BAHAN 1 (list penyakit)by : MDA.org

Neuromuscular Disease Descriptions

Below is a general overview of the characteristics of the neuromuscular diseases that affect children and teens. The disorders are grouped into six categories.

For more detailed, up-to-date information about a specific disease, visit the Muscular Dystrophy Association’s disease information centers. The centers also include a collection of current news articles and other content on the MDA website relating to each disease.

Muscular dystrophies (involving the structure of the muscle cells)

Becker (BMD) • Age of onset: 2 to 16 yearsCharacteristics: A milder, more slowly progressing form of Duchenne MD (see below).

Congenital (CMD) • Age of onset: birthCharacteristics: Generalized muscle weakness with possible joint deformities. Progresses very slowly.

Possible cognitive effects: Some of the most serious brain effects in neuromuscular diseases are found among people with CMD, although not everyone is affected. Children with structural brain abnormalities and those with seizures are most at risk for a wide range of problems, from learning disabilities, to vision and reading difficulties, to severe mental retardation.

Duchenne (DMD) • Age of onset: 2 to 6 yearsCharacteristics: General muscle weakness and wasting, beginning in upper arms and legs and eventually involving all voluntary muscles. DMD affects mainly boys but in rare cases may affect girls, who have a slower and less severe progression.

Boys in the primary grades may run more slowly, have trouble walking long distances, difficulty climbing stairs and getting up from the floor. By age 10, boys are likely to be using a wheelchair at least part time, and their arms are weakened. Around age 15, the arms, legs and torso all are affected and wheelchair use usually is full time. The student may need help writing and lifting, and may show early signs of respiratory and heart weakness.

Possible cognitive effects: About a third of children with DMD have some degree of learning disability, especially in three areas: attention focusing, verbal learning and memory, and emotional interaction. Sometimes this impairment is mistaken for attention deficit disorder. DMD sometimes causes children to have poor social skills, be emotionally distant and moody, or inappropriately impulsive and lacking good social boundaries.

Emery-Dreifuss (EDMD) • Age of onset: childhood to early teensCharacteristics: Weakness and wasting of shoulder, upper arm and shin muscles. Joint deformities are common, and heart complications can be serious.

Facioscapulohumeral (FSH or FSHD) • Age of onset: childhood to early adulthoodCharacteristics: Childhood onset causes more severe symptoms than adult onset. Weakness and wasting affect face muscles, speech, eyelids, shoulders and upper arms. Progresses slowly with periods of rapid deterioration.

Limb-girdle (LGMD) • Age of onset: childhood to middle ageCharacteristics: Muscle wasting begins in the shoulder and pelvic girdles. Scoliosis and heart-lung problems are common. Progression rate varies. Therapy helps maintain mobility and avoid respiratory illness.

Myotonic (MMD, Steinert disease) • Age of onset: birth to early childhoodCharacteristics: An inability to relax muscles (myotonia), combined with muscle weakness. Affects face, feet, hands and neck first. Progression is slow.

Possible cognitive effects: When MMD appears in infancy or childhood, about 75 percent of children have mental retardation, as well as severe facial weakness and speech abnormalities. Later-onset MMD (adolescence through adulthood) isn’t as closely associated with mental retardation, but may cause teens to be overly sleepy during the day and to lack initiative and seem apathetic.

Medication helps students stay more alert, as does addressing any underlying respiratory or heart problems.

Peripheral motor neuron diseases (involving muscle-controlling nerve cells of the arms, legs, neck, face)

Charcot-Marie-Tooth (CMT) disease • Age of onset: childhood to young adulthoodCharacteristics: Weakness and atrophy of muscles and nerves of the arms from the elbows down and legs from the knees down. May involve foot deformities and some numbness. Ankle sprains are common. About 10 percent of children experience muscle cramping or burning nerve pain. Children may need leg braces, wrist braces and/or surgery, and may use a wheelchair for mobility.

Dejerine-Sottas (DS) disease • Age of onset: infancyCharacteristics: Slow development of early motor skills, leading often to loss of skill. Hands and legs are weak and may have impaired sensation. Severity and progression vary.

Freidreich's ataxia (FA) • Age of onset: 7-13 yearsCharacteristics: Symptoms include shaky movements, lack of coordination, poor balance, slurred speech, muscle weakness and loss of sensation. Severity and progression vary. Often associated with diabetes and heart disease.

Motor neuron diseases (involving nerve cells in the spinal cord)

Infantile progressive spinal muscular atrophy (SMA Type 1) • Age of onset: birth-6 monthsCharacteristics: Generalized muscle weakness, trouble swallowing and sucking, breathingdistress, paralysis of legs and arms. Death often comes in very early childhood, but medical technology is expanding life span

Intermediate SMA (SMA Type 2) (Werdnig-Hoffman disease) • Age of onset: 6 months-3 yearsCharacteristics: Weakness in arms, legs, upper and lower torso, often with skeletal deformities. Lung disease is common. Rapid progression. Survival into early adulthood is common but respiratory problems are a constant threat.

Possible Cognitive Effects: Although not scientifically validated, high intelligence often is noted in people with SMA.

Juvenile SMA (SMA Type 3) (Kugelberg-Welander disease) • Age of onset: 1-15 yearsCharacteristics: A milder form of intermediate SMA, with slower progression. Weakness in leg, hip, shoulder, arm and respiratory muscles. Calf muscles often are enlarged. A wheelchair may not be required in youth.

Spinal-bulbar muscular atrophy (SBMA) (Kennedy disease) • Age of onset: 15-60 yearsCharacteristics: Occurs only in males, causing weakness in limbs and muscles involved in talking, chewing and swallowing. Some males experience breast enlargement. This disease progresses very slowly.

Neuromuscular junction diseases (involving the site where nerves and muscles meet)

Congenital myasthenic syndromes (CMS) (Sometimes diagnosed as myasthenia gravis) Age of onset: infancy to childhoodCharacteristics: Generalized weakness and fatigability of voluntary muscles, including those controlling mobility, eye movement, swallowing and breathing. Rest can help restore strength. Varies in severity and weakness can fluctuate. May be controlled with medication.

Myopathies (involving tone and contraction of muscles controlling voluntary movements; may include inflammation of muscles or related tissues)

Central core disease • Age of onset: birth to infancyCharacteristics: Slow development of motor skills. Hip displacement common.

Dermatomyositis • Age of onset: childhood to age 60Characteristics: Symptoms include skin rashes, muscle pain and tenderness, fever, gastrointestinal distress, and progressive weakness, especially affecting the shoulders, upper arms, hips, thighs and neck muscles. Swelling of the upper eyelids also is common. Hard painful nodules may appear under the skin. Progression and severity vary by individual. Corticosteroid drugs and restricted diet may result in remission.

Hyperthyroid/hypothyroid myopathy • Age of onset: childhood to adulthoodCharacteristics: Weakness in arms and legs. Stiffness and cramps common. Severity depends on success in treating underlying thyroid condition.

Myotonia congenita (Thomsen's disease) • Age of onset: infancy to childhoodCharacteristics: Muscle stiffness and difficulty moving after periods of rest. With exercise, muscle strength and movement may return to normal.

Myotubular myopathy (centronuclear myopathy ) • Age of onset: birth to infancyCharacteristics: Drooping of upper eyelids, facial weakness, foot drop and some weakness of the limbs and trunk. Individuals usually have no reflexes. Slow progression.

Nemaline myopathy (rod body disease) • Age of onset: birth to infancyCharacteristics: Low muscle tone and weakness of arms, legs, trunk, face and throat muscles. Severe cases have respiratory weakness.

Paramyotonia congenita • Age of onset: childhood to early adulthoodCharacteristics: Muscle stiffness and difficulty relaxing muscles, especially after repeated use or exercise.

Polymyositis • Age of onset: childhood to age 60Characteristics: Weakness of neck and throat, shoulder, hip and thigh muscles, and generalized muscle swelling. Swallowing difficulties are common. Severity and progression vary. Corticosteroid drugs may help.

