Multiple Sclerosis Flashcards
Definition
Potentially disabling disease of the brain and spinal cord (CNS)
Chronic and progressive autoimmune disorder
Demyelinating disease, where the immune system attacks the myelin that covers the nerve fibres and causes communication problems between your brain and the rest of your body.
Eventually, the disease can cause permanent damage or deterioration of the nerve fibres. Causing sensory, motor and cognitive problems.
Oligodendrocytes
Cells that make up the myelin on neurons
How MS occurs
The brain, and the neurons inside the brain are protected from things in the blood by the blood-brain barrier.
– this barrier only lets certain t and B cells through from the blood.
– they will have to have the right ligand/surface molecule to get through.
– when a T cell (type of white blood cell) gets in, it can get activated by something it encounters, in the case of MS, it is activated by myelin.
– Once the T cell is activated, it changes the blood-brain barrier cells to express more receptors, so this allows more immune cells to get in.
MS IS A TYPE IV (CELL MEDIATED) HYPERSENSITIVITY
– meaning that the myelin specific T-cells release cytokines like:
—- interleukin-1
—- interleukin-6
—- TNF-alpha
—- Interferon-gamma
– which altogether ^^, dilate the blood vessels, allowing more immune cells to get in.
– As well as directly causing damage to the oligodendrocytes
– these cytokines attract B-cells and macrophages as part of the inflammatory response
– B-cells start to make antibodies that mark the myelin sheath proteins
– Then the macrophages use the antibody markers to engulf and destroy the oligodendrocytes
– without oligodendrocytes there’s no myelin to cover the neurons (also leaves scar tissue known as ‘plaques or sclera’
MS happening in bouts
Occurs in bouts, so there can be an attack of MS, then regulatory T-cells may come in and calm down other immune cells reducing the inflammation.
Early on:
– oligodendrocytes will heal and extend out new myelin, in a process called demyelination
Over time:
– as the oligodendrocytes die off demyelination stops and the damage becomes irreversible
Aetiology
Cause is unknown
Can be linked to genetic and environmental factors
Genetic factors:
– females more common
– HLA-DR2 gene increases likelihood (used to identify and bind foreign molecules)
Environmental factors:
– infections
– vitamin D deficiency
—- higher rates at northern and southern poles (where there is less sunlight compared to the equator)
Epidemiology
Affects 20-40
Women 2 to 3 times more likely than men
Family history
Relapsing-remitting multiple sclerosis (RRMS)
Relapsing-remitting multiple sclerosis (most common):
– bout of autoimmune attacks happening months or years apart.
– in between bouts, the remylination process is usually not complete, meaning there is some residual disability that remains, meaning disability will increase even more per bout, and the disability is going to get worse over time.
Types of of MS
Relapsing-remitting multiple sclerosis (RRMS)
Secondary progressive multiple sclerosis (SPMS)
Primary progressive multiple sclerosis (PPMS)
Progressive relapsing multiple sclerosis (PRMS)
Secondary progressive multiple sclerosis (SPMS)
Similar at the start to RRMS, as there are bouts of attacks, but over time the attack becomes a constant attacks leading to steady progression of the disability
Primary progressive multiple sclerosis (PPMS)
One constant attacks on the myelin, meaning a steady progression of disability over a persons lifetime.
Progressive relapsing multiple sclerosis (PRMS)
Also one constant attack, but there are also bouts superimposed which means during these bouts the disease will process even faster than it already is
Clinical presentation
Symptoms can vary from person to person and largely depends on the location of scarring
Symptoms during bouts, can worsen over weeks and linger for months without treatment.
Charcot’s neurologic triad:
– dysarthria (difficulty speaking and swallowing)- due to plaques in the brain stem, that affect nerve fibres that control muscles to the mouth and throat
– nystagmus (involuntary rapid eye movement)- due to plaques in the nerves of the eyes, controlling eye movements. Damage to optic nerve (optic neuritis). Eye movements can be painful and lead to double vision. Can be blurred vision, or have black spot in the middle of vision.
– intention tremor- due to plaques along the motor pathways, that affect outbound signals like skeletal muscle control. Muscle weakness.
slurred speech
cognitive problems
mood disturbances
unsteady gait or inability to walk
lack of coordination
electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign)
Numbness or weakness in one or more limbs that typically occur on one side of your body at a time.
Diagnosis
MS is suspected when there is symptoms that are spread out over time in bouts, and also space, like where the symptoms affecting the body are. If they are more spread then this is more of a hint towards MS.
Investigations
MRI:
– will show multiple lesions called ‘white matter plaques’ (can be seen due to these areas containing a lot of myelin)
Lumbar puncture (cerebrospinal fluid):
– will show high levels of antibodies within the cerebrospinal fluid, which indicates an autoimmune process.
Visual evoked potential:
– measures nervous systems response to visual stimuli
Treatment
No cure for MS
Medications that can be taken for RRMS (to make it easier):
– corticosteroids
– cyclophosphamide (cell cycle inhibitor)
– intravenous immunoglobulin
Plasmapheresis:
– where the plasma is filtered to remover disease-causing antibodies
Immunosuppressants:
– Recombinant interferon beta (decreases levels of inflammatory cytokines in the brain, and increases the function of T-regulatory cells.
– Other immunosuppressants can block inflammatory cytokines from getting into the brain.
Fewer treatment options are available for progressive MS:
– treatment is usually targeted at managing specific treatments
—- e.g: depressing, bladder dysfunction
Physical therapy and cognitive rehabilitation therapy:
– can be helpful with sensory, motor and cognitive symptoms
Increased interest to VITAMIN D as a treatment for MS
