MS

Question 1

MS diagnostic score

Answer 1

McDonald Criteria (2017)

Question 2

Key features required for diagnosis of MS

Answer 2

Dissemination in space and dissemination in time

Question 3

Differentials for MS

Answer 3

Inflammatory: ADEM, Behcets, NMOSD, MOG, SLE, Vasculitis
Infectious: HIV, Lyme, Neurosyphilis, PML, TB
Genetic: ALD
Granulomatous disease: sarcoidosis, GPA
Vascular: antiphospholipid disease, chronic small vessel ischaemia, migraine
Neoplastic: lymphoma, glioma, GBM, metastases

Question 4

Neuromyelitis optica spectrum disorder

Answer 4

Immune mediated disease causing demyelination and axonal damage
- prediliction for optic nerve and spinal cord
- most have Ab to aquaporin 4
- causes loss of oligodendrocyte then axonal loss
- NMOSD often long segments of spinal cord

Question 5

NMOSD diagnostic criteria

Answer 5

Need one of the following:
1. optic neuritis
2. acute myelitis
3. area postrema syndrome (intractable hiccups, nausea / vomiting)
4. Acute brainstem syndrome
5. Symptomatic cerebral syndrome with NMOSD-typical brain lesions

Question 6

Differences between NMOSD and MS

Answer 6

NMOSD usually severe attacks restricted to optic nerve and spinal cord, long segments of spinal cord lesions with pleocytosis during attack. Oligoclonal bands usually absent. Have serum NMO antibodies

Question 7

What effect does MS treatment have in NMOSD?

Answer 7

usually worsens disease

Question 8

NMOSD treatment

Answer 8

PLEX + steroids
MMF / Azathioprine
Rituximab

Emerging therapies: IL-6 blockade, Complement pathway blockade (eculizumab), anti-CD19 MAB

Question 9

MOG antibody disease antibody

Answer 9

myelin oligodendrocyte glycoprotein (MOG)

Question 10

MOGAD treatment

Answer 10

treat as per NMOSD

Question 11

MS treatment

Answer 11

Most for relapsing remitting MS

Question 12

Natalizumab
- trial
- target
- effect
- precautions

Answer 12

AFFIRM trial
MAB that targets integrin found on monocytes and lymphocytes
70% reduction in relapse rate, 90% reduction in MRI activity
PML - (JCV)

Question 13

Alemtuzumab
- trial
- target
- effect
- precautions

Answer 13

CARE-MSI
binds CD52 found on all differentiated lymphocytes and monocytes
reduces risk by 50% compared to interferon based treatment
infusion reactions common, new autoimmune disease, infection risk increased

Question 14

Ocrelizumab
- trial
- target
- effect
- precautions

Answer 14

OPERA I and II
anti-CD20
Reduces relapses by 50% compared to IFN
infusion reactions, HBV reactivation, PML (low)

Question 15

Ofatumumab
- target

Answer 15

anti-CD20

Question 16

Cladribine
- target
- effect
- precautions

Answer 16

deoxyadenosine analogue prodrug that selectively targets lymphocytes due to preferential intracellular activation

Reduces relapse rate by 50%

VZV

Question 17

Fingolimod
- target
- effect
- precautions

Answer 17

S1P receptor on lymphocytes, blocking egress from lymph nodes
reduces relapse rate by 50%

Bradycardia, LFT derangement, lymphopenia, herpes virus reactivation, PML risk

Question 18

Ozanimod
- target
- effect
-

Answer 18

Sphingosine-1-phosphate inhibitor
similar efficacy to fingolimod
no cardiac monitoring

Question 19

Dimethyl fumarate
- target
- effect
- risks

Answer 19

modulates antioxidative pathways via activation of Nfr2
45-55% reduction in relapses
SE: flushing, GI symptoms, LFT derangement

Question 20

Diroximel fumarate

Answer 20

similar to dimethyl fumarate but less GI symptoms

Question 21

Teriflunomide
- target
- effect
- SE

Answer 21

inhibits dihydroorotate dehydrogenase and interferes with pyrimidine synthesis

reduces relapses by 30%
SE: hepatotoxicity, hair thinning, hypertension, teratogenic

Question 22

Only therapy listed for secondary progressive MS

Answer 22

siponimod

Question 23

Pregnancy and MS

Answer 23

MS relapses fall during pregnancy but increases in 3 months post partum
Use glatiramer or dimethyl fumarate, consider natalizumab