The document provides a comprehensive overview of demyelination and its key aspects, particularly focusing on multiple sclerosis (MS), a chronic degenerative disorder characterized by inflammation, demyelination, and gliosis. It discusses the disease's epidemiology, risk factors, pathophysiology, clinical features, diagnosis, and management strategies, emphasizing the importance of MRI and clinical findings in diagnosing MS. Furthermore, it outlines the various clinical presentations and types of MS, as well as treatment options such as corticosteroids and disease-modifying therapies.

1. BY
DR SABU AUGUSTINE
ASSOCIATE PROFESSOR
DEPT. OF GENERAL MEDICINE
DEMYELINATION
Dr Sabu Augustine
Associate Professor
Dept Of General Medicine
Dr S.M C.S.I Medical College, Karakonam, Trivandrum

2. DEMYELINATION
• INTRODUCTION
• BRIEF ANATOMY
• MULTIPLE SCLEROSIS
– DEFINITION
– EPIDEMIOLOGY
– AETIOLOGY & RISK FACTORS
– RISK FACTORS
– PATHOPHYSIOLOGY
– CLASSIFICATION
– CLINICAL FEATURES
– DIAGNOSIS
– INVESTIGATIONS
– TREATMENT

3. INTRODUCTION
• Demyelinating diseases comprise of diseases of central
and peripheral nervous system in which disruption of
myelin is a dominant feature.
• whether a primary biochemical abnormality of myelin
exists (dysmyelinating) or
• whether some other process damages the myelin or
oligodendroglial cells (demyelinating).
• Demyelinating diseases include autoimmune, infectious,
toxic, metabolic, and vascular processes; dysmyelinating
diseases in which a primary abnormality of the formation
of myelin exists include several hereditary disorders.

5. PARTS OF A NEURON
• Cell Body
– Contains the nucleus
• Dendrites
– Receptive regions; transmit
impulse to cell body
– Short, often highly branched
– May be modified to form receptors
• Axons
– Transmit impulses away from cell body
– Axon hillock; trigger zone
• Where action potentials first develop
– Presynaptic terminals (terminal boutons)
• Contain neurotransmitter substance (NT)
• Release of NT stimulates impulse in
next neuron
– Bundles of axons form nerves

6. MYELIN AND WHITE MATTER
• The gray matter primarily contains neurons and their
processes, the white matter is composed predominantly of
myelinated bundles of axons
• The oligodendroglial cell membrane is the source of the
myelin sheath, which is a tightly wrapped, multilayered
membrane composed of a repeating structure characterized
by lipid- cytoplasm-lipid-water and which ensheathes
axons.
• Any process, including metabolic injury or ischemia, that changes
the chemical composition of myelin will result in a less stable
structure that is more susceptible to injury .

7. MYELIN AND WHITE MATTER
• Neuroglial cells, namely oligodendrocytes,
astrocytes, and microglia, are primarily
responsible for the maintenance or “well- being”
of the white matter- by providing structural and
nutritional support of neurons, regulating the
extracellular environment, and acting as
scavenger cells.
• As white matter becomes myelinated, it appears
hyperintense on T1-weighted and hypointense on
T2-weighted images relative to gray matter

8. CONDUCTION OF NERVE FIBRES BEFORE &
AFTER DEMYELINATION

9. Normal myelinated
axon
nodes of Ranvier
• Lipid-rich myelin sheath
produced by oligodendrocytes
• Axon insulation
• Sodium channels clustered at
• Increased conduction speed and
metabolic efficiency
Demyelination
or block
cytoskeleton
• Decreased conduction velocity
• Destablization of axonal
• Remodelling of internodal
membrane
• Progressive axonal loss

10. MULTIPLE
SCLEROSIS

11. DEFINITION
• Multiple sclerosis is a chronic progressive,
degenerative disorder of the CNS
characterized by disseminated demyelination
of the nerve fibres of the brain and spinal
cord.
• Multiple sclerosis (MS) is characterized by a
triad of inflammation, demyelination, and
gliosis (scarring); the course can be relapsing-
remitting or progressive.

12. EPIDEMIOLOGY
• MS is 2-3 times more common in women
than men.
• MS is predominantly a disease of young adults
with a mean age of onset around 30 years old.

13. AETIOLOGY & RISK FACTORS
• The aetiology of MS remains poorly
understood.
• Like most inflammatory conditions of
unknown aetiology, the cause is thought to be
due to an abnormal immune reaction to an
unknown environmental trigger in a
genetically predisposed individual.

