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What is frontotemporal dementia (Pick’s disease)?

Frontotemporal dementia (FTD) describes a clinical syndrome associated with shrinking of the frontal and temporal anterior lobes of the brain. Originally known as Pick’s disease, the name and classification of frontotemporal dementia has been a topic of discussion for over a century. The current designation of the syndrome groups together Pick’s disease, primary progressive aphasia, and semantic dementia as FTD. Some doctors propose adding corticobasal degeneration and progressive supranuclear palsy to frontotemporal dementia and calling the group Pick Complex. These designations will continue to be debated.

What are the symptoms of frontotemporal dementia?

As it is defined today, the symptoms of frontotemporal dementia fall into two clinical patterns that involve either (1) changes in behavior, or (2) problems with language.

The first type features behavior that can be either impulsive (disinhibited) or bored and listless (apathetic) and includes:

• inappropriate social behavior;
• lack of social tact;
• lack of empathy;
• distractibility;
• loss of insight into the behaviors of oneself and others;
• an increased interest in sex;
• changes in food preferences;
• agitation or, conversely, blunted emotions;
• neglect of personal hygiene;
• repetitive or compulsive behavior; and
• decreased energy and motivation.

The second type primarily features symptoms of language disturbance, including difficulty making or understanding speech, often in conjunction with the behavioral type’s symptoms. Spatial skills and memory remain intact.

Is frontotemporal dementia inherited?

There is a strong genetic component to the disease; frontotemporal dementia often runs in families.

Is there any treatment for frontotemporal dementia?

No treatment has been shown to slow the progression of frontotemporal dementia. Behavior modification may help control unacceptable or dangerous behaviors. Aggressive, agitated, or dangerous behaviors could require medication. Anti-depressants have been shown to improve some symptoms.

What is the prognosis (the outlook) for frontotemporal dementia?

The outcome for people with frontotemporal dementia is poor. The disease progresses steadily and often rapidly, ranging from less than 2 years in some individuals to more than 10 years in others. Eventually some individuals with frontotemporal dementia will need 24-hour care and monitoring at home or in an institutionalized care setting.

What are Repetitive Motion Disorders?

Repetitive motion disorders (RMDs) are a family of muscular conditions that result from repeated motions performed in the course of normal work or daily activities. RMDs include carpal tunnel syndrome, bursitis, tendonitis, epicondylitis, ganglion cyst, tenosynovitis, and trigger finger. RMDs are caused by too many uninterrupted repetitions of an activity or motion, unnatural or awkward motions such as twisting the arm or wrist, overexertion, incorrect posture, or muscle fatigue. RMDs occur most commonly in the hands, wrists, elbows, and shoulders, but can also happen in the neck, back, hips, knees, feet, legs, and ankles. The disorders are characterized by pain, tingling, numbness, visible swelling or redness of the affected area, and the loss of flexibility and strength. For some individuals, there may be no visible sign of injury, although they may find it hard to perform easy tasks. Over time, RMDs can cause temporary or permanent damage to the soft tissues in the body — such as the muscles, nerves, tendons, and ligaments – and compression of nerves or tissue. Generally, RMDs affect individuals who perform repetitive tasks such as assembly line work, meat-packing, sewing, playing musical instruments, and computer work. The disorders may also affect individuals who engage in activities such as carpentry, gardening, and tennis.

Is there any treatment for repetitive motion disorders?

Treatment for RMDs usually includes reducing or stopping the motions that cause symptoms. Options include taking breaks to give the affected area time to rest, and adopting stretching and relaxation exercises. Applying ice to the affected area and using medications such as pain relievers, cortisone, and anti-inflammatory drugs can reduce pain and swelling. Splints may be able to relieve pressure on the muscles and nerves. Physical therapy may relieve the soreness and pain in the muscles and joints. In rare cases,surgery may be required to relieve symptoms and prevent permanent damage. Some employers have developed ergonomic programs to help workers adjust their pace of work and arrange office equipment to minimize problems.

What is the prognosis for repetitive motion disorders?

Most individuals with RMDs recover completely and can avoid re-injury by changing the way they perform repetitive movements, the frequency with which they perform them, and the amount of time they rest between movements. Without treatment, RMDs may result in permanent injury and complete loss of function in the affected area.

What research is being done?

Much of the on-going research on RMDs is aimed at prevention and rehabilitation. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) funds research on RMDs.

What is Leigh’s Disease?

Leigh’s disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults.

What causes Leigh’s disease?

Leigh’s disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase.

What are the symptoms of Leigh’s disease?

Symptoms of Leigh’s disease usually progress rapidly. The earliest signs may be poor sucking ability, and the loss of head control and motor skills. These symptoms may be accompanied by loss of appetite,vomiting, irritability, continuous crying, and seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.

In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance called adenosine triphosphate (ATP). The energy in ATP drives virtually all of a cell’s metabolic functions. Genetic mutations in mitochondrial DNA, therefore, result in a chronic lack of energy in these cells, which in turn affects the central nervous system and causes progressive degeneration of motor functions.

Is there any treatment for Leigh’s disease?

The most common treatment for Leigh’s disease is thiamine or Vitamin B1. Oral sodium bicarbonate or sodium citrate may also be prescribed to manage lactic acidosis. Researchers are currently testing dichloroacetate to establish its effectiveness in treating lactic acidosis. In individuals who have the X-linked form of Leigh’s disease, a high-fat, low-carbohydrate diet may be recommended.

Are there other forms of Leigh’s disease?

There is also a form of Leigh’s disease (called X-linked Leigh’s disease) which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome.

What is the prognosis for Leigh’s disease?

The prognosis for individuals with Leigh’s disease is poor. Individuals who lack mitochondrial complex IV activity and those with pyruvate dehydrogenase deficiency tend to have the worst prognosis and die within a few years. Those with partial deficiencies have a better prognosis, and may live to be 6 or 7 years of age. Some have survived to their mid-teenage years.

What research is being done with Leigh’s disease?

The NINDS supports and encourages a broad range of basic and clinical research on neurogenetic disorders such as Leigh’s disease. The goal of this research is to understand what causes these disorders and then to apply these findings to new ways to diagnose, treat, and prevent them.

