Tag: Huntingtons Disease

Categories
Ailmemts & Remedies

Huntington’s Disease

Definition:
Huntington’s disease (also referred to in more formal medical research as Huntington Disease) is an hereditary neurological disorder of the central nervous system that causes progressive degeneration of cells in the brain, slowly impairing a person’s ability to walk, think, talk and reason.

Most people with Huntington’s disease develop signs and symptoms in their 40s or 50s, but the onset of disease may be earlier or later in life. When disease onset begins before age 20, the condition is called juvenile Huntington’s disease. Earlier onset often results in a somewhat different presentation of symptoms and faster disease progression.

CLICK & SEE THE PICTURES

Medications are available to help manage the symptoms of Huntington’s disease, but treatments can’t prevent the physical, mental and behavioral decline associated with the condition.

It was first described in 1872 by an American doctor, George Huntington, who studied an extended family in Long Island affected by the condition.

Symptoms:
Symptoms of Huntington’s disease commonly become noticeable between the ages of 35 and 44 years, but they can begin at any age from infancy to old age. In the early stages, there are subtle changes in personality, cognition, and physical skills. The physical symptoms are usually the first to be noticed, as cognitive and psychiatric symptoms are generally not severe enough to be recognized on their own at the earlier stages. Almost everyone with Huntington’s disease eventually exhibits similar physical symptoms, but the onset, progression and extent of cognitive and psychiatric symptoms vary significantly between individuals.

The most characteristic initial physical symptoms are jerky, random, and uncontrollable movements called chorea. Chorea may be initially exhibited as general restlessness, small unintentionally initiated or uncompleted motions, lack of coordination, or slowed saccadic eye movements. These minor motor abnormalities usually precede more obvious signs of motor dysfunction by at least three years. The clear appearance of symptoms such as rigidity, writhing motions or abnormal posturing appear as the disorder progresses. These are signs that the system in the brain that is responsible for movement is affected.[6] Psychomotor functions become increasingly impaired, such that any action that requires muscle control is affected. Common consequences are physical instability, abnormal facial expression, and difficulties chewing, swallowing and speaking. Eating difficulties commonly cause weight loss and may lead to malnutrition.  Sleep disturbances are also associated symptoms. Juvenile HD differs from these symptoms in that it generally progresses faster and chorea is exhibited briefly, if at all, with rigidity being the dominant symptom. Seizures are also a common symptom of this form of HD.

Cognitive abilities are impaired progressively. Especially affected are executive functions which include planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions. As the disease progresses, memory deficits tend to appear. Reported impairments range from short-term memory deficits to long-term memory difficulties, including deficits in episodic (memory of one’s life), procedural (memory of the body of how to perform an activity) and working memory. Cognitive problems tend to worsen over time, ultimately leading to dementia. This pattern of deficits has been called a subcortical dementia syndrome to distinguish it from the typical effects of cortical dementias e.g. Alzheimer‘s disease.

Reported neuropsychiatric manifestations are anxiety, depression, a reduced display of emotions (blunted affect), egocentrism, aggression, and compulsive behavior, the latter of which can cause or worsen addictions, including alcoholism, gambling, and hypersexuality.  Difficulties in recognizing other people’s negative expressions have also been observed. Prevalence of these symptoms is also highly variable between studies, with estimated rates for lifetime prevalence of psychiatric disorders between 33% and 76%.  For many sufferers and their families these symptoms are among the most distressing aspects of the disease, often affecting daily functioning and constituting reason for institutionalisation. Suicidal thoughts and suicide attempts are more common than in the general population.

Mutant Huntingtin is expressed throughout the body and associated with abnormalities in peripheral tissues that are directly caused by such expression outside the brain. These abnormalities include muscle atrophy, cardiac failure, impaired glucose tolerance, weight loss, osteoporosis and testicular atrophy

Reported prevalences of behavioral and psychiatric symptoms in Huntington’s disease :
Irritability 38–73%
Apathy 34–76%
Anxiety 34–61%
Depressed mood 33–69%
Obsessive and compulsive 10–52%
Psychotic 3–11%

Causes:
Huntington’s disease is caused by a single defective gene on chromosome 4. This leads to damage of the nerve cells in areas of the brain including the basal ganglia and cerebral cortex, and to the gradual onset of physical, mental and emotional changes.

The Huntington’s Disease Association estimates between 6,500 and 8,000 people in the UK have the disease.

The tragedy is that by the time symptoms appear, the person has often had a family and may have passed on the gene to their children. Each person whose parent has Huntington’s disease has a 50 per cent chance of inheriting the gene, and everyone who inherits the gene will at some stage develop the disease.

