MS

Question 1

Definition

Answer 1

chronic, progressive, autoimmune inflammatory disorder of the CNS characterized by disseminated demyelination resulting in formation of plaques and variable degrees of axonal loss.

It’s the most important cause of progressive neurological disability.

Question 2

Epidemiology

Answer 2

-more common in the northern hemisphere

-increased genetic susceptibility has been shown in individuals of Scandinavian or northern European ancestry.

-highest in young adults in their 20-30s

-mostly young women (between 20 and 40 years of age),

Question 3

Etiology

Answer 3

The etiology of MS is multifactorial, both genetic and environmental factors play an important role.

- MHC alleles have been found with an increased frequency in patients with MS, particularly the DRB1*15:01 allele.
 More than 110 genes have been identified as being predisposing, these are mostly genes that code for immunomodulatory molecules (HLA-DR2, IL7RA, IL2RA, CLEC16A, CD58, TNFRSF1A, IRF8 and CD6)

 Epstein Barr virus infection: there is a 15 times greater risk of developing MS if an EBV infection occurs during childhood, and a 30 times greater chance if the infection occurs in adolescence and results in mononucleosis.
 Smoking
 Latitude (Ultraviolet radiation, lack of sunlight exposure)
 Low Vitamin D levels
 Month of birth (May)
 Timing of exposure (migration studies

Question 4

Pathological counterpart

Answer 4

*demyelinating plaques
(result of active inflammation, then demyelination, and glial reaction (reactive gliosis). )

Question 5

PLAQUES

Answer 5

ACUTE :lesions produce in active inflammation

CHRONIC: old remnants of past inflammatory episodes

Question 6

LOCATION OF PLAQUES

Answer 6

Optic nerve –> optic neuritis ( very first)

• Corpus callosum
• Brainstem
• Spinal cord
• Periventricular areas
• Cerebellum

Plaques occur predominantly in the perivascular region of white matter, later areas of demyelination with gliotic reaction can be seen

Question 7

Characteristics of the plaques

Answer 7

these are irregular in shape and can vary in size from a few millimeters to several centimeters.

recent: rosy, soft and with blurred margins

long lasting : gray, hard and with defined margins

Question 8

Plaques only in white matter?

Answer 8

Plaques can cross the border between the white and gray matter.

Other types of plaques can occur only in the gray matter, both with a scattered or a diffused pattern of distribution.

Question 9

What happens with demyelination?

Answer 9

the conduction velocity decreases, or the spikes are totally blocked.

Question 10

3 types of cortical lesions

Answer 10

-Type I lesions affect both white and gray matter

-Type II lesions are small perivascular areas of demyelination

-Type III lesions extend from the oial surface into the cortex and often demyelinate multiple gyri.

Question 11

Pathophysiology of axons

Answer 11

Axons are transected during inflammatory demyelination

The axon on the right ends in a large swelling (white arrow), or axonal retraction bulb, which is the hallmark of the proximal end of a transected axon.

Question 12

KEY POINTS

Answer 12

. While inflammatory-mediated white matter demyelination is an underlying cause of axonal loss during early stages of MS, the transition from acute to progressive MS is though to occur when axonal loss exceeds the compensatory capacity of the CNS. Subpial demyelination is a prominent feature of progressive MS and it is important to determine mechanisms that lead to subpial demyelination.

Question 13

PATHOLOGY OF MS

Answer 13

the plaque; plaques are multiple focal areas of myelin loss within the CNS.

demyelination; this process is accompanied by variable gliosis and inflammation and by relative axonal preservation

PARALEL TO DEMYELINATION :axonal injury; this process is not strictly dependent on demyelination.

Question 14

• Acute active MS lesions

Answer 14

hypercellular demyelinated plaques massively infiltrated by macrophages, evenly distributed throughout the lesion, forming the classic “sea of macrophages” . These macrophages contain myelin debris, an indication that they have taken up and degraded the remnants of the destroyed myelin sheaths (ie, active demyelination)

Question 15

Perivascular and parenchymal inflammatory infiltrates

Answer 15

are invariably present, suggesting that demyelination and axonal degeneration are inflammatory in nature.

Besides activated macrophages/microglia, inflammatory infiltrates are composed of lymphocytes, the vast majority of which are CD8-positive cytotoxic T lymphocytes, and fewer CD4-positive helper T cells, B cells, and plasma cells

Question 16

MRI

Answer 16

Gadolinium enhancement characterizes lesions with damaged blood-brain barrier (BBB), which enables infiltration of inflammatory cells into the CNS. The inflammation together with the demyelination and vasogenic edema present in early MS lesions are responsible for their pinkish- yellow, soft, and poorly demarcated appearance on fresh slices of brain and spinal cord.

Demyelination with relative axonal sparing is important for the diagnosis of demyelinating lesions, whereas an infarct is more likely if axons and myelin in lesions are depleted to the same extent.

Question 17

Axonal injury is most pronounced during active inflammatory demyelination. Acute axonal injury occurring in early MS lesions likely contributes to relapse-related disability observed predominantly during the inflammatory disease phases. The extent of axonal damage in active lesions correlates significantly with the number of lymphocytes and activated microglia.