Metabolic diseases of muscle (involving errors in metabolism in producing energy in muscle cells)

Acid maltase deficiency (Pompe disease) • Age of onset: infancy to adulthoodCharacteristics: For infants, the disease is generalized and severe, impairing the heart and liver. Later-onset forms involve weakness of mid-body and respiratory muscles. Progression varies.

Carnitine deficiency • Age of onset: early childhoodCharacteristics: Varied weakness of shoulder, hip, face and neck muscles. Often occurs with other metabolic conditions. Progression varies. Carnitine supplementation can be effective.

Debrancher enzyme deficiency (Cori or Forbes disease) • Age of onset: 1 yearCharacteristics: General muscle weakness, poor muscle control and an enlarged liver with low blood sugar. Slow progression.

Mitochondrial myopathy • Age of onset: early childhood to adulthoodCharacteristics: Severe muscle weakness. Progression and severity vary. In some cases the brain is involved, causing seizures, deafness, loss of balance and vision, and mental retardation. Other systems in the body also can be affected.

Possible cognitive effects: Some children have impaired cognition, especially if they experience seizures, strokes or high levels of lactic acid in the blood. But others have high intelligence, such as the late MDA National Goodwill Ambassador Mattie J.T. Stepanek, who was a New York Times best-selling poet.

Phosphorylase deficiency (McArdle disease)Phosphofructokinase deficiency (Tarui disease)Phosphoglycerate kinase deficiencyPhosphoglycerate mutase deficiencyLactate dehydrogenase deficiencyAge of onset: childhood, adolescence or adulthoodCharacteristics: Children with these disorders may not appear to be impaired until they exert themselves physically, and so often are unfairly thought to be lazy. These metabolic conditions cause a low tolerance for exercise, with symptoms including cramps, muscle pain and weakness, nausea, vomiting, muscle damage and discoloration of the urine (due to muscle breakdown).

Rest usually helps restore strength. Severity varies, increasing with age. Children often are advised to avoid strenuous exercise

BAHAN 2by : NLM, 2014

What are motor neuron diseases?

The motor neuron diseases (MNDs) are a group of progressive neurological disorders that destroy motor neurons, the cells that control essential voluntary muscle activity such as speaking, walking, breathing, and swallowing.  Normally, messages from nerve cells in the brain (called upper motor neurons) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons) and from them to particular muscles.  Upper motor neurons direct the lower motor neurons to produce movements such as walking or chewing.  Lower motor neurons control movement in the arms, legs, chest, face, throat, and tongue. Spinal motor neurons are also called anterior horn cells.  Upper motor neurons are also called corticospinal neurons.

When there are disruptions in the signals between the lowest motor neurons and the muscle, the muscles do not work properly; the muscles gradually weaken and may begin wasting away and develop uncontrollable twitching (calledfasciculations).  When there are disruptions in the signals between the upper motor neurons and the lower motor neurons, the limb muscles develop stiffness (called spasticity), movements become slow and effortful, and tendon reflexes such as knee and ankle jerks become overactive.  Over time, the ability to control voluntary movement can be lost.

Who is at risk?

MNDs occur in adults and children.  In children, particularly in inherited or familial forms of the disease, symptoms can be present at birth or appear before the child learns to walk.  In adults, MNDs occur more commonly in men than in women, with symptoms appearing after age 40.

What causes motor neuron diseases?

Some MNDs are inherited, but the causes of most MNDs are not known.  In sporadic or noninherited MNDs, environmental, toxic, viral, or genetic factors may be implicated.   

How are they classified?

MNDs are classified according to whether they are inherited or sporadic, and to whether degeneration affects upper motor neurons, lower motor

neurons, or both.  In adults, the most common MND is amyotrophic lateral sclerosis (ALS), which affects both upper and lower motor neurons.  It has inherited and sporadic forms and can affect the arms, legs, or facial muscles.  Primary lateral sclerosis is a disease of the upper motor neurons, while progressive muscular atrophy affects only lower motor neurons in the spinal cord.  In progressive bulbar palsy, the lowest motor neurons of the brain stem are most affected, causing slurred speech and difficulty chewing and swallowing.  There are almost always mildly abnormal signs in the arms and legs.

If the MND is inherited, it is also classified according to the mode of inheritance.  Autosomal dominant means that a person needs to inherit only one copy of the defective gene from one affected parent to be at risk of the disease.  There is a 50 percent chance that each child of an affected person will be affected.  Autosomal recessive means the individual must inherit a copy of the defective gene from both parents. These parents are likely to be asymptomatic (without symptoms of the disease).  Autosomal recessive diseases often affect more than one person in the same generation (siblings or cousins).  In X-linked inheritance, the mother carries the defective gene on one of her X chromosomes and passes the disorder along to her sons.  Males inherit an X chromosome from their mother and a Y chromosome from their father, while females inherit an X chromosome from each parent.  Daughters have a 50 percent chance of inheriting their mother's faulty X chromosome and a safe X chromosome from their father, which would make them asymptomatic carriers of the mutation

What are the symptoms of motor neuron diseases?

A brief description of the symptoms of some of the more common MNDs follows.

Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease or classical motor neuron disease, is a progressive, ultimately fatal disorder that disrupts signals to all voluntary muscles.  Many doctors use the terms motor neuron disease and ALS interchangeably.  Both upper and lower motor neurons are affected.  Symptoms are usually noticed first in the arms and hands, legs, or swallowing muscles.  Approximately 75 percent of people with classic ALS will develop weakness and wasting of the bulbar muscles (muscles that control speech, swallowing, and chewing).  Muscle weakness and atrophy occur on both sides of the body. Affected individuals lose strength and the ability to move their arms and legs, and to hold the body upright.  Other symptoms include spasticity, spasms, muscle cramps, and fasciculations.  Speech can become slurred or nasal.  When muscles of the diaphragm and chest wall fail to function properly, individuals lose the ability to breathe without mechanical support.  Although the disease does not usually impair a person's mind or personality, several recent studies suggest that some people with ALS

may develop cognitive problems involving word fluency, decision-making, and memory.  Most individuals with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms.  However, about 10 percent of affected individuals survive for 10 or more years.

ALS most commonly strikes people between 40 and 60 years of age, but younger and older individuals also can develop the disease.  Men are affected more often than women.  Most cases of ALS occur sporadically, and family members of those individuals are not considered to be at increased risk for developing the disease.  Familial forms of ALS account for 10 percent or less of cases of ALS, with more than 10 genes identified to date.  However, most of the gene mutations discovered account for a very small number of cases.  The most common familial forms of ALS in adults are caused by mutations of the superoxide dismutase gene, or SOD1, located on chromosome 21. There are also rare juvenile-onset forms of familial ALS.

Progressive bulbar palsy, also called progressive bulbar atrophy, involves the brain stem—the bulb-shaped region containing lower motor neurons needed for swallowing, speaking, chewing, and other functions. Symptoms include pharyngeal muscle weakness (involved with swallowing), weak jaw and facial muscles, progressive loss of speech, and tongue muscle atrophy.  Limb weakness with both lower and upper motor neuron signs is almost always evident but less prominent.  Individuals are at increased risk of choking and aspiration pneumonia, which is caused by the passage of liquids and food through the vocal folds and into the lower airways and lungs.  Affected persons have outbursts of laughing or crying (called emotional lability).  Stroke and myasthenia gravis may have certain symptoms that are similar to those of progressive bulbar palsy and must be ruled out prior to diagnosing this disorder.  In about 25 percent of individuals with ALS, early symptoms begin with bulbar involvement. Some 75 percent of individuals with classic ALS eventually show some bulbar involvement.  Many clinicians believe that progressive bulbar palsy by itself, without evidence of abnormalities in the arms or legs, is extremely rare.