In three per cent of cases, there’s no family history of Huntington’s disease and the genetic fault may be a new mutation.

The disease can’t be prevented from developing if someone has the faulty gene. To inherit the illness, the gene only has to come from one parent, making it autosomal dominant.

CLICK & SEE

The gene for Huntington’s disease can be detected with a blood test, which is available to those aged over 18, before symptoms begin. This can determine whether someone has the faulty gene and help them in their family planning

Risk Factors:
If one of your parents has Huntington’s disease, you have a 50 percent chance of developing the disease. In rare cases, you may develop Huntington’s disease without having a family history of the condition. Such an occurrence may be the result of a genetic mutation that happened during your father’s sperm development.

Complications:
After the onset of Huntington’s disease, a person’s functional abilities gradually worsen over time. The rate of disease progression and duration varies. The time from disease onset to death is often about 10 to 30 years. Juvenile onset usually results in death in fewer than 15 years.

The clinical depression associated with Huntington’s disease may increase the risk of suicide. Some research suggests that the greater risk of suicide occurs before a diagnosis is made and in middle stages of the disease when a person has begun to lose independence.

Eventually, a person with Huntington’s disease requires help with all activities of daily living and care. Late in the disease, he or she will likely be confined to a bed and unable to speak. However, a person’s understanding of surroundings and interactions remain intact for a long time.

Common causes of death include:

*Pneumonia or other infections
*Injuries related to falls
*Complications related to the inability to swallow

Diagnosis:
Medical diagnosis of the onset of HD can be made following the appearance of physical symptoms specific to the disease. Genetic testing can be used to confirm a physical diagnosis if there is no family history of HD. Even before the onset of symptoms, genetic testing can confirm if an individual or embryo carries an expanded copy of the trinucleotide repeat in the HTT gene that causes the disease. Genetic counseling is available to provide advice and guidance throughout the testing procedure, and on the implications of a confirmed diagnosis. These implications include the impact on an individual’s psychology, career, family planning decisions, relatives and relationships. Despite the availability of pre-symptomatic testing, only 5% of those at risk of inheriting HD choose to do so

Clinical:
A physical examination, sometimes combined with a psychological examination, can determine whether the onset of the disease has begun. Excessive unintentional movements of any part of the body are often the reason for seeking medical consultation. If these are abrupt and have random timing and distribution, they suggest a diagnosis of HD. Cognitive or psychiatric symptoms are rarely the first diagnosed; they are usually only recognized in hindsight or when they develop further. How far the disease has progressed can be measured using the unified Huntington’s disease rating scale which provides an overall rating system based on motor, behavioral, cognitive, and functional assessments. Medical imaging, such as computerized tomography (CT) and magnetic resonance imaging (MRI), only shows visible cerebral atrophy in the advanced stages of the disease. Functional neuroimaging techniques such as fMRI and PET can show changes in brain activity before the onset of physical symptoms.

Grenetic:
Because HD follows an autosomal dominant pattern of inheritance, there is a strong motivation for individuals who are at risk of inheriting it to seek a diagnosis. The genetic test for HD consists of a blood test which counts the numbers of CAG repeats in each of the HTT alleles.[38] A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop HD.

A pre-symptomatic test is a life-changing event and a very personal decision. The main reason given for choosing testing for HD is to aid in career and family decisions. Over 95% of individuals at risk of inheriting HD do not proceed with testing, mostly because there is no treatment. A key issue is the anxiety an individual experiences about not knowing whether they will eventually develop HD, compared to the impact of a positive result.  Irrespective of the result, stress levels have been found to be lower two years after being tested, but the risk of suicide is increased after a positive test result. Individuals found to have not inherited the disorder may experience survivor guilt with regard to family members who are affected. Other factors taken into account when considering testing include the possibility of discrimination and the implications of a positive result, which usually means a parent has an affected gene and that the individual’s siblings will be at risk of inheriting it. Genetic counseling in HD can provide information, advice and support for initial decision-making, and then, if chosen, throughout all stages of the testing process. Counseling and guidelines on the use of genetic testing for HD have become models for other genetic disorders, such as autosomal dominant cerebellar ataxias. Presymptomatic testing for HD has also influenced testing for other illnesses with genetic variants such as polycystic kidney disease, familial Alzheimer’s disease and breast cancer

Embryonic:
Embryos produced using in vitro fertilisation may be genetically tested for HD using preimplantation genetic diagnosis. This technique, where a single cell is extracted from a 4 to 8 cell embryo and then tested for the genetic abnormality, can then be used to ensure embryos with affected HTT genes are not implanted, and therefore any offspring will not inherit the disease. It is also possible to obtain a prenatal diagnosis for an embryo or fetus in the womb.

