March 20 - Multiple Sclerosis Flashcards
What is the incidence of multiple sclerosis in Canada?
1:500 to 1:1000 (it is about 3x higher in the Manitoba area)
How much money, on average, is invested in one MS patient?
1.6 million/patient
What are contributing factors of multiple sclerosis?
Race (caucasians), age (25-38), sex (females are more likely to be diagnosed, males have a poor prognosis), infection (Epstein-Barr, HHV6, chlamydia, pneumoniae, etc.), injury, genetics (it’s not hereditary, but there can be a genetic predisposition), geography, diet/sunshine (make sure patients are supplemented with vitamin D
Explain genetics as a contributing factor for MS
In a first degree family relative of patient with MS, absolute risk of MS is: <5% which equates to 20 to 40 times increased risk compared to general population. In monozygotic twins: concordance rate for MS is higher (31%) than in dizygotic twins (5%). As such since not 100% concordance rates in identical twins, this is proof that genetics alone is not solely responsible for this disease. Presence of HLA-DR2 allele increases the risk of MS. MS is not hereditary disease but patient may have a genetic predisposition for the disease
What are the theories associated with the development of MS?
Infectious theory (measles, mumps, rubella, EBV, HHV-6)
Molecular mimicry
Autoimmune disease
Explain the pathophysiology leading to multiple sclerosis
MS is an autoimmune disorder that is caused by the pathological activation of inflammatory Th1 cells. A foreign antigen enters our blood. An antigen-presenting cell (APC; macrophages, monocytes, dendritic cells) picks it up by binding it to the HLA-DR2. It presents the antigen to a naive T cell and it activates it to an inflammatory Th1 cell.
What are mediators of inflammation?
IL-12, IL-2, IL-6, IFN-gamma, TNF-alpha. There are too many of these in MS
What are protective mediators (anti-inflammatory)?
Il-4, IL-10, TGF-beta
Describe a model of MS immunology
An antigen binds to an APC. There is the production of inflammatory mediators. These mediators make the blood-brain barrier (BBB; area between PNS and CNS) very sticky with adhesion molecules. Th1 cells dock to adhesion molecules. The production of mediators of inflammation continues. A protease on the surface of the BBB is activated. The BBB is usually really tight but the protease causes it the integrity of the BBB to loosen up. Th1 cells pass into the CNS, where they can’t differentiate between the foreign antigen they are supposed to protect against and myeline
How do Th1 cell damage the myeline
They create lesions in the myeline sheaths which causes the dissipation of the electrical activity (neurological deficits). As the disease progresses, the lesions get bigger and eventually there is no more myeline around the neuron. The nerve cell dies, causing cognitive deficits
What is the median time to requiring cane/crutch?
15 years
What is the median time to wheelchair confinement?
25 years
What are current opinions regarding treatment effects?
Someone who decides they don’t want treatment will have tremendously worse disabilities. Starting treatment right at the diagnose results in minimal disability
What is one clinical diagnostic tool?
Cerebrospinal fluid exam - determine the presence or absence for IgG antibodies against oligodendrocytes (Oligoclonal IgG bands)
Describe the clinical course of the disease
Patients will have first clinical attack (loss of vision, numbness, can’t move a limb, etc. - very pronounced). After a few weeks, the patient gets better. Several years later, they have a second clinical attack. For a while the attack will descend below clinical threshold (the patient will not notice any symptoms below threshold). This is called relapsing remitting (RR) MS (80% of patients are RR MS). As the disease progress, the attack doesn’t go back to below threshold. This is called secondary progressive (SP) MS.
What is it called when an MS patient only has one attack?
Clinically isolated syndrome (CIS) MS
What is primary progression MS?
When the patient has the first attack, it never comes back down to baseline. So the after the first attack, they never recover and it only gets worse. This is the most debilitating form of MS (it’s the rarest - predominantly found in males)
What are symptoms of MS?
Fatigue and weakness, bladder control problems, neuropathic pain, cognitive defects, optic neuritis, sexual dysfunction, ataxia, depression
Why would a patient experience fatigue and weakness?
Their immune system is always fighting. But also because more energy is lost through the dissipation of electrical impulses (like when you have a gas leak, you could put the peddle to the metal and still only go 40 km/hour)
Why would a patient experience bladder and bowel control problems?
The myelination on the nerve that controls either inhibition (results in incontinence) or excitatory (results in bladder retention) nerves are damaged
What are the McDonald clinical criteria for RRMS-Definitive diagnosis?
Clinical attack(s) +/- MRI must show dissemination in time and space
2 clinical attacks where each attack lasted greater than 24 hours; dissemination in time (at least 30 days apart)
Does not require an MRI
How is a clinically isolated syndrome diagnosed?
1 attack that lasted greater than 24 hours even with a postive or negative MRI that doesn’t fulfill McDonald’s criteria in regard to dissemination in time and/or space. This is not a definitive diagnosis of MS
What is required for Manitoba/Alberta IMA drug coverage?
2 attack where each attack lasts greater than 24 hours and is separated in space by at least 30 days with a positive MRI that meets McDonald criteria within the past 2 years
What is a reasonable clinical end point in the treatment of MS?
Stop myeline from being attacked. These drugs (interferon-beta 1a and 1b and glatiramer acetate) suppress the production of Th1 cells. So these drugs stop the production of Th1 cells (block the immune system response)
