Multiple Sclerosis
Summary
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterised by episodes of neurological dysfunction disseminated in time and space. It is the most common cause of non-traumatic disability in young adults. The disease course is classified as relapsing-remitting (RRMS, 85%), secondary progressive (SPMS), primary progressive (PPMS), or progressive-relapsing. Diagnosis relies on the McDonald criteria (clinical + MRI evidence of dissemination in time and space). Acute relapses are treated with IV methylprednisolone. Disease-modifying therapies (DMTs) reduce relapse frequency and disability accumulation. Early treatment with highly effective therapies is increasingly favoured.
Key Facts
- Definition: Inflammatory demyelinating CNS disease disseminated in time and space
- Prevalence: 100-300 per 100,000 (higher in northern latitudes)
- Age of Onset: 20-40 years (peak ~30)
- Types: RRMS (85%), SPMS, PPMS (10-15%)
- Relapse Treatment: IV methylprednisolone 1g x 3-5 days
- DMTs: Reduce relapse rate by 30-70%
- Goal: Prevent disability accumulation (NEDA — No Evidence of Disease Activity)
Clinical Pearls
"Time + Space": MS diagnosis requires evidence of CNS lesions disseminated in both time (different episodes) and space (different anatomical regions).
"Treat Early, Treat Effectively": Early initiation of highly effective DMTs may prevent long-term disability better than starting with less effective therapies.
"Not All Relapses Need Steroids": Mild sensory relapses may be observed. Steroids shorten relapse duration but don't affect long-term outcome.
Why This Matters Clinically
MS is the most common cause of non-traumatic neurological disability in young adults. Early diagnosis and treatment can prevent irreversible disability. Modern DMTs have transformed outcomes — many patients now have minimal disability.
Prevalence
| Region | Prevalence |
|---|---|
| Northern Europe, Canada | 100-300 per 100,000 |
| UK | ~130,000 people |
| Global | 2.8 million |
Demographics
| Factor | Details |
|---|---|
| Age of Onset | 20-40 years (peak ~30) |
| Sex | Female:Male 3:1 (RRMS); 1:1 (PPMS) |
| Latitude | Higher prevalence at higher latitudes |
Risk Factors
| Factor | Details |
|---|---|
| Genetics | HLA-DRB1*15:01; 25-30% concordance in monozygotic twins |
| Vitamin D Deficiency | Associated with higher risk |
| EBV Infection | Strong association (near universal in MS) |
| Smoking | Increases risk and progression |
| Obesity (adolescent) | Increases risk |
Immune-Mediated Demyelination
Step 1: Peripheral Activation
- Autoreactive T-cells activated in periphery
- Cross blood-brain barrier
Step 2: CNS Inflammation
- T-cells, B-cells, macrophages attack myelin
- Inflammatory demyelination
- Axonal damage
Step 3: Repair and Scarring
- Partial remyelination
- Glial scar (sclerosis)
Step 4: Neurodegeneration
- Axonal loss
- Brain atrophy
- Progressive disability
Relapse vs Progression
| Relapse | Progression |
|---|---|
| Focal inflammation | Diffuse neurodegeneration |
| Gadolinium enhancement | Brain/spinal atrophy |
| Responds to steroids/DMTs | Less responsive to DMTs |
Common Presentations
| Syndrome | Features |
|---|---|
| Optic Neuritis | Unilateral visual loss, eye pain, RAPD |
| Transverse Myelitis | Weakness, sensory level, bladder dysfunction |
| Brainstem | Diplopia, INO, vertigo |
| Cerebellar | Ataxia, intention tremor |
| Sensory | Paraesthesia, numbness |
Characteristic Phenomena
| Phenomenon | Description |
|---|---|
| Lhermitte's | Electric shock down spine on neck flexion |
| Uhthoff's | Symptoms worsen with heat |
Red Flags
[!CAUTION] Red Flags:
- Optic neuritis (visual loss)
- Transverse myelitis (weakness, bladder)
- Rapid progression
- New neurological deficit in known MS
Neurological Examination
| Domain | Findings |
|---|---|
| Vision | Reduced acuity, colour desaturation, RAPD |
| Eye Movements | INO, nystagmus |
| Motor | UMN pattern weakness, hyperreflexia, spasticity |
| Sensory | Sensory level, dorsal column signs |
| Cerebellar | Ataxia, intention tremor, dysarthria |
| Bladder | Urgency, retention |
First-Line
| Test | Purpose |
|---|---|
| MRI Brain + Spine | Dissemination in space/time |
| Lumbar Puncture | OCBs, IgG index |
| VEPs | Subclinical optic neuritis |
| Bloods | Vitamin B12, HIV, syphilis, NMO-IgG, MOG-IgG |
MRI Findings
- T2/FLAIR hyperintense lesions
- Periventricular "Dawson's fingers"
- Gadolinium enhancement (active)
- Spinal cord lesions
Acute Relapse
- IV Methylprednisolone 1g x 3-5 days
- Plasma exchange if severe/refractory
Disease-Modifying Therapy
| Efficacy | Options |
|---|---|
| Moderate | Interferons, Glatiramer, Teriflunomide, DMF |
| High | Natalizumab, Ocrelizumab, Ofatumumab, Cladribine |
| Very High | Alemtuzumab, HSCT |
Symptomatic
- Fatigue: Amantadine, modafinil
- Spasticity: Baclofen, tizanidine
- Bladder: Anticholinergics, ISC
- Pain: Gabapentin, amitriptyline
| Complication | Notes |
|---|---|
| Disability | EDSS progression |
| Bladder Dysfunction | UTIs, catheterisation |
| Falls | Mobility impairment |
| Cognitive Impairment | 50% affected |
| Depression | 50% lifetime prevalence |
| DMT Side Effects | PML (natalizumab), infections |
Natural History
| Variable | Notes |
|---|---|
| RRMS → SPMS | ~50% by 15-20 years (less with DMTs) |
| Disability | Variable; DMTs improve outcomes |
| Life Expectancy | Reduced by 7-10 years |
Prognostic Factors
| Good | Poor |
|---|---|
| Female | Male |
| Younger onset | Older onset |
| Sensory/optic presentation | Motor/cerebellar presentation |
| Complete recovery from relapses | Incomplete recovery |
| Low lesion burden | High lesion burden |
Key Guidelines
-
NICE NG220: Multiple sclerosis (2022)
-
ABN Guidelines for DMT Prescribing (2021)
Landmark Trials
CLARITY (2010) — Cladribine
- Key finding: Reduced relapses by 58% vs placebo
ORATORIO (2017) — Ocrelizumab for PPMS
- Key finding: First DMT to show benefit in PPMS
What is MS?
Multiple sclerosis is a condition where your immune system mistakenly attacks the protective covering of nerves (myelin) in your brain and spinal cord. This causes communication problems between your brain and body.
What are the symptoms?
- Vision problems (blurred or double vision)
- Numbness or tingling
- Weakness in legs or arms
- Difficulty with balance and walking
- Fatigue
- Bladder problems
How is it treated?
- Relapse treatment: High-dose steroids to speed recovery
- Disease-modifying drugs: Reduce relapses and slow progression
- Symptom management: Medications and therapy for specific symptoms
What to expect
- Most people start with relapsing-remitting MS
- Modern treatments have improved outcomes significantly
- Many people with MS live full, active lives
Primary Guidelines
- National Institute for Health and Care Excellence. Multiple sclerosis in adults: management (NG220). 2022. nice.org.uk/guidance/ng220
Key Studies
- Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. PMID: 29275977
Further Resources
- MS Society: mssociety.org.uk
- MS Trust: mstrust.org.uk
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances.