MS

Question 1

Common PO therapies MS

Answer 1

Fingolimod,
Teriflunomide,
Dimethyl Fumuarate,
Cladribine

Question 2

Clinical Features MS

Answer 2

– sensory, motor, cerebellar, cognitive

– optic neuritis

– internuclear ophthalmoplegia

– acute partial myelopathy

– partial/almost complete resolution of deficits with MS

– Lhermitte’s & Uhthoff’s symptoms

– Exercise induced symptoms

Question 3

Smoking and MS

Answer 3

Increased relapse rate in smokers

Question 4

Mimickers of MS

Answer 4

Neuromyelitis Optica Spectrum Disorder (NMOSD) - Separate disease
- NMO antibodies to aquaporin 4

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)
- separate disease

Question 5

Classic MRI findings in MS

Answer 5

Characteristic sites
– periventricular, corpus callosum, centrum semiovale
– radiating out from corpus callosum = Dawson’s fingers
– brainstem, cerebellum

Question 6

Test in MS

Answer 6

• Magnetic Resonance Imaging
• Evoked Potentials (EPs) - good to find lesions you can’t see clinically or on MRI
  – VEP = visual EP (optic neuritis – subclinical disease)
  – SEP = somatosensory (limbs)
  – BAER = brainstem EP = auditory pathways.
• Central Motor Conduction Time (CMCT)
  – motor pathways = corticospinal tracts to limbs
  – MEPs = Motor Evoked Potentials
• Lumbar puncture - CSF
  – basic CSF studies normal, maybe a few lymphocytes.
  Oligoclonal bands +ve in CSF but NOT in serum, Increased CSF IgG synthesis.

Question 7

Other Ddx for MS

Answer 7

– NMOSD & MOGAD

– Inflammatory diseases
* SLE, Sjogren’s, PAN, Behcet’s, ADEM etc

– Infectious diseases
* HIV, HTLV 1, PML, Lyme disease, Syphilis

– Granulomatous disease
* Sarcoidosis, Wegener’s granulomatosis

– Diseases of Myelin
* Adrenoleukodystrophy, Metachromatic Leucodystrophy

– Miscellaneous
* Spinocerebellar ataxia, vitamin B12 deficiency, ACM, mitochondrial cytopathy, vascular disease, CADASIL, Susac’s syndrome etc etc

Question 8

Pregnancy and MS

Answer 8

– Relapse rate reduced during pregnancy, especially in 3rd trimester.

– Increase in relapse rate in 6 months after delivery

– No increase in sustained neurological disability due to pregnancy

– No increase in
* stillbirths, ectopic pregnancy, etc

• Discontinuation of DMTS before attempting a planned pregnancy is usually recommended
• Caution in using Gonadotropin-releasing hormone (GnRH) protocols for IVF in women with MS as this may significantly increase the MS relapse rate

Question 9

MS Poorer Prognostic Factors

Answer 9

• Demographics
  – Male
  – Older than 40 years at onset of disease
• Relapse Characteristics
  – Frequent relapses early in disease course
  – Multifocal relapses
  – More severe relapses
  – Shorter inter-attack interval
  – Poorer recovery from relapses
• Disease Course
  – Rapid accrual of disability
  – Progressive rather than relapsing remitting course from onset
• MRI Features at onset predicting poorer prognosis
  – High T2 lesion load
  – >2 GAD enhancing lesions
  – >T1 hypointense lesions (“Black Holes”)
  – Early atrophy
  – Infratentorial as opposed to supratentorial lesions
• MRI Features during Treatment predicting poorer prognosis
  – New T2 lesions
  – >1 GAD enhancing lesion

Question 10

MS treatment acute exacerbations

Answer 10

PO/ IV steroids

Question 11

Natalizumab brand/ MOA

Answer 11

Tysabri (alpha 4 integrin antagonist)

Question 12

monoclonals in MS

Answer 12

Alemtuzumab, Rituximab, Ocrelizumab

Question 13

Sx of PML

Answer 13

Progressive multifocal leucoencephalopathy

• Rapidly progressive demyelination in brain
• Dementia, motor dysfunction, visual loss
• Previously mortality 30-50% in 3 months if untreated & late Dx

