Demyelinating disorders

Dr. Mehzabin Ahmed

 MYELIN
• Protective sheath that envelopes the neuronal
processes.

• Made up of cholesterol and phospholipids.

• In the CNS most of the myelin is located in the

white matter.
 Functions:
1) Protect and insulate the
axons
2) Allow rapid transmission
of electrical impulses

Saltatory conduction
of nerve impulses
 DEMYELINATION
• A process by which the myelin sheath is
damaged & destroyed.

• It occurs either as:

• Primary process: here only the myelin sheath is
destroyed & the axon remains intact.

• Secondary process: here the damage occurs first

(primarily) to the axons & the myelin
surrounding these damaged axons is secondarily
broken down.
Myelin (cholesterol &phospholipids)

(broken down)

Phagocytosed by macrophages

Neutral lipids or Cholesterol esters 

 Causes of demyelination
• Autoimmune: Multiple sclerosis
• Viral infections: JC papova virus infections
especially in the immunocompromised.
• Chemical injury: Hexachlorophene (an
antiseptic) causes demyelination in infants.
• Immunological: Delayed hypersensitivity to
Measles, Mumps, Rubella, Small pox, Rabies
virus infections
• Metabolic: Alcoholism, Malnutrition, and
Electrolyte disturbances.
 Demyelinating diseases of the CNS
Multiple Sclerosis
• It is the most common & the most important of
the demyelinating diseases. The demyelination
occurs at multiple sites & is followed by gliosis.

• This results in the sclerosis or hardening of the

involved tissue.

• Any part of the CNS may be involved.

 Etiopathogenesis
• Peak incidence is 20-40 Yrs & F : M = 2 : 1
• Associated with HLA-DR2
• It is autoimmune disease (epitope sharing of viral
antigen with myelin), ?Ebstein Barr virus, Human
Herpes Virus 6).
• Geographic distribution:
Prevalent in the West- Europe, North America,
Australia and New Zealand.
Very much rarer in the eastern countries,
May be related to the climatic conditions, genetic
make up of the races, or dietary differences.
Destruction of the myelin by the
autoreactive lymphocytes
 Clinical presentation

• The course of the disease is variable ranging

from mild to progressive disease.

• Demyelination results in the slowing of the

conduction velocities in the axons.

• The symptoms worsen when exposed to heat as

there is a further decrease in the conduction.
Cold baths & swimming exercises are beneficial.
 In the cerebral involvement
• Limb weakness

• Loss of sensation over the limbs

• Abnormal sensations of pins & needles and a

tingling sensation

• Blurring of vision due to optic neuritis

• Facial pain
 In the cerebellum & brainstem

• Loss of balance & tremors

• Nystagmus

• Involvement of the cranial nerves

 Spinal cord
• Motor & sensory impairment of the limbs

• Decreased muscle strength

• Spasticity

• Loss of bladder control

• Impotence
Natural course of MS
1. Relapsing/Remitting
(RRMS)
Patients are
typically in their 20s
and 30s

F > M = 2:1

Relapse
days/wks/mths
old & new symptoms

Remission
2. Secondary Progressive
(SPMS)

Gradual worsening of the

disease between relapses

RRMS

SPMS
3. Progressive Relapsing
Multiple Sclerosis
(PRMS)

Progressive course from

onset, punctuated by
relapses.

Relapse & Significant

recovery

Gradual
worsening
Relapse
4. Primary Progressive
(PPMS)

Gradual progression of the

disease from its onset with
no remissions
Onset is typically in the
late 30s/ early 40s
M:F=1:1

Initial disease activity is in

the spinal cord and not in
the brain
 Diagnosis
• Clinical evaluation

• Electrophysiology: shows a slow nerve

conduction velocity due to an increased
latency in transmission.

• MRI: multiple plaques are seen

• CSF: shows increased proteins & gamma

globulins.
Grey-tan colored plaques are seen in the white mater
Plaques- gray tan lesions in the white mater
Heidenhains stain for the myelin shows areas of
demyelination (plaques) in the
cerebrum, optic chiasma & midbrain
 Variants of Multiple Sclerosis
Devic disease:
• Found in the Asians.
• Present with bilateral optic nerve & spinal cord
involvement.
• More rapid & progressive with involvement of the gray
matter as well.
• MRI shows more destructive plaques.

Marburg disease
• Young individuals are more commonly affected.
• It has a very rapid course
• MRI show large numerous plaques with widespread
demyelination & axonal loss.
 Demyelinating diseases of the
peripheral nerves
Guillian-Barrè syndrome

• A common, life threatening demyelinating disease

of the peripheral nervous system.

• Demyelination of the peripheral nerves & spinal

nerve roots occurs resulting in weakness of the
distal limbs and rapidly advances to proximal
muscles (ascending paralysis).

• Death in the patient may be due to respiratory

paralysis or due to complications of tracheostomy
 Etiopathogenesis

• It follows after the recovery from flu like

illness, resulting from a viral infection.

• It is probably immune mediated by T cells

and circulating immunoglobulins.
 Clinical features
• Ascending paralysis with the disappearance of
the deep tendon reflexes early in the course of the
illness.
• Sensory loss also occurs.
• Death is usually due to respiratory muscle
paralysis or complication of tracheostomy.
• Electrophysiological studies show a slow nerve
conduction velocity.
• CSF examination shows raised proteins.
In diphtheria a selective pattern of

demyelination can occur due to the

effect of the diphtheria toxin on the ganglia.

 Neurotransplantation

Procedure by which fetal neuronal tissue is

implanted into the brain of patients of chronic
debilitating and incurable CNS conditions like
Alzheimer, Huntington, Parkinsons, Amyotropic
lateral sclerosis, cerebral palsy, brain and spinal
cord injury and stroke.
 Risks & Complications
• Loss of voluntary movement (paralysis) in part of
the body.
• Loss of sensation.
• Stroke caused by bleeding in the brain.
• Temporary balance problems.
• Numbness around the mouth (leading to drooling)
and in the hands.
• Weakness in one side of the body.
• Infection.
• Seizures.