Download demielinisation diseases of the nervous system actuality

DEMIELINISATION
DISEASES OF THE
NERVOUS SYSTEM
ACTUALITY
Patients
with the multiple sclerosis often initially
appear to ophthalmologist (retrobulbar neuritis),
urologist (disorders of urination). A question about the
presence of tumor of spinal cord is typical, so a patient
is examined by neurosurgeon. In the clinic of internal
diseases it is possible to meet the neurological
manifestations of funicular myelosis. At the study of this
problem a necessity to have knowledge of the
theoretical subjects of medical education (biochemistry,
immunology, genetics) is proved brightly.
PLAN

Classification of demyelinating diseases.

Pathomorphology of demyelinization process.




Symptoms and syndromes those are
characteristic for demyelinating diseases.
Features of clinical course of demyelinating
diseases (multiple sclerosis, acute disseminated
encephalomyelitis).
Additional methods which are used with the
purpose of diagnostics of these diseases.
Treatment of patients with demyelinating
diseases.
Multiple sclerosis (abbreviated
MS, also known as disseminated
sclerosis or encephalomyelitis
disseminata)
is
a
chronic,
inflammatory,
demyelinating
disease that affects the central
nervous system (CNS).
HISTORY
The French neurologist Jean-Martin Charcot (1825–93)
was the first person to recognize multiple sclerosis as a
distinct, separate disease in 1868. Summarizing
previous reports and adding his own important clinical
and pathological observations, Charcot called the
disease sclerose en plaques. The three signs of MS now
known as Charcot's triad are dysarthria (problems with
speech), ataxia (problems with coordination), and
tremor. Charcot also observed cognition changes in MS
since he described his patients as having a "marked
enfeeblement of the memory" and "with conceptions
that formed slowly“.
Multiple sclerosis affects neurons, the
cells of the brain and spinal cord that
carry information, create thought and
perception, and allow the brain to
control the body. Surrounding many of
these neurons is a fatty layer known as
the myelin sheath, which helps
neurons carry electrical signals.
MS causes gradual destruction of myelin
(demyelination) and transection of neuron
axons in patches throughout the brain and
spinal cord. When the myelin is
destroyed, the neurons can no longer
effectively conduct their electrical
signals. The name multiple sclerosis refers
to the multiple scars (or scleroses) on the
myelin sheaths.
The predominant theory today is that
MS results from attacks by an
individual's immune system on the
nervous system and it is therefore
usually categorized as an
autoimmune disease.
Multiple sclerosis may take several
different forms, with new symptoms
occurring either in discrete attacks or
slowly accruing over time. Between
attacks,
symptoms
may
resolve
completely, but permanent neurologic
problems often persist, especially as the
disease advances.
MS primarily affects adults, with an age of
onset typically between 20 and 40 years,
and is more common in women than in
men.
CAUSES
No definitive cause has been found.
MS likely occurs as a result of some
combination of both environmental and
genetic factors. Although most accept
theory an autoimmune explanation. It
suggests that MS is an appropriate
immune response to an underlying
condition.
EPIDEMIOLOGY
EPIDEMIOLOGY
In
northern Europe, continental North America,
and Australasia, about one of every 1000 citizens
suffers from multiple sclerosis, whereas in the
Arabian peninsula, Asia, and continental South
America, the frequency is much lower. In subSaharan Africa, MS is extremely rare. With
important exceptions, there is a north-to-south
gradient in the northern hemisphere and a southto-north gradient in the southern hemisphere, with
MS being much less common in people living near
the equator. Climate, diet, geomagnetism, toxins,
sunlight exposure, genetic factors, and infectious
diseases have all been discussed as possible
reasons for these regional differences.
GENETIC
MS is not considered a hereditary disease. Some
populations, such as the Roma, Inuit, and Bantus, rarely
if ever get MS. The indigenous peoples of the Americas
and Asians have very low incidence rates.
If one person in a family has MS, that person's firstdegree relatives—parents, children, and siblings—have
a one to three percent chance of getting the disease.
For identical twins, the likelihood that the second twin
may develop MS if the first twin does is about 30%; for
fraternal twins (who do not inherit identical gene pools),
the likelihood is closer to that for non-twin siblings, or
about 4%.
Of particular interest is the human leukocyte antigen
(HLA) or major histocompatibility complex region on
chromosome 6. HLAs are genetically determined
proteins that influence the immune system.
SIGNS AND SYMPTOMS
MS can cause a variety of symptoms:

changes in sensation (hypoesthesia),

muscle weakness,

abnormal muscle spasms, or difficulty in moving;

difficulties with coordination and balance (ataxia);

problems in speech (dysarthria) or swallowing (dysphagia),

visual problems (nystagmus, optic neuritis, or diplopia),

fatigue and acute or chronic pain syndromes,

bladder and bowel difficulties,

cognitive impairment, or emotional symptomatology (mainly
depression).
The main clinical measure of disability progression and severity
of the symptoms is the Expanded Disability Status Scale or
EDSS.
SIGNS AND SYMPTOMS

