Case study no.

1
A thirty-two year-old female instructor at a large Midwestern university
began having problems with her coordination. She noticed it particularly
when she was coaching the softball team because she could not toss and
hit that ball with her usual accuracy during practice. She also has some
other signs that something was wrong including numbness, tingling and
some mood wings. When she went to bar doctor, He examine her and
immediately ordered a CAT scan. The diagnosis was multiple sclerosis.
Not long after beginning drug therapy, she realized the symptoms were
less and less pronounced until she had none. The doctor told her that the
disease was in remission. She was able to continue teaching and
coaching.
Medical Terminologies and abbreviations:

Multiple sclerosis
- also known as disseminated sclerosis or encephalomyelitis
disseminata, is an inflammatory disease in which the insulating
covers of nerve cells in the brain and spinal cord are damaged.
This damage disrupts the ability of parts of the nervous system to
communicate, resulting in a wide range of signs and symptoms,
including physical, mental, and sometimes psychiatric
problems.MS takes several forms, with new symptoms either
occurring in isolated attacks (relapsing forms) or building up over
time (progressive forms). Between attacks, symptoms may
disappear completely; however, permanent neurological problems
often occur, especially as the disease advances.
CAT or CT
-Computed tomography, a radiologic imaging that uses computer
processing to generate an image of tissue density in slices through the
patient's body.
Numbness and tingling
- are decreased or abnormal sensations caused by altered sensory nerve
function.
The feeling of having a foot "fall asleep" is a familiar one
Signs and symptoms:
Symptoms of MS depend on the area of the central nervous system that losses myelin.
Early symptoms may include:
- Numbness or tingling in parts of the body, usually the leg or arm
- Unexplained weakness, dizziness and fatique
-Double vision ,blurry vision, or blindness
During periods of remission, the patient may feel better but the arm or leg may feel
stiff. Some weakness, numbness, and vision problems may remain.
As the symptoms come back. They may become more severe and include:
-muscle spasm
-bowel and bladder problems
-slurred speech
-blindness
-sexual problems
-paralysis
-confusion and fortgetfulness

Diagnosis:
Physical examination and medical history are very important in diagnosing MS.
Physical exams include a variety of test to check the health of the nerves and
muscles. A diagnosis of MS relies primarily on seeing patches of destroyed
myelin on a magnetic resonance imaging(MRI) scan. As doctor tracks the
progress of the disease, Multiple MRIs may need to be done.

If a diagnosis is still questionable, spinal fluid may be taken from the back to
test for abnormalities. Other tests aim at measuring the speed of the brain
connections. For example, the visual evoked response test measure the speed of
brain of the visual pathway.

The brain stem evoked response test measure the speed of the auditory or
hearing, pathways.

Your doctor may ask for blood test to determine if diseases other than MS are
causing symptoms similar to MS.


Etiology:
* Immunologic-MS is considered an immune-mediated disease. That is, the immune system
malfunctions and attacks the CNS. Researchers know that the myelin sheath is directly affected,
but dont know what triggers the immune system to attack the myelin.
* A Genetic Connection-Several genes are believed to play a role in MS. Your chance of developing
MS is slightly higher if a close relative, such as a parent or sibling, has the disease. According to
the Multiple Sclerosis Foundation (MSF), if one parent has MS, the risk of their children getting the
disease is estimated between two and five percent. Scientists believe that people with MS are born
with a genetic susceptibility to react to certain (unknown) environmental agents. An autoimmune
response is triggered when they encounter these agents.
* Environment-Epidemiologists have seen an increased pattern of MS cases in countries located
farthest from the equator. This correlation causes some to believe that vitamin D may play a
role.Vitamin D benefits the function of the immune system. People who live near the equator are
exposed to more sunlight. As a result, their bodies produce more vitamin D.The longer your skin is
exposed to sunlight, the more your body naturally produces the vitamin. Since MS is considered an
immune-mediated disease, vitamin D and sunlight exposure may be linked.
* Infections-Researchers are considering the possibility that viruses and bacteria may cause MS.
Viruses are known to cause inflammation and a breakdown of myelin (called demyelination).
Therefore, its possible that a virus will trigger MS.
Several viruses and bacteria are being investigated to determine if theyre involved in the
development of MS. These include:
* measles
* human herpes virus-6
* Epstein-Barr






Pathophysiology

*Multiple sclerosis (MS) is a chronic inflammatory demyelinating
disease of the central nervous system (CNS). Both genetic and
environmental causes for MS have been suggested. Recent
genome-wide association studies revealed new susceptibility
alleles for MS besides the HLA complex that are all related with
immune functions. Whereas there is little evidence to support a
purely environmental trigger for the disease in the sense of an
infectious agent, the autoimmune hypothesis of MS is well
established. Myelin antigen-specific CD4+ T cells become
activated in the peripheral immune compartment, cross the
blood-brain barrier and trigger the disease. Here, current
concepts of the commitment of T cells to pro-inflammatory
effector T helper cell lineages including Th17 cells that appear to
be important inducers of organ-specific autoimmunity will be
discussed.


Identified predisposing factors:

*Age. MS can occur at any age, but most commonly affects people between the ages of 15
and 60.
*Sex. Women are about twice as likely as men are to develop MS.
*Family history. If one of your parents or siblings has had MS, you are at higher risk of
developing the disease.
*Certain infections. A variety of viruses have been linked to MS, including Epstein-Barr, the
virus that causes infectious mononucleosis.
*Race. White people, particularly those of Northern European descent, are at highest risk
of developing MS. People of Asian, African or Native American descent have the lowest
risk.
*Climate. MS is far more common in countries with temperate climates, including southern
Canada, northern United States, New Zealand, southeastern Australia and Europe.
*Certain autoimmune diseases. You have a slightly higher risk of developing MS if you
have thyroid disease, type 1 diabetes or inflammatory bowel disease.
*Smoking. Smokers who experience an initial event of symptoms that may signal MS are
more likely than nonsmokers to develop a second event that confirms relapsing-
remitting MS.


Medications and the rationale:
Medication approved by FDA:
Avonex and Rebif (both interferon beta-1a) as well as Betaseronand Extavia (both
interferonbeta-1b) reduce disease activity through a number of mechanisms, including the
reduction of T cell inflammatory activity (Th1 cells). This reduces the number of T cells that
damage myelin. They also stabilize the BBB, which helps to keep damaging cells out of the brain.
The interferons also perform other positive actions as well.
Copaxone (glatiramer acetate) is a mixture of four amino acids found in myelin basic protein,
whichis a key component of the myelin sheath that is damaged in MS. It diminishes several of the
damaging MS disease processes, including the promotion of a shift in Th1 cells (pro-inflammatory)
to Th2(anti-inflammatory) responses. Copaxone increases T-regulatory cells that reduce immune
system damage. It may also improve nerve function in the brain by increasing brain-derived
neurotrophic factor (BDNF), which may provide neuroprotective effects.
Novantrone (mitoxantrone) is an immunosuppressant that has been used for years to treat
cancer.It targets rapidly dividing cells, including those believed to be involved in MS.
Tysabri (natalizumab) is a laboratory-produced monoclonal antibody that prevents lymphocytes
from migrating across the BBB and into the central nervous system (CNS). Recent data suggest that
it may also enhance remyelination and stabilize damage to the myelin sheath. These and other
results suggest that the drug may improve CNS function.