What is myasthenia gravis?

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. The name myasthenia gravis, which is Latin and Greek in origin, literally means “grave muscle weakness.” With current therapies, however, most cases of myasthenia gravis are not as “grave” as the name implies. In fact, for the majority of individuals with myasthenia gravis, life expectancy is not lessened by the disorder.

The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest. Certain muscles such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are often, but not always, involved in the disorder. The muscles that control breathing and neck and limb movements may also be affected.

What causes myasthenia gravis?

Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction – the place where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine. Acetylcholine travels through the neuromuscular junction and binds to acetylcholine receptors which are activated and generate a muscle contraction.

In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction which prevents the muscle contraction from occurring. These antibodies are produced by the body’s own immune system. Thus, myasthenia gravis is an autoimmune disease because the immune system – which normally protects the body from foreign organisms – mistakenly attacks itself.

What is the role of the thymus gland in myasthenia gravis?

The thymus gland, which lies in the upper chest area beneath the breastbone, plays an important role in the development of the immune system in early life. Its cells form a part of the body’s normal immune system. The gland is somewhat large in infants, grows gradually until puberty, and then gets smaller and is replaced by fat with age. In adults with myasthenia gravis, the thymus gland is abnormal. It contains certain clusters of immune cells indicative of lymphoid hyperplasia – a condition usually found only in the spleen and lymph nodes during an active immune response. Some individuals with myasthenia gravis develop thymomas or tumors of the thymus gland. Generally thymomas are benign, but they can become malignant.

The relationship between the thymus gland and myasthenia gravis is not yet fully understood. Scientists believe the thymus gland may give incorrect instructions to developing immune cells, ultimately resulting in autoimmunity and the production of the acetylcholine receptor antibodies, thereby setting the stage for the attack on neuromuscular transmission.

What are the symptoms of myasthenia gravis?

Although myasthenia gravis may affect any voluntary muscle, muscles that control eye and eyelid movement, facial expression, and swallowing are most frequently affected. The onset of the disorder may be sudden. Symptoms often are not immediately recognized as myasthenia gravis.

In most cases, the first noticeable symptom is weakness of the eye muscles. In others, difficulty in swallowing and slurred speech may be the first signs. The degree of muscle weakness involved in myasthenia gravis varies greatly among patients, ranging from a localized form, limited to eye muscles (ocular myasthenia), to a severe or generalized form in which many muscles – sometimes including those that control breathing – are affected. Symptoms, which vary in type and severity, may include a drooping of one or both eyelids (ptosis), blurred or double vision (diplopia) due to weakness of the muscles that control eye movements, unstable or waddling gait, weakness in arms, hands, fingers, legs, and neck, a change in facial expression, difficulty in swallowing and shortness of breath, and impaired speech (dysarthria).

Who gets myasthenia gravis?

Myasthenia gravis occurs in all ethnic groups and both genders. It most commonly affects young adult women (under 40) and older men (over 60), but it can occur at any age.

In neonatal myasthenia, the fetus may acquire immune proteins (antibodies) from a mother affected with myasthenia gravis. Generally, cases of neonatal myasthenia gravis are transient (temporary) and the child’s symptoms usually disappear within 2-3 months after birth. Other children develop myasthenia gravis indistinguishable from adults. Myasthenia gravis in juveniles is common.

Myasthenia gravis is not directly inherited nor is it contagious. Occasionally, the disease may occur in more than one member of the same family.

Rarely, children may show signs of congenital myasthenia or congenital myasthenic syndrome. These are not autoimmune disorders, but are caused by defective genes that produce proteins in the acetylcholine receptor or in acetylcholinesterase.

How is myasthenia gravis diagnosed?

Unfortunately, a delay in diagnosis of one or two years is not unusual in cases of myasthenia gravis. Because weakness is a common symptom of many other disorders, the diagnosis is often missed in people who experience mild weakness or in those individuals whose weakness is restricted to only a few muscles.

The first steps of diagnosing myasthenia gravis include a review of the individual’s medical history, and physical and neurological examinations. The signs a physician must look for are impairment of eye movements or muscle weakness without any changes in the individual’s ability to feel things. If the doctor suspects myasthenia gravis, several tests are available to confirm the diagnosis.

A special blood test can detect the presence of immune molecules or acetylcholine receptor antibodies. Most patients with myasthenia gravis have abnormally elevated levels of these antibodies. However, antibodies may not be detected in patients with only ocular forms of the disease.

Another test is called the edrophonium test. This approach requires the intravenous administration of edrophonium chloride or Tensilon(r), a drug that blocks the degradation (breakdown) of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction. In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness. Other methods to confirm the diagnosis include a version of nerve conduction study which tests for specific muscle “fatigue” by repetitive nerve stimulation. This test records weakening muscle responses when the nerves are repetitively stimulated. Repetitive stimulation of a nerve during a nerve conduction study may demonstrate decrements of the muscle action potential due to impaired nerve-to-muscle transmission.

A different test called single fiber electromyography (EMG), in which single muscle fibers are stimulated by electrical impulses, can also detect impaired nerve-to-muscle transmission. EMG measures the electrical potential of muscle cells. Muscle fibers in myasthenia gravis, as well as other neuromuscular disorders, do not respond as well to repeated electrical stimulation compared to muscles from normal individuals. Computed tomography (CT) may be used to identify an abnormal thymus gland or the presence of a thymoma.

A special examination called pulmonary function testing – which measures breathing strength – helps to predict whether respiration may fail and lead to a myasthenic crisis.

What is leprosy?

Leprosy is a disease caused by the bacteria Mycobacterium leprae, which causes damage to the skin and the peripheral nervous system. The disease develops slowly (from six months to 40 years!) and results in skin lesions and deformities, most often affecting the cooler places on the body (for example, eyes, nose, earlobes, hands, feet, and testicles). The skin lesions and deformities can be very disfiguring and are the reason that infected individuals historically were considered outcasts in many cultures. Although human-to-human transmission is the primary source of infection, three other species can carry and (rarely) transfer M. leprae to humans: chimpanzees, mangabey monkeys, and nine-banded armadillos. The disease is termed a chronic granulomatous disease, similar to tuberculosis, because it produces inflammatory nodules (granulomas) in the skin and nerves over time.

