Quadriplegia is a neurological condition which affects the upper and lower body of the affected individual, including all 4 limbs. The condition is also commonly called Tetraplegia. The name comes from the Latin word “quattuor” (or Greek word “tetra”) meaning 4 and the Greek word “plege” meaning stroke. Full body paralysis is another name for the quadriplegic condition.

What is Quadriplegia?

Quadriplegia (kwod-rih-PLEE-jah) is a type of spinal cord injury (SCI) that also may be called tetraplegia (tet-ruh-PLEE-jah). You may become paralyzed (PER-e-liz-ed) if your spinal cord is injured or if you have certain diseases. The spinal cord is part of the central nervous system, which allows your brain to communicate with your body. The spine is made up of bones called vertebrae (VER-te-bray) that are stacked on top of each other. The spinal cord runs from the brain down through the center of the vertebrae. Tough fibrous discs separate the vertebrae, acting as cushions or shock absorbers.

• Quadriplegia means that the part of the spinal cord inside your neck has been injured. This injury causes loss of feeling and movement in your arms, legs, and trunk (center of your body). Spinal cord injuries are described by where on the spinal cord they have happened. Caregivers use letters and numbers to describe where your spinal cord is injured. The letter “C” stands for cervical (SER-vi-kl) or neck. There are eight cervical, 12 thoracic, five lumbar, and four sacral bones. If you have a C3 spinal cord injury, the damage is at the level of the third cervical spinal cord section.
• Spinal cord injuries are also described as complete or incomplete. This refers to how much function (movement and feeling) is left after you have healed from the injury. A complete SCI means that you have lost total (all) movement and feeling below the injured level. An incomplete SCI does not cause total loss of movement or feeling.

Symptoms

Although the most obvious symptom is impairment to the limbs, functioning is also impaired in the torso. This can mean a loss or impairment in controlling bowel and bladder, sexual function, digestion, breathing, and other autonomic functions. Furthermore, sensation is usually impaired in affected areas. This can manifest as numbness, reduced sensation, or burning neuropathic pain.
Secondarily, because of their depressed functioning and immobility, quadriplegics are often more vulnerable to pressure sores, osteoporosis and fractures, frozen joints, spasticity, respiratory complications and infections, autonomic dysreflexia, deep vein thrombosis, and cardiovascular disease.
Severity depends on both the level at which the spinal cord is injured and the extent of the injury.
An individual with an injury at C1 (the highest cervical vertebra, at the base of the skull) will likely lose function from the neck down and be ventilator-dependent. An individual with a C7 injury may lose function from the chest down but still retain use of the arms and much of the hands.
The extent of the injury is also important. A complete severing of the spinal cord will result in complete loss of function from that vertebra down. A partial severing or even bruising of the spinal cord results in varying degrees of mixed function and paralysis. For example, there are quadriplegics who have impairment in all four limbs but can still walk and use their hands due to the relatively minor extent of their injury. Others cannot walk but are able to maintain control of bladder, bowel, and sexual function.
It is common to have partial use of some limbs, such as the ability to move the arms but not the hands, or to be able to use the fingers but not have enough grip strength to lift objects. Furthermore, the deficit in the limbs may not be the same on both sides of the body; the left or right side may be more affected, depending on the location of the lesion on the spinal cord.

Prognosis

Delayed diagnosis of cervical spine injury has grave consequences for the victim. About one in twenty cervical fractures are missed, and about two-thirds of these patients have further spinal-cord damage as a result. About 30% of cases of delayed diagnosis of cervical spine injury develop permanent neurological deficits. In high-level cervical injuries, total paralysis from the neck can result. High-level quadriplegics (C5 and above) will likely need constant care and assistance in things such as getting dressed, eating, and bowel and bladder help. Low-level quadriplegics (C6-C7) can often live independently.
Even with “complete” injuries, in some rare cases, through intensive rehabilitation, slight movement can be regained through “rewiring” neural connections, as in the case of the late actor Christopher Reeve.

Tests

Tests help caregivers find out more about your spinal cord injury. They may also help caregivers plan your treatment. You may need one or more of the following tests.

• Neurologic (nu-roh-LAH-jik) tests: Caregivers may ask you questions and do other tests to learn what area of your spinal cord is injured.
• X-rays: X-rays help caregivers see the part of the spine that is damaged.
• CT scan: This test is also called a “CAT” scan. A special x-ray machine uses a computer to take pictures of your neck and spine. Your caregivers look at the pictures to see areas that might be injured.
• MRI: This test is also called magnetic resonance (REZ-oh-nans) imaging. This test may be done to show where and how much damage has occurred. You may need an MRI if you are having pain or muscle spasms.

Treatment

You will need to stay in the hospital right after the injury. Soon after, you may be moved to a rehabilitation (ree-hah-bil-ih-TAY-shun) center. The goal of rehabilitation is to help you learn to take care of yourself as much as possible. You may have one or more of the following treatments during rehabilitation:

• Bowel and bladder programs: Being paralyzed makes you unable to control when you urinate or have a BM. Caregivers will teach you how to manage your bowels and bladder.
• Braces: You may need a halo brace or a Philadelphia collar if the bones or ligaments that support your spine are injured. Another type of brace may be used if the injury is in your chest or lower back area. These braces include a clamshell (plastic body jacket) or a plaster or plastic body cast.
• Medications: Caregivers will teach you what medicines you need, why you need them, and how to take them. You may need one or more of the following medicines:
  • Steroids: This medicine is used to prevent and reduce spinal cord swelling and improve blood flow.
  • Osmotic diuretics: An osmotic (oz-MAH-tik) diuretic (deye-yoo-RET-ik) is medicine that may help decrease and prevent spinal cord swelling.
  • Blood pressure medicine: This medicine may be given to lower your blood pressure. Keeping your blood pressure under control protects your heart, lungs, brain, kidneys, and other organs.

• Mental health therapy: Being quadriplegic can cause you and your family to be depressed or sad. Mental health therapists help you and your family learn to cope with your spinal cord injury.
• Occupational therapy: Occupational (ok-u-PAY-shun-al) therapists (OT) teach you how to use special equipment so that you can care for yourself. They help you relearn how to perform your activities of daily living. This means learning how to eat, get dressed, and care for yourself. Your OT also teaches you work-related skills.
• Physical therapy: Physical (FIZ-i-kal) therapists (PT) teach you how to keep your muscles strong. They also help your joints stay limber (able to move easily) and teach you how to stay active. This therapy includes learning how to use a wheelchair. Caregivers teach you how to move from your bed to the chair and to the commode (toilet).
• Recreational therapy: Recreational therapists continue your skills training so that you can be active in your community. You may also learn fun activities.
• Respiratory care: Depending on how high on the spinal cord your injury is, you may have trouble breathing. You may need a machine called a ventilator (VEN-ti-lay-ter) to breathe for you. Respiratory (RES-pir-ah-tohr-ee) therapists make sure that your respiratory system (breathing system) stays healthy.
• Skin care: Being paralyzed puts your skin at risk for getting decubitus (de-KU-bi-tus) ulcers (sores). These also are called pressure sores. Caregivers help you learn how to keep your skin healthy, and what to do if you develop skin problems.

Surgeries

The injury to your spinal cord cannot be repaired, even with surgery.

• You may need surgery to stabilize (support) the bones in your spine. Pieces of vertebra or disc may be pressing on the spinal cord or nerve roots coming out of the spinal cord. You may need surgery to remove these pieces of bone or disc. Surgery also can be done to line up the bony spinal column. Caregivers may use bone from your hip or metal rods and screws to support your spine.
• You may be able to have surgery or use pieces of equipment to help you move better. Some of these procedures are called muscle tendon transfer, or functional electrical stimulation (FES). These procedures may be done about a year after your spinal cord injury. This will allow you to recover as much as possible.
• If your injury is high up on your spinal cord, you may need a ventilator to help you breathe. You may be able to have a phrenic (FREH-nik) nerve pacer. This surgery is expensive, but has some advantages over a ventilator. Talk to your caregiver about a phrenic nerve pacer.

Advice

Although this condition is very limiting, today’s tetraplegics still enjoy a better quality and duration of life than ever before. Technological breakthroughs have increased patient mobility, functionality and communicative abilities. Portable support systems have given all but the most dire of patients some measure of independence and autonomy.
Preventative and maintenance care is crucial for keeping up good health. There are far too many opportunistic conditions which might seriously affect a tetraplegic at any point in life… Make sure to see your doctor regularly and get checked out if you even suspect that something might be wrong. Keeping a positive mental state will help improve both the quality of life and your remaining physical functionality. Remember that the mind is still important to protect the remaining functions of the physical body. Life is a gift and there is no reason why even a high level quadriplegic can not find joy and peace while still living with their considerable hardships

Source

• Wikipedia
• Times of India
• Spinal Injury.Net
• Disease Condition.com
• Origins of Cerebral Plasy.Com
  

Introduction

Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy.

Gestational diabetes generally has few symptoms and it is most commonly diagnosed by screening during pregnancy. Diagnostic tests detect inappropriately high levels of glucose in blood samples. Gestational diabetes affects 3-10% of pregnancies, depending on the population studied.No specific cause has been identified, but it is believed that the hormones produced during pregnancy increase a woman’s resistance to insulin, resulting in impaired glucose tolerance.