Differential diagnosis:
About 90% of HD diagnoses based on the typical symptoms and a family history of the disease are confirmed by genetic testing to have the expanded trinucleotide repeat that causes HD. Most of the remaining are called HD-like disorders.  Most of these other disorders are collectively labelled HD-like (HDL). The cause of most HDL diseases is unknown, but those with known causes are due to mutations in the prion protein gene (HDL1), the junctophilin 3 gene (HDL2), a recessively inherited HTT gene (HDL3—only found in one family and poorly understood), and the gene encoding the TATA box-binding protein (HDL4/SCA17). Other autosomal dominant diseases that can be misdiagnosed as HD are dentatorubral-pallidoluysian atrophy and neuroferritinopathy. There are also autosomal recessive disorders that resemble sporadic cases of HD. Main examples are chorea acanthocytosis, pantothenate kinase-associated neurodegeneration and X-linked McLeod syndrome

Treatment:
There’s no cure, but supportive care can ease many symptoms and help a person with Huntington’s disease, and their family, lead as normal a life as possible.

Drugs can relieve symptoms of involuntary movements, depression and mood swings. Speech therapy can help improve speech and swallowing problems. A high-calorie diet can help maintain weight and improve symptoms such as involuntary movement and behavioural problems.

Cognitive changes often result in loss of enthusiasm, initiative and organisational skills, which can make multi-tasking difficult. Constant nursing care is needed in the later stages of the disease and support for carers is important, too.

Secondary illnesses, such as pneumonia, are often the cause of death.

There’s extensive research into possible treatments for Huntington’s disease. One technique is the use of transplants of foetal brain cells, which appear in some cases to repair and rejuvenate the damaged area.

Meanwhile, researchers at the University of Leeds have found that one of the body’s naturally occurring proteins is causing some of the disruption that occurs in the brains of those with Huntington’s, and its effects may be modified by using drugs that are already being used to help cancer patients. But it is likely to be years, if at all, before these developments result in an effective treatment.

Prognosis:
The length of the trinucleotide repeat accounts for 60% of the variation in the age of onset and the rate of progression of symptoms. A longer repeat results in an earlier age of onset and a faster progression of symptoms. For example, individuals with a trinucleotide repeat greater than sixty repeats often develop the disease before twenty years of age, and those with less than forty repeats may not develop noticeable symptoms. The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.

Life expectancy in HD is generally around 20 years following the onset of visible symptoms.  Most of the complications that are life-threatening result from muscle coordination issues, or to a lesser extent from behavioural changes resulting from the decline in cognitive function. The largest risk is pneumonia, which is the cause of death of one-third of those with HD. As the ability to synchronise movements deteriorates, difficulty clearing the lungs and an increased risk of aspirating food or drink both increase the risk of contracting pneumonia. The second greatest risk is heart disease, which causes almost a quarter of fatalities of those with HD. Suicide is the next greatest cause of fatalities, with 7.3% of those with HD taking their own lives and up to 27% attempting to do so. It is unclear to what extent suicidal thoughts are influenced by psychiatric symptoms, as they may be considered to be a response of an individual to retain a sense of control of their life or to avoid the later stages of the disease.  Other associated risks include choking, physical injury from falls, and malnutrition.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/huntingtons1.shtml
http://en.wikipedia.org/wiki/Huntington’s_disease
http://www.mayoclinic.com/health/huntingtons-disease/DS00401

http://www.healthtree.com/articles/huntingtons-disease/causes/

http://www.bothbrainsandbeauty.com/academic-discussions/huntingtons-disease-991

Related articles
Enhanced by Zemanta
Categories
News on Health & Science

Slowing Down Life’s Clock

[amazon_link asins=’0307462889,0230112056,1612432735,192912533X,1929125313,0746011091,1499729901,1592409326,147673609X’ template=’ProductCarousel’ store=’finmeacur-20′ marketplace=’US’ link_id=’6d82fbd4-f81d-11e7-ba94-395c1f0614e3′]

Decades of research on aging are beginning to pay off, although it doesn’t mean that increasing longevity is a pill away, writes T.V. Jayan

click & see
It’s been a decade and a half since Cynthia Kenyon genetically tweaked roundworms to expand their lifespan to twice the normal length. Science has not been able to uncork the fountain of youth yet, but the jump-start Kenyon and her colleagues at the University of California, San Francisco, gave to longevity research    by making the wrigglers, through the manipulation of a single gene, live for 40 days instead of 20  has helped resolve many mysteries surrounding the issue of ageing.

