other, and because PrP is continuously produced by cells, PrP accumulates in the brain, harming neurons and eventually causing clinical disease.

Prion diseases are marked by mental and physical deterioration that worsens over time. A defining pathologic characteristic of prion diseases is the appearance of small vacuoles in various parts of the central nervous system that create a sponge-like appearance when brain tissue obtained at autopsy is examined under a microscope. Other changes in affected regions include the buildup of PrP, gliosis, and the loss of neurons.

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension (high blood pressure) is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

A stroke usually presents with an abrupt onset of a neurologic deficit – such as hemiplegia (one-sided weakness), numbness, aphasia (language impairment), or ataxia (loss of coordination) – attributable to a focal vascular lesion. The neurologic symptoms manifest within seconds because neurons need a continual supply of nutrients, including glucose and oxygen, that are provided by the blood. Therefore, if blood supply to the brain is impeded, injury and energy failure is rapid.

Wernicke encephalopathy (WE), also Wernicke's encephalopathy, or wet brain is the presence of neurological symptoms caused by biochemical lesions of the central nervous system after exhaustion of B-vitamin reserves, in particular thiamine (vitamin B₁). The condition is part of a larger group of thiamine deficiency disorders that includes beriberi, in all its forms, and alcoholic Korsakoff syndrome. When it occurs simultaneously with alcoholic Korsakoff syndrome it is known as Wernicke–Korsakoff syndrome.

Classically, Wernicke encephalopathy is characterised by a triad of symptoms: ophthalmoplegia, ataxia, and confusion. Around 10% of patients exhibit all three features, and other symptoms may also be present. While it is commonly regarded as a condition particular to malnourished people with alcohol misuse, it can be caused by a variety of diseases.It is treated with thiamine supplementation, which can lead to improvement of the symptoms and often complete resolution, particularly in those where alcohol misuse is not the underlying cause. Often other nutrients also need to be replaced, depending on the cause. Medical literature notes how managing the condition in a timely fashion can avoid worsening symptoms.

Dissociatives, colloquially dissos, are a subclass of hallucinogens that distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such an effect, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia.

Despite most dissociatives' main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical "hard drugs" or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.

Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of vitamin B₁₂. Those affected often have a gradual onset. The most common initial symptoms are feeling tired and weak. Other symptoms may include shortness of breath, feeling faint, a smooth red tongue, pale skin, chest pain, nausea and vomiting, loss of appetite, heartburn, numbness in the hands and feet, difficulty walking, memory loss, muscle weakness, poor reflexes, blurred vision, clumsiness, depression, and confusion. Without treatment, some of these problems may become permanent.

Pernicious anemia refers to a type of vitamin B₁₂ deficiency anemia that results from lack of intrinsic factor. Lack of intrinsic factor is most commonly due to an autoimmune attack on the cells that create it in the stomach. It can also occur following the surgical removal of all or part of the stomach or small intestine; from an inherited disorder or illnesses that damage the stomach lining. When suspected, diagnosis is made by blood tests initially a complete blood count, and occasionally, bone marrow tests. Blood tests may show fewer but larger red blood cells, low numbers of young red blood cells, low levels of vitamin B₁₂, and antibodies to intrinsic factor. Diagnosis is not always straightforward and can be challenging.

Vitamin B₁₂ deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B₁₂. Symptoms can vary from none to severe. Mild deficiency may have few or absent symptoms. In moderate deficiency, feeling tired, headaches, soreness of the tongue, mouth ulcers, breathlessness, feeling faint, rapid heartbeat, low blood pressure, pallor, hair loss, decreased ability to think and severe joint pain and the beginning of neurological symptoms, including abnormal sensations such as pins and needles, numbness and tinnitus may occur. Severe deficiency may include symptoms of reduced heart function as well as more severe neurological symptoms, including changes in reflexes, poor muscle function, memory problems, blurred vision, irritability, ataxia, decreased smell and taste, decreased level of consciousness, depression, anxiety, guilt and psychosis. If left untreated, some of these changes can become permanent. Temporary infertility, reversible with treatment, may occur. A late finding type of anemia known as megaloblastic anemia is often but not always present. In exclusively breastfed infants of vegan mothers, undetected and untreated deficiency can lead to poor growth, poor development, and difficulties with movement.

Causes are usually related to conditions that give rise to malabsorption of vitamin B₁₂ particularly autoimmune gastritis in pernicious anemia. Other conditions giving rise to malabsorption include surgical removal of the stomach, chronic inflammation of the pancreas, intestinal parasites, certain medications such as long-term use of proton pump inhibitors, H2-receptor blockers, and metformin, and some genetic disorders.