302 Neurobiology of multiple sclerosis (not finished)

Question 1

Where do symptoms of neuropathies appear first?

Answer 1

In the feet because the nerves are the longest there and then they progress upwards

Question 2

What are the features of Lower motor neurone disease?

Answer 2

Decreased tone and reflexes
Muscle atrophy

Because it can’t receive info from the upper motor neurones

Question 3

What are the features of upper motor neurone disease?

Answer 3

Increased tone and reflexes
Muscle weakness

Question 4

What are the risks for MS?

Answer 4

Lower Vit. D / UVB exposure
past EBV infection
obesity and smoking
certain genes ~200

Question 5

What is the pathophysiology of MS?

Answer 5

Multifocal neuroinflammation “plaques” form within white matter, subcortical, and cortical grey matter

Mediated by infiltrates (via BBB) of auto-reactive T lymphocytes (CD8+ > CD4+)&raquo_space; B lymphocytes

Results in oligodendrocyte damage (demyelination) and axon degeneration (axonopathy) and gliosis

Begins prior to the first clinical attack

Question 6

How is MS triggered?

Answer 6

Auto-(CNS)-reactive T cells are felt to arise in the periphery but by an as yet unknown mechanism

Question 7

What physical changes occur in the brain with MS?

Answer 7

-Global atrophy / volume loss
-Hydrocephalus ex vacuo
-Thinned Corpus collosum
-Extensive PVWM and juxtacortical demyelination

Question 8

What are the microscopic differences between early active phase and late chronic phase of MS?

Answer 8

Early active phase:
-florid myelin destruction with macrophages
-infiltration of lymphocytes T&raquo_space; B cells
-axonal damage &reactive astrocytes

Late chronic phase:
-macrophages laden with myelin debris
-inner core of increasing axon loss & gliosis
-surrounding edge of activated microglia

Question 9

What is the difference in grey matter and white matter plaques in MS?

Answer 9

-White matter lesions are often more apparent
-There is more cumulative volume in grey matter
-Grey matter lesions contain fewer B + T cells
-Grey matter lesions contribute to cognitive impairment

Question 10

What are the abnormalities found in normal appearing grey and white matter in MS?

Answer 10

-Reduced neurons, synapses
& neurites
-Oxidative stress
-Reduced axonal transport
-Diffuse microglial activation

Question 11

What are the 2 sources of CNS damage accumulation?

Answer 11

Inflammatory demyelination
Progressive neurodegeneration

Question 12

What are the 3 classical phenotypes of MS?

Answer 12

RRMS (Relapsing remitting MS)
- Predominant inflammatory and/or relapse activity from outset
with complete (remyelination) or incomplete recovery (R.A.W.)

SPMS (Secondary progressive MS)
-Fading relapse activity in favour of predominant progression

PPMS (Primary progressive MS)
- Progressive disease can be associated
with inflammatory / relapse activity

Question 13

What is the extended disability status scale (EDSS)?

Answer 13

A way of measuring how much someone is affected by their MS

From minimal neurological development to bedridden or in a wheelchair

Question 14

What is radiologically isolated syndrome in MS?

Answer 14

MRI abnormalities found incidentally & compatible with demyelination but without clinical signs or symptoms

30-40% develop MS within 5 years

Question 15

What is clinically isolated syndrome in MS?

Answer 15

a single clinical (symptomatic) event typical
for demyelination – such as an optic neuritis

Question 16

How is MS diagnosed?

Answer 16

At least 1 clinical “relapse” corresponding to at least one demyelinating MRI lesion

AND Dissemination in Space
(relapses of ≥ 2 CNS sites or MRI lesions criteria*)

AND Dissemination in Time
≥2 relapses separated by a month / new silent lesions on 2

AND MRI / CSF OCBs indicating ongoing inflammation

AND No other plausible explanation / likely mimic

Question 17

What is McDonald criteria used for?

Answer 17

For MS

Question 18

What are the differential diagnosis’s for MS?

Answer 18

-Acute disseminated encephalomyelitis (ADEM)
-Sarcoidosis can be isolated CNS
-SLE
-Rarely Behcet’s; Sjogren’s
-Vasculitis / vasculopathy (dural AV fistula)
-Infections HIV, Lyme, Syphilis
-Metabolic Mitochondrial
-Neoplastic / Trauma / Compressive

Question 19

What is Behcets disease?

Answer 19

Inflammation of the blood vessels and tissues

Question 20

What is Sjogren’s disease?

Answer 20

A condition that affects parts of the body that produce fluids, like tears and saliva

Question 21

What are the investigations for suspected MS?

Answer 21

CSF analysis:
WCC, Glucose, Viral PCR
OCBs = Polyclonal IgG to a range of epitopes

Bloods:
HIV / Syphilis / TB / autoimmune screen

CXR: normal lung / hila / heart appearances

VEP’s:
Visual Evoked Potentials
It looks at nerve impulses

Question 22

What is the treatment for acute MS relapses?

Answer 22

Depends on the severity / impairment in function

Treated with steroids or plasma exchange

Question 23

How does plasma exchange treat MS?

Answer 23

It removes the autoimmune proteins

Question 24

What are disease modifying drugs used for MS?

Answer 24

They’re drugs that reduce disease activity

Eg. four forms of interferon (IFN) beta (from four different companies), glatiramer acetate, natalizumab, fingolimod, alemtuzumab, teriflunomide, and dimethyl fumarate (BG-12)