‫ﻛــــــــﻠــــــــﻴــــــــﺔ اﻟــــــــﻄـــــــــﺐ‬

‫‪Baserah Team‬‬
Introduction and
epidemiology of MS:
Multiple sclerosis (MS) is a chronic autoimmune, T- cell- mediated, inflammatory disor-
der of the CNS. Multiple plaques of demyelination are found throughout the brain and
spinal cord. It occurs over years and causes permanent damage to nerves.

MS is a major cause of disability in young adults

The estimated number of people with MS worldwide has increased to 2.8 million
in 2020. MS prevalence has increased in every world region since 2013.
- Women outnumber men by 2 : 1 (and the ratio is widening).
- Presentation is typically between 20 and 40 years of age.
- Presentation after age 60 is rare.
Myelin sheath and
Pathogensis of MS
The myelin sheath is a greatly extended and modified plasma
membrane wrapped around the nerve axon in a spiral fash-
ion. The myelin membranes originate from and are a part of
the Schwann cells in the peripheral nervous system (PNS) and
the oligodendroglial cells in the central nervous system
(CNS). The functions of Myelin sheath are acceleration of the
conduction and isolation.
Myelin subserves saltatory conduction of the impulse in the
healthy nervous system Saltatory conduction the action
potentials are initiated only at the nodes of Ranvier, “jumping
over” the internodal segments. This mechanism enables
myelinated nerve fibers to conduct action potentials much
more rapidly than unmyelinated fibers.
Demyelinating diseases are the most common pathologies
affecting myelin sheath. The most common demyelinating
disease is MS. MS is characterised by an immune-mediated
attack against myelin sheaths mainly oligodendrocytes. In
MS, the ability to remyelinate efficiently declines with age
and disease progression

Pathogensis of MS:
- The cause of MS is unknown; genetic factors, environmental
influences, and disturbances of the immune system all play
a role in its pathogenesis.
- It is clear, in any case, that autoimmune processes with auto
reactive T-lymphocytes and monocytes play a role in the
pathogenesis of the disease and cause episodes of inflamma
tion and demyelination.
- At the beginning of the disease, myelin sheath will be degen
erated and Oligodendrocytes will remyelinate the damaged
neuron (it means build the myelin sheath again).
- After a while, Oligodendrocytes will die and they will not be
able to re-myelinate the neurons (if another attack happens).
- When the neurons lose their myelin sheath and become
demyelinated , they do not conduct any signals in the CNS .as
a result, the CNS loses the connection between its neurons.
- The more active these inflammatory cellular autoimmune
mechanisms are, the more axons and neurons are lost, and
the more sclerotic glial scarring takes their place. Cumula
tive scarring over the course of the disease leads to progres
sive atrophy of the brain and spinal cord.
Common
symptoms in MS:
Disability and neurological impairments accumulate gradually over the
years. Several symptoms are common:
Cranial nerve dysfunction
- Impairment of ocular motor nerves, and pathways is caused by demyelination of
medial longitudinal fasciculus which control the three nerves (3-4-6) which inner
vate eye muscles.
- Impaired facial sensations, and trigeminal neuralgia which will lead to cause facial
weakness or Hemifacial spasm.
- Deafness, unsteadiness, and vertigo.
Motor system
- Paraparesis, quadriparesis, pseudo bulbar palsy syndrome hemiparesis, Monoparesis.
- Fatigue
-Signs: Weakness, hyperreflexia with or w/o clonus, hypertonia (Spasticity), early loss of
abdominal jerks, extensor plantar response (Babinski).
Sensory system
- Pain.
- Transient numbness and paresthesia
- Lhermitte’s phenomenon: Electric shock-like sensations radiate down the trunk and
limbs on neck flexion. This points to a cervical cord lesion.
-Signs: Impaired vibration and proprioception with decrease pain and touch sense.
Cerebellar Impairment
- Gait imbalance or ataxia
- Difficulty in performing coordinated actions
- Speech changes
-Signs: Nystagmus, Speech: stacatto, scanning, Intension tremor, Gait disturbances. It is
always present in advanced MS.
Cognitive and affective symptoms
- Impairment of memory and learning ability
- Depression and suicide
- Euphoria, hypomania
- Emotional labiality (pathological laughter and crying)
Autonomic disturbance
- Constipation and urinary symptoms: bladder precipitancy, hesitancy, and hyperreflexia
causing urine incontinence.
- Temperature sensitivity: temporary worsening of pre-existing symptoms with increases
in body temperature, e.g. after exercise or a hot bath, is known as Uhthoff’s phenomenon.
- Sexual dysfunction
Course and
clinical features of MS
The course of MS is variable. Over time, it is usually gradual, often step-
wise, accumulation of neurological deficits. The clinical patterns can be
subdivided into four types:
Relapsing- remitting (RRMS)
(85-90%) The most common pattern of MS. Symptoms occurs in attacks (relapses) with a
characteristic time course: onset over days and typically recovery, either partial or com-
plete, over weeks. On average, patients have one relapse per year but occasionally many
years may separate relapses. Patients may accumulate disability over time if they do not
recover fully after relapses.
Secondary progressive MS
This late stage of MS consists of gradually worsening disability progressing slowly over
years (possibly punctuated by further episodes. Occasional relapses but symptoms remain
constant, no remission.
Primary progressive (PPMS)
(10–15%) This pattern is characterized by Slow onset but continuous worsening condition.
It typically presents later and is associated with fewer inflammatory changes on MRI. Most
seen in older patients with spastic paraparesis MS.
Progressive relapsing MS
(<5%) This is the rarest and least common form of MS. It is similar to PPMS but with occa-
sional superadded relapses on a background of progressive disability from the outset.

