From : Jerin Xavier Polackal

Submitted to : Dr Ivane Verulashvili

MULTIPLE SCLEROSIS

INDRODUCTION-
Multiple sclerosis (MS) is a chronic disease affecting the central nervous
system (the brain and spinal cord).MS occurs when the immune system
attacks nerve fibers and myelin sheathing (a fatty substance which
surrounds/insulates healthy nerve fibers) in the brain and spinal cord.
This attack causes inflammation, which destroys nerve cell processes
and myelin – altering electrical messages in the brain.
Symptoms of multiple sclerosis may be mild, such as numbness in the
limbs, or severe such as paralysis or loss of vision. The progress,
severity and specific symptoms of multiple sclerosis in any one person
cannot yet be predicted. However, advances in research, diagnosis and
treatment of multiple sclerosis are giving hope to those affected by the
disease.

DEFINITION-
It is chronic, progressive and non-contagious degenerative disease of
CNS characterized by the demyelination of neurons

INCIDENCE
It occurs between the age 20-55 years. It mostly affects female than
males
ETIOLOGY
 UNKNOWN
 Immune system attacks its own tissue so it is considered an
autoimmune disease
 Age- 20-50 years of age
 Gender- Female
 Certain infection- Epstein barr virus
 Smoking
 Autoimmune- Diabetes Mellitus
PATHOPHYSIOLOGY
EPIDEMIOLOGY

