Multiple Sclerosis Flashcards
Define Multiple Sclerosis
A neurodegenerative autoimmune condition that affects the CNS. Caused by a complex interaction of genetic and environmental triggers
What are the two interesting aspects of the incidence of MS
- The incidence has increased significantly over the last 100 years
- There are remarkable differences in incidence between continents and countries
How is MS characterised and what are the symptoms?
Characterised by multiple episodes of the same or different neurological symptoms separated by periods of remission.
Symptoms can include: Weakness Numbness Loss of sense (taste, sight) Loss of balance
What is Uhthoff’s phenomenon?
Symptoms of MS worsen upon an increase in body temperature e.g. hot bath
What does primary progression mean?
20% people, present with MS as the progressive form from the beginning
What does secondary progression mean?
This is when the patient initially suffers from periods of relapse and remission but then develops the progressive form
Describe the techniques used to diagnose
Diagnosis uses a combination of clinical observations, MRI and use of CSF markers.
MRI scans - detect white matter abnormalities and spinal lesions
What can be seen from CSF as the distinguishing factor for progressive form of MS?
Detection of oligoclonal bands (immunoglobulins not normally found in the CNS) in CSF is used to discriminate from other neurological disorders.
What is the biological basis of MS? and what are their consequences (3)
- Inflammation in the brain and spinal cord - acute loss of function
- Demyelination - repairable damage
- Axonal damage and neuronal loss - chronic damage
What is the cause of Inflammation a key biological feature of MS?
Cause = unclear
Autoimmune response - Immune cells infiltrate the CNS and attack cells within brain and CNS
Describe how inflammation causes the damage
Inflammatory infiltrates = Lymphocytes and Macrophages
Active MS plaques characterised by lymphocyte infiltration
Active plaques also contain numerous macrophages containing myelin at various stages of degradation.
What are the stages of myelin degradation?
- Myelin Whorls
- Myelin Proteins
- Neutral Lipids
What is the myelin sheath in the CNS made from? What is it made up of and it’s purpose?
Oligodendrocytes
Lipid 70% and Protein 30%
Provides insulation to help the electrochemical transmission of action potentials.
What impact does demyelination have on neurons? And what occurs after?
Negative impact on the ability of nerve cells to transmit action potentials
Remyelination occurs in the early stages of MS to re-store function. but eventually fails.
What is neurodegenaration the result of?
This is the culmination of demyelination and inflammation leading to axonal loss and neuronal cell death. Axonal degeneration is a major cause of irreversible deficit with no effective therapy
What % of spinal cord cross area is lost in those with progressive MS?
5%
What is the cause of relapse and what occurs (pathology?
Conduction block due to Demyelination and Inflammation
What is the cause of remission and what occurs (pathology)?
Restoration of conduction due to Remyelination and Decreased inflammation
What is the cause of positive/ Uhtoff phenomenaand what occurs (pathology)?
Hyper-excitability: ectopic impulses and mechanosensitivity due to Demyelination?
What is the cause of progression and what occurs (pathology)?
Persistent loss of conduction due to demyelination and axonal loss
What are the causes of MS?
Environmental:
Infection with Epstein Barr Virus
Decreased exposure to Vit D
Genetic:
Increased risk linked to close family member developing the disease
Risk alleles
What therapy is available for an acute relapse episode?
High dose corticosteroid
Or
Oral methylprednisolone 500mg daily, 3-5 days
IV methylprednisolone 1g daily, 3-5 days
How does Natalizumab (Tysabri) work?
It is a monoclonal antibody which inhibits leucoyte migration into CNS
Binds to a4 subunit of a4b1 and a4b7 integrins, expressed on activated T cells
Prevents binding of cells to receptors on the endothelium
Anti-inflammatory effects
What are the NICE guidleines on the use of Natalizumab?
Licensed for adults with rapidly evolving severe relapsing-remitting MS
Deemed NOT cost-effective treatment in some groups of people - those who failed to respond to beta interferon