14. RISK FACTORS
Risk factors that may be associated with triggering an
autoimmune response that subsequently leads to the
disease.
• Viral infections: several viruses linked with MS.
Increased risk of MS following Epstein-Barr virus (EBV)
infection (i.e. glandular fever)
• Geographic latitude: prevalence of MS increases the
greater the distance north or south from the equator.
Migration after puberty carries risk from former
geographic location.
• Sunlight exposure: inverse relationship between MS,
sunlight exposure and vitamin D levels.
• Other: obesity during adolescence, smoking, gender
(females at increased risk).

15. PATHOPHYSIOLOGY
• MS is an inflammatory, demyelinating disease
of the CNS, which is characterised by the
presence of plaques.
• In MS, oligodendrocytes are destroyed, which
leads to demyelination and can cause axonal
loss.

16. Classical plaque sites
• Optic nerves: affects 40% during course of disease.
Presenting demyelinating event in 20%.
• Spinal cord: affects 50-75% during course of disease.
Majority associated with concomitant brain lesions.
Predilection for cervical spine.
• Brainstem: may present with ophthalmoplegia (e.g.
intranuclear ophthalmoplegia - discussed below).
• Cerebellum: characteristically causes ataxia and gait
disturbance.
• Juxtacortical white matter (near the cerebral cortex).
• Periventricular white matter (near the ventricular
system).

17. • The BBB prevent entrance of T cells into the nervous
system.
The blood–brain barrier is normally not permeable to
these types of cells, unless triggered by infection or a
virus, which decreases the integrity of the tight junctions.
When the blood–brain barrier regains its integrity, usually
after infection or virus has cleared, the T cells are trapped
inside the brain.
Blood-brain
barrier
breakdown
• The immune system attacks the nervous system, forming
plaques or lesions.
Commonly involves white matter.
Destroys oligodendrocytes- causing demyelination
Remyelination occurs in early phase but not completely.
Repeated attacks lead to fewer remyelination.
Autoimmunology
• T-cells attacks on myelin triggers inflammatory processes,
stimulating other immune cells and soluble factors like
cytokines and antibodies.
Leaks form in the BBB cause swelling, activation of
macrophages, and more activation of cytokines and other
destructive protein
Inflammation

18. CLASSIFICATION
• There are eight types of multiple sclerosis. They
are:
• Progressive Relapsing (PRMS)
• Secondary Progressive (SPMS)
• Primary Progressive (PPMS)
• Relapsing / Remitting (RRMS)
• Benign
• Spinal form
• Neuromyelitis optica
• Marburg variant

20. 13-03-2016 DEMYELINATING DIS
•changes in sensation (33%)
•Optic neuritis (20%)
•Weakness(exercise induced) (13%)
•double vision- internuclear opthalmoplegia (7%)
•unsteadiness while walking (5%)
•and balance problems (3%)
Lhermitte's sign (25-40%) is an electrical
sensation that runs down the back and into the
limbs and is produced by bending the neck
forwards. The sign suggests a lesion of the dorsal
columns of the cervical cord or of the caudal
medulla.
Uhthoff's phenomenon is the worsening of
neurologic symptoms in multiple sclerosis when
the body gets overheated from hot weather,
exercise, fever,
The most common initial symptoms
CLINICAL FEATURES

21. CLINICAL FEATURES
• Clinical features associated with MS are
determined by plaque locations within the
CNS.
Visual- Optic neuritis and Eye movement
abnormalities.
• Optic neuritis characteristically presents with
partial or total unilateral visual loss that
develops over days.

22. • Eye movement disorders may be due to
brainstem lesions that affect cranial nerves or
the pathways that connect visual tracts
together.
• Two commonly seen are INO and Abducens
palsy.

23. INO: disorder of conjugate lateral gaze due to demyelination of the
medial longitudinal fasciculus (MLF). MLF is heavily myelinated.
Connects the abducens nucleus complex with the contralateral
oculomotor nucleus. If affected, when looking to the right, the
right eye will abduct but the left will remain central (failure in
adduction).

24. Motor & coordination
• The prominent motor feature in MS is progressive
paraparesis and evidence of upper motor neuron signs
(Spasticity, reduced power, hyper-reflexia).
• Motor and coordination abnormalities may present as
a typical clinical syndrome such as
transverse myelitis
or
cerebellar syndrome (ataxia, slurred speech, intension
tremor, nystagmus, vertigo and clumsiness).

