MS

Question 1

what is MS?

Answer 1

MS: chronic, immune-mediated inflame disease of CNS
- Demyelinating neuroinflam condition which affects CNS  brain and spinal cord

Question 2

who is most likely to get MS?

Answer 2

females
20s-40s

Question 3

what is the aetiology?

Answer 3

though to be abnormal immune reaction to unknown environmental trigger in genetically predisposed individual
- Genetics: plays slight role

Question 4

what are the RF for MS?

Answer 4

viral infections
geography
vit D
obesity during adolescence
smoking

Question 5

what viral infection is linked to MS onset?

Answer 5

EBV

Question 6

where are you are most at risk from MS and why?

Answer 6

further from equator
vitD deficiency link

Question 7

what is the pathophysiology of MS?

Answer 7

inflame
demyelinating disease characterised by presence of plaques
oligodendrocytes are destroyed –> demylination axonal loss
immune dsyregulation

Question 8

what do oligodendrites do?

Answer 8

type of glial cell important in the formation of myelin sheath

Question 9

what is the autoimmune aspect of the pathophysiology of MS?

Answer 9

1. Activation of myeline-reactive T lymphocytes and disruption of BBB
2. Pro-inflam recruiting B cells. microglia (macrophages of CNS) mediate cytokine, phagocytosis and APC cells
3. Marked immune response including AB-mediated with Immunoglobulins (oligobands in CSF)
4. Continued reaction causes damage to oligodendrites  subsequent demyelination  formation of MS plaques
5. Focal areas of demyelination/ plaques – inflame,s carring (gliosis), axonal injury

Question 10

what are the MS plaques made up of?

Answer 10

hypercellular
containing reactive T, B and macrophages

Question 11

where are classic plaque sites?

Answer 11

• Optic nerve – affects 40% of those with disease
• Spinal cord – 50-75%, majority associated with concomitant brain lesions
• Brainstem: may present with ophthalmoplegia
• Cerebellum: ataxia and gait disturbances
• Juxtacortical white matter: near cerebral cortex
• Periventricular white matter: near ventricles

Question 12

what is the most common type of MS?

Answer 12

90% have relapsing- remitting disease

Question 13

what is relapsing remitting disease?

Answer 13

• Episodes of exacerbation are followed by periods of recovery
• As disease progresses they are likely to retain damage with each relapse

Question 14

10-15% of MS is primary progressive, what is it?

Answer 14

• Sustained progression of disease severity from onset
• May have periods of active or non progressive
• No evidence of clinical remission

Question 15

how many RRD progress to secondary progressive?

Answer 15

50% of relapsing will develop this within 15yrs

Question 16

what is secondary progressive?

Answer 16

• Disease gradually worsens
• Relapses may occur but without remission

Question 17

what is clinically isolated syndrome?

Answer 17

first episode of suspected MS

Question 18

what is seen within clinically isolated syndrome?

Answer 18

• No previous evidence of demyelination clinically or neuroimaging
• Oligobands in CSF  support diagnosis

Question 19

what is a MS exacerbation?

Answer 19

relapse/ episode of new or worsening symptoms for at least 24hrs that can either spontaneously resolve or resolve with management

Question 20

how do symptoms within MS differ?

Answer 20

determined by plaque locations within CNS

Question 21

what are the most common visual pathologies of MS?

Answer 21

optic neuritis and eye movement abnormalities

Question 22

what is optic neuritis?

Answer 22

inflame of optic nerve and characteristically presents with partial or total unilateral visual loss that develops over days

Question 23

what visual symptoms can be seen within MS?

Answer 23

optic neuritis
- Visual loss, blurred vision
- Pain: especially on eye movement
scotoma
poor colour differentiation, relative afferent pupillary defect, optic nerve swelling seen on fundoscopy

Question 24

what is scotoma?

Answer 24

partial visual field loss

Question 25

how do eye movement disorders arise?

Answer 25

due to brainstem lesions that affect cranial nerves or pathways

Question 26

what eye movement disorders can occur?

Answer 26

INO abducens palsy

Question 27

what motor and coordination signs may manifest within MS?

Answer 27

weakness and ataxia  upper motor neurone signs eg spasticity, reduced power and hyper-reflexia

Question 28

what is transverse myelitis?

Answer 28

focal inflame within spine – sensory and motor symptoms below level of lesion eg bladder/ bowel involvement

Question 29

what is cerebellar syndrome?

Answer 29

ataxia, slurred speech, intension tremor, nystagmus

Question 30

what is nystagmus?

Answer 30

(uncontrolled, repetitive eye movements – side to side , up and down or circular pattern)

Question 31

what sensory and autonomic manifestations may occur within MS?

Answer 31

paraesthesia, pain, heat sensitivity (uhtoff phenomenon), sexual dysfunction, bladder and bowel

Question 32

what cognitive and psychological symptoms may arise within MS?

Answer 32

cognitive impairment, depression, fatigue

Question 33

how is MS diagnosed?

Answer 33

clinical judgement with MRI to support lumbar puncture

Question 34

what general care is involved within MS management?

Answer 34

- Bladder dysfunction: may require anticholinergic seg oxybutynin for detrusor overactivity, retention  intermittent self -catheterisation or long term catheters - Depression: duloxetine may be preferred if co-existing neuropathic pain/ fatigue. SSRIs - Fatigue: physical activity and treat co-morbidity eg modafinil - Gait disturbance: occupational and physio - Pain: neuropathic pain is significant issue  amitriptyline, gabapentin/ pregabalin - Spasticity: can lead to functional disability  may need physio and baclofen (skeletal muscle relaxants)

Question 35

how do you manage an acute relapse of MS?

Answer 35

1. Need to rule out infection 2. Need to distinguish from fluctuations in disease course or pregressive disease - Steroids: oral methylpred 500mg for 5days or IV 1g OD for 3-5days - Gastroprotection: PPI - Discuss risk/ benefit or treatment: acute changes in blood glucose/ mental health

Question 36

how long can it take to recover from a relapse?

Answer 36

Recovery may be 2-3months byt in some cases can be 12months - If severe can lead to residual functional disability

Question 37

what are DMTs?

Answer 37

Disease modifying therapies: immunomodulatory meds that aim to decrease the number of relapses and slow progression

Question 38

what is the MOA of teriflunomide - DMT?

Answer 38

Inhibits pyrimidine synthesis  antiproliferative and anti inflame

Question 38

what is the MOA of glatirameter acetate - DMT?

Answer 38

Induce and activate T suppressor cells for myelin antigen

Question 38

what is the MOA of interferon - beta (DMT)?

Answer 38

Modulates immune response

Question 38

when is DMTs indicated?

Answer 38

no evidence of non-relapsing and sustained disability

Question 39

what is the MOA of alemtuzumab?

Answer 39

Monoclonal AB targeting CD52 – found in many immune cell lines – immunomodulatory

Question 40

what is the MOA of cladribine - DMT?

Answer 40

Purine nucleoside analogue – cytotoxic effects on B and T lymphocytes preventing DNA synthesis

Question 41

what is the MOA of natalizumab - DMT?

Answer 41

Monoclonal AB against alpha 4 subunit of integrin molecules. Prevents migration of leucocytes across BBB

Question 42

what is linked to worse prognosis?

Answer 42

primary rather than relapsing-remitting not recovering from first attack having pyramidal, brainstem, cerebellar path symptoms more lesions and cerebral atrophy

Question 43

how is pregnancy linked to MS?

Answer 43

pregnancy - protective postpartum: increased risk of relapse

Question 44

what are complications of MS?

Answer 44

- fatigue - mobility balance problems - spasticity - bowel and bladder dysfunction - emotional lability - ophthalmic complications - pain - cognition including memory