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Lewy Body Dementia

 Lewy Body Dementia

What Is LBD?

LBD is not a rare disease. It affects an estimated 1.3 million individuals and their families in the United States. Because LBD symptoms can closely resemble other more commonly known diseases like Alzheimer’s and Parkinson’s, it is currently widely underdiagnosed. Many doctors or other medical professionals still are not familiar with LBD.LBD is an umbrella term for two related diagnoses. LBD refers to both Parkinson’s disease dementia and dementia with Lewy bodies. The earliest symptoms of these two diseases differ, but reflect the same underlying biological changes in the brain. Over time, people with both diagnoses will develop very similar cognitive, physical, sleep, and behavioral symptoms.While it may take more than a year or two for enough symptoms to develop for a doctor to diagnose LBD, it is critical to pursue a formal diagnosis. Early diagnosis allows for important early treatment that may extend quality of life and independence.LBD is a multisystem disease and typically requires a comprehensive treatment approach. This approach involves a team of physicians from different specialties who collaborate to provide optimum treatment of each symptom without worsening other LBD symptoms. Many people with LBD enjoy significant improvement of their symptoms with a comprehensive approach to treatment, and some can have remarkably little change from year to year.Some people with LBD are extremely sensitive or may react negatively to certain medications used to treat Alzheimer’s or Parkinson’s in addition to certain over-the-counter medications.

Who was Lewy?
In the early 1900s, while researching Parkinson’s disease, the scientist Friederich H. Lewy discovered abnormal protein deposits that disrupt the brain’s normal functioning. These Lewy body proteins are found in an area of the brain stem where they deplete the neurotransmitter dopamine, causing Parkinsonian symptoms. In Lewy body dementia, these abnormal proteins are diffuse throughout other areas of the brain, including the cerebral cortex. The brain chemical acetylcholine is depleted, causing disruption of perception, thinking and behavior. Lewy body dementia exists either in pure form, or in conjunction with other brain changes, including those typically seen in Alzheimer’s disease and Parkinson’s disease.

Early and accurate diagnosis of LBD, while not always easy to do, is of critical importance for two reasons.

  • First, people with LBD may respond more favorably to certain dementia medications than people with Alzheimer’s, allowing for early treatment that may improve or extend the quality of life for both the person with LBD and their caregiver.
  • Secondly, many people with LBD respond more poorly to certain medications for behavior and movement than people with Alzheimer’s or Parkinson’s, sometimes with dangerous or permanent side effects.

By learning about common forms of dementia, you can help your physician most quickly identify what type of dementia has developed.

Common Forms of Dementia

Alzheimer’s disease symptoms include a progressive loss of recent memory; problems with language, calculation, abstract thinking, and judgment; depression or anxiety; personality and behavioral changes; and disorientation to time and place.

Lewy body dementia (LBD) is an umbrella term for a form of dementia that has three common presentations.

  • Some individuals will start out with a memory or cognitive disorder that may resemble Alzheimer’s disease, but over time two or more distinctive features become apparent leading to the diagnosis of ‘dementia with Lewy bodies’ (DLB). Symptoms that differentiate it from Alzheimer’s include unpredictable levels of cognitive ability, attention or alertness, changes in walking or movement, visual hallucinations, a sleep disorder called REM sleep behavior disorder, in which people physically act out their dreams, and severe sensitivity to medications for hallucinations. In some cases, the sleep disorder can precede the dementia and other symptoms of LBD by decades.
  • Others will start out with a movement disorder leading to the diagnosis of Parkinson’s disease and later develop dementia and other symptoms common in DLB.
  • Lastly, a small group will first present with neuropsychiatric symptoms, which can include hallucinations, behavioral problems, and difficulty with complex mental activities, leading to an initial diagnosis of DLB.

Regardless of the initial symptom, over time all three presentations of LBD will develop very similar cognitive, physical, sleep and behavioral features, all caused by the presence of Lewy bodies throughout the brain.

Vascular dementia is caused by a series of small strokes that deprive the brain of vital oxygen. Symptoms, such as disorientation in familiar locations; walking with rapid, shuffling steps; incontinence; laughing or crying inappropriately; difficulty following instructions; and problems handling money may appear suddenly and worsen with additional strokes. High blood pressure, cigarette smoking, and high cholesterol are some of the risk factors for stroke that may be controlled to prevent vascular dementia.