Currently, there are about 3 million people with multiple sclerosis in

the world. It is customary
to distinguish three zones that differ in prevalence.
 High-risk zone : The prevalence of more than 50 cases per
100,000 of population includes
northern Europe, northern parts of the United States, southern
Canada, southern Australia,
Russia, and New Zealand.
 The zone of medium risk (10-50 cases) includes southern
Europe, southern United States,
northern Africa, and the rest of Australia.
 A low risk zone - less than 10 cases per 100,000 of
population - most regions of Central and
South America, Asia, Africa, the Caribbean, and Oceania.
Statistics show that women get sick more often than men, the
white population suffers more
often than black people. The average age, which accounts for the
incidence is between 20 and 40
CLINICAL MANISFESTATIONS-
Clinical manifestations can be divided into seven major
groups.
 The most frequently observed symptoms of lesions of the pyramidal
tract. Depending on the
localization of the lesion, paraparesis may occur, less frequently monoparesis
and hemiparesis.
Upper extremities tend to suffer less often or become involved in the process
at later stages.
Paresis is always accompanied by pathological pyramidal signs, an increase
in deep reflexes and
a decrease in superficial abdominal reflexes. The latter symptom is an early
manifestation of
pyramidal pathway interest in multiple sclerosis, but is certainly not a specific
sign for it.
 Central paralysis in multiple sclerosis is accompanied by various
changes in tone – often spasticity, less often hypotonia or dystonia. A
peculiar clinical manifestation of the multifocal demyelinating process is
the combination of signs of central paralysis with hyperreflexia and
clonuses, pathological signs and at the same time severe hypotension due to
damage to the posterior spinal cord and / or conductors of the cerebellum
(variant of clinical dissociation syndrome). Symptoms of damage to the
cerebellum conductors have a significant place in the clinical picture.
 Static and dynamic ataxia, dysmetry, hypermetry, asynergia, intentional
trembling and intermittent detection with paltsenosovoy and heel-knee
samples, scanned speech and macrography are identified. With
simultaneous lesion of the pyramidal tract and violation of deep
sensitivity, only intentional tremor and asynergia, especially one-sided,
can be confidently regarded as signs of damage to the cerebellum. In
severe cases, trembling of the hands, head, and body can also be
detected at rest, acquiring the character of severe hyperkinesis
(titubation).These forms are referred to as hyperkinetic variants of
multiple sclerosis. Cerebellar hypotonia can be manifested by
hyperdistension in the joints and equinovarus installation of the feet
alone. At the same time, these symptoms are not specific for the
development of foci in the white matter of the cerebellum, but can also
be observed with a different location of the lesion, for example, in the
posterior cords of the spinal cord.
 Symptoms of cranial nerve damage are noted in more than half of
the patients. Most often, there is a lesion of the oculomotor (II),
trigeminal (V), abducent (VI) and facial (VIN) nerves less commonty the
bulbar group of nerves. In some patients, unilateral, impaired sensitivity
in the face, in the tongue can be detected. The most frequent symptom
of a brain stem lesion is oculomotor disturbances; only characteristic of
multiple sclerosis is internuclear
 ophthalmoplegia syndrome associated with foci of demyelination in the
fibers of the medial longitudinal bundle. Often found horizontal
nystagmus. Vertical nystagmus can be detected in a non-severe
general condition, indicating the defeat of the upper sections of the
brain stem.
 Among the various manifestations of visual impairment, the most
frequent is a decrease in visual acuity and a change in visual fields due
to retrobulbar neuritis. The diagnosis of retrobulbar or optic neuritis is
established in the presence of an acute or subacute decrease in
visual acuity, usually one eye, accompanied by painful movement of
the eyeballs, with a duration of at least 24 hours and usually with full or
partial restoration of vision. The development of repeated retrobulbar
neuritis is characteristic. Almost always there is a blanching
of the temporal halves of the optic nerve discs. This symptom indicates
a lesion of the papillomacular bundle. However, the decolorization of
the temporal halves of the discs should
not be considered specific only for multiple sclerosis. Changes in the
fundus without a clinic of optic neuritis indicate the presence of
subclinical damage to the optic nerve (I). The change in visual acuity is
one of the most unstable symptoms of multiple sclerosis
 Characterized by changes in deep and surface sensitivity. Usually, in
the early stages, asymmetry of vibration sensitivity and disorders of
pain sensitivity without precise localization are noted, often having the
character of dysesthesia. At later stages of development, violations of
the sensitivity of the conductor type are detected. Nearly half of the
patients with a disease duration of more than 5 years may experience
significant muscular-articular dysfunction, leading to afferent paresis
and ataxia.
 Often there is a violation of the functions of the pelvic organs. These
manifestations of a demyelinating disease can be a more important
cause of disability than paresis and impaired coordination, negatively
affecting the mental state of patients. Imperative urges, more frequent
urination, and urinary retention appear at an early stage, urinary
incontinence. The cause of impaired urination in multiple sclerosis is
the dyssynergia of the urine-pushing muscle and the sphincter. Of
great importance in patients with delayed or incomplete emptying of the
bladder is regular urinalysis for microflora, leukocyturia, determination
of residual nitrogen and the level of creatinine in the blood, if
necessary, urography is shown. Infectious complications can cause
additional urinary disorders that mask the background symptom
complex.
Mental changes in multiple sclerosis include both reduced intelligence and
behavioral disorders.
Depression (moderate or severe), accompanied by a feeling of anxiety,
deserves special
 attention, more often in combination with a negative attitude towards the
environment, à
decrease in interest and motivation. Depression in multiple sclerosis develops
in significantly
more cases than in patients with other chronic neurological diseases.

Uhthoff’s phenomenon- Also known as Uhthoff sign is described a transient

worsening of neurological symptoms related to demyelinating disorder such
as multiple sclerosis when the body becomes overheated in hot weather,
exercise, fever, saunas, or hot tubs

Lhermitte’s sign- The sign mostly describes as an electric shock like

condition by some patients

SYMPTOMS

1. DYESTHESIA-
Often a first symptom of MS or a relapse, an MS hug is a
squeezing sensation around the torso that feels like a blood
pressure cuff when it tightens.

2. WALKING (GAIT) DIFFICULTY

Difficulty in walking — also known as problems with gait is among the most common
mobility limitations in MS.  Walking difficulties are related to several factors:

 Spasticity: Muscle tightness or spasticity can interfere with gait.

