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MSExplained
A str
aight
forwar
d guide to m
ultiple sclerosis
Simon Webster
Alison Whittam
3rd Edition
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Introduction
Welcome to the third edition of
‘MS Explained’.
Contents
Introduction3
MS stands for multiple sclerosis
which is a condition that affects the
central nervous system (the brain
and spinal cord). MS is a life long
condition which affects different
people in different ways.
Who gets MS?
MS Explained aims to give a basic
introduction to what MS can do to
the body, as well as an extensive
look at research and areas where
advances might be made in the
future. An explanation of the terms
highlighted in bold can be found in
the extended glossary at the end of
the book.
The immune system
Readers could include people with
MS, their family and friends; people
caring for someone with MS; and
those simply interested in this most
enigmatic condition.
Future research
This book purposely avoids
discussing the treatment and
management of symptoms as this
is covered extensively by other MS
Trust publications, details of which
are given in relevant sections and
on page 72.
Index74-77
The possible causes
of MS
4-9
10-15
The central nervous
system16-19
20-23
What happens in MS? 24-25
Diagnosis26-29
Types of MS
30-33
The cause of
symptoms34-53
54-63
Glossary64-71
More information from
the MS Trust
72-73
Tel: 01462 476700 3
Who gets MS?
How many people have MS?
Multiple sclerosis is the most
common disease of the central
nervous system diagnosed in young
adults. An estimated 2,500,000
people in the world have MS.
There is currently no comprehensive
register of people with MS in the
UK and so the number of people
with MS is an estimate based on a
number of studies of local areas.
The studies look at the number
of people with the condition in a
particular geographic area, which
is referred to as the prevalence,
and are usually expressed as the
number of cases per 100,000
people. The prevalence rates from
the studies are then applied to the
national population, and from this
it is estimated that around 100,000
people live with MS in the UK.
Similarly, if the results of local area
studies are applied nationwide it
suggests that nearly 3,000 people
are diagnosed with MS in the UK
each year, or around 50 to 60 a
week. The number of new cases in
the population within a specified
period of time is known as the
incidence rate.
4www.mstrust.org.uk
The University of Swansea is
working with the MS Society to
develop a UK MS Register that will
combine personal information with
clinical and NHS data to provide a
more accurate picture of the number
of people with MS in the UK. More
information about the register,
including how to join, can be found
at: www.ukmsregister.org/
An incidence register of MS in
Scotland has also been launched,
which will collate data on all new
cases of MS in Scotland from
the 1st January 2010. As well as
collecting data about the number
of new cases of MS in Scotland
each year, the register will examine
patient management from referral
to diagnosis. More information
about the register can be found at:
www.msr.scot.nhs.uk/
Age
Most people with MS are diagnosed
in their 20s or 30s, although it can
be diagnosed in people who are
older than this, and, less frequently,
in teenagers and children. However,
the number of cases of MS in this
age group is rising and research
suggests that somewhere between
1 in 37 and 1 in 50 people with
MS are diagnosed in their teens or
younger, although precise figures
are unknown.
Due to the age at which it is
diagnosed, MS is often thought of
as a condition that affects younger
people. However, as it only has
a small effect on life expectancy,
most people live with the condition
for a long time.
Gender
More women than men are
diagnosed with MS. Roughly two
women have MS for every man
with the condition, although it has
been suggested that the proportion
of women with MS may be
growing. Recent studies in North
America indicate that the figure
may be closer to three women to
each man diagnosed.
When MS is diagnosed in people in
their teens, the proportion is about
three women to one man. When
MS is diagnosed in older people,
or in whose MS is progressive from
onset, the numbers of women and
men are equal (see page 30 for
more on types of MS).
The reason for the larger proportion
of women with MS is unknown but
this pattern also occurs in most
other autoimmune conditions
(see page 10 for more on
autoimmune conditions).
Where is MS more common?
The distribution of MS around the
world is uneven. As a rough guide,
the prevalence increases as you
travel further north or south from
the equator. Those parts of Asia,
Africa and America that lie on
the equator have extremely low
levels of MS, whilst countries such
as Canada and Scotland have
particularly high rates.
Studies in countries near the
equator have shown a prevalence
rate of about 4 cases per 100,000
in Peru, 8 in Saudi Arabia and just
1 amongst Indians in Mumbai. In
contrast, studies in Australia show
a range from 11 in the north to 68
in Tasmania in the south.
This increasing prevalence is
more marked in the northern
hemisphere. Studies in the UK
suggest that the rate in England
and Wales is between 120 and 140
Tel: 01462 476700 5
Who gets MS?
per 100,000, about 180 in Northern
Ireland and as high as 210 in
Scotland. Individual studies in
Orkney have recorded rates of over
400 per 100,000.
Race
A simple geographical spread is
not the whole picture. Studies show
that some ethnic groups have a
markedly lower prevalence of MS,
despite living in countries where MS
is relatively common. For instance,
the Sami (Lapps) of northern
Scandinavia and the Inuit in Canada
have very low rates of MS. A similar
pattern is observed amongst the
Maoris of New Zealand.
In contrast, a study in Kuwait
showed that the rate in Kuwaitis
was half that of the ethnic
Palestinian population - many of
whom had been born and raised
in Kuwait. Similarly, the studies in
India that showed very low rates
for Indians also found that the
rate in Parsis, an ethnic group that
originated in Persia, was much
higher and equivalent to the rates
seen in areas in southern Europe.
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Vikings and Scots
The fact that MS is more prevalent
in northern Europe, North America,
Australia and New Zealand has led
to speculation that it was carried
around the world by European
colonists and settlers. It has been
suggested that the origins can be
traced back to the Vikings who
colonised those parts of Northern
Europe where MS is now most
pronounced and that ‘Viking’
genes can make people particularly
susceptible to MS.
It has also been noted that Scotland
has a much higher rate of MS than
England or Wales and that areas
of high MS prevalence around
the world have been settled by
Scottish immigrants. In Ireland for
instance, the national rate of MS
in the Irish Republic was looked
at in 2007 and was shown to vary
from 145 per 100,000 in Wexford
in the south, to 290 in Donegal in
the northwest. In Northern Ireland,
which was extensively settled by
immigrants from Scotland from the
17th century, the rate was recorded
in 2004 as 230 per 100,000.
Migration
Research looking at the effect of
migration on the risk of developing
MS suggests that the age
someone moves is important. If
someone moves from an area of
low risk to an area of high risk as
an adult, they retain the risk level
of the location from which they
originally came. People who move
as children, and their subsequent
offspring, have a risk of MS similar
to that found locally.
This explains the outdated belief
that MS is a condition that only
affects white people and is rare or
unknown amongst black or Asian
people. Whilst this might have
been true for the first generation
immigrants, it is not the case for
successive generations born and
brought up in the UK, with MS
increasingly being seen in black
and Asian communities.
The geographic spread of MS
suggests the genetic make up of
people from different parts of the
world has an impact on risk of MS;
the migration studies point to there
being an environmental element at
play as well.
Cases of MS
<5/100 000
5-30/100 000
>30/100 000
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Who gets MS?
Bibliography
Alonso A, et al. Incidence of multiple
sclerosis in the United Kingdom: findings
from a population-based cohort. Journal of
Neurology 2007; 254(12): 1736-41.
Burgess M. Multiple sclerosis: theory and
practice for nurses. London: Whurr; 2002.
Canadian MS Society. International
Pediatric MS Study Group’s
Recommendations on Clinical Trials
Published. 2013 Jun 10 [cited 2013 July 2].
Available from: URL: http://mssociety.ca/
en/help/msupdates/msupdate_20130610.
htm
Compston A, et al. McAlpine’s multiple
sclerosis. 4th ed. London: Churchill
Livingstone; 2006.
Gray OM, et al. Factors in the rising
prevalence of multiple sclerosis in the
north-east of Ireland. Multiple Sclerosis
2008; 14(7): 880-6.
Lonergan R, et al. Multiple sclerosis
prevalence in Ireland: relationship to
vitamin D status and HLA genotype.
Journal of Neurology, Neurosurgery and
Psychiatry 2011; 82(3): 317-22.
Orton SM, et al. Sex ratio of multiple
sclerosis in Canada: a longitudinal study.
Lancet Neurology 2006; 5(11): 932-936.
Richard RG, et al. A review of the natural
history and epidemiology of multiple
sclerosis. Health Technology Assessment
2002; 6(10).
Rosati G. The prevalence of multiple
sclerosis in the world: an update.
Neurological Sciences 2001; 22: 117-139.
8www.mstrust.org.uk
Thomas T, et al. Multiple sclerosis in
children. Seminars in Neurology 2008;
28(1): 69-83.
Visser EM, et al. A new prevalence study
of multiple sclerosis in Orkney, Shetland
and Aberdeen city. Journal of Neurology,
Neurosurgery and Psychiatry 2012; 83(7):
719-24.
Zajicek J, et al. Multiple sclerosis: a
practical manual. Oxford: Oxford University
Press; 2007.
Tel: 01462 476700 9
The possible causes of MS
Multiple sclerosis was first
described as a distinct condition
by the French neurologist JeanMartin Charcot in 1868. However,
the cause of MS still remains a
mystery. There has been a great
deal of research looking for the
solution to this problem and a
number of theories have held sway
as to what triggers MS.
Over the years, speculation on
the cause of the condition has
included:
acute fevers or exposure to
damp or cold
blood clots or poor circulation
in the brain
environmental poisons
dietary factors such as a food
allergy or food intolerance
mercury leakage from dental
amalgam fillings.
Research has failed to prove any
of these theories, but it has been
widely held that MS is primarily an
autoimmune disease. However,
there is currently a debate going
on as to whether MS may in fact
be due to a neurodegenerative
process, which in turn triggers a
10www.mstrust.org.uk
secondary inflammatory response,
but this theory is not yet universally
accepted.
Autoimmune disease
An autoimmune disease is one
in which the immune system,
which should only target invading
germs, instead targets the body’s
own tissues. Other autoimmune
conditions include diabetes mellitus
type 1, in which the insulin making
cells of the pancreas are destroyed;
and rheumatoid arthritis, where the
immune system primarily attacks
the joints, but can also affect organs
such as the lining of the lungs and
the heart. In the case of MS, the
immune system attacks myelin, the
substance covering and protecting
nerves in the central nervous system.
The reason for this reaction is
unknown but it is thought that
the genetic make up of some
people means that MS can be
triggered by something in the
environment, possibly an infectious
agent or agents. In response to
the infection, some cells from the
immune system come into contact
with the central nervous system
and attack myelin.
Genetics
It is important to state that MS is
not hereditary and the majority
of people who develop MS have
no previous family history of the
condition. However, there is a slight
increased risk of developing MS for
someone with a relative with the
condition.
Whilst the rate of MS within
families indicates that there
is a genetic factor involved in
developing the condition, studies
of identical twins show that genes
are not the whole story. Identical
twins have exactly the same
genetic make up. If MS were solely
dependent on genes, it would be
expected that if one identical twin
developed the condition, so would
the other. Studies have shown that
rather than this 100% risk, the
actual risk of developing MS for the
identical twin of someone with MS
is about 1 in 4.
The risk of developing MS
In the general population in the UK, the prevalence of MS is about 1 in
700. Studies have shown that the risk for first degree relatives (parents,
children, siblings) of someone with MS is about 1 in 40. For second degree
relatives (cousins, uncles/aunts, nephews/nieces) it is around 1 in 100.
It is worth putting MS in context with other conditions:
1 in 3 people will develop some form of cancer
1 in 8 women will develop breast cancer at some point in their lives
1 in 9 men will develop prostate cancer
1 in 20 people over the age of 65 have dementia
1 in 33 people have diabetes
1 in 500 people have Parkinson’s disease
1 in 520 people in England and Wales have a stroke each year.
1 in 700 people have MS.
Tel: 01462 476700 11
The possible causes of MS
Which genes are involved in MS
Genetic research has started to
identify conditions such as cystic
fibrosis that result from variations
in a single gene. This is not the
case with MS and it is believed
that the interaction of a number of
genes determines whether or not
an individual is susceptible.
The first gene to be identified
as contributing to the risk of MS
was discovered in the 1970s.
With recent advances in gene
technology, more than 50 genes
have now been identified. In fact
researchers suggest there might
be a hundred or more genes that
contribute to an individual’s risk
of MS. On its own, each gene
raises the MS risk by a negligible
amount. However, if an individual
has enough of these genes, the
combined effect will make them
more susceptible to MS.
A major reason why the
identification of genes has been so
slow is that none of those found to
be associated with MS is unique
to people with the condition. For
instance, one of the discovered
genes, called IL7R, is carried
12www.mstrust.org.uk
by nine out of ten people in the
general population. Having the
IL7R gene does not mean that an
individual will get MS, but the bit
of risk that it carries adds to an
individuals susceptibility to MS.