Frontotemporal dementia (FTD) includes several disorders with a variety of symptoms. The most common signs of FTD include changes in personality and behavior, such as inappropriate or compulsive behavior, euphoria, apathy, decline in personal hygiene, and a lack of awareness concerning these changes. Some forms of FTD involve language and speech symptoms or movement changes.

An experienced clinician within the medical community should perform a diagnostic evaluation. If one is not available, the neurology department of the nearest medical university should be able to recommend appropriate resources or may even provide an experienced diagnostic team skilled in Lewy body dementia.

A thorough dementia diagnostic evaluation includes physical and neurological examinations, patient and family interviews (including a detailed lifestyle and medical history), and neuro-psychological and mental status tests. The patient’s functional ability, attention, language, visuospatial skills, memory and executive functioning are assessed. In addition, brain imaging (CT or MRI scans), blood tests and other laboratory studies may be performed. The evaluation will provide a clinical diagnosis. Currently, a conclusive diagnosis of LBD can be obtained only from a postmortem autopsy for which arrangements should be made in advance. Some research studies may offer brain autopsies as part of their protocols. Participating in research studies is a good way to benefit others with Lewy body dementia.

Medications
Medications are one of the most controversial subjects in dealing with LBD. A medication that doesn’t work for one person may work for another person.

Prescribing should only be done by a physician who is thoroughly knowledgeable about LBD. With new medications and even ‘over-the-counter,’ the patient should be closely monitored. At the first sign of an adverse reaction, consult with the patient’s physician. Consider joining an online caregiver support group to see what others have observed with prescription and over-the-counter medicines.

Risk Factors
Advanced age is considered to be the greatest risk factor for Lewy body dementia, with onset typically, but not always, between the ages of 50 and 85. Some cases have been reported much earlier. It appears to affect slightly more men than women. Having a family member with Lewy body dementia may increase a person’s risk. Observational studies suggest that adopting a healthy lifestyle (exercise, mental stimulation, nutrition) might delay age-associated dementias.

Clinical Trials
The recruitment of LBD patients for participation in clinical trials for studies on LBD, other dementias and Parkinsonian studies is now steadily increasing.

Prognosis and Stages
No cure or definitive treatment for Lewy body dementia has been discovered as yet. The disease has an average duration of 5 to 7 years. It is possible, though, for the time span to be anywhere from 2 to 20 years, depending on several factors, including the person’s overall health, age and severity of symptoms.

Defining the stages of disease progression for LBD is difficult. The symptoms, medicine management and duration of LBD vary greatly from person to person. To further complicate the stages assessment, LBD has a progressive but vacillating clinical course, and one of its defining symptoms is fluctuating levels of cognitive abilities, alertness and attention. Sudden decline is often caused by medications, infections or other compromises to the immune system and usually the person with LBD returns to their baseline upon resolution of the problem.  But for some individuals, it may also be due to the natural course of the disease.

Symptoms

Lewy body dementia symptoms and diagnostic criteria
Every person with LBD is different and will manifest different degrees of the following symptoms. Some will show no signs of certain features, especially in the early stages of the disease. Symptoms may fluctuate as often as moment-to-moment, hour-to-hour or day-to-day. NOTE: Some patients meet the criteria for LBD yet score in the normal range of some cognitive assessment tools. The Mini-Mental State Examination (MMSE), for example, cannot be relied upon to distinguish LBD from other common syndromes.

LBD is a an umbrella term for two related clinical diagnoses, dementia with Lewy bodies and Parkinson’s disease dementia.

The latest clinical diagnostic criteria for dementia with Lewy bodies (DLB) categorizes symptoms into three types, listed below.  A diagnosis of Parkinsons’ disease dementia (PDD) requires a well established diagnosis of Parkinson’s disease that later progresses into dementia, along with very similar features to DLB.  A rather arbirary time cutoff was established to differentiate between DLB and PDD.  People whose dementia occurs before or within 1 year of Parkinson’s symptoms are diagnosed with DLB.  People who have an existing diagnosis of Parkinson’s for more than a year and later develop dementia are diagnosed with PDD.