The initial attacks are often
transient, mild (or asymptomatic),
and self-limited. They often do not
prompt a health care visit and
sometimes are only identified in
retrospect once the diagnosis has
been made based on further
attacks.
SIGNS AND SYMPTOMS
The most common initial symptoms reported
are:
 changes in sensation in the arms, legs or face
(33%),
 complete or partial vision loss (optic neuritis)
(16%),
 weakness (13%),
 double vision (7%),
 unsteadiness when walking (5%),
 balance problems (3%);
 aphasia or psychosis.
DISEASE COURSE AND CLINICAL
SUBTYPES
United States National Multiple Sclerosis Society
(1996):
Relapsing-remitting describes the initial course of
85% to 90% of individuals with MS. This subtype is
characterized by unpredictable attacks (relapses)
followed by periods of months to years of relative
quiet (remission) with no new signs of disease
activity. Deficits suffered during the attacks may
either resolve or may be permanent.
DISEASE COURSE AND CLINICAL
SUBTYPES
Secondary progressive describes around 80% of
those with initial relapsing-remitting MS, who
then begin to have neurologic decline between
their acute attacks without any definite
periods of remission. This decline may include
new neurologic symptoms, worsening cognitive
function, or other deficits. Secondary
progressive is the most common type of MS
and causes the greatest amount of disability.
DISEASE COURSE AND CLINICAL SUBTYPES
Primary
progressive
describes
the
approximately 10% of individuals who never
have remission after their initial MS
symptoms. Decline occurs continuously
without
clear
attacks.
The
primary
progressive subtype tends to affect people
who are older at disease onset.
Progressive
relapsing
describes
those
individuals who, from the onset of their MS,
have a steady neurologic decline but also
suffer superimposed attacks; and is the least
common of all subtypes
FACTORS TRIGGERING A RELAPSE
In general, relapses occur more frequently during
spring and summer than during autumn and winter.
Infections, such as the common cold, influenza, and
gastroenteritis, increase the risk for a relapse.
Emotional and physical stress may also trigger an
attack, as can severe illness of any kind.
Heat (saunas or hot showers) can transiently increase
symptoms, which is known as Uhthoff's phenomenon.
Pregnancy can directly affect the susceptibility for
relapse. The last three months of pregnancy offer a
natural protection against relapses.
DEMYELINIZATION IN MS. ON KLÜVER-BARRERA
MYELIN STAINING, DECOLORATION IN THE AREA OF
THE LESION CAN BE APPRECIATED
DIAGNOSIS
T1-weighted MRI scans (post-contrast) of
same brain slice at monthly intervals. Bright
spots indicate active lesions.
In fact, definite diagnosis of MS cannot be
made until there is evidence of at least two
anatomically separate demyelinating events
occurring at least thirty days apart.
McDonald`s criteria
represents international efforts to standardize the
diagnosis of MS using clinical data, laboratory
data, and radiologic data.
Clinical data alone may be sufficient for a
diagnosis of MS. If an individual has suffered two
separate episodes of neurologic symptoms
characteristic of MS, and the individual also has
consistent abnormalities on physical examination,
a diagnosis of MS can be made with no further
testing.
MCDONALD CRITERIA
Magnetic resonance imaging (MRI) shows areas
of demyelination as bright lesions on T2weighted images or FLAIR (fluid attenuated
inversion recovery) sequences.
Gadolinium contrast is used to demonstrate
active plaques on T1-weighted images.
Because MRI can reveal lesions which occurred
previously but produced no clinical symptoms,
it can provide the evidence of chronicity
needed for a definite diagnosis of MS.
Another test which may become
important
in the
future
is
measurement of antibodies against
myelin proteins such as myelin
oligodendrocyte glycoprotein (MOG)
and myelin basic protein (MBP).
DIAGNOSTIC
Testing of cerebrospinal fluid (CSF) can
provide evidence of chronic inflammation of
the central nervous system. The CSF is tested
for
oligoclonal
bands,
which
are
immunoglobulins found in 85% to 95% of
people with definite MS (but also found in
people with other diseases). Combined with
MRI and clinical data, the presence of
oligoclonal bands can help make a definite
diagnosis of MS.
TREATMENT
There is no known definitive cure for multiple sclerosis. Different
therapies are used for patients experiencing acute attacks, for patients
who have the relapsing-remitting subtype, for patients who have the
progressive subtypes, for patients without a diagnosis of MS who have
a demyelinating event, and for managing the various consequences of
MS attacks. Treatment is aimed at returning function after an attack,
preventing new attacks, and preventing disability.
Management of acute attacks
During symptomatic attacks administration of high doses of
intravenous corticosteroids, such as methylprednisolone, is the routine
therapy for acute relapses. The aim of this kind of treatment is to end
the attack sooner and leave fewer lasting deficits in the patient.
Although generally effective in the short term for relieving symptoms,