External factors
Whilst a specific combination of
genes can mean that an individual
is at risk of developing MS,
this in itself does not cause the
condition. It is believed that other
external factors are involved. When
people with a particular genetic
make up are exposed to a trigger,
their body reacts in a way that
starts the development of MS,
although it may be years before
any symptoms become apparent.
Many people believe that one of
the possible triggers is probably an
infection of some sort.
Infection
Research into the role of an
infection or infections in the onset
of MS has been carried out since
the 19th century. Initial work looked
into the theory that MS was directly
caused by an infectious agent, but
failed to find any positive results.
Subsequent research, has worked
on the theory that an infection may
act as a trigger, which sets off a
train of events in some people
that then develops into MS over a
period of time.
A number of common infections
have been investigated, including
chicken pox, measles, mumps,
canine distemper and several
herpes viruses.
When someone is infected with
a virus or bacteria, the immune
system creates antibodies to
help it fight off the invasion. The
antibodies remain in the blood
to help fight off subsequent
infections. Researchers can
identify antibodies in the blood
that indicate infections to which
someone has been exposed.
It is not yet clear if there is a
particular virus, or combination of
viruses, that might trigger MS, or if
this varies from person to person.
This type of research is challenging
because most adults carry evidence
of common infections, even if their
immune system prevented any
symptoms developing.
For example, a virus that has
been a focus of investigation is
the Epstein Barr virus (EBV), which
causes glandular fever. Children
have a lower level of exposure to
some infections, so researchers in
Canada compared exposure to EBV
in a group of children with MS and
a control group who did not have
the condition. They found that 83%
of the MS group had been infected
with EBV compared to 42% of
the controls. Whilst this suggests
that EBV might have a role in the
development of MS, almost one in
five of the children with MS had no
evidence of exposure.
Vitamin D
The role of vitamin D in multiple
sclerosis has also been the focus
of much debate and research has
focused on two areas:
Does vitamin D affect the risk of
getting MS?
Does vitamin D affect the course
of MS?
Vitamin D and risk of MS
Recent reviews suggest that vitamin
D may influence MS susceptibility.
Vitamin D is manufactured by the
skin when it is exposed to sunlight.
Tel: 01462 476700 13
The possible causes of MS
Many studies of the geographical
distribution of MS have shown that
the prevalence of MS increases
with distance from the equator,
supporting the link between lack of
sunlight exposure, consequent lack
of vitamin D production, and the
development of MS.
A review of blood samples taken
from US military personnel found
that levels of vitamin D in people
who subsequently developed MS
were lower than levels in people
without the condition. This effect
only seemed to occur in samples
from white people, and was not
demonstrated in the smaller set
of samples from black or Hispanic
people. Another study found that
amongst sets of identical twins,
where only one of the twins had
MS, the twin who had engaged in
less outdoor activity as a child and
had been less exposed to sunlight
was the twin more likely to have
developed MS.
A number of studies have drawn a
connection between vitamin D levels
in mothers and the subsequent risk of
their children developing MS. Studies
have found that more people with
MS are born in spring than autumn,
14www.mstrust.org.uk
suggesting that decreased maternal
exposure to the sun during winter
pregnancies results in low vitamin D
levels, which in some way increases
the risk of developing MS later in
life for children who are genetically
susceptible.
Vitamin D and the course of MS
Despite the accumulating evidence
which suggests its importance in
MS, so far there have only been
a limited number of studies on
the effect of vitamin D treatment
in MS. These studies have been
in relatively small numbers of
people, and differing levels of
supplementation have been tested.
The results generated have been
very variable, making it difficult to
draw conclusions, but no significant
association has been found.
Studies are currently underway,
or in the planning stages, to
look at how common vitamin D
deficiency is in people with MS
and to establish the safety of high
doses of vitamin D. Further studies
are needed to evaluate the role of
vitamin D during pregnancy and
early years for reducing the risk of
children developing MS in later life.
Bibliography
Alotaibi S, et al. Epstein-Barr virus in
pediatric multiple sclerosis. JAMA. 2004;
291(15): 1875-1879.
Burgess M. Multiple sclerosis: theory and
practice for nurses. London: Whurr; 2002.
Burton JM, et al. A phase I/II doseescalation trial of oral vitamin D3 with
calcium supplementation in patients with
multiple sclerosis. Multiple Sclerosis 2008;
14(Suppl 1): S34.
Compston A, et al. McAlpine’s multiple
sclerosis. 4th ed. London: Churchill
Livingstone; 2006.
Dobson R, et al. The month of birth effect
in multiple sclerosis: systematic review,
meta-analysis and effect of latitude.
Journal of Neurology, Neurosurgery and
Psychiatry 2013; 18(4): 427-32.
Goldberg P, et al. Multiple sclerosis
decreased relapse rate through dietary
supplementation with calcium, magnesium
and vitamin D. Medical Hypotheses 1986;
21: 193-200.
Goris A, et al. Progress in multiple sclerosis
genetics. Current Genomics 2012; 13(8):
646-63.
Islam T, et al. Childhood sun exposure
influences risk of multiple sclerosis in
monozygotic twins. Neurology 2007; 69:
381-388.
James E, et al. The effect of vitamin
D-related interventions on multiple
sclerosis relapses: a meta-analysis.
Multiple Sclerosis 2013; May 22 [Epub
ahead of print]
Munger KL, et al. Serum 25-hydroxyvitamin
D levels and risk of multiple sclerosis.
JAMA 2006; 296(23): 2832-2838.
Munger KL, et al. Vitamin D intake and
incidence of multiple sclerosis. Neurology
2004; 62(1): 60-65.
O’Gorman C, et al. Modelling genetic
susceptibility to multiple sclerosis with
family data. Neuroepidemiology 2013;
40(1): 1-12.
Sawcer S. The genes jigsaw. MS Matters
2008; 77(Jan): 8-9.
Trapp BD, et al. Multiple sclerosis: an
immune or neurodegenerative disorder?
Annual Reviews in Neuroscience 2008; 31:
1247-69.
Wingerchuck DM, et al. A pilot study of
oral calcitriol (1,25-dihydroxyvitamin D3)
for relapsing-remitting multiple sclerosis.
Journal of Neurology, Neurosurgery and
Psychiatry 2005; 76: 1294-1296.
Statistics from
Cancer Research UK – www.
cancerresearchuk.org [cited June 2013].
Alzheimer’s Society - www.alzheimers.
org.uk [cited February 2013].
Diabetes UK - www.diabetes.org.uk [cited
February 2013].
Stroke Association - www.stroke.org.uk
[cited February 2013].
Parkinson’s UK - www.parkinsons.org.uk
[cited February 2013].
Tel: 01462 476700 15
The central nervous system
MS is a condition in which damage occurs within the central nervous system.
The nervous system
The nervous system is the means
by which the body communicates
messages to and from muscles
and organs and maintains
awareness of the outside world
through the senses. It controls
every function in our body, all that
we say, do, or think.
The nervous system is divided into
two areas
the central nervous system (CNS),
which consists of the brain and
spinal cord and is enclosed within
the skull and spine
the peripheral nervous system
(PNS) comprises all other nerves.
brain
spinal
cord
16www.mstrust.org.uk
The peripheral nervous system
The peripheral nervous system is the
cabling that transmits information to
and from the central nervous system
from the rest of the body.
There are two main types of nerve
in the peripheral nervous system:
sensory nerves - collect information
from the body’s sense organs responding to touch, temperature,
pain, position, smell, sound and sight
motor nerves - pass messages
from the central nervous system.
When information has been
processed centrally, these nerves
carry instructions for action to the
muscles controlling movement,
speech, internal organs, and to the
various glands, such as the sweat
glands in the skin.
The part of the peripheral nervous
system that regulates the function of
our internal organs (heart, stomach,
intestines) is known as the autonomic
nervous system (ANS). Often we are
not aware of the ANS as it is involved in
involuntary or reflex functions such as
breathing, dilation/constriction of blood
vessels and increases/decreases in
heart rate. The ANS also controls some
of the muscles within the body.
The central nervous system
The central nervous system receives,
processes and stores information
from the peripheral nervous system
and initiates instructions for the
body’s responses.
The central nervous system is
divided into two major parts:
the brain - analyses and stores
information and directs the
action of the body
the spinal cord - passes
information to the brain and is
responsible for reflex reactions.
The central nervous system is
made up of two types of cells nerve cells and support cells.
Nerve cells
Nerve cells are called neurons.
The human brain and spinal cord
contain about 100 billion neurons.
The brain develops rapidly in the
unborn child and in the first years
of life. By the age of two, a person
has most of the neurons that they
will have during their lifetime.
Although cells in the body such as
blood cells die and are replaced,
many neurons are never replaced
when they die. As a result, disease
activity caused by MS that leads
to the damage or destruction of
neurons can cause permanent
disabilities.
dendrites
cell body
myelin sheath
axon
synapses
Nerve cell
nodes of
Ranvier
Tel: 01462 476700 17
The central nervous system
Neurons have specialised extensions
called dendrites and axons. A
neuron usually has a number of
dendrites but only one axon.
Information enters the neuron via
the dendrites, passes through the
cell body and then along the axon.
At the end of the axon, chemicals
called neurotransmitters carry the
message over a small gap, called
a synapse, to the dendrite of
another neuron.
The axon can be as long as a
metre, making neurons some of
the longest cells in the body. The
axon is surrounded by a protective
sheath of fatty protein called
myelin, which acts as insulation.
The myelin sheath has short
gaps about one micrometre apart
known as nodes of Ranvier, which
assist in the fast conduction of
messages. Nerve messages pass
along the axon from node to node.
The thickness of the myelin sheath,
and the size of the gap between
nodes, determines the speed of
messages, which can travel as fast
as 120 metres/second (268mph).
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Support cells
About 40 per cent of the total
volume of the brain and spinal cord
is made up of cells that support
neurons in various ways but which
do not carry information themselves.
The collective name for these
support cells is glial cells. Glia
comes from the Greek word for
glue and one of the roles of these
cells is to hold the nerve cells in
place. Other functions include
transporting nutrients to neurons,
cleaning up debris and digesting
parts of dead neurons.
Glial cells also provide the
insulation to neurons through the
production of myelin. The specific
glial cells that produce myelin in
the central nervous system are
called oligodendrocytes. Each
oligodendrocyte can supply
myelin for several axons and each
axon can be supplied by several
oligodendrocytes. The myelin
produced by oligodendrocytes
wraps around the axons in thin
sheets like a Swiss roll.
Damage to myelin, and the
interruption or delay to nerve
messages along the axon that this
causes, leads to the symptoms
of MS. If the protection of myelin
is lost, the axon itself can be
destroyed, which may cause
permanent problems.
Cerebrospinal fluid and the blood
brain barrier
The entire surface of the central
nervous system is surrounded by
a clear, colourless liquid called
cerebrospinal fluid (CSF). This
cushions the brain and spinal cord
within the bony casing of the skull
and spine and helps support the
weight of the brain.
Bibliography
National MS Society. Multiple sclerosis
information sourcebook. New York:
National MS Society; 2006 - www.
nationalmssociety.org/Sourcebook.asp
Neuroscience for kids - http://faculty.
washington.edu/chudler/neurok.html
Zajicek J, et al. Multiple sclerosis: a
practical manual. Oxford: Oxford University
Press; 2007.
The cerebrospinal fluid and
the central nervous system are
surrounded by a layer of cells
called the blood brain barrier.
This prevents large molecules
circulating in the blood from
reaching the central nervous
system. In MS, the blood brain
barrier is breached, allowing
immune cells to move across from
the blood stream and into the
central nervous system.
axons
myelin
oligodendrocyte
Tel: 01462 476700 19
The immune system
How does the immune
process work?
The immune system is the body’s
main defence system against
infection. It consists of a complex
collection of special cells and
chemicals that patrol the body,
identifying and fighting off material
that it identifies as foreign, such as
bacteria and viruses.
When a cell is attacked by a virus
or other invader, it sends out a
chemical as a warning signal. This
alerts a type of white blood cell
called macrophages which mount
the initial immune response. When
macrophages encounter foreign
matter they encircle and digest it [1].
antigen
helper T-cell
2. Macrophages use particles of the debris
called antigens to tell T-cells which cells
to attack.
virus
macrophage
cells
1. When macrophages encounter foreign
matter they encircle and digest it.
20www.mstrust.org.uk
Once some of the invading germs
have been destroyed, macrophages
use particles of the debris, called
antigens, to tell other immune
system cells which cells to attack
and to encourage a greater
response to the invasion. When this
happens, macrophages are known
as antigen presenting cells [2].
The cells that are prompted to
respond are a type of white blood
cell called lymphocytes. There are
two main groups of lymphocytes
B-lymphocytes or B-cells, which
mature in the bone marrow, are
programmed to recognise a
specific virus or bacterium.