Central feature

  • Progressive dementia – deficits in attention and executive function are typical. Prominent memory impairment may not be evident in the early stages.

Core features

  • Fluctuating cognition with pronounced variations in attention and alertness.
  • Recurrent complex visual hallucinations, typically well formed and detailed.
  • Spontaneous features of parkinsonism.

Suggestive features

  • REM sleep behavior disorder (RBD), which can appear years before the onset of dementia and parkinsonism.
  • Severe sensitivity to neuroleptics occurs in up to 50% of LBD patients who take them.
  • Low dopamine transporter uptake in the brain’s basal ganglia as seen on SPECT and PET imaging scans. (These scans are not yet available outside of research settings.)

Supportive features

  • Repeated falls and syncope (fainting).
  • Transient, unexplained loss of consciousness.
  • Autonomic dysfunction.
  • Hallucinations of other senses, like touch or hearing.
  • Visuospatial abnormalities.
  • Other psychiatric disturbances.

A clinical diagnosis of LBD can be probable or possible based on different symptom combinations.

A probable LBD diagnosis requires either:

  • Dementia plus two or more core features, or
  • Dementia plus one core feature and one or more suggestive features.

A possible LBD diagnosis requires:

  • Dementia plus one core feature, or
  • Dementia plus one or more suggestive features.

Symptoms Explained
In this section we’ll discuss each of the symptoms, starting with the key word: dementia. Dementia is a process whereby the person becomes progressively confused. The earliest signs are usually memory problems, changes in their way of speaking, such as forgetting words, and personality problems. Cognitive symptoms of dementia include poor problem solving, difficulty with learning new skills and impaired decision making.

Other causes of dementia should be ruled out first, such as alcoholism, overuse of medication, thyroid or metabolic problems. Strokes can also cause dementia. If these reasons are ruled out then the person is said to have a degenerative dementia. Lewy Body Dementia is second only to Alzheimer’s disease as the most common form of dementia.

Fluctuations in cognition will be noticeable to those who are close to the person with LBD, such as their partner. At times the person will be alert and then suddenly have acute episodes of confusion. These may last hours or days. Because of these fluctuations, it is not uncommon for it to be thought that the person is “faking”. This fluctuation is not related to the well-known “sundowning” of Alzheimer’s. In other words, there is no specific time of day when confusion can be seen to occur.

Hallucinations are usually, but not always, visual and often are more pronounced when the person is most confused. They are not necessarily frightening to the person. Other modalities of hallucinations include sound, taste, smell, and touch.

Parkinsonism or Parkinson’s Disease symptoms, take the form of changes in gait; the person may shuffle or walk stiffly. There may also be frequent falls. Body stiffness in the arms or legs, or tremors may also occur. Parkinson’s mask (blank stare, emotionless look on face), stooped posture, drooling and runny nose may be present.

REM Sleep Behavior Disorder (RBD) is often noted in persons with Lewy Body Dementia. During periods of REM sleep, the person will move, gesture and/or speak. There may be more pronounced confusion between the dream and waking reality when the person awakens. RBD may actually be the earliest symptom of LBD in some patients, and is now considered a significant risk factor for developing LBD. (One recent study found that nearly two-thirds of patients diagnosed with RBD developed degenerative brain diseases, including Lewy body dementia, Parkinson’s disease, and multiple system atrophy, after an average of 11 years of receiving an RBD diagnosis. All three diseases are called synucleinopathies, due to the presence of a mis-folded protein in the brain called alpha-synuclein.)

Sensitivity to neuroleptic (anti-psychotic) drugs is another significant symptom that may occur. These medications can worsen the Parkinsonism and/or decrease the cognition and/or increase the hallucinations. Neuroleptic Malignancy Syndrome, a life-threatening illness, has been reported in persons with Lewy Body Dementia. For this reason, it is very important that the proper diagnosis is made and that healthcare providers are educated about the disease.

Other Symptoms
Visuospatial difficulties, including depth perception, object orientation, directional sense and illusions may occur.

Autonomic dysfunction, including blood pressure fluctuations (e.g. postural/orthostatic hypotension) heart rate variability (HRV), sexual disturbances/impotence, constipation, urinary problems, hyperhidrosis (excessive sweating), decreased sweating/heat intolerance, syncope (fainting), dry eyes/mouth, and difficulty swallowing which may lead to aspiration pneumonia.