Question 14

Patients who get PML

Answer 14

immunocompromised
- AIDS,
- transplant Pt,
- Immune system altering drugs eg , MS Pt on DMTs

Question 15

Alemtuzumab MOA

Answer 15

Humanised monoclonal Ab binds CD52 (on B cells)

Question 16

AE Alemtuzumab

Answer 16

– 2-3% ITP ( may be fatal)

– 20-30 % autoimmune thyroid disease at 5 years

– DON’T give live vaccines after Alemtuzumab Rx

– Listeria meningitis & cryptosporidial infections (rarely)

– Immune mediated conditions including hepatitis and haemophagocytic lymphohistiocytosis, bleeding in lungs, MI, stroke, arterial dissection and severe neutropaenia

Question 16

Ocrelizumab MOA

Answer 16

Humanized anti CD20 monoclonal antibody

• Depletes B lymphocytes

Question 17

Fingolimod MOA

Answer 17

• Decreases ability of lymphocytes to enter CNS by preventing the egress of lymphocytes from lymphatic tissues.

Question 18

Fingolimod AE

Answer 18

• Potential serious cardiac side effects.
• 1 st dose monitoring for bradycardia. Heart block.
• OCT monitoring for macula edema (?1% Pts)
• Need to have antibodies or to immunise patients against Varicella Zoster before Rx
• > 15 PML cases reported so far

Question 19

Teriflunomide MOA

Answer 19

Inhibits pyrimidine synthesis (dihydroorotate dehydrogenase inhibitor)

Question 20

AE Teriflunamide

Answer 20

• Hypertension
• LFT & FBS abnormal
• Alopecia, diarrhea

– X categorisation regarding pregnancy

– Prolonged half-life due to enterohepatic circulation

– Cholestyramine or activated charcoal can hasten elimination

Question 21

Dimethyl Fumarate MOA

Answer 21

Mechanism of action in MS is unclear.

Question 22

Dimethyl Fumarate AE

Answer 22

– Flushing -30%

– Self limited GI side effects -30%

• Lymphocytes decrease by = 20-30% (possibly more)
  – Monitoring required
  – Discontinue if lymphocytes <0.5 for 6 months

Question 23

Pathophys NMO Disorder

Answer 23

Astrocytopathy – Aquaporin 4 Abs in high concentrations in foot processes of astrocytes along endothelial lining of blood brain barrier

Pathology is ?? complement mediated destruction of astrocytes with secondary demyelination

Question 24

demographics NMO Disorder

Answer 24

90% patients are women. Disproportionately affects non-Caucasians.

Question 25

NMOD clinically vs MS and with Ix

Answer 25

* Optic Nerve disease important (often more severe than ON in MS) * Spinal Cord disease important (often more severe than myelitis in MS) * May be significant pleocytosis on CSF. Usually no OCBs (maybe transientlypresent during a relapse). Doesn’t respond to interferon or other MS treatments NO decrease in chance of relapse during pregnancy (cf MS) NMOSD has a worse prognosis than MS – 50% walking problems at 5 years

Question 26

MOGAD

Answer 26

Myelin Oligodendrocyte Glycoprotein Associated Disease – MS mimicker (screen ?MS patients for this & for NMOSD). – Important to differentiate from RRMS – ADEM presentation in children – Opticospinal (NMO type) presentation in adolescents & adults – Maybe monophasic or recurrent disease course

Question 27

Pathophys MOGAD

Answer 27

– Oligodendrocyte directed pathology = Oligodendrocytopathy

Question 28

MS and vaccinations

Answer 28

Question 29

Basic INO presentation

Answer 29

– complex eye movement disorder * loss or slowed aDduction * horizontal nystagmus of aBducting eye * lesion in MLF on side of decreased Adduction * if bilateral is usually coupled with vertical nystagmus on upward gaze. – maybe bilateral or unilateral