Multiple Sclerosis

Pathology
Multiple sclerosis (MS) is a chronic disorder of the central nervous system which is inflamatory
in nature. Multiple demyelination plaques are found distributed within the spinal cord and brain.
Pozzilli (2002) however suggested that as MS is a disease of the myelin sheath, its lesions are
present in both the White Matter (WM) and Gray matter (GM). The difference is that the lesions
found within the GM are present as myelinated fibres so they are visible too in the GM. The
plaques are said to be disseminated in time and place, hence the diseases former name:
disseminated sclerosis.
Though the precise etiology of multiple sclerosis is largely unknown, Chlamydia has been
questioned as a cause for the disease (Kumar & Clark- p. 1233). There are however no known
links existing between MS and any infection. Within the white matter of the spinal cord and
brain there is an inflammatory process against molecules of the self. This process is mediated by
CD4 T cells. Active lesions of the disease are called plaques. In the plaques, there is an increase
in inflammatory cells in the plaques which effect the active degradation of myelin and
phagocytosis. Monocytes and lymphocytes are able to reach the brain parenchyma from the
circulation. They adhere to vascular endothelial cells via the glycoprotein 41, integrin
expressed on their surface in order to gain this access. This integrin (also called very late antigen
VLA4) is also an immune-cell activation regulator. Autoreactive humoral and cellular responses
against myelin may be primed by an incipient (or initial) inflammatory event of demyelination.
Antibody-mediated demyelination e.g. against a protein called myelin basic protein, may appear
early in MS. Antibodies against MOG (myelin oligodendrocyte glycoprotein) - a protein specific

to the CNS - have also been found in vitro (Kumar & Clark, 2006 p. 1234).
The plaques of demyelination characteristic of MS are around 2-10mm in size at first, and are the
cardinal features of the disease. They may be classified into two: purely cortical lesions found in
the inner surface of the brain and general cortical subpial demyelination lesions. Plaques are
perivenular with a predilection for distinct CNS sites: optic nerves, the periventricular region,
brainstem and its cerebellar connections and the cervical spinal cord (corticospinal tracts and
posterior columns). The median longitudinal fasciculus is eventually affected in many cases,
causing the almost pathognomonic internuclear ophthalmoplegia (Orrell et al, 1995).
After that, the lesions vary in size and the size may be used to differentiate the ages of the
various lesions. Focal inflammatory demyelination causes acute relapses, which leads to a block
in the conduction of impulses. Nitric oxide is produced locally during the inflammatory process
by macrophages and this damages the axons (nerve fibres). This stage is followed by remission
as inflammation declines, while recovery is further aided by remyelination. If damage is severe,
axons are permanently destroyed. Plaques in the cord sometimes destroy groups of anterior horn
cells - therefore focal muscle wasting e.g. of small hand muscles though this is unusual.
Physiology
Every nerve has motor or sensory function each. This function is effected by an electrical
impulse conducted though nerves. For the impulses to be propagated, the axon of the nerve needs
to have a myelin sheath (myelinated) which is produced by oligodendrocytes or astrocytes. The
myelin sheath has interruptions known as nodes of ranvier. Axons have a high resistance to the
electrical impulse which makes the speed of conduction to be too slow. Nerves therefore use an
alternative conduction mechanism known as 'saltatory conduction'. In this type of conduction,

the electrical impulse jumps from one node of Ranvier to the next, causing the conduction
velocity to be as high as required. If for one reason or another, the distance between available
nodes is too great because of e.g. destruction of myelin segments, the impulse is unable bridge
the gap and saltatory conduction fails. This therefore forces the electrical impulse to travel via
the slow axonal route. (Kirk et al, 2006).
For a nerve to function as it should, its myelin sheath must be intact. In MS, this sheath is
compromised leading to the symptoms observed. The physical manifestations of MS are due to
the diseases demyelinating effects on nerves. They stem from the lack of or slowed impulse
conduction.
A rise in body temperature as a result of either ambient heat or fever (Uhthoff's phenomenon)
may cause signs and symptoms to appear in some MS patients due to slowing of nerve
conduction. The latter is a common cause of pseudo-exacerbations. A body temperature increase
of as little as 0.1C may be sufficient to cause such signs and symptoms, which disappear upon
cooling. By far the most common cause of these pseudo-exacerbations is an unsuspected urinary
tract infection; this causes fever and a rise in ambient body temperature. (Markus
&Oppenheimer, 2006).