Other psychiatric disturbances may include systematized delusions, aggression and depression. The onset of aggression in LBD may have a variety of causes, including infections (e.g., UTI), medications, misinterpretation of the environment or personal interactions, and the natural progression of the disease.

Treatment Options

LBD is a multi-system disease and typically requires a comprehensive treatment approach, meaning a team of physicians from different specialties, who collaborate to provide optimum treatment of each symptom without worsening other LBD symptoms.  It is important to remember that some people with LBD are extremely sensitive or may react negatively to certain medications used to treat Alzheimer’s or Parkinson’s in addition to certain over-the-counter medications.

Cognitive Symptoms
Medications called cholinesterase inhibitors are considered the standard treatment for cognitive symptoms in LBD. These medications were developed to treat Alzheimer’s disease. However, some researchers believe that people with LBD may be even more responsive to these types of medications than those with Alzheimer’s.

Movement Symptoms
Movement symptoms may be treated with a Parkinson’s medication called levodopa, but if the symptoms are mild, it may be best to not treat them in order to avoid potential medication side-effects.

Visual Hallucinations
If hallucinations are disruptive or upsetting, your physician may recommend a cautious trial of a newer antipsychotic medication. (Please see WARNING below.)  Of note, the dementia medications called cholinesterase inhibitors have also been shown to be effective in treating hallucinations and other psychiatric symptoms of LBD.

REM Sleep Behavior Disorder (RBD)
RBD can be quite responsive to treatment, so your physician may recommend a medication like melatonin and/or clonazepam.

Neuroleptic Sensitivity
Severe sensitivity to neuroleptics is common in LBD. Neuroleptics, also known as antipsychotics, are medications used to treat hallucinations or other serious mental disorders. While traditional antipsychotic medications (e.g. haloperidol) are commonly prescribed for individuals with Alzheimer’s with disruptive behavior, these medications can affect the brain of an individual with LBD differently, sometimes causing severe side effects (see below). For this reason, traditional antipsychotic medications like haloperidol should be avoided. Some newer ‘atypical’ antipsychotic medications like risperidone may also be problematic for someone with LBD. Quetiapine is preferred by some LBD experts. If quetiapine is not tolerated or is not helpful, clozapine should be considered, but requires ongoing blood tests to assure a rare but serious blood condition does not develop. Hallucinations must be treated very conservatively, using the lowest doses possible under careful observation for side effects.

WARNING:
Up to 50% of patients with LBD who are treated with any antipsychotic medication may experience severe neuroleptic sensitivity, such as worsening cognition, heavy sedation, increased or possibly irreversible parkinsonism, or symptoms resembling neuroleptic malignant syndrome (NMS), which can be fatal. (NMS causes severe fever, muscle rigidity and breakdown that can lead to kidney failure.)

Medication Side Effects
Speak with your doctor about possible side effects. The following drugs may cause sedation, motor impairment or confusion:

  • Benzodiazepines, tranquilizers like diazepam and lorazepam
  • Anticholinergics (antispasmodics), such as oxybutynin and glycopyrrolate
  • Some surgical anesthetics
  • Older antidepressants
  • Certain over-the-counter medications, including diphenhydramine and dimenhydrinate.
  • Some medications, like anticholinergics, amantadine and dopamine agonists, which help relieve parkinsonian symptoms, might increase confusion, delusions or hallucinations.

NOTE: Be sure to meet with your anesthesiologist in advance of any surgery to discuss medication sensitivities and risks unique to LBD. People with LBD often respond to certain anesthetics and surgery with acute states of confusion or delirium and may have a sudden significant drop in functional abilities, which may or may not be permanent.

Possible alternatives to general anesthesia include a spinal or regional block. These methods are less likely to result in postoperative confusion. If you are told to stop taking all medications prior to surgery, consult with your doctor to develop a plan for careful withdrawal.

Non-Medical Treatments

Physical therapy options include cardiovascular, strengthening, and flexibility exercises, as well as gait training. Physicians may also recommend general physical fitness programs such as aerobic, strengthening, or water exercise.

Speech therapy may be helpful for low voice volume and poor enunciation. Speech therapy may also improve muscular strength and swallowing difficulties.