 Balance: Balance problems typically result in a swaying and “drunken” type of
gait known as ataxia.
 Sensory deficit: Some people with MS have such severe numbness in their
feet that they cannot feel the floor or know where their feet are. This is
referred to as a sensory ataxia.
 Fatigue: Many people will experience increased gait problems
when fatigue increases.
 Weakness: Weakness in your leg muscles can lead to changing your normal
walking stride. This change in your walking can then lead to pain, which can
make your walking even worse.
 3. SPASTICITY

Spasticity refers to feelings of stiffness and a wide range of involuntary

muscle spasms (sustained muscle contractions or sudden movements)

 In flexor spasticity the muscles are so tight that the limbs are bent and
difficult to straighten.
 In extensor spasticity the muscles are so tight that the limbs remain straight
and are difficult to bend.

4. VISION PROBLEM
Optic neuritis
A common visual symptom of MS is optic neuritis — inflammation of
the optic (vision) nerve.    Optic neuritis usually occurs in one eye and
may cause aching pain with eye movement, blurred vision, dim vision,
or loss of colour vision. For example, the colour red may appear
washed out or grey.

Nystagmus
Nystagmus is involuntary and uncontrolled movement of the eyes that can impair
your vision. Movement is usually rapid and can be up and down, side to side or
rotating. Nystagmus may occur when looking straight ahead or may occur when the
eyes are moved. Sometimes nystagmus is called “dancing eyes”.

Diplopia
In MS, diplopia, or double vision, occurs when the nerves that control your eye
movement are inflamed or damaged. The nerves control muscles that allow eye
movement. Normally, the muscles work in a coordinated way, but when diplopia
occurs, muscles on one side may be weak from nerve damage and the eye
movements are no longer coordinated. This may produce two side by side images or
one image on top of another.  Diplopia may be temporary or persistent and may
resolve without treatment. 

5. BLADDER
Bladder dysfunction, which occurs in at least 80 percent of people with MS, happens
when MS lesions block or delay transmission of nerve signals in areas of the central
nervous system (CNS) that control the bladder and urinary sphincters. A spastic
(overactive) bladder that is unable to hold the normal amount of urine, or a bladder
that does not empty properly (retains some urine in it) can cause symptoms
including:
 Frequency and/or urgency of urination
 Hesitancy in starting urination
 Frequent night time urination (nocturia)
 Incontinence (the inability to hold in urine)
 Inability to empty the bladder completely

6. NUMBNESS AND TINGLING

 Numbness of the face, body or extremities (arms and legs) is one of the most
common symptoms of MS. It may be the first MS symptom you experienced.
The numbness may be mild or so severe that it interferes with your ability to
use the affected body part. For example, if you have very numb feet, and
cannot feel the floor, you may have difficulty walking. Numb hands may
prevent writing, dressing, or holding objects safely.

7.WEAKNESS
Damage to the nerve fibers (demyelination) in the spinal cord and brain
that stimulate the muscles can also cause weakness. The muscles are
not receiving the nerve impulses they require in order to work
effectively – which often results in decreased endurance.  Because the
source of this type of weakness is impaired nerve conduction, weight
training to strengthen the affected muscles is not effective – and may
even increase feelings of weakness and fatigue. The recommended
strategy is to maintain the tone of those muscles that are not receiving
adequate nerve conduction with regular use, while working to
strengthen the surrounding muscles that are receiving adequate
conduction.

8. SEXUAL WEAKNESS
Sexual arousal begins in the central nervous system, as the brain
sends messages to the sexual organs along nerves running through
the spinal cord. If MS damages these nerve pathways, sexual
response — including arousal and orgasm — can be directly affected.
Sexual problems also stem from MS symptoms such as fatigue or
spasticity, as well as from psychological factors relating to self-esteem
and mood changes
 SYMPTOMS-
A feature of multiple sclerosis is a wide variety of symptoms. The first signs of
multiple sclerosis
often occur after the provocative effects of any factors: trauma, surgery,
illness, nervous stress,
childbirth, etc. Multiple sclerosis can begin with changes in sensitivity in the
form of transient
tingling sensations and goose bumps in the hands and feet, visual
disturbances, vestibular
disorders in the form of dizziness, with reversible motor disorders. In the far
advanced stage of
multiple sclerosis, the following groups of symptoms usually occur;
Disorders of motor activity - paresis, spasticity (abnormal
increase in muscle tone),
pathological reflexes.
Coordination disorders - shakiness, intentional trembling, nystagmus,
instability in an upright
position, etc.
Sensory impairment - decreased sensitivity, numbness, tingling,
pain, etc.
Visual impairment - reduced acuity, change of visual fields, etc.
Speech disorders - slow speech, scanned speech, etc.
Impaired pelvic function - an imperative (sudden and strong)
urge to urinate, delay or
incontinence, impotence, constipation or fecal incontinence