Pathogenicity
T-helper cells are thought to be the main mediators of the autoimmune inflammatory reaction in
the pathogenesis of multiple sclerosis. The function of the T-helper cells is to identify myelin
derived antigens on the cell surface of antigen presenting cells of the nervous system, and
microglia. They also undergo clonal proliferation. An inflammatory cascade results, leading to
the release of cytokines while initiating a macrophage destruction of the oligodendrocyte- myelin

unit. The histological characteristic lesion is a plaque of the inflammatory demyelination

occurring most commonly in the periventricular regions of the spinal cord. Initially, this is a
circumscribed area of the disintegration of the myelin sheath, accompanied by the macrophage
and activated lymphocytes infiltration, often with distinct perivascular inflammation. Following
an acute attack gliosis develops, leaving a shrunken grey scar.
Majority of the primary acute clinical deficit is brought about by the effect of inflammatory
cytokines on nerve impulse transmission rather than structural disruption of the myelin. This
explains the rapid recovery of some deficit and probably the ability of steroids to ameliorate the
acute deficit. Nevertheless, myelin loss which results from an attack reduces the safety factor for
impulse propagation or causes complete conduction block, which lowers the efficiency of central
nervous system function. Confirmed multiple sclerosis is characterized by progressive axonal
loss, probably caused by direct damage to axons by mediators of inflammation released during
acute attack. This includes nitrous oxide, and is the cause of the diseases phase characterized by
persistent and progressive disability.
Blood leaks into the tissue of the inflamed area from blood vessels, and releases inflammatory
white blood cells. In a normal individual, White blood cells are used to fight foreign substances
that may cause disease or infection by the immune system. Conversely, in MS, these cells are
driven to attack myelin, a self-tissue.
Clinical Aspects
Though there is no single group of symptoms or signs that is absolutely diagnostic for MS, it is
often clinically recognizable by various patterns. The definite symptoms include unilateral
optic/retrobulbar monocular color blindness, oscillopsia, transient scanning speech, transverse
myelitis, Lhermitte's symptom, gait ataxia, unilateral dysmetria/intention tremor/incoordination,

sensory useless hand syndrome, and transient weakness/paresthesias of the entire limb. The
following are also considered to be definite, but only if the patient is below 40 years of age: tic
douloureux, hemifacial spasm, acute unilateral diminution of hearing, transient acute nonpositional vertigo, transient painless urinary retention, and transient painless urinary urgency or
incontinence in men.
For the following possible symptoms to be considered markers of MS onset, they must be
followed by a definite symptom within 2 years: unilateral facial palsy, organic erectile
dysfunction, and painful tonic spasms. Transient painless urinary frequency in men and transient
hemiparesis are acceptable only in patients under age 40 (Namerow & Thompson, 1969).
The course of MS is usually classified as: (Barnes, 1991).
(1) Classic relapsing and remitting type (RRMS), which represents about one-third of the cases;
(2) Primary progressive (PPMS), which represents about 10% of cases; and
(3) Secondary progressive (SPMS), which follows a relapsing-remitting course.
Conclusion
Multiple Sclerosis is an inflammatory disorder of the central nervous system. As its symptoms
are not often easy to recognize, MS is quite often misdiagnosed. It is an autoimmune disorder
and may be inherited or not. Determination of the exact clinical onset of the disease is important
for epidemiological investigations. Often, non-specific symptoms like headache, seizure,
dizziness or back pain are mentioned as the first clinical manifestations of the illness. These
onset symptoms of MS may be divided into those which are 'definite' and those which are
'possible'. These symptoms must last for at least 24 hours. (American Academy of

