Diseases & Autoimmune Mechanisms Underlying Multiple Sclerosis Flashcards Preview

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Flashcards in Diseases & Autoimmune Mechanisms Underlying Multiple Sclerosis Deck (30)
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1
Q

Where is the white matter and what does it contain ?

A

In the medulla, contains MAINLY axons and some microglial cells

2
Q

Grey matter

A

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

3
Q

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

A

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

4
Q

What is neuropil ?

A

Cytoplasm of neurons and glial cells

5
Q

Microglial cells are :

A

Astrocytes in CNS

Schwann cells in PNS

6
Q

Function of oligodendtrocytes :

A

Secrete myelin

7
Q

Function of myelin

A

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

8
Q

Nodes of Ranvier

A

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

9
Q

Jumping of AP from one node to another is called

A

Saltatory Conduction

10
Q

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

A

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

11
Q

Leukodystrophies ( METABOLIC )

A

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

12
Q

MS Incidence in general pop

A

1/1000

13
Q

MS

A

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

14
Q

Why learn about the pathogenesis

and molecular basis of disease ?

A

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

15
Q

IFN BETA function

A

Reduce antigen presentation and T cell proliferation

16
Q

Pathogenesis of MS

A

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

17
Q

Function of TH1 and TH17

A

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 )

18
Q

Plaques

A

Patches of demyelination in the WHITE matter

19
Q

One of the most common presenting signs in MS

A

OPTIC NEURITIS

20
Q

Plaques involve

A

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

21
Q

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

A

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.

22
Q

Foamy histocytes :

A

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

23
Q

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

A

MRI : gives u a clear picture of the demyelination areas

24
Q

Secondary progressive MS

A

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

25
Q

Involvment of optic nerve

A

Unilateral visual impairment

26
Q

Involvment of brainstem

A

Cranial nerve signs/ataxia/nystagmus/internuclear opthalmoplegia

27
Q

Spinal cord lesions

A

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

28
Q

PML

A

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 )

29
Q

Krabbe disease

A

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

30
Q

Central pontine myelinolysis

A

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 )