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Multiple Sclerosis (MS)

NICE guideline [NG220] Multiple sclerosis in adults: management. Published: Jun 2022. NICE CKS Multiple sclerosis. Last revised: May 2024. ECTRIMS International Advisory Committee on Clinical Trials in MS. McDonald Diagnostic Criteria

Background Information

Typical presents in 20-50 y/o and more common in female

MS-indicative patterns:
  • Symptoms tend to evolve over >24 hours
  • Symptoms may persist over days and weeks then improve (relapse remitting)
  • History of previous neurological symptoms
  • No signs of infection

Most common initial presentations:
 
Presentation Clinical features
Optic neuritis (20-30%)
  • Eye pain, esp. on eye movement
  • Partial or total unilateral visual loss (developing over a few day, not sudden onset)
  • Loss of colour discrimination, particular red
  • Relative afferent pupillary defect

Optic neuritis is more commonly unilateral, if bilateral one must exclude neuromyelitis optica which is often confused with MS and needs urgent treatment
Transverse myelitis
  • Sensory (e.g. paraesthesia) symptoms below the affected spinal level
  • Upper motor neuron signs below the affected spinal level
    • NB that there is an initial spinal shock phase where there are lower motor neuron signs (e.g. reduced tone, areflexia) before transiting into upper motor neuron signs
  • Lhermitte's phenomena: shock-like sensation radiating down the spine on neck flexion
  • Urinary symptoms (e.g. urgency, frequency, retention)
Cerebellar features
  • Ataxia
  • Vertigo
  • Dysmetria
  • Clumsiness
Brainstem syndromes
  • Ataxia
  • Diplopia, oscillopsia, nystagmus
  • Internuclear ophthalmoplegia (ipsilateral eye fails to adduct and contralateral eye abducts with nystagmus)
  • Pseudobulbar palsy (e.g. dysarthria, dysphagia)

Guidelines

If MS is suspected based on clinical features → refer to consultant neurologist (only a consultant neurologist should make a diagnosis of MS)

1st line investigations for susecpted MS
  • MRI brain + spinal cord (with and without gadolinium) - most important investigation
  • Lumbar puncture for CSF analysis
 

This section is more likely to be examined, instead of having to learn the full McDonald Criteria which is reserved for specialist.
 
Investigation Findings in MS
MRI Multiple sclerotic plaques and Dawson fingers(finger-like radial extensions)
  • Most common location: periventricualr white matter
  • Lesion in the corpus callosum is almost pathognomonic
 
  • Hyperintense in T2 and FLAIR, hypointense in T1
CSF analysis Presence of oligoclonal bands in the CSF but NOT in the blood
 

The previous 2017 revision McDonald Criteria requires both dissemination in space and time to make a diagnosis of MS. The key update in the 2024 update is that either dissemination in space OR time is sufficient, when combined with additional features listed below.

The key take away from the McDonald Criteria is that MS is typically characterised by dissemination in space and/or time reflected by the clinical presentation and supported by MRI and/or CSF findings.

The 2024 revised McDonald Criteria provides 2 diagnostic criterias.
 
Disease presentation MS diagnostic criteria
Typical MS presentation
  • At least 2 CNS lesions OR progressive symptoms for at least 12 months with at least 2 spinal cord lesions, AND
  • At least 1 of the following
    • Central vein sign
    • +ve CSF (presence of oligoclonal bands or kappa free light chains)
    • Presence of lesions in 4 out of 5 CNS locations
    • Dissemination in time
Objective progression
  • 1 CNS lesion, AND
  • At least 1 of the following
    • Dissemination in time and central vein sign
    • Dissemination in time and paramagnetic rim lesion
    • +ve CSF (presence of oligoclonal bands or kappa free light chains) and paramagnetic rim lesion
    • +ve CSF (presence of oligoclonal bands or kappa free light chains) and central vein sign
 

Modifiable risk factors for relapse and progression:
  • Regular exercise may have beneficial effects
  • Stop smoking
  • Offer routinely recommended vaccinations
    • Live vaccines should be avoided if patient is on immunosuppressive treatment

  • 1st line: oral methylprednisolone 0.5g daily for 5 days
  • Alternative: IV methylprednisolone 1g daily for 3-5 days
    • Should be used if oral steroids failed / not tolerated, or patient admitted to hospital for a severe relapse
 

Before diagnosing and treating relapse:
  • Rule out infection (esp. UTI and RTI), and
  • Discriminate between the relapse and fluctuations in disease or progression

Do not routinely diagnose a MS relapse if symptoms are present for >3 months

NICE guideline did not incorporate recommendations regarding disease-modifying therapies in NG220, instead provided a list of separate technology apprasials, see the full listings here.

Due to the above mentioned reason, a summary of international EAN and AAN guidelines is deemed for appropriate for educational purposes:
 
MS Phenotype Commonly used disease-modifying therapies
Clinically isolated syndrome (CIS)
  • Interferon-beta (inhibit T cell activation)
  • Glatiramer acetate
Relapsing-remitting MS (RRMS)
  • Interferon-beta (inhibit T cell activation)
  • Natalizumab (antianti-α4-integrin)
  • Dimethyl fumarate
  • Fingolimod
Secondary progressive MS (SPMS)
Primary progressive MS (PPMS)
  • Ocrelizumab (anti-CD20 on B cells)
 

Disclaimer: this section focuses on three of the most common and clinically relevant MS symptoms, which NICE provides clear management strategies, and which are frequently encountered in both clinical practice and assessments. The remaining is deemed low-yield thus made redundant. 
 
Complication Management Notes
Fatigue Non-pharmacological
  • Mindfulness-based training
  • CBTCognitive behavioural therapy
  • Fatigue management educational programmes
  • Supervised exercise programmes involving moderate progressive resistance training and aerobic exercise

Pharmacological (all off-label)
  • Amatadine
  • Modafinil
  • SSRI
 MS-related fatigue is very common, affecting up to 80% of patients
Spasticity Consider referral to physiotherapy

Drug treatment
  • 1st line: baclofen
  • 2nd line: gabapentin
  
Oscillopsia Consider (all off-label)
  • 1st line: gabapentin 
  • 2nd line: memantine
 Oscillopsia: subjective sensation that the environment is moving or bouncing
 

Advise that patients should discuss with their healthcare professionals if they are planning to start or extend their family or become pregnant, espeically in those who take disease-modifying therapies.

Explain that MS should not stop them from planning a family, and advise the following important points:

  • Impact on disease
    • Pregnancy does not increase the risk of MS progression
    • MS relapses may decrease during pregnancy and may increase 3 to 6 months after childbirth before returning to pre-pregnancy rates
  • Impact on pregnancy and outcome
    • Pregnancy can be well managed
    • Risk of the child developing MS is slightly higher than average (but overall risk is low)

References

Author: Kirk F, Adams Lau
Reviewer:
Last edited: 19/07/25