Multiple Sclerosis (MS)
Multiple sclerosis (MS) is an acquired, chronic, immune-mediated, inflammatory demyelinating condition of the central nervous system that can affect the brain, brainstem, and spinal cord.
This updated UKMLA guide to MS is based on NICE NG220, which covers causes, risk factors, types, symptoms, diagnosis, and management.
Causes and Risk Factors
The exact cause of MS is unknown. It is thought to involve immune-mediated inflammation, triggered by an abnormal response to environmental factors in genetically predisposed individuals
- T-cell-mediated inflammation damages oligodendrocytes, leading to demyelination and secondary axonal damage
- Progressive damage within the nervous system may lead to irreversible loss of nerve function, resulting in permanent neurological symptoms and signs
Risk factors:
- Genetics (>200 alleles have been identified)
- Family history
- Females (2-3x risk)
- Vitamin D deficiency
- Smoking
- Diet and obesity in early life
- EBV infection
- Latitude
Clinical Features
Typical onset is in 20-50 y/o and is more common in females
MS may present with a wide range of symptoms affecting different body parts, most common ones (ANY of the following):
- Optic neuritis (loss or reduction of vision in 1 eye with painful eye movements)
- Double vision
- Ascending sensory disturbance and/or weakness
- Lhermitte’s sign: shock-like sensation radiating down the spine on neck flexion
- Progressive difficulties with balance and gait
Additional supportive patterns:
- 20-50 y/o female
- History of previous neurological symptoms
- Symptoms evolved >24 hours
- Symptoms may persist over several days or weeks then improve
- No fever or signs of infection
Key presentation patterns
| Presentation | Clinical features |
|---|---|
| Optic neuritis (20-30%) | Optic neuritis is typically unilateral (CRAP is a useful mnemonic):
|
| Transverse myelitis |
|
| Spinal cord tract demyelination |
|
| Cerebellar features |
|
| Brainstem syndromes |
|
| Other |
|
Disability in MS can be measured and documented using the EDSS, which can be monitored for changes in disability over time
- 0 = no signs or symptoms during assessment; 10 = death from MS
- Increases in increments of 0.5
- Key hallmarks
- 5.0 = Disability severe enough to impair full daily activities
- 6.0 = Walking aid is necessary
- 7.0 = Restricted to wheelchair
Acute MS relapse
Characterised by:
- Developing new symptoms OR worsening of existing symptoms, AND
- Lasting >24 hours after a stable period of at least 1 month
It is important to rule out infection (esp. UTIs and RTIs) and to discriminate between a relapse and fluctuation in disease or progression.
Do not routinely diagnose a relapse of MS if symptoms are present for >3 months
MS Disease Patterns
There are 3 main disease patterns:
| Pattern | Description |
|---|---|
| Relapsing-remitting MS (RRMS) | Most common disease pattern (seen in 85% of MS patients at onset)
Characterised by episodes of relapses (new or worsening symptoms), followed by remissions (partial or complete recovery) and periods of clinical stability |
| Secondary progressive MS (SPMS) | ~2/3 of RRMS progress to SPMS
Characterised by gradual worsening symptoms and/or disability, with relapses becoming less frequent or stopping completely |
| Primary progressive MS (PPMS) | Seen in 10-15% cases of MS
Characterised by steady progression and worsening symptoms and/or disability from the onset, without clear relapses or remissions |
Differential Diagnosis
| Differential diagnoses | Causes and clinical clues |
|---|---|
| Other demyelinating diseases | Neuromyelitis optica spectrum disorder (NMOSD)
Myelin oligodendrocyte glycoprotein antibody-associated Disease (MOGAD)
Isolated optic neuritis – optic neuritis may occur as an isolated event |
| Metabolic disorders |
|
| Infections | |
| Systemic inflammatory disorders |
|
| Tumours |
Investigation and Diagnosis
Note: NICE NG220 refers to the 2024 revised McDonald criteria when outlining the diagnostic approach to MS. The criteria summarised below are based on these 2024 revisions. [Ref]
If MS is suspected based on clinical features → refer to a consultant neurologist (only a consultant neurologist should make a diagnosis of MS)
1st line investigations for suspected MS
- Clinical history and neurological examination
- MRI brain + spinal cord (with and without gadolinium contrast) – most important investigation
- Optic nerve imaging (MRI / OCT / VEPs) (esp. if the patient has a history of possible optic neuritis)
Further investigations:
- Lumbar puncture for CSF analysis
- MOG-IgG testing
- Strongly recommended in <12 y/o presenting with a first demyelinating event to exclude MOGAD)
- Routine testing is NOT necessary in other patients (unless clinical findings and/or MRI findings are atypical or suggestive of MOGAD rather than typical MS)
Investigation Findings
| Investigation | Findings in MS |