MS is unpredictable and affects each patient differently –

some individuals may be mildly affected, while others may
lose their ability to write, speak or walk. There are several
courses of multiple sclerosis that have been described:

Relapsing-Remitting Multiple Sclerosis (MS)

At the time of diagnosis, 90% of patients will have relapsing-remitting course of disease.
This form of multiple sclerosis is characterized by the onset of the neurological symptoms
over a period of hours to days. Common symptoms of a relapse may include:
 Fatigue

 Numbness
 Tingling
 Blurred vision, double vision or loss of vision
 Unsteady gait
 Weakness
These symptoms tend to persist for days or weeks, and then disappear partially or
completely on their own or with treatment. Patients may then remain symptom-free for
weeks, months or even years (known as remission). Without treatment, most people with MS
will develop disease symptoms that will gradually worsen over time (known as relapsing).

Secondary Progressive Multiple Sclerosis (MS)

If the relapsing-remitting condition changes to a point where there are no discernable
relapses and remissions; the course of the disease has transitioned to secondary
progressive MS. All those with secondary progressive MS began the disease with a
relapsing-remitting disease course. In secondary progressive MS, symptoms accumulate
and worsen without any remission.
There may be periods where symptoms are stable, but the overall course is one of
worsening over time. Often an individual will describe a change in their abilities when
comparing current function to past function but without identifying an episode that led to the
worsening. Sometimes, after the onset of secondary progressive MS an individual may
experience a relapse. The course would then be considered secondary progressive MS with
relapses.

Primary Progressive Multiple Sclerosis (MS)

About 10-15% of patients will have gradual worsening from the start of their MS disease.
This is referred to as primary progressive MS. People with primary-progressive MS describe
a gradual change in mobility; often walking, over time. They often describe heaviness and
stiffness in the lower limbs. People with primary-progressive MS almost never have an
exacerbation (relapse). If a relapse occurs after a primary progressive course is well
established, the pattern is known as Progressive-Relapsing MS.

Benign Multiple Sclerosis (MS)

Benign MS is a mild course where an individual will have mild disease after having MS for
about 15 years. This occurs in about 5-10% of patients. There is no good way of predicting
which patients will follow this course. The only way to identify benign MS is AFTER someone
has had the diagnosis of MS for at least 15 years and has had no evidence of worsening
(both in functional ability and as evidenced on the MRI). Benign MS cannot be predicted at
the time of diagnosis or even after a few years with MS.
DIAGNOSIS
There are no specific tests for MS. Instead, a diagnosis of
multiple sclerosis often relies on ruling out other conditions that
might produce similar signs and symptoms, known as a
differential diagnosis
 BLOOD TEST

While there is no definitive blood test for MS, blood tests

can rule out other conditions that cause symptoms similar
to those of MS, including lupus erythematosis, Sjogren's,
vitamin and mineral deficiencies, some infections, and
rare hereditary diseases.
 NEUROLOGICAL EXAM
Your neurologist will look for abnormalities, changes or weakness in your
vision, eye movements, hand or leg strength, balance and co-ordination,
speech and reflexes.

These may show whether your nerves are damaged in a way that might
suggest MS.

 MRI SCAN
An MRI scan is a painless scan that uses strong magnetic fields and
radio waves to produce detailed images of the inside of the body. It can
show whether there's any damage or scarring of the myelin sheath (the
layer surrounding your nerves) in your brain and spinal cord. Finding this
can help confirm a diagnosis in most people with MS.