What is the history of leprosy (Hansen’s disease)?

Unfortunately, the history of leprosy and its interaction with man is one of suffering and misunderstanding. The newest research suggests that at least as early as 4000 B.C. individuals had been infected with M. leprae, while the first known written reference to the disease was found on Egyptian papyrus in about 1550 B.C. The disease was well recognized in ancient China, Egypt, and India, and there are several references to the disease in the Bible. Because the disease was poorly understood, very disfiguring, slow to show symptoms, and had no known treatment, many cultures thought the disease was a curse or punishment from the gods. Consequently, leprosy was left to be “treated” by priests or holy men, not physicians.

Picture of a person with leprosy (Hansen’s disease)

Since the disease often appeared in family members, some people thought it was hereditary; other people noted that if there was little or no contact with infected individuals, the disease did not infect others. Consequently, some cultures considered infected people (and occasionally their close relatives) as “unclean” or as “lepers” and ruled they could not associate with uninfected people. Often infected people had to wear special clothing and ring bells so uninfected people could avoid them.

The Romans and the Crusaders brought the disease to Europe, and the Europeans brought it to the Americas. In 1873, Dr. Hansen discovered bacteria in leprosy lesions, suggesting leprosy was an infectious disease, not a hereditary disease or a punishment from the gods. However, patients with the disease were still ostracized by many societies and cared for only at missions by religious personnel. Patients with leprosy were encouraged or forced to live in seclusion up to the 1940s, even in the U.S. (for example, the leper colony on Molokai, Hawaii, and at Carville, La.), often because no effective treatments were available.

Because of Hansen’s discovery of M. leprae, efforts were made to find treatments that would stop or eliminate M. leprae; in the early 1900s to about 1940, oil from Chaulmoogra nuts was used with questionable efficacy by injecting it into patients’ skin. At Carville in 1941, promin, a sulfone drug, showed efficacy but required many painful injections. Dapsone pills were found to be effective in the 1950s, but soon (1960s-1970s), M. lepraedeveloped resistance to dapsone. Fortunately, drug trials on the island of Malta in the 1970s showed that a three-drug combination (dapsone,rifampicin [Rifadin], and clofazimine [Lamprene]) was very effective in killingM. leprae. This multi-drug treatment (MDT) was recommended by the WHO in 1981 and remains, with minor changes, the therapy of choice. MDT, however, does not alter the damage done to an individual by M. lepraebefore MDT is started.

Currently, there are several areas (India, East Timor) of the world where the WHO and other agencies (for example, the Leprosy Mission) are working to decrease the number of clinical cases of leprosy and other diseases such asrabies and schistosomiasis that occur in remote regions. Although researchers hope to eliminate leprosy like smallpox, endemic (meaning prevalent or embedded in a region) leprosy makes complete eradication unlikely. In the U.S., leprosy has occurred infrequently but is considered endemic in Texas, Louisiana, Hawaii, and the U.S. Virgin Islands by some investigators.

Leprosy is often termed “Hansen’s disease” by many clinicians in an attempt to have patients forgo the stigmas attached to being diagnosed with leprosy.

What causes leprosy?

Leprosy is caused mainly by Mycobacterium leprae, a rod-shaped bacillus that is an obligate intracellular (only grows inside of certain human and animal cells) bacterium.M. leprae is termed an “acid fast” bacterium because of its chemical characteristics. When special stains are used for microscopic analysis, it stains red on a blue background due to mycolic acid content in its cell walls. The Ziehl-Neelsen stain is an example of the special staining techniques used to view the acid-fast organisms under the microscope.

Currently, the organisms cannot be cultured on artificial media. The bacteria take an extremely long time to reproduce inside of cells (about 12-14 days as compared to minutes to hours for most bacteria). The bacteria grow best at 80.9 F-86 F, so cooler areas of the body tend to develop the infection. The bacteria grow very well in the body’s macrophages and Schwann cells (cells that cover and protect nerve axons). M. leprae is genetically related to M. tuberculosis (the type of bacteria that cause tuberculosis) and other mycobacteria that infect humans. As with malaria, patients with leprosy produce anti-endothelial antibodies (antibodies against the lining tissues of blood vessels), but the role of these antibodies in these diseases is still under investigation.

In 2009, investigators discovered a new Mycobacterium species, M. lepromatosis, which causes diffuse disease (lepromatous leprosy). This new species (determined by genetic analysis) was found in patients located in Mexico and the Caribbean islands.

What are leprosy symptoms and signs?

Unfortunately, the early signs and symptoms of leprosy are very subtle and occur slowly (usually over years). The symptoms are similar to those that may occur with syphilis, tetanus, and leptospirosis. Numbness and loss of temperature sensation (cannot sense very hot or cold temperatures) are some of the first symptoms that patients experience. As the disease progresses, the sensations of touch, then pain, and eventually deep pressure are decreased or lost. Signs that occur, such as relatively painless ulcers, skin lesions of hypopigmented macules (flat, pale areas of skin), and eye damage (dryness, reduced blinking) are experienced before the large ulcerations, loss of digits, and facial disfigurement develop. This long-term developing sequence of events begins and continues on the cooler areas of the body (for example, hands, feet, face, and knees).

Are there different forms (classifications) of leprosy?

