Multiple sclerosis

Question 1

Side effects of beta interferon

Answer 1

Flu like symptoms, injection site reactions

Question 2

Fingolimod in MS

Answer 2

Daily oral tablet

SE: Ist dose bradycardia, macular edema

Question 3

SE of fumarate

Answer 3

Flushing, GI upset

Chronic lymphopenia -risk of PML

Question 4

Main SE of natalizumab

Answer 4

PML

Question 5

Alemtuzumab in MS

Answer 5

Anti CD52
Most powerful drug for MS
SE - Autoimmune complications -ITP,thyroid, Good pasteurs

Question 6

Natalizumab MOA

Answer 6

Recombinant monoclonal Ab against alpha-4 subunit of integrin
Risk of PML

Question 7

Ocrelizumab in MS

Answer 7

Anti -CD20, used in PPMS

Question 8

Optic neuritis in MS

Answer 8

Onset hrs to days, trough by 1week, recovery over weeks
Fundus initially normal -> swollen,pale
Field loss can take any form
Reduced color vision and visual acuity
Eye pain on movement
ON + Normal MRI -> 20% chance of MS in 15 yrs
ON+ >2MRI lesions->80% chance

Question 9

Common sites of lesions in MS

Answer 9

periventricular(Dawsons fingers), optic nerve, juxta cortical(U fibres),posterior fossa, spinal cord

Question 10

Oligoconal bands in MS

Answer 10

Present in upto 50% of MS at diagnosis

Question 11

PPMS diagnostic criteria

Answer 11

1 yr of disease progression plus 2of the following 3 criteria
Evidence of DIS based on >1 T2 brain lesions in atleast 1 area characteristic for MS
Evidence of DIS in spinal cord based on >2 T2 lesions in cord
Positive CSF oligoclonal bands

Question 12

Methyl prednisolone effects in MS relapse

Answer 12

*Closes BBB
*Reduction of inflammatory edema
*Suppression of inflammation -induction of T cell apoptosis, downregulation of endothelial adheion molecules
Given as 1gm daily x3 days

Question 13

Indication of plasma exchange in MS

Answer 13

Very severe relapse including severe ON, brain stem relapse, spina cord relapse

Question 14

Effect of MS drugs -interferon/glatiramer/ teriflunomaide

on disease

Answer 14

Delays onset of another attack by 45% ar 2-3 yrs
Reduces new MRI lesions markedly (80-90%)
Reduced cerebral atrophy by 30%
Better cognitive outcomes after 5 years

Question 15

Most well tolerated drug in MS

Answer 15

Natalizumab>Fingolimod>cladribine

Question 16

Drug that is worst tolerated

Answer 16

Dimethylfumarate

Question 17

Main SE that need to be monitored in MS drugs

Answer 17

Glatiramer - no monitoring,local site reaction
INF beta-LFTs, flu like symptoms
Dimethyfumarate -lymphocyte counts 6monthly, PML, flushing,diarrhoea
Terifluonamide -LFT, hair loss
Fingolimod -Macular edema (oph-3mon), LFT 3mon,lymphopenia, HTN, increased BCC
Natalizumab - JC virus 6monthly, PML
Ocrelizumab - infusion reactions,B cell depletion
Alemtuzumab-monthly FBE, UE for 5 yrs, TSH (Graves)
Cladribine -HSV,lymphopenia, monitor FBC

Question 18

Drugs safe in pregnancy

Answer 18

Glatiramer, dimethyl fumarate, Natalizumab

Question 19

Drug contraindicated in pregnancy

Answer 19

Terifluonamide

Question 20

Galtiramer MOA

Answer 20

Synthetic polypeptide containing myelin basic protein
May promote proliferation of TH2 cytokines
Alters macrophage function
SE -injection reactions
Safe in preg

Question 21

Natalizumab MOA

Answer 21

Monoclonal Ab to alpha 4 integrin/VCAM-1
Inhibits tissue migration of monocytes and lymphocytes into CNS. Monthly injection
Median risk of development on PML 49months
Risk of PML - *Duration of exposure> 2yrs
*Previous exposure to immunosuppressant-Mtx,AZA,Cycl
*JCV positive
If all 3 risk factors positive -10 in 100 risk
25% patients with PML die

Question 22

Factors associated with decreased survival in PML

Answer 22

Older age
Higher pre PML EDSS (diability)
Longer time from symptom onset to diagnosis
Widespread PML lesion on MRI
Higher JC viral load at diagnosis

Close surveillance with MRI -if picked up early when asymptomatic, 95% survival rate

Question 23

Clinical features s/o PML

Answer 23

Subacute onset and progression over weeks
Cortical symptoms/signs
Behavioural and neuropsychological alteration
Retrochiasmal visual field defects
Hemiparesis
Diagnosis -JC Virus PCR on CSF, Bx occasionally

Question 24

Management of PML on Tysabri

Answer 24

Stop drug
Plasma exchange to remove residual antibodies
Can cause rebound IRIS -managed with steroids IV MP
Some case reports show benefit with Maraviroc

Question 25

Fingolimod

Answer 25

S1P receptor modulator -derived from mushrooms
Induces internalisation of S1P -leads to selective retention of CCR7+T naive cells in lymph nodes and lymph tissues
Hence cant circulate and cause autoimmune responses

Transient bradycardia on initiation, BP increase

Question 26

Dimethyl fumarate

Answer 26

MOA- Regulation of immune homeostasis
Attenuation of pro inflammatory cytokine production
Regulation of NF-kB activation
Reduced activation of macrophages,microglia,astrocytes
Shift Th1/Th2/Th17 balance

Question 27

Terifluonamide

Answer 27

Active metabolite of lefluonamide
Interferes with lymphocyte proliferation by inhibiting
pyrimidine synthesis, reducing tyrosine kinase activity
May prevent interaction of lymphocytes and APC

Question 28

Alemtuzumab

Answer 28

Lysing anti CD52 antibody
Depletes B cells more that Tcells though CD52 present on both
Given as 5 days infusion once a yr
Secondary autoimmunity -ITP, Graves, Good pasteurs
Acalculous cholangitis

Question 29

Ocrelizumab

Answer 29

Humanised Anti CD20 antibody
Well tolerated
SE:Infusion reactions,Skin malignancies
First effective therapy for PPMS

Question 30

AHSCT in MS

Answer 30

Reduced relapse in RRMS when failing other therapies

On trial

Question 31

Cladribine in MS

Answer 31

Synthetic deoxyadenosine analogue
Sustained reduction in no of circulating B and T lymphocytes
SE -lymphopenia

Question 32

Indications for switching therapies

Answer 32

Unacceptable breakthrough activity
Intolerable side effects
Reducing long term risk (JC virus positivity in Natalizumab)

Question 33

Kennedy syndrome features

Answer 33

X linked MND
Progressive wasting of bulbar and limb muscles
Androgen insensitivity
Defect -trinucleotide repeat CAG