 LUMBAR PUNCTURE
A lumbar puncture is a procedure to remove a sample of your spinal fluid
by inserting a needle into the lower back. The procedure is done under
local anaesthetic, which means you'll be awake, but the area the needle
goes in will be numbed.
The sample is then tested for immune cells and antibodies, which is a
sign that your immune system has been fighting a disease in your brain
and spinal cord.

 IMMUNOLOGICAL STUDY

Since multiple sclerosis is an autoimmune disease,

assessment and monitoring of cellular and humoral
immunity parameters is of great importance. A number
of studies have shown that determining the ratio of
CD4 + and CD8 + T-lymphocytes can be the most
informative and
accessible method of immunological monitoring in
multiple sclerosis. In healthy people, it is about 1.3, in
patients with MS, it is increased to 1.7-1.8. A number of
studies have demonstrated
that an increase in serum interferon may indicate an
acute stage of the disease, and its
normalization usually coincides with remission.
Thus, the most informative and accessible
immunological indicators in multiple sclerosis are the
following;
-CD4 + T-lymphocytes
-CD8 + T-lymphocytes
-The ratio of CD4 + / CDS +
-Interferon-gamma level

TREATMENT
Treatment of relapse

The treatment of relapse is irrespective of whether it occurs in patients

with relapsing-remitting disease or those with the secondary progressive
phase of the disease. Although almost all patients with relapse show some
degree of spontaneous recovery, most clinicians advise treatment of
relapse that has an important effect on function. For many years,
corticosteroids have been the first-choice treatment. Corticosteroids
shorten the duration of the relapse and accelerate recovery, but there is no
convincing evidence that the overall degree of recovery or the long-term
course of the disease is affected.

The most commonly applied regimen consists of a brief

course of high-dose methylprednisolone sodium
succinate given intravenously IV (500-1,000 mg per day
for 3-5 days). Some clinicians substitute oral
prednisone for IV methylprednisolone because it is
easier to use and costs less. Data substantiating the
comparable benefits of oral prednisone and IV
methylprednisolone in acute relapses have been
presented but are not definitive.6 In various studies—all
of them small—different dosage regimens of oral
steroids have been applied

Disease-modifying treatment of relapsing-remitting multiple

sclerosis

The goal of treatment in patients with relapsing-remitting multiple

sclerosis is to reduce the frequency and severity of relapses (and
thereby prevent exacerbations) and to prevent or postpone the onset
of the progressive phase of the disease. To achieve this goal, in the
past especially, immunosuppressive drugs were used, but they have
never found widespread acceptance owing to limited efficacy and
considerable toxicity.

More recently, large randomized controlled trials have been performed

successfully with interferon beta-1a, interferon beta-1b, and glatiramer
acetate. These substances should be seen as immune modulators rather than
immune suppressors. The trials have led to the regulatory approval of 4 agents
—Avonex, Biogen, United States; Betaseron, Berlex, United States (Betaferon,
Schering, Germany); Copaxone, Teva, Israel; and Rebif, Serono, Switzerland—
for reducing the severity and frequency of relapses

Interferon beta 

Currently 2 forms of recombinant interferon beta, interferon beta-1a and

interferon beta-1b, have been approved by US and European regulatory
authorities for the treatment of relapsing-remitting multiple sclerosis. Interferon
beta-1a (Avonex, Rebif) is a glycosylated, recombinant product from
mammalian cells, with an amino acid sequence identical to that of natural
interferon beta. Interferon beta-1b (Betaseron [Betaferon]) is a nonglycosylated
recombinant product from bacterial cells in which serine is substituted for
cysteine at position.

Glatiramer acetate

Glatiramer acetate (Copaxone) is a synthetic copolymer with some

immunologic similarities to myelin basic protein, 1 of the major
components of myelin. Daily treatment with subcutaneous
administration of 20 mg of glatiramer acetate resulted in a 29%
reduction of the annual relapse rate in a 2-year trial. These clinical
observations were later supported by findings on MRI in a separate
study. Adverse effects of glatiramer acetate are usually mild. Definitive
data on the effect of glatiramer acetate on disease progression are not
available.

