Multiple sclerosis (N)

Question 1

Define MS.

Answer 1

Chronic, inflammatory demyelinating disease of the CNS characterised by the presence of episodic neurological dysfunction in at least two areas of the CNS (brain, SC and optic nerves) separated in time and space

Question 2

What does MS result in?

Answer 2

Discrete plaques of demyelination and axonal degeneration in the brain and spinal cord

Question 3

What response is involved in MS?

Answer 3

T-cell mediated immune response

Question 4

What is a specific condition the features have to fulfil to be classed as MS?

Answer 4

Separation in time and space - lesions in the CNS must have occurred in at least 2 different places and at least 2 different times

Two episodes of neurological dysfunction that are separated in time and space

Question 5

What are the different forms of MS? (5)

Answer 5

• relapsing-remitting MS
• primary progressive MS
• secondary progressive MS
• clinically isolated syndrome
• Marburg variant

Question 6

What is relapsing-remitting MS like?

Answer 6

• most common (85%)
• acute attacks (last 1-2 months) with complete recovery in between attacks

Question 7

What is primary progressive MS like?

Answer 7

• 10% of patients
• progressive deterioration from onset - no relapsing/remitting, straight progressive, steady accumulation of disability

Question 8

What is secondary progressive MS like?

Answer 8

• progressive accumulation of disability AFTER initial relapsing-remitting course
• relapsing-remitting patients who have deteriorated and developed neurological signs between relapses
• 65% progress from relapsing-remitting –> secondary progression

Question 9

What is clinically isolated syndrome (MS) like?

Answer 9

• single clinical attack of demyelination
• attack itself does not count as MS
• 10-50% progress to MS

Question 10

What is Marburg variant (MS) like?

Answer 10

Severe fulminant variation of MS –> advanced disability or death within weeks

Question 11

Which demographics is MS most common in? (3)

Answer 11

Most common is young, white female

• female
• 20-40 years old
• white

Question 12

What are the causes of MS? (2)

Answer 12

• genetic predisposition
• environmental factors e.g. low vitamin D, smoking, EBV

Question 13

What is the earliest manifestation of MS? (1+6)

Answer 13

Optic neuritis (inflammation of the optic nerve) - earliest and most common presentation

• unilateral, impaired vision
• colour blindness
• rapid loss of central vision
• pain on eye movement
• RAPD - both pupils appear dilated when eye illuminated in swinging torch test
• central scotoma

Question 14

What is another visual phenomenon that may be seen in MS?

(Apart from optic neuritis)

Answer 14

Intranuclear ophthalmoplegia - lesion of the medial longitudinal fasciculus, blocking connection between contralateral CN6 nucleus and ipsilateral CN3 nucleus, affecting horizontal gaze

–> nystagmus of the abducting eye with absent adduction of the other (ipsilateral) eye
(or isolated nystagmus)

Question 15

What would a right intranuclear ophthalmoplegia look like (MS)?

Answer 15

Right eye unable to adduct, and nystagmus will occur in left eye simultaneously i.e. when it is abducting

Question 16

What types of symptoms might we see in MS? (6)

Answer 16

• visual
• sensory
• motor
• cerebellar
• autonomic
• others - psychological/cognitive

Question 17

What are some visual symptoms of MS? (5)

Answer 17

• optic neuritis (initial and most common) - vision loss, pain
• intranuclear ophthalmoplegia (contralateral medial longitudinal fasciculus lesion) = lateral horizontal gaze
• spastic paraparesis - papillitis, transverse myelitis
• acute paraparesis - visual loss, neuromyelitis optica
• Uhtoff’s phemomenon - worsening of vision following rise in body temperature

Question 18

What are some sensory symptoms of MS? (5)

Answer 18

• paraesthesia, pins and needles, numbness
• burning
• odd sensation of patch of wetness/burning
• hemibody sensory loss or tingling
• Lhermitte’s sign - paraesthesia in limbs on neck flexion

Question 19

What are some motor symptoms of MS? (4)

Answer 19

• limb weakness - after walking, leg cramping
• spasms
• stiffness
• heaviness

Question 20

What are some cerebellar symptoms of MS? (6)

Answer 20

• trunk and limb ataxia + ataxic gait
• intention tremor
• scanning speech
• falls
• dysdiadochokinesia
• tremor

Question 21

What are some autonomic symptoms seen in MS? (2)

Answer 21

• urinary urgency/frequency/hesitation
• impotence / ED

Urinary incontinence often first sign

Question 22

What specific signs might be seen in MS? (3)

Answer 22

• Lhermitte’s sign - paraesthesia in limbs on neck flexion
• Uhtoff’s sign - worsening of neurological Sx (eyesight) as body gets overheated
• Hoffman’s sign - flicking/pressure on nail bed causes twitching of thumb/fingers

Question 23

What visual signs might you see on examination in MS? (3)

Answer 23

• RAPD
• central scotoma (if optic nerve affected)
• field defects (if optic radiation affected)

Question 24

What UMN signs might you see in MS? (3)

Answer 24

• positive Babinski’s sign
• spasticity (common in legs)
• hyperreflexia

Question 25

What are some risk factors for MS? (7)

Answer 25

- female sex - Fx of MS - Northern latitude - genetic factors - vitamin D deficiency - smoking - EBV

Question 26

What is the first-line investigation for MS?

