MULTIPLE SCLEROSIS

Haseeb Safdar Ali

Roll no. 178
What is MULTIPLE SCLEROSIS ?

• Autoimmune inflammation and demyelination of CNS (brain

and spinal cord) with subsequent axonal damage.

• More common in females in males , age 20-40 , more

common in individuals who grew up farther from equator +
low Vitamin D levels.

• Epstein-Barr infection is a risk factor

Pathophysiology

• MS is an autoimmune disorder involving both T-

lymphocytes and B-lymphocytes that mistakenly attack
the myelin sheath in the CNS Inflammation around small
veins (perivenular inflammation) leads to loss of
oligodendrocytes (myelin-producing cells) and
demyelination of nerve fibers
• Repeated immune attacks create multiple demyelinated
plaques (areas of myelin loss and gliosis) scattered
throughout the CNS white matter. These lesions are often
periventricular (around the brain’s ventricles) and can
cause secondary axonal injury over time. Pathologically,
MS lesions typically show infiltrating immune cells,
CLINCAL FEATURES- Symptoms

• Sensory Disturbance ; Numbness, tingling

• Muscle weakness / spasticity in limbs
• Visual Problems ; vision loss , diplopia
• Impaired balance / ataxia
• Bladder and bowel dysfunction
• Fatigue
• Cognitive Changes ; memory or concentration issues
• Neuropathic pain or Trigeminal Neuralgia in some
cases
Signs

• Optic Neuritis ; blurred vision , Afferent pupillary

defect
• Internuclear Ophthalmoplegia
• Pyramidal tract signs (hyperreflexia , Babinski
sign)
• Ataxic gait
• Sensory loss in dermatomes
Lhermitte's sign and Uhthoff's sign

• an electric shock-like sensation down the spine

on neck flexion, indicating a cervical cord lesion -
Lhermitte’s sign

• temporary worsening of neurologic symptoms

when the body is overheated (e.g. after exercise
or a hot bath) - Uhthoff’s sign
Typical Presentation

• Single episode of neurologic dysfunction

• Onset is usually subacute (developing over hours to
days)
• initial event is optic neuritis, experienced as
unilateral painful vision loss with reduced color vision
• brainstem syndrome (e.g. double vision, vertigo) or
partial myelitis (limb weakness/numbness)
• early attacks often improve spontaneously -
relapsing-remitting pattern
Aggravated by
• Heat Exposure – hot bath , exercise, fever
• Stress
• infections

RELIEVED BY

• Cool drinks, cool environment

• Rest
• Stress reduction
Disease Progression
• Relapsing-Remitting - Patients experience clearly defined
relapses (acute or subacute episodes of neurological
dysfunction) followed by partial or complete remissions.

• Secondary Progressive - gradual worsening of

neurologic function over time independent of acute relapses

• Primary Progressive - PPMS is characterized by

continuous worsening of symptoms and disability
without distinct relapses or remissions.
INVESTIGATIONS

• MRI – Gold standard - periventricular lesions (often

oriented perpendicular to the ventricles, known as
Dawson’s fingers) +

• as well as lesions in the juxtacortical, infratentorial

(brainstem/cerebellum), or spinal cord

• Radiologically, demonstrating lesions that are

disseminated in space and time on MRI (new and
old lesions in different CNS areas)
Cerebrospinal fluid analysis

• typically shows oligoclonal bands of IgG on

electrophoresis

• Oligoclonal bands indicate intrathecal IgG

production (chronic CNS inflammation) and
support the diagnosis of MS

• Mild pleocytosis (a slight increase in white cells)

or elevated protein may also be seen, but are
Evoked potentials

• visual evoked potentials (VEPs) often show

delayed conduction in the optic pathways of
MS patients , reflecting past optic nerve
demyelination

• provide evidence of lesions disseminated in

space ; an abnormal VEP could uncover an
asymptomatic optic nerve lesion
Management - Acute Management

• intravenous methylprednisolone (e.g. 1 gram

daily for 3–5 days) is given, often followed by an
oral steroid taper

• If a severe relapse does not respond to steroids,

plasma exchange (PLEX) is sometimes used as a
second-line treatment.
Disease-Modifying Therapies
• immunomodulatory or immunosuppressive
treatments
• interferon-β and glatiramer acetate