corticosteroid treatments do not appear to have a significant impact on
long-term recovery. Potential side effects include osteoporosis and
impaired memory, the latter being reversible.
Interferons:
These
are medications derived from human
cytokines which help regulate the immune
system.
Interferon beta-1a: (trade names Avonex , Rebif
and Avonex)
beta-1b: (trade name Betaferon). Betaferon has
been approved by the FDA for relapsing forms of
secondary progressive MS.
Glatiramer acetate: (trade name Copaxone)
A synthetic medication made of four amino
acids that are found in myelin. This drug
stimulates T cells in the body's immune system to
change from harmful, pro-inflammatory agents to
beneficial, anti-inflammatory agents that work to
reduce inflammation at lesion sites.
Mitoxantrone:
(trade name Novantrone)
This medication is effective, but is limited by cardiac
toxicity. Novantrone has been approved by the USA's FDA
for secondary progressive, progressive-relapsing, and
worsening relapsing-remitting MS.
Natalizumab: (trade name Tysabri).
Relapsing-remitting
symptomatic attacks can be
treated.
Patients
are typically given high doses of intravenous
corticosteroids, such as methylprednisolone, to end the
attack sooner and leave fewer lasting deficits. Patients'
self-reporting indicates that many find benefit from a
number of other medicines.
There are no approved treatments for primary
progressive
multiple
sclerosis,
though
several
medications are being studied.
PROGNOSIS
The
prognosis for a person with multiple sclerosis depends on the
subtype of the disease; the individual's sex, race, age, and initial
symptoms; and the degree of disability the person experiences.
The life expectancy of people with MS is now nearly the same as
that of unaffected people.
This is due mainly to improved methods of limiting disability, such
as physical therapy, occupational therapy, speech therapy and
manipulative therapy from a chiropractor or osteopath for the
reduction in musculoskeletal pain, along with more successful
treatment of common complications of disability, such as pneumonia
and urinary tract infections.
Nevertheless half of the deaths in people with MS are directly
related to the consequences of the disease, while 15% more are due
to suicide.
wheelchair or standing frame
slower disability progresses
symptoms of visual loss or sensory problems, such as numbness or
tingling
 difficulty walking and weakness
AMYOTROPHIC LATERAL SCLEROSIS
is
a progressive, usually fatal, neurodegenerative disease
caused by the degeneration of motor neurons, the nerve cells in
the central nervous system that control voluntary muscle
movement. Causes muscle weakness and atrophy throughout the
body as both the upper and lower motor neurons degenerate and
die, ceasing to send messages to muscles. Unable to function, the
muscles gradually weaken, develop fasciculations (twitches)
because of denervation, and eventually atrophy due to that
denervation. The patient may ultimately lose their ability to initiate
and control all voluntary movement except of the eyes.
Cognitive
function is generally spared . Sensory nerves and the
autonomic nervous system, which controls functions like
sweating, generally remain functional.
EPIDEMIOLOGY
ALS is one of the most common neuromuscular diseases
worldwide,
and
people
of
all
races
and
ethnic
backgrounds are affected. Between 1 to 2 people per
100,000 develop ALS each year. ALS most commonly
strikes people between 40 and 60 years of age, but
younger and older people can also develop the disease.
Men are affected slightly more often than women.
ALS is classified into two groups, familial ALS and
sporadic ALS.
CAUSES AND RISK FACTORS
Scientists have not found a definitive
cause for ALS and the onset of the
disease can be linked to a variety of risk
factors. Researchers suspect a virus,
exposure to neurotoxins or heavy metals,
DNA
defects,
immune
system
abnormalities, and enzyme abnormalities
as the leading causes of the disease.
There is a hereditary factor in familial ALS
(FALS) however there is no known
hereditary component in the 90-95%
cases diagnosed as sporadic ALS.
SYMPTOMS
Initial Symptoms
The earliest symptoms may include twitching,
cramping, or stiffness of muscles; muscle
weakness affecting an arm or a leg; and/or
slurred and nasal speech. These general
complaints then develop into more obvious
weakness or atrophy that may cause a physician
to suspect ALS.
About 25% of cases are "bulbar onset" ALS.
These patients first notice difficulty speaking
clearly. Speech becomes garbled and slurred.
Nasality and loss of volume are frequently the
first symptoms. Difficulty swallowing, and loss of
tongue mobility follow. Eventually total loss of
speech and the inability to protect the airway
when swallowing are experienced.
Regardless of the part of the body first affected by the
disease, muscle weakness and atrophy spread to other parts
of the body as the disease progresses. Patients experience
increasing difficulty moving, swallowing (dysphagia), and
speaking or forming words (dysarthria). Symptoms of upper
motor neuron involvement include tight and stiff muscles
(spasticity) and exaggerated reflexes (hyperreflexia)