There are multiple forms of leprosy described in the literature. The forms of leprosy are based on the person’s immune response toM. leprae. A good immune response can produce the so-called tuberculoid form of the disease, with limited skin lesions and some asymmetric nerve involvement. A poor immune response can result in the lepromatous form, characterized by extensive skin and symmetric nerve involvement. Some patients may have aspects of both forms. Currently, two classification systems exist in the medical literature: the WHO system and the Ridley-Jopling system. The Ridley-Jopling system is composed of six forms or classifications, listed below according to increasing severity of symptoms:

• Indeterminate leprosy: a few hypopigmented macules; can heal spontaneously, persists or advances to other forms

• Tuberculoid leprosy: a few hypopigmented macules, some are large and some become anesthetic (lose pain sensation); some neural involvement in which nerves become enlarged; spontaneous resolution in a few years, persists or advances to other forms

• Borderline tuberculoid leprosy: lesions like tuberculoid leprosy but smaller and more numerous with less nerve enlargement; this form may persist, revert to tuberculoid leprosy, or advance to other forms

• Mid-borderline leprosy: many reddish plaques that are asymmetrically distributed, moderately anesthetic, with regional adenopathy (swollen lymph nodes); the form may persist, regress to another form, or progress

• Borderline lepromatous leprosy: many skin lesions with macules (flat lesions) papules (raised bumps), plaques, and nodules, sometimes with or without anesthesia; the form may persist, regress or progress to lepromatous leprosy

• Lepromatous leprosy: Early lesions are pale macules (flat areas) that are diffuse and symmetric; later many M. leprae organisms can be found in them. Alopecia (hair loss) occurs; often patients have no eyebrows or eyelashes. As the disease progresses, nerve involvement leads to anesthetic areas and limb weakness; progression leads toaseptic necrosis (tissue death from lack of blood to area), lepromas (skin nodules), and disfigurement of many areas including the face. The lepromatous form does not regress to the other less severe forms. Histoid leprosy is a clinical variant of lepromatous leprosy that presents with clusters of histiocytes (a type of cell involved in the inflammatory response) and a grenz zone (an area of collagen separating the lesion from normal tissue) seen in microscopic tissue sections.

The Ridley-Jopling classification is used globally in evaluating patients in clinical studies. However, the WHO classification system is more widely used; it has only two forms or classifications of leprosy. The 2009 WHO classifications are simply based on the number of skin lesions as follows:

• Paucibacillary leprosy: skin lesions with no bacilli (M. leprae) seen in a skin smear

• Multibacillary leprosy: skin lesions with bacilli (M. leprae) seen in a skin smear

However, the WHO further modifies these two classifications with clinical criteria because “of the non-availability or non-dependability of the skin-smear services. The clinical system of classification for the purpose of treatment includes the use of number of skin lesions and nerves involved as the basis for grouping leprosy patients into multibacillary (MB) and paucibacillary (PB) leprosy.” Investigators state that up to about four to five skin lesions constitutes paucibacillary leprosy, while about five or more constitutes multibacillary leprosy.

Multidrug therapy (MDT) with three antibiotics (dapsone, rifampicin, and clofazimine) is used for multibacillary leprosy, while a modified MDT with two antibiotics (dapsone and rifampicin) is recommended for paucibacillary leprosy and composes most current treatments today (see treatment section below). Paucibacillary leprosy usually includes indeterminate, tuberculoid, and borderline tuberculoid leprosy from the Ridley-Jopling classification, while multibacillary leprosy usually includes the double (mid-) borderline, borderline lepromatous, and lepromatous leprosy.

How is leprosy transmitted?

Researchers suggest that M. leprae are spread person to person by nasal secretions or droplets. They speculate that infected droplets reach other peoples’ nasal passages and begin the infection there. Some investigators suggest the infected droplets can infect others by entering breaks in the skin. M. leprae apparently cannot infect intact skin. Rarely, humans get leprosy from the few animal species mentioned above. Occurrence in animals makes it difficult to eradicate leprosy from these endemic sources. Routes of transmission are still being researched for leprosy. Recent genetic studies have demonstrated that several genes (about seven) are associated with an increased susceptibility to leprosy; some researchers now conclude that susceptibility to leprosy may be partially inheritable.

How is leprosy diagnosed?

The majority of cases of leprosy are diagnosed by clinical findings, especially since most current cases are diagnosed in areas that have limited or no laboratory equipment available. Hypopigmented patches of skin or reddish skin patches with loss of sensation, thickened peripheral nerves, or both clinical findings together often comprise the clinical diagnosis. Skin smears or biopsy material that show acid-fast bacilli with the Ziehl-Neelsen stain or the Fite stain (biopsy) can diagnose multibacillary leprosy, or if bacteria are absent, diagnose paucibacillary leprosy. Other tests can be done, but most of these are done by specialized labs and may help a clinician to place the patient in the more detailed Ridley-Jopling classification and are not routinely done (lepromin test, phenolic glycolipid-1 test, PCR, lymphocyte migration inhibition test or LMIT). Other tests such as CBC test,liver function tests, creatinine test, or a nerve biopsy may be done to help determine if other organ systems have been affected.

What is the treatment for leprosy?

The majority of cases (mainly clinically diagnosed) are treated with antibiotics. The recommended antibiotics, their dosages, and length of time of administration are based on the form or classification of the disease and whether or not the patient is supervised by a medical professional. In general, paucibacillary leprosy is treated with two antibiotics, dapsone and rifampicin, while multibacillary leprosy is treated with the same two plus a third antibiotic, clofazimine. Usually, the antibiotics are given for at least six to 12 months or more.

Antibiotics can treat paucibacillary leprosy with little or no residual effects on the patient. Multibacillary leprosy can be kept from advancing, and living M. leprae can be essentially eliminated from the person by antibiotics, but the damage done before antibiotics are administered is usually not reversible. Recently, the WHO suggested that single-dose treatment of patients with only one skin lesion with rifampicin, minocycline (Minocin), or ofloxacin (Floxin) is effective. Studies of other antibiotics are ongoing. Each patient, depending on the above criteria, has a schedule for their individual treatment, so treatment schedules should be planned by a clinician knowledgeable about that patient’s initial diagnostic classification.

The role for surgery in the treatment of leprosy occurs after medical treatment (antibiotics) has been completed with negative skin smears (no detectable acid-fast bacilli) and is often only needed in advanced cases. Surgery is individualized for each patient with the goal to attempt cosmetic improvements and, if possible, to restore limb function and some neural functions that were lost to the disease.

How is leprosy prevented?

Prevention of contact with droplets from nasal and other secretions from patients with untreated M. leprae infection currently is a way recommended to avoid the disease. Treatment of patients with appropriate antibiotics stops the person from spreading the disease. People who live with individuals who have untreated leprosy are about eight times as likely to develop the disease, because investigators speculate that family members have close proximity to infectious droplets. Leprosy is not hereditary, but recent findings suggest susceptibility to the disease may have a genetic basis.

