302 Neurobiology of multiple sclerosis (not finished) Flashcards
Where do symptoms of neuropathies appear first?
In the feet because the nerves are the longest there and then they progress upwards
What are the features of Lower motor neurone disease?
Decreased tone and reflexes
Muscle atrophy
Because it can’t receive info from the upper motor neurones
What are the features of upper motor neurone disease?
Increased tone and reflexes
Muscle weakness
What are the risks for MS?
Lower Vit. D / UVB exposure
past EBV infection
obesity and smoking
certain genes ~200
What is the pathophysiology of MS?
Multifocal neuroinflammation “plaques” form within white matter, subcortical, and cortical grey matter
Mediated by infiltrates (via BBB) of auto-reactive T lymphocytes (CD8+ > CD4+)»_space; B lymphocytes
Results in oligodendrocyte damage (demyelination) and axon degeneration (axonopathy) and gliosis
Begins prior to the first clinical attack
How is MS triggered?
Auto-(CNS)-reactive T cells are felt to arise in the periphery but by an as yet unknown mechanism
What physical changes occur in the brain with MS?
-Global atrophy / volume loss
-Hydrocephalus ex vacuo
-Thinned Corpus collosum
-Extensive PVWM and juxtacortical demyelination
What are the microscopic differences between early active phase and late chronic phase of MS?
Early active phase:
-florid myelin destruction with macrophages
-infiltration of lymphocytes T»_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
What is the difference in grey matter and white matter plaques in MS?
-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
What are the abnormalities found in normal appearing grey and white matter in MS?
-Reduced neurons, synapses
& neurites
-Oxidative stress
-Reduced axonal transport
-Diffuse microglial activation
What are the 2 sources of CNS damage accumulation?
Inflammatory demyelination
Progressive neurodegeneration
What are the 3 classical phenotypes of MS?
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
What is the extended disability status scale (EDSS)?
A way of measuring how much someone is affected by their MS
From minimal neurological development to bedridden or in a wheelchair
What is radiologically isolated syndrome in MS?
MRI abnormalities found incidentally & compatible with demyelination but without clinical signs or symptoms
30-40% develop MS within 5 years
What is clinically isolated syndrome in MS?
a single clinical (symptomatic) event typical
for demyelination – such as an optic neuritis
How is MS diagnosed?
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
What is McDonald criteria used for?
For MS
What are the differential diagnosis’s for MS?
-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
What is Behcets disease?
Inflammation of the blood vessels and tissues
What is Sjogren’s disease?
A condition that affects parts of the body that produce fluids, like tears and saliva
What are the investigations for suspected MS?
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
What is the treatment for acute MS relapses?
Depends on the severity / impairment in function
Treated with steroids or plasma exchange
How does plasma exchange treat MS?
It removes the autoimmune proteins
What are disease modifying drugs used for MS?
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)
