(PM3B) Multiple Sclerosis – MS Flashcards by thurica jeyaselan

What is multiple sclerosis?

Autoimmune disease of the central nervous system (brain + spinal cord)

Typically affects young adults

Onset between 20-40yrs old

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What is the male to female ratio of multiple sclerosis incidence?

3:1

was 2:1 in the 1950s

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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

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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

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What are the different clinical presentations of multiple sclerosis?

(1) Relapsing
(2) Remitting
(3) Progressive

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What is primary progressive multiple sclerosis?

Progressive multiple sclerosis from the start

~20% of MS patients

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What is secondary progressive multiple sclerosis?

MS patients with relapsing/ remitting MS

Who go on to develop progressive

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What is Uhthoff’s phenomenon?

Significant worsening of multiple sclerosis symptoms

In response to increase in temperature

e.g. immersion in hot bath

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What is Lhermitte’s sign?

Electrical sensation running down the spine

Following neck flexion

Present in multiple sclerosis

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What test can be used to help diagnose multiple sclerosis?

MRI

Detection of white matter abnormalities + spinal lesions

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What is the McDonald diagnostic criteria?

Assessment of additional diagnostic data needed

Based on clinical presentation observed

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Ho wis multiple sclerosis diagnosed?

(1) Abnormalities on MRI
(2) Time-course for clinical episodes
(3) Cerebrospinal fluid markers

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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

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What does the pathology of multiple sclerosis cause?

(1) Acute loss of function
(2) Repairable damage
(3) Chronic damage

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What is a major cause of irreversible deficit in multiple sclerosis?

Axon degeneration

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How much of the spinal cord cross section can be lost annually in primary progressive multiple sclerosis?

~5%

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What is the primary cause of a release of multiple sclerosis?

Conduction block

Due to demyelination + inflammation

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What is the primary cause of remission of multiple sclerosis?

Restoration of conduction

Remyelination + decreased inflammation

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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