Multiple sclerosis Flashcards

1
Q

Side effects of beta interferon

A

Flu like symptoms, injection site reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Fingolimod in MS

A

Daily oral tablet

SE: Ist dose bradycardia, macular edema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

SE of fumarate

A

Flushing, GI upset

Chronic lymphopenia -risk of PML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Main SE of natalizumab

A

PML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Alemtuzumab in MS

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Natalizumab MOA

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Ocrelizumab in MS

A

Anti -CD20, used in PPMS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Optic neuritis in MS

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Common sites of lesions in MS

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Oligoconal bands in MS

A

Present in upto 50% of MS at diagnosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

PPMS diagnostic criteria

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Methyl prednisolone effects in MS relapse

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Indication of plasma exchange in MS

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Effect of MS drugs -interferon/glatiramer/ teriflunomaide

on disease

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Most well tolerated drug in MS

A

Natalizumab>Fingolimod>cladribine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Drug that is worst tolerated

A

Dimethylfumarate

17
Q

Main SE that need to be monitored in MS drugs

A

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

18
Q

Drugs safe in pregnancy

A

Glatiramer, dimethyl fumarate, Natalizumab

19
Q

Drug contraindicated in pregnancy

A

Terifluonamide

20
Q

Galtiramer MOA

A

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

21
Q

Natalizumab MOA

A

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

22
Q

Factors associated with decreased survival in PML

A
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

23
Q

Clinical features s/o PML

A

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

24
Q

Management of PML on Tysabri

A

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

25
Fingolimod
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
26
Dimethyl fumarate
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
27
Terifluonamide
Active metabolite of lefluonamide Interferes with lymphocyte proliferation by inhibiting pyrimidine synthesis, reducing tyrosine kinase activity May prevent interaction of lymphocytes and APC
28
Alemtuzumab
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
29
Ocrelizumab
Humanised Anti CD20 antibody Well tolerated SE:Infusion reactions,Skin malignancies First effective therapy for PPMS
30
AHSCT in MS
Reduced relapse in RRMS when failing other therapies | On trial
31
Cladribine in MS
Synthetic deoxyadenosine analogue Sustained reduction in no of circulating B and T lymphocytes SE -lymphopenia
32
Indications for switching therapies
Unacceptable breakthrough activity Intolerable side effects Reducing long term risk (JC virus positivity in Natalizumab)
33
Kennedy syndrome features
X linked MND Progressive wasting of bulbar and limb muscles Androgen insensitivity Defect -trinucleotide repeat CAG