Multiple Sclerosis Flashcards
What is a multiple sclerosis?
A neurodegenerative autoimmune conditions that strikes the central nervous system
What are the symptoms of Multiple sclerosis and what is it characterised by?
Weakness
Numbness
Loss of sense- taste and sight
Loss of balance
Multiple episodes of the same or different neurological symptoms separated by periods of remission- relapse and remitting
What is multiple sclerosis in terms of primary progressive?
Start of disease
What is multiple sclerosis in terms of secondary progressive?
Relapsing and remitting form of MS
How do you diagnose multiple sclerosis and describe each one?
- Combination of time course for clinical episodes
- Lesions detected by MRI: able to see white matter
- CSF markers
What is detected in progressive MS?
Detection of oligoclonal bands- these are immunoglobulins not found in CNS
What is the biological basis of multiple sclerosis
- Inflammation in the brain and spinal cord
- Loss myelin sheaths: demyelination
- Axonal damage and neuronal loss
What are the consequences of multiple sclerosis
- Acute loss of function
- Chronic damage
- Repairable damage
Describe inflammation in multiple sclerosis
- Immune cells infiltrate CNS and attack cells within the brain and spinal cord involved in myelination- infiltrate consists of lymphocytes and macrophages
- Autoimmune response: body targets own cells
- Active MS plaques also contain myelin whorls, proteins and lipids
What is the myelin sheath formed by and what is it made of to assist in
- Oligodendrocytes in the CNS
2. Sheath: Lipid 70% and Protein 30% insulation to help the electrochemical transmission of action potentials
What does a damaged myelin sheath lead to
Ability of nerve cells to transmit action potential
When does remyelination occur and does it work
- Early stages of MS: rapid and extensive remyelination
- Complete remyelination of lesions can occur
- Commonly fails
In neurodegeneration, how many axons are lost in the chronic lesions
Loss of 68%
Describe conduction block in relapse where symptoms get worse
Demyelination and increase in inflammation
Describe restoration of conduction in remission
Remylination and decrease in inflammation
Uhtoff’s is described as a positive phenomena, what is it?
- Worsening of neurological conditions when the body gets overheated from hot weather, exercise etc
- Leads to nerves getting blocked
Lhermitte’s is described as a positive phenomena, what is it?
An electrical sensation that runs down the spine and into the limbs- generally uncomfortable
What are the environmental concerns of MS
- Epstein Barr virus: Evidence of increased infection during early adulthood
- Decreased sunlight exposure or low vitamin D are contributing factors
What are the genetic concerns of MS
- Increased risk linked to close family members developing disease
- Major histocompatibility locus
- Genome wide association study identified with further immune related genes
What is stoppable in MS
Inflammation in the brain and spinal cord
What is repairable in MS
Loss of myelin sheaths- demyelination
What is irreparable but preventable in MS
Axonal damage and neuronal loss
What are the treatment episodes in acute relapse?
- High dose: corticosteroid
- Oral methylpredinisolone: 500mg
- IV methylprednisolone: 1g
What is the monoclonal antibody to use in rapidly evolving severe relapsing MS and its mechanism
- Natalizumab-Tysabri
- Inhibits leucocyte migration into CNS, binds to a4 subunit of a4b1, a4b7 intergrins, expressed on surface of activated T cells
- Prevents binding of cells to receptors on endothelium
Describe the mechanism of action of Fingolimod (Gileyna)
- Sequesters lymphocytes in lymph nodes: prevents them from crossing blood brain barrier
- Reduces relapse
- Possible treat: highly active relapsing remitting MS
What is the role of alemtiuzumab?
Anti-CD20 antibody: reducing anti-inflammatory response in MS early
What is the Teriflunomide?
- ONCE daily oral immunomodulator
- Inhibition of dihydro-orotate dehydrogenase
- This is necessary for rapidly dividing lymphocytes
What is the first line management of spasticity and spasms in MS
Baclofen: GabaB receptor agonist, inhibition of spinal reflexes
GABAPENTIN: Ca channel blockers
What is the second line management of spasticity and spasms in MS
Tizanidine (Alpha 2 agonist,muscle relaxant)
Diazepam and Clonazepam: Benzodiazepines, GABAa agonists
Dantrolene, Intrathecal Baclofen
Sativex
What mediation is used for retention and urgency/incontinence
Retention: Alfuzosin
Urgency and incontinence: Trospium and Flavoxate
What drugs do you use for fatigue, emotionalism, depression, anxiety and walking
- Fatigue: Modafinil
- Emotionalism: TCA or SSRI
- Depression: standard treatment
- Walking: Famipridrine
What can cannabinoids be used MS patients
- Many MS patients self medicate by smoking cannabis
- Ameliorate:
Tremor and spascity
Pain
Bladder Function