Babies born to mothers with gestational diabetes are at increased risk of problems typically such as being large for gestastional age (which may lead to delivery complications), low blood sugar, and jaundice. Gestational diabetes is a treatable condition and women who have adequate control of glucose levels can effectively decrease these risks.

Women with gestational diabetes are at increased risk of developing type 2 diabetes mellitus after pregnancy, while their offspring are prone to developing childhood obesity, with type 2 diabetes later in life. Most patients are treated only with diet modification and moderate exercise but some take anti-diabetic drugs, including insulin.

Definition

Gestational diabetes is formally defined as “any degree of glucose intolerance with onset or first recognition during pregnancy”. This definition acknowledges the possibility that patients may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis .

How gestational diabetes can affect the baby?

Gestational diabetes affects the mother in late pregnancy, after the baby’s body has been formed, but while the baby is busy growing. Because of this, gestational diabetes does not cause the kinds of birth defects sometimes seen in babies whose mothers had diabetes before pregnancy.

However, untreated or poorly controlled gestational diabetes can hurt your baby. When you have gestational diabetes, your pancreas works overtime to produce insulin, but the insulin does not lower your blood glucose levels. Although insulin does not cross the placenta, glucose and other nutrients do. So extra blood glucose goes through the placenta, giving the baby high blood glucose levels. This causes the baby’s pancreas to make extra insulin to get rid of the blood glucose. Since the baby is getting more energy than it needs to grow and develop, the extra energy is stored as fat.

This can lead to macrosomia, or a “fat” baby. Babies with macrosomia face health problems of their own, including damage to their shoulders during birth. Because of the extra insulin made by the baby’s pancreas, newborns may have very low blood glucose levels at birth and are also at higher risk for breathing problems. Babies with excess insulin become children who are at risk for obesity and adults who are at risk for type 2 diabetes.

Classification

The White classification, named after Priscilla Whitewho pioneered in research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and diabetes that existed prior to pregnancy (pregestational diabetes). These two groups are further subdivided according to their associated risks and management.[54]

There are 2 subtypes of gestational diabetes (diabetes which began during pregnancy):

• Type A1: abnormal oral glucose tolerance test (OGTT) but normal blood glucose levels during fasting and 2 hours after meals; diet modification is sufficient to control glucose levels
• Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is required

The second group of diabetes which existed prior to pregnancy is also split up into several subtypes.

Treatment

The goal of treatment is to reduce the risks of GDM for mother and child. Scientific evidence is beginning to show that controlling glucose levels can result in less serious fetal complications (such as macrosomia) and increased maternal quality of life. Unfortunately, treatment of GDM is also accompanied by more infants admitted to neonatal wards and more inductions of labour, with no proven decrease in cesarean section rates or perinatal mortality. These findings are still recent and controversial.

Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes.[58] Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.

Any diet needs to provide sufficient calories for pregnancy, typically 2,000 – 2,500 kcal with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more.

Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM.

Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low.Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:

• fasting capillary blood glucose levels <5.5 mmol/L
• 1 hour postprandial capillary blood glucose levels <8.0 mmol/L
• 2 hour postprandial blood glucose levels <6.7 mmol/L

Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.

If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might become necessary. The most common therapeutic regime involves premeal fast-acting insulin to blunt sharp glucose rises after meals.Care needs to be taken to avoid low blood sugar levels (hypoglycemia) due to excessive insulin injections. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits.

There is some evidence that certain oral glycemic agents might be safe in pregnancy, or at least, are significantly less dangerous to the developing fetus than poorly controlled diabetes. However, few studies have been performed as of this time and this is not a generally accepted treatment. These agents may be used in research settings, or if the patient needs intervention but refuses insulin therapy, and is aware of the risks.Glyburide, a second generation sulfonylurea, has been shown to be an effective alternative to insulin therapy.In one study, 4% of women needed supplemental insulin to reach blood sugar targets.

Metformin has shown promising results. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.A recent randomized controlled trial of metformin versus insulin showed that women preferred metformin tablets to insulin injections, and that metformin is safe and equally effective as insulin. Severe neonatal hypoglycemia was less common in insulin-treated women, but preterm delivery was more common. Almost half of patients did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight.There remains a possibility of long-term complications from metformin therapy, although follow-up at the age of 18 months of children born to women with polycystic ovarian syndrome and treated with metformin revealed no developmental abnormalities.

If diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary.

The development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with ouvert diabetes.

Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.

A repeat OGTT should be carried out 2-4 months after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised.

Source

Wikipedia

American Diabetes Association

Definition

Situs inversus is a condition in which the organs of the chest and abdomen are arranged in a perfect mirror image reversal of the normal positioning.

Description

Normal human development results in an asymmetrical arrangement of the organs within the chest and abdomen. Typically, the heart lies on the left side of the body (levocardia), the liver and spleen lie on the right, and the lung on the left has two lobes while the lung on the right has three lobes. This normal arrangement is known as situs solitus.
However, in about 1 in 8,500 people, the organs of the chest and abdomen are arranged in the exact opposite position: the heart is on the right (dextrocardia), as is the two-lobed lung, and the liver, spleen, and three-lobed lung are on the left. Yet because this arrangement, called situs inversus, is a perfect mirror image, the relationship between the organs is not changed, so functional problems rarely occur.

Causes and Symptoms

Early in the normal development of an embryo, the tube-like structure that becomes the heart forms a loop toward the left, identifying the left/right axis along which the other organs should be positioned. Although the mechanism that causes the heart loop to go left is not fully understood, at least one gene has been identified to have a role in this process. However, it is thought that many factors may be involved in causing situs inversus. Rarely, situs inversus can run in families, but most often it is an isolated and accidental event occurring in an individual for the first time in the family.
Most people with situs inversus have no medical symptoms or complications resulting from the condition. Although only 3-5% of people with situs inversus have any type of functional heart defect, this is higher than the rate of heart defects in the general population, which is less than 1%.
It is estimated that about 25% of people with situs inversus have an underlying condition called primary ciliary dyskinesia (PCD). PCD, also known as Kartagener’s syndrome, is characterized as situs inversus, chronic sinus infections, increased mucous secretions from the lungs, and increased susceptibility to respiratory infections. PCD is caused by a defect in the cilia that impairs their normal movements.

Diagnosis

Situs inversus should detected by a thorough physical examination. It is often picked up when a physician, using a stethoscope, hears otherwise normal heart sounds on the right side of the body instead of the left. To confirm the a suspected diagnosis of situs inversus, imaging studies such as MRI, CT, or ultrasound may be ordered, and a referral may be made to a cardiologist or internist for completeness. Imaging studies will also rule out the possibility of random arrangement of the organs, or heterotaxy, which has a much higher risk for serious medical complications.

Treatment

There is no treatment for situs inversus. In the unlikely case that a heart defect is present, it should be treated accordingly by a cardiologist.
Individuals who have situs inversus should be sure to inform all physicians involved in their medical care. In addition to preventing unnecessary confusion, this will reduce the risk of missing a crucial diagnosis that presents with location-specific symptoms (such as appendicitis).

Alternative Treatment

Not applicable.

Prognosis

The prognosis for an individual with situs inversus is good, and in the absence of a heart defect or other underlying diagnosis, life expectancy is normal.

Prevention

There is no known method of preventing situs inversus.

Significance

Situs inversus has an autosomal recessive pattern of inheritance.
Situs inversus is generally an autosomal recessive genetic condition, although it can be X-linked or found in identical “mirror” twins.
In the absence of congenital heart defects, individuals with situs inversus are phenotypically unimpaired, and can lead normal healthy lives, without any complications related to their medical condition. There is a 5-10% prevalence of congenital heart disease in individuals with situs inversus totalis, most commonly transposition of the great vessels. The incidence of congenital heart disease is 95% in situs inversus with levocardia.
Many people with situs inversus totalis are unaware of their unusual anatomy until they seek medical attention for an unrelated condition. The reversal of the organs may then lead to some confusion, as many signs and symptoms will be on the ‘wrong’ side. For example, if an individual with situs inversus develops appendicitis, they will present to the physician with left lower abdominal pain, since that is where their appendix lies. Thus, in the event of a medical problem, the knowledge that the individual has situs inversus can expedite diagnosis. People with this rare condition should inform their physicians before an examination, so they may redirect their search for heart sounds and other signs.
Situs inversus also complicates organ transplantation operations as donor organs will almost certainly come from situs solitus donors. As hearts and livers are chiral, geometric problems arise placing an organ into a cavity shaped in the mirror image. For example, a person with situs inversus who requires a heart transplant needs all the vessels to the transplant donor heart reattached to their existing ones. However, the orientation of these vessels in a person with situs inversus is reversed, necessitating steps so that the blood vessels join properly.

Kartagener syndrome

About 25% of individuals with situs inversus have an underlying condition known as primary ciliary dyskinesia (PCD). PCD is a dysfunction of the cilia that manifests itself during the embryologic phase of development. Normally-functioning cilia determine the position of the internal organs during early embryological development, and so individuals with PCD have a 50% chance of developing situs inversus. If they do, they are said to have Kartagener syndrome, characterized by the triad of situs inversus, chronic sinusitis, and bronchiectasis. Cilia are also responsible for clearing mucus from the lung, and the dysfunction causes increased susceptibility to lung infections.

