Multiple Sclerosis

Question 1

Define multiple sclerosis

Answer 1

Inflammatory demyelinating disease of the CNS – discrete plaques of demyelination occur at multiple CNS sites, from T-cell mediated immune respons

Question 2

Explain the aetiology / risk factors of multiple sclerosis

Answer 2

AETIOLOGY:

• Autoimmune basis with potential environmental trigger in genetically susceptible individuals (no specific antigen/antibody has been identified)
• Immune-mediated damage to myelin sheaths results in impaired axonal conduction
• Clinically defined by two episodes of neurological dysfunction (brain, spinal cord, or optic nerves) that are separated in space (location in CNS) and time
• The MOST COMMON form is the relapsing-remitting form (relapse can be causes by infection/illness)

Risk Factors

• Young Female (20-40)
• FHx of autoimmine disorders
• EBV exposure
• Vitamin D deficnecy (countries like Norway, Greenland, Iceland have low sun)

Question 3

Summarise the epidemiology of multiple sclerosis

Answer 3

• MS is most commonly diagnosed between 20 and 40 years old.
• Female > Male (F:M = 3:1)

Question 4

Recognise the presenting symptoms of multiple sclerosis

Answer 4

Symptoms usually progress over more than 24 hours. Symptoms tend to last days to weeks at the first presentation and then improve. There are many ways MS can present, depending on the location of the lesions.

In early disease, re-myelination can occur, and the symptoms can resolve. In the later stages of the disease, re-myelination is incomplete, and the symptoms gradually become more permanent.

• LETHARGY
• Optic neuritis ( MOST COMMON initial presentation)
  
  • Sudden-onset blurred vision (like looking through vaseline)
  • Central scotoma (oscillopsia)
  • Loss of colour discrimination (esp. red)
  • Painful eye movements
  • A key differential to exclude is neuromyelitis optica which needs urgent referral and steroid treatment
• ​Uhthoff’s phenomenon: worsening of symptoms on exercise/in warm environments e.g. in a bath (particularly optic symptoms)
• Sensory
  
  • Parasthesia/tingling
  • Trigeminal neuralgia
  • Odd sensations:
    
    • burning
    • a patch of wetness
    • electric shock going down cervical spine to limbs upon neck flexion (Lhermitte’s sign)
• Motor
  
  • Limb weakness
  • Dysphagia
• Autonomic:
  
  • Bowel dysmotility (constipation)
  • Urinary retention
  • Horner’s syndrome

Question 5

Recognise the signs of multiple sclerosis on physical examination

Answer 5

• EYE SIGNS
  
  • Intranuclear Ophthalmoplegia (INO)
    
    • damage to medial longitdudinal fasciculus which co-ordinates simultaenous adduction and abduction of eyes on right/left gaze
    • When levo/dextreversion is attempted, the affected eye will FAIL TO ADDUCT and the normal eye will show a NYSTAGMUS

Optic neuritis:
* Pale optic disc
* May see RAPD
* Reduced visual acuity
* Abnormal result from Isihara test (due to red colour blindness)
* CEREBELLAR SIGNS: Assess gait by making them walk 7.6m
* Ataxic gait
* Wide-based gait/Foot dragging gait
* DANISH
* MOTOR SIGNS: UMNL Signs
* Hypertonia (spastic)
* Hyperreflexia
* Paresis (MRC < 5) - most commonly paraparesis but can present w/ monoparesis
* Clonus
* SENSORY SIGNS:
* Reduced sensation
* Facial paraesthesia (trigeminal neuralgia)

Question 6

Identify appropriate investigations for multiple sclerosis and interpret the results (diagnostic & excluding tests)

Answer 6

• contrast MRI brain & spinal cord: T2 Hyperintensities showing demylinated white matter plaques in paraventricular area and cervical spinal cord
• LP for CSF (if radological not enough): electrophoresis will show oligoclonal bands & high IgG
  
  • The presence of oligoclonal bands is due to presence of IgG auto-antibodies
  • Compare CSF electrophoresis to plasma’s and if present in plasma, then the elevated antibodies is more likely due to infection - so in MS the oligoclonal bands should only be in the CSF

Excluding tests:

• Serum B12
• Vitamin D levels
• FBC look for infection/inflammation
• CRP, U&E, TFTs

Question 7

McDonald’s Criteria for DIT & DIS

Answer 7

The McDonald criteria are used to diagnose MS based on the dissemination of the CNS lesions in time and space.

If somebody complains of Sx that suggest MS

Dissemination in time (DIT): defined as the appearance of new lesions over time that can be confirmed by one of the following:

• Two or more exacerbations occurring at least 30 days apart
• MRI demonstrates the presence of a new (not on previous MRI) hyperintense T2 lesion on follow-up MRI
• Alternatively to DIT: +ve CSF oligoclonal bands with no serum oligoclonal bands (indicate ongoing intrathecal inflammation)

Dissemination in space (DIS): defined as the presence of lesions in different regions of the CNS that can be confirmed by one of the following:

• Presence of two or more lesions with objective clinical evidence
  
  • Objective clinical evidence of a lesion refers to the correlation between reported symptoms and corresponding objective findings (e.g. T2 hyperintensities in the somatosensory tracts in a patient who reports sensory loss)
• Presence of one or more hyperintense lesions on MRI in T2 sequence in at least 2 of the following regions: periventricular, juxtacortical, infratentorial, spinal

Question 8

Referral pathway

Answer 8

If a person has symptoms and signs suggestive of multiple sclerosis (MS):
* Refer promptly to a consultant neurologist — Only a consultant neurologist can diagnose MS.
* If they present with sudden onset visual loss speak to a neurologist (suspected neuromyelitis optica) - neuromyelitis optica presents with BILATERAL OPTIC NEURITIS
* Once the diagnosis is confirmed, the person should be under the care of a consultant neurologist and a multidisciplinary MS team.

Question 9

Management

Answer 9

General health advice
* encourage smoking cessation
* encourage exercise (may help with mobility and fatigue)

Managing a Relapse

• Rule out infection (UTI/Pneumonia)
• Consider admission if relapse is severe
• DISCUSS with their designated MS specialist to decide on treatment
  
  • oral methylprednisolone 500mg for 5 days (a short course given as early as possible)
  • IV methylprednisolone may be given

Disease Modifying Therapies

• Only to be started under direction of a specialist
• they aim to induce long-term remission with no disease activity.
• examples include: anti-lymphocyte monoclonal antibodies, interferons, immunomodulators

Symptomatic management

• Oscillopsia –> Gabapentin
• Spasticity –> Baclofen
• Fatigue & mobility issues –> Exercise, CBT, amantadine
• Emotional lability –> Amytriptylline
• Bladder dysfunction
  may take the form of urgency, incontinence, overflow etc
  guidelines stress the importance of getting an ultrasound first to assess bladder emptying - anticholinergics may worsen symptoms in some patients
  if significant residual volume → intermittent self-catheterisation
  if no significant residual volume → anticholinergics may improve urinary frequency
• Oscillopsia (visual fields appear to oscillate)
  gabapentin is first-line