Huntington's disease in the context of "Neurocognitive disorder"

A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

Within neurodegenerative diseases, it is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people.

Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia is a life-limiting condition, having a significant effect on the individual, their caregivers, and their social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process.

Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, the most common cause is Alzheimer's disease, a neurodegenerative disorder. Dementia is a neurocognitive disorder with varying degrees of severity (mild to major) and many forms or subtypes. Dementia is an acquired brain syndrome, marked by a decline in cognitive function, and is contrasted with neurodevelopmental disorders. It has also been described as a spectrum of disorders with subtypes of dementia based on which known disorder caused its development, such as Parkinson's disease for Parkinson's disease dementia, Huntington's disease for Huntington's disease dementia, vascular disease for vascular dementia, HIV infection causing HIV dementia, frontotemporal lobar degeneration for frontotemporal dementia, Lewy body disease for dementia with Lewy bodies, and prion diseases. Subtypes of neurodegenerative dementias may also be based on the underlying pathology of misfolded proteins, such as synucleinopathies and tauopathies. The coexistence of more than one type of dementia is known as mixed dementia.

Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the HPRT1 gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins.

The HGPRT deficiency causes a build-up of uric acid in all body fluids. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production. This results in both high levels of uric acid in the blood and urine, associated with severe gout and kidney problems. Neurological signs include poor muscle control and moderate intellectual disability. These complications usually appear in the first year of life. Beginning in the second year of life, a particularly striking feature of LNS is self-mutilating behaviors, characterized by lip and finger biting. Neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in Huntington's disease. The cause of the neurological abnormalities remains unknown. Because a lack of HGPRT causes the body to poorly utilize vitamin B₁₂, some males may develop megaloblastic anemia.

In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as NMDA receptors or AMPA receptors encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Different mechanisms might lead to increased extracellular glutamate concentrations, e.g. reduced uptake by glutamate transporters (EAATs), synaptic hyperactivity, or abnormal release from different neural cell types. Excess glutamate allows high levels of calcium ions (Ca) to enter the cell. Ca influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA, in subtoxic amounts, can block glutamate toxicity and induce neuronal survival. In addition to abnormally high neurotransmitter concentrations, also elevation of the extracellular potassium concentration, acidification and other mechanisms may contribute to excitotoxicity.

Excitotoxicity may be involved in cancers, spinal cord injury, stroke, traumatic brain injury, hearing loss (through noise overexposure or ototoxicity), and in neurodegenerative diseases of the central nervous system such as multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, alcoholism, alcohol withdrawal or hyperammonemia and especially over-rapid benzodiazepine withdrawal, and also Huntington's disease. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia. Blood sugars are the primary energy source for glutamate removal from inter-synaptic spaces at the NMDA and AMPA receptor site. Persons in excitotoxic shock must never fall into hypoglycemia. Patients should be given 5% glucose (dextrose) IV drip during excitotoxic shock to avoid a dangerous build up of glutamate. When 5% glucose (dextrose) IV drip is not available high levels of fructose are given orally. Treatment is administered during the acute stages of excitotoxic shock along with glutamate receptor antagonists. Dehydration should be avoided as this also contributes to the concentrations of glutamate in the inter-synaptic cleft and "status epilepticus can also be triggered by a build up of glutamate around inter-synaptic neurons."

Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo- "muscle", clonus "spasm") describes a medical sign and, generally, is not a diagnosis of a disease. It belongs to the hyperkinetic movement disorders, among tremor and chorea for example. These myoclonic twitches, jerks, or seizures are usually caused by sudden muscle contractions (positive myoclonus) or brief lapses of contraction (negative myoclonus). The most common circumstance under which they occur is while falling asleep (hypnic jerk). Myoclonic jerks occur in healthy people and are experienced occasionally by everyone. However, when they appear with more persistence and become more widespread they can be a sign of various neurological disorders. Hiccups are a kind of myoclonic jerk specifically affecting the diaphragm. When a spasm is caused by another person it is known as a provoked spasm. Shuddering attacks in babies fall in this category.

Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern. They may occur infrequently or many times each minute. Most often, myoclonus is one of several signs in a wide variety of nervous system disorders such as multiple sclerosis, Parkinson's disease, dystonia, cerebral palsy, Alzheimer's disease, Gaucher's disease, subacute sclerosing panencephalitis, Creutzfeldt–Jakob disease (CJD), serotonin toxicity, some cases of Huntington's disease, some forms of epilepsy, and occasionally in intracranial hypotension.

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinson's disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases.

The other category of movement disorder is hyperkinesia that features an exaggeration of unwanted movement, such as twitching or writhing in Huntington's disease or Tourette syndrome.

The caudate nucleus is one of the structures that make up the corpus striatum, which is part of the basal ganglia in the human brain. Although the caudate nucleus has long been associated with motor processes because of its relation to Parkinson's disease and Huntington's disease, it also plays important roles in nonmotor functions, such as procedural learning, associative learning, and inhibitory control of action. The caudate is also one of the brain structures that compose the reward system, and it functions as part of the cortico-basal ganglia-thalamo-cortical loop.

Clinical neuroscience is a branch of neuroscience that focuses on the scientific study of fundamental mechanisms that underlie diseases and disorders of the brain and central nervous system. It seeks to develop new ways of conceptualizing and diagnosing such disorders and ultimately of developing novel treatments.

A clinical neuroscientist is a scientist who has specialized knowledge in the field. Not all clinicians are clinical neuroscientists. Clinicians and scientists -including psychiatrists, neurologists, clinical psychologists, neuroscientists, and other specialists—use basic research findings from neuroscience in general and clinical neuroscience in particular to develop diagnostic methods and ways to prevent and treat neurobiological disorders. Such disorders include addiction, Alzheimer's disease, amyotrophic lateral sclerosis, anxiety disorders, attention deficit hyperactivity disorder, autism, bipolar disorder, brain tumors, depression, Down syndrome, dyslexia, epilepsy, Huntington's disease, multiple sclerosis, neurological AIDS, neurological trauma, pain, obsessive-compulsive disorder, Parkinson's disease, schizophrenia, sleep disorders, stroke and Tourette syndrome.

Cholesteryl esters are a type of dietary lipid and are ester derivatives of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Cholesteryl esters have a lower solubility in water due to their increased hydrophobicity. Esters are formed by replacing at least one –OH (hydroxyl) group with an –O–alkyl (alkoxy) group. They are hydrolyzed by pancreatic enzymes, such as cholesterol esterase, to produce cholesterol and free fatty acids. They are associated with atherosclerosis.

Cholesteryl esters are found in human brains as lipid droplets which store and transport cholesterol. Increased levels of cholesteryl esters have been found in certain parts of the brain of people with Huntington's disease. Higher concentrations of cholesteryl esters have been found in the caudate and putamen, but not the cerebellum, of people with Huntington disease compared with levels in controls. Increase in cholesteryl esters has also been found in other neurological disorders like multiple sclerosis and Alzheimer's disease.