Many people get exposed to leprosy throughout the world, but the disease in not highly contagious; researchers suggest that over 95% of exposures result in no disease, and further studies suggest that susceptibility may be based,  in part, by a person’s genetic makeup. In the U.S., there are about 200-300 new cases diagnosed per year, with most coming from exposures during foreign travel. The majority of worldwide cases are found in the tropics or subtropics (for example, Brazil, India, and Indonesia). The WHO reports about 500,000 to 700,000 new cases per year worldwide, with curing of about 14 million cases since 1985.

There is no commercially available vaccine available to prevent leprosy. However, there are reports of using BCG vaccine, the BCG vaccine along with heat-killed M. leprae organisms, and other preparations that may be protective or help to clear the infection or to shorten treatment. Except for BCG in some countries, these preparations are not readily available.

Animals (chimpanzees, mangabey monkeys, and nine-banded armadillos) rarely transfer M. leprae to humans; nonetheless, handling such animals in the wild is not advised. These animals are a source for endemic infections.

What is Gilbert syndrome?

Gilbert Syndrome is a common, harmless genetic condition in which a liverenzyme essential to the disposal of bilirubin (the chemical that results from the normal breakdown of hemoglobin from red blood cells) is abnormal. The condition has also been referred to as constitutional hepatic dysfunction and familial nonhemolytic jaundice. The enzyme abnormality in Gilbert syndrome results in mild elevations of bilirubin in the blood, particularly after starvation or dehydration.

What causes Gilbert syndrome?

Gilbert syndrome is the result of a genetic mutation in the promoter region of a gene for the enzyme UGT1A (one of the enzymes called UGT glucuronosyltransferases that are important for bilirubin metabolism). The gene is located on chromosome 2. Other types of mutations in the same gene cause the Crigler-Najjar syndrome, which is a more severe and dangerous form of hyperbilirubinemia (high bilirubin in the blood).

People with two copies of the abnormal promoter region for the UGT1A gene (one inherited from each parent) have Gilbert’s syndrome and elevated bilirubin levels, suggesting an autosomal recessive mode of inheritance. This means that both parents require the gene for expression of the abnormality in the offspring.

Gilbert syndrome is a frequent finding in people in the United States and Europe. The condition is usually detected serendipitously (purely by accident) in the course of routine blood screening.

What are the symptoms of Gilbert syndrome?

The elevated bilirubin pigment can sometimes cause mild yellowing (jaundice) of the eyes. People with Gilbert syndrome are otherwise entirely normal with no other signs or symptoms. Their liver enzyme levels in blood serum are also entirely normal.

Gilbert syndrome is most commonly diagnosed after puberty, when alterations in sex hormone levels cause the blood bilirubin levels to rise. Situations that aggravate elevated blood bilirubin levels (such as fasting, destruction of red blood cells, or illnesses) may be the initial factors that cause the patient to seek medical attention.

What is the treatment for Gilbert syndrome?

There is no need for treatment, and the prognosis (outlook) is excellent.

What is Peyronie’s disease?

Peyronie’s disease is characterized by a plaque, or hard lump, that forms within the penis. The plaque, a flat plate of scar tissue, develops on the top or bottom side of the penis inside a thick membrane called the tunica albuginea, which envelopes the erectile tissues. The plaque begins as a localized inflammation and develops into a hardened scar. This plaque has no relationship to the plaque that can develop in arteries.

What are the symptoms of Peyronie’s disease?

Cases of Peyronie’s disease range from mild to severe. Symptoms may develop slowly or appear overnight. In severe cases, the hardened plaque reduces flexibility, causing pain and forcing the penis to bend or arc during erection. In many cases, the pain decreases over time, but the bend in the penis may remain a problem, making sexual intercourse difficult. The sexual problems that result can disrupt a couple’s physical and emotional relationship and can lower a man’s self-esteem. In a small percentage of men with the milder form of the disease, inflammation may resolve without causing significant pain or permanent bending.

The plaque itself is benign, or noncancerous. It is not a tumor. Peyronie’s disease is not contagious and is not known to be caused by any transmittable disease.

What causes Peyronie’s disease?

A plaque on the topside of the shaft, which is most common, causes the penis to bend upward; a plaque on the underside causes it to bend downward. In some cases, the plaque develops on both top and bottom, leading to indentation and shortening of the penis. At times, pain, bending, and emotional distress prohibit sexual intercourse.

ABOVE: A cross-section of the penis (left) displays the internal cavity that runs the length of the penis and is divided into two chambers – corpora cavernosa – by a vertical connecting tissue known as a septum. Scientists theorize that, during trauma such as bending, bleeding might occur at a point of attachment of the septum to the tunica albuginea lining the chamber wall (center). The bleeding results in a hard scar, or plaque, which is characteristic of Peyronie’s disease. The plaque reduces flexibility on one side of the penis during erection, leading to curvature (right).

Estimates of the prevalence of Peyronie’s disease range from less than 1 percent to 23 percent.¹ A recent study in Germany found Peyronie’s disease in 3.2 percent of men between 30 and 80 years of age.² Although the disease occurs mostly in middle age, younger and older men can develop it. About 30 percent of men with Peyronie’s disease develop hardened tissue on other parts of the body, such as the hand or foot. A common example is a condition known as Dupuytren’s contracture of the hand. In some cases, Peyronie’s disease runs in families, which suggests that genetic factors might make a man vulnerable to the disease.

A French surgeon, François de la Peyronie, first described Peyronie’s disease in 1743. The problem was noted in print as early as 1687. Early writers classified it as a form of impotence, now called erectile dysfunction(ED). Peyronie’s disease can be associated with ED – the inability to achieve or sustain an erection firm enough for intercourse.

However, experts now recognize ED as only one factor associated with the disease – a factor that is not always present.

How does Peyronie’s disease develop?

Many researchers believe the plaque of Peyronie’s disease develops following trauma, such as hitting or bending, that causes localized bleeding inside the penis. Two chambers known as the corpora cavernosa run the length of the penis. A connecting tissue, called a septum, runs between the two chambers and attaches at the top and bottom of the tunica albuginea.