Notable persons with situs inversus

Notable individuals with documented cases of situs inversus include:

• Randy Foye, an American basketball player for the NBA’s Minnesota Timberwolves. He has suffered no discernible complications, and the condition is not expected to jeopardize his career as a professional athlete.
• Catherine O’Hara, the Canadian comedic actress has said in interviews that her organs are reversed and her heart is on the right side of her chest.
• Donny Osmond, whose appendicitis was initially dismissed as a less serious condition because nobody realized he had situs inversus. It was discovered when he was taken to hospital when on tour with his family in England.
• Enrique Iglesias, the Spanish singer told the press that he was born with situs inversus.

Fictional characters with situs inversus

• In the Ian Fleming novel Dr. No, Julius No explains to James Bond that he once survived a murder attempt because his heart is located on his right side, which his would-be-killers did not know when they stabbed the spot on the left where the heart of a normal human being would be.
• Souther, from the anime/manga Fist of the North Star, has situs inversus totalis, making him immune to standard pressure-points martial arts.
• In the webcomic It’s Walky!, anyone who goes through the Martian resurrection process ends up being completely reversed, with their organs mirrored within their bodies and their primary hand becoming the opposite of what it had been before. This process happens to several major characters throughout the comic’s run.
• In the WB series Jack & Jill, Simon Rex played a young man with situs inversus.
• Fortune, from Metal Gear Solid 2: Sons of Liberty. Revolver Ocelot points this out when he shoots Fortune on the left side of her chest, then remembers and states that her heart was on the right side.
• In Margaret Mahy’s novel The Tricksters, the character Hadfield is said to be an exact mirror image of his otherwise identical twin Felix, including having his vital organs in mirror-image layout.
• In the Lord Peter Wimsey short story The Image in the Mirror by Dorothy Sayers, a character with reversed organs has long been haunted by dreams of a doppelgänger and by fears that he himself might be only the reflection of someone else.
• In the Max Brooks novel World War Z, a character describes operating on a patient who had dextrocardia with situs inversus, and transplants a heart from someone with the same condition. Unbeknownst to him, the transplant heart is infected with the virus Solanum, thus turning the patient into a zombie.

Sources

• Wikipedia
• Health At OZ

Intelligent pill’ knows where to release drug

Dutch group Philips has developed an “intelligent pill” that contains a microprocessor, battery, wireless radio, pump and a drug reservoir to release medication in a specific area in the body. Philips, one of the world’s biggest hospital equipment makers, said on Tuesday that the “iPill” capsule, measures acidity with a sensor to determine its location in the gut, and can then release drugs where they are needed. Delivering drugs to treat digestive tract disorders such as Crohn’s disease directly to the location of the disease means doses can be lower, reducing side effects, Philips said. While capsules containing miniature cameras are already used as diagnostic tools, those lack the ability to deliver drugs, Philips said. The “iPill” can also measure the local temperature and report it wirelessly to an external receiver

What is Pulmonary Hypertension?

The human body has two major areas of blood vessels that distribute from and return blood to the left and right heart. The portion of the circulation that distributes the blood from the left side of the heart, throughout the body, is referred to as systemic circulation. The portion of the circulation that distributes the blood from the right side of the heart, to the lungs, is referred to as the pulmonary (lung) circulation. When the doctor or a nurse measures the blood pressure on a person’s arm, it is the systemic blood pressure that is being measured. When these pressures are abnormally high, the person is diagnosed as having high blood pressure or hypertension.

The right ventricle pumps venous blood returning from the body into the arteries of the lungs to receive oxygen. The pressures in the lung arteries (pulmonary arteries) are normally lower than the pressures in the systemic circulation. When pressure in the pulmonary circulation becomes abnormally elevated, it is referred to as pulmonary hypertension.

What Causes Pulmonary Hypertension?

Pulmonary hypertension results from constriction, or tightening, of the blood vessels that supply blood to the lungs. Consequently it becomes difficult for blood to pass through the lungs. Consequently, it becomes difficult for the blood to pass through the lungs, making it harder for the heart to pump blood forward. This stress on the heart leads to enlargement of the heart and eventually fluid build up in the liver and tissues, such as in the legs. Affected patients can sometimes notice increasing shortness of breath and dizziness.

Pulmonary hypertension can be caused by diseases of the heart and the lungs such as chronic obstructive pulmonary disease (COPD) or emphysema, failure of the left heart ventricle, recurrent pulmonary embolism (blood clots traveling from the legs or pelvic veins obstructing th epulmonary arteries), or underlying disease such as scleroderma. Pulmonary hypertension can also be caused by chronic low blood oxygen levels as in some patients with sleep apnea. If pulmonary hpertension is caused by other illnesses it is called secondary pulmonary hypertension.

When pulmonary hypertension occurs without underlying heart and lung disease or other illnesses, it is called primary pulmonary hypertension. Primary pulmonary hypertension is more common in young females.

History of the disease

The first reported case of primary pulmonary hypertension occured in 1891 with a published description of an autopsy that showed thickening of the deceased’s pulmonary artery, but with no indications of heart or lung disease. In 1951, when 39 cases were reported in the US, the disease got its name.

Between 1967 and 1973, an unexplained increase in primary pulmonary hypertension was reported in central Europe. The increase in the number of cases was eventually attributed to aminorex fumarate, an amphetamine like drug introduced in Europe in 1965 to control appetite. When aminorex was removed form the market, the incidence of primary pulmonary hypertension went down to normal levels.

Signs and Symptoms

Because symptoms may develop very gradually, patients may delay seeing a physician for years. A history usually reveals gradual onset of shortness of breath, fatigue, non productive cough, angina pectoris, fainting or syncope, peripheral edema (Swelling of the limbs, especially around the ankles and feet), and rarely hemoptysis (coughing up blood). Pulmonary arterial hypertension typically does not present with orthopnea or paroxysmal nocturnal dyspnea while pulmonary venous hypertension typically does.

In order to establish the cause, the physician will generally conduct a thorough medical history. A detailed family history is taken to determine whether the disease might be familial. A history of exposure to cocaine, methamphetamine, alcohol leading to cirrhosis, and smoking leading to emphysema are considered significant. A physical examination is performed to look for typical signs of pulmonary hypertension including a loud P₂ (pulmonic valve closure sound), (para)sternal heave, jugular venous distension, pedal edema, ascites hepatojugular reflux, clubbing etc. Evidence of tricuspid insufficiency is also sought and, if present is consistent with the presence of pulmonary hypertension.

Diagnosis

Because pulmonary hypertension can be of five major types, a series of tests must be performed to to distinguish pulmonary arterial hypertension from venous, hypoxic, thomboembolic or miscellaneous varieties. A physical examination is performed to look for typical signs of pulmonary hypertension. These include altered heart sounds, such as a widely split S₂ or second heart sound, a loud P₂ or pulmonic valve closure, (para)sternal heave, possible S₃ or third heart sound, and pulmonary regurgitation. Other signs include an elevated jugular venous pressure, pheripheral edema (swelling of the ankles and feet), ascites (abdominal swelling due to he accumulation of fluid), hepatojugular reflux, and clubbing.

Further procedures are required to confirm the presence of pulmonary hypertension and exclude other possible diagnoses. These generally include pulmonary function tests, blood tests to exclude HIV, autoimmune diseases and liver disease, ECG, arterial blood gas measurements, xrays of the chest (followed by high resolutiion CT Scanning if interstitial lung disease is suspected), and ventilation perfusion or V/Q scanning to exclude thromboembolic pulmonary hypertension. Biopsy of the lung is usually not indicated unless the pulmonary hypertension is thought to be due to an underlying interstitial lung disease. But lung biopsies are fraught with risks of bleeding due to the high intrapulmonary blood pressure. Clinical improvement is often measured by a six minute walk test, ie the distance a patient can walk in six minutes. Stability and improvement in this measurement correlate with better survival. Blood BNP level is also being used now to follow progress of patients with pulmonary hypertension.

Diagnosis of PAH requires the presence of pulmonary hypertension with two other conditions. Pulmonary artery occlusion pressure (PAOP OR PCWP) must be less than 15mm Hg (2000 Pa) and pulmonary vascular resistance (PVR) must be greater than 3 wood units (240 dyn*s*cm^-5 or 2.4 mN*s*cm^-5)

Although pulmonary arterial pressure can be estimated on the basis of echocardiography, pressure measurements with a Swan-Ganz catheter provides the most definite assessment. PAOP and PVR cannot be measured directly with echocardiography. Therefore diagnosis of PAH requires right-sided cardiac catheterization. A Swan-Ganz catheter can also measure the cardiac output, which is far more important in measuring disease severity than the pulmonary arterial pressure.
Normal pulmonary arterial pressure in a person living at sea level has a mean value of 12–16 mm Hg (1600–2100 Pa). Pulmonary hypertension is present when mean pulmonary artery pressure exceeds 25 mm Hg (3300 Pa) at rest or 30 mm Hg (4000 Pa) with exercise.
Mean pulmonary artery pressure (mPAP) should not be confused with systolic pulmonary artery pressure (sPAP), which is often reported on echocardiogram reports. A systolic pressure of 40 mm Hg typically implies a mean pressure more than 25 mm Hg. Roughly, mPAP = 0.61*sPAP + 2.

Treatment

Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. Since pulmonary venous hypertension is synonymous with congestive heart failure, the treatment is to optimize left ventricular function by the use of diuretics, beta blockers, ACE inhibitors, etc., or to repair/replace the mitral valve or aortic valve. In PAH, lifestyle changes, digoxin, diuretics, oral anticoagulants, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner. High dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blockers in the long term. A number of agents has recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the “6 minute walking test”. Many have no data on mortality benefit or time to progression.

