Multiple sclerosis
Exam Tips
- A true relapse is new/worsening neurological deficit lasting >24 hours, separated by at least 30 days from prior relapse, and not explained by fever/infection (pseudo-relapse).
- Use McDonald principles: demonstrate dissemination in space and time clinically/MRI; CSF oligoclonal bands can substitute for dissemination in time in appropriate contexts.
- Common OSCE stem: painful monocular visual loss in a young woman plus RAPD suggests optic neuritis in demyelinating disease.
- Differentiate UMN signs (spasticity, brisk reflexes, extensor plantars) from peripheral neuropathy signs when localising lesions.
- In management stations, mention steroid dosing for disabling relapse and explicitly state that steroids shorten relapse duration but do not modify long-term prognosis.
- Safety marks: screen for infection before relapse steroids and before DMT initiation; include pregnancy/contraception counselling for teratogenic or fetotoxic agents.
Definition
Multiple sclerosis is a chronic immune-mediated inflammatory disease of the central nervous system (brain, optic nerves, and spinal cord) characterized by demyelination, gliosis, and neuroaxonal injury. It typically begins in early adult life and causes neurological episodes separated in time and anatomical site, with patterns of relapsing-remitting disease, secondary progression, or primary progressive decline.
Pathophysiology
In genetically susceptible people, environmental triggers (notably prior EBV exposure, smoking, and low vitamin D states) are thought to provoke dysregulated adaptive immunity. Autoreactive T cells and B-cell-driven inflammation cross the blood-brain barrier, damaging oligodendrocytes and myelin; acute plaques may partially remyelinate, but repeated inflammation leads to incomplete repair, axonal transection, and progressive neurodegeneration. This explains dissemination in time and space clinically, and the transition from inflammatory relapses to disability accumulation in progressive phenotypes. MRI classically shows periventricular, juxtacortical/cortical, infratentorial, and spinal cord lesions (e. g, Dawson-finger pattern; see standard neuroimaging teaching figure of periventricular ovoid plaques).
Risk Factors
- Female sex (approximately 2-3:1 female predominance)
- Family history/genetic susceptibility (including HLA-region risk variants)
- Previous Epstein-Barr virus infection/mononucleosis
- Low vitamin D exposure and higher latitude residence
- Cigarette smoking (dose-related risk; may worsen disease course)
- Obesity in childhood/adolescence
Clinical Features
Symptoms
- Subacute unilateral visual loss with painful eye movement (optic neuritis)
- Diplopia or oscillopsia
- Sensory disturbance (numbness, paraesthesia, dysaesthesia), often ascending
- Limb weakness and fatigability
- Gait imbalance, clumsiness, vertigo, or ataxia
- Lhermitte phenomenon (electric-shock sensation down spine on neck flexion)
- Urinary urgency/frequency/nocturia/urge incontinence; bowel dysfunction
- Sexual dysfunction
- Neuropathic pain (including trigeminal neuralgia) and severe fatigue
- Cognitive slowing, low mood, anxiety, emotional lability
Signs
- Relative afferent pupillary defect and reduced visual acuity/colour vision
- Internuclear ophthalmoplegia, nystagmus, or other brainstem ocular motor signs
- Pyramidal signs: spasticity, hyperreflexia, extensor plantar responses
- Cerebellar signs: intention tremor, dysmetria, dysdiadochokinesis, broad-based gait
- Objective sensory level or dorsal column loss (vibration/proprioception)
- Gait disturbance with mixed pyramidal-cerebellar pattern
Investigations
Management
Lifestyle Modifications
- Specialist MS multidisciplinary care (neurology, MS nurse, physiotherapy, OT, continence, psychology)
- Smoking cessation, regular graded exercise, weight management, sleep and fatigue pacing strategies
- Vaccination review before immunosuppressive DMTs; avoid live vaccines during/after some therapies
- Relapse trigger review (infection, postpartum period, stress) and prompt treatment of intercurrent infection
- Discuss pregnancy planning, contraception, and postpartum relapse risk
Pharmacological Treatment
Acute relapse treatment (when relapse significantly affects function)
- Methylprednisolone 500 mg orally once daily for 5 days
- Alternative: methylprednisolone 1 g IV once daily for 3-5 days in severe relapse or if oral not suitable
Exclude pseudo-relapse from infection (especially UTI) before steroids. Steroids shorten relapse duration but do not change long-term disability trajectory. Use caution in diabetes, active peptic ulcer disease, severe hypertension, psychosis risk, and osteoporosis; counsel on mood change, insomnia, hyperglycaemia, and infection risk.
Disease-modifying therapy for relapsing disease (specialist initiation)
- Interferon beta-1a 30 micrograms IM weekly (or 44 micrograms SC three times weekly, preparation dependent)
- Glatiramer acetate 20 mg SC daily (or 40 mg SC three times weekly)
- Dimethyl fumarate 240 mg orally twice daily (after titration)
- Teriflunomide 14 mg orally once daily
- Fingolimod 0.5 mg orally once daily
- Natalizumab 300 mg IV every 4 weeks
- Ocrelizumab 600 mg IV every 6 months (after initial split dosing)
- Ofatumumab 20 mg SC monthly after loading doses
- Cladribine tablets cumulative 3.5 mg/kg over 2 years (specialist cycle regimen)
- Alemtuzumab 12 mg IV daily for 5 days, then 12 mg IV daily for 3 days 12 months later
Choice is phenotype/risk based and follows UK commissioning criteria. Safety-critical checks include baseline and ongoing FBC, LFTs, U&Es, infection screening (HBV/HCV/HIV/TB/JCV where relevant), MRI surveillance, and pregnancy counselling. Key warnings: teriflunomide is teratogenic; fingolimod causes first-dose bradycardia and is contraindicated in pregnancy; natalizumab carries PML risk (higher with JCV positivity and longer exposure); anti-CD20 therapies increase infection risk and require immunisation planning.
Symptom control
- Baclofen initially 5 mg three times daily, titrate (usual max 100 mg/day) for spasticity
- Gabapentin initially 300 mg at night then titrate for neuropathic pain
- Amitriptyline 10-25 mg at night, titrate for neuropathic pain/sleep
- Oxybutynin 2.5-5 mg two to three times daily for overactive bladder symptoms
Tailor to dominant symptom burden and adverse-effect profile. Anticholinergics can worsen cognition, dry mouth, and constipation; baclofen can cause weakness/sedation; gabapentinoids increase dizziness/somnolence and fall risk.
Complications
- Progressive physical disability and gait impairment
- Severe fatigue and reduced participation in work/social roles
- Spasticity with painful spasms, contractures, and immobility complications
- Visual morbidity (optic neuritis sequelae, diplopia, nystagmus-related oscillopsia)
- Bladder dysfunction with recurrent urinary infections
- Neuropathic and musculoskeletal pain syndromes
- Depression, anxiety, emotional lability, and cognitive impairment
- Sexual dysfunction and relationship impact
Prognosis
There is no current cure, and long-term outcome is heterogeneous. Most people initially have relapsing-remitting disease, with many later developing secondary progression over 10-20 years; primary progressive disease tends to accumulate disability faster. Poorer prognostic markers include older age at onset, male sex, multifocal/pyramidal-cerebellar onset, high early relapse burden, incomplete relapse recovery, and higher MRI lesion load. Early diagnosis and timely DMT use reduce relapse activity and can delay disability progression.
Sources & References
🏥BMJ Best Practice(4)
✅NICE Guidelines(1)
- Multiple sclerosis[overview]