Answer 26

MRI brain and spinal cord with gadolinium contrast

Question 27

What do we see in MS on MRI brain with contrast?

Answer 27

Hyperintensities in periventricular white matter (white) - periventricular plaques Dawson fingers: often seen on FLAIR images - hyperintense lesions perpendicular to the corpus callosum High signal T2 lesions

Question 28

What do we see in MS on MRI spinal cord with contrast?

Answer 28

Demyelinating lesion in SC, hyperintensities (white)

Question 29

How can we see separation of time and space in MS in MRI?

Answer 29

Lesions with varying degrees of contrast enhancement and restricted diffusion indicating active/recent demyelination

Question 30

What more invasive investigation can we do for MS?

Answer 30

Lumbar puncture --> CSF analysis: - unmatched oligoclonal bands - elevated IgG antibodies

Question 31

What would evoked potentials be like in MS?

Answer 31

Visual, auditory and somatosensory evoked potentials may show delayed conduction velocity (but well-preserved waveform)

Question 32

How would visually evoked potential results be affected in MS?

Answer 32

Optic neuritis --> demyelination of optic nerve --> slower conduction along nerve --> visual evoked potential will take longer to travel along axon = delayed conduction velocity

Question 33

What are some differential diagnoses for MS? (9)

Answer 33

- myelopathy due to cervical spondylosis - fibromyalgia - generalised weakness and non-specific fatigue - sleep disorders - Sjogren syndrome - dry eyes and mouth - vitamin B12 deficiency - ischaemic stroke - peripheral neuropathy - amyotrophic lateral sclerosis - UMN&LMN (atrophy and fasciculations), no visual changes - GBS - loss of reflexes, motor Sx, CSF shows cytoalbumin dissociation

Question 34

What is the diagnostic criteria for MS?

Answer 34

McDonald criteria - diagnosis is based on the finding of two or more CNS lesions on MRI with corresponding symptoms, separated in time and space

Question 35

How do we approach treatment of MS? (3)

Answer 35

- treatment of acute attack - prevention of future attacks - reduce triggers, use disease-modifying therapies - symptomatic treatment of neurological deficits e.g. spasticity, pain, fatigue, bladder dysfunction

Question 36

What is the 1st and 2nd line management for an acute exacerbation of MS?

Answer 36

- 1st line: IV methylprednisolone (high-dose glucocorticoid) for 5d - 2nd line: plasma exchange

Question 37

How do we treat relapsing MS?

Answer 37

Immunomodulators (beta-interferon) or natalizumab

Question 38

What are typical indications for disease-modifying drugs in MS?

Answer 38

- relapsing-remitting disease + 2 relapses in past 2y + able to walk 100m unaided - secondary progressive disease + 2 relapses in past 2y + able to walk 10m aided/unaided

Question 39

What are some drug options for reducing risk of relapse in MS? (5)

Answer 39

- natalizumab (recombinant monoclonal antibody --> a4b1 integrin) - often 1st line - ocrelizumab (anti-CD20 monoclonal AB) - often 1st line - fingolimod (S1P receptor modulator) - beta-interferon (not as effective) - glatiramer acetate (not as effective)

Question 40

How do we manage primary progressive MS?

Answer 40

Ocrelizumab if early stage

Question 41

What is the 1st and 2nd line management for secondary progressive MS?

Answer 41

- 1st line: methylprednisolone OR siponimod - 2nd line: cladribine

Question 42

How do we manage spasticity in MS?

Answer 42

Baclofen or gabapentin

Question 43

How do we manage sensory symptoms (pain and paraesthesia) in MS?

Answer 43

Low-dose anticonvulsant or antidepressant --> gabapentin, pregabalin, carbamazepine, duloxetine, amitriptyline

Question 44

How do we manage fatigue in MS?

Answer 44

Once other problems (e.g. anaemia, thyroid or depression) have been excluded, NICE recommend a trial of **amantadine** Mindfulness training, CBT

Question 45

How do we manage bladder dysfunction in MS?

Answer 45

- US to assess bladder emptying - anticholinergics may worsen Sx in some patients - if significant residual volume --> intermittent self-catheterisation - if no significant residual volume --> anticholinergics may improve urinary frequency - frequency: oxybutynin, reduce caffeine

Question 46

How do we manage oscillopsia (visual fields appear to oscillate) in MS?

Answer 46

Gabapentin is 1st line

Question 47

How do we manage tremor in MS?

Answer 47

Propranolol

Question 48

What are some complications of MS? (7)

Answer 48

- UTIs - osteoporosis - depression - visual impairment - erectile dysfunction - cognitive impairment - impaired mobility

Question 49

Describe the prognosis of MS.

Answer 49

High relapse rate in first two years after MS onset