Vascoactive Substances

Many pathways are involved in the abnormal proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension. Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin derivatives.
Because inexpensive generic drugs for this disease are not widely available, the World Health Organization does not include them in its model list of essential medicines.

Prostaglandins

Prostacyclin (prostaglandin I₂) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin, marketed as Flolan) is given via continuous infusion that requires a semi-permanent central venous catheter. This delivery system can cause sepsis and thrombosis. Flolan is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous (24/7), and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil (Remodulin) can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC. Iloprost (Ilomedin) is also used in Europe intravenously and has a longer half life. Iloprost (marketed as Ventavis) is the only inhaled form of prostacyclin approved for use in the US and Europe. This form of administration has the advantage of selective deposition in the lungs with less systemic side effects. Oral and inhaled forms of Remodulin are under development. Beraprost is an oral prostanoid available in Japan and South Korea.

Endothelin receptor antagonists

The dual (ET_A and ET_B) endothelin receptor antagonist bosentan (marketed as Tracleer) was approved in 2001. Sitaxsentan, a selective endothelin receptor antagonist that blocks only the action of ET_A, has been approved for use in Canada, Australia, and the European Union, to be marketed under the name Thelin. Sitaxsentan has not been approved for marketing by the US FDA. A new trial to address the FDA’s concerns will begin in 2008. A similar drug, ambrisentan is marketed as Letairis in U.S. by Gilead Sciences. In addition, another dual/nonselective endothelin antagonist, Actelion-1, from the makers of Tracleer, will enter clinical trials in 2008.

Phosphodiesterase type 5 inhibitors

Sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), was approved for the treatment of PAH in 2005. It is marketed for PAH as Revatio.

Surgical

Atrial septostomy is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia). It is best performed in experienced centers. Lung transplantation cures pulmonary arterial hypertension, but leaves the patient with the complications of transplantation, and a post-surgical median survival of just over five years
Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. It is the surgical removal of an organized thrombus (clot) along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers. Case series show remarkable success in most patients.
Treatment for hypoxic and miscellaneous varieties of pulmonary hypertension have not been established. However, studies of several agents are currently enrolling patients. Many physicians will treat these diseases with the same medications as for PAH, until better options become available. Such treatment is called off-label use.

Monitoring

Patients are normally monitored through commonly available tests such as:

• pulse oximetry,
• arterial blood gas tests,
• chest X-rays,
• serial ECG tests,
• serial echocardiography, and
• spirometry or more advanced lung function studies.

Sources

• American Heart Association

• Wikipedia

• Medicine Net.Com

• MediaFact.Com

• Ohio State University Medical Center

Recent report in Mumbai Mirror prompted me to post this. Click here to read the full story

Definition

Long QT syndrome or LQTS is a heart rhythm disorder that can potentially causes fast, chaotic heartbeats. The rapid heartbeats, caused by changes in the part of the heart that causes it to beat, may lead to fainting. In some cases the hearts rhythm may beat so erratically that it can cause sudden death.

History.

The first case of LQTS is back in the 19th century where a deaf mute girl was described. She died after her teacher yelled at her. When the parents were told about her death, they told that her older brother who also was deaf mute died during similar circumstances in his school during a fight. This was before the ECG was invented but is likely the first described case of Jervell and Lange Nielsen syndrome. In 1959, the first case documented by ECG was described Jervell Lange and Nielsen. Romano, in 1963, and Ward, in 1964, separately described the more common variant of LQTS with normal hearing, later called Romano Ward Syndrome.

Causes

The Chambers of Heart - Image Courtesy Mayoclinic.com

The heart beats about 100,000 times a day to circulate blood throughout the body. To pump blood, the heart’s chambers contract and relax. These actions are controlled by electrical impulses created in the sinus node, a group of cells in the upper right chamber of your heart. The impulses travel through the heart and cause it to beat.

After each heartbeat, the heart’s electrical system recharges itself in preparation for the next heartbeat. In LQTS, however, the heart’s muscle takes longer than normal to recharge between beats (a process known as repolarization). The electrical disturbance can be seen on an ECG.

Symptoms

About half of those affected with LQTS don’t have any signs or symptoms. They might be aware of their condition only from results of an ECG performed for an unrelated reason or because they have a family history of long QT or because of genetic testing results.

For people who do experience signs and symptoms of LQTS, the most common symptoms include:-

• Fainting:- This is the most common sign of LQTS. In people with LQTS, fainting spells (syncope) are caused by the heart temporarily beating in an erratic way. Syncope may happen when one is excited, scared or during exercise. Fainting in people with LQTS can occur without warning, such as losing consciousness after being startled by a ringing telephone.

• Seizures:- If the heart continues to beat erratically, the brain becomes increasingly deprived of oxygen. This can the cause generalized seizures. Due to this, some people with LQTS have been wrongly diagonised as having a seizure and even have been treated with anti epileptic medicines.

• Sudden Death:- Normally, the heart beat returns to its normal rhythm. If this doesnot happen spontaneously and if paramedics don’t arrive in time to convert the rhythm bac to normal with an external defibrillator, sudden death will occur.

Types of QT Syndrome

There are two types of QT syndrome:-

• Inherited Long QT Syndrome

At least 12 genes associated with LQTS have been discovered so far, and hundreds of mutations within these genes haven been identified. Mutations in three of these genes account for about 75 percent of long QT Syndrome

Doctors have described two forms of inherited long QT syndrome:-

• Romano-Ward Syndrome:- This more common form occurs in people who inherit only a single genetic variant from one of their parents. This type of LQTS affects about one in 2500 people.
• Jervell and Lange-Nielson syndrome:- Sings and symptoms of this rare form usually occur earlier and are more severe than in Romano-Ward syndrome. It is seen in children who are born deaf and have LQTS because they inherited genetic variants from each parent.

Additionally, Scientists have been investigating a possible link between Sudden Infant Death Syndrome (SIDS) and LQTS. It has been discovered that about 10-15 percent of babies wwith SIDS had a genetic defect or mutation for LQTS.

• Acquired Long QT Syndrome

More than 50 medications, many of them common, can lengthen the QT interval in otherwise healthy people and cause a form of acquired LQTS known as drug induced LQTS. Medications that can lengthen the QT interval and upset heart rhythm include certain antibiotics, anti depressants, antihistamines, diuretics, heart medications, cholesterol lowering drugs, diabetes medications and well as some anti fungal and anti psychotic drugs

Tests and Diagnosis

If doctor suspects that you have LQTS, the following tests may be carried out to confirm diagnosis:-

• An Electrocardiogram (ECG):- An ECG measures electrical impulses as they travel through the heart.
  

  Image courtesy Mayoclinic.com

  Patches with wires attached to the skin measure these impulses, which are displayed on a monitor or printed on paper as waves of electrical activity. An ECG measures electrical impulses as 5 distinct waves. Doctors label these waves as P, Q, R, S and T. The waves labeled Q through T show electrical activity in the heart’s lower chamber. The space between the start of the Q wave and the end of the T Wave (the QT interval) corresponds to the time taken by the hearts lower chamber to electrically discharge and then recharge (repolarization). By measuring the QT interval, doctors can tell whether it occurs in a normal amount of time. If it takes more than normal, it is called a prolonged QT interval. This test may be taken while at rest or while exercising by running on a treadmill or pedaling a stationary bike.

• Ambulatory ECG monitoring:-This test, also called Holter monitoring is used to monitor the heart for rhythm irregularities during normal activity for an uninterrupted 24 hour period. During the test, electrodes attached to the chest are connected to a portable recorder that is attached to a belt or is carried by a shoulder strap. The recorded information can then be analyzed to check for heart rhythm irregularities, such as prolonged QT intervals.

• Event ECG Recording:- This is similar to ambulatory ECG except that you need to wear a portable ECG recorder for days or weeks as it records your heart rhythms.

While some people with suspected LQTS have a visibly lengthened QT interval on an ECG, others dont making the condition more difficult to diagnose. Other testing may then be necessary.

• A nonexercise (Medication) stress test:- This ECG test is performed while a medication is given that stimulates the heart in a way similar to exercise. In this test, doctors monitor the effects of the adrenaline on the way your heart recharges. (Adrenaline is a substance that the body releases in response to stress.) This test can in some patients unmask a condition known as concealed QT syndrome which is a normal QT interval at rest, although they still have the syndrome. In some people with LQTS, fainting spells are triggered by sudden bursts of adrenaline in the body such as are experienced during intense exercise or emotional upset.

• An Electroencephalogram (EEG):-This test looks for neurological causes of fainting, such as a seizure disorder. The procedure measures the waves of electrical activity the brain produces. Small electrodes attached to the head pick up the electrical impulses from the brain and send to the EEG machine, which records brain waves.

• Genetic Testing:- A genetic screening test for five of the most common genes associated with LQTS is available. These five genes explain about three out of every four cases of LQTS. Therefore, its possible to test negative with the genetic test but still have LQTS. If the genetic test is positive, then family members can be tested to prove definitively whether they inherited the same genetic mutation.

In addition, doctor will need to know medical history and details of medications taken by the patient.