Ophthalmology, 1997).
There are three major variants of MS: malignant type, schilder type (or diffuse sclerosis), and
balo type (or concentric sclerosis). A few other neurological disorders follow the pattern of
multiple sclerosis, and the lesions of the disease must be distinguished from a mass or tumor.
Investigations needed are: an MRI, a CSF examination and electrophysiological tests. MS is
usually inherited and is more commonly occurring in men than women. The increase in
prevalence of MS is directly proportional to distance from the equator.
MS is a chronic disorder for which there is no curative treatment available. Therefore once
diagnosed practical decisions about home, employment, and plans for the future while combating
a potentially disabling disease need to be considered. Though the course of MS may be
unpredictable, future disability may be predicted by a florid MRI lesion load at initial
presentation. severity varis widely an; many patients continue to live productive and selfsufficient lives while others become gravely disabled.
Persons living with MS must remember to make complete life changes all through their lives,
including in their diet; they must now taken a gluten-free diet for example. Like any other
chronic disease, MS may become quickly debilitating if not well managed. Straightforward
advice, coupled with reassurance of the benign course of many MS cases is important. Normal
medical therapies will not be enough to ensure that the patients live a normal, healthy life
(Polman & Uitdehaag 2003).
A lot can be done for a person with any chronic debilitating disease. Practical advice for work,
on wheelchairs, walking aids, car conversions, adjustment of gardens and houses is needed from
professionals with rehabilitation experience. Various support forms - for reactive depression, fear

and sexual impediments - are also helpful. A liaison between a multidisciplinary team, carers, the
patient, therapists and doctors is essential. All infections should be treated. Urinary infection
frequently worsens symptoms. Frequent self catheterization may help with Urinary incontinence.
Physiotherapy is especially of value in the reduction of pain and spastistic discomfort, especially
lower limb flexor spasms. It is also essential to prevent pressure sores.
Due to the nature and effects of the disease, MS usually has a great emotional impact on the
patient and their family. The cause of these emotional effects has been found to be especially due
to two main factors: the functional loss associated with the disease and the frequent
exacerbations and remissions. Its almost as if an MS patient has to constantly deal with the very
heavy burden of the fear of when the disease will next strike. These effects are largely ignored in
the management of MS patients even though they play a big role in the patients general wellbeing (Devins, & Seland, 1987).
Several modes of disease modifying treatments for MS exist. These treatments are expensive and
impose a financial burden that the patient may not be able to bare. Moreover, just like any other
medical treatments, the disease modifying treatments of MS are not without their fair share of
adverse effects. These effects range from as simple as irritation at the site of injection to as
serious as cardiotoxicity and acute myeloid leukemia caused by mitoxantrone (Leslie and
Pozzilli 2002). Infertility is another of the undesirable effects of the treatments. This is especially
distressing for one who is interested in conceiving and having children. Moreover, the constant
knowledge that if one does succeed in having children while they have MS, that it is possible to
pass on such a burden to them is disconcerting at the very the least. One might even argue that
the worst effects of MS are those which are psychological and emotional in nature.

Those diagnosed with MS may have a reduced life expectancy due to the morbidities associated
with MS. The numbers are not specific, but depending on a number of factors, the life
expectancy of an MS patient is reduced by about 5-10 years if it is severe or is left without
treatment or as low as 2-3 years if well managed. Management is key in reducing the morbidities
and functional losses that are usually caused by MS. Though treatments are not curative, they
may help slow disease progression as well as improve the quality of life.
MS savors connections. It disconnects nerves, the brain from the body, and people from other
people. Even so, if properly managed, MS will cause much less suffering than it could without it.

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