Multiple sclerosis Flashcards
Side effects of beta interferon
Flu like symptoms, injection site reactions
Fingolimod in MS
Daily oral tablet
SE: Ist dose bradycardia, macular edema
SE of fumarate
Flushing, GI upset
Chronic lymphopenia -risk of PML
Main SE of natalizumab
PML
Alemtuzumab in MS
Anti CD52
Most powerful drug for MS
SE - Autoimmune complications -ITP,thyroid, Good pasteurs
Natalizumab MOA
Recombinant monoclonal Ab against alpha-4 subunit of integrin
Risk of PML
Ocrelizumab in MS
Anti -CD20, used in PPMS
Optic neuritis in MS
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
Common sites of lesions in MS
periventricular(Dawsons fingers), optic nerve, juxta cortical(U fibres),posterior fossa, spinal cord
Oligoconal bands in MS
Present in upto 50% of MS at diagnosis
PPMS diagnostic criteria
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
Methyl prednisolone effects in MS relapse
*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
Indication of plasma exchange in MS
Very severe relapse including severe ON, brain stem relapse, spina cord relapse
Effect of MS drugs -interferon/glatiramer/ teriflunomaide
on disease
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
Most well tolerated drug in MS
Natalizumab>Fingolimod>cladribine
Drug that is worst tolerated
Dimethylfumarate
Main SE that need to be monitored in MS drugs
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
Drugs safe in pregnancy
Glatiramer, dimethyl fumarate, Natalizumab
Drug contraindicated in pregnancy
Terifluonamide
Galtiramer MOA
Synthetic polypeptide containing myelin basic protein
May promote proliferation of TH2 cytokines
Alters macrophage function
SE -injection reactions
Safe in preg
Natalizumab MOA
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
Factors associated with decreased survival in PML
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
Clinical features s/o PML
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
Management of PML on Tysabri
Stop drug
Plasma exchange to remove residual antibodies
Can cause rebound IRIS -managed with steroids IV MP
Some case reports show benefit with Maraviroc
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
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
Terifluonamide
Active metabolite of lefluonamide
Interferes with lymphocyte proliferation by inhibiting
pyrimidine synthesis, reducing tyrosine kinase activity
May prevent interaction of lymphocytes and APC
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
Ocrelizumab
Humanised Anti CD20 antibody
Well tolerated
SE:Infusion reactions,Skin malignancies
First effective therapy for PPMS
AHSCT in MS
Reduced relapse in RRMS when failing other therapies
On trial
Cladribine in MS
Synthetic deoxyadenosine analogue
Sustained reduction in no of circulating B and T lymphocytes
SE -lymphopenia
Indications for switching therapies
Unacceptable breakthrough activity
Intolerable side effects
Reducing long term risk (JC virus positivity in Natalizumab)
Kennedy syndrome features
X linked MND
Progressive wasting of bulbar and limb muscles
Androgen insensitivity
Defect -trinucleotide repeat CAG