Complications

Prolonged QT intervals may never cause any problems. However, physical or emotional stress may cause the heart’s rhythm to spin out of control. A prolonged QT interval may trigger a particular irregular heart rhythm (arrhythmia) called torsades de pointes (twists of the points) in which hearts ventricles beat fast, making the waves on an ECG monitor look twisted. When this arrhythmia occurs, less blood is pumped from the heart and less blood reaches the brain causing a person to faint.

If a torsades de pointes episode is short – lasting less than one minute – the heart can correct itself seconds later, and one regains consciousness on own. However, if episode persists, it can lead to life threatening arrhythmia called ventricular fibrillation.

In ventricular fibrillation, the ventricles beat so fast that heart quivers and ceases pumping blood. Unless the heart is shocked back into a normal rhythm by a device called a defibrillator, ventricular fibrillation can lead to brain damage and death.

Treatments and Drugs

Treatment for inherited LQTS can involve medications, medical devices surgery or lifestyle changes. The goal of the treatment is either to prevent the LQTS heart from ever beating out of control or to prevent sudden death. It is often possible to eliminate drug induced LQTS by simply switching medicines with doctors advice.

Medications

Medications used to treat LQTS include:-

• Beta Blockers:- Examples of this heart drug include nadolol and propranolol. These drugs slow the heart rate and prevent the dangerously fast heartbeats that can come about i times of stress, fear or exertion for pople with LQTS.
• Potassium:-Potassium is a mineral in the body, derived from the diet, thats important for the health of heart’s electrical system. Potassium supplements may improve the heart’s recharging system and may be helpful for people with certain form of LQTS.

Medical Devices and Surgical Procedures

Doctors may consider two other treatments

• A pacemaker or implantable cardioverter defibrillator (ICD):- These devices can monitor for fatal arrhythmia and if necessary stop it. Each device is implanted under the skin of the chest and will correct heart’s rhythm if it detects a disrupted heart rhythm
• Left Sided Sympathetic denervation surgery:- In this procedure, specific nerves in the chest are surgically cut. These nerves are part of body’s sympathetic nervous system, which controls automatic functions in the body including regulation of heart rhythm. This surgery is generally reserved for people considered at high risk of sudden death.

Lifestyle Changes

In addition to medications or surgery, the doctor is most likely to recommend lifestyle changes to reduce your symptoms. These could include avoiding strenuous exercise or contact sports, reducing loud and startling noises and staying away from situations that could make one excited or angry.

Coping and Support

LQTS can be a worrisome condition because of its serious potential outcomes. Families with inherited LQTS may find it helpful to talk to a cardiologist with expertise in diagnosing and treating LQTS, a genetics counselor, a psychiatrist or psychologist as well as other families with the condition. Several websites provide help for families with the disorder.

Sources

MayoClinic.Com

Wikipedia

QTS Syndrome.Ch

Texas Heart Institute and St. Luke’s Episcopal Hospital

What is Parkinson’s Disease?

Parkinsons Disease (PD) is a progressive, neurodegenartive, movement disorder.

Progressive:- PD gets worse over time

Neurodegenerative:- It is caused by the degeneration of the cells in brain.

Movement Disorder:- The most prominent symptoms of PD affect movement, although many other symptoms may also occur, some of which can be even more disabling than the movement symptoms.

History

Frontespiece of Parkinson's classical essay on shaking palsy Image Courtesy Answers.com

Symptoms of PD have been known and treated since ancient times. However, it was not formally recognized and its symptoms were not documented until 1817 in “An Essay on the Shaking Palsy” by the British physician James Parkinson. PD was then known as paralysis agitans, the term “Parkinson Disease” being coined later by Jean-Martin Charcot. The underlying biochemical changes in the brain were identified in the 1950s due to the work of Swedish Scientist Arvid Carlsson, who later went on to win a Nobel Prize. L-dopa (the treatment for PD described later) entered practice in 1967, and the first large study reporting improvements in patients with PD resulting from treatment with L-dopa was published in 1968.

Who Gets Parkinsons’ Disease?

PD affects both men and women. The average age of onset of PD is 61, but it may begin as early as 40 or even before. The number of people in the US with PD is estimated to be between 500,000 to one million with about 50000 to 60000 new diagnoses every year. The disease progresses at different rates in different people. A more severe course is often seen in people who develop PD at an earlier age. PD reduces life expectancy by an average of three to nine years. PD is now the 14th leading cause of death in the US.

Causes of Parkinsons’ Disease

Image showing brain affected by Parkinsons Disease Image Courtesy deaconess.com

The neurons that degenerate in PD are located in several areas of the brain, but most significant is the loss of dopamine producing neurons in the substantia nigra. The dopamine produced by these neurons is crucial for another brain region, called the striatum. Under the influence of dopamine, signals from the striatum regulate all forms of voluntary movement. The loss of dopamine in PD accounts for most of the movement related symptoms of the disease

Dopamine neurons die over the course of many years. PD symptoms begin when the loss of dopamine reaches a critical point, typically when 50 to 80 percent dopamine have died. The reason for the loss of dopamine is still being widely investigated world over by scientists. Even though rapid progress has been made, there is still no definitive answer. However it is now widely accepted that there is no single cause that triggers the disease. Instead, PD likely results from a confluence of inherited (genetic) and environmental factors that react in complex ways to set disease processes in motion. A small percentage of cases are hereditary in the classic sense that, if one or both parents have it, children are at higher risk. But in the vast majority of cases, no obvious family link is present. Instead, it is believed that individuals may inherit a degree of susceptibility to the disease, which only causes PD when other factors are present.

Symptoms

The symptoms of PD (parkinsonism) vary from person to person. Early signs may be subtle and can go unnoticed for months or years. Symptoms typically being on one side of the body and usually remain worse on that side.

Parkinson’s signs and symptoms may include:-

Tremor:- The characteristic shaking associated with PD often begins in a hand. A back and forth rubbing of the thumb and forefinger, known as pill rolling is common. However, many people with PD do not experience substantial tremor.

Slowed Motion (bradykineisa):- Over time, PD may reduce ones ability to initiate voluntary movement. This may make even the simplest tasks difficult and time consuming. While walking, the steps may become short and shuffling or the feet may freeze to the floor, making it hard to take the first step.

Rigid Muscle:- Muscle stiffness often occurs in the limbs and neck. Sometimes the stiffness can be so severe that it limits the range of movement and causes pain.

Impaired Posture and Balance:- The posture of the patient may become stooped as a result of PD. Imbalance also is common, although this is usually mild until the later stages of the disease.

Loss of Automatic Movements:- Blinking, smiling and swing of arms while waling are all unconscious acts that area normal part of being human. In PD, these acts tend to be diminished and even lost. Some people may develop a fixed staring expression and unblinking eyes. Others may no longer gesture or seem animated when they speak.

Speech Changes:- Many people with PD have problems with speech. They might speak more softly, rapidly or in a monotone, sometimes slurring or repeating words, or hesitating before speaking.

Dementia:- In the later stages of PD, some people develop problems with memory and mental clarity.

Complications

Apart from those mentioned above, PD is often accompanied by these additional problems:-

Depression:- This can occur even before other Parkinson’s symptoms. Receiving treatment for depression can make it easier to handle the other challenges of PD.

Sleep Problems:- People with PD often have trouble falling asleep and may wake up frequently throughout the night. They may also experience sudden sleep onset, called sleep attacks, during the day.

Difficulty in chewing and Swallowing:- The muscles used to swallow may be affected in the later stages of the disease, making eating more difficult.

Urinary Problems:- PD may cause either urinary incontinence or urine retention. Certan medications used to treat PD also can make it difficult to urinate.

Constipation:- Many people with PD develop constipation because the digestive tract works more slowly. Constipation may also be a side effect of meidcations used to treat the disease.

Sexual Dysfunction:- Some people with PD may notice a decrease in sexual desire. This may stem from a combination of psychological and physical factors, or it may be the result of physical factors alone.

Medications for PD also may cause a number of complications, including involuntary twitching or jerking movements of the arms or legs, hallucinations, sleepiness, and a drop in blood pressure when standing up.

The initial response to PD treatment can be dramatic but over time the benefits of drugs frequently diminish or be come less consistent, although the symptoms may still be fairly well controlled. Doctors may recommend lifestyle changes such as physical therapy, a healthy diet and exercise, in addition to medications. In some cases surgery might be useful.

Risk Factors

Risk factors for PD include:-

Age:- Young adults very rarely experience PD. it ordinarily begins in middle or late life, and the risk continues to increase with age.

Heredity:- Having one or more close relatives with PD increases the chances of having the disease, although the risk is still less than 5 percent. Recent evidence suggests a crucial role for small contributions from many different genes that program brain architecture.

Sex:- Men are more likely to develop PD than women.

Exposure to toxins:- Ongoing exposure to herbicides and pesticides increases the risk of getting PD slightly.

Tests and Diagnosis

No definitive tests exist for PD, so it can be difficult to diagnose, especially in the early stages. And the symptoms of PD can also be caused by many other type of problems:-

Examples include:-

Other neurological disorders:- Essential tremor, dementia, multiple system atrophy and progressive supranuclear palsy each feature some symptoms common to PD.

Medications:- Anti psychotic medications and anti nausea drugs block dopamine. If any of these medications are taken then symptoms of PD may develop, although it is reversible and stops when one stops taking these medicines.

Toxins:- Exposure to carbon monoxide, cyanide or certain other toxins can produce symptoms similar to PD.

