Multiple Scleorsis

Question 1

Definition of Multiple Sclerosis

Answer 1

Autoimmune condition where the immune system attacks he CNS leading to demyleination

Question 2

Epidiemiology of Multiple Scleorsis

Answer 2

Europeans, disease of young women

Question 3

Cause of Multiple Sclerosis

Answer 3

Genetic - familial risk

Env- infection trigger EBV

Question 4

Pathology of Multiple Sclerosis

Answer 4

Micrograph of plaque - Cellular Increase, macrophages filled with myelin
fluroscent stain mirograph - Axons don’t show continous myelin sheath

Question 5

Pathophysiology of multiple sclerosis

Answer 5

1. Ag presentation of myelin proteins to T cells which become activated
2. T cells cross the BBB, cause inflammatory cascade
3. Microglia & macrophages recruited, result is destruction of myelin

overtime:
retraction of nerve - loss of function permanently (20%)
partial remyelination - conducts less efficiently and slower
regeneration of channels across demyelinated nerve

Question 6

Types of disease Courses of MS

Answer 6

relapsing remitting MS (80%)
secondary progressive MS
Primary progressive MS
Progressive relapsing MS

Question 7

Relapsing remitting MS

Answer 7

he most common disease course — is characterized by clearly defined attacks of worsening neurologic function. These attacks — also called relapses, flare-ups or exacerbations — are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely and there is no apparent progression of disease.

Question 8

Secondary progressive MS

Answer 8

follows after the relapsing-remitting course. Most people will transition to SPMS, which means that the disease will begin to progress more steadily (although not necessarily more quickly), with or without relapses

Question 9

Primary progressive MS

Answer 9

patients get slowly worse from the beginning affects bladder and legs without any attacks

Question 10

Progressive relapsing

Answer 10

Relapse and progression from onset

Question 11

Clinically isolated syndromes

Answer 11

Optic neuritis

brain stem syndrome

Question 12

Optic neuritis

Answer 12

1/5 people
- painful usually on movement
on fundoscopy
- pallor of the disc margin, loss of central visiom (central scootoma) and loss of colour vision - even whent he patient has revovered

Question 13

Brainstem syndrome

Answer 13

opthalmoplegia (intranuclear, lesion between 3rd nerve on onse side and 6 nerve nucleus on the other)

• problems with speech
• ataxia (cerebellar)

Question 14

Spinal cord syndrome

Answer 14

transverse myelitis (pins and needles in the legs()

Question 15

What is an MS attack?

Answer 15

-Sub-acute or insidious onset – comes on over time. Hours to days. Reaches its worse in days to weeks.
-Appearance of new symptom(s)/ reappearance of old symptoms – tends to affect same places – same symptoms.
-Symptom(s) last at least 24 hours Usually days to weeks
Gradual recovery to pre-relapse state
-Possible residual deficit – over time this worsens
-May take up to 6(+) months for recover

Question 16

Diagnosis of MS

Answer 16

Clinical

• At least 2 clinical attacks (relapses) at least one month apart and examination evidence of two lesions
• Progressive disease over 12 months – usually progressive lower limb symtpoms

Para clinical

• MR brain and spine – sometimes giving contrast
• Evoked potentials – visual, somato-sensory, and brainstem auditory – slowing
• CSF – looking for inflammatory response
• Exclusion of other disorders e.g. vasculitis

Question 17

Investigations for MS

Answer 17

MRI

• 1st investigation
• T2 flair
• abnormalities in ventricles, corpus callosum, brainstem
• gallodium –> differentiates new lesion from old, new lesions enhanced by gallodium –> active disease

CSF puncture
- Test for IgG heavy chains(olgiclonal bands), multiple bands show up but not in serum are indicative of inflammation confined to the CNS

Evoke responses
- VER: delay is the most sensitive method of demonstrating previous optic neuritis.
-Somatosensory evoked potential (SSEP) and brainstem evoked potential
`

Question 18

When to suspect MS?

Answer 18

1. new neurological symptoms
2. young adults
3. previous history
4. subacute evolution- come on gradually
5. polysymptomatic
6. clinically isolated syndromes
7. signs/symptoms mismatch - often present with one set of symtpoms then more is wrong than anticipated

Question 19

Questions to ask?

Answer 19

1. bladder symptoms (unexpected frequency and urgency
2. fatigue- even in early stages can be marked
3. cognitive problems - mutlitasking, memory problems
4. balance - falling without a reason
5. Previous neurological symptoms
6. famly history

Question 20

Aims of diagosis

Answer 20

1. to establish an early diagnosis
2. To give subclassification - for treatment and prognosis
3. inform patent
4. earlier treatment

Question 21

Treatment of MS

Answer 21

No cure for MS
for Acute relapses–> corticosteroids and immunosuppresants
for symptomatic relief –> muscle relaxants and anti-cholinerergics
Disease-Modifying treatments (DMTs) –> Interferone beta and glatiramer acetate

Question 22

Disease modifying treatments (DMTs)

Answer 22

reduce/stop relapse rate
reduce progression of disability
reduce MRI activity

First line 
- interferon betas
- glatimarer acetate
second line 
- natalizumab

Question 23

Natalizumab

Answer 23

selective adhesion molecule (SAM) inhibitor
mab against a4b1 integrin on leukocytes
Tcell binds to BBB normally so they can move trhough it. Drugs bings the integrin on the T-cell surface so it cannot bind to VCAM receptor on BBB and therefore no inflammatory response.

Question 24

Side effect of Natalizumba

Answer 24

Progressive Multifocal leucoencephalopathy .

Common in people who are JCV sero-positive

treat with plasma exchange an then steroids

Question 25

Role of MRI in diagnosis

Answer 25

Magnetic resonance imaging MRI can detect the lesions of MS. These are demonstrated as bright lesions on T2-weighted MRI (or fluid attenuated inversion recovery [FLAIR] MRI where the high signal from cerebro-spinal fluid (CSF) is suppressed to make the lesion more obvious).

Question 26

McDonald Criteria -MRI in MS

Answer 26

The McDonald criteria require dissemination in space, a lesion in at least two of:

a) periventricular (around the ventricles),
b) juxtacortical (at the grey : white matter junction),
c) infratentorial e.g. cerebellum,
d) spinal cord

Question 27

VERS

Answer 27

Visual evoked responses are measured as the speed at which impulses travel along the optic nerve. These impulses are generated as the patient sits in front of an alternating checkerboard pattern. Optic nerve involvement may be asymptomatic, and detection may allow the clinician to demonstrate dissemination in space of there is a symptomatic lesion elsewhere.

Question 28

Drugs used to decrease frequency of relapses

Answer 28

-interferon B and glatiramer acetate reduce relapse frequency offered to adults who have had 2 or more relapses in the previous year

Question 29

Clinical features of MS

Answer 29

Transverse myelitis
- Weakness, sensory symptoms, urinary urgency and retention; flexor spasms
Brainstem
- ataxia, diploplia, dysarthria; facial numbnes; internuclear ophthalmoplegia; gaze palsy
Cerebellum
- Ataxia, dysarthria, nystagmus
Optic Neuritis
- visual loss, painful eye movements, impaired colour vision
Cerebral Hemispheres
- poor memory
Cortical
- epilepsy
Characteristic symptom/Signs
- Internuclear opthalmoplegia
- Uhthoff’s phenomenon: worsening of symptoms (eg vision) when body temperature is raised

Question 30

Course of disease

Answer 30

-85% present with relapsing-remitting disease (RRMS)
-after 10-15 years, 50-60% enter secondary progressive phase
10% have PPMS with gradual accumulation of disability