Occupational therapy may help maintain skills and promote function and independence. In addition to these forms of therapy and treatment, music and aroma therapy can also reduce anxiety and improve mood.

Individual and family psychotherapy can be useful for learning strategies to manage emotional and behavioral symptoms and to help make plans that address individual and family concerns about the future.

Support groups may be helpful for caregivers and persons with LBD to identify practical solutions to day-to-day frustrations, and to obtain emotional support from others.

End-of-Life
Planning for the end of life can be a valuable activity for any family. The links below offer general guidance and some specific suggestions for families who face the burden of a disease such as Lewy body dementia.

Advanced Directives – a Caring Connections site with state-specific advanced directives

Caring Connections – home page of consumer Web site about hospice and palliative care managed by the National Hospice and Palliative Care Organization

Palliative Doctors – a Web site for consumers managed by the American Academy of Hospice and Palliative Care about palliative care

Friedreich’s Ataxia

Friedreich’s ataxia (also called FA or FRDA) is a rare inherited disease that causes nervous system damage and movement problems. It usually begins in childhood and leads to impaired muscle coordination (ataxia) that worsens over time. The disorder is named after Nicholaus Friedreich, a German doctor who first described the condition in the 1860s.

In Friedreich’s ataxia the spinal cord and peripheral nerves degenerate, becoming thinner. The cerebellum, part of the brain that coordinates balance and movement, also degenerates to a lesser extent. This damage results in awkward, unsteady movements and impaired sensory functions. The disorder also causes problems in the heart and spine, and some people with the condition develop diabetes. The disorder does not affect thinking and reasoning abilities (cognitive functions).

Friedreich’s ataxia is caused by a defect (mutation) in a gene labeled FXN. The disorder is recessive, meaning it occurs only in someone who inherits two defective copies of the gene, one from each parent. Although rare, Friedreich’s ataxia is the most common form of hereditary ataxia, affecting about 1 in every 50,000 people in the United States. Both male and female children can inherit the disorder.

What are the signs and symptoms?
Symptoms typically begin between the ages of 5 and 15 years, although they sometimes appear in adulthood and on rare occasions as late as age 75. The first symptom to appear is usually gait ataxia, or difficulty walking. The ataxia gradually worsens and slowly spreads to the arms and the trunk. There is often loss of sensation in the extremities, which may spread to other parts of the body. Other features include loss of tendon reflexes, especially in the knees and ankles. Most people with Friedreich’s ataxia develop scoliosis (a curving of the spine to one side), which often requires surgical intervention for treatment.

Dysarthria (slowness and slurring of speech) develops and can get progressively worse. Many individuals with later stages of Friedreich’s ataxia develop hearing and vision loss.

Other symptoms that may occur include chest pain, shortness of breath, and heart palpitations. These symptoms are the result of various forms of heart disease that often accompany Friedreich’s ataxia, such as hypertrophic cardiomyopathy (enlargement of the heart), myocardial fibrosis (formation of fiber-like material in the muscles of the heart), and cardiac failure. Heart rhythm abnormalities such as tachycardia (fast heart rate) and heart block (impaired conduction of cardiac impulses within the heart) are also common.

About 20 percent of people with Friedreich’s ataxia develop carbohydrate intolerance and 10 percent develop diabetes. Most individuals with Friedreich’s ataxia tire very easily and find that they require more rest and take a longer time to recover from common illnesses such as colds and flu.

The rate of progression varies from person to person. Generally, within 10 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease individuals may become completely incapacitated.

Friedreich’s ataxia can shorten life expectancy, and heart disease is the most common cause of death. However, some people with less severe features of Friedreich’s ataxia live into their sixties, seventies, or older.

How is Friedreich’s ataxia diagnosed?
A diagnosis of Friedreich’s ataxia requires a careful clinical examination, which includes a medical history and a thorough physical exam, in particular looking for balance difficulty, loss of proprioception (joint sensation), absence of reflexes, and signs of neurological problems. Genetic testing now provides a conclusive diagnosis. Other tests that may aid in the diagnosis or management of the disorder include:

  • electromyogram (EMG), which measures the electrical activity of muscle cells,
  • nerve conduction studies, which measure the speed with which nerves transmit impulses,
  • electrocardiogram (ECG), which gives a graphic presentation of the electrical activity or beat pattern of the heart,
  • echocardiogram, which records the position and motion of the heart muscle,
  • blood tests to check for elevated glucose levels and vitamin E levels, and
  • magnetic resonance imaging (MRI) or computed tomography (CT) scans, tests which provide brain and spinal cord images that are useful for ruling out other neurological conditions.

