Diseases & Autoimmune Mechanisms Underlying Multiple Sclerosis

Question 1

Where is the white matter and what does it contain ?

Answer 1

In the medulla, contains MAINLY axons and some microglial cells

Question 2

Grey matter

Answer 2

Cortex - neurons and some of their axons/ some microglial cells

Question 3

What is the stain used to highlight myelin ? Where can we find myelin

Answer 3

Luxol blue stain and immunohistochemical stains for myelin / White and grey matter

Question 4

What is neuropil ?

Answer 4

Cytoplasm of neurons and glial cells

Question 5

Microglial cells are :

Answer 5

Astrocytes in CNS

Schwann cells in PNS

Question 6

Function of oligodendtrocytes :

Answer 6

Secrete myelin

Question 7

Function of myelin

Answer 7

Insulator that prefents current from leaking, increasing the speed of conduction

Question 8

Nodes of Ranvier

Answer 8

gaps in the myelinated sheath ( unmyelinated spaces ) where the signsal is RECHARGED as it travels along the axon

Question 9

Jumping of AP from one node to another is called

Answer 9

Saltatory Conduction

Question 10

Demyelinating diseases affect CNS (and PNS ) are characterized by :

Answer 10

Damage to myelin with relative preservation of axons BUT with long standing damage it could affect axons ( in infarcts axons and peri-axonal myelin are depleted to the same extent

Question 11

Leukodystrophies ( METABOLIC )

Answer 11

Inherited - some enzymes deficiency can also affect the formation of myelin - INFANTS are mostly affected

Question 12

MS Incidence in general pop

Answer 12

1/1000

Question 13

MS

Answer 13

Autoimmune demyelinating disorder : distinct episodes of neurologic deficits - seperate in time - seperate in space
CHRONIC INFLAM resulting in demyelination and destruction of OLIGODENDROCYTES ( reactive ASTROCYTES )
Affect young adults - women

Question 14

Why learn about the pathogenesis

and molecular basis of disease ?

Answer 14

One of the key reasons is to devise
strategies of drug development for targeted
therapy

Question 15

IFN BETA function

Answer 15

Reduce antigen presentation and T cell proliferation

Question 16

Pathogenesis of MS

Answer 16

Viral/environmental/genetic (HLA-DRB1*1501 ellele)
T cells cross the BBB encounter myelin presented by MICROGLIA (MBP)
Re-exposure TH1 and TH17 secrete cytokines

Question 17

Function of TH1 and TH17

Answer 17

TH1 > IFN gamma activate MQs
TH17 > recruit leukocytes which release more inflam mediators and cause damage
B Cells differentiate to plasma cells and produce ANTI MYELIN Abs
( both humoral and cell mediated immunity contribute )

Question 18

Plaques

Answer 18

Patches of demyelination in the WHITE matter

Question 19

One of the most common presenting signs in MS

Answer 19

OPTIC NEURITIS

Question 20

Plaques involve

Answer 20

Periventricular white matter/Subpial cortex/leptomeninges/brain stem/spinal cord/optic nerve/retina
( there’s also gonna be symptoms related to bowel and bladder )

Question 21

The plaques ( areas of demyelination ) are usually in a perivascular areas ( around a blood vessel ) Why ?

Answer 21

because of the presence of inflammatory cells ( they come from the blood ) So when the inflammatory cascade takes place, first area that’s gonna affected is perivascular areas.

Question 22

Foamy histocytes :

Answer 22

MQs ( histocytes ) engulf myelin debris and released lipid material. This indicates active plaque ( active plaques : myelin breakdown )

Question 23

What is the main diagnostic tool after clinical impression in MS ?

Answer 23

MRI : gives u a clear picture of the demyelination areas

Question 24

Secondary progressive MS

Answer 24

Relapsing-Remitting stage may be followed by a phase of uninterrupted disease progression

Question 25

Involvment of optic nerve

Answer 25

Unilateral visual impairment

Question 26

Involvment of brainstem

Answer 26

Cranial nerve signs/ataxia/nystagmus/internuclear opthalmoplegia

Question 27

Spinal cord lesions

Answer 27

Motor and sensory impairment of trunk and limbs/ spasticity / difficulties with voluntary control of bladder function

Question 28

PML

Answer 28

Encephalitis caused by JC pyloma virus infection of oligodentrocytes - deadly demyelinative - in immunosupressed pt’s : AIDS (1) cancer/inflam disorders/chemotherapy/organ transplant/Natalizumab ( for MS and Crohn’s )
Latent in kidneys and lymphoid tissues then reactivate when immunity is low ( visual impairment, paralysis, dementia )

Question 29

Krabbe disease

Answer 29

Also called : globoid leukodystrophy- autosomal recessive- deficiency of galactorebrosidase, an enzyme required for the catabolism of galactorebroside to ceramide and galactose. Consequence : an alternative catabolic pathway shunts galatocerebroside to galactosylsphingosine in the brain which is cytotoxic > loss of myelin and oligodendrocytes

Question 30

Central pontine myelinolysis

Answer 30

Acute disorder characterized by loss of myelin in the basis pontis, typically in a roughly SYMMETRIC pattern.
Occurs in hyponatermic patients when hyponatermia is rapidly corrected ( osmotic demyelination syndome ).
Luckily if some patients get it, they recover only some have neurological deficits.
Rapid increased in osmolality damages oligodendrocytes
Clinically : rapidly evolving quadriplegia which may be fatal or lead to severe deficits, including locked in syndrome ( conscious but unresponsive )