Pseudobulbar palsy, which shares many symptoms of progressive bulbar palsy, is characterized by degeneration of upper motor neurons that transmit signals to the lower motor neurons in the brain stem.  Affected individuals have progressive loss of the ability to speak, chew, and swallow.  Progressive weakness in facial muscles leads to an expressionless face.  Individuals may develop a gravelly voice and an increased gag reflex.  The tongue may become immobile and unable to protrude from the mouth.  Individuals may have outbursts of laughing or crying.

Primary lateral sclerosis (PLS) affects the upper motor neurons of the arms, legs, and face.  It occurs when specific nerve cells in the motor regions of the cerebral cortex (the thin layer of cells covering the brain which is responsible for most high-level brain functions) gradually

degenerate, causing the movements to be slow and effortful.  The disorder often affects the legs first, followed by the body trunk, arms and hands, and, finally, the bulbar muscles.  Speech may become slowed and slurred.  When affected, the legs and arms become stiff, clumsy, slow and weak, leading to an inability to walk or carry out tasks requiring fine hand coordination.  Difficulty with balance may lead to falls.  Speech may become slow and slurred.  Affected individuals commonly experience pseudobulbar affect and an overactive startle response. PLS is more common in men than in women, with a very gradual onset that generally occurs between ages 40 and 60.  The cause is unknown.  The symptoms progress gradually over years, leading to progressive stiffness and clumsiness of the affected muscles.  PLS is sometimes considered a variant of ALS, but the major difference is the sparing of lower motor neurons, the slow rate of disease progression, and normal lifespan.  PLS may be mistaken for spastic paraplegia, a hereditary disorder of the upper motor neurons that causes spasticity in the legs and usually starts in adolescence.  Most neurologists follow the affected individual's clinical course for at least 3 to 4 years before making a diagnosis of PLS.  The disorder is not fatal but may affect quality of life.  

Progressive muscular atrophy is marked by slow but progressive degeneration of only the lower motor neurons.  It largely affects men, with onset earlier than in other MNDs.  Weakness is typically seen first in the hands and then spreads into the lower body, where it can be severe. Other symptoms may include muscle wasting, clumsy hand movements, fasciculations, and muscle cramps.  The trunk muscles and respiration may become affected.  Exposure to cold can worsen symptoms.  The disease develops into ALS in many instances.

Spinal muscular atrophy (SMA) is a hereditary disease affecting the lower motor neurons.  It is an autosomal recessive disorder caused by defects in the gene SMN1, which makes a protein that is important for the survival of motor neurons (SMN protein).  In SMA, insufficient levels of the SMN protein lead to degeneration of the lower motor neurons, producing weakness and wasting of the skeletal muscles.  This weakness is often more severe in the trunk and upper leg and arm muscles than in muscles of the hands and feet.  SMA in children is classified into three types, based on ages of onset, severity, and progression of symptoms.  All three types are caused by defects in the SMN1 gene.

SMA type I, also called Werdnig-Hoffmann disease, is evident by the time a child is 6 months old.  Symptoms may include hypotonia (severely reduced muscle tone), diminished limb movements, lack of tendon reflexes, fasciculations, tremors, swallowing and feeding difficulties, and impaired breathing.  Some children also develop scoliosis (curvature of the spine) or other skeletal abnormalities.  Affected children never sit or stand and the vast majority usually die of respiratory failure before the age of 2.  However, the survival in individuals with SMA type I has increased in recent years, in relation to the growing trend toward more proactive clinical care.

Symptoms of SMA type II, the intermediate form, usually begin between 6 and 18 months of age.  Children may be able to sit but are unable to stand or walk unaided, and may have respiratory difficulties.  The progression of disease is variable.  Life expectancy is reduced but some individuals live into adolescence or young adulthood.

Symptoms of SMA type III (Kugelberg-Welander disease) appear between 2 and 17 years of age and include abnormal gait; difficulty running, climbing steps, or rising from a chair; and a fine tremor of the fingers. The lower extremities are most often affected.  Complications include scoliosis and joint contractures—chronic shortening of muscles or tendons around joints, caused by abnormal muscle tone and weakness, which prevents the joints from moving freely.  Individuals with SMA type III may be prone to respiratory infections, but with care may have a normal lifespan.

Congenital SMA with arthrogryposis (persistent contracture of joints with fixed abnormal posture of the limb) is a rare disorder.  Manifestations include severe contractures, scoliosis, chest deformity, respiratory problems, unusually small jaws, and drooping of the upper eyelids.

Kennedy’s disease, also known as progressive spinobulbar muscular atrophy, is an X-linked recessive disease caused by mutations in the gene for the androgen receptor.  Daughters of individuals with Kennedy’s disease are carriers and have a 50 percent chance of having a son affected with the disease.  The onset of symptoms is variable and the disease may first be recognized between 15 and 60 years of age. Symptoms include weakness and atrophy of the facial, jaw, and tongue muscles, leading to problems with chewing, swallowing, and changes in speech.  Early symptoms may include muscle pain and fatigue.  Weakness in arm and leg muscles closest to the trunk of the body develops over time, with muscle atrophy and fasciculations.  Individuals with Kennedy’s disease also develop sensory loss in the feet and hands.  Nerve conduction studies confirm that nearly all individuals have a sensory neuropathy (pain from sensory nerve inflammation or degeneration).  Affected individuals may have enlargement of the male breasts or develop noninsulin-dependent diabetes mellitus.

The course of the disorder varies but is generally slowly progressive. Individuals tend to remain ambulatory until late in the disease.  The life expectancy for individuals with Kennedy disease is usually normal.

Post-polio syndrome (PPS) is a condition that can strike polio survivors decades after their recovery from poliomyelitis.  Polio is an acute viral disease that destroys motor neurons.  Many people who are affected early in life recover and develop new symptoms many decades later.  After acute polio, the surviving motor neurons expand the amount of muscle that each controls.  PPS and Post-Polio Muscular Atrophy (PPMA) are thought to occur when the surviving motor neurons are lost in the aging process or through injury or illness.  Many scientists believe PPS is latent

weakness among muscles previously affected by poliomyelitis and not a new MND.  Symptoms include fatigue, slowly progressive muscle weakness, muscle atrophy, fasciculations, cold intolerance, and muscle and joint pain.  These symptoms appear most often among muscle groups affected by the initial disease, and may consist of difficulty breathing, swallowing, or sleeping.  Other symptoms of PPS may be caused by skeletal deformities such as long-standing scoliosis that led to chronic changes in the biomechanics of the joints and spine.  Symptoms are more frequent among older people and those individuals most severely affected by the earlier disease.  Some individuals experience only minor symptoms, while others develop muscle atrophy that may be mistaken for ALS.  PPS is not usually life threatening.  Doctors estimate that 25 to 50 percent of survivors of paralytic poliomyelitis usually develop PPS

How are motor neuron diseases diagnosed?

There are no specific tests to diagnose most MNDs although there are now gene tests for SMA.  Symptoms may vary among individuals and, in the early stages of the disease, may be similar to those of other diseases, making diagnosis difficult.  A physical exam should be followed by a thorough neurological exam.  The neurological exam will assess motor and sensory skills, nerve function, hearing and speech, vision, coordination and balance, mental status, and changes in mood or behavior.

Tests to rule out other diseases or to measure muscle involvement may include the following:

Electromyography (EMG) is used to diagnose disorders of lower motor neurons, as well as disorders of muscle and peripheral nerves.  In an EMG, a physician inserts a thin needle electrode, attached to a recording instrument, into a muscle to assess the electrical activity during a voluntary contraction and at rest.   The electrical activity in the muscle is caused by the lower motor neurons.  When motor neurons degenerate, characteristic abnormal electrical signals occur in the muscle.  Testing usually lasts about an hour or more, depending on the number of muscles and nerves tested.

EMG is usually done in conjunction with a nerve conduction velocity study. Nerve conduction studies measure the speed and size of the impulses in the nerves from small electrodes taped to the skin.  A small pulse of electricity (similar to a jolt from static electricity) is applied to the skin to stimulate the nerve that directs a particular muscle.  The second set of electrodes transmits the responding electrical signal to a recording machine.  Nerve conduction studies help to differentiate lower motor neuron diseases from peripheral neuropathy and can detect abnormalities in sensory nerves.  