T-lymphocytes or T-cells, which
mature in the thymus, respond to
the antigen presenting cells.
There are different types of T-cells:
helper T-cells help to influence how
the immune system responds, whilst
killer T-cells (also known as cytotoxic
T-cells) attack and destroy cells.
Prompted by the antigen presenting
cells, helper T-cells become activated
and direct other immune system cells
by producing ‘messenger’ molecules,
called interferons, which tell other
elements in the immune system how
to act.
Killer T-cells attack and destroy
cells which contain the antigen –
this includes both the invading cell
and any of the body’s cells which
have been infected. This prevents
the germ from reproducing and
infecting other cells. B-cells are
tuned to specific invaders. When
the germ is found in the body, the
B-cell clones itself and produces
millions of antibodies against that
germ. Antibodies are proteins
that lock onto the surface of the
specific invading germ helping the
body to kill it off [4].
At the start of an immune response,
one of the molecules produced is
gamma interferon which stimulates
B-cells and killer T-cells to attack [3].
killer T-cell
antigen
helper T-cell
4. B-cells produce millions of antibodies,
which lock onto an invader, helping the
body to destroy it.
3. Helper T-cells produce gamma interferon
to stimulate B-cells and killer T-cells.
Tel: 01462 476700 21
The immune system
The immune response causes
inflammation in damaged or
infected tissue. Inflammation
causes local blood vessels to
dilate, which increases blood flow
to the injured site and allows more
white blood cells to attack invaders
in the affected area.
Once the infection is under control,
helper T-cells release a messenger
molecule called beta interferon that
helps to calm down the immune
response.
Once an infection is over, some of
the antibodies developed to fight
it remain in the immune system.
This creates an ‘immune memory’,
which means that should the same
organism invade again, the body is
already prepared to combat it. This
is why many infectious diseases
such as mumps or chicken
pox usually only occur once.
Vaccination uses this principle to
forewarn the immune memory.
A small amount of matter from a
weakened version of an infection is
injected into the body. Whilst this is
not strong enough to cause illness,
it allows the immune system to
recognise the disease and to fight
it off should it appear again.
22www.mstrust.org.uk
Why does a white blood cell not
attack every cell in the body?
The antigen presenting cells are
controlled by genes called the
Major Histocompatibility Complex
(MHC) or the Human Leukocyte
Antigen (HLA). These genes, which
are different in every person, allow
the immune system to indentify
which cells belong to the body and
which are ‘foreign’.
It is these genes that create the
problems with rejection in organ
transplantation. Unless the genes
of the donor and the recipient are
closely matched, the immune
system will treat the new organ as
an invader and start to attack it.
In some conditions, for reasons
that are unknown, this protective
mechanism fails to work. The
immune system turns on the body’s
own tissue and attacks it as if it
were an invader. These conditions
are called autoimmune diseases.
How this causes the symptoms of
MS will be explored in more detail
later in this book.
Bibliography
Coles A. The immunology of multiple
sclerosis. Way Ahead 2003; 7(2): 4-5.
Tel: 01462 476700 23
What happens in MS?
It is widely believed that MS
is an autoimmune and/or
neurodegenerative condition. For
some reason - possibly following
exposure to an as yet unidentified
infection - the body’s immune
system starts to attack cells
within the central nervous system.
Activated T-cells pass through the
blood brain barrier where they
mistake the myelin sheath for a
foreign body and start to destroy it.
The process of damaging or
stripping away myelin from an axon
is called demyelination. Messages
that pass along a demyelinated
nerve become delayed or blocked.
As the central nervous system
controls processes throughout the
body, a wide range of symptoms
can occur, depending on where the
nerve damage has happened. For
example, damage to areas in the
spinal cord can lead to problems
with mobility or weakness.
For reasons that are not yet
understood, the attack by the
immune system tends to stop
after an indefinite period and scar
tissue develops on the damaged
nerve. The forming of scar tissue
over an area of damaged myelin is
24www.mstrust.org.uk
what forms the plaques, lesions or
scarring (‘sclerosis’) that show up
as white regions on T2 magnetic
resonance imaging (MRI) scans.
The name multiple sclerosis comes
from the fact that it causes areas of
sclerosis in multiple places in the
central nervous system.
Once the inflammation caused
by the immune attack is over, it
is possible for damaged myelin
to be replaced, a process known
as remyelination. Whether this
happens or not depends on the
level of damage to the surrounding
oligodendrocytes, the supporting
cells that produce myelin and
which are also attacked by this
process. Although the new myelin
can work effectively, it tends to be
thinner than unaffected myelin and
so messages through the affected
nerves may not be as fast as before
the attack. If there are several
periods of damage, the amount of
remyelination is reduced.
Remyelination tends to occur in the
earlier stages of MS. Over time, with
repeated attacks, oligodendrocytes
are damaged and destroyed and
myelin is not as easily replaced. If an
axon is left without the nourishment
and protection of myelin it is more
vulnerable to damage.
The central nervous system is
able to overcome small areas
of axon loss by finding ways to
reroute messages around an area
of damage through undamaged
nerve cells. This ability to adapt to
avoid areas of damage is called
plasticity. Should the area of
damage become too large, this
rerouting process is no longer able
to compensate and messages
to or from that part of the central
nervous system are permanently
blocked, resulting in symptoms
that do not improve.
Remyelination and rerouting
occur in the stage of MS where an
attack of worsening symptoms, or
relapse, is followed by a period of
remission when some or all of the
function returns.
Remyelination, rerouting and the
loss of axons can happen at the
same time in different parts of the
central nervous system.
Bibliography
Burgess M. Multiple sclerosis: theory and
practice for nurses. London: Whurr; 2002.
Compston A, et al. McAlpine’s multiple
sclerosis. 4th ed. London: Churchill
Livingstone; 2006.
healthy nerve cell
axon
nerve cell with damaged myelin
myelin
an axon left without myelin will die
Tel: 01462 476700 25
Diagnosis
There is no single test that will
conclusively show that someone
has multiple sclerosis and
diagnosis usually involves a
combination of investigations.
Similarly, none of the individual
symptoms people can experience
are unique to the condition. This
means that in order to reach
a diagnosis, a range of other
possible explanations has to be
ruled out and so the process can
be difficult and take some time.
The diagnosis of MS is made by a
neurologist. To show that someone
has MS, the neurologist is usually
looking for evidence of two or more
areas of scarring in different parts
of the central nervous system that
have occurred at different points in
time. The diagnostic criteria used
in MS are known as the McDonald
criteria.
Brain imaging or scanning is
becoming more powerful and it is
now technically possible to make
a diagnosis based on information
from one attack of symptoms
and evidence of further disease
activity from scans. However, it is
still unusual to diagnose MS from
26www.mstrust.org.uk
just a single attack of symptoms. In
this instance it is more likely that a
clinically isolated syndrome (CIS)
would be diagnosed.
A number of tests are used to try and
find information to help a neurologist
decide if someone has MS.
Patient history
As the neurologist needs to
establish that different symptoms
have occurred at different times, a
discussion of someone’s previous
symptoms and health is important
in establishing a diagnosis of MS.
Sometimes a previous episode of
numbness or double vision, for
instance, that might have passed
of its own accord or been treated
without thought of MS at the time,
can prove significant.
Neurological examination
There are a number of simple tests
that a neurologist can carry out that
may suggest whether or not MS is a
cause of symptoms. These include
checks on movement, coordination,
vision, balance, reflexes and
other functions of the five senses.
Information from these tests may
also give an indication as to where
in the central nervous system
damage has occurred and which
further tests might be useful.
Blood may be taken for testing.
There is no blood test that can
determine whether someone has
MS, but if there are abnormalities,
it is an indication that another
condition may be present and
might be causing symptoms.
Although the patient history and
neurological examinations might
suggest the diagnosis of MS, the
process usually involves one or
more tests to look for evidence of
MS within the body.
Magnetic resonance
imaging (MRI)
First used in MS in the early
1980s, MRI has become a key
diagnostic test.
monitor the behaviour of hydrogen
atoms in the body.
The nucleus at the centre of an
atom spins like a top. The powerful
magnetic field in an MRI machine
(more than 10,000 times stronger
than gravity) makes the atoms line up
in the direction of the magnetic field.
The machine then fires a pulse of
radio waves that causes the atoms
to spin in a different direction
(causing ‘resonance’). When the
pulse is turned off, the atoms
return to their natural alignment
within the magnetic field and
release energy. The machine picks
up this signal and sends it to a
computer, which converts it into an
image of a slice through the body.
An MRI machine is essentially a
large magnet, shaped as a tube,
within which the person being
scanned lies. The procedure is
painless, although the machines
can be noisy.
Images are created by using
magnetic fields and radio waves to
Tel: 01462 476700 27
Diagnosis
There are two main types of
MRI scan:
T1 weighted scans show areas
of permanent axonal damage
(black holes)
T2 weighted scans show the
total number of lesions, both
active and non active.
Typically a T2 scan is used for
diagnosis, scars caused by MS
show up as white patches on MRI
images, giving a very clear picture
of the effects of MS on the brain
and spinal cord.
White blood cells
Generally the number of cells
from the immune system in the
cerebrospinal fluid is low. For many
people with MS the count of white
cells in cerebrospinal fluid is up to
seven times higher than normal. A
count that is even higher than this
is probably due to an infection of
some sort, such as Lyme disease
and not MS.
Oligoclonal bands
In MS, cells from the immune
system cross the blood brain
barrier and attack the myelin that
surrounds nerves. As a result, the
level of proteins from the immune
system in the cerebrospinal fluid
of someone with MS is higher than
it should be and is higher than the
level in the blood.
Some people may undergo a third
type of scan. Here they are injected
with a contrast enhancing agent
called gadolinium before the scan.
This allows the MRI to show damage
to the blood brain barrier, which
indicates areas of active MS lesions
The test that shows the presence
and ongoing episodes of inflammation.
of immune system proteins in
cerebrospinal fluid is called
Lumbar puncture
A lumbar puncture involves inserting electrophoresis. A sample of fluid
a hollow needle into the base of the is placed on a gel and voltage is
applied. This causes proteins of
spine and drawing off a quantity of
the same size to bunch together,
cerebrospinal fluid (CSF), the fluid
forming visible ‘bands’. A sample
that surrounds the brain and spinal
of serum from the blood is also
cord within the skull and spine.
analysed for comparison with the
In the diagnosis of MS, analysis of
CSF sample.
cerebrospinal fluid is looking for:
28www.mstrust.org.uk
One band (monoclonal) in the
cerebrospinal fluid is normal.
‘Oligoclonal bands’ refers to the
presence of two or more bands. If
oligoclonal bands are seen in the
CSF, but not in the corresponding
serum sample, this is an indication
of immune activity in the central
nervous system. While this does
not necessarily mean that someone
has MS, more than 95% of people
with MS do have oligoclonal
banding in their cerebrospinal fluid.
Evoked potentials
Evoked potentials are tests that
measure the speed of nerve
messages along sensory nerves to
the brain.
The most commonly used test is
called visual evoked potentials
(VEP). Electrodes placed on the
skin measure messages sent from
the eyes in response to being
shown a flashing chessboard
pattern on a computer screen.
Less frequently, tests of sensations
from the skin (somatosensory
evoked potentials), which
involve tiny electric impulses,
and of hearing (auditory evoked
potentials), using clicks, can also
be carried out.
Visual evoked potentials work
on the basis that it is possible to
measure how long it takes for input
from the eye to get to the visual
cortex at the back of the brain
where this information is processed.
As damage to the optic nerve in
MS can slow messages down,
evoked potentials tests can indicate
the presence of an area of scarring
that is not causing any obvious
symptoms (described as clinically
silent). Delays of as little as 10
milliseconds can indicate that there
is damage to the nerve pathway.
Bibliography
Burgess M. Multiple sclerosis: theory and
practice for nurses. London: Whurr; 2002.
Compston A, et al. McAlpine’s multiple
sclerosis. 4th ed. London: Churchill
Livingstone; 2006.
How Stuff Works www.howstuffworks.com/mri.htm
Link H, Huang YM. Oligoclonal bands
in multiple sclerosis cerebrospinal fluid:
an update on methodology and clinical
usefulness. Journal of Neuroimmunology
2006; 180(1-2): 17-28.
Polman CH, et al. Diagnostic criteria for
multiple sclerosis: 2010 revisions to the
McDonald criteria. Annals of Neurology
2011; 69(3): 292-302.
Zajicek J, et al. Multiple sclerosis: a
practical manual. Oxford: Oxford University
Press; 2007.
