Multiple Sclerosis

Question 1

MS is a disease of what age

Answer 1

Young people

Question 2

Definition of MS

Answer 2

Demyelinating inflammatory disease of the CNS

Question 3

What occurs to axons in MS in the CNS

Answer 3

They demyelinate due to inflammation of axons –> disturbing conductance of the impulse

Question 4

MS is a disease of grey or white matter

Answer 4

White

Question 5

Pathophysiology of MS

Answer 5

Autoimmune process where myelin is mistaken as foreign which activates T cells to cross BBB and bind to it

The activated T cells cause the BBB to express more receptors which attracts more leukocytes to enter brain; they also produce cytokines which dilate the vessels of the BBB and allow more leukocytes to get in to promote inflammation

The activated T cells also attract B cells and macrophages - B cells produce antibodies and mark the myelin sheath proteins; macrophages recognise the marked myelin and phagocytose them which destroys the oligodendrocytes

–> ALL LEADING TO DEMYELINATION (–> plaques)

Question 6

What is the equivalent of fibrosis in the brain

Answer 6

Gliosis - proliferation of glial cells after inflammation

Question 7

MS is inflammatory but also…

Answer 7

Degenerative due to axonal degeneration and loss

Question 8

Axonal loss in MS ultimately leads to what

Answer 8

Cerebral atrophy and the development of disability

Question 9

MS risk factors (5)

Answer 9

Genetics - polymorphism of MHC
Existing autoimmune disease
Females>males
Northern latitude
Environmental - EBV infection

Question 10

Initial presentation of MS lasts usually how long

Answer 10

Few days, gradual onset

Question 11

List the different things MS can present or relapse as (6)

Answer 11

Optic neuritis
Myelitis
Odd sensory symptoms - numbness, burning etc
Limb weakness
Brainstem relapse - maybe diplopia, vertigo, ataxia, aphasia, dysphagia
Neuromyelitis optica spectrum disorder

Question 12

Brainstem relapse can present as what symptoms (5)

Answer 12

Diplopia
vertigo
ataxia
dysphagia
aphasia

Question 13

Definition of a relapse

Answer 13

Episode of new symptoms occurring at least 30 days from the start of the last episode

Question 14

Describe optic neuritis + symptoms (3) /signs (3)

Answer 14

Demyelinating inflammation of optic nerve

Symptoms:
Partial visual loss
Pain on moving eye
Loss of colour vision

Signs:
Loss of visual acuity
Optic disc swelling
Relative afferent pupillary defect

Question 15

What is relative afferent pupillary defect

Answer 15

Light directed in the affected eye will cause only mild constriction of both pupils (due to decreased response to light from the afferent defect), while light in the unaffected eye will cause a normal constriction of both pupils

Question 16

What is retrobulbar neuritis

Answer 16

Demyelination of the posterior optic nerve

Question 17

Investigations of optic neuritis (2)

Answer 17

Visual evoked potentials

MRI of optic nerves

Question 18

Demyelinating inflammation of nerves in the cerebellum cause relapses presenting as (3)

Answer 18

Vertigo
Nystagmus
Ataxia

Question 19

Demyelinating inflammation of nerves in the pons can present as

Answer 19

Internuclear ophthalmoplegia - affected eye can’t adduct properly

Question 20

MS can relapse or present as partial or transverse myelitis - describe what this is + symptoms (3) /signs (3)

Answer 20

Demyelinating inflammation of spinal cord

Symptoms:
Motor weakness
Paraesthesia (tingling, numb etc)
Bladder/bowel dysfunction - e.g. urinary retention, constipation

Signs:
L’hermitte sign - paraesthesias (tingling, an ‘electrical sensation’) down the spine and to the limbs, elicited by bending neck forward
UMN signs
Sensory loss/level

Question 21

MS can relapse as neuromyelitis spectrum disorder (devic’s disease) - what is this

Answer 21

If someone has optic neuritis AND transverse myelitis, associated with aquaporin-4 antibodies in the blood then they’re said to have this

Question 22

Name the 3 different types/courses of MS

Answer 22

Relapsing remitting
Secondary progressive
Primary progressive

Question 23

What is a clinically isolated syndrome in regards to MS (2)

Answer 23

First episode of neuro symptoms lasting at least 24hrs

Not all of people who experience CIS go on to develop MS

Question 24

Symptoms (6) /signs (6) of MS (hint: about the list of conditions it can relapse as)

Answer 24

Symptoms:
Motor weakness - esp foot dragging/slapping after walking too long
Fatigue
Visual disturbance in one eye
Paraesthesia
Urinary frequency
Bowel dysfunction - constipation