Laboratory tests of blood, urine, or other substances can rule out muscle diseases and other disorders that may have symptoms similar to those of MND.  For example, analysis of the fluid that surrounds the brain and spinal cord can detect infections or inflammation that can also cause muscle stiffness.  Blood tests may be ordered to measure levels of the protein creatine kinase (which is needed for the chemical reactions that produce energy for muscle contractions); high levels may help diagnose muscle diseases such as muscular dystrophy. 

Magnetic resonance imaging (MRI) uses a powerful magnetic field to produce detailed images of tissues, organs, bones, nerves, and other body structures.  MRI is often used to rule out diseases that affect the head, neck, and spinal cord.  MRI images can help diagnose brain and spinal cord tumors, eye disease, inflammation, infection, and vascular irregularities that may lead to stroke.  MRI can also detect and monitor inflammatory disorders such as multiple sclerosis and can document brain injury from trauma.  Magnetic resonance spectroscopy is a type of MRI scan that measures chemicals in the brain and may be used to evaluate the integrity of the upper motor neurons.

Muscle or nerve biopsy can help confirm nerve disease and nerve regeneration.  A small sample of the muscle or nerve is removed under local anesthetic and studied under a microscope.  The sample may be removed either surgically, through a slit made in the skin, or by needle biopsy, in which a thin hollow needle is inserted through the skin and into the muscle.  A small piece of muscle remains in the hollow needle when it is removed from the body.  Although this test can provide valuable information about the degree of damage, it is an invasive procedure and many experts do not believe that a biopsy is always needed for diagnosis.

Transcranial magnetic stimulation was first developed as a diagnostic tool to study areas of the brain related to motor activity.  It is also used as a treatment for certain disorders.  This noninvasive procedure creates a magnetic pulse inside the brain that evokes motor activity in an area of the body.  Electrodes taped to different areas of the body pick up and record the electrical activity in the muscles.  Measures of the evoked activity may help in diagnosing upper motor neural dysfunction in MND or monitoring disease progression.

How are motor neuron diseases treated?

There is no cure or standard treatment for the MNDs.  Symptomatic and supportive treatment can help people be more comfortable while maintaining their quality of life.  Multidisciplinary clinics, with specialists from neurology, physical therapy, respiratory therapy, and social work are particularly important in the care of individuals with MNDs.

The drug riluzole (Rilutek®), the only prescribed drug approved by the U.S. Food and Drug Administration to treat ALS, prolongs life by 2-3

months but does not relieve symptoms.  The drug reduces the body's natural production of the neurotransmitter glutamate, which carries signals to the motor neurons.  Scientists believe that too much glutamate can harm motor neurons and inhibit nerve signaling.

Other medicines may help with symptoms.  Muscle relaxants such as baclofen, tizanidine, and the benzodiazepines may reduce spasticity. Botulinum toxin may be used to treat jaw spasms or drooling.  Excessive saliva can be treated with amitriptyline, glycopyolate, and atropine or by botulinum injections into the salivary glands.  Combinations of dextromethorphan and quinidine have been shown to reduce pseudobulbar affect.  Anticonvulsants and nonsteroidal anti-inflammatory drugs may help relieve pain, and antidepressants may be helpful in treating depression.  Panic attacks can be treated with benzodiazepines.  Some individuals may eventually require stronger medicines such as morphine to cope with musculoskeletal abnormalities or pain, and opiates are used to provide comfort care in terminal stages of the disease.

Physical therapy, occupational therapy, and rehabilitation may help to improve posture, prevent joint immobility, and slow muscle weakness and atrophy.  Stretching and strengthening exercises may help reduce spasticity, increase range of motion, and keep circulation flowing.  Some individuals require additional therapy for speech, chewing, and swallowing difficulties.  Applying heat may relieve muscle pain.  Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs may help some people retain independence.

Proper nutrition and a balanced diet are essential to maintaining weight and strength.  People who cannot chew or swallow may require insertion of a feeding tube.  In ALS, insertion of a percutaneous gastronomy tube (to help with feeding) is frequently carried out even before it is needed, when the individual is strong enough to undergo this minor surgery.  Non-invasive ventilation at night can prevent apnea in sleep, and some individuals may also require assisted ventilation due to muscle weakness in the neck, throat, and chest during daytime.

What is the prognosis?

Prognosis varies depending on the type of MND and the age of onset. Some MNDs, such as PLS or Kennedy’s disease, are not fatal and progress slowly.  People with SMA may appear to be stable for long periods, but improvement should not be expected.  Some MNDs, such as ALS and some forms of SMA, are fatal.

What research is being done?

The NINDS supports a broad range of research aimed at discovering the cause of MNDs, finding better treatments, and, ultimately, preventing and curing the disorders.  Various MND animal models (animals that have been manipulated to mimic the disease in humans) are being used to study disease pathology and identify chemical and molecular processes involved in cellular degeneration.

Research options fall largely into three categories:  drugs, gene therapy, and stem cells.

Clinical trials are testing whether different drugs or interventions are safe and effective in slowing the progression of MNDs in patient volunteers. 

The antibiotic ceftriaxone has been shown to protect nerves by reducing glutamate toxicity—believed by many scientists to play a critical role in the development of ALS—in a mouse model of the disease.  One study found that cellular ability to manage glutamate can alter the course of ALS.  The drug is currently being tested in a NINDS-sponsored multi-center human clinical trial.

The novel compound dexpramipexole has shown neuroprotective properties in multiple preclinical studies of ALS, and may work by increasing the efficiency of mitochondria—the energy-producing portion of the body’s cells.  Mitochondria in the motor neurons undergo significant stress in ALS patients.  The compound is currently being tested in an industry-sponsored multi-center clinical trial.

Several early-stage clinical trials are testing the safety and feasibility of novel treatment strategies for ALS.  These include cell-based approaches such as the transplantation of neural precursor cells into the spinal cord of ALS patients, and the infusion of so-called “anti-sense” compounds into the fluid that surrounds the spinal cord and brain to block production of toxic SOD1 protein in ALS patients who carry SOD1 mutations.

Other compounds, including minocycline, coenzyme Q10, and lithium, have been tested and found ineffective in treating motor neuron diseases.

Cellular and molecular studies seek to understand the mechanisms that trigger motor neurons to degenerate.  Examples include the following:

Scientists are developing a broad range of model systems in animals and cells to investigate disease processes and expedite the testing of potential therapies.  Among these efforts, a NINDS-sponsored consortium of scientists is deriving a type of stem cell from ALS patients and using these stem cells to form motor neurons and surrounding support cells.

Scientists have used gene therapy to halt motor neuron destruction and slow disease progression in mouse models of SMA and inherited ALS.  The NINDS supports research to further explore this method and to provide a path toward clinical tests in patients.

Scientists have found that a specific class of compounds referred to as anti-sense oligonucleotides can either block or correct the processing of RNA molecules, which are the intermediates between genes and proteins.  These compounds have shown

therapeutic promise in model systems of ALS and SMA, and early-stage clinical testing is underway in ALS patients who carry SOD1 mutations.

Scientists are using advance sequencing technologies to identify new gene mutations that are associated with MNDs.  These gene discoveries have provided new insights into the cellular disease processed and identified possible intervention points for therapy.

The excessive accumulation of free radicals, which has been implicated in ALS and a number of other neurodegenerative diseases, is being closely studied.  Free radicals are highly reactive molecules that bind with other body chemicals and are believed to contribute to cell degeneration, disease development, and aging.

BAHAN 3 (periferal neuropati)by : mayoclinic

DefinitionPeripheral neuropathy, a result of damage to your peripheral nerves, often causes weakness, numbness and pain, usually in your hands and feet. It can also affect other areas of your body.