Head Trauma:- Both solitary head injuries and the repetitive variety of head trauma common in boxing have been linked to parkinsonism, although risks are small.

Structural Problems:- Strokes or fluid build up in the brain (hydrocephalus) may occasionally mimic PD.

A diagnosis of PD is based on the medical history and a neurological examination. As the part of medical history, doctor will most probably enquire about any medications taken and whether there is a family history of PD. The neurological examination includes an evaluation of walking and coordination as well as some simple hand tasks.

A diagnosis of PD is most likely if:-

At least two of three symptoms of parkinsonism viz tremor, slowing of motion and muscle rigidity are present.

Onset of symptoms on one side of the body only.

Tremors more pronounced at rest for eg when hands are resting in lap.

Strong response to levodopa, a Parkinson’s drug.

Treatments

Medications

Medications can help manage problems with walking, movement and tremor by increasing brains supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter the brain

Levodopa:- The most effective drug for PD is levodopa, which is a natural substance that we all have in our body. When taken orally in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing so it also prevent nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar,

As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane. This then requires medication adjustments. Side effects of levodopa include confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These are resolved with dose reductions, but sometimes at the expense of reduced parkinsonsim control.

Dopamine Agonists:- Unlike levodopa, these drugs are not converted to dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms as levodopa. However, they last longer and are often used to smooth the sometimes off and on effect of levodopa. The side effects of dopamine agonists include those of carbidopa-levodopa although they are less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. These medicines may also risk of compulsive behaviors such as hypersexuality, compulsive and gambling and compulsive overeating.

MAO B inhibitors:-These type of drugs, help prevent the breakdown of both, naturally occuring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B)- the enzyme that metabolizes dopamine in the brain.

Catechol O methyltransferase (COMT) inhibitors:- These drugs prolong the effect of carbidopa levodopa therapy by blocking an enzyme that breaks down levodopa

Anticholinergics:- These medicines have been used for many years to help control the tremor associated with PD. Their modest benefits, may, however be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention – especially men with an enlarged prostate and severe constipation.

Anti virals:- Doctors may prescribe amantadine alone to provide short term relief of mild early stage PD. It may also be added to carbidopa-levodopa therapy for people in the later stages of PD, especially if they have problems with involuntary movements induced by carbidopa-levodopa. Side effects include swollen ankles and a purple mottling of the skin.

Physical Therapy

Exercise helps in maintaining function in PD. Physical therapy may be advisable and can help improve mobility, range of motion and muscle tone. Although specific exercise cant stop the progress of the disease, improving muscle strength can help the patient feel more confident and capable.

Surgery

Image showing electrodes placed inside the brain after Deep Brain Surgery Image Courtesy:- SFN.org

Deep brain stimulation is the most common surgical procedure to treat PD. It involves planting an electrode deep within the brain that control movement. The amount of simulation delivered by the electrode is controlled by a pacemaker like device placed under the skin in the upper chest. A wire that travels under the skin connects the device, called a pulse generator, to the electrode. This method is used for people who have advanced PD and have unstable medication responses. It can stabilize medication fluctuations and reduce or eliminate dyskineasis. Tremor is especially response to this therapy. This method doesnot help dementia, but may make it worse.

Like any other brain surgery, this procedure has risks such as brain hemorrhage or stroke like problems. Infection may also occur, requiring parts of the devices to be replaced. In addition the units battery beneath the skin of the chest wall must be surgically replaced every few years. This method is not beneficial for people who donot respond to carbidopa levodopa

Future Research Directions

Gene Therapy

Currently under investigation is gene therapy. This involves using a non infectious virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decaboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor on the overactive cells in the STN.

GDNF infusion involves the infusion of GDNF (Glial derived neurotrophic factor) into the basal ganglia using surgically implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still in development.

Implantation of stem cells genetically engineered to produce dopamine or stem cells that transform into dopamine producing cells has already started being used. These could not constitute cures as they donot address the considerable loss of activity of the dopaminergic neurons. Initial results have been unsatisfactory, with patients still retaining their drugs and symptoms.

Neuroprotective Treatments

Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny. These agents could protect neurons from cell death induced by disease presence resulting in a slower progression of disease. Agents currently under investigation as neuroprotective agents include anti-apoptotic drugs, lazaroids, bionenergetics, antiglutamatergic agents and dopamine receptors. Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitors selegiline and rasagiline, dopamine agonists and the complex I mitochondrial fortifier coenzyme Q10.

Alternative Treatments

Nutrients have been used in clinical studies and are used by people with PD in order to partially treat PD or slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70 percent of symptoms. Ferrous iron, the essential cofactor for l-dopa biosynthesis was shown to relieve between 10 percent and 60 percent of symptoms. More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine- coenzymes and coenzyme precursors involved in dopamine biosynthesis. Vitamin C and Vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in PD. This is because the enzymes super oxide dismutase and catalase require these vitamins in order to nullify the super oxide anion, a toxin commonly produced in damaged cells. However, in the randomised controlled trial, DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen. Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to coenzyme Q10. Mucuna pruriens, is a natural source of therapeutic quantites of l-dopa and has been under some investigation.

Source

• Wikipedia

• The Micheal Sterns Parkinson’s Research Foundation

• National Institute of Neurological Disorder and Strokes

• Mayo Clinic

Arnold Chiari Malformation is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF (cerebrospinal fluid) outflow.

Terminology

Some sources use the term “Chiari Malformation” to describe four specific grades of the condition reserving the term “Arnold-Chiari” for type II only. Other sources use “Arnold Chiari” for all four types. This article uses the latter convention. One advantage of using the term “Arnold Chiari” is that the term “Chiari’s Syndrome” can refer to Budd-Chiari syndrome a hepatic conditon also named after Hans Chiari

What is Chiari Malformation?

An image showing a brain affected the chiari malformation image courtesy braincatalognucleusinc.com

Chiari Malformations (CMs) are structural defects in the cerebellum, the part of the brain that controls balance. When indented bony space at the lower rear of the skull is smaller than normal, the cerebellum and brainstem can be pushed downward. The resulting pressure on the cerebellum can block the flow cerebrospinal fluid (the liquid that surrounds and protects the brain and spinal cord) and can cause a range of symptoms including dizziness, muscle weakness, numbness, vision problems, headache and problems with balance and coordination. There are three primary types of CMs:- Type I :- Most common. It may not cause symptoms and is often found by accident during an examination for another condition. Type II :-Also called Arnold Chiari Malformation is usually accompanied by a myelomeningocele- a form of spina bifida that occurs when the spinal canal and backbone donot close before birth, causing the spinal cord to protrude through an opening in the back. This can cause either partial or complete paralysis below the spinal opening in the back. Type III :- This is the most serious form of CM, and causes severe neurological defects. Other conditons sometimes associated with CM include hydrocephalus, syringomyelia and spinal curvature.

History

Hans chiari, an austrian pathologist first described these hindbrain malformations in the 1890s Image courtesy weborionpharma.se

An Austiran pathologist, Hans Chiari, first described these hindbrain malformations in the 1890s. A colleague of Professor Chiari, Dr. Julius Arnold, later contributed to the definiton of the condition, and students of Dr. Arnold (Schwalbe and Gredig) suggested the term “Arnold – Chiari Malformation” to henceforth refer to the condition. Between 1891 and 1896, German pathologist Hans Chiari described a series of anomalies of the caudal cerebellum and brainstem on the basis of autopsy observations. In 1891, he described an anomaly consisting of elongated peglike cerebellar tonsils that are displaced into the upper cervical canal through the foramen magnum. This is now designated as the Chiari Type I malformation. Five years later, he published a further report on a hindbrain anomaly, now known as the Chiari type II malformation. He also reported a single case of cervical spina bifida associated with herniation of the cerebellum through the foramen magnum, which has since been called Chairi III malformation. Some authors have added a form of severe cerebellar hypoplasia without displacement of brain through the foramen magnum, the so-called Chiari IV malformation. The Chiari II is a complex congenital malformation of the brain, nearly always associated with myelomeningocele. This condition includes downward displacement of the medulla, fourth ventricle and cerebellum into the cervical spinal canal as well as elongation of the pons and fourth ventricle probably due to a relatively small posterior fossa

Mortality / Morbidity

Neonatal Chiari II malformation continue to result in significant morbidity and mortality. Hindbrain dysfunction is the major cause of the mortality. The mortality rate is 15% in first years of life among the patients with Chiari II malformation. Symptomic Chiari II malformation is the leading cause of mortality in the myelodysplastic population. One third of the patients with myelomeningocele develop brainstem dysfunction by the age of 5 years. Of these one third die in infancy. Cranial nerve and brainstem dysfunction are the most serious and potentially life threatening problems. Respiratory difficulties occur in about 29-76 percent of patients; which are the most common and leathal manifestation of the conditon.