Role of traditional immunosuppressants

Given that both interferon beta and glatiramer acetate, although

convincingly shown to be effective, have major limitations, including
cost, inconvenience (given parenterally), and a relatively modest
overall effect on disease course, several experts have urged
reconsideration of the role of immunosuppressants like azathioprine
or methotrexate. Compared with interferon and glatiramer acetate,
these drugs are much cheaper, easier to give, and might also have a
favorable effect on the natural course of the disease.

Haemopoietic stem cell therapy

HSCT (haematopoietic stem cell transplantation) is an intense

chemotherapy treatment for MS. It aims to stop the damage MS causes by
wiping out and then regrowing your immune system, using your stem cells.
Physiotherapy for Multiple Sclerosis
Physiotherapy is often recommended when there is a specific problem or ongoing
symptoms that affect day-to-day activities, mobility and independence. It can help
whatever your level of disability, but can be a particularly valuable when physical
symptoms progress or you are recovering from a relapse. 

If MS is affecting the sports or activities, you are able to do, they might suggest new
ways to stay fit, or ways to adapt your preferred exercises to suit your situation. A
physiotherapist can also suggest particular exercises to treat and manage specific
problems such as difficulties with mobility, balance, posture and fatigue.

Bladder problems, pain and muscle spasms and stiffness can also be targeted by

physiotherapy.
PROGNOSIS
Prognosis is affected by the type of MS. Primary progressive MS (PPMS) is
characterized by a steady decline in function without significant relapses or
remissions. Every case is different, so there may be some periods of inactive
decline. But the steady progression continues.

For the relapsing forms of MS, there are several guidelines that may help predict
prognosis. People with MS tend to do better if they experience:

 few symptom attacks in the initial few years post-diagnosis

 a longer amount of time passing between attacks

 a complete or almost complete recovery from their attacks

 symptoms related to exclusively to sensory problems, like tingling, vision loss,

or numbness

 neurological exams that are almost normal 5 years after diagnosis

MS isn’t a fatal condition in most cases, and most people with MS have a close-to-
normal life expectancy. But since the disease varies so much from person to person,
it can be difficult for doctors to predict whether their condition will worsen or improve.
Another way of evaluating the prognosis for MS is to examine how disabilities
resulting from the condition’s symptoms may affect people.

According to the NMSS, around two-thirds of people with MS are able to walk

without a wheelchair 2 decades after their diagnosis. Some people will need a cane
or a walker to remain ambulatory. Others use an electric scooter or wheelchair to
help them cope with fatigue or balance difficulties.

CONCLUSION
Multiple sclerosis continues to be a challenging and disabling condition
but there is now greater understanding of the underlying genetic and
environmental factors that drive the condition, including low vitamin D
levels, cigarette smoking, and obesity. Early and accurate diagnosis is
crucial and is supported by diagnostic criteria, incorporating imaging and
spinal fluid abnormalities for those presenting with a clinically isolated
syndrome. Importantly, there is an extensive therapeutic
armamentarium, both oral and by infusion, for those with the relapsing
remitting form of the disease. Finally, a comprehensive management
programme is strongly recommended for all patients with multiple
sclerosis, enhancing health-related quality of life through advocating
wellness, addressing aggravating factors, and managing comorbidities.
The greatest remaining challenge for multiple sclerosis is the
development of treatments incorporating neuroprotection and
remyelination to treat and ultimately prevent the disabling, progressive
forms of the condition.
BIBLIOGRAPHY

https://www.nhs.uk/conditions/multiple-sclerosis/
treatment/

https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3004998/

https://www.mssociety.org.uk/research/explore-our-
research/emerging-research-and-treatments/
immunomodulation

https://www.mayoclinic.org/diseases-conditions/
multiple-sclerosis/diagnosis-treatment/drc-20350274

https://www.hopkinsmedicine.org/
neurology_neurosurgery/centers_clinics/
multiple_sclerosis/conditions/

https://www.medicalnewstoday.com/articles/37556