Your peripheral nervous system sends information from your brain and spinal cord (central nervous system) to the rest of your body. Peripheral neuropathy can result from traumatic injuries, infections, metabolic problems, inherited causes and exposure to toxins. One of the most common causes is diabetes mellitus.

People with peripheral neuropathy generally describe the pain as stabbing or burning. Often, there's tingling. In many cases, symptoms improve, especially if caused by a treatable underlying condition. Medications can reduce the pain of peripheral neuropathy.

SymptomsEvery nerve in your peripheral system has a specific function, so symptoms depend on the type of nerves affected. Nerves are classified into:

Sensory nerves that receive sensation from the skin such as temperature, pain, vibration

or touch

Motor nerves that control how your muscles move

Autonomic nerves that control functions such as blood pressure, heart rate, digestion

and bladder

Signs and symptoms of peripheral neuropathy may include:

Gradual onset of numbness and tingling in your feet or hands, which may spread upward

into your legs and arms

Sharp, jabbing or burning pain

Extreme sensitivity to touch

Lack of coordination and falling

Muscle weakness or paralysis if motor nerves are affected

If autonomic nerves are affected, signs and symptoms may include:

Heat intolerance and altered sweating

Bowel, bladder or digestive problems

Changes in blood pressure, causing dizziness or lightheadedness

Peripheral neuropathy may affect one nerve (mononeuropathy), two or more nerves in different areas (multiple mononeuropathy) or many nerves (polyneuropathy).

When to see a doctor

Seek medical care right away if you notice unusual tingling, weakness or pain in your hands or feet. Early diagnosis and treatment offer the best chance for controlling your symptoms and preventing further damage to your peripheral nerves.

CauseA number of factors can cause neuropathies, including:

Alcoholism. Poor dietary choices made by alcoholics can lead to vitamin deficiencies.

Autoimmune diseases.These include Sjogren's syndrome, lupus, rheumatoid arthritis,

Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and

necrotizing vasculitis.

Diabetes. More than half of people with diabetes develop some type of neuropathy.

Exposure to poisons. Toxic substances include heavy metals or chemicals.

Medications. Certain medications, especially those used to treat cancer

(chemotherapy), may cause peripheral neuropathy.

Infections. These include certain viral or bacterial infections, including Lyme disease,

shingles (varicella-zoster), Epstein-Barr virus, hepatitis C, leprosy, diphtheria and HIV.

Inherited disorders. Disorders such as Charcot-Marie-Tooth disease are hereditary

types of neuropathy.

Trauma or pressure on the nerve. Traumas, such as motor vehicle accidents, falls or

sports injuries, can sever or damage peripheral nerves. Nerve pressure can result from

having a cast or using crutches or repeating a motion many times, such as typing.

Tumors. Growths, cancerous (malignant) and noncancerous (benign), can develop on

the nerves themselves or they can put pressure on surrounding nerves.

Vitamin deficiencies. B vitamins, including B-1, B-6 and B-12, vitamin E and niacin are

crucial to nerve health.

Bone marrow disorders. These include abnormal protein in the blood (monoclonal

gammopathies), a form of bone cancer (osteosclerotic myeloma), lymphoma and

amyloidosis.

Other diseases. These include kidney disease, liver disease, connective tissue

disorders and an underactive thyroid (hypothyroidism).

Risk factors

Peripheral neuropathy risk factors include:

Diabetes mellitus, especially if your sugar levels are poorly controlled

Alcohol abuse

Vitamin deficiencies, particularly B vitamins

Infections, such as Lyme disease, shingles (varicella-zoster), Epstein-Barr virus,

hepatitis C and HIV

Autoimmune diseases, such as rheumatoid arthritis and lupus, in which your immune

system attacks your own tissues

Kidney, liver or thyroid disorders

Exposure to toxins

Repetitive motion, such as those performed for certain jobs

Family history of neuropathy

ComplicationsComplications of peripheral neuropathy may include:

Burns and skin trauma. If parts of your body are numb, you may not feel temperature

changes or pain.

Infection. Your feet and other areas lacking sensation can become injured without your

knowing. Check these areas regularly and treat minor injuries before they become

infected, especially if you have diabetes mellitus.

Tests and diagnosisPeripheral neuropathy isn't a single disease, but rather damage to nerves that produces symptoms with many potential causes. Your doctor will need to determine where the nerve damage is and what's causing it.

Besides a physical exam, which may include blood tests, diagnosis usually requires:

A full medical history.Your doctor will review your medical history, including your

symptoms, your lifestyle, exposure to toxins, drinking habits and a family history of

nervous system (neurological) diseases.

Neurological examination. Your doctor may check your tendon reflexes, your muscle

strength and tone, your ability to feel certain sensations, and your posture and

coordination.

Your doctor may order tests, including:

Imaging tests. CT or MRI scans can look for herniated disks, tumors or other

abnormalities.

Nerve function tests. Electromyography, a nerve function test, records electrical activity in your muscles to determine if your symptoms, including weakness, are caused by muscle or nerve damage.

For nerve conduction studies, a probe sends electrical signals to a nerve, and an electrode placed along the nerve's pathway records the nerve's response to the signals. Nerve conduction studies record signals from both motor and sensory nerves.

Other nerve function tests. These may include an autonomic reflex screen that records

how the autonomic nerve fibers work, a sweat test that records how you sweat, and

sensory tests that record how you feel touch, vibration, cooling and heat.

Nerve biopsy. Your doctor may recommend removing a small portion of a nerve, usually

a sensory nerve, to examine for abnormalities to determine the cause of your nerve

damage.

Skin biopsy. Your doctor removes a small portion of skin to examine the number of

nerve endings. A reduction in nerve endings indicates neuropathy.

Treatments and drugsTreatment goals are to manage the condition causing your neuropathy and to relieve symptoms. If your lab tests indicate no underlying condition, your doctor may recommend watchful waiting to see if your neuropathy improves. If exposure to toxins or alcohol is causing your conditions, your doctor will recommend avoiding those substances.

Medications

Medications used to relieve peripheral neuropathy pain include:

Pain relievers. Over-the-counter pain medications, such as nonsteroidal anti-inflammatory drugs, can relieve mild symptoms. For more-severe symptoms, your doctor may recommend prescription painkillers.

Medications containing opioids, such as tramadol (Conzip, Ultram ER, others) or oxycodone (Oxycontin, Roxicodone, others), can lead to dependence and addiction, so these drugs generally are prescribed only when other treatments fail.

Anti-seizure medications. Medications such as gabapentin (Gralise, Neurontin) and

pregabalin (Lyrica), developed to treat epilepsy, may relieve nerve pain. Side effects may

include drowsiness and dizziness.

Capsaicin. A cream containing this substance found naturally in hot peppers can cause

modest improvements in peripheral neuropathy symptoms. Doctors may suggest you

use this cream with other treatments. Skin burning and irritation where you apply the

cream may occur, but usually lessens over time. However, some people can't tolerate it.

Antidepressants. Certain tricyclic antidepressants, such as amitriptyline, doxepin and nortriptyline (Pamelor), have been found to help relieve pain by interfering with chemical processes in your brain and spinal cord that cause you to feel pain.

The serotonin and norepinephrine reuptake inhibitor duloxetine (Cymbalta) and the extended-release antidepressant venlafaxine (Effexor XR) also may ease the pain of peripheral neuropathy caused by diabetes. Side effects may include dry mouth, nausea, drowsiness, dizziness, decreased appetite and constipation.

Your doctor also may prescribe medication to treat the underlying condition that's causing the neuropathy. For example, medications to reduce your immune system's reaction, such as prednisone, cyclosporine (Neoral, Sandimmune, others), mycophenolate mofetil (CellCept) and azathioprine (Azasan, Imuran), may help people with peripheral neuropathy associated with autoimmune conditions.

Intravenous immunoglobulin is a mainstay of treatment for chronic inflammatory demyelinating polyneuropathy and other inflammatory neuropathy.

Therapies

Various therapies and procedures may help ease the signs and symptoms of peripheral neuropathy.