If the penis is bumped or bent, an area where the septum attaches to the tunica albuginea may stretch beyond a limit, injuring the tunica albuginea and rupturing small blood vessels. As a result of aging, diminished elasticity near the point of attachment of the septum might increase the chances of injury. In addition, the septum can also be damaged and form tough, fibrous tissue, called fibrosis.

The tunica albuginea has many layers, and little blood flows through those layers. Therefore, the inflammation can be trapped between the layers for many months. During that time, the inflammatory cells may release substances that cause excessive fibrosis and reduce elasticity. This chronic process eventually forms a plaque with excessive amounts of scar tissue and causes calcification, loss of elasticity in spots, and penile deformity.

While trauma might explain some cases of Peyronie’s disease, it does not explain why most cases develop slowly and with no apparent traumatic event. It also does not explain why some cases resolve or why similar conditions such as Dupuytren’s contracture do not seem to result from severe trauma.

Some researchers theorize that Peyronie’s disease may be an autoimmune disorder.

How is Peyronie’s disease evaluated?

Doctors can usually diagnose Peyronie’s disease based on a physical examination. The plaque can be felt when the penis is limp. Full evaluation, however, may require examination during erection to determine the severity of the deformity. The erection may be induced by injecting medicine into the penis or through self-stimulation. Some patients may eliminate the need to induce an erection in the doctor’s office by taking a digital or Polaroid picture at home. The examination may include an ultrasound scan of the penis to pinpoint the location(s) and calcification of the plaque. The ultrasound can also be used to evaluate blood flow into and out of the penis if there is a concern about erectile dysfunction.

How is Peyronie’s disease treated?

Men with Peyronie’s disease usually seek medical attention because of painful erections, penile deformity, or difficulty with intercourse. Because the cause of Peyronie’s disease and its development are not well understood, doctors treat the disease empirically; that is, they prescribe and continue methods that seem to help. The goal of therapy is to restore and maintain the ability to have intercourse. Providing education about the disease and its course often is all that is required. No strong evidence shows that any treatment other than surgery is universally effective. Experts usually recommend surgery only in long-term cases in which the disease is stabilized and the deformity prevents intercourse.

Because the course of Peyronie’s disease is different in each patient and because some patients experience improvement without treatment, medical experts suggest waiting 1 year or longer before having surgery. During that wait, patients often are willing to undergo treatments whose effectiveness has not been proven.

Medical Treatments

Researchers conducted small-scale studies in which men with Peyronie’s disease who were given vitamin E orally reported improvements. Yet, no controlled studies have established the effectiveness of vitamin E therapy. Similar inconclusive success has been attributed to aminobenzoate potassium (Potaba). Other oral medications that have been used includecolchicine, tamoxifen, and pentoxifylline. Again, no controlled studies have been conducted on these medications.

Researchers have also tried injecting chemical agents such as verapamil, collagenase, steroids, and interferon alpha-2b directly into the plaques. Verapamil and interferon alpha-2b seem to diminish curvature of the penis. The other injectable agent, collagenase, is undergoing clinical trial and results are not yet available. Steroids, such as cortisone, have produced unwanted side effects, such as the atrophy or death of healthy tissues. Another intervention involves iontophoresis, the use of a painless current of electricity to deliver verapamil or some other agent under the skin into the plaque.

Radiation therapy, in which high-energy rays are aimed at the plaque, has also been used. Like some of the chemical treatments, radiation appears to reduce pain, but it has no effect on the plaque itself and can cause unwelcome side effects such as erectile dysfunction. Although the variety of agents and methods used points to the lack of a proven treatment, new insights into the wound healing process may one day yield more effective therapies.

Surgery

Three surgical procedures for Peyronie’s disease have had some success. One procedure involves removing or cutting of the plaque and attaching a patch of skin, vein, or material made from animal organs. This method may straighten the penis and restore some lost length from Peyronie’s disease. However, some patients may experience numbness of the penis and loss of erectile function.

A second procedure, called plication, involves removing or pinching a piece of the tunica albuginea from the side of the penis opposite the plaque, which cancels out the bending effect. This method is less likely to cause numbness or erectile dysfunction, but it cannot restore length or girth of the penis.

A third surgical option is to implant a device that increases rigidity of the penis. In some cases, an implant alone will straighten the penis adequately. If the implant alone does not straighten the penis, implantation is combined with one of the other two surgical procedures.

Most types of surgery produce positive results. But because complications can occur, and because many of the effects of Peyronie’s disease – for example, shortening of the penis – are not usually corrected by surgery, most doctors prefer to perform surgery only on the small number of men with curvature severe enough to prevent sexual intercourse….

Vertigo introduction

Balance is defined as a state of equilibrium. It takes significant amount of work for this to occur in the body. The brain uses inputs from many sources to understand where the body is located in relationship to the world and to allow it to function. Sensory information from the eyes, ears, and position receptors in the rest of the body help keep the body upright and allow it to move in a coordinated fashion.

Information comes to cerebellar lobes located in the base of the brain from the vestibular system in the inner ear, vision from the eyes, and proprioception (position) receptors located throughout the body that send signals through the spinal cord. The cerebellum uses that information to maintain posture, coordinate body motions like walking and also coordinate fine motor skills like using a pen to write.

Vertigo, a feeling of spinning movement and sometimes accompanied bynausea and vomiting, occurs when any part of the system breaks down. However, people tend not to use that word to describe their symptoms but instead use the word dizziness or lightheadedness. It is up to the health care practitioner to understand the person’s symptoms and define vertigo as the cause of the their situation.

Dizziness is a difficult word to understand and needs to be divided into two categories, either lightheadedness or vertigo. Lightheadedness is the feeling that a person might faint while vertigo is most often described as a spinning sensation with loss of balance. The direction of care is markedly different since lightheadedness may suggest to the health care practitioner to investigate decreased oxygen or nutrient supply to the brain due a variety of causes including heart rhythm disturbances or dehydration, while vertigo sends the health care practitioner looking for a neurologic or inner ear cause.