The latest in the list is the revelation that the ubiquitous molecule, insulin, comes in the way of a prolonged lifespan. Another independent study points to the benefits calorie restriction has on longevity by making nearly starved roundworms live 40 per cent longer than their well-fed peers.

Too much insulin ” a hormone that tells our cells to use sugar from the bloodstream, thus helping us to avoid metabolic complications that lead to diseases such as diabetes  in the brain may not be a good sign, said a team of researchers from the Howard Hughes Medical Institute in Boston.

By saying so, the researchers  led by endocrinologist Morris White  scientifically reinforced what every mother might tell her child: Eat a good diet and exercise; it will keep you healthy.

The researchers, who sought to understand the role of the insulin-signalling pathway in extending lifespan, found actually the opposite of what most scientists and clinicians believed. Because, according to White, most would find it difficult to accept the idea that insulin can reduce lifespan. This signalling pathway of insulin governs growth and metabolic processes in cells throughout the body.

Tests on lab mice showed that when both the copies of a gene responsible for insulin signalling called Irs2  were knocked off in the brain but retained in cells in other organs, the animals lived about six months longer than usual. This is nearly 18 per cent more than the animal  normal lifespan.

This even though the genetically modified mice were overweight and had higher blood insulin levels. To the scientist’s  surprise, they became more active with age and their glucose metabolism resembled that of younger mice. Besides, their brains showed higher levels of superoxide dismutase, an antioxidant enzyme that protects cells from damage caused by highly reactive chemicals called free radicals.

So diet, physical activity and lower weight keep one’s peripheral tissues sensitive to insulin. This reduces the amount and duration of insulin secretion required to keep glucose under control when one eats. This way, the brain is exposed to less insulin. And since insulin turns on Irs2, the lower the insulin, the lower the IRs2 activity, White observed. The findings were reported in the July 20 issue of the journal Science.

While White’s team pointed to a balanced diet and keeping fit as the recipe for a long life, Andrew Dillin of the Salk Institute of Biological Studies in the US   who had co-authored several papers on ageing with Kenyon  found a gene in roundworms that specifically links calorie restriction to longevity. Interestingly, an Indian scientist, Kalluri Subba Rao, arrived at a similar conclusion more than a decade ago by studying undernourished people and comparing them with those who ate a normal diet.

Dillin and his colleagues in a way cracked open the black box of how persistent hunger increases longevity. “After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel the underlying molecular programme required for increased longevity in response to calorie restriction,” he said.

What is significant about his work is that the gene they identified, pha-4, is independent of those involved in the insulin pathway, which has been the focus of most longevity research so far. The loss of only this gene       which encodes for the protein PHA-4  negated the lifespan-enhancing effects of calorie restriction in worms. So the scientists did the opposite  that is, overexpress the pha-4 gene in the worms. It worked, and the worms lived as much as 40 per cent longer.

Human beings, says Dillin, possess three genes similar to the pha-4 gene of worms, all belonging to what is called the Foxa family. These three genes play an important role in the development and later, the regulation, of glucagon — a pancreatic hormone that, unlike insulin, increases the blood sugar concentration and maintains the body’s energy balance, especially during fasting.

Subba Rao, an emeritus professor at the University of Hyderabad who in 1996 reported the benefits of diet restriction on ageing, agrees. Down-regulating glucose signalling has several positive effects, longevity being one of them.  The body is programmed to metabolise, say, one tonne of sugar over a lifetime. In how much time one does it is entirely up to that person,” said Subba Rao, coordinator of the university’s Centre for Research and Education in Ageing.

Concerted efforts over the last 15 years in the biology of ageing are paying off, although it doesn’t mean that increasing one’s lifespan is a pill away. But scientists are already taking the research to the next level: studying the proteins involved in the process. Examining the process of ageing from the protein perspective may lead to therapeutic methods of delaying ageing in the not-so-distant future, provided the scientists repeat in humans the feats they have achieved in worms and mice.

Last week, a team of researchers at the Scripps Research Institute in La Jolla, California, identified some 86 proteins whose abundance varied in mutant round worms as compared to normal ones. While 47 of the proteins were more abundant in worms that were genetically altered to live twice longer, another 39 were less abundant than in the controls. “Proteins are harder to study but they are closer to the enzymatic processes involved,” John Yates, who led the study, told KnowHow.

Enzymatic processes are the closest one can get when it comes to therapeutics as they are part of the bodys routine biochemical processes. It is for the same reason that many new-generation drugs today have enzymes as their key component.

Source: The Telegraph (Kolkata, India)

Related articles
css.php