Demyelinating Disease

Subacute sclerosis panencephalitis is associated with which viral infection?

Measles

Progressive multifocal leukoencephalopathy is associated with:

JC virus which is reactivated in immunocompromised hosts (affects oligos)

Bacterial induced demyelination of cranial and peripheral nerves is associated with which bacterial toxin?

Diptheria

Diffuse monophasic demyleinating disease following viral infection and usually presents with HA, lethargy and coma and not focal deficits like MS. CT scan shows ring-enhancing lesions.

acute disseminated encephalomyelitis

Young patient with a history of an URT infection. Now presents with a fulminant CNS demylinating condition characterized by perivenular, diffuse demyleination, hemorrhage of blood vessels and PMN infiltration. The condition is likely:

Acute Necrotizing Hemorrhagic Leukoencephalitis

A person presents with rapidly evolving quadraplesia following rapid correction of hyponaturemia. What is the condition? What region is affected? Is there inflammation associated with it?

The condition is central pontine myelinolysis. The basis pontis and pontine tegmentum are usually affected where there is demyelination but preservation of the neurons and the underlying axons. There is no inflammation associated with the condition.

Define MS

It is a chronic disease manifest as recurrent attacks of neurological dysfunction caused by multiple areas of inflammation and myelin loss in the brian and spinal cord. It is a highly unpredictable and variable disease

What is the most common course of MS?

Relapsing-remitting where there is an episode, months-years of remission and then another episode. Disease slowly climbs in disability as the number of episodes accumulates

Secondary progressive MS:

-2nd most common disease progression
-there are episodes and the patient recovers but not all the way back to baseline. This means that with each subsequent episode, the patient is left with deficits. Later in life, the disease progresses much more rapidl

What is the pathological definition of MS?

MS is a chronic inflammatory disease of the CNS causing demyelination, death of oligos and variable degrees of tissue damage including axonal damage

What are Dawson's fingers:

MS plaques that tend to form around veins where inflammatory cells are released and surround the plaque region.

What is the most common demyelinating condition?

MS

What is the incidence of MS? What is the difference between men and women? When does it usually present?

1 out of 1000. 2x more common in women. Disease can present at any age but it is rare to be diagnosed in childhood or after 50 years

What is the underlying pathogenesis of MS?

It is an autoimmune condition where the inflammatory cells target the oligos and lead to degeneration

Discuss the axonal loss associated with Acute MS plaques, chronic active plaques (edge), chronic active plaques (center) and "normal WM

Acute plaques: 11,000 dead axons
Chronic active plaques (edge): 3000 dead axons
Chronic active plaques (center): 800
Normal WM: 20

What are the three processes causing the clinical signs in MS?

1. Inflammation: acute and reversible
2. Demyelination: variable and cumulative (some remyelination, but some permanent damage)
3. Axonal loss: Progressive and permanent

Discuss how the MS pathology correlates to the disease:

It does not correlate with the clinical picture, it has no predicative value, and does little or nothing to direct us to the etiology

Do you want to biopsy MS plaques?

NO: clinical picture does not match pathology and pathology has no predictive value or direct us to determine underling cause

MS is more common as you move ______ from the equator:

away

Discuss the evidence for the environmental causes of MS

People who migrate from a low incidence to an area of high incidence before the age of 15 have a higher risk of developing MS
Migrants to a low incidence area have a smaller risk of developing MS than if they remained in their home environment
After 15 ye

A 20 year old man migrated from Alaska to Ecuador, does his risk of developing MS increase, decrease or stay the same? What if he was 10?

Stays the same;
If he was 10, his risk would decrease

Discuss the findings of the Faroe Islands:

Before the British arrived to the islands, there were no cases of MS. After they occupied the island, however, there were four epidemics. This is suggestive that the British brought a potential virus to the island that triggered MS.

Concordance of MS in monozygotic twins is:

30%

Is there a mendelian locus associated with MS?

No

True or false: Low vitamin D levels correlates with MS?

True

Discuss the role of vitamin D in the development of MS:

Transmanian children expose to large amounts of sun are 1/3 as likely to develop MS later in life
Nurses taking Vitamin D supplements are 40% less likely to develop MS
MS pt have low vitamin D and bone demineralization early in the disease even if they ha

True or false: autoimmune diseases such as Myasthenia gravis, inflammatory bowel disease, diabetes etc. are more commonly seen in MS:

True

Asthma and allergies, cancer, Down syndrome, Lupus and gout are _____ common in patients with MS.

Less common

How would you image an MS plaque?

Axial T1 MRI with gadolinium contrast
Axial FLAIR MRI

How do you manage a patient with MS? What medications?

Immune suppression agents
-Interferons: (beta-1a and 1b)
-Glatiramer acetate
-Natalizumab
-Fingolimod
-Teriflunimide
-Vitamin D

DR2 haplotype of MHC is associated with increased risk of:

MS

MS plaque is surrounded by what cell types?

T cells and macs

What are common locations of the MS plaques?

lateral ventricles, optic chiasm, cerebellum and spinal cord

Active MS plaques are often centered around ____ and have evidence of what cell types?

veins; lipid-filled macs, destroyed oligos and relatively intact axons

In an inactive plaque you will find:

no myelin, decreased oligo nuclei and astrocyte proliferation and gliosis