Tel: 01462 476700 29
Types of MS
Typically MS is a condition
in which there are periods of
relapse - also called episodes or
attacks - which initially improve
but are then followed by episodes
where recovery is not complete,
and eventually a period of slow
progression with more persistent
symptoms. However, some people
experience a slow progression
of symptoms and disability
from the outset. This is a broad
generalisation of a wide spectrum of
experiences of MS.
The range of possible symptoms
and the levels of severity of those
symptoms mean the way MS
affects one person may vary widely
from someone else. Some people
will live with MS for many years with
few or very minor symptoms, whilst
others find that they progress much
more rapidly. The majority of people
will fall somewhere in between
these two ends of the spectrum.
There are a number of ‘types’ of
MS that are used to try to broadly
group individuals in accordance with
how the condition has developed.
However, each type encompasses a
wide range of experiences of MS and
30www.mstrust.org.uk
it is sometimes difficult to ascertain
what type an individual has. It is also
difficult to predict how an individual’s
MS will develop over time.
Relapsing remitting MS
The majority of people with MS
are diagnosed with the relapsing
remitting form. This means they
will have periods when symptoms
flare up - a relapse - followed by
periods of recovery - remission.
A relapse is the appearance of a
new symptom, or the reappearance
of old symptoms, which last more
than 24 hours in the absence of an
infection. A relapse often lasts for
considerably longer than that and
may persist for weeks or months.
Many people also find that some of
their symptoms will vary from day
to day, being worse one day and
better the next. This fluctuation is
not classed as a relapse.
As a very broad average, people with
relapsing remitting MS have one or
two attacks a year, although for the
individual, the number and frequency
of relapses and the nature and
severity of symptoms experienced
are unpredictable.
Some people with relapsing
remitting MS have very mild attacks
separated by very long periods with
no symptoms; this is sometimes
referred to as ‘benign’ MS. However,
the use of the term ‘benign’ is
controversial as many people find
that as the years pass their MS starts
to follow a more typical relapsing
remitting pattern, where the number
of relapses increase and the period
between relapses decreases, at
which point their MS would no longer
be considered ‘benign’.
Secondary progressive MS
Many people who are initially
diagnosed with relapsing
remitting MS find that over time
the frequency of their relapses
decreases but their disability
increases. As this progressive
phase follows a period of relapsing
remitting MS it is known as
secondary progressive MS.
As with relapsing remitting MS,
an individual’s experience of
secondary progressive MS can
vary widely. Some people find
that the increase or progression of
disability is very gradual, whilst for
others it can occur more quickly.
Studies that have monitored
people with MS over a long period
of time suggest that on average
the relapsing remitting phase lasts
around 19 years.
secondary progressive MS
disability
disability
relapsing remitting MS
time
time
Tel: 01462 476700 31
Types of MS
Primary progressive MS
About 10-15% of people with
MS are diagnosed with a form in
which disability increases from the
outset, usually with the absence
of distinct relapses. As this type is
progressive from onset, it is known
as primary progressive MS.
More women than men have the
relapsing remitting and secondary
progressive forms of MS. However,
this gender difference is not seen
in primary progressive MS, where
similar numbers of men and
women are affected.
disability
primary progressive MS
time
32www.mstrust.org.uk
Again, there is a variety of
experience of primary progressive
MS. Some people can have a
persistent increase in disability,
whilst others experience a more
gradual worsening of symptoms,
and many reach a plateau after a
period of steady progression.
Some people with MS which
has been progressive from the
outset can experience occasional
relapses; some textbooks refer to
this as progressive relapsing MS.
Bibliography
Burgess M. Multiple sclerosis: theory and
practice for nurses. London: Whurr; 2002.
Leray E, et al. Clinically definite benign
multiple sclerosis, an unwarranted
conceptual hodgepodge: evidence from
a 30-year observational study. Multiple
Sclerosis 2013; 19(4): 458-465.
Lublin FD, et al. Defining the clinical course
of multiple sclerosis. Neurology 1996; 46:
907-911.
Sayao AL, et al. Longitudinal follow-up
of ‘benign’ multiple sclerosis at 20 years.
Neurology 2007; 68(7): 496-500.
Tremlett H, et al. Natural history of
secondary progressive multiple sclerosis.
Multiple Sclerosis 2008; 14(3): 314-24.
Tel: 01462 476700 33
The cause of symptoms
In MS, only nerves in the brain
and/or spinal cord are damaged.
However, because these nerves
control the functions of the whole
body, MS can cause a wide variety
of symptoms. The type, severity
and duration of symptoms will vary
from person to person.
How MS affects an individual
depends on where damage
occurs and which nerve messages
are interrupted or blocked. For
example, some people can have an
MRI scan that shows a number of
areas of scarring, but they may not
experience noticeable symptoms
because the scarring has occurred
in areas of the brain which are not
associated with a major function.
Conversely, a single scar that
damages an area controlling
bladder function, for instance, can
have a serious impact.
Similarly, the actual level of disease
activity can remain constant with
a consistent number of areas of
scarring. However, if a new scar
interrupts an important function,
such as walking, it can seem to the
individual as though the MS has
accelerated.
34www.mstrust.org.uk
Whilst the complexity of the brain
and how it handles information are
still far from fully understood, certain
areas are associated with specific
functions. The following pages give
a very broad overview of how
damage caused by MS to these
areas can lead to certain symptoms
being experienced.
The following pages cover a range of
symptoms that MS can cause, but it is
important to stress that most people
only experience a small number of
these. Although there are no drugs
to cure MS, there are treatments for
many of the symptoms. There are
also treatments that aim to modify
the course of MS. Information on
treatments can be found in other MS
Trust publications or by contacting the
MS Trust Information Service.
MS Trust Information
Service
Spirella Building, Bridge Road,
Letchworth Garden City,
SG6 4ET
T: 0800 032 3839
or 01462 476700
e: [email protected]
www.mstrust.org.uk/publications
5
3
2
4
1
Site of damage
Symptom
1 Spinal cordSpasticity
Bladder problems
Bowel problems
Weakness
2 Brainstem
Double vision and nystagmus
3 Optic nerve
Optic neuritis
4 Cerebellum
Balance and dizziness
Tremor
5 Areas involved with thought Cognition
and emotionDepression
Symptoms not associated with a single area
Fatigue
Speech and swallowing
Pain
Tel: 01462 476700 35
The cause of symptoms
1. Spinal cord
Most nerves in the peripheral
nervous system are not connected
directly to the brain but to the
spinal cord, which acts as the main
route for nerve messages to and
from the brain.
The spinal cord also controls reflex
reactions. Reflex reactions are
automatic responses to stimuli,
such as pulling the hand away if it
touches something hot.
Spasticity
This causes the affected limb to
feel stiff or tight and often to be
difficult to move.
The instruction to contract a
muscle can be triggered by
sensory signals from peripheral
nerves in a muscle. When the
signal reaches the spinal cord, it
responds with an automatic, reflex
response and also by passing the
message to the brain. The brain
assesses the situation and sends
a message back down the spinal
cord telling the muscle how to
respond. The whole process is
normally almost instantaneous.
Spasticity is a condition in which
muscle tone becomes greatly
increased. Muscle tone refers to
the level of tension or resistance to
movement in a muscle and is what
enables people to move limbs or
hold a position. For instance, to
bend your arm, you must shorten
or contract the bicep muscle at the
front of the arm (increasing the tone)
and at the same time lengthen or
relax the tricep muscle at the back of
the arm (reducing the tone).
In MS, spasticity occurs if there is an
area of scarring between the brain
and the point where the nerve from
the muscle joins the spinal cord. The
reflex action still takes place, but
the message to or from the brain
is interrupted. Thus no message to
relax the muscle is received, or it is
delayed, and the muscle remains
contracted and stiff.
When someone has spasticity in a
limb, the signals from the brain are
interrupted and the muscle remains
in its shortened, contracted state.
Depending on the area of damage
in the process, spasticity can occur
in any muscle in the body. This
can lead to a number of problems
36www.mstrust.org.uk
including difficulties with walking,
speech or swallowing, and
bladder control.
The degree of spasticity can vary
from mild muscle stiffness to
severe, painful muscle spasms.
More information from the
MS Trust:
Spasticity factsheet
Spasticity triggers
Bladder problems
Types of bladder problem
Frequency - an increase in
the number of times someone
needs to urinate in a day
Urgency - the feeling of
having to empty the bladder
immediately, an inability to
‘hold on’
Hesitancy - difficulty in starting
to urinate
Incontinence - the inability to
hold urine in the bladder until
an appropriate time
The wall of the bladder consists
of muscle called the detrusor
muscle, which stretches to store
urine. At the base of the bladder
is a valve called the urethral
sphincter, which opens to let
urine out.
The average capacity of the
bladder is between 300 and 500ml
(about three quarters of a pint). On
average, people produce about
1ml of urine every minute.
The urge to empty the bladder
usually occurs when it contains
about 200ml. At this point the
bladder is expanded enough to
stimulate nerve endings in the
detrusor muscle. This triggers a
message to an area of the spinal
cord that controls the reflex
action that causes the bladder to
contract. A message is also sent
to the brain, signalling the need to
urinate. When the brain assesses
that it is appropriate to do so it
passes simultaneous messages
back through the spinal cord telling
the valve to open and the detrusor
muscle to contract, and urine is
passed. Normally this occurs six to
eight times a day.
Tel: 01462 476700 37
The cause of symptoms
Damage to areas of the spinal cord
or brain that control the phases of
this process can cause different
types of problem.
Failure to store
In this situation, damage occurs to
the spinal cord between the area
controlling the bladder reflex and
the brain. When this happens, the
controlling message from the brain
is interrupted and the reflex action
means the bladder will empty
automatically. For the individual
this means they will need to go
to the toilet often (frequency),
but usually with little or no notice
(urgency), resulting in incontinence.
Failure to empty
This happens when the scarring
occurs in the reflex area of the
spinal cord interrupting the
instruction to empty the bladder.
This means that even when
someone goes to the toilet, they find
it difficult to pass urine (hesitancy).
The bladder does not empty
properly and keeps filling beyond its
normal level until it overflows. This
leads to frequent, urgent needs to
go to the toilet, often accompanied
by overflow incontinence.
38www.mstrust.org.uk
Combination of failure to store and
failure to empty
This occurs when scarring causes
a loss of coordination between the
contracting of the bladder and the
opening of the valve. Depending on
where the damage occurs this can
either mean:
the bladder contracts but the valve
remains closed, so that urine can
not be released – the individual
feels a strong urge to go to the toilet
(urgency) but is unable to properly
empty their bladder (hesitancy)
brain
spinal
cord
reflex
urine
urine
Normal function
The bladder triggers a message to the
reflex area of the spinal cord and a
message is also sent to the brain. The
brain passes instructions to the bladder
the bladder relaxes and the
valve opens resulting in an
inability to store any urine which causes incontinence.
Rather than helping the problem,
reducing fluid intake can in fact
make bladder symptoms worse.
If the body does not have sufficient
fluid, urine becomes concentrated
and flow slows down. This allows
painful crystals to form and
bacteria to grow, which can lead
to infections.
Difficulty with both bladder control
and walking often go together in
MS. The wiring of the nervous
system means that the connections
to the bladder from the spinal cord
are below those to the legs. If there
is damage to the nerves further up
the spinal cord, both functions can
be affected.
More information from the
MS Trust:
Bladder management factsheet
brain
brain
spinal
cord
spinal
cord
reflex
reflex
urine
urine
Failure to store
Failure to empty
Damage occurs between area controlling
the bladder reflex and the brain
Scarring occurs in the reflex area of the
spinal cord interrupting the instruction to
empty the bladder
Tel: 01462 476700 39
The cause of symptoms
Bowel problems
In the healthy bowel, once food
has passed through the digestive
system, waste material is collected in
the colon where it forms into stools.
When the colon is stretched to a
certain size, nerve responses trigger
a reflex process that causes a bowel
movement. The stool is passed into
the rectum - the area occupying
the last six inches of the digestive
system. As the rectum fills, it triggers
another reflex action that causes the
stool to pass to the anal canal.
The anal canal is about an inch
long with a valve, or sphincter, at
each end. The internal sphincter,
which separates the anal canal
from the rectum, is opened by an
involuntary reflex action under
the control of the spinal cord. The
external sphincter can be controlled
to prevent inappropriate defecation.
When someone wishes to defecate,
the external sphincter is relaxed and
they ‘bear down’ - increasing the
pressure in their abdomen to help
push the stool out.
Although the causes of bowel
disorders in MS are not fully
known, it is thought that damage
to nerves controlling different parts
of this process can lead to different
bowel problems.
stomach
rectum
interior
sphincter
small
intestine
rectum
colon
(large intestine)
anus
exterior sphincter
40www.mstrust.org.uk
Constipation
Constipation can be caused
by interruptions to the sensory
messages from the colon or rectum
that signal fullness. The body does
not realise that there is a need to
move the stool on to the next stage
in the process.