including an overactive gag reflex. An abnormal reflex
commonly called Babinski's sign (the large toe extends
upward as the sole of the foot is stimulated) also indicates
upper motor neuron damage. Symptoms of lower motor
neuron degeneration include muscle weakness and atrophy,
muscle cramps, and fleeting twitches of muscles that can be
seen under the skin (fasciculations). Around 15–45% of
patients experience pseudobulbar affect, also known as
"emotional lability", which consists of uncontrollable
laughter, crying or smiling.
To be diagnosed with ALS, patients must have signs and
symptoms of both upper and lower motor neuron damage
that cannot be attributed to other causes.
SYMPTOMS
Emerging Symptoms
Although the sequence of emerging symptoms and the rate
of disease progression vary from person to person,
eventually patients will not be able to stand or walk, get in or
out of bed on their own, or use their hands and arms.
Difficulty swallowing and chewing impair the patient's ability
to eat normally and increase the risk of choking.
ALS predominantly affects the motor neurons, and in the
majority of cases the disease does not impair a patient's
mind, personality, intelligence, or memory. Nor does it affect
a person's ability to see, smell, taste, hear, or feel touch.
Control of eye muscles is the most preserved function,
although some patients with an extremely long duration of
disease (20+ years) may lose eye control too. Unlike multiple
sclerosis, bladder and bowel control are usually preserved in
ALS, although as a result of immobility and diet changes,
intestinal problems such as constipation can require
intensive management.
DIAGNOSIS
No test can provide a definite diagnosis of ALS, although the
presence of upper and lower motor neuron signs in a single limb
is strongly suggestive. Instead, the diagnosis of ALS is primarily
based on the symptoms and signs the physician observes in the
patient and a series of tests, whether symptoms such as muscle
weakness, atrophy of muscles, hyperreflexia, and spasticity are
getting progressively worse.
Because symptoms of ALS can be similar to those of a wide
variety of other, more treatable diseases or disorders,
appropriate tests must be conducted to exclude the possibility of
other conditions. One of these tests is electromyography (EMG).
Another common test measures nerve conduction velocity (NCV).
Specific abnormalities in the NCV results may suggest, for
example, that the patient has a form of peripheral neuropathy
(damage to peripheral nerves) or myopathy (muscle disease)
rather than ALS. The physician may order magnetic resonance
imaging (MRI). Although these MRI scans are often normal in
patients with ALS, they can reveal evidence of other problems
that may be causing the symptoms, such as a spinal cord tumor,
multiple sclerosis, a herniated disk in the neck, syringomyelia, or
cervical spondylosis.
TREATMENT
No cure has yet been found for ALS. However, the Food and Drug
Administration (FDA) has approved the first drug treatment for the
disease: Riluzole (Rilutek). Riluzole is believed to reduce damage to
motor neurons by decreasing the release of glutamate.
Other treatments for ALS are designed to relieve symptoms and improve
the quality of life for patients. This supportive care is best provided by
multidisciplinary teams of health care professionals such as physicians;
pharmacists; physical, occupational, and speech therapists; nutritionists;
social workers; and home care and hospice nurses. Working with patients
and caregivers, these teams can design an individualized plan of medical
and physical therapy and provide special equipment aimed at keeping
patients as mobile and comfortable as possible.
Physicians can prescribe medications to help reduce fatigue, ease
muscle cramps, control spasticity, and reduce excess saliva and phlegm.
Drugs also are available to help patients with pain, depression, sleep
disturbances, and constipation. Pharmacists can give advice on the
proper use of medications and monitor a patient's prescriptions to avoid
risks of drug interactions.
PROGNOSIS
Regardless of the part of the body first affected by the
disease, it is usual for muscle weakness and atrophy to
spread to other parts of the body as the disease progresses.
It is important to remember that some patients with ALS have
an arrested course with no progression beyond a certain
point despite extensive follow-up. Such a pattern is
particularly true for young males with predominant upper
limb weakness especially on one side (so called "monomelic
or Hirayama type" motor neuron disease). Eventually people
with ALS will not be able to stand or walk, get in or out of bed
on their own, or use their hands and arms. In later stages of
the disease, individuals have difficulty breathing as the
muscles of the respiratory system weaken. Although
ventilation support can ease problems with breathing and
prolong survival, it does not affect the progression of ALS.
Most people with ALS die from respiratory failure, usually
within 3 to 5 years from the onset of symptoms. However,
about 10 percent of those individuals with ALS survive for 10
or more years.