BIO616

PRINCIPLES OF NEUROBIOLOGY

ASSIGNMENT

NAME : SARAH AFIQAH BINTI YAHAYA

STUDENT ID : 2016589421
GROUP : AS2015B1
LECTURER’S NAME : MDM FAIKAH
SYNOPSIS

100 Metros, 2016

100 Metros is a 2016 Spanish film directed by Marcel Barrena. The plot is based on the true
story of a Spanish man Ramon Arroyo with Multiple sclerosis who tried to finish an Iron-Man
challenge which need to perform 3.8 km swimming, 180 km cycling and 42 running. Ramon
Arroyo is a man who lives in Bilbao his wife Inma working as CEO in an important company
with friends and job partners as Mario. One day he wakes up and found himself briefly
paralyzed, being unable to stand up from the bed. Trying to know what happens, Inma and
Ramon go to the hospital and they found out that Ramon is diagnosed with multiple sclerosis,
a muscular degeneration that progressively will stop any movement of his body, leaving him
in a wheelchair the rest of his life. Starting a treatment in the hospital to minimize the
symptoms, where he meets other patients with a more advanced state of the disease, Inma has
her own troubles due her father Manolo, who has tried commit suicide in his country house
where he lives alone after the death of his wife and Inma's mother. Moving Manolo to the city
to live with them, things complicate by the so much bad relation between Ramon and Manolo,
causing the frustration and desperation in Inma. But things change the day that Ramon reads
in the hospital an info post about an Iron Man competition. Ramon enlists to participate,
receiving an unwanted help of Manolo, a former professional athlete in his youth days. Unable
to training him in the city, Manolo moves with Ramon to the country house, where Ramon
discovers casually that the reason of Manolo's failed try of suicide is his pain by his wife's loss.
Meeting a few later the charming Noelia in the beach during a training, Ramon decides deceive
Manolo to date her hoping help him. According the Iron Man's date is coming, Ramon looking
for the way to prove that the real Iron Man are not superheroes embodied in a metal suit, but
ordinary people ready to fight until the end to defeat their inner evil and show that human being
can be extraordinary.
Gallop, 2012
 CAUSES OF MULTIPLE SCLEROSIS

Multiple sclerosis is an autoimmune disease in which the body's immune system attacks its
own tissues. In multiple sclerosis, this immune system malfunction destroys the fatty substance
that coats and protects nerve fibers in the brain and spinal cord (myelin). Myelin can be
compared to the insulation coating on electrical wires. When the protective myelin is damaged
and nerve fiber is exposed, the messages that travel along that nerve may be slowed or blocked.
The nerve may also become damaged itself. It isn't clear why MS develops in some people and
not others. A combination of genetics and environmental factors appears to be responsible.

1. Immunologic factors
In Multiple sclerosis, an abnormal immune response causes inflammation and damage in the
central nervous system. Many different cells are involved in the abnormal immune response.
Two important types of immune cells are T cells and B cells. T cells become activated in the
lymph system and in multiple sclerosis, enter the central nervous system through blood vessels.
Once in the central nervous system, T cells release chemicals that cause inflammation and
damage. This results in damage to myelin, nerve fibers and the cells that make myelin. T cells
are also important to help activate B cells and call on other immune system cells to participate
in the immune attack. T regulatory cells, a type of T cell, dampen or turn off inflammation. In
multiple sclerosis, T regulatory cells to not function correctly and do not effectively turn off
inflammation. Cytotoxic T cells directly attack and destroy cells. B cells become activated with
the help of T cells. B cells produce antibodies and stimulate other proteins and in multiple
sclerosis, these cause damage in the central nervous system.

2. Genetic factors
Multiple sclerosis is not an inherited disease, meaning it is not a disease that is passed down
from generation to generation. However, in Multiple sclerosis, there is genetic risk that may
be inherited. In the general population, the risk of developing Multiple sclerosis is about 1 in
750 - 1000. In identical twins, if one twin has Multiple sclerosis the risk that the other twin will
develop Multiple sclerosis is about 1 in 4. The risk of developing Multiple sclerosis is also
increased when other first degree relative which is parents, siblings and children have Multiple
sclerosis but far less than in identical twins. About 200 genes have been identified that each
contribute a small amount to the overall risk of developing Multiple sclerosis.
3. Environmental factors
i. Geographic gradient

Multiple sclerosis is known to occur more frequently in areas that are farther from the equator.
Epidemiologists who study disease patterns in large groups of people are looking at variations
in geography, demographics (age, gender and ethnic background), genetics, infectious
causes and migration patterns in an effort to understand why. Studies have shown that people
born in an area with a high risk of Multiple sclerosis who then move or migrate to an area
with a lower risk before the age of 15 assume the risk of their new area. Such data suggest
that exposure to some environmental agent before puberty may predispose a person to
develop Multiple sclerosis later on.

ii. Vitamin D

Growing evidence suggests that vitamin D plays an important role in Multiple sclerosis. Low
vitamin D levels in the blood have been identified as a risk factor for the development of
Multiple sclerosis. Some researchers believe that sun exposure which is the natural source of
Vitamin D may help to explain the north-south distribution of Multiple sclerosis. People who
live closer to the equator are exposed to greater amounts of sunlight year-round. As a result,
they tend to have higher levels of naturally-produced vitamin D, which is thought to support
immune function and may help protect against immune-mediated diseases like Multiple
sclerosis.