Signs:
UMN signs (4)
Imbalance/ incoordination
Afferent pupillary defect

Question 25

Most people with relapsing remitting MS go on to develop what type of MS

Answer 25

Secondary progressive --> which leads to progressive disability as an attack becomes constant and you never go into remission again

Question 26

What is primary progressive MS

Answer 26

From first episode, symptoms gradually get worse NO RELAPSES, just continuous worsening but can be periods where symptoms are stable

Question 27

What is relapsing remitting MS

Answer 27

After an episode symptoms resolve and there's a period of remission where everything is fine but then another episode occurs maybe months or years later Symptoms improve during remission due to some remyelination but remyelination is never complete between the bouts of attack so there's always residual disability (which builds up over time so with more and more attacks, there's more irreversible CNS damage)

Question 28

MS definitive diagnosis

Answer 28

2 episodes of neurological dysfunction in a different area (MULTIFOCAL) of the CNS (brain, spinal cord, and optic nerves) each time that are separated in time and space

Question 29

MS diagnosis may be clinical or MRI based - name the criteria system for these 2 types of diagnoses

Answer 29

Posers criteria - clinically diagnosing 2 episodes, may use LP also McDonald criteria - MRI showing 2 lesions from 2 episodes, may use LP also

Question 30

For every 10 lesions, there's approx how many relapses

Answer 30

1

Question 31

Treatment of MS can be divided into 3 parts:

Answer 31

Treat acute attack Prevent future attacks by reducing triggers and using disease modifying treatment (immunomodulators) Symptomatic treatment

Question 32

Initial investigations of MS (3) Further investigations (2)

Answer 32

MRI brain MRI spinal cord Routine bloods - FBC, glucose etc LP - shows raised IgG antibodies Visual evoke potentials - somatosensory evoked potentials less so

Question 33

Acute attack treatment of MS

Answer 33

``` IV methyprednisolone (IV steroids) Symptomatic treatment ```

Question 34

List the options for 1st line disease modifying treatment* (immunomodulators) of RRMS *prevent future attacks

Answer 34

Subcutaneous/intramuscular: -interferon beta (either) or -glatiramer (s/c) OR Oral: -teriflunomide or -dimethyl fumarate i.e. you just pick one

Question 35

List the 2nd line disease modifying treatment (immunomodulators) for RRMS (3) + when they're indicated

Answer 35

Indicated in more aggressive disease that doesn't respond to/tolerate other agents IV natalizumab Oral fingolimod IV alemtuzumab

Question 36

List the symptomatic treatment for MS - For spasticity - For sensory symptom/dysaesthesia - For urinary frequency - For constipation - For sexual dysfunction - For fatigue - For tremor - For depression

Answer 36

For spasticity - physio + muscle relaxants/antispasmodics For sensory symptom/dysaesthesia - gabapentin (Anticonvulsant), amitriptyline For urinary frequency - lifestyle measures (avoid caffeine, yoga/relaxation) For constipation - laxatives For sexual dysfunction - sildenafil For fatigue - exercise, good sleep pattern For tremor - propranolol For depression - cognitive behavioural therapy, anti-depressants

Question 37

Side effects of 1st line disease modifying treatments (immunomodulators) of MS ``` i.e. : subcutaneous/intramuscular: -interferon beta (either) or -glatiramer (s/c) ``` OR Oral: -teriflunomide or -dimethyl fumarate

Answer 37

Flu symptoms - fever, cough, sore throat, runny nose etc Injection site reaction Abnormal FBC and LFTs

Question 38

Side effects of 2nd line disease modifying treatments (immunomodulators) of MS

Answer 38

Suppress the immune system which can re-activate the JC virus --> progressive multifocal leukencephalopathy (PML) = fatal inflammation of brain

Question 39

MS is what type hypersensitivity reaction

Answer 39

Type IV

Question 40

Charcot's neurological triad is a common symptom profile associated with MS - what are the 3 symptoms

Answer 40

Dysarthria Nystagmus Intention tremor

Question 41

A common presenting symptom of MS is damage to the medial longitudinal fasiculus (a white matter tract of CN III, IV & VI in the brainstem) - what does this present as

Answer 41

Internuclear ophthalmoplegia - impaired horizontal eye movement with weak adduction of the affected eye and abduction nystagmus of the contralateral eye.

Question 42

MS patients are sensitive to/exacerbated by cold OR heat + what implication does this have

Answer 42

heat - elevated temperatures further impair the ability of demyelinated nerves to conduct electrical impulses - heat temporarily worsens neuro symptoms; doesn't actually cause the demyelination - often experienced as vision blurring after a hot bath or exercise (--> raised body temp)