what is the first cause of non-traumatic disability in young adults of north america and europe
MS
where is MS more common geographically?
more as you move up and down the equator … in canada its more in the prairies and atlantic
Approx how many people in alberta are diagnosed with MS?
14,000
What is average age of onset of MS?
15-45 years old (mainly young)
what percentage accounts for paediatric MS? how many of them are less than or equal to age 18?
6% of total MS is paediatric and 3-10% of MS patients have their onset before 18
What is the ratio of females to males with MS?
females to males ratio of 3:1 (most autoimmune systems are more common in woman than men)
what are possible causes of MS?
MS is a multifactorial disease meaning that many things can contribute to its cause
- infections like measles and EBV can trigger MS
- sun exposure or lack of
- smoking can worsen symptoms of MS
- more salt can cause activation or over activation of immune cells
- genes… and genetic background
What are some clinical manifestations of MS?
- ocular manifestations include: blurred vision and diplopia
- cerebellar manifestations include: nystagmus (fast moving of eyes), ataxia, vertigo
- autonomic manifestations include urinary incompetence with bladder
- sensory manifestations include severe neuropathic pain
What is the disease course of MS?
initially, the symptoms present themselves as waves so they come and ago during periods called relapsing and remissions for about 10 years then it starts to increase in progression and stop remission because conditions get worse
what is the EDSS scale? what does it do?
its used to assess disability stage of MS.. its flawed because it focuses too much on the motor disabilities and not much the cognitive
What is the MS disease course in steps?
- clinically isolated syndrome (CIS) –> people who had their first attack can become or manifest it into MS if theres any chance of another attack
- relapsing and remitting periods (approx 80% of people get it) for about 10 years
- secondary progressive: 75-80% of relapsing-remitting … this is where the RR’s stop but MS can still develop
- primary progressive (10-15%) –> don’t have relapse course
What is focal demyelination?
this is where specific areas of the brain have demyelination… includes optic neuritis (you can have this as a symptom or just as a condition alone) and idiopathic transverse myelitis (inflammation of spinal cord that can be due to things other than MS)
what is diffuse demyelination?
this is generalized demyelination …
incldues
- neuromyelitis optica
- ADEM
- vasculitis
- lyme disease
- viral infection
- neurolupus
- neurosarcoidois
- paraneoplastic syndrome
How do we diagnose MS?
- History –> through clinical record
- neurological examination: looks at weakness and changes in sensation
- lumbar puncture to check CSF for proteins
- Blood test
- MRI to see white spots in the brain
- EEG’s to measure brain activity
What is MS?
multiple sclerosis means (many scars) –> it is described as demyelination, demyelination and axonal transection
first, myelin start degenerating
- Then, it can either start to re-myelinate –> not as strong as before but better than nothing
- OR it can cause axonal transection (axonal cutting) which myelin degenerates and exposes axons to damage
Where in the brain does MS mainly affect?
it can cause a lesion around the paraventricular areas and white spots in staining show lesions of degeneration
Decreased axonal density in MS plaques… shows that along with demyelination, theres also neurogeneration of axons as well .. less white matter
What are of the brain is severely affected by MS?
the corpus callosum is affected because its a big white matter tract and results for 56% of lost density in the brains of people with MS
What are some examples of neurodegenerative diseases.?
- parkinson’s diseases
- huntington’s disease
- ALS
- spinocerebellar taxis
- alzheimer’s disease
these are important to note because we can compare the symptoms of these disorders to the symptoms of MS to see if MS is a neurodegenerative disorder or not
What are some characteristics of Neurodegenerative diseases? How can these be compared to MS?
- they affect specific parts or functional systems of the nervous system (MS affects multiple areas and is not specific)
- they begin insidiously, after a long period of normal nervous system function and pursue a gradual progressive course (you need a lot of cells to be gone to notice neurodegenerative disorders but thats not the case for MS)
- the CSF shows minimal changes (usually mild increase in proteins) but in MS. the CSF seems normal
- imaging shows either no change or only a volumetric reduction (atrophy) –> MS shows a lot of white spots that are easily detected initially
In what ways can MS be a disease of immune dysfunction?
the destruction within the CNS in MS is through to be immune-mediated
- many inflam cell types are localized to lesion sites in the MS
- the activity of several inflam cell types is dysregulated
- levels of several inflam cytokines are increased in the serum, CSF and CNS of patients with MS (these should NOT be in CSF in the first place)
What does genetic testing tell us about MS?
- also in genetic testing it shows that all genes involve din MS are involved in regulation immune responses
- theres also more % of MS occurring in monozygotic twins showing theres a genetic link
What are some immune privileged sites (areas where immunity isn’t present due to preventative measures)?
- eyes (cornea, anterior chambers, …etc..)
- brain –> ventricles, and striatum … BBB
- pregnant uterus
- ovary
- testes
- adrenal cortex
- hair follicles
What is EAE? How was it replicated in animals?
mice were injected with myelin basic protein developing demyelinated disease (EAE)
- the disease is mediated by the TH1 cells which are pro-inflammatory ones
- the disease can be transferred from animal to animal through transfer of T-cells
- indicates the involvement of T-cells in the spread of MS-like symptoms?
What is the immunology of EAE? and molecular mimicry?
immunology:
- inject MBP
- pool of native t-cells… one T-cell recognizes this MBP
- that T-cell makes the pro-inflammatory cells for that specific MBP
- these inflam cells replicate
- once exposed to the MBP again, these pro-inflam are re-activated in the CNS and products produce the CNS pathology once they enter the CNS