Preferred Examination

The Chiari II malformation is a complex anomaly with skull, dural, brain, spinal and spinal cord maifestations. Traditionally, when suggestions and symptoms were suggestive of a Chiari II malformation, plain radiography of the head or spine was performed, followed by myelography. Because myelography is a invasive procedure, clinicians were reluctant to perform the test until the severity of the symptoms warranted it. The introduction of modern imaging techniques, specifically, MRI, has radically changed the evaluation of symptoms referable to the brain and spinal cord. MRI is usually used for the detailed evaluation of lesions and complications due to Chiari II malformations. Chiari II malformations are also diagnosed with the help of CT scan and UltraSonography. CT is especially useful after the neonatal period in following up obstructive hydrocephalus in infants who have undergone a ventriculoperitoneal shunt procedure. Ultrasonography or US, is routinely used during gestation for screening purposes and in the neonatal period for diagnosis and follow up of hydrocephalus

Treatment

Once symptomatic onset occurs, a common treatment is decompression surgery in which a nuerosurgeon usually removes the first and part of the second and sometimes third crevical vertebrae and part of the occipital bone of the skull to allow the flow of spinal fluid and may be accompanied by a shunt. This treatment is well recognised and accepted. Medications may ease certain symptoms, such as pain but surgery is the only treatment.

Source:-

• Wikipedia
• National Institute of Neurological Disorders and Strokes
• Dizziness and Balance.Com
• Details about Hans Chiari on Whonamedit.com
• Details about Julius Arnold on Whonamedit.com
• Chiari Malformation Syringomyleia News
• The Fetus.Net
• Online Medical Dictionary (For explainations of Medical terms and definitions)

Alzheimer’s disease (AD), also called Alzheimer Disease or simply Alzheimer’s is the most common cause of dementia. It is a degenerative and terminal disease for which there is no known cure. In its most common form, it afflicts indviduals over 65 years old, although a less prevalent early onset form also exists.

History

Alois Alzheimer - German Psychiatrist who indentified the first case of AD in 1901

Although the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians, it was in 1901 when Alois Alzheimer, a German psychiatrist identified the first case of what became known as Alzheimer’s disease in a fifty year old woman he called Auguste D. Alois Alzheimer followed her until she died in 1906, when he first reported the case publicly. In the following five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer’s Disease. The official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included Alzheirmer’s disease or presenile dementia as a subtype of senile dementia in the eighth edition of his book “Textbook of Psychiatry“, published in 1910. For the most of the twentieth century, the diagnosis of AD was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this didnot rule out the possiblility of different etiologies. This eventually led to the use of Alzheimer’s disease independently of onset age of the disease. The term “senile dementia of the Alzheimer type” (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer’s disease being used for those younger. Eventually, the term Alzheimer’s disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course and neuropathology.

Symptoms

Auguste Deter or Auguste D - The first described patient with AD by Alois Alzheimer in 1901 Image Courtesy:- Pajamdeen.Com

Each individual experiences the symptoms of AD in unique ways. Generally, the symptoms are reported to a physician when memory loss becomes apparent. If AD is suspected as the cause, the physician or healthcare specialist will confirm the diagnosis with behavioral assessments and cognitive tests often followed by a brain scan, if available. A prognosis for AD is hard to make, as the duration of the disease varies per individual.  The disease can develop for an indeterminate time before becoming fully apparent, sometimes escaping diagnosis for years. Generally, life with the AD lasts between 5 and 20 years. In the early stages, the most commonly recognised symptom is memory loss, such as  difficulty to remember recently learned facts. Earliest occuring symptoms are often mistaken as being noncritical age-related complaints or forms of stress. As the disease advances, progressive symptoms include confusion, anger, mood swings, language breakdown, long term memory  loss and the general withdrawal of the sufferer as his or her senses decline. Gradually, minor and major bodily functions are lost, leading ultimately to death.

Ten Warning signs of Alzheimer’s disease

The Alzheimer’s Association has developed the following list of warning signs that include common symptoms of AD.

1. Memory Loss
2. Difficulty in performing familiar tasks
3. Problems with language
4. Disorientation to time and place
5. Poor or decreased judgement
6. Problems with abstract thinking
7. Misplacing things
8. Changes in mood or behaviour
9. Changes in personality
10. Loss of initiative

If an individual exhibits several of these functions, then a thorough examination by a physician is recommended to confirm AD

Diagnosis

An Image showing pics of normal brain, and one that is affected by AD - Image courtesy :- Rauljuardo.com

Dementia is by definiton a clinical condition but not an exact diagnosis. AD is usually diagnosed clinically from the patient history, collateral history from relatives and clinical observations, based on the presence of characteristic neurological and neuropsychological features and absence of alternative conditons. Advance medical imaging with CT or MRI scan and with SPECT (Single Photon Emitted Computer Tomography) or PET are generally used to help to diagnose the subtype of dementia and exclude other cerebral pathology. Neuropsychological evalution including memory testing and assessment of intellectual functioning can further characterize the dementia. Medical organizations have created diagnostic criteria to ease and standardize the process for practicing physiscans.

Diagnosis Criteria

The diagnostic criteria for Alzheimer of the NINCDS-ADRDA (National Institute of Neurological and Communication Disorders and Stroke – Alzheimer’s Disease and Related Disorders Association ) are amongst the most used. These critera require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuro psychological testing for a clinical diagnosis of possible or probable AD while they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. They have shown good reliablility and validity. They specify as well eight cognitive domains that may be impaired in AD, viz:-

1. Memory
2. Language
3. Perceptual Skills
4. Attention
5. Constructive abilities
6. Orientation
7. Problem Solving and
8. Functional abilities.

The DSM – IV-TR (Diagnostic and Statistical Manual of Mental Disorders) criteria published by the American Psychiatric Association is another set of criteria similar to that of NINCDS-ADRDA.

Diagnostic Tools

Neuropsychological screening tests can help in the diagnosis of AD. In them patients have to copy drawings similar to the one shown in the picture, remember words, read or sum. Neuropsychological screening tests such as the Mini mental state examination (MMSE) are widely used to evalute the cognitive impairments needed for diagnosis, but more comprehensive tests arrays are necessary for high reliablity by this method especially in the earliest stages of the disease. Neurological examination in early AD will usually be normal, independent of cognitive impairment; but for many of the other dementing disorders is key for diagnosis. Therefore, neurological examination is crucial in the differential diagnosis of AD and other diseases. In addition, interviews with family memebers are also utilized in the assessment of AD. Caregivers can supply important information on the daily living abilities, as well as on the decrease over time of the patient’s mental function. This is especially important since a patient with AD is commonly unaware of his or her own deficits. Many times families also have difficulties in the detection of initial dementia symptoms and in communicating them to a physician. Finally, supplemental testing provides extra information on some features of the disease or are used to rule out other diagnosis. Examples are blood tests, which an identify other causes for dementia different than AD, which rarely may even be reversible or psychological tests for depression, as depression can both co-occur with AD or, on the contrary be at the origin of the patient’s cognitive impairment. Increasingly, the functional neuroimaging modalities of of SPECT and PET are being used to diagnose AD, as they have shown similar ability to diagnose AD as methods involving mental status examination. Furthermore, the ability of SPECT to differrentiate from dementia, appears to be superior to attempts to differentiate the cause of dementia case by mental testing and history. A new technique known as “PiB PET” has been developed for directly and clearly imaging beta amyloid deposits in vivo using a contrasting tracer that binds selectively to the A-Beta deposits. Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins. Both advances have led to the proposal of new diagnostic criteria.

Characterstics

The disease course is divided into four stages, with a progressive pattern of cognitive and functional impairment expressed during each stage

Predementia

Detailed neuropsychological testing can reveal mild cognitive difficulties upto eight years before a person fulfills the clinical criteria of diagnosis. These early symptoms can have an effect on the most complex daily living activities. The most noticeable deficit is memory loss, shown as a difficulty to remember recently learned facts and an inablility to acquire new information. In additon, subtle executive function problems (attention, planning, flexibility, abstraction ) or impairments in semantic memory (memory of meanings and concept relationships can also occur. Apathy can be observed at this stage, and is the most common and persistent neuropsychiatric symptom throughout the course of the disease.

Early Dementia

In most people with the disease the increasing impairments in learning and memory will lead to diagnosis, while in a small proportion of them difficulties with language, executive functions, recognition of perception or execution of movements will be more salient. Nevertheless, memory problems do not affect entire memory equally. Older memories of the patient’s life (episodic memory), facts learned (semantic memory) and implicit memory (the memory of the body on how to do things, such as using a fork to eat) are affected to a much lesser degree than the capacities needed to learn new facts or make new memories. Language problems are mainly characterised by a shrinking vocabulary and a decreased word fluency which leads to a general impoverishment of oral and written language. The patient is usually capable of adequately communicating baisc ideas. While performing fine motor tasks such as writing, drawing or dressing certain visoconstructional difficulties or apraxia, may be present which may appear as clumsiness.  As the disease progresses to the middle stage, patients might still be able to live and perform tasks independently for most of the time, but may need assisstance or supervison with the most complicated activites.

Moderate Dementia

In the early stage, people with AD can usually care for themselves. At the moderate stage, progressive detoriation seriously hinders the possiblilty of independence. Speech difficulties become clearly noticeable. Due to difficulties in finding words, the person makes frequent incorrect substitutions, and content is poor. Reading and writing are also progressively forgotten. As the time passes, complex motor sequences become less coordinated, costing the patient most of their daily living abilities. Memory problems become worse and the person may not recognise close relatives. Long term memory also gets affected. At this stage, behavior changes are the norm. Common neuropsychiatric manifestations in this stage are irritability and labile affectleading to crying or outbursts of unpremediated agression and physical violence, even in patients whose life long behavior has been peaceful. Approximately 30 percentage of patients develop  illusionary misidentifactions and other delusional symptons. Often urinary incontinence develops. Because of the communication deficit along with delusions, patient often resist when caregivers attempt to give care. It is also important to prevent esclation of resistiveness to care into combativeness when patient might stirke out. All these symptoms create stress for relatives and caretakers, increasing the likelihood of moving the patient from home care to other long term care facilities.

