Multiple sclerosis

Question 1

Definition

Answer 1

Potentially disabling disease of the CNS

Chronic and progressive autoimmune disorder

A 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 and deterioration of the nerve fibres:
– sensory, motor and cognitive problems

Myelin is made up of oligodendrocytes

Question 2

Pathophysiology

Answer 2

The brain and the neurons in the brain are protects from substances in the blood by the blood-brain barrier (BBB):
– it only lets certain molecules and cells through from the blood
– they have to show the right ligand/surface molecules to get through

When a T cell gets in, it can get activated by something it encounters, in the case of MS it is the myelin

Once the T cell is activated, the BBB expresses more receptors, meaning it will allow more immune cells to get in

MS is a TYPE IV HYPERSENSITIVY OR CELL MEDIATED HYPERSENSITIVITY:
– meaning that the myelin specific immune cells (activated by myelin) release cytokines like:
—- interleukin-1
—- interleukin-6
—- TNF-alpha
—- interferon-gamma

These dilate the blood vessels of the BBB allowing more immune cells to get in
– it also causes direct damage to the oligodendrocytes while attracting B cells, macrophages and also regulatory T cells

B cells and macrophages are apart of an inflammatory reaction:
— B cells make antibodies that mark the myelin sheath proteins and then the macrophages use them to engulf and destroy the oligodendrocytes
—- leaving the neurons demyelinated and scarred (sclera)

Early on:
– oligodendrocytes can heal and extend out new myelin in the demyelination process however over time it becomes more and more irreversible

Presence of T regulatory cells:
– they may come in and calm down the other immune cells reducing the inflammation
– this is how that in some types of MS it occurs in bouts and there are times where the disease gets even worse

Question 3

Aetiology

Answer 3

Cause is unknown and like most autoimmune diseases it is linked to genetic and environmental factors

Genetic- female more common, HLA-DR2 gene increases the incidence as it identifies and binds to foreign molecules

Environmental factors:
– infections
– likelihood more common in northern and southern poles where there is less sun, meaning that there may be some sort of vitamin D deficiency involved with MS

Question 4

Epidemiology

Answer 4

Affects 20-40 year olds mostly, this is when it starts to develop

Women are 2-3 times more likely than men to get RRMS

Family history

Question 5

Different types of multiple sclerosis

Answer 5

Relapsing remitting multiple sclerosis (RRMS):
– most common form
– due to the presence of T regulatory cells it occurs in bouts
– there are bouts where the disease gets worse (these can occur months or even years apart)
– in between there is the remyelination process but over time it becomes harder and harder to reverse

Secondary progressive:
– firstly starts off similar to that of relapsing remitting, but over time it becomes constant leading to a steady progression of the disease in the second half

Primary progressive multiple sclerosis (PPMS):
– one constant on the myelin, leading to a constant steady progression of the disease

Progressive relapsing multiple sclerosis (PRMS):
– also one constant attack, but there is superimposed bouts which means that the disease will progress even faster

Question 6

Clinical presentation

Answer 6

Can vary from person to person and can largely depend on the location of the plaques

Symptoms during the bouts can worsen over weeks and even linger for months without treatment:

– Charcots neurological triad:
—- dysarthria (due to plaques in the brain stem that affect the nerve fibres that control the muscles of the mouth and throat)

—- nystagmus (due to plaques in the eyes, controlling eye movements)

—- intention tremor (due to plaques along the motor pathways, that affect outbound signals like skeletal muscle control)

– plaques in sensory pathways from the skin (causing numbness, pins and needles parasthesias)

– poor concentration and critical thinking
– depression
– anxiety

– bowel and bladder symptoms
– sexual dysfunction

– muscles spasms
– muscle weakness
– ataxia
– paralysis in serious cases

Question 7

Investigations

Answer 7

Neurological examination

MRI to look for any damage to the myelin

Question 8

Treatment

Answer 8

There is no cure for MS, but medicines and other treatments can help control the condition