How is Friedreich’s ataxia inherited?
Friedreich’s ataxia is an autosomal recessive disease, meaning individuals only develop symptoms if they inherit two copies of the defective FXN gene, one from their father and one from their mother. A person who has only one abnormal copy of the gene is called a carrier. A carrier will not develop the disease but could pass the gene mutation on to his or her children. If both parents are carriers, their children will have a 1 in 4 chance of having the disease and a 1 in 2 chance of inheriting one abnormal gene that they, in turn, could pass on to their children. About one in 90 Americans of European ancestry carries an abnormal FXN gene.

In 1996, an international research team identified the Friedreich’s ataxia gene on chromosome 9. The FXN gene codes for production of a protein called “frataxin.” In the normal version of the gene, a sequence of DNA (labeled “GAA”) is repeated between 7 and 22 times. In the defective FXN gene, the repeat occurs over and over again—hundreds, even up to a thousand times.

This abnormal pattern, called a triplet repeat expansion, has been implicated as the cause of several dominantly inherited diseases, but Friedreich’s ataxia is the only known recessive genetic disorder caused by the problem. Almost all people with Friedreich’s ataxia have two copies of this mutant form of FXN, but it is not found in all cases of the disease. About two percent of affected individuals have other defects in the FXN gene that are responsible for causing the disease.

The triplet repeat expansion greatly disrupts the normal production of frataxin. Frataxin is found in the energy-producing parts of the cell called mitochondria. Research suggests that without a normal level of frataxin, certain cells in the body (especially peripheral nerve, spinal cord, brain and heart muscle cells) cannot effectively produce energy and have been hypothesized to have a buildup of toxic byproducts leading to what is called “oxidative stress.” It also may lead to increased levels of iron in the mitochondria. When the excess iron reacts with oxygen, free radicals can be produced. Although free radicals are essential molecules in the body’s metabolism, they can also destroy cells and harm the body. Research continues on this subject (see section on “What research is being done?”).

Can Friedreich’s ataxia be cured or treated?
As with many degenerative diseases of the nervous system, there is currently no cure or effective treatment for Friedreich’s ataxia. However, many of the symptoms and accompanying complications can be treated to help individuals maintain optimal functioning as long as possible. Doctors can prescribe treatments for diabetes, if present; some of the heart problems can be treated with medication as well. Orthopedic problems such as foot deformities and scoliosis can be corrected with braces or surgery. Physical therapy may prolong use of the arms and legs. Advances in understanding the genetics of Friedreich’s ataxia are leading to breakthroughs in treatment. Research has moved forward to the point where clinical trials of proposed treatments are presently occurring for Friedreich’s ataxia.

What services are useful to Friedreich’s ataxia patients and their families?
Genetic testing is essential for proper clinical diagnosis, and can aid in prenatal diagnosis and determining a person’s carrier status. Genetic counselors can help explain how Friedreich’s ataxia is inherited. Psychological counseling and support groups for people with genetic diseases may also help affected individuals and their families cope with the disease.

A primary care physician can screen people for complications such as heart disease, diabetes and scoliosis, and can refer individuals to specialists such as cardiologists, physical therapists, and speech therapists to help deal with some of the other associated problems.

Support and information for families is also available through a number of private organizations. These groups can offer ways to network and communicate with others affected by Friedreich’s ataxia. They can also provide access to patient registries, clinical trials information, and other useful resources.

What research is being done?
Within the Federal government the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), has primary responsibility for sponsoring research on neurological disorders. As part of this mission, the NINDS conducts research on Friedreich’s ataxia and other forms of inherited ataxias at its facilities at the NIH and supports additional studies at medical centers throughout the United States. Several nonprofit organizations also provide substantial support research (see the section on “Where can I get more information?”).

Researchers are optimistic that they have begun to understand the causes of the disease, and work has begun to develop effective treatments and prevention strategies for Friedreich’s ataxia. Scientists have been able to create various models of the disease in yeast and mice which have facilitated understanding the cause of the disease and are now being used for drug discovery and the development of novel treatments.