iii. Smoking
The evidence is also growing that smoking plays an important role in Multiple sclerosis.
Studies have shown that smoking increases a person’s risk of developing Multiple sclerosis
and is associated with more severe disease and more rapid disease progression. Fortunately,
the evidence also suggests that stopping smoking whether before or after the onset of Multiple
sclerosis is associated with a slower progression of disability.

iv. Obesity
Several studies have shown that obesity in childhood and adolescence, particularly in girls,
increased the risk of later developing Multiple sclerosis. Other studies have shown that
obesity in early adulthood may also contribute to an increased risk of developing Multiple
sclerosis. Also, obesity may contribute to inflammation and more Multiple sclerosis activity
in those already diagnosed with Multiple sclerosis.
 METHOD OF TREATMENT FOR MULTIPLE SCLEROSIS

1. Treatment for MS attack

i. Corticosteroids
Oral prednisone and intravenous methylprednisolone, are prescribed to reduce nerve
inflammation. Side effects may include insomnia, increased blood pressure, mood swings and
fluid retention.

ii. Plasma exchange

The liquid portion of part of the blood (plasma) is removed and separated from the blood
cells. The blood cells are then mixed with a protein solution (albumin) and put back into the
body. Plasma exchange may be used if the symptoms are new, severe and haven't responded
to steroids.

2. Treatment to modify progression

i. Beta interferons
The medicine are injected under the skin or into muscle and can reduce the frequency and
severity of relapses. The side effects of beta interferons may include flu-like symptoms and
injection-site reactions. People taking interferons may develop neutralizing antibodies that
can reduce drug effectiveness.

ii. Glatiramer acetate (Copaxone, Glatopa)

This medication may help block your immune system's attack on myelin and must be injected
beneath the skin. Side effects may include skin irritation at the injection site.

iii. Fingolimod (Gilenya)

This once-daily oral medication reduces relapse rate. Patience heart rate will be monitored
for six hours after the first dose because the heartbeat may be slowed. The side effects include
rare serious infections, headaches, high blood pressure and blurred vision.
iv. Dimethyl fumarate (Tecfidera)
This twice-daily oral medication can reduce relapses. Side effects may include flushing,
diarrhea, nausea and lowered white blood cell count.

v. Teriflunomide (Aubagio)
This once-daily oral medication can reduce relapse rate. Teriflunomide can cause liver
damage, hair loss and other side effects. It is harmful to a developing fetus and should not be
used by women who may become pregnant or their male partner are not using appropriate
contraception.

vi. Siponimod (Mayzent)

Research shows that this once-daily oral medication can reduce relapse rate and help slow
progression of Multiple sclerosis. It's also approved for secondary-progressive MS. Possible
side effects include viral infections, liver problems and low white blood cell count. Other
possible side effects include changes in heart rate, headaches and vision problems. Siponimod
is harmful to a developing fetus, so women who may become pregnant should use
contraception when taking this medication and for 10 days after stopping the medication.

vii. Ocrelizumab (Ocrevus)

This humanized immunoglobulin antibody medication is the only DMT approved by the FDA
to treat both the relapse-remitting and primary-progressive forms of Multiple sclerosis.
Clinical trials showed it reduced relapse rate in relapsing disease and slowed worsening of
disability in both forms of the disease. Ocrevus is given via an intravenous infusion by a
medical professional. Infusion-related side effects may include irritation at the injection site,
low blood pressure, a fever and nausea, among others. Ocrevus may also increase the risk of
some types of cancer, particularly breast cancer.

viii. Natalizumab (Tysabri)

This medication is designed to block the movement of potentially damaging immune cells from
your bloodstream to brain and spinal cord. It may be considered a first line treatment for some
people with severe Multiple sclerosis or as a second line treatment in others. This medication
increases the risk of a potentially serious viral infection of the brain called progressive
multifocal leukoencephalopathy (PML) in people who are positive for antibodies to the
causative agent of PML JC virus.
ix. Alemtuzumab (Campath, Lemtrada)
This drug helps reduce relapses of Multiple sclerosis by targeting a protein on the surface of
immune cells and depleting white blood cells. This effect can limit potential nerve damage
caused by the white blood cells. But it also increases the risk of infections and autoimmune
disorders, including a high risk of thyroid autoimmune diseases and rare immune mediated
kidney disease. Treatment with alemtuzumab involves five consecutive days of drug
infusions followed by another three days of infusions a year later. Infusion reactions are
common with alemtuzumab. The drug is only available from registered providers, and people
treated with the drug must be registered in a special drug safety monitoring program.

x. Mitoxantrone
This immunosuppressant drug can be harmful to the heart and is associated with development
of blood cancers. As a result, its use in treating Multiple sclerosis is extremely limited.
Mitoxantrone is only rarely used to treat severe, advanced Multiple sclerosis.

xi. Physical therapy

A physical or occupational therapist teach the patience on how to stretching and strengthening
exercises and show how to use devices to make it easier to perform daily tasks. Physical
therapy along with the use of a mobility aid when necessary can also help manage leg
weakness and other gait problems often associated with Multiple sclerosis.