|---|---|
| MRI | Key finding: T2-weighted hyperintense foci (plaques) in the CNS white matter
Some typical findings / pattern:
Dissemination in space (DIS) and dissemination in time (DIT) on MRI are fundamental components of the diagnostic criteria: DIS: demonstrating the disease has affected distinct areas (“space”) of the CNS:
DIT: demonstrating inflammatory activity is ongoing over time:
Novel MRI markers (only seen on non-conventional susceptibility-sensitive MRI sequence):
|
| Lumbar puncture and CSF analysis | Classic finding: CSF-restricted oligoclonal bands
Biomarker: positive kFLC Index (↑ kappa free-light chain: albumin ratio) For diagnosis purposes, either the oligoclonal bands or biomarker can be used to fulfil the CSF criteria. |
2024 McDonald Diagnostic Criteria
Key takeaway (exam-friendly and non-specialist level):
- Classic diagnostic criteria: typical symptoms + dissemination in space (DIS) + dissemination in time (DIT)
- In the 2024 criteria, DIT is NOT always mandatory
- High-burden DIS alone can be diagnostic: lesions in ≥4 out of 5 typical CNS locations without DIT
- DIS + positive CSF may also support diagnosis without separate DIT
- The optic nerve is now recognised as a 5th CNS location to be used for DIS
- Kappa free light chains as an alternative CSF marker to oligoclonal bands
Radiologically isolated syndrome (RIS) – i.e. asymptomatic MS criteria:
- MRI lesions in at least 2 CNS locations, and
- At least 1 of the following
- +ve CSF
- CVS on MRI
See the full diagnostic criteria here.
Management
MS management requires an MDT approach involving MS nurses, neurologists, physiotherapists, speech language therapists, psychologist, dietitians, social care etc.
Acute Relapse Management
- 1st line: oral methylprednisolone 0.5g daily for 5 days
- 2nd line: IV methylprednisolone 1g daily for 3-5 days
- If oral steroids failed / not tolerated, or the patient is admitted to hospital for a severe relapse
Long-Term Management
General / Conservative Management
Manage modifiable risk factors for MS relapse / progression:
- Regular exercise may have beneficial effects and has no harmful effects
- Stop smoking
- Offer routinely recommended vaccinations
- Live vaccines should be avoided if the patient is on immunosuppressive treatment
Long-Term Management (Disease-Modifying Therapy)
Disclaimer:
NICE NG220 does not provide a single disease-modifying therapy treatment algorithm. Instead, it links to separate NICE technology appraisals for individual disease-modifying therapies and to the NHS England treatment algorithm for multiple sclerosis disease-modifying therapies.
These technology appraisals and treatment algorithms are highly specialist and extensive, with treatment choice depending on factors such as MS phenotype, disease activity, MRI findings, relapse history, safety profile, monitoring requirements, comorbidities and pregnancy plans.
For exam purposes, it should be sufficient to recognise a few classic disease-modifying therapies and, importantly, to distinguish long-term disease-modifying treatment from the acute management of MS relapses.
| MS phenotype | Disease-modifying therapy summary |
|---|---|
| Relapsing-remitting MS | No clear 1st line option
NICE listed options include:
Options for highly active disease (presence of disease activity despite treatment):
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| Secondary progressive MS | Disease-modifying therapy is only considered when there are signs of active disease:
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| Primary progressive MS |
|
Do not offer vitamin D and omega-3 / omega-6 fatty acid compounds solely for the purpose of treating MS.
Symptom / Complications Management
| Complication | Management |
|---|---|
| Fatigue | Non-pharmacological
Pharmacological (all off-label)
|
| Mobility problems |
|
| Spasticity | Consider referral to physiotherapy
Pharmacological:
|
| Oscillopsia | Consider (all off-label):
|
| Urinary dysfunction (usually overactive bladder) | Managed similarly to those without MS, see the Urinary Incontinence in Women article for more information
Prior to treatment, the following assessment should be performed:
|
| Pain | Neuropathic pain should be managed according to standard neuropathic pain guidelines, see the Neuropathic pain article |
| Emotional lability | Consider amitriptyline for emotional lability (involuntary laughing and crying related to a frontal lobe lesion) |
MS and Pregnancy
Advise that patients should discuss with their healthcare professionals if they are planning to start or extend their family or become pregnant, especially in those who take disease-modifying therapies.
- 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 is usually manageable with specialist input
- Risk of the child developing MS is slightly higher than average (but overall risk is low)
References