• monoclonal antibody therapies such as

natalizumab, ocrelizumab, alemtuzumab

• choice of DMT is individualized based on disease

severity, patient factors, and risk tolerance
Symptomatic Treatment
• Fatigue - energy conservation, rest
• Spasticity - muscle relaxants like baclofen
• Pain – gabapentin, carbamazepine
• Bladder dysfunction - anticholinergic medications
(oxybutynin)
• Depression – SSRIs
• Rehabilitation therapy
• Training or mobility aids.
MS in Pregnancy

• Relapse rates generally decrease during

pregnancy, especially in the 3rd trimester,
when endogenous immunosuppressive changes
occur

• After delivery, however, there is a rebound

increase in disease activity – the relapse rate
often rises in the first 3–6 months
postpartum
Management :
• DMTs are contraindicated or not
recommended in pregnancy due to potential
teratogenic

• Relapses during pregnancy are generally

treated with short courses of corticosteroids
(2nd+3rd Trimester)

• interferon and glatiramer are now often

continued during pregnancy in highly active MS,
A 32-year-old woman comes to the office due to left eye pain that
is accentuated by ocular movements. She also has periodic
dimming of vision in the same eye. The patient has had several
such episodes over the last month, most often after a hot shower
or intense workout. A year ago, she had an episode of numbness
and tingling in her left arm that resolved spontaneously. The
patient has no other medical issues and takes no medication.
She smokes half a pack of cigarettes a day and does not use
alcohol or illicit drugs. Vital signs are normal. BMI is 26 kg/m2.
Ophthalmologic examination shows swelling of the optic disc on
the left. Neurologic examination shows a mild intention tremor
and broad-based gait. Which of the following is the most likely
cause of the patient's current condition?

A. Atherosclerosis of the carotid arteries

B. Brain metastasis
C. Demyelinating plaques
A 35-year-old woman comes to the office due to trouble seeing out
of her right eye. The patient started having blurry vision and pain
with eye movement 2 days ago. She has no headache, vertigo,
slurred speech, numbness, or weakness. Two years ago, the
patient had an episode of double vision that spontaneously
resolved after a few weeks. On physical examination, she has an
afferent pupillary defect with markedly reduced visual acuity on
the right. Fundoscopy reveals blurring of the optic disc margins in
the right eye. MRI of the brain reveals multiple, ovoid white
matter lesions with perpendicular orientation to the lateral
ventricles. This patient's condition is most likely caused by an
inappropriate immune response directed against which of the
following cells?

A. Astrocytes
B. Ependymal cells
C. Microglial cells
D. Oligodendrocytes
• A 34-year-old woman comes to the office due to a 2-day
history of reduced sensation in her legs. Lately, the patient
has also had significant fatigue, especially with exercise. Six
months ago, she had an episode of visual blurring that
resolved spontaneously after a few days. Medical history is
significant for psoriasis, for which she uses a topical
glucocorticoid ointment. The patient does not use tobacco or
illicit drugs. Vital signs are normal. Examination indicates
decreased pain and light touch perception in both legs below
the level of the umbilicus. Mild bilateral spasticity is noted.
Which of the following pathologic brain lesions is most specific
for this patient's disease process?

• A. Microglial nodules
• B. Neuritic plaques and neurofibrillary tangles
• C. Perivenular inflammatory cells
• D. Spongiform changes
• E. Viral inclusions
• A 26-year-old woman is brought to the emergency department due to
acute-onset diplopia. Medical history is significant for episodes of
blurry vision involving her right eye that occurred 6 months and 2
years ago. These episodes were associated with deficits in color
vision and pain made worse with eye movement. The patient
recovered the majority of her visual acuity after a few months in both
cases. On neurologic examination, she has a visual acuity of 20/20
OS and 20/40 OD, mild right optic disk atrophy, and a relative afferent
pupillary defect in the right eye. There is slowed and impaired
adduction of the left eye with right lateral gaze. Convergence testing
shows normal adduction in both eyes. The remainder of the
neurologic examination is unremarkable. This patient's diplopia is
most likely caused by which of the following mechanisms?

• A. Impaired neuromuscular transmission

• B. Loss of axons
• C. Muscle fiber inflammation and necrosis
• D. Nerve compression
• E. Reduced saltatory conduction