Constipation can also be due to
the slowing down of the digestive
process that can occur in people
who do not undertake much
physical activity or who cannot
bear down with sufficient pressure
due to weakness.
Not drinking enough can also
cause constipation. As food
passes through the body, water is
extracted. If there is not enough
fluid in the diet, by the time food
reaches the end of the process, it
has become a dry, hard stool which
does not move as easily through
the system.
Faecal incontinence
Faecal incontinence is the inability
to control defecation. This happens
when damage to nerves occurs
between the reflex area in the
spinal cord and the areas of the
brain that give voluntary control to
bowel movements. This does not
necessarily mean that the individual
experiences diarrhoea, but if this
lack of coordination affects the parts
of the process where stools are
formed, it can result in ill formed and
runny stools.
Faecal incontinence can also
be caused by constipation. A
build up of constipated matter
can sometimes mean that the
sphincters in the anus and the
rectum do not close properly,
allowing runny stools to escape
around the blockage.
More information from the
MS Trust:
Bowel management
factsheet
Weakness
One of the causes of weakness
in muscles in MS is the poor
transmission of messages by
damaged nerves, mainly within the
spinal cord. It is often associated
with fatigue. As the nerve damage
makes muscles less responsive, it
requires more energy to carry out
actions. Feeling weak can cause
Tel: 01462 476700 41
The cause of symptoms
an individual to become less active
in an attempt to conserve energy,
but this can cause weakness to
increase. An already weak muscle
that is not used will become
weakened further, a process known
as atrophy.
However, as muscle weakness in
MS is primarily due to problems
with nerves rather than within
muscles, expending a great deal
of energy by exercising to the
point of exhaustion can also make
weakness worse.
For many years people with MS
were advised to avoid exercise
due to the impact it could have on
weakness and fatigue. It is now felt
that exercise is beneficial if it works
on gently building up endurance
and strength in muscles without
increasing weakness and fatigue.
More information from the
MS Trust:
Move it for MS DVD
Exercises for people
with MS
www.mstrust.org.uk/exercise
42www.mstrust.org.uk
2. Brainstem
The brainstem is the area at the
base of the brain that connects to
the spinal cord. It contains areas
responsible for basic functions
such as breathing, heart rate,
blood pressure and control of the
bladder. Many of the processes
controlled by the brainstem are
outside conscious control. The
peripheral nerves that maintain
processes such as breathing and
digestion are referred to as the
autonomic nervous system.
The midbrain area of the brainstem
controls vision, hearing, body
movement and the movement of
the eyes.
Visual problems
Visual problems are common in
MS and are often one of the first
symptoms people experience.
Double vision
Visual disturbances in MS can be
caused by damage to the nerve
pathways that connect to the 12
muscles that control the movement
of the eyes. A reduction of
coordination in the eyeballs leads
to double vision (diplopia).
Nystagmus
Sometimes nerve damage can
result in a flickering or jerking
motion of the eyeballs, often
when moving the eyes to a certain
position. This disorder is called
nystagmus.
3. Optic nerve
Another common visual problem
experienced by people with MS is
due to damage to the optic nerves,
which carry information from the
back of the eyes to the brain.
optic nerve
eye ball
Uhthoff’s phenomenon
Some people find that an increase
in temperature affects their vision
in some way. This effect is known
as Uhthoff’s phenomenon or
Uhthoff’s sign. These symptoms
lessen or disappear when the
individual cools down again.
visual cortex
Optic neuritis
Inflammation of the optic nerve is
called optic neuritis. Optic neuritis
can cause a sudden, usually
temporary, loss of vision. An attack
usually occurs on one side only and
is often accompanied by pain behind
the affected eye. The effects of an
Tel: 01462 476700 43
The cause of symptoms
attack of optic neuritis can include
complete loss of sight, partial blind
spots (called scotomas), blurred or
foggy vision, or the loss or worsening
of colour vision.
More information from the
MS Trust:
A to Z of MS optic neuritis
www.mstrust.org.uk/atoz/
optic-neuritis.jsp
4. Cerebellum
The cerebellum controls
movement, balance and posture.
Balance problems and
dizziness
The body uses the complex
interaction of a variety of sources
to maintain an idea of how it fits
in with its environment, such as
whether it is upright or maintaining
balance. This requires the
coordination of information from
vision, from the balance systems in
the inner ear and information from
movement, touch and joint sensors
throughout the body.
44www.mstrust.org.uk
For instance, when someone turns
their head, their eyes, neck muscle
sensors and two inner ears all give
matching information to the brain.
If something causes a mismatch in
the information, it affects the sense
of orientation and causes feelings of
dizziness, vertigo or loss of balance.
These outgoing and incoming
messages are coordinated in the
cerebellum. If MS causes damage to
the nerves in this part of the brain,
balance can be affected.
More information from the
MS Trust:
A to Z of MS balance
www.mstrust.org.uk/atoz/
balance.jsp
Ataxia and tremor
Disruption to the coordination of
movements is called ataxia. In its
mildest form this can be mistaken
for clumsiness. If damage to the
cerebellum is more severe, the
disruption to coordination can lead
to shaking or tremor.
Tremor in MS usually does not
happen in completely relaxed limbs,
but is triggered by a mismatching of
messages when trying to perform
a function. This makes tremor in
MS distinct from that found in
Parkinson’s disease, where shaking
occurs in muscles at rest.
There are two main types of tremor
that can affect people with MS.
Intention tremor
This occurs when someone tries
to carry out a task. For instance,
an arm can start to shake as it
moves to pick up a teacup or
the telephone, with the shaking
worsening as the hand approaches
the object.
5. Areas of the brain
involved with thought and
emotion
Cerebral cortex
The cerebrum makes up nearly
70 per cent of the brain. It is the
outer layer of the brain which has
the familiar walnut like bumps and
grooves (called gyri and sulci). The
cerebral cortex controls thought,
voluntary movement, language,
reasoning and perception.
cerebral cortex
limbic system
Postural tremor
This occurs when the body has
been held in a particular position
for a period of time. It usually
affects the head, neck and trunk.
More information from the
MS Trust:
A to Z of MS ataxia
w
ww.mstrust.org.uk/atoz/
ataxia.jsp
A to Z of MS tremor
www.mstrust.org.uk/atoz/
tremor.jsp
hypothalamus
Tel: 01462 476700 45
The cause of symptoms
Hypothalamus
The hypothalamus is a small
structure at the base of the brain
that controls body temperature,
emotions, hunger, thirst and the
circadian rhythms - the natural
variations in the body’s activities
throughout the day.
Limbic system
The limbic system (or the limbic
area) is important for controlling the
emotional response to situations. It
includes the hippocampus, which
is important for memory.
Cognition
As well as affecting the control of
muscles and actions in different
parts of the body, damage to the
brain caused by MS can also affect
mental processes. These are called
cognitive or cognition problems.
Generally, cognition problems
in MS affect the speed or ease
with which someone can process
information, and do not indicate a
loss of underlying intelligence.
46www.mstrust.org.uk
Memory difficulties
Memory difficulties are primarily
related to the recall of recent events
or information and forgetting to
carry out planned actions.
Information processing problems
This results in difficulties when
following complicated instructions
or a series of instructions, especially
if the information is given rapidly.
Problem solving difficulties
When there is an inability to hold a
number of pieces of information in
the head at once and being unable to
mentally structure thoughts to carry
out a series of separate actions.
Word finding
The inability to find the word
you need when speaking, also
called the ‘tip of the tongue’
phenomenon, is a short-term recall
problem rather than the loss of
memory for that word.
Concentration and attention
span problems
This tends to occur when a lot of
information is being delivered to a
person at once, for example where
several people are talking or in a
noisy, bustling environment.
Cognitive problems can fluctuate
from day to day and can worsen
during relapse or periods of fatigue.
Some medications, including those
used to counteract pain, fatigue
and depression, may also have an
impact on these problems.
Although research suggests that
these symptoms can affect almost
half of all people with MS, many
people may not recognise them as
symptoms of MS or may find ways
to compensate for the problems
without seeking treatment.
Difficulties can arise early in the
course of someone’s MS, although
the greater the disease duration
and severity the more likely
problems are to occur.
More information from the
MS Trust:
Cognition factsheet
Mood swings and depression
The effects of MS can cause
alterations in an individual’s mood
and many people with MS experience
depression. Depression involves
persistent sadness lasting more than
two weeks, accompanied by other
symptoms such as an altered sleep
pattern, feelings of hopelessness,
guilt and low self esteem, thoughts
of death, reduced energy and the
inability to concentrate and to take
pleasure in anything.
Mood swings and depression in
MS can be due to a number of
factors. The uncertainty and
frustrations of living with the
condition can have a negative effect
on mood and the side effects of
some medication, such as steroids,
can also affect emotional responses.
Episodes of fatigue can be
particularly associated with affected
mood. Depression may
also be caused directly by MS
damage to the nerves in the brain.
MS can also directly affect
emotional responses and cause
episodes of uncontrolled laughter or
crying. Referred to as ‘pseudobulbar
affect’, ‘emotional lability’ or
Tel: 01462 476700 47
The cause of symptoms
‘pathological laughter and crying’,
the exaggerated response will have
little or no relationship to actual
events or the individual’s feelings.
Recognition of these disorders as
symptoms of MS has only occurred
relatively recently and the precise
causes are poorly understood.
More information from the
MS Trust:
A to Z of MS emotionalism
www.mstrust.org.uk/atoz/
emotionalism.jsp
Depression factsheet
6. Symptoms not
associated with a single
area of damage
For some symptoms it is not
possible to identify a single area of
the central nervous system that is
the chief area of damage. In other
cases, the cause of the symptom
remains unclear.
Fatigue
Fatigue is one of the commonest
symptoms of MS and one that can
often cause major problems to a
person’s life.
The cause of fatigue in MS is not
well understood. It is thought
to result from a combination of
factors, partly caused by MS itself
(known as primary fatigue) and
partly by other factors (secondary
fatigue) that affect the person with
MS more significantly than those
without the condition.
Primary fatigue is thought to be
a combination of slowed nerve
messages from the brain and
spinal cord and a build up of
weakness in muscles due to lack
of stimulation. The level of fatigue
48www.mstrust.org.uk
does not reflect the severity of
someone’s MS and people can
experience fatigue that prevents
them from working, or which
interrupts their daily life, whilst
having no other symptoms.
MS fatigue or ‘lassitude’ is very
different from the tiredness or
exhaustion that people without MS
experience following strenuous
exercise or a busy day at work.
Fatigue is described as interfering
with normal activity and being out
of all proportion to any activity
undertaken. It is characterised by
the sudden loss of energy and the
inability to continue an activity.
MS can also cause ‘shortcircuiting’ or neuromuscular
fatigue. This happens if nerve
messages to muscles become
confused when someone is
performing repeated movements.
Messages start to ‘leak’ into other
nerve cells and it becomes harder
for the brain to get instructions
through. For example, the legs may
become increasingly heavy and
difficult to move when walking, or
the arms may be affected when
writing for a period of time.
Secondary fatigue is fatigue that
results from another symptom or
cause, rather than being caused
by the condition directly. Factors
that can add to fatigue include lack
of sleep, low mood or depression,
stress, inadequate diet, lack of
exercise, infections or side effects
of medication.
Heat can increase fatigue in MS
and some people with MS find that
symptoms get worse during spells of
hot weather. This was first observed
in the late nineteenth century, and for
a time, one of the diagnostic tests
for MS was to put the patient into a
hot bath and observe if this made
symptoms worse.
More information from the
MS Trust:
Living with fatigue
Tel: 01462 476700 49
The cause of symptoms
Speech and swallowing
There are a number of different
speech and swallowing problems
that can affect people with MS.
Damage to the various parts of the
brain that control thought, memory,
verbal fluency or attention can
lead to difficulty in finding words or
forming sentences. This disorder is
called dysphasia.
soft palate
Speech requires the complicated
interaction and coordination of
several parts of the body including
the lungs, diaphragm, vocal cords,
lips, tongue and nasal cavity.
Damage to areas of the central
nervous system that control any of
these elements can have an effect
on speech. Similarly, fatigue or
weakness can affect any part of the
process. When a speech disorder
is due to damage affecting the
muscles used in speech, it is called
dysarthria. This can lead to slurred
speech, or difficulty in controlling
volume, articulation or intonation.
epiglottis
Many of the muscles used in speech
also have a role in swallowing and
a lack of coordination can cause
difficulties when a person is eating
or drinking. This is known as
dysphagia.
nasal cavity
tongue
lips
larynx
vocal cords
windpipe
(trachea)
50www.mstrust.org.uk
oesophagus
If the various processes involved
in holding food in the mouth,
chewing and swallowing are not
synchronised, a number of different
problems can occur. Food may
get stuck in the throat, which
causes choking; may move too
slowly in the oesophagus (the
tube connecting the mouth to the
stomach), which causes coughing
and spluttering; or may go into the
windpipe (which should be closed
during swallowing) or the lungs,
which is known as aspiration.