25. Sensory & autonomic
• Sensory symptoms are common in MS and seen
in almost all patients during the course of the
disease.
• Paraesthesia
• Pain
• Heat sensitivity (Uhthoff phenomenon)
• Sexual dysfunction
• Bladder & bowel dysfunction

26. Cognitive & psychological
• Cognitive impairment,
depression and fatigue
are all extremely
common.
• depression can have a
negative impact on
memory, attention, and
concentration.

27. DIAGNOSIS
• MS is primarily a clinical diagnosis, which is
supported by the use of MRI.
• There is no pathognomonic test for MS. All labs
are nonspecific and are to be interpreted within
the clinical picture.
• Lesions scattered in time and space”; a lesion
must occur in different locations in the CNS at
different points of time.
• The diagnosis of MS is based on the clinical
presentation (called an ‘attack’ or ‘relapse’),
which is then confirmed by objective clinical
evidence.

28. DIAGNOSIS
• MS attack: defined simply as an episode of
neurological symptoms that relate to an
inflammatory demyelinating lesion. Lasts > 24
hours with or without recovery. Typically sensory
disturbances, motor weakness, or visual
complaints. There must be more than 30 days
between attacks to count as a separate episode.
• Objective clinical evidence: identification of an
abnormality (usually on clinical examination or
MRI), which corresponds to the anatomical
location suggested by the current, or past,
symptoms of a MS attack.

29. Revised McDonald criteria
• The McDonald criteria was revised in 2017
and it is based on the principle that
demyelinating lesions (in brain +/- spinal cord)
are disseminated in time and space.
• In other words, two independent clinical
attacks would be evidence of dissemination in
time and two separate lesions on MRI would
be evidence of dissemination in space.

30. INVESTIGATIONS
• Additional investigations can be used to help
support the diagnosis and exclude an alternative
pathology.
Cerebral Spinal Fluid (CSF) Examination
• Increased in Protein (myelin basic, 25%),
Oligoclonal IgG bands (greatest sensitivity), IgG
and WBCs.
• The test is considered positive if oligoclonal
bands identified in the CSF are not present in the
serum. Therefore, a paired serum sample should
be taken at the time of the lumbar puncture.

31. VEP (Visual Evoked Potentials) (high sensitivity
along with MRI)
• VER involves measuring electrical activity via a
transducer over the occipital cortex in response
to a light stimulus.
• not useful during acute episodes.
BAER (Brainstem Auditory Evoked Response)
• Investigates the pontine area displaying an
absence or delay of wave formation secondary
to the demyelinating process
SEP (Sensory Evoked Potentials)
•Prolongation of absolute peak or interpeak
latency
Evoked potentials

32. MANAGEMENT
• MS management is broadly divided into
general care, managing acute relapses and
disease modifying therapies.
• The principle management of an acute relapse
or ‘attack’ in RRMS is the use of
corticosteroids.
• Before treating a relapse, it is essential to rule
out infection, which can lead to a
deterioration in symptoms.

33. Medications
• Immunomodulator agents- Disease modifying.
• Corticosteroids (Methylprednisolone).
• Agents to Alter the Course of theDisease.
Interferon-A
Interferon-B
Glatiramer acetate
• Immunosuppression agents are reserved for
patients with unresponsive disabling MS.

34. Mental function (Hmf): Mild cognitive changes, apathy,
inattention, depression, euphoria
Upper motor neuron weakness
Uthoff's phenomenon
Language: Dysarthria
Tingling numbness
Trigeminal neuralgia
Intention tremors
Internuclear ophthalmoplegia
Posterior column features
Pulfrich phenomenon (sense of disorientation in moving traffic)
Lesions disseminated in time and space
Exercise worsens symptom
Mnemonic to remember

35. • Sensory: Posterior column involvement
Cerebellar signs
Lhermitte sign
Exercise worsens symptoms
Remitting features
Optic neuritis
Oligoclonal bands in CSF electrophoresis
Spasticity
Internuclear ophthalmoplegia
Immunotherapy (Disease modifying drugs): ABC –
Interferon Beta-1A, Interferon Beta-1B, Copaxone
(Glatiramer)
Incontinence (bowel and bladder involvement)
Steroids for acute exacerbation
Mnemonic to remember