Transcutaneous electrical nerve stimulation (TENS).Adhesive electrodes placed on

the skin deliver a gentle electric current at varying frequencies. TENS should be applied

for 30 minutes daily for about a month.

Plasma exchange and intravenous immune globulin.People with certain inflammatory conditions may benefit from these procedures, which help suppress immune system activity.

Plasma exchange involves removing your blood, then removing antibodies and other proteins from the blood and returning the blood to your body. In immune globulin therapy, you receive high levels of proteins that work as antibodies (immunoglobulins).

Physical therapy. If you have muscle weakness, physical therapy can help improve

your movements. You may also need hand or foot braces, a cane, a walker, or a

wheelchair.

Surgery. If you have neuropathies caused by pressure on nerves, such as pressure

from tumors, you may need surgery to reduce the pressure.

Alternative medicineSome people with peripheral neuropathy try complementary and alternative treatments for relief of their symptoms. Although researchers haven't studied these techniques as thoroughly as they have most medications, the following therapies have shown some promise:

Acupuncture.Acupuncture, which involves inserting thin needles into various points on

your body, may reduce peripheral neuropathy symptoms. You may need multiple

sessions before you notice improvement. Acupuncture is generally considered safe

when performed by a certified practitioner using sterile needles.

Alpha-lipoic acid. Used as a treatment for peripheral neuropathy in Europe for years,

this antioxidant may help reduce symptoms. Discuss using alpha-lipoic acid with your

doctor because it may affect blood sugar levels. Other side effects may include stomach

upset and skin rash.

Herbs. Certain herbs, such as evening primrose oil, may help reduce neuropathy pain in

people with diabetes. Some herbs interact with medications, so discuss herbs you're

considering with your doctor.

Amino acids. Amino acids, such as acetyl-L-carnitine, may help improve peripheral

neuropathy in people who have undergone chemotherapy and in people with diabetes.

Side effects may include nausea and vomiting.

Fish oil. These supplements, which have omega-3 fatty acids, may reduce inflammation,

improve blood flow and improve neuropathy symptoms in people with diabetes. Check

with your doctor before taking fish oil supplements if you're taking anti-clotting

medications.

BAHAN 4by : mayoclinic

PERIPHERAL NERVE DISORDERS

There are many types of peripheral neuropathy, often brought on by diabetes; genetic predispositions (hereditary causes); exposure to toxic chemicals, alcoholism, malnutrition, inflammation (infectious or autoimmune), injury, and nerve compression; and by taking certain medications such as those used to treat cancer and HIV/AIDS. Mayo Clinic researchers are working toward earlier and better diagnosis and treatment, and ultimately prevention of these debilitating nerve diseases. The following are the major types of peripheral neuropathy:

Neuropathy is the disease of the nervous system in which there is a disturbance in the

function of a nerve or particular group of nerves. The three major forms of nerve damage

are: peripheral neuropathy, autonomic neuropathy, and mononeuropathy. The most

common form is peripheral neuropathy, which mainly affects the feet and legs.

Sciatica is pain, tingling, or numbness produced by an irritation of the sciatic nerve.

Sciatica is a pain in the leg due to irritation of the sciatic nerve. Sciatica most commonly

occurs when a branch of the sciatic nerve is compressed at the base of the spine.

Carpal tunnel syndrome occurs when tendons in the wrist become inflamed after being

aggravated. Tendons can become aggravated when the carpals (a tunnel of bones) and

the ligaments in the wrist narrow, pinching nerves that reach the fingers and the muscle

at the base of the thumb.

Polyneuropathy is any illness that attacks numerous nerves in the body, sometimes

causing weakness and/or pain. It tends to be a systemic problem that affects more than

one nerve group at a time. Polyneuropathies are relatively symmetric, often affecting

sensory, motor, and vasomotor fibers simultaneously.

Diabetic neuropathies are neuropathic disorders that are associated with diabetes

mellitus. These conditions usually result from diabetic microvascular injury involving

small blood vessels that supply nerves (vasa nervorum).

Autonomic neuropathy is a group of symptoms caused by damage to nerves supplying

the internal body structures that regulate functions such as blood pressure, heart rate,

bowel and bladder emptying, and digestion.

Postherpetic neuralgia is pain that persists after an episode of shingles (herpes zoster)

has resolved, resulting from damaged nerve fibers from the shingles.

Thoracic outlet syndrome is a condition in which the nerves or vessels behind the collar

bone (clavicle) become compressed or stretched, causing pain, weakness, or numbness

in the arm on the same side. The thoracic outlet is an area at the top of the rib cage,

between the neck and the chest. Several anatomical structures pass through this area,

including the esophagus, trachea, and nerves and blood vessels that lead to the arm and

neck region.

Ongoing research

The Peripheral Nerve Research Laboratory (PNRL), under the direction of Peter James Dyck, M.D., has engaged in research on peripheral nerve and its diseases for the last 40 years. Initial studies were done in collaboration with E. H. Lambert, but in recent years, they have been done in association with Phillip A. Low, M.D., P. James B. Dyck, M.D., and Christopher Klein, M.D. The research focusing on human diseases can be categorized as follows:

1. Experimental neuropathies including permanent axotomy, lead intoxication, ischemia,

regeneration, irradiation.

2. Natural history, gene identification, and treatment of inherited neuropathies such as

Charcot-Marie-Tooth syndrome types 1, 2 and other; and hereditary sensory

neuropathy (HSN) including congenital insensitivity to pain, HSN with dementia,

inherited brachial plexus neuropathy, progressive muscular atrophy, and spastic

paraplegia.

3. Diabetic sensorimotor polyneuropathy, including its natural history, course, outcome,

pathogenic factors, risk factors, and treatment trials.

4. Diabetic multifocal neuropathies including the natural history, underlying mechanisms,

and treatment trials of the disease.

5. Acute and chronic immune neuropathies–their natural history, pathologic alterations,

outcome, and treatment trials. The diseases studied include AIDP (Gillian-Barr

syndrome), chronic inflammatory demyelinating polyneuropathy (CIDP) and idiopathic

axonal polyneuropathy (CIAP), multifocal motor neuropathy (MMN), chronic

inflammatory multiple mononeuropathy (CIMM, also called MADSAM), or chronic

inflammatory sensory polyradiculopathy (CISP). The laboratory did the first prospective

controlled double-blind trials of CIDP.

6. Monoclonal gammopathy of unknown significance with neuropathy (MGUS

neuropathy), including its natural history, pathologic alterations, and treatment trials.

Dr. Dyck’s laboratory did the first prospective double-blind trials of treatment.

7. Studies of other approaches for evaluations of symptoms, deficits, disabilities, and

outcomes in neuropathy—using symptoms scores (e.g., NSS, NSC, and others),

impairment scores (e.g., NIS), composite scores of nerve conduction, quantitative

sensation testing, and disability scores This laboratory has been a leading reading and

quality assurance center for many multi-center trials.

Caterina Giannini, M.D., is doing research focused on tumors of the central and peripheral nervous system and the pathologic features predictive of patient outcome. She is conducting correlative studies to determine the clinical significance of

histologic and genetic variables in brain tumor tissue, in particular in the setting of clinical trials of patients with gliomas. Dr. Giannini is responsible for the Mayo Clinic Brain Cancer SPORE Tissue Core for the collection of fresh and fixed brain tissues for research. The Brain SPORE Tissue Core also supports high-throughput tissue microarray construction, laser capture microdissection, immunohistochemistry, FISH, in situ hybridization, and a variety of other techniques. A recent research development, in collaboration with the Mayo lymphoma SPORE investigators, has been the study of primary CNS malignant lymphoma cytogenetics, including low- and high-grade B-cell lymphomas.

