Multiple Sclerosis

Question 1

What is multiple sclerosis (MS)?

Answer 1

Multiple sclerosis is a chronic autoimmune, T-cell mediated inflammatory disorder of the CNS.

Multiple plaques of demyelination are found throughout the brain and spinal cord, occurring radically over years

Demylination heals poorly => axonal loss => progressive disability
*dissemination over space and time is important for diagnosis

Question 2

Who does multiple sclerosis affect?

Answer 2

MS is the most common neuroinflammatory disorder in western population

Women > men (3:1)

Onset between 20-40 yrs

Major cause of disability in young adults

Question 3

What is the underlying pathology behind multiple sclerosis?

Answer 3

Plaques of demyelination => cardinal feature of MS

Plaques occur anywhere in white matter but common areas are: optic nerve, corpus collosum, brainstem, cerebellar connections and cervical cord (corticospinal tracts and posterior columns)

Acute relapses are caused by focal inflammation => myelin damage + conduction block

Recovery follows as inflammation subsides & remylination occurs.

If severe => permanent axonal loss
=> Progressive axonal loss => progressive disability
=> Extent of grey matter damage => severity of disability and cognitive involvement

Question 4

What are the 4 types of multiple sclerosis?

Answer 4

1. Relapsing-remitting MS (RRMS)
2. Secondary progressive MS
3. Primary progressive MS (PPMS)
4. Relapsing-progressive MS

Question 5

Describe relapsing-remitting MS.

Answer 5

Most common pattern of MS [85-90%]

Symptoms occur in attacks (relapses) with a characteristic time course i.e.
=> onset over days and partial or complete recovery over weeks
=> with time remission is incomplete => worsening disability => secondary progression

Question 6

Describe secondary progressive MS.

Answer 6

Late stage MS => gradually worsening disability over years

~75% of patients with relapsing-remitting MS evolve into a secondary progressive phase by 35yrs after onset

Question 7

Describe progressive MS.

Answer 7

Gradually worsening disability without relapses or remissions
=> presents later
=> assoc. with fewer inflammatory changes

Question 8

Describe relapsing-progressive MS.

Answer 8

Least common form of MS => similar to primary progressive MS but with occasional relapses

Question 9

What are the 3 most common characteristics of MS?

Answer 9

1. Optic neuropathy (neuritis)
2. Brainstem demyelination
3. Spinal cord lesions

Question 10

What are the poor prognostic features?

Answer 10

Older female

Motor signs at onset

Many early relapses

Many MRI lesions

Axonal loss

Question 11

What are the signs and symptoms of MS?

Include:

Sensory deficits

Visual deficits

Motor deficits

Genito-urinary deficits

Cognitive deficits

Answer 11

1. Sensory: 
=>abnormal sensation i.e. trickling water down the skin,
=> pins & needles, 
=> reduced vibration sense, 
=> loss of proprioception 
=> trigeminal neuralgia + fatigue 

2. Visual:
   => diplopia ; hemianopia ; optic neuritis ; pupil defect
3. Motor:
   => spastic weakness ; unsteadiness or ataxia
   Cerebellar => clumsy due to loss of proprioception ; intention tremor ; monotonous (scanning) speech ; falls
4. Sexual/GU:
   => Sexual dysfunction
   => urine retention or incontinence due to bladder hyper-reflexia causing urinary urgency and frequency
5. Cognitive/visuospatial decline:
   => big cause of unemployment, accidents, amnesia, low mood, reduced executive functioning
   => depression

Question 12

How do you diagnose MS?

Answer 12

Clinical diagnosis made by consultant neurologist

=> 2 or more attacks affecting different parts of the CNS (dissemination in time and space)
=> exclusion of other differentials

Hx and investigations i.e. MRI support diagnosis

*Early diagnosis and treatment reduce relapse rates and disability

Question 13

What investigations are carried out in MS?

Answer 13

MRI 
=> definitive investigation 
=> shows areas of demyelination with high sensitivity 
=> low specificity 
=> help exclude other causes

CSF
=> oligoclonal bands of IgG => CNS inflammation

Evoked responses i.e. delayed visual, auditory, somatosensory may be silent lesions

Blood tests to exclude other inflammatory causes i.e. SLE, sarcoidosis etc

Question 14

There is no cure for MS.

How do you manage MS?

Answer 14

Disease modifying drugs

=> dimethyl fumarate for mild/moderate RRMS

=> monoclonal antibodies alemtuzumab (acts against T-cells) and natalizumab (VLA-4 receptor that allows immune-cell to cross BBB) for RRMS

Lifestyle advice: stop smoking, regular exercise, avoid stress

Question 15

How do you manage acute MS relapses?

Answer 15

Methylprednisolone

Question 16

How do you control symptoms of MS?

Answer 16

Spasticity: baclofen or gabapentin

Tremor: Botulinum toxin type A injections ; beta-blocker

Urinary symptoms:
=> anti-muscurinics i.e. solifenacin
=> intermittent self-catheterisation
=> botulinum toxin type A injections

Pain:
=> gabapentin ; pregabalin
=> Carbamazepine / lamotrigine trigeminal neuralgia

Depression: CBT ; anti-depressants

Impaired mobility: physiotherapy ; treat spasticity

Erectile dysfunction: sildenafil ; tadafil