L15 Multiple Sclerosis Flashcards
What is Multiple Sclerosis
Auto-immune disorder
Immune Sytem attacks the myelinated axons in the CNS
What system does MS affect
Central Nervous System
When does the onset of MS begin
Ages of 20-50
Frequency of MS in society
Twice as common in women
1-1000 people in ireland diagnosed
2.8 globally affected
What does growing evidence show about the geography of MS
More frequent in areas further from equator
Studies linking the Vitamin D
3 Characteristics of MS
Destruction of Myelin Sheaths around neurons
Formation of lesions in CNS
Chronic Inflammation (activated microglia cells)
What do areas of myelin loss show in images
plaques/lesions
What is myelin
Insulating layer, or sheath that forms around nerves (brain and spinal cord)
Function of Myelin Sheath
Propogation of electrical impulses along axons is highly accelerated by myelin sheath
Produces saltating or jumping action potentials across internodes, from one node of ranvier to the next
Myelination in CNS and PNS
Oligodendrocytes (CNS)
Schwann Cells (PNS)
Both types of glia (non-neuronal cells in nervous system )
Glia Cells in the CNS (Brain, Spinal Cord)
Astrocytes: support immune function
Oligodendrocytes: insulation, myelination
Microglia: immune function, phagocytes
Ependymal Cells: create CSF
Glia Cells in PNS
Schwann Cells: insulation, myelination
Oligodendrocytes
Location: CNS
Function: Myelinating Axons
Disease Associated: MS
Schwann Cells
Location: PNS (myelinate the nerve cells that project to and from muscles, internal organs)
Function: responsible for myelinating a small portion of an axon
Disease Associated: Guillain- Barre syndrome
What is a multi-factorIal disease?
No single cause has been found, but a number of risk factors have been identified
Risk factors that may cause MS
Exposure to certain Viruses (Epstein-Barr = Glandular Fever)
Genetic Susceptibility
Environmental Factors: lack of sunlight, smoking, teenage obesity, pollutants, gut microbiota, stress and exercise
What causes demyelination resulting in MS
Risk factors together cause abnormal immune response against self antigen Myelin, leads to demyelination of axons
Pathophysiology of MS
Activated T & B lymphocytes
Cross the Blood Brain Barrier
Infiltrate brain and spinal cord
Activate Microglia
Release Cytokines
Macrophages attack myelin and phagocytes large chunks of the myelin sheath
Loss of Myelin
Plaques of demyelination in white matter, demyelinating lesions in grey matter
Disappearance of oligodendrocytes and proliferation of astrocytes
Axonal loss and degeneration
Loss of signal conduction
Symptoms of MS
Often unpredictable
Differ greatly between people
May be mild or severe, short term or long term
> > this dependent on the location of the affected nerve fibres
Symptoms of Multiple Sclerosis
Vision Problems: such as optic neurotis (blurriness and pain in one eye) are often one of the first signs of MS
Changes in gait
Fatigue
Loss of Balance
Muscle Spasms
Muscle Weakness
Tingling pr numbness, especially in arms or legs
Course of MS
Most people with MS have a relapsing- remitting disease course
- experience periods of new symptoms or relapse that develop over days or weeks and usually improve partially or completely
these relapses are followed by quiet periods or remission that can last months to years
Types of MS
Relapsing- Remitting MS (RRMS)
Secondary Progressive MS (SPMS)
Primary Progressive MS (PPMS)
Progression Relapsing MS (PRMS)
Relapsing Remitting MS
Flare ups and periods of remission
Secondary Progressive MS
Starts like RRMS but there is stable progression of the disease and symptoms between relapses
Primary Progressive MS
Symptoms that slowly and gradually worsen without any periods of relapse or remission
Progressive Relapsing MS
Steadily worsens from the onset of the first symptoms, regardless of relapses or periods of remission
What are complications of MS
If MS progresses, worsening symptoms may lead to complications such as :
- Difficulty walking
-Loss of bowel or bladder control - Memory problems
- Speech Difficulties
- Increase risk of life - threatening conditions
How is MS diagnosed
1) Detailed Neurological examination - shows whether nerve pathways are damaged
2) Lumbar Puncture- reveals if there has been a breakdown of antibodies and oligoclonal bands which are suggestive of MS
3) MRI scans of the brain and spinal cord- to look for characteristic lesions of MS
4) Evoked potential tests -
What shows in MRI if MS is present
white spots correspond to demyelinating lesions
Treatment of MS
No cure
Treatment focuses on
-speedy recovery from attacks
reducing new clinical relapses
slowing the progression of the disease
managing MS symptoms
Treatment for an MS attack
Corticosteroids
Oral Prednisone
Intravenous Methlyprednisolone
> > inhibit the synthesis of inflammatory proteins, through the suppression of the
Plasma exchange
> > the liquid portion of blood is removed and seperated from the blood cells. Mixed with protein solution and put back into body
Treatment to modify disease progression
Injectable :
- Interferon beta medications
- Glatiramer
-Monoclonal
> > Lowere relapse rater
slow the formation of new lesions
potentially reduce risk of brain atrophy and disability accumation
Interferon Beta Medication
Balances the expression of pro and anti- inflammatory agents in the brain, and reduces the number of inflammatory cells that cross the BBB
Increase the production of nerve growth factors
-Avonex
-Betaseron
-Rebif
Glatiramer Acetate
Modifiy the immune processes that are believed to be responsible for the pathogenesis of MS
Inhibit the secretion of proinflammatory cytokines
Inducing the T-cells to cross the BBB and produce anti-inflammatory cytokines
Examples
- copaxine
- glatopa
Monoclonal Antibodies
Reduces the level of B cells which contribute to the development and progression of MS
Binds to and blocks the action of CD-20, a molecule expressed on the surface of both healthy and leukimic B Lymphocytes
Eg.
- Kesimpta
-Arzerra
Oral Medications for MS Progression
Teriflunomide
Fingolimid
Dimethyl Fumarate
> > reduces the relapse rate
Teriflunomide
ORAL
Reduces the proliferation of activated T and B lymphocytes
eg. aubagio
Fingolimid
Shifts macrophages to an anti-inflammatory phenotype. It modulated their proliferation
Eg. gilenya
Dimethyl Fumarate
Lower levels of B lymphocytes
Blocks pro-inflammatory cytokine productiong. Tecfidera
Cannabis
No cannagis based FDA approved medications for MS
Clinical Trials have shown it improves pain and spasticity, bladder issues in people with MS
