(PM3B) Multiple Sclerosis – MS Flashcards
What is multiple sclerosis?
Autoimmune disease of the central nervous system (brain + spinal cord)
Typically affects young adults
Onset between 20-40yrs old
What is the male to female ratio of multiple sclerosis incidence?
3:1
was 2:1 in the 1950s
What are some potential environmental risk factors for multiple sclerosis?
(1) Viral exposure – Epstein Barr Virus
(2) Tobacco exposure
(3) Obesity
(4) Sunlight – vitamin D
What are some potential genetic risk factors for multiple sclerosis?
(1) Close family members with the disease
(2) 1st degree relatives have 2.5-5% risk
(3) Identical twin has a 20-25% risk
(4) Specific immune-related genes
What are the different clinical presentations of multiple sclerosis?
(1) Relapsing
(2) Remitting
(3) Progressive
What is primary progressive multiple sclerosis?
Progressive multiple sclerosis from the start
~20% of MS patients
What is secondary progressive multiple sclerosis?
MS patients with relapsing/ remitting MS
Who go on to develop progressive
What is Uhthoff’s phenomenon?
Significant worsening of multiple sclerosis symptoms
In response to increase in temperature
e.g. immersion in hot bath
What is Lhermitte’s sign?
Electrical sensation running down the spine
Following neck flexion
Present in multiple sclerosis
What test can be used to help diagnose multiple sclerosis?
MRI
Detection of white matter abnormalities + spinal lesions
What is the McDonald diagnostic criteria?
Assessment of additional diagnostic data needed
Based on clinical presentation observed
Ho wis multiple sclerosis diagnosed?
(1) Abnormalities on MRI
(2) Time-course for clinical episodes
(3) Cerebrospinal fluid markers
Describe the pathology of multiple sclerosis?
(1) Inflammation of brain + spinal fluid
(2) Inflammatory molecules are primarily lymphocytes + macrophages
(3) Demyelination of neurones
(4) Leads to axonal damage + neuronal loss
(5) Initial cause of inflammation in multiple sclerosis is unclear
What does the pathology of multiple sclerosis cause?
(1) Acute loss of function
(2) Repairable damage
(3) Chronic damage
What is a major cause of irreversible deficit in multiple sclerosis?
Axon degeneration
How much of the spinal cord cross section can be lost annually in primary progressive multiple sclerosis?
~5%
What is the primary cause of a release of multiple sclerosis?
Conduction block
Due to demyelination + inflammation
What is the primary cause of remission of multiple sclerosis?
Restoration of conduction
Remyelination + decreased inflammation
What is the primary cause of positive phenomena (Uhthoff’s/ Lhermitte’s) in multiple sclerosis?
Hyperexcitability due to ectopic impulses + mechanosensitivity
Potentially caused by demyelination
What is the primary cause of progression of multiple sclerosis?
Persistent loss of conduction
Due to demyelination + axonal loss
What are the generic types of treatment used for multiple sclerosis?
(1) Symptomatic relief
(2) Disease-modifying therapy
What are the stages in multiple sclerosis development?
(1) Inflammation + demyelination of neurones in CNS
(2) Oligodendrocyte loss + impaired remyelination
(3) Neuronal (axon) damage + death
What are steroids used for in the treatment of multiple sclerosis?
Acute relapse episodes
Use of a high dose corticosteroid
(1) ORAL: methylprednisolone 500 mg daily for 3-5 days
(2) IV: Methylprednisolone 1g daily for 3-5 days
What is natalizumab used for in the treatment of multiple sclerosis?
Monoclonal antibody which inhibits leucocyte
migration into CNS
Exhibits anti-inflammatory effects
What is the mechanism of action of natalizumab?
Binds to alpha4 subunit of alpha4ß1 and alpha4ß7 integrins
Expressed on the surface of activated T-cells
Prevents binding of cells to receptors on endothelium
When is natalizumab licensed for use?
Treatment of rapidly evolving severe relapsing-remitting multiple sclerosis
How is natalizumab administered for multiple sclerosis?
IV infusion
300 mg every 28 days
What is fingolimod?
Sphingosine analogue
Sequesters lymphocytes in lymph nodes to prevent them crossing BBB
Branded = Gilenya
When is fingolimod used for treatment of multiple sclerosis?
Highly active relapsing–remitting multiple sclerosis in adults IF both factors apply:
(1) Unchanged/ increased relapse rate OR ongoing severe relapses compared with the previous year (despite treatment with beta interferon)
(2) Manufacturer provides fingolimod with agreed discount as part of patient access scheme
What has the manufacturer of fingolimod agreed with the Department of Health?
Patient Access Scheme
Discount on list price
What is dimethyl fumarate?
Tecfidera
Developed by Biogen as anti-MS therapy
Anti-inflammatory agent
Why do NICE guidelines not recommend use of beta interferon or glatiramer for treatment of multiple sclerosis?
Cost/ benefit analysis not sufficient
Why may a patient be being treated with beta interferon?
Despite NICE not recommending
They may have started treatment prior to NICE decision
What is alemtuzumab?
Anti-CD52 antibody (available on NHS)
Reduces inflammatory response in early MS
CD52: antigens expressed on B and T cells
What is CD52?
Antigens present on B and T cells
What is teriflunomide?
Once daily oral immunomodulator
Inhibits dihydro-orotate dehydrogenase
Required for de-novo pyrimidine synthesis pathway needed by rapidly dividing lymphocytes
Treatment of multiple sclerosis
What is the first line treatment for spasticity or spasms in multiple sclerosis?
First line:
(1) Baclofen – GABAb receptor antagonist (inhibition of spinal reflexes)
(2) Gabapentin – calcium channel blocker (class C substance)
What are some of the second line treatments for spasticity or spasms in multiple sclerosis?
(1) tizanidine (alpha2 agonist, muscle relaxant)
(2) diazepam, clonazepam (benzodiazepines, GABAa agonists, act at level of spinal cord to cause muscle relaxation)
(3) dantrolene (ryanodine receptor agonist, muscle relaxant)
(4) Intrathecal baclofen
(5) Sativex
What are some of the common symptoms of multiple sclerosis?
(1) Bladder symptoms – incontinence
(2) Pain
(3) Fatigue
(4) Emotionalism
(5) Depression
(6) Anxiety
(7) Walking issues
How is incontinence in multiple sclerosis treated?
(1) Alfuzosin – retention
(2) Trospium/ flavoxate – incontinence
How is fatigue in multiple sclerosis treated?
Modafinil
How is emotionalism treated in multiple sclerosis?
SSRI
(OR)
Tricyclic antidepressant
How is walking improved in patients with multiple sclerosis?
Fampridine
Potassium channel blocker
(Used in USA, not indicated in UK)
How is cannabis used in multiple sclerosis?
Many use it to self-medicate
Can ameliorate tremor/ spasticity + pain + bladder function
Not currently recommended by NICE
How is vitamin D used in multiple sclerosis?
Lower incidence of MS in countries with increased sunlight
Not recommended by NICE + no clinical trial data supporting use
