Sheet 4

Question 1

What are some other acquired demyelinating diseases?

Answer 1

1) Post infectious demyelination
2) Neuromyelitis Optica
3) Central pontine myelinolysis

Question 2

What is Post Infectious Demyelination?

Answer 2

Immune-mediated demyelination that follows a number of systemic infectious illnesses, including relatively mild viral infections and some types of vaccinations. (Very few cases were reported following bacterial infection)

Question 3

Which viruses play a role in Post Infectious Demyelination?

Answer 3

1) Measles
2) Mumps
3) Rubella

Question 4

Is Post Infectious Demyelination related to direct spread of infectious agents to CNS?

Answer 4

NO

Question 5

How does the immune process happen in Post Infectious Demyelination?

Answer 5

The immune process is either cell mediated or humoral.

Question 6

What is the mechanism of Post Infectious Demyelination?

Answer 6

Immune cells response to pathogen-associated antigens cross-react
against myelin antigens, causing myelin damage.

Question 7

What are the two general patterns of post-infectious autoimmune reactions to myelin?

Answer 7

1) Acute disseminating encephalitis

2) Acute necrotizing hemorrhagic encephalomyelitis

Question 8

What is acute disseminating encephalitis characterized by?

Answer 8

Non-localizing symptoms that appear 1-2 weeks following infection.

Question 9

What are the non-localizing symptoms of acute disseminating encephalitis?

Answer 9

1) Headache
2) Deterioration in the level of consciousness
3) Lethargy
4) Coma

Question 10

What is the course of acute disseminating encephalitis?

Answer 10

Acute, rapid progression, fatal in 20% of cases.

Question 11

What happens if patents survive the acute disseminating encephalitis attack?

Answer 11

They have complete recovery.

Question 12

Is Progressive Multifocal Leukoencephalopathy related to direct spread of infectious agents to CNS?

Answer 12

YES

Question 13

What is Progressive Multifocal Leukoencephalopathy?

Answer 13

A disease of the white matter of the brain, caused by JC virus infection in immunocompromised patients. It affects multiple locations in the brain and worsens over time.

Question 14

What does Progressive Multifocal Leukoencephalopathy directly infect and destroy?

Answer 14

Oligodendrocytes that synthesize myelin.

Question 15

What is the result of Progressive Multifocal Leukoencephalopathy?

Answer 15

Loss of coordination and weakness

Question 16

What is Neuromyelitis Optica?

Answer 16

An antibody-mediated (autoimmune) inflammatory demyelinating disease that affects mainly the optic nerve ± spinal cord

Question 17

What causes myelin destruction in Neuromyelitis Optica?

Answer 17

Antibodies secreted by B cells (antibodies to aquaporin-4).

Question 18

What is diagnostic for Neuromyelitis Optica?

Answer 18

Antibodies to aquaporin-4

Question 19

What are the symptoms of Neuromyelitis Optica?

Answer 19

Optic nerve: diplopia, vision impairment, vision loss.

If spinal cord affected: weakness, bladder dysfunction, etc.

Question 20

What is Central pontine myelinolysis?

Answer 20

A non-immune neurological disorder that most frequently occurs after too rapid medical correction of sodium deficiency (hyponatremia) = (Rapid osmotic changes).

Question 21

What is the mechanism behind central pontine myelinolysis?

Answer 21

Damage to oligodendrocytes (separation of myelin from the axons in the pons) from edema due to sudden change in osmotic pressure

Question 22

What is extrapontine myelinolysis (EPM)?

Answer 22

Damage in other areas of the brain (other than the pons)

Question 23

Who is susceptible to developing central pontine myelinolysis?

Answer 23

People with chronic electrolyte abnormalities like:

1) Alcohol abuse.
2) Malnutrition.
3) Severe burns.
4) Liver transplantation.
5) Anorexia nervosa.
6) Hyperemesis gravidarum.
7) Hyperglycemic states.

Question 24

What are the outcomes of central pontine myelinolysis?

Answer 24

Life threatening, causes rapid quadriplegia (widespread paralysis) and can cause ‘lockedin’ syndrome (complete paralysis of voluntary muscles, except for those that control the eyes) and might even lead to death.

Question 25

How do we prevent central pontine myelinolysis?

Answer 25

Hyponatremia should be corrected at a rate of no more than 8-12 mmol/L of sodium per day to prevent central pontine myelinolysis.

Question 26

What are Leukodystrophies?

Answer 26

Inherited dysmyelinating diseases caused by abnormal myelin synthesis or turnover.

Question 27

What causes Leukodystrophies?

Answer 27

Mutations of genes whose products are involved in the generation, turnover, or maintenance of myelin.

Question 28

Some mutations of Leukodystrophies affect:

Answer 28

1) Lysosomal enzymes
2) Peroxisomal enzymes
3) Myelin proteins

Question 29

How are leukodystrophies inherited?

Answer 29

1) Autosomal recessive
OR
2) X-linked

Question 30

What are leukodystrophies named according to?

Answer 30

To the specific mutation the patient has.

Question 31

Leukodystrophies differ from demyelinating diseases in that Leukodystrophies
present as:

Answer 31

1) Insidious and progressive loss of function.
2) Often begin at younger ages (childhood).
3) Associated with diffuse and symmetric changes in white matter on imaging
studies

Question 32

What are the symptoms of Leukodystrophies?

Answer 32

1) Deterioration of motor skills
2) Spasticity
3) Hypotonia
4) Ataxia

Question 33

How do leukodystrophies appear on imaging?

Answer 33

Diffuse symmetric involvement of white matter.

Question 34

How do leukodystrophies appear grossly?

Answer 34

White matter is abnormal in color (gray and

translucent) and volume (decreased).

Question 35

How do leukodystrophies appear grossly (early on)?

Answer 35

Patchy involvement, or a predilection for certain site of involvement.

Question 36

How do leukodystrophies appear grossly (later on)?

Answer 36

All of white matter is affected.

Question 37

What happens with the loss of white matter in leukodystrophies?

Answer 37

1) Brain becomes atrophic.
2) Ventricles enlarge (compensatory change).
3) Secondary changes in gray matter can be found.

Question 38

Histology may differ according to the specific type of leukodystrophy:

Answer 38

1) Myelin loss associated with infiltration of macrophages.
2) Macrophages often become stuffed with lipid.
3) Some diseases show specific inclusions created by the accumulation of
particular substances in affected cells.