Phillip Low, M.D., focuses his research on peripheral nerve microenvironment with particular emphasis on the basic mechanisms underlying the pathogenesis of diabetic neuropathy. His specific hypothesis is that diabetic neuropathy is mediated by oxidative injury to nerve target, especially sensory neuron. A related focus is on the pathophysiology of ischemic neuropathies and mechanisms of neuroprotection. Techniques used include immunohistochemical, molecular, microelectrode, and autoradiographic methods of studying nerve tissues. Another area of focus is human and experimental autonomic dysfunction. In the Autonomic Physiology Laboratory, he is studying the pathophysiology of orthostatic intolerance and its amelioration. Diseases studied include multiple system atrophy, autoimmune autonomic neuropathy, and postural tachycardia syndrome. The lab has the capabilities to non-invasively measure beat-to-beat blood pressure and flow (systemic, splanchnic-mesenteric, cerebral), heart rate, cardiac output, stroke volume, total peripheral resistance, as well as sudorometric and laser Doppler methods of measuring sudomotor and vasomotor activity. Direct measurements of muscle sympathetic activity are available using microneurography of peripheral nerve.

Brachial plexus injuries

Mayo Clinic in Minnesota has two laboratory research projects under way that are related to brachial plexus injuries.

Nerve Conduits. Mayo has developed a multichanneled nerve tube for peripheral nerve repair. This nerve tube is made of PCLF [poly(caprolactone fumarate)], a new biomaterial invented at Mayo Clinic in Rochester that is flexible and easy to suture. The current line of research is investigating the influence of structure on the support of regeneration for the possibility of bridging larger gaps and improving regeneration by separate guidance of regenerating axons. Use of a nerve conduit would decrease disadvantages of autograft, the current gold standard, such as donor-site morbidity (pain, sensory abnormality, separate incisions, etc.) and limited availability.

Choline Acetyltransferase (CAT) Assay: Application for Diagnosis and Treatment of Brachial Plexus Injuries. This research project is evaluating the relationship between CAT activity level in injured nerves and muscle function in a rat nerve repair model.

The measurement of CAT activity in brachial plexus nerves can determine the level of motor fibers present. If there is a relationship between the level of CAT activity and functional recovery of muscle, then high CAT activity areas of the nerve can be targeted to specific muscles to improve motor activity.

BAHAN 3 ( VITAMIN E DAN NEURO)

by : harvard

Could Vitamin E Supplements Be Harmful?

The occasional reports of harm from studies of high-dose vitamin E supplements highlight a question that researchers have been debating for years: Could high-dose vitamin E supplements potentially increase the risk of dying? Researchers have tried to answer this question by combining the results of multiple studies. In one such analysis, (31) the authors gathered and re-analyzed data from 19 clinical trials of vitamin E, including the GISSI and HOPE studies; they found a higher rate of death in trials where patients consumed more than 400 IU of supplements per day. While this meta-analysis drew headlines when it was released, there are limitations to the conclusions that can be drawn from it. Some of the findings are based on very small studies, and in some of these trials, vitamin E was combined with high doses of beta-carotene, which itself has been related to excess mortality.  Furthermore, many of the high-dose vitamin E trials included in the analysis were done on people who had chronic diseases, such as heart disease or Alzheimer’s disease. Also, other meta-analyses have come to different conclusions. So it is not clear that these findings would apply to healthy people. The Physicians’ Health Study II, for example, did not find that any difference in death rates between the study participants who took vitamin E and those who took a placebo. (12)

Vitamin E and Other Chronic Diseases

Investigators have explored whether vitamin E supplements can protect against other chronic diseases, and here, too, the findings have been mixed:

Age-Related Vision DiseasesA six-year trial found that vitamin E, in combination with vitamin C, beta carotene, and zinc, offers some protection against the development of advanced age-related macular degeneration (AMD), but not cataract, in people who were at high risk of the disease. (32,33) On its own, however, vitamin E does not seem to offer much benefit against either AMD or cataract. (34,35)

Cognitive Function and Neurodegenerative DiseasesScientists seeking to untangle the causes of Alzheimer’s, Parkinson’s, and other diseases of the brain and nervous system have focused on the role that free radical damage plays in these diseases’ development. (36) But to date, there is little evidence as to whether vitamin E can help

protect against these diseases or that it offers any benefit to people who already have these diseases.

Dementia: Some prospective studies suggest that vitamin E supplements, particularly in combination with vitamin C, may be associated with small improvements in cognitive function or lowered risk of Alzheimer’s disease and other forms of dementia, while other studies have failed to find any such benefit. (37-40)  A three-year randomized controlled trial in people with mild cognitive impairment—often a precursor to Alzheimer’s disease—found that taking 2,000 IU of vitamin E daily failed to slow the progression to Alzheimer’s disease. (41) Keep in mind, however, that the progression from mild cognitive impairment to Alzheimer’s disease can take many years, and this study was fairly short, so it is probably not the last word on vitamin E and dementia.

Parkinson’s Disease: Some, but not all, prospective studies suggest that getting higher intakes of vitamin E from diet—not from high-dose supplements—is associated with a reduced risk of Parkinson’s disease. (42-44)  In people who already have Parkinson’s, high-dose vitamin E supplements do not slow the disease’s progression. (45) Why the difference between vitamin E from foods versus that from supplements? It’s possible that foods rich in vitamin E, such as nuts or legumes, contain other nutrients that protect against Parkinson’s disease. More research is needed.

Amyotrophic Lateral Sclerosis (ALS): One large prospective study that followed nearly 1 million people for up to 16 years found that people who regularly took vitamin E supplements had a lower risk of dying from ALS than people who never took vitamin E supplements. (46) More recently, a combined analysis of multiple studies with more than 1 million participants found that the longer people used vitamin E supplements, the lower their risk of ALS. (47) Clinical trials of vitamin E supplements in people who already have ALS have generally failed to show any benefit, however. (48) This may be a situation where vitamin E is beneficial for prevention, rather than treatment, but more research is needed.

Terjemahan

GANGGUAN SARAF PERIFER

Ada banyak jenis neuropati perifer, sering disebabkan oleh diabetes; kecenderungan genetik (keturunan penyebab); paparan bahan kimia beracun, alkoholisme, malnutrisi, peradangan (infeksi atau autoimun), cedera, dan kompresi saraf; dan dengan mengambil obat tertentu seperti yang digunakan untuk mengobati kanker dan HIV / AIDS. Peneliti Mayo Clinic bekerja menuju diagnosis dini dan pengobatan yang lebih baik dan, dan akhirnya pencegahan penyakit-penyakit saraf yang melemahkan. Berikut ini adalah jenis utama dari neuropati perifer:

Neuropati adalah penyakit sistem saraf yang di dalamnya ada gangguan dalam fungsi

kelompok saraf atau saraf tertentu.Tiga bentuk utama dari kerusakan saraf

adalah: neuropati perifer, neuropati otonom, dan mononeuropati. Bentuk yang paling

umum adalah neuropati perifer, yang terutama mempengaruhi kaki dan kaki.

Linu panggul adalah rasa sakit, kesemutan, atau mati rasa yang dihasilkan oleh iritasi

pada saraf sciatic. Linu panggul adalah rasa sakit di kaki karena iritasi pada saraf

sciatic. Linu panggul paling sering terjadi ketika sebuah cabang dari saraf sciatic

dikompresi di dasar tulang belakang.

Carpal tunnel syndrome terjadi ketika tendon di pergelangan tangan menjadi meradang

setelah diperburuk. Tendon bisa menjadi diperparah ketika carpals (terowongan tulang)

dan ligamen di pergelangan tangan yang sempit, mencubit saraf yang mencapai jari-jari

dan otot pada pangkal ibu jari.

Polineuropati adalah penyakit yang menyerang banyak saraf di dalam tubuh, kadang-

kadang menyebabkan kelemahan dan / atau nyeri. Ini cenderung menjadi masalah

sistemik yang mempengaruhi lebih dari satu kelompok saraf pada suatu

waktu. Polineuropati relatif simetris, sering mempengaruhi serabut sensorik, motorik, dan

vasomotor bersamaan.