Three characteristics common presentations of MS which are considered

as a risk factor and a symptom of MS:
Optic neuritis
It's one of the most common cause of subacute visual loss. Symptoms may vary from a
mild fogging of central vision with color desaturation to a dense central scotoma, but very
rarely complete blindness. Pain on eye movements is almost unilateral.
Brainstem demyelination
A relapse affecting the brainstem causes combinations of diplopia, vertigo, facial numb-
ness/weakness, dysarthria, or dysphagia. Pyramidal signs in the limbs occur when the corti-
cospinal tracts are involved.
Spinal cord lesions
Paraparesis developing over days or weeks is a typical result of a plaque in the cervical or
thoracic cord, causing difficulty in walking and limb numbness with tingling, often asym-
metric. Lhermitte’s sign may be present.
MS Diagnosis and
McDonald criteria
MRI (with contrast): to reveal abnormal white matter signal in the following typical
areas:periventricular - Juxtacortical (near the cortex) - Posterior fossa (also called infraten-
torial), which include cerebellum and brainstem) - spinal cord.

McDonald criteria:
It is useful to diagnose MS. There are two things have to be considered:

Disseminated in space Disseminated in time

1 T2 lesion or more in at least two MS - Simultaneous asymptomatic con-
typical CNS regions: trast enhancing and non enhancing
- Periventricular lesions at any time OR
- Juxtacortical - A new T2 and/or contrast- enhanc-
- Infratentorial ing lesions(s) on follow-up MRI,
- Spinal cord irrespective of its timing OR
- Await a second clinical attack
How to know there is dissemination in time radiologically?
Dissemination in time by the active and non-active lesion.
- Active lesion: take up contrast medium (called enhanced).
- Non active lesion: do not take the contrast.

CSF analysis:
- Protein: mild elevation
- WBCs: mild increase up to 50 cells per cubic millimeter
- Glucose: normal
- Oligoclonal bands: antibodies present in the CSF and serum sometimes in MS and some
other diseases.
- If the bands present (positive result) that confirm the diagnosis of MS if it is clinically fits.
- Negative result cannot exclude the diseases.

Visual evoked potentials VEP:

Delayed latency; a result of demyelination of axons in the visual pathway

Relapses features:
- Duration of at least 24 hours: If a patient present with the picture of relapse but the symp
toms last for 2 hours it is not a real relapse
- Interval of at least 30 days since the last relapse
- The episode is not a pseudo-relapse: infection, fever

Uhthoff phenomenon: Potential Triggers of Uhthoff's Phenomenon

Exacerbating of symptoms with
external \ internal elevated temperature
in some patients.
MS
Treatment
Acute management: Methylprednisolone 500 – 1000mg IV infusion per day for 3 - 5 days
(one time a day).

long-term management: Immune-modulating drugs. They have three categories:

Injectable, Oral and IV.

All these medications are not used in pregnancy except

Glatiramer acetate
First line: Interferon-β.
References:
- Kumar and Clark's Clinical Medicine - 10th Edition, chapter 26.
- Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide:
Insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816-1821.
doi:10.1177/1352458520970841
- Fundamental of neurology chapter 1 and 8
- Dr. Ashraf Zaher lecture

Prepared by:
Amnah Alkhawajah
Abdulelah Alshebly
Walaa Almousa
Majd Alsaleh

Designed by:
Farah Althikrallah