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
Associations 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 years
Characteristics: A milder, more slowly progressing form of Duchenne MD (see below).
Congenital (CMD) Age of onset: birth
Characteristics: 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 years
Characteristics: 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 teens

Characteristics: 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 adulthood
Characteristics: 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 age
Characteristics: 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 childhood
Characteristics: 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) isnt 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 adulthood
Characteristics: 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: infancy
Characteristics: 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 years
Characteristics: 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 months
Characteristics: 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 years
Characteristics: 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 years
Characteristics: 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 years
Characteristics: 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 childhood
Characteristics: 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 infancy
Characteristics: Slow development of motor skills. Hip displacement common.
Dermatomyositis Age of onset: childhood to age 60
Characteristics: 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 adulthood
Characteristics: 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 childhood
Characteristics: 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 infancy
Characteristics: 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 infancy
Characteristics: 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 adulthood
Characteristics: Muscle stiffness and difficulty relaxing muscles, especially after repeated use or
exercise.
Polymyositis Age of onset: childhood to age 60
Characteristics: 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 adulthood
Characteristics: For infants, the disease is generalized and severe, impairing the heart and liver. Lateronset forms involve weakness of mid-body and respiratory muscles. Progression varies.
Carnitine deficiency Age of onset: early childhood
Characteristics: 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 year
Characteristics: General muscle weakness, poor muscle control and an enlarged liver with low blood
sugar. Slow progression.
Mitochondrial myopathy Age of onset: early childhood to adulthood
Characteristics: 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 bestselling poet.
Phosphorylase deficiency (McArdle disease)
Phosphofructokinase deficiency (Tarui disease)
Phosphoglycerate kinase deficiency
Phosphoglycerate mutase deficiency
Lactate dehydrogenase deficiency
Age of onset: childhood, adolescence or adulthood
Characteristics: 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 2
by : 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 stemthe 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 contractureschronic 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.
Kennedys 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 Kennedys
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 Kennedys
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. Noninvasive 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 Kennedys 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
toxicitybelieved by many scientists to play a critical role in the development of
ALSin 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
mitochondriathe energy-producing portion of the bodys 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

Definition
Peripheral 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.

Symptoms
Every 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.

Cause
A 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

Complications

Complications 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 diagnosis

Peripheral 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 drugs

Treatment 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 antiinflammatory 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 medicine

Some 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 anticlotting medications.

BAHAN 4
by : 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 neuropathiestheir 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.
Dycks laboratory did the first prospective double-blind trials of treatment.

7.

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

outcomes in neuropathyusing 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 noninvasively measure beat-to-beat blood pressure and flow (systemic, splanchnicmesenteric, 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 betacarotene, 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 Alzheimers disease. Also, other metaanalyses 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 Diseases

A 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 Diseases

Scientists seeking to untangle the causes of Alzheimers, Parkinsons, 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 Alzheimers 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 Alzheimers diseasefound that taking 2,000 IU of vitamin E
daily failed to slow the progression to Alzheimers disease. (41) Keep in mind,
however, that the progression from mild cognitive impairment to Alzheimers disease
can take many years, and this study was fairly short, so it is probably not the last
word on vitamin E and dementia.

Parkinsons Disease: Some, but not all, prospective studies suggest that getting
higher intakes of vitamin E from dietnot from high-dose supplementsis
associated with a reduced risk of Parkinsons disease. (42-44) In people who already
have Parkinsons, high-dose vitamin E supplements do not slow the diseases
progression. (45) Why the difference between vitamin E from foods versus that from
supplements? Its possible that foods rich in vitamin E, such as nuts or legumes,
contain other nutrients that protect against Parkinsons 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 neuropatimenggunakan 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.