Advanced

In the last stage of AD, the subject is fully dependent. Language is reduced to simple phrases or even single words before being lost altogether. Nevertheless, many patients can receive and return emotional signals long after  the loss of verbal languague. Although aggressiveness can still be present, extreme apathy and exhaustion are more common. Patients will ultimately not be able to perform even the most simple tasks independently. Finally, deterioration of muscle and mobility will develop, leading the patient to become bedridden, and to lose the ability to feed oneself, if death from some external cause, such as infection due to pressure ulcers or pneumonia, doesnot occur first.

Causes

Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is known as the Cholinergic Hypothesis. This suggests that AD  is due to reduced biosynthesis of neurotransmitter “acetylcholine” . However, medications that treat acetylcholine deficiency only affect symptoms of the disease and neither halt or reverse it. This hypothesis has not got widespread support in the face of this evidence, although cholinergic effects have been proposed to initiate large scale aggregation, leading to generalise neuroinflammation. In 1991 the amyloid hypothesis was proposed, while research after 2000 is also center on tau proteins. The two positions differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aß) deposits are the causative factor in the disease. The tau hypothesis is supported by the long standing oservation that depositiion of amyloid plaques doesnot correlate well with neuron loss. In this model, hyperphosphorylated tau  begins to pair with other threads of tau and they become tangled up together inside nerve cell bodies in masses known as neurofibrillary tangles. When this happens, the microtubules disintegrate, collapsing the neurons transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells. A majority of researchers support the alternative hypothesis that Aß is the primary causative agent. The amyloid hypethesis is compelling because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and patients with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD like disorders by 40 years of age.  It should be noted further that APOE4, the major genetic risk factor for AD, leads to excess amyloid build up in the brain before AD symptoms arise. Thus Aß deposition precedes clinical AD.

Prevention

At present contradictory results in global studies, incapacity to prove causual relationships between risk factors and the disease, and possible secondary effects indicate a lack of specific measures to prevent or delay the onset of AD. Different epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities amongst others, and populations likelihood of developing AD. Only further research, including clinical trails, will reveal whether, in fact, these factors can help to prevent AD. The componenets of Mediterranean diet, which include fruit and vegetables, bread, wheat and other cereals, olive oil, fish, and red wine, may all individually or together reduce the risk and course of AD. Vitamins B and C, or folic acid have appeared to be related to a reduced risk of AD, but other studies indicate that they donot have any significant effect on the onset or course of the disease and may have important secondary effects. Although, cardiovascular risk factors, such as hyperchloesterolemia, hpertension, diabetes and smoking are associated with a higher risk of onset and course of AD, statins, which are cholesterol lowering drugs, have not been effective in preventing or improvingthe course of the disease. However long term of usage of non sterodial anti inflammatory drug (NSAIDS) is associated with a reduced likelihood of developing AD in some individuals. Other pharmaceutical therapies such as female hormone replacement therapy are no longer thought to prevent dementia. Intellectual activies such as playing chess, completing crossword puzzles or regular social interaction may also delay the onset or reduce the severity of AD. Bilingualism is also related to a later onset of AD. Some studies have shown a positive relationship between risk of developing AD  and different occupational exposures such as magnetic field exposure, metals intake and specifically aluminium or solvents. The quality of some of these studies has been criticized and other research doesnot confirm this link.

Treatment

There is no known cure for AD. Available treatments offer relatively small symptomatic bebefit but remain palliative in nature. Current treatments can be divided into pharmaceutical, psychosocial and caregiving.

Pharmaceutical

Four medications to treat the cognitive manifestations of AD, are currently approved by regulatory agencies, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Three are acetylcholinesterase inhibitors and the other is mematine, an NMDA receptor antagonist. No drug has an indication for delaying or halting the progression of the disease.

Because reduction in the activity of the Cholinergic neurons in the disease is well known, acetylcholinesterase inhibitors are employed to reduce the reate at which acetylcholine (ACh) is broken down and so to increase the concentration of ACh in the brain thereby combatting the loss of ACh casued by the death of the cholinergin neurons. There is also evidence for the efficacy of these medications in mild to moderate AD and some evidence for their use in the advanced stage. The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD. Most common side effects include nausea and vomitting, which are linked to cholinergic excess. These side effects arise in approximately 10-20 percent of users and are mild to moderate in severity. Less common secondary effects include muscle cramps, decreased heart rate, decrease appetite and weight, and increased gastric acid.

Glutamate is a useful excitatory neurotransmitter of the nervous system, although excessive amounts in the brain can lead to cell death through a process called excitotoxicity which consists of the overstimulation of glutamate receptors. Exctitotoxicity occurs not only in AD, but also in other neurological diseases such as Parkinsons disease and multiple sclerosis. Memantine is a noncompetitve NMDA receptor antagonist first used as an anti influenza agent. It acts on the glutamatergic system by blocking MDA glutamate receptors and inhibits their overstimulation by glutamate. Memantine has been shown to be moderately efficacious in the treatment of moderate to severe AD. Its effects in the iitial stages are unknown. Reported adverse evenets with memantine are infrequent and mild including hallucinations, confusion dizzines, headache and fatigue.

Neuroleptic anti psychotic drugs commonly given to Alzheimer’s patients with behavioural problems are modestly useful in reducing aggression and psychosis, but are associated with serious adverse effects, such as cerebrovascular events, movement difficulties or cognitive decline, that donot permit their regular use.

Psychosocial Intervention

Psychosocial Interventions are used as an adjunct to pharmaceutical treatment and can be calssified as behaviour, emotion, cogniton or stimulation oriented approaches. Research on efficacy is unavailable and rarely specific to the disease, focusing instead on dementia.

Behavioural Interventions

Behavioural interventions attempt to identify and reduce the antecendents and consequences of problem behaviours. This approach has not shown success in the overall functioning of patients, but can help to reduce some specific problem behaviours, such as incontinence. There is still a lack of high quality data on the effectiveness fo these techniques in other behaviour problems such as wandering.

Emotion Oriented Interventions

Emotion oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory intergation and simulated presence therapy. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired patients adjust to their illness. Reminiscence therapy (RT) involves the discussion of past experiences individually or in a group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Although there are few quality studies on the effectiveness of RT, it may be beneficial for cognition and mood. Simulated presence therapy (SPT) is based on attachment theories and is normally carried out playing a recording with voices of the closest relatives of the patient. There is preliminary evidence indicationg that SPT may reduce anxiety and challenging behaviours. Finally, validation therapy is based on acceptance of the reality and personal truth of another’s experience, while sensory integration is based on exercises aimed to stimualte senses. There is little evidence to support the usefulness of these therapies.

Cognition Oriented Treatments

The aim of cognition oriented treatments, which include reality orientation and cognitive retraining is the restoration of cognitive deficits. Reality orientation consists in the presentation of information about time, place or person in order to ease the understanding of the person about its surroundings and his place in them. On the other hand cognitive retraining tries to improve impaired capacites by exercitation of mental abilities. Both have shown some efficacy improving cognitive capacities although in some works these effects were transient and negative effects such as frustration, have also been reported.

Stimulation oriented Treatments

Stimulation oriented treatments include art, music and pet therapies, exercise and any other kind of recreational activities for patients.  This has modest support for improving behavior, mood, and, to a lesser extent function.

Caregiving

Since there is no cure for AD, caregiving is an essential part of the treatment. Due to the eventual inablility for the sufferer to self care, Alzheimer’s has to be carefully managed. Home care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care.

Modifications to the living environment and lifestyle of the patient can improve functional performance and ease caretaker burden. Adherence to simplified routines and labelling of household items to cue the patient can aid with activites of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitaiton, whereas well lit rooms, adequate rest and avoidance of excess stimulation all help prevent such episodes. Appropriate social and visual stimulation can improve funtion by increasing awareness and orientation.

Caregiving burden

AD is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects. Dementia caregivers are themselves subject to high rates of physical and mental disorders. Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviours of the patient such as depression, behavioural disturbance, hallucinations, sleep problems or walking disruptions and social isolations.

Individual behavioural therapy and the teaching of coping strategies either individually or in group have both demonstrated their efficacy improving care givers psychological health.

Future Research Directions

As of 2008, the safety and efficacy of more than 400 pharmaceutical treatments are being investigated in clinical trials worldwide, and approximately one-fourth of these compounds are in Phase III trials which is the last step prior to review by regulatory agencies. A critical area of clinical research is focused on treating the underlying disease pathology. Reduction of amyloid beta levels is a common target of compunds under investigation. Immunotherapy or vaccination for the amyloid protein is one treatment modality under study. Unlike vaccines which seek to prevent disease, this therapy would be used to treat diagnosed patients, and is based upon the concept of training the immune system to recognize, attack and reverse deposition of amyloid thereby altering the course of the disease. There are also many basic investigations attempting to increase the knowledge on the origin and mechanisms of the disease that may lead to new treatments.

Source

1. Wikipedia

2. Medicinenet.com

3. Medicial Dictionary Online (For Medical Terms and Definitions)

4. AcronymFinder.Com (For Acronyms used in this write up)

This writeup contains lots of medical terms. You can click on the highlighted items to view the definition

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