Neuropati diabetik adalah gangguan neuropatik yang berhubungan dengan diabetes

mellitus. Kondisi ini biasanya akibat dari cedera mikrovaskuler diabetes yang melibatkan

pembuluh darah kecil yang memasok saraf (vasa nervorum).

Neuropati otonom adalah sekelompok gejala yang disebabkan oleh kerusakan saraf

memasok struktur tubuh internal yang mengatur fungsi seperti tekanan darah, denyut

jantung, usus dan kandung kemih pengosongan, dan pencernaan.

Postherpetic neuralgia adalah nyeri yang bertahan setelah sebuah episode herpes

zoster (herpes zoster) telah diselesaikan, yang dihasilkan dari serabut saraf yang rusak

dari herpes zoster.

Sindrom outlet Thoracic adalah suatu kondisi di mana saraf atau pembuluh balik tulang

selangka (klavikula) menjadi dikompresi atau diregangkan, menyebabkan rasa sakit,

kelemahan, atau mati rasa di lengan pada sisi yang sama.Outlet dada adalah daerah di

bagian atas tulang rusuk, antara leher dan dada. Beberapa struktur anatomi melewati

daerah ini, termasuk esofagus, trakea, dan saraf dan pembuluh darah yang mengarah

ke daerah lengan dan leher.

Penelitian yang sedang berlangsung

Peripheral Nerve Research Laboratory (PNRL), di bawah arahanPeter James Dyck, MD, telah terlibat dalam penelitian pada saraf perifer dan penyakit selama 40 tahun terakhir. Studi awal yang dilakukan bekerja sama dengan EH Lambert, tetapi dalam beberapa tahun terakhir, mereka telah dilakukan dalam hubungan dengan Phillip A. Rendah, MD, P. James B. Dyck, MD, dan Christopher Klein, MD Penelitian berfokus pada penyakit manusia bisa dikategorikan sebagai berikut:

1. Neuropati eksperimental termasuk axotomy permanen, keracunan timbal, iskemia,

regenerasi, iradiasi.

2. Sejarah alam, identifikasi gen, dan pengobatan neuropati warisan seperti jenis sindrom

Charcot-Marie-Tooth 1, 2 dan lainnya; dan neuropati sensorik herediter (HSN)

termasuk ketidakpekaan bawaan untuk nyeri, HSN dengan demensia, mewarisi

brakialis pleksus neuropati, atrofi otot progresif, dan paraplegia spastik.

3. Diabetes polineuropati sensorimotor, termasuk sejarah alam, tentu saja, hasil, faktor

patogen, faktor risiko, dan uji coba pengobatan.

4. Neuropati diabetik multifokal termasuk sejarah alam, mekanisme yang mendasari, dan

uji coba pengobatan penyakit.

5. Akut dan kronis neuropati-mereka kekebalan sejarah alam, perubahan patologis, hasil,

dan uji coba pengobatan.Penyakit dipelajari meliputi AIDP (sindrom Gillian-Barr),

kronis polineuropati demielinasi inflamasi (CIDP) dan idiopatik polineuropati aksonal

(CIAP), multifokal bermotor neuropati (MMN), beberapa mononeuropati inflamasi

kronik (CIMM, juga disebut MADSAM), atau kronis inflamasi sensorik poliradikulopati

(CISP). Laboratorium lakukan pertama calon terkontrol double-blind dari CIDP.

6. Gammopathy monoklonal signifikansi diketahui dengan neuropati (MGUS neuropati),

termasuk sejarah alam, perubahan patologis, dan uji coba pengobatan.Laboratorium

Dr. Dyck yang lakukan pertama calon percobaan double-blind pengobatan.

7. Studi pendekatan lain untuk evaluasi gejala, defisit, cacat, dan hasil dalam neuropati-

menggunakan gejala skor (misalnya, NSS, NSC, dan lain-lain), skor penurunan

(misalnya, NIS), skor komposit konduksi saraf, pengujian sensasi kuantitatif, dan skor

cacat laboratorium ini telah membaca dan jaminan kualitas pusat terkemuka untuk

banyak cobaan multi-pusat.

Caterina Giannini, MD, melakukan penelitian difokuskan pada tumor sistem saraf pusat dan perifer dan patologis fitur prediksi hasil pasien. Dia melakukan penelitian korelatif untuk menentukan signifikansi klinis histologis dan variabel genetik dalam jaringan tumor otak, khususnya dalam pengaturan uji klinis pasien dengan glioma. Dr. Giannini bertanggung jawab atas Kanker Mayo Clinic Otak SPORE Tissue Inti untuk pengumpulan jaringan otak segar dan tetap untuk penelitian. Otak SPORE Tissue Inti juga mendukung high-throughput konstruksi jaringan microarray, menangkap Laser microdissection, imunohistokimia, FISH, hibridisasi in situ, dan berbagai teknik lainnya. Sebuah perkembangan penelitian terbaru, bekerja sama dengan peneliti SPORE limfoma Mayo, telah studi CNS Sitogenetika limfoma ganas primer, termasuk rendah dan bermutu tinggi limfoma sel-B.

Phillip Rendah, MD, memfokuskan penelitiannya pada saraf perifer mikro dengan penekanan khusus pada mekanisme dasar yang mendasari patogenesis neuropati diabetes. Hipotesis spesifik adalah bahwa neuropati diabetes dimediasi oleh cedera oksidatif target saraf, terutama neuron sensorik. Fokus terkait pada patofisiologi neuropati dan mekanisme pelindung saraf iskemik. Teknik yang digunakan termasuk imunohistokimia, molekul, microelectrode, dan metode autoradiografik mempelajari jaringan saraf. Bidang lain fokus disfungsi otonom manusia dan eksperimental. Dalam otonom Laboratorium Fisiologi, ia mempelajari patofisiologi intoleransi ortostatik dan perbaikan nya.Penyakit dipelajari meliputi multiple system atrophy, neuropati otonom autoimun, dan sindrom takikardia postural. Laboratorium ini memiliki kemampuan untuk mengukur tekanan non-invasif beat-to-beat dan aliran darah (sistemik, splanchnic-mesenterika, otak), denyut jantung, curah jantung, stroke volume, resistensi perifer total, serta metode Doppler sudorometric dan laser mengukur sudomotor dan vasomotor aktivitas. Pengukuran langsung dari otot aktivitas simpatis yang tersedia menggunakan microneurography saraf perifer.

Cedera pleksus brakialis

Mayo Clinic di Minnesota memiliki dua proyek penelitian laboratorium berlangsung yang terkait dengan brakialis cedera pleksus.

Saluran saraf. Mayo telah mengembangkan sebuah tabung saraf multichanneled untuk saraf perifer perbaikan. Tabung saraf ini terbuat dari PCLF [poli (kaprolakton fumarat)], biomaterial baru ditemukan di Mayo Clinic di Rochester yang fleksibel dan mudah untuk jahitan. Baris saat penelitian sedang menyelidiki pengaruh struktur pada dukungan regenerasi untuk kemungkinan menjembatani kesenjangan yang lebih besar dan meningkatkan regenerasi dengan bimbingan terpisah regenerasi akson.Penggunaan saluran saraf akan menurunkan kerugian dari autograft, standar emas saat ini, seperti morbiditas donor-situs (nyeri, kelainan sensorik, sayatan terpisah, dll) dan ketersediaan terbatas.

Kolin Acetyltransferase (CAT) Assay:. Aplikasi untuk Diagnosa dan Pengobatan Cedera brakialis Plexus Proyek penelitian ini adalah mengevaluasi hubungan antara tingkat aktivitas CAT di saraf yang terluka dan fungsi otot dalam model perbaikan tikus saraf. Pengukuran aktivitas CAT di saraf pleksus brakialis dapat menentukan tingkat serabut motorik ini. Jika ada hubungan antara tingkat aktivitas CAT dan pemulihan fungsional otot, maka bidang kegiatan CAT tinggi saraf dapat ditargetkan untuk otot tertentu untuk meningkatkan aktivitas motorik.