More information from the
MS Trust:
A to Z of MS
speech problems
www.mstrust.org.uk/
speech.jsp
A to Z of MS
swallowing problems
www.mstrust.org.uk/
swallowing.jsp
Pain
For many years, the medical world
considered MS to be a pain free
condition. This idea has now been
completely overturned and studies
suggest that the majority of people
with MS experience some form of
pain as a symptom at some stage.
There are two main types of pain
in MS.
Muscle pain
Muscle pain (called nociceptive
pain or musculoskeletal pain)
is generated by damage to the
muscles, tendons, ligaments and
soft tissue of the body.
This is the sort of pain that is felt
when someone falls over or cuts
themselves. In MS, this pain is not
caused directly by damage to the
nerves but develops as a result
of other symptoms. For instance,
spasticity in a leg can cause
someone to alter the way they walk
or alter their posture, which can
result in added strain on the back,
legs or arms.
Nerve pain
Pain that results from damage to
nerves is known as neurogenic,
neuropathic or nerve pain. With
this type of pain, nerve messages
are interrupted, or blocked, and
the brain interprets the incomplete
information it is receiving as pain.
Whilst the pain experienced can be
severe or long lasting, unlike muscle
pain, there is no physical cause of
the symptom.
Tel: 01462 476700 51
The cause of symptoms
Examples of nerve pain include:
Paraesthesia or dysaesthesia
Persistent, uncomfortable,
abnormal sensations are
experienced differently from
person to person. The pain can
be described as sensations such
as pins and needles, burning and
crawling feelings, numbness or
tightness.
L’hermitte’s sign
Sometimes referred to as the
‘Barber Chair’ phenomenon, this
is caused by damage to the spinal
cord in the neck. Movements of
the neck cause a brief but sharp,
painful, buzzing, electric shock
feeling running down the spine and
into the legs.
Trigeminal neuralgia
The trigeminal nerve controls
movements and sensation in the
face and mouth. Damage to this
nerve at the point where it meets
the central nervous system at
the base of the brain can lead
to episodes of sharp pain in the
face triggered by actions such
as talking, chewing, smiling or
brushing teeth.
52www.mstrust.org.uk
More information from the
MS Trust:
Pain factsheet
Bibliography
Burgess M. Multiple sclerosis: theory and
practice for nurses. London: Whurr; 2002.
Burks JS, et al. Multiple sclerosis:
diagnosis, medical management and
rehabilitation. New York: Demos; 2000.
Fowler CJ. Pathophysiology of micturation
disturbances in multiple sclerosis.
Sexuality & Disability 1996; 14(1): 7-12.
MS Trust. Multiple sclerosis information
for health and social care professionals.
Letchworth: MS Trust; 2011.
National MS Society. Multiple sclerosis
information sourcebook. New York:
National MS Society; 2006.
Neuroscience for kids. Available from: URL:
http://faculty.washington.edu/chudler/
neurok.html [Accessed 21 Feb 2013]
Schapiro RT. Managing the symptoms
of multiple sclerosis. 4th ed. New York:
Demos; 2003.
Tel: 01462 476700 53
Future research
Where will we find an answer?
Despite being first described in
1868, MS still remains a condition
of many mysteries: no known
cause, no means of prevention,
and no cure - but there have been
significant advances.
Until the 1990s, there were no
drugs that had any effect on the
underlying disease activity of
MS, and treatment was focused
on medication and management
techniques for the various
symptoms that people experienced.
Whilst symptomatic treatment
remains at the core of the medical
management of MS, the last few
decades have seen breakthroughs
that have shown the possibility
of developing therapies that may
effectively tackle MS itself.
Typically in the past, research has
primarily focused on the relapsing
remitting form of MS, however
today more and more resources
are being directed at research into
progressive MS.
Very broadly, there are three main
focuses of research for altering the
course of MS:
54www.mstrust.org.uk
immune system - altering the
processes that cause damage to
nerves
neuroprotection - protecting
nerves to prevent any further
damage
repair - repairing or replacing
damaged nerve cells to reverse
disability.
Immune system
Initial experimental therapies for
modifying the course of MS were
based on attempts to control the
activity of the immune system.
The first drug to be licensed was beta
interferon - a commercially produced
version of a substance that occurs
naturally in the immune system. The
role of beta interferon is to calm
down the immune system once an
infection has been dealt with. As a
drug it was hoped that this would
limit the effect of the immune cells
that mistakenly attack the myelin
surrounding nerves (see page 20).
Several different beta interferon drugs
are now available (Avonex, Betaferon,
Extavia, Rebif).
Another drug called glatiramer
acetate (Copaxone) was developed
at the same time as beta interferon.
This is a synthetic combination
of four molecules that resembles
the myelin protein surrounding
nerve fibres.
Studies showed that on average
both the beta interferon drugs and
glatiramer acetate helped to slow
the relapse rate of someone with
MS by a third and to reduce the
severity of those relapses that did
still occur.
Attempts to produce more powerful
drugs that reduce the immune
response further have come up
against the problem that this
approach is not focused on any
specific part of the system. As
a result these drugs can attack
aspects of the immune system
needed to fight infections as well as
the elements that might be involved
in MS.
Targeting antibodies
Some researchers have looked at
ways of targeting specific elements
within the immune system that
play a role in MS, while leaving the
remaining immune system intact.
This approach has led to the
development of a new class of
drugs called monoclonal antibodies.
Antibodies are proteins in the
immune system that bind onto
an invading cell or germ and help
to destroy it (see page 21). Each
antibody has a single target, when
that target is found in the body
millions of antibodies are produced
against it from a single B-cell. This
means that if antibodies can be
identified that bind to cells involved
in attacking nerve cells and causing
disease activity in MS, maybe drugs
can be developed that will only
affect those cells.
Monoclonal antibodies are created
by cloning a cell that produces a
single antibody and this has led
to the creation of several new
drugs that may be used to treat
MS. Examples of monoclonal
antibodies include:
natalizumab (Tysabri), which
binds to and disables the area
of white blood cells that allows
them to cross the blood brain
barrier, effectively keeping cells
that might attack myelin from
coming into contact with the
brain or spinal cord
Tel: 01462 476700 55
Future research
alemtuzumab (Lemtrada),
which binds to proteins on the
surface of the white blood cells
associated with attacking the
myelin on nerves.
The World Health Organisation’s
standards for naming drugs means
that all monoclonal antibodies end
with -mab.
Research has shown that these
drugs are more effective than
beta interferon and glatiramer
acetate at reducing the number of
relapses. However, the research
has also shown that there are
also more serious side effects
and so treatment requires regular
monitoring for, and treatment of,
these effects.
Oral treatments
All of the drug treatments mentioned
so far have to be injected or given
intravenously. If taken as tablets, the
active ingredients would be digested
before they could work.
More recently a number of drugs
have been developed that provide
a disease modifying effect in
tablet form:
56www.mstrust.org.uk
BG-12 (Tecfidera) is thought
to work by reducing the
inflammation caused when the
immune system attacks myelin
and by protecting the nerve
cells from damage caused by
chemicals released during the
immune attack
fingolimod (Gilenya) works by
binding to the surface of white
blood cells in the immune
system, trapping them in the
lymph nodes and preventing
them from attacking cells in the
central nervous system
laquinimod is thought to work
by affecting the levels of
certain substances released
by immune cells to reduce the
inflammation caused when the
immune system attacks myelin.
Thus preventing immune cells
that cause the damage in MS
from entering the brain and
spinal cord and by triggering
the production and release of
brain-derived neurotrophic factor
(BDNF) which plays a key role in
nerve survival and growth
teriflunomide (Aubagio) is
thought to work by reducing
the number of white blood cells
(T-cells and B-cells) involved in
the MS immune response.
More information from the
MS Trust:
Disease modifying drug
therapy: what you need
to know
Alemtuzumab (Lemtrada)
factsheet
BG-12 (Tecfidera) factsheet
Laquinimod factsheet
Teriflunomide (Aubagio)
factsheet
Future drug development
All of the current disease modifying
drugs treat the relapsing remitting
type of MS. Increasingly, research
suggests that early, aggressive
treatment of MS, effectively before
someone is showing any signs of
disability, may prevent or greatly
reduce subsequent damage from
occurring. If treatment is carried
out once MS has started to attack
and destroy nerve cells, then
drugs are much less effective in
controlling progression.
The disease modifying drugs work
by altering some of the processes
within the body that cause MS
relapses to happen and thus
protect nerves from damage.
The following are just some of the
drugs that are currently in research:
Relapsing remitting MS
daclizumab – a monoclonal
antibody that interferes with
the activation and growth of
lymphocytes
ocrelizumab - a monoclonal
antibody that targets a marker
on the surface of B-cells which
are thought to influence the
abnormal immune response that
causes the immune system to
attack myelin
Secondary progressive MS
masitinib – a drug that targets
a type of cell involved in allergy
and inflammation, which is
known as a mast cell, leading to
a reduction in immune response
and inflammatory processes
natalizumab (Tysabri) – already
licensed for use in RRMS
siponimod – belongs to the
same class of drugs as
fingolimod and works by binding
to the surface of white blood
cells in the immune system,
trapping them in the lymph
nodes and preventing them from
attacking cells in the central
nervous system
Tel: 01462 476700 57
Future research
Primary progressive MS
natalizumab (Tysabri) – already
licensed for use in RRMS and
also being tested in SPMS
fingolimod (Gilenya) – already
licensed for use in RRMS
masitinib – also being tested
in SPMS
ocrelizumab – also being tested
in RRMS
The processes that cause MS to
become progressive, once nerves
have been damaged or destroyed,
are less well understood than the
processes that occur in relapsing
remitting MS. To date there is
no disease modifying treatment
for progressive MS. In the past a
number of different drugs have
been studied as treatments for
progressive MS, but any positive
results were very modest.
As can be seen from the list above,
many drugs are currently being
investigated to determine whether
they have any modifying effect
on progressive MS. However,
alternative approaches will
probably also be needed to protect
existing nerves and to repair or
replace those that have been lost.
58www.mstrust.org.uk
Neuroprotection
Neuroprotection is a relatively
new area of research in MS.
The permanent symptoms of
the progressive types of MS
develop when nerve cells are
destroyed. This is thought to
occur when nerve fibres are
exposed to chemicals produced
by the inflammation of tissue
that MS causes. The theory of
neuroprotection is that, if the nerve
cells can be protected from these
chemicals, destruction - and thus
further permanent problems - can
be lessened or prevented.
Different aspects of neuroprotection
are being examined, concentrating
on different elements that lead to
loss of nerve cells. Inflammation
leads to the increase in levels of
nitric oxide, calcium and sodium.
Contact with high levels of these
chemicals can damage nerve cells
and research is underway to examine
the impact of blocking their effects.
Another approach is looking at
a type of drug called glutamate
receptor blockers. Glutamate is
one of the chemicals involved in
transmitting messages from nerve
cell to nerve cell, but excessive
glutamate can also damage nerves.
Research in this area is at a
relatively early stage and many
studies are exploring the potential
of neuroprotection as a strategy
rather than the possibility of
bringing a particular drug to market
in the short-term.
Neuroprotective drugs will not
be able to reverse progression or
restore function that has already
been lost. However, if suitable
drugs can be developed, it is
hoped that the progression of MS
can be significantly slowed down.
Repairing and replacing myelin
Whilst drugs that alter the action
of the immune system or that
protect nerves may help to limit the
accumulation of damage, neither
will reverse the progressive effects
of MS. Exploration of processes
that might repair areas of damage
and thus allow people to recover
function that has been lost is another
important area of MS research.
From observing areas of the central
nervous system that have been
damaged by MS it is known that, in
the earlier stages of the condition,
the body can replace lost myelin
to some extent. If the affected area
Tel: 01462 476700 59
Future research
is no longer being attacked by
the immune system, new myelin
can be formed, which will repair
damage to nerve cells and reverse,
at least to a degree, some of the
disability caused.
Various strategies for repairing
and replacing myelin have been
investigated. For instance,
chemicals within the immune
system have been identified that
can accelerate the growth of
myelin. There is a large body of
work going on in this field in the
UK at centres in Cambridge and
Edinburgh, but the research is still
at a very early stage.
Repurposing drugs
Another approach that is currently
being explored is the ‘repurposing’
of drugs. This is where treatments
whose safety profile is known
due to their use in other medical
conditions are being looked at
to see if they could be useful in
MS. If this approach is successful
it has the potential to speed up
the development of drugs, as the
treatments are already known to be
safe in humans.