Studies have revealed that frataxin is an important mitochondrial protein for proper function of several organs. Yet in people with the disease, the amount of frataxin in affected cells is severely reduced. It is believed that the loss of frataxin makes the nervous system, heart, and pancreas particularly susceptible to damage from free radicals (produced when the excess iron reacts with oxygen). Once certain cells in these tissues are destroyed by free radicals they cannot be replaced. Nerve and muscle cells also have metabolic needs that may make them particularly vulnerable to this damage. Free radicals have been implicated in other degenerative diseases such as Parkinson’s and Alzheimer’s diseases.

Based upon this information, scientists and physicians have tried to reduce the levels of free radicals, also called oxidants, using treatment with “antioxidants.” Initial clinical studies in Europe suggested that antioxidants like coenzyme Q10, vitamin E, and idebenone may offer individuals some limited benefit. However, recent clinical trials in the United States and Europe have not revealed effectiveness of idebenone in people with Friedreich’s ataxia, but more powerful modified forms of this agent and other antioxidants are in trials at this time. There is also a clinical trial to examine the efficacy of selectively removing excess iron from the mitochondria.

Scientists also are exploring ways to increase frataxin levels through drug treatments, genetic engineering and protein delivery systems. Several compounds that are directed at increasing levels of frataxin may be brought to clinical trials in the near future. To check for current trials, visit http://www.clinicaltrials.gov. Additional information is available from the groups listed in the following section.

Armed with what they currently know about frataxin and Friedreich’s ataxia, scientists are working to better define fraxatin’s role, clarify how defects in iron metabolism may be involved in the disease process, and explore new therapeutic approaches for therapy.

Triple X Syndrome

Triple X syndrome, also known as Trisomy X, 47,XXX aneuploidy, and Triplo-X, XXX Syndrome is a chromosomal abnormality that affects approximately 1 in every 1,000 females. A healthy female has two X chromosomes, one from her father and one from her mother. A female with triple-X syndrome has three X chromosomes.

According to the NIH (National Institutes of Health), USA, 5 to 10 girls with triple X syndrome are born in the USA each day.

A female with triple-X syndrome does not inherit it from her parents. The syndrome generally results from a mistake in the formation of the father’s sperm cell or the mother’s egg. In some cases triple-X syndrome may be the result of something that went wrong in the development of the embryo.

A girl with triple X syndrome may either have no symptoms, just mild ones, or more severe ones with developmental delays. Developmental delays may include learning disabilities, delayed development of speech and language skills, as well as motor skills. There may be behavioral and emotional difficulties. Approximately 10% of affected females have seizures or kidney abnormalities. Among those who do have symptoms, they will vary widely from person-to-person.

Triple X syndrome treatment varies and depends on which symptoms are present, and how severe they are.

Unlike the majority of other chromosomal conditions, there is usually no clear visual difference between a female with triple X syndrome and other females. Some females with triple X syndrome may be taller than average. Most individuals with the syndrome have normal sexual development and can conceive children. Infertility is possible in some cases, but it is rare.

Most medical professionals do not regard the condition as a disability.

What are the signs and symptoms of triple X syndrome?
A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

In all female cells, only one X chromosome is active at any time. Consequently, triple X syndrome generally does not cause unusual physical features or medical problems. In other words, in the majority of cases there are no signs or symptoms. If symptoms do occur, they may include:

  • Delayed language skill development
  • Delayed motor skill development, resulting in poor coordination, awkwardness, and/or clumsiness.
  • In very rare cases, infertility
  • Some may have menstrual irregularities
  • Some may experience an early onset of menstruation

If physical features are present they will be very mild:

  • Tall stature
  • Microcephaly (small head)
  • Epicanthal folds – a vertical fold of skin that comes down across the inner angle of the eye.
  • Increased width between the eyes

22q11.2 Deletion Syndrome

Defining 22q11.2 Deletion Syndrome
22q deletion syndrome has been called by many names, reflecting the constellation of clinical manifestations that have been identified over time. More recently, molecular genetic research has revealed that all of the syndromes listed below have one common link … there is a small amount of genetic material missing, termed a microdeletion, on the long arm (referred to as the q arm) of chromosome 22. Many now simply refer to all of these syndromes as 22q11.2 deletion syndrome:

  • DiGeorge Syndrome (DGS)
  • Velocardiofacial Syndrome (VCFS)
  • Conotruncal Anomaly Face Syndrome
  • Autosomal Dominant Opitz G/BBB Syndrome
  • Cayler Cardiofacial Syndrome
  • Shprintzen Syndrome

The 22q11.2 deletion syndrome occurs in approximately 1 out of every 4,000 live births. In most cases, the 22q deletion occurs de novo (the patient is the first in the family to have this deletion).  In approximately one in 10 families (10%) the deletion is present because one of the parents has the same deletion and passes it on to their baby. As a result, parents of a baby born with 22q11.2 deletion syndrome should have a blood test to determine their chances of having other children with the syndrome.

Signs and Symptoms
There are a variety of physical and behavioral disorders that have been linked to 22q11.2 deletion syndrome. The syndrome has the potential to impact every system in the body and can therefore lead to a wide-range of health issues.  The majority of 22q11.2 deletion syndrome patients have congenital heart defects, most often conotruncal abnormalities (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect (VSD), vascular ring, and  truncus arteriosus) and palatal defects, including submucosal cleft palate and velopharyngeal dysfunction (VPD).   VPD (also referred to as velopharyngeal insufficiency, or VPI) is usually manifest as abnormal nasal air escape and hypernasal speech.  Some of the other common problems associated with 22q11.2 deletion syndrome include:

  • Feeding difficulties, including nasal regurgitation of food and fluids, vomiting or “spitting up”, gastroesophageal reflux (GERD)
  • Hypocalcemia
  • Gastrointestinal problems, including constipation, and GERD
  • Immune system disorders, including recurrent ear infections (otitis) and sinusitis, respiratory infections, and autoimmune diseases
  • Kidney disorders – approximately 35 percent of these patients may have a missing or malformed kidney.
  • ENT problems, including laryngeal webs and external ear anomalies
  • Asymmetric crying facies
  • Cleft lip and palate
  • Orthopedic issues, such as scoliosis, club feet, cervical spine abnormalities, and extra fingers or toes
  • Inguinal, umbilical and diaphragmatic hernias
  • Growth problems, sometimes associated with growth hormone deficiency
  • Developmental delays, including both language and motor skills delays
  • Autism
  • Obsessive-compulsive disorder (OCD)

5 secret symptoms of Parkinson’s Disease

5 secret symptoms of Parkinson’s Disease
Here are 5 secret symptoms of Parkinson’s Disease every family caregiver and health care professional should know:

  • Loss of smell – Early in the course of the disease, many people with PD report a loss of olfaction or sense of smell. This happens slowly without the patient noticing and may occur several years before diagnosis. Difficulty detecting and discerning different odors is typically reported.
  • R.E.M sleep disturbances – Sleep problems are common for many people with Parkinson’s Disease. This can include difficulty falling and staying asleep (insomnia) as well as a more serious sleep problem known as R.E.M sleep behavior disorder. People with RBD experience vivid dreams and nightmares, often acting out their dreams causing self-inflicted injuries or hurting a partner by kicking, choking, or punching.  In later stages of the disease, patients report leg stiffness at nighttime, frequent urination, and (no surprise) daytime sleepiness and fatigue.
  • Urinary incontinence – Problems with the autonomic nervous system, which controls unconscious or automatic bodily functions (heart rate, respiration, etc), are more pronounced for persons with advanced Parkinsonism. As a result, bladder control and urinary incontinence can be an issue for PD sufferers. Lightheadedness upon standing and dizziness often occur  due to poor blood pressure regulation. Trouble swallowing, abnormal sweating, and sexual dysfunction are common as well.
  • Mood and mental problems – Because PD is related to alterations in brain chemicals, depression affects nearly half of those with Parkinson’s Disease and worsens with the progressing course of the illness. Common symptoms include loss of interest in activities, and decreased pleasures; panic attacks and excessive worry are also common.
  • Pain – Over 40% of persons with Parkinson’s Disease report painful sensations across the body including, stabbing, burning, and tingling.  Pain often accompanies the motor symptoms and can be reported in different areas such as the face, abdomen, and joints