The most important initial step in helping a person with vertigo is to take a history and understand that the person is complaining of spinning symptoms that may be associated with nausea and vomiting and loss of balance among other symptoms.

What is vertigo?

Vertigo is an abnormal sensation that is described by the person as a feeling they are spinning or that the world is spinning around them. It is most often associated with an inner ear problem.

The inner ear has two parts, the semicircular canals and the vestibule, that helps the body know where it is in relationship to gravity. There are three semicircular canals that are aligned at right angles to each other and act as the gyroscope for the body. The canals are filled with fluid and are lined with a nerve filled, crystal encrusted membrane that transmits information to the cerebellum, the part of the brain that deals with balance and coordination. The cerebellum adds information from sight and from nerve endings in muscles that deal with proprioception, the perception of movement, to help the brain know where it is in relationship to gravity and the world.

Normally, when the head moves, fluid in the semicircular canals shifts and that information is relayed to the brain. When the head stops moving, the fluid stops as well. There may be a slight delay and is the basis for the vertigo experienced after people participate in many children’s games and carnival rides. When a person goes on a merry-go-round or spins quickly around in circles, the fluid in the canals develops momentum and even though the head stops spinning, the fluid may continue to move. This causes vertigo or a spinning sensation and may cause the person to fall or stumble in a crooked line. It also may be associated with vomiting.

In patients with vertigo, inflammation of the fluid or irritation of the crystals on the nerve membrane that lines the walls of the semicircular canals may cause the spinning sensation even without much head movement. Often, only one canal is involved and the person may be symptom free if they don’t move.

What are the causes of vertigo?

While there are many causes of vertigo, the major distinction is between central causes of vertigo and peripheral causes. Central causes occur because of an abnormality in the cerebellum of the brain.

Distinguishing between central and peripheral causes for disease is an important concept in evaluating neurologic problems. The brain and spinal cord make up the central nervous system while the peripheral nervous system describes the nerves outside the central area. Sometimes it is easy to make the distinction, other times it is more difficult to distinguish between central and peripheral causes. For example, if a person hits their funny bone (elbow) and develops pain and numbness in their hand, it is mainly due to a direct blow to the ulnar nerve at the elbow. This is a peripheral nerve problem and most people would not seek medical care. If however, a person’s leg became numb and weak, the cause may be central (perhaps a stroke in the brain) or there may be a peripheral cause (sciaticaor nerve impingement).

Our orientation in space and, therefore, our balance or equilibrium, is primarily measured by three sensory systems:

1. The eye (visual) system
2. The balance (vestibular) system of the inner ear
3. The general sensory system including motion, pressure, and position (proprioception) sensors in joints, muscles, and skin.

These three systems continuously feed information to the brainstem and brain about our position in space relative to gravity and the world. The brainstem connects the brain to the spinal cord. The brain, in turn, processes these data and uses the information to make adjustments of our head, body, joints, and eyes. When all three sensory systems and the brain are properly functioning, the final result is a healthy balance system.

Visual input shows the brain where it is in space, what direction it is facing, what direction it is moving, and whether it is turning or standing still. Simple tasks like walking and picking up an object are much easier if we can see our surroundings. Feeling seasick is a problem resulting from a miscommunication between a healthy visual system and a healthy inner ear (vestibular) system. In this circumstance, the ears are telling the brain that there is movement, while the eyes may be seeing the fixed surroundings of the cabin. Changes in visual acuity, glaucoma, and cataracts are examples of visual problems that in some individuals may be enough to give them a balance disorder.

Vestibular system

The inner ear, or labyrinth, is located deep to the outer ear and middle ear, and is encased within petrous portion of the temporal bone of the skull.

Figure 1. Diagram of outer, middle, and inner ear. The outer ear is labeled in the figure and includes the ear canal. The middle ear includes the eardrum (tympanic membrane) and three tiny bones for hearing. The bones are called the hammer (malleus), anvil (incus), and stirrup (stapes) to reflect their shapes. The middle ear connects to the back of the throat by the Eustachian tube. The inner ear (labyrinth) contains the semicircular canals and vestibule for balance, and the cochlea for hearing.

The vestibular structures of the inner ear are the vestibule (which is made up of the utricle and saccule) and the three semicircular canals. These structures work somewhat like a carpenter’s level (a tool used to show how “level” a horizontal or vertical surface is) or a gyroscope. Information is sent by way of the vestibulocochlear nerve to the cerebellum of the brain, the part that processes information regarding body balance and position. The rest of the inner ear, the cochlea, is concerned with hearing.

The vestibular system measures linear and rotational movement. A number of disorders can cause this system to stop working or provide inappropriate information. These disorders include Meniere’s syndrome, labyrinthitis, benign paroxysmal positional vertigo, ear infections, tumors, or trauma.

Peripheral sensory system

The sensory system consists of motion, position, and pressure sensors in the skin, muscles, and joints. These sensors provide important touch and position information to keep us balanced. For example, if someone pushes you from behind, a slight increase will occur in the activity of the pressure sensors in the ball of the feet. As these sensors note the increased pressure, the brain is notified, and it knows from experience that the body is being pushed forward. The brain then uses this information to tell the body to shift a small amount of weight backward to prevent the body from toppling forward.

Brain

The brain processes the information from the three sensory systems. Any problem that interferes with the proper functioning of the central nervous system (CNS) can lead to a balance disorder. Unlike the problems associated with the three sensory input systems discussed above, however, with CNS problems, it is unusual to have vertigo as the only symptom. The most common causes of vertigo are peripheral and involve the inner ear or labyrinth.