60www.mstrust.org.uk
Teams in London and Edinburgh
are using this approach to test
three neuroprotective drugs which
have shown early promise in small
studies in secondary progressive
MS (SPMS). Amiloride (a blood
pressure tablet), ibudilast (asthma)
and riluzole (motor neurone disease)
will be tested against a placebo
(dummy pill) to see if one or more
of these drugs could be helpful in
slowing SPMS.
More information from the
MS Trust:
Treatments in development
www.mstrust.org.uk/
research/
drugsindevelopment
Stem cells
Interest has also focused on the
possibility of using stem cells to
repair damaged cells in the central
nervous system.
Stem cells are unspecialised cells
that can develop, or differentiate,
into any of the specialised cells of
the body, such as those in heart
muscle or the insulin-producing
cells of the pancreas. Stem cells
are the first cells to develop in
embryos and allow the foetus to
develop the specialised functions
and mechanisms that occur in the
human body. Stem cells derived
from an embryo are capable of
developing into all the cell types that
make up the tissues and organs,
such as the heart, skin and brain.
The use of stem cells from embryos
is the cause of much ethical debate.
This has also affected the issue of
‘hybrid’ embryos in which human
genetic material is implanted into
animal cells that have had most of
their own genetic material removed.
After six days, stem cells can be
extracted for research and the
hybrid is destroyed.
Not all stem cell research involves
the use of embryos. Stem cells
also occur in adults and are used
by the body to replace areas of
damage. For instance, stem cells in
bone marrow produce the different
types of blood cells. Although
more limited in the types of cells
into which they can differentiate,
research is now looking at how stem
cells can be stimulated to turn into
oligodendrocyte cells that produce
myelin or into nerve cells in sufficient
quantity to be used in treatment.
Work is also looking at how best to
deliver stem cells so that they go to
the appropriate places to carry out
repair, and also at ways to ensure
that transplanted stem cells do
not harm the recipient or grow into
unwanted tissue.
Stem cell treatment is still at the
experimental stage in MS. In the
UK, pilot studies in humans have
focused principally on safety rather
than effectiveness, although trials
looking at efficacy are due to
begin soon. If processes can be
developed, it opens the possibility
that cells destroyed by MS might be
replaced and disabilities caused by
the loss of nerve pathways reversed.
More information from the
MS Trust:
Stem cells factsheet
Tel: 01462 476700 61
Future research
Genetics
As we have seen earlier, it is
thought that there is a genetic
element to MS and that people
with MS have a particular genetic
make up that can be triggered by
an as yet unidentified virus or toxin
in the environment.
Advances in biotechnology
mean that genes are now far
better understood. Although any
treatments may be some way
off, greater understanding of
the genetic basis of MS means
researchers will be able to identify
how it develops and theoretically
create the opportunity to target
genes that are malfunctioning.
It will also allow for the potential
evolution of treatments that may
prevent those with a genetic risk
from developing the condition.
However, this approach is made
more complicated by the fact that
MS is not a single gene condition.
Environmental factors
There is also a large body of work
that is looking at environmental
factors which may be implicated
in the development of MS,
including research on vitamin D,
62www.mstrust.org.uk
the protective effect of hormones
such as oestrogen, the effect of
smoking on progression, and
possible viral triggers such as the
Epstein Barr virus.
More information from the
MS Trust:
Vitamin D factsheet
Summary
Although the nature of MS remains
unclear, new areas of research
offer the chance to increase
understanding of the condition.
Increasing levels of research
since the 1990s have seen some
major advances. This period has
witnessed the arrival of the first
drugs to have some effect on
the underlying disease activity of
MS and new ones in the pipeline;
continuing discoveries about the
nature of the immune system
and how it can be manipulated;
knowledge of the involvement of
genes in the development of disease;
and breakthroughs in stem cell
technology. This momentum offers
the hope that multiple sclerosis will
eventually be controlled.
More information from the
MS Trust:
Medicine 2012; 367: 1098-107.
Gold R, et al. Daclizumab high-yield
process (HYP) in relapsing-remitting
multiple sclerosis (SELECT): a randomised,
double-blind, placebo-controlled trial.
Lancet 2013; 381(9884): 2167-75.
MS Trust website
Research section
www.mstrust.org.uk/
Kapoor R. Neuroprotection in multiple
research
Bibliography
Bruck W, et al. Insight into the mechanism
of laquinimod action. Journal of the
Neurological Sciences 2011; 306: 173-9.
Claussen MC, et al. Immune mechanisms
of new therapeutic strategies in MS –
teriflunomide. Clinical Immunology 2012;
142: 49-56.
Coles AJ, et al. Alemtuzumab for patients
with relapsing multiple sclerosis after
disease-modifying therapy: a randomised
controlled phase 3 trial. Lancet 2012; 380:
1829-1839.
Compston A, et al. Multiple sclerosis.
Lancet 2002; 359: 1221-1231.
Compston A. MS research - theories and
areas for progress. Open Door 2007; Feb:
8-9.
Fassas A, et al. Stem cell transplantation
for multiple sclerosis: what is the
evidence? Blood Reviews 2003; 17: 233240.
sclerosis: therapeutic strategies and
clinical trial design. Current Opinions in
Neurology 2006; 19(3): 255-259.
Kappos L, et al. Ocrelizumab in relapsingremitting multiple sclerosis: a phase
2, randomised, placebo-controlled,
multicentre trial. Lancet 2011; 378(9805):
1779-87.
Reingold SC. Research directions in
multiple sclerosis. New York: National MS
Society; 2004.
Selmaj K, et al. Siponimod for patients
with relapsing-remitting multiple sclerosis
(BOLD): an adaptive, dose-ranging,
randomised, phase 2 study. Lancet
Neurology 2013 June 11. [Epub ahead of
print]
Vermersch P, et al. Masitinib treatment
in patients with progressive multiple
sclerosis: a randomized pilot study. BMC
Neurology 2012; 12: 36.
Yuen TJ, et al. Identification of endothelin
2 as an inflammatory factor that promotes
central nervous system remyelination.
Brain 2013; 136(Part4): 1035-47.
Gold R, et al. Placebo-controlled phase
3 study of oral BG-12 for relapsing
multiple sclerosis. New England Journal of
Tel: 01462 476700 63
Glossary
Aetiology (or etiology in
American English) - the study of
the causes of a disease
Axon - the long extension of a
nerve cell along which the nerve
message is passed
Antibody - proteins in the immune
system that help target the attack
on invaders
B-lymphocytes (B-cells) - a
type of white blood cell which
mature in the bone marrow and
are programmed to recognise a
specific virus or bacterium
Antigen - a substance that causes
the formation of an antibody
and reacts specifically with that
antibody
Aspiration – the entry of secretions
or foreign bodies, for example
food, into the trachea or lungs
Ataxia – disruption to the
coordination of movement
Autoimmune disease - a condition
in which the immune system attacks
the body’s own tissue
Autonomic nervous system
(ANS) - the part of the peripheral
nervous system that regulates
the function of our internal organs
(heart, stomach, intestines). The ANS
is involved in involuntary or reflex
functions such as breathing, dilation/
constriction of blood vessels and
increases/decreases in heart rate.
64www.mstrust.org.uk
Benign MS – a form of relapsing
remitting MS where there are
very mild attacks separated
by very long periods with no
symptoms. Can only be diagnosed
retrospectively
Blood brain barrier - the layer of
cells that keeps cells in the blood
from coming into contact with the
central nervous system
Bone marrow - the spongy tissue
found in the hollow centre of some
bones. It contains stem cells which
produce red blood cells
Brainstem - the area at the base of
the brain that connects to the spinal
cord. It contains areas responsible
for basic functions such as
breathing, heart rate, blood pressure
and control of the bladder
Central nervous system - the
brain and spinal cord
Cerebellum – the part of the brain
that controls movement, balance
and posture
Cerebrospinal fluid (CSF) - the
fluid that surrounds the brain and
the spinal cord
Cerebrum - the outer layer of the
brain which has the familiar walnut
like bumps and grooves (called gyri
and sulci)
Circadian rhythms - the natural
variations in the body’s activities
throughout the day
Clinically isolated syndrome (CIS)
– a single episode of demyelination
in one area of the central nervous
system (a monofocal episode) or
several areas of the central nervous
system (a multifocal episode)
which lasts for at least 24 hours
Constipation - the passage of
hard stools, less frequently than
the patient’s usual bowel pattern
Cognition - the entire range of
mental skills and abilities that
each of us possess. This includes
memory, concentration, planning,
thinking things out, decisionmaking and understanding
Demyelination - the destruction
of myelin
Dendrite - extensions of the nerve
cell body through which incoming
messages are received
Depression - persistent sadness
lasting more than two weeks,
accompanied by other symptoms
such as an altered sleep pattern,
feelings of hopelessness, guilt and
low self esteem, thoughts of death,
reduced energy and the inability
to concentrate and to take
pleasure in anything
Detrusor muscle – the bag-like
muscle of the bladder wall
Differentiation – the process
by which a less specialised cell
(stem cell) develops or matures to
possess a more distinct form and
function
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Glossary
Diplopia – double vision
Dysaesthesia - abnormal skin
sensations, such as tingling or
tickling or itching or burning
Dysarthria – a speech disorder
caused by damage to the muscles
involved in speech, often leads
to slurred speech, difficulty in
controlling volume, articulation or
intonation
Dysphagia – a lack of coordination
of the muscles involved in speech
and swallowing that causes
difficulties when eating and
drinking
Dysphasia – a condition arising
when the parts of the brain that
control thought, memory, verbal
fluency or attention are damaged.
Can lead to difficulty in finding
words or forming sentences
Electrophoresis - a method of
separating substances, especially
proteins, based on the rate of
movement of each component
in a suspension while under the
influence of an electric field
66www.mstrust.org.uk
Emotional lability - an excessive
emotional response to a minor
stimulus, for example laughing or
crying with minimal provocation or
at inappropriate times
Epidemiology - the study of the
geographical distribution of a
condition and patterns of disease
as it affects groups of people
Faecal incontinence - having no
control over when the bowel opens
Frequency – an increase in the
number of times someone needs to
urinate in a day
Glial cells - support cells in the
central nervous system
Hereditary - determined by
genetic factors and therefore able
to be passed directly on from
parents to their offspring
Hesitancy – difficulty in starting
to urinate
Hippocampus – part of the brain
which is important for memory
Hypothalamus - a small structure
at the base of the brain that
controls body temperature,
emotions, hunger, thirst and the
circadian rhythms
Incidence - the number of new
cases of a condition within a set
period of time, usually a year
Inflammation - a localised
protective reaction of tissue
to irritation, injury, or infection,
characterised by pain, redness,
swelling, and sometimes loss of
function
Interferon - a chemical generated
by the immune system to alter the
response to an invasion
Lassitude - a state or feeling of
weariness, diminished energy, or
listlessness
Lesion - the scar tissue over
an area of damaged myelin that
shows up as white regions on
T2 magnetic resonance imaging
(MRI) scans
L’hermitte’s sign - a brief but
sharp, painful, buzzing, electric
shock feeling running down the
spine and into the legs
Limbic system – the area of the
brain responsible for controlling the
emotional response to situations
Lumbar puncture – the insertion
of a hollow needle into the lower
region of the spinal cord to
withdraw cerebrospinal fluid or to
introduce drugs
Lymphocyte – type of white blood
cell involved in the immune system
Lymph nodes - small bean-shaped
structures scattered along the
vessels of the lymphatic system,
particularly at the neck, armpit and
groin. The lymph nodes produce
white blood cells and filter bacteria
and cancer cells that may travel
through the system
Macrophage - immune system
cell that attacks foreign particles in
the body
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Glossary
Magnetic resonance imaging
(MRI) – a test used in the diagnosis
of MS. Images of the brain and/or
spinal cord are created by using
magnetic fields and radio waves
McDonald criteria – the criteria
used to diagnose MS
Muscle atrophy - the wasting of
muscle tissue, especially resulting
from lack of use
Muscle tone – the level of tension
or resistance to movement in a
muscle which enables you to move
a limb or hold a position
Myelin - the substance covering
nerve axons in the central nervous
system
Neuron - nerve cell
Neurogenic pain – pain that
results from damage to nerves
Neurotransmitter - chemicals that
pass messages from one nerve cell
to the next
Nodes of Ranvier - a small gap in
the myelin sheath of a myelinated
nerve axon
Nociceptive pain – pain caused by
damage to the muscles, tendons,
ligaments or soft tissue of the body
Nystagmus - a repetitive,
involuntary, to-and-fro oscillation of
the eyes
Oesophagus – the part of the
alimentary canal between the
mouth and the stomach
Oligoclonal bands - proteins
(called immunoglobulins) which
suggest inflammation of the
central nervous system
Neuropathic pain – see
neurogenic pain
Oligodendrocyte - cells in the
central nervous system that
make myelin
Neuroprotection - a therapeutic
strategy intended to slow or halt
the progression of nerve cell loss
and thereby alter the natural history
of disease
Optic nerve – the nerve which
carries information from the back
of the eye to the brain
68www.mstrust.org.uk
Optic neuritis – inflammation of
the optic nerve
Primary fatigue – fatigue caused
by the condition itself
Overflow incontinence - urinary
incontinence that occurs when the
bladder is so full that it continually
leaks urine
Progression - a period of gradual
increase in disability unrelated to
relapses
Paraesthesia - abnormal skin
sensations, such as tingling or
tickling or itching or burning
Peripheral nervous system nerves other than the brain and
spinal cord
Plaque - the scar tissue over
an area of damaged myelin that
shows up as white regions on
T2 magnetic resonance imaging
(MRI) scans
Plasticity - changes in neural
pathways and synapses which
are due to changes in behaviour,
environment or neural processes,
as well as changes resulting from
bodily injury
Prevalence - the number of people
with a condition, usually measured
in cases per 100,000
Progressive relapsing MS – MS
that is progressive from the outset,
but with occasional relapses
Pseudobulbar affect - an
excessive emotional response to a
minor stimulus, for example laughing
or crying with minimal provocation or
at inappropriate times
Reflex reaction - physical
response automatically generated
by the spinal cord with no
involvement from the brain
Relapse - an episode of new or
worsened symptoms that lasts
more than 24 hours in the absence
of an infection
Remission - a period of partial or
complete recovery from symptoms
Remyelination - the replacement
of myelin
Tel: 01462 476700 69
Glossary
Scotoma – a partial loss of vision
or a blind spot in an otherwise
normal visual field
Secondary fatigue – fatigue
caused by another symptom or
cause rather than the condition
itself, for example lack of sleep,
depression, stress, infection
Serum - the clear yellowish fluid
obtained upon separating whole
blood into its solid and liquid
components after it has been
allowed to clot
Spasticity – a condition in which
muscle tone becomes greatly
increased
Spinal cord - the long, cordlike
part of the central nervous system
that is enclosed within the vertebral
column (spine) and descends from
the base of the brain. The spinal cord
branches to form the nerves that
convey motor and sensory impulses
to and from the tissues of the body
Stem cells - an unspecialised
cell which has the ability to divide
and self-renew while it is in an
undifferentiated state, and the
capacity to give rise to various
70www.mstrust.org.uk
specialised cell types by cell
differentiation
Synapse - the gap between nerve
cells across which nerve messages
are passed from one cell to the next
Thymus - a lymphoid organ
located in the chest cavity behind
the breastbone and above
the heart. It is central to the
development and function of the
immune system. It is not directly
involved in the immune response,
but a population of lymphocytes
which become known as T-cells
travel from the bone marrow to
mature here
T- lymphocytes (T- cells) – a type
of white blood cell which mature
in the thymus, they respond to the
antigen presenting cells
Trachea - the tube which extends
from the larynx to the bronchi,
which conveys air to and from the
lungs; also known as the windpipe
Trigeminal nerve – the nerve that
controls movements and sensation
in the face and mouth
Trigeminal neuralgia – facial
pain caused by damage to the
trigeminal nerve which can be
triggered by actions such as
talking, chewing and smiling
Visual evoked potential – a
diagnostic test that measures the
speed of the nerve message from
the eye to the visual cortex at the
back of the brain
Uhthoff’s phenomenon (or sign)
- the worsening of neurologic
symptoms in multiple sclerosis and
other neurological, demyelinating
conditions when the body gets
overheated
Urethral sphincter – the valve
at the base of the bladder which
opens to let urine out
Urinary incontinence – the
inability to hold urine in the bladder
until an appropriate time
Urgency – the feeling of having to
empty the bladder immediately, an
inability to ‘hold on’
Vaccination – the administration
of a preparation of a weakened
or killed pathogen, such as a
bacterium or virus, or of a portion of
the pathogen’s structure that upon
administration stimulates antibody
production or cellular immunity
against the pathogen, but is
incapable of causing severe infection
Tel: 01462 476700 71
More information
from the MS Trust
MS Trust publications
All our publications are free
Books
Disease modifying drug therapy: what you need to know
Living with fatigue
MS: what does it mean for me?
Primary progressive MS exposed
Spasticity triggers
DVD
Move it for MS
A DVD of exercises for people with MS
Factsheets
Alemtuzumab (Lemtrada)
BG-12 (Tecfidera)
Bladder management
Bowel management
Cognition
Depression
Laquinimod
Pain
Spasticity
Stem cells
Teriflunomide (Aubagio)
Vitamin D
72www.mstrust.org.uk
Website
The MS Trust website includes:
A comprehensive A to Z of MS covering a wide range of information
about symptoms, treatments and more
Sections on exercises for people with MS and Staying Active with MS
A complete list of MS Trust publications, which can also be
downloaded or read online
A section discussing ongoing research and developments
Videos from people with MS and health professionals.
Tel: 01462 476700 73
Index
A
Abnormal sensations....................52
Aetiology.......................................64
Age at diagnosis.............................4
Antibodies....... 13, 20-22, 55-58, 64
Antigen............................. 20-21, 64
Antigen presenting cells......... 20-21
Aspiration...............................51, 64
Ataxia......................................44, 64
Attention span........................47, 50
Auditory evoked potentials...........29
Autoimmunity...............5, 10, 24, 64
Autonomic
nervous system.................. 16, 42, 64
Axon...................... 17-18, 24-25, 64
B
Balance...................................35, 44
Barber chair syndrome.................52
Benign MS....................................31
Beta interferon........................22, 54
Bladder symptoms........... 35, 37-39
Blood brain barrier......19, 24, 28, 64
B-lymphocytes or B-cells.21-22, 64
Bowel symptoms........ 35, 40-41, 64
Brainstem................... 35, 42-43, 64
Burning sensations.......................52
C
Calcium........................................58
Cause of MS........................... 10-15
Central nervous system.... 16-19, 65
Cerebellum................. 35, 44-45, 65
74www.mstrust.org.uk
Cerebral cortex.............................45
Cerebrospinal fluid (CSF).......28, 65
Clumsiness...................................44
Cognition.................... 35, 46-47, 65
Concentration...............................47
Constipation.................................41
Crawling sensations.....................52
D
Demyelination................... 24-25, 65
Dendrites.......................... 17-18, 65
Depression.................35, 47, 49, 65
Detrusor muscle............... 37-39, 65
Diagnostic tests...................... 26-29
Diplopia............................35, 42, 66
Dizziness................................35, 44
Double vision..........................35, 42
Dysaesthesia..........................52, 66
Dysarthria...............................50, 66
Dysphagia...............................50, 66
Dysphasia...............................50, 66
E
Emotional lability.............. 47-48, 66
Environmental factors......... 7, 12-14
Epidemiology........................ 4-7, 66
Epstein Barr virus.........................13
Evoked potentials.........................29
Exercise........................................42
F
Fatigue........................ 35, 42, 48-49
G
Gadolinium...................................28
Gamma interferon.........................21
Gender differences...................5, 32
Genes..................... 6, 11-12, 22, 62
Geographic spread of MS.......... 5-7
Glatiramer acetate.................. 54-55
Glial cells................................18, 66
Glutamate............................... 58-59
L
Lassitude................................49, 67
Lesion.....................................24, 67
L’hermitte’s sign.....................52, 67
Life expectancy..............................5
Limbic system........................46, 67
Low mood..............................47, 49
Lumbar puncture.............. 28-29, 67
Lymphocytes.................... 20-22, 67
H
Heat sensitivity.......................43, 49
Helper T-cells.......................... 20-22
Hot bath test.................................49
Human leukocyte antigen (HLA)...22
Hypothalamus........................46, 67
M
Macrophage...........................20, 67
Magnetic resonance
imaging....................... 27-28, 34, 68
Major histocompatibility
complex (MHC).............................22
Memory..................................46, 50
Messenger molecules............ 21-22
Migration........................................7
Monoclonal antibodies........... 55-56
Mood swings.......................... 47-48
Motor nerves................................16
MRI............................. 27-28, 34, 68
MS Trust
Information Service..................2, 34
Muscle pain..................................51
Muscle stiffness...................... 36-37
Musculoskeletal pain....................51
Myelin.....................................18, 68
I
IL7R..............................................12
Immune memory..........................22
Immune system................ 20-22, 28
Incidence..................................4, 67
Incontinence, bladder....... 35, 37-39
Incontinence, faecal......... 35, 40-41
Infection (as trigger).......... 12-13, 24
Inflammation...........................22, 67
Intention tremor......................35, 45
Interferons..................21, 22, 54, 67
K
Killer T-cells..................................21
Tel: 01462 476700 75
Index
N
Nerve cells........................ 17-18, 68
Nerve pain........................ 51-52, 68
Nervous system...................... 16-17
Neurogenic pain............... 51-52, 68
Neurological examination....... 26-27
Neurologist...................................26
Neuromuscular fatigue.................49
Neuron ............................. 17-18, 68
Neuroprotection............... 58-59, 68
Neurotransmittors.............18, 58, 68
Nitric oxide...................................58
Nociceptive pain.....................51, 68
Nodes of Ranvier....................18, 68
Numbness..............................26, 52
Nystagmus.......................35, 43, 68
O
Oligoclonal bands............. 28-29, 68
Oligodendrocytes.............18, 24, 68
Optic nerve.............................43, 68
Optic neuritis..........................43, 69
P
Pain.................................. 35, 51-52
Paraesthesia...........................52, 69
Pathological
laughter and crying................. 47-48
Patient history........................ 26-27
Peripheral
nervous system..........16, 36, 42, 69
Pins and needles..........................52
Plaque....................................24, 69
76www.mstrust.org.uk
Plasticity.................................25, 69
Postural tremor.......................33, 45
Prevalence........................ 4, 5-6, 69
Primary progressive MS...............32
Problem solving difficulties..........46
Progressive MS........... 31-32, 57-60
R
Racial variations.............................6
Reflex reaction........................16, 42
Relapse....................... 25, 30-31, 69
Relapsing remitting MS................31
Remission................... 25, 30-31, 69
Remyelination................... 24-25, 69
Risk of developing MS.................11
S
Secondary progressive MS..........31
Sensory nerves.............................16
Short-circuiting fatigue.................49
Somatosensory
evoked potentials.........................29
Spasticity
and spasms................ 35, 36-37, 70
Speech....................... 35, 37, 50-51
Spinal cord.................16, 35, 36, 70
Stem cells......................... 60-61, 70
Support cells..........................18, 66
Swallowing.......................35, 37, 50
Synapse..................................18, 70
T
T-lymphocytes
or T-cells..................... 21-22, 24, 70
Tremor.............................. 35, 44-45
Trigeminal neuralgia................52, 71
Twins.......................................11, 14
U
Urethral sphincter...................37, 71
Urinary tract infections.................39
Uhthoff’s phenomenon
or sign...............................43, 49, 71
V
Vertigo..........................................44
Viking genes...................................6
Visual evoked
potentials (VEP)......................29, 71
Visual problems................ 35, 42-44
Vitamin D................................ 13-14
W
Weakness......................... 35, 41-42
White blood cells.............. 20-21, 28
Word finding.................................46
Tel: 01462 476700 77
About the authors
Simon Webster, Information Officer, MS Trust;
Alison Whittam, Information Officer, MS Trust
The MS Trust is a UK charity for people with MS, their family and friends.
The MS Trust Information Service offers a personalised enquiry service;
produces a wide range of publications including Open Door, a quarterly
newsletter; and provides web based information.
We would like to thank the people with MS and health professionals who
reviewed this book and provided invaluable comments, without which this
revision would not have been possible.
Please contact the MS Trust information team if you would like any further
information about the reference sources used in the production of this
publication.
This publication will be reviewed in three years.
Simon Webster, Alison Whittam
MS Explained
ISBN 1-904156-28-2
© 2013 Multiple Sclerosis Trust
Registered charity no. 1088353
All rights reserved. No part of this book may be produced, stored in a retrieval system or transmitted
in any form by any means, electronic, electrostatic, magnetic tape, mechanical, photocopying,
recording or otherwise without written permission of the publisher.
78www.mstrust.org.uk
Tel: 01462 476700 79
We provide:
• information that is tailored to what people want to know
• education for health professionals about what people with MS need
• research into better management of MS
• support for anyone affected by MS
Multiple Sclerosis Trust
Spirella Building, Bridge Road
Letchworth Garden City
Hertfordshire SG6 4ET
T 01462 476700
E [email protected]
www.mstrust.org.uk
Registered charity no. 1088353
MSExplained.07.13.12K
The MS Trust is a charity working with and for the 100,000 people in the
UK with multiple sclerosis (MS). Our vision is to enable people with MS
to live their lives to the full.