Some of the most common causes of vertigo are listed below:

• Benign paroxysmal positional vertigo (BPPV) may be caused when the crystals in the inner ear become dislodged and irritate the semicircular canals. Often the cause is not found but there may be an association with unusual positioning or movement of the head. It is most frequently seen in people older than 60.
• Labyrinthitis may follow a viral infection which causes inflammation within the middle ear.
• Meniere’s disease is a group of symptoms associated with vertigo, hearing loss and tinnitus or ringing in the ears.
• Acoustic neuroma is a benign tumor of the ear that can present with vertigo.
• Inner ear trauma may be due to a variety of mechanisms. A basilar skull fracture may damage the labyrinth system directly or aconcussion, where that area of the skull is shaken and may dislodge some of the inner ear crystals causing symptoms of vertigo.
• The inner ear may also be affected by barotrauma, a condition where pressure changes may be the causes of damage and vertigo. This type of injury is seen when an individual dives into water and the air in the external ear canal is compressed and damages the ear drum, middle, and inner ear. Barotrauma may also occur as a consequence of diving where an increase of air pressure within the middle and inner ear can cause structures to rupture. This may cause loss of hearing if the tympanic membrane ruptures or it may cause vertigo if the round and oval windows in the inner ear are damaged.
• Central causes of vertigo that arise in the brain are much less common. Strokes, tumors, seizures, and multiple sclerosis may be associated with vertigo.
• Vestibular migraines describe migraine headaches associated with vertigo and are a common cause of balance disorders. Migraine is a blood vessel (vascular) disease characterized by periodic, usually one-sided, headaches. These headaches are often preceded for a variable time by associated neurological symptoms, called the aura. Vertigo may occur in individuals with migraine as part of the migraine aura or separately. In younger patients, the vertigo may predate the onset of headaches entirely. A family history of migraine is very common and may be a clue that a balance disorder may be migraine related.

What are the symptoms of vertigo?

While individuals may use the word dizziness, vertigo symptoms are described by the feeling that either the world is spinning around the person or that the person themselves is spinning. This is the same type of sensation that happens when a person quickly steps off a merry-go-round or when they twirl themselves and then quickly stop. The feeling of spinning may be associated with loss of balance to the point that the person walks unsteadily or falls down. The individual or family member may describe the person walking as if they were drunk. Vertigo itself is a symptom or indicator of an underlying balance problem, either involving the labyrinth of the inner ear or the cerebellum of the brain.

If other structures of the ear are involved, associated symptoms may include decreased hearing and ringing in the ear (tinnitus).

If there are issues with the cerebellum, the person may also complain of difficulty with coordination.

Nausea and vomiting are often associated symptoms with vertigo. Frequently, the more intense the vertigo, the more intense the nausea and vomiting become. These symptoms may be so severe that the individual becomes dehydrated and weak.

How is vertigo diagnosed?

Vertigo is diagnosed by history and physical examination. It is important to confirm the symptom before proceeding to the cause. The key begins with the health care practitioner understanding the patient’s complaint and proceeding from there. Questions may be asked in regard to what makes the vertigo worse, what makes the spinning better, and whether there are other associated signs including loss of hearing, tinnitus (ringing in the ear), and nausea and vomiting. Past medical history and medication use may offer clues as to the cause.

Physical examination is helpful in confirming the presence of nystagmus, the abnormal eye motion that the body uses to try to compensate for the abnormal balance signals coming to the brain. A full neurologic exam may be done to make certain that the cause of vertigo is peripheral and due to inner ear issues rather than central problems with the brain. Testing for balance and coordination may help decide if the cerebellum is working properly.

Hearing tests may be appropriate to make certain that the middle ear, the cochlea, and the auditory nerve are functioning properly and it is only the labyrinth that is the cause of vertigo.

The Dix-Hallpike test can be performed by the health care practitioner and help with the diagnosis. By moving the head in different directions, eye movements can be assessed and see whether they correlate with the vertigo symptoms.

If there is concern that there is a central brain problem may be the cause of vertigo, CT or MRI imaging of the brain may be considered. Screening blood tests may also be done.

Specialist consultation with a neurologist or otolaryngologist (ear, nose and throat specialist) may be considered to help with the diagnosis and treatment. Physical therapists specially trained in vestibular rehabilitation may be helpful, not only in making the diagnosis, but also in treating peripheral causes like benign paroxysmal positional vertigo or labyrinthitis.

What is the treatment for vertigo?

While some vertigo is self limited and may be treated with medications, vertigo from BPPV or labyrinthitis is often treated with physical therapy. Using Epley maneuvers, the head is taken through a variety of positions and manipulated to clear debris (crystals) from the semicircular canals and to reduce the inflammation that the debris causes.

Medications like diazepam (Valium) andmeclizine (Antivert) are used to decrease inflammation within the vestibular system.

Some patients are placed in a soft collar to limit range of motion of their heads while the vertigo gradually resolves.

If there is concern that there is a viral infection causing the labyrinthitis or neuritis, antiviral medications likeacyclovir (Zovirax) or valacyclovir (Valtrex) may be considered.

Patients with acoustic neuroma or other structural problems of the ear may require surgery.

Patients with central causes of vertigo need further investigation and treatment will be tailored to their specific underlying diagnosis.

Can I care for vertigo at home, and can vertigo be prevented?

Balance disorders are often unpredictable. Depending on the cause, symptoms may occur at any time, even after long periods of without any symptoms. It is important to be cautious in order to avoid accidents that could be caused by a balance disorder.

People with vertigo symptoms or people that have a tendency to develop vertigo may reduce or eliminate the symptoms by doing the following:

• Change your position slowly, especially when going from a lying or sitting position to a standing position. When you get out of bed, sit on the side of the bed for a few seconds to gain your orientation and allow your circulatory system to adjust.
• When walking, focus on distant objects. Do not look down at your feet. Avoid walking in dark areas or on unstable ground. Falls at home occur when the floor covering changes from carpet to tile or linoleum.
• When riding in a car, try to sit in the front seat. Look out the window at a fixed point. When going around curves, look at a distant object beyond the curve.
• Make certain eye glass and hearing aid prescriptions are current.
• Use a cane, walking stick, or walker for support and to give additional pressure and touch (tactile) orientation.
• Avoid activities that move the head up and down repetitively.
• Try to avoid keeping the head tilted back for long periods of time, for example painting or dusting above your head.
• Be cautious when using medications that may cause balance problems as a side effect.

If a person is having an episode of vertigo, he/she should not drive or operate machinery until their doctor says it is safe to do so. People who are subject to sudden instances of vertigo should also avoid climbing ladders or participate in other situations that may be dangerous to themselves or others (for example, hiking alone or taking care of children), should they suddenly feel an episode of vertigo coming on.