Multiple sclerosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Multiple sclerosis creates focal inflammatory demyelination and more diffuse axonal injury within brain, optic nerves and spinal cord. Most people initially have relapsing-remitting disease, with attacks and periods of partial or complete recovery. Some later develop secondary progression, defined by accumulating disability independent of relapses. Primary progressive disease worsens from onset, although superimposed inflammatory activity may occur. Phenotype is reviewed over time rather than treated as a permanent label from the first consultation.

Diagnosis is made by a consultant neurologist or supervised specialist using the 2024 revised McDonald criteria, a compatible clinical context and objective evidence. The optic nerve now joins periventricular, cortical or juxtacortical, infratentorial and spinal-cord regions as a fifth anatomical location. In defined situations, central-vein sign, paramagnetic-rim lesions and cerebrospinal-fluid kappa free-light chains can add diagnostic evidence, and selected radiologically isolated presentations can fulfil criteria. Ageing, hypertension and migraine generate common MRI mimics, so a radiology phrase such as demyelination is not a diagnosis without lesion morphology, clinical concordance and exclusion of neuromyelitis optica spectrum disorder, MOG-associated disease, infection, nutritional deficiency, vasculitis and structural myelopathy.

Care has three simultaneous strands. Relapses require confirmation and proportionate corticosteroid treatment; long-term inflammatory risk may justify a disease-modifying therapy ranging from platform treatment to early high-efficacy therapy; and established symptoms require active rehabilitation and medicine review. Shared decisions should describe relative relapse and MRI benefits, uncertain individual disability benefit, infection and malignancy signals, infusion or tablet burden, rebound after stopping some agents and family-planning implications.

Key points

Multiple sclerosis is an immune-mediated inflammatory and neurodegenerative disorder diagnosed by a specialist using the 2024 revised McDonald criteria after reasonable alternatives are excluded; defined diagnostic routes do not always require the classic demonstration of dissemination in time.
Typical attacks include painful monocular optic neuritis, partial transverse myelitis, a brainstem syndrome such as internuclear ophthalmoplegia, and a cerebellar or sensory syndrome developing over hours to days.
A relapse is new or worsening neurological dysfunction lasting more than 24 hours without fever or infection, usually after at least a month of stability; transient heat-related worsening is a pseudo-relapse.
MRI brain and often cervical or thoracic spinal cord imaging demonstrate characteristic lesion distribution and new inflammatory activity, but non-specific white-matter spots from migraine or vascular disease do not diagnose multiple sclerosis.
Cerebrospinal-fluid-specific oligoclonal bands support intrathecal inflammation and can contribute to diagnostic criteria, while absence should prompt careful review rather than automatically exclude disease.
Atypical severe bilateral optic neuritis, longitudinally extensive myelitis, area-postrema symptoms, encephalopathy or marked systemic inflammation raises aquaporin-4, MOG-associated, infectious, vascular or systemic inflammatory alternatives.
Treat functionally significant relapse early with high-dose methylprednisolone after infection assessment; steroids shorten recovery but do not improve the long-term disability trajectory of that attack.
Disease-modifying therapy selection depends on inflammatory activity, prognostic features, pregnancy plans, comorbidity, infection risk, monitoring burden and patient preference, not on an examination score alone.
Symptom care addresses fatigue, spasticity, neuropathic pain, mobility, bladder and bowel dysfunction, cognition, mood, sexual health, sleep and work through coordinated multidisciplinary review.
Live vaccines, latent infection screening, immunoglobulins, blood counts and reproductive timing vary by disease-modifying medicine; use current NHS England, NICE and product-specific safety pathways.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Multifactorial immune susceptibility

MS arises from interacting genetic and environmental influences that permit an immune response against central nervous-system myelin and associated structures.

Polygenic risk

Many common immune-regulatory variants modestly alter susceptibility, while ordinary family history increases probability without determining that disease will occur.

Environmental modifiers

Prior infections, smoking, vitamin-related and geographical influences are associated with risk at population level, but no single exposure explains an individual's MS.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Blood–brain barrier entry
Activated immune cells cross into brain, optic nerve and spinal cord and recruit local inflammatory responses.
2
Demyelinating plaque formation
T cells, B cells, antibodies and macrophages injure oligodendrocytes, myelin and variable numbers of axons, producing focal lesions.
3
Conduction failure and relapse
Inflammation and demyelination slow or block impulses, causing neurological attacks that may improve as oedema resolves and conduction adapts.
4
Axonal loss and progression
Repeated inflammation and compartmentalised degeneration reduce neural reserve, leading to accumulating fixed disability independent of obvious relapses.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Optic neuritis

Subacute monocular visual loss with pain on eye movement, impaired colour saturation and a relative afferent pupillary defect is a common typical first demyelinating event.

Partial myelitis

Sensory disturbance, weakness, sphincter symptoms and a sensory level evolve over hours or days, often with an incomplete rather than complete transverse-cord syndrome.

Internuclear ophthalmoplegia

Impaired adduction of one eye with abducting nystagmus of the other localises to the medial longitudinal fasciculus and is particularly suggestive in a young adult.

Heat sensitivity

Old deficits transiently worsen during fever, exercise or a hot environment because conduction falters in demyelinated axons; this Uhthoff phenomenon is not automatically a relapse.

Severe acute syndromeRed flag

Rapid paraplegia, respiratory weakness, bilateral visual loss or disabling ataxia needs urgent admission and assessment for severe relapse and alternative inflammatory disease.

Progressive course

Gradual gait, spasticity or balance decline independent of discrete attacks suggests progressive disease but also requires assessment for deconditioning, compression and comorbidity.

Atypical inflammatory clue

Persistent vomiting or hiccups, longitudinally extensive cord disease, bilateral optic-disc swelling or poor recovery increases suspicion for aquaporin-4 or MOG antibody disease.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
MRI brain with multiple-sclerosis protocolFirst step
Why
Demonstrate characteristic lesion morphology, dissemination and active enhancement.
Interpretation and limitations
Ovoid periventricular, callosal, cortical or juxtacortical and infratentorial lesions support disease; central vein or other newer markers require specialist criteria and technique.
02
MRI cervical and thoracic spine
Why
Identify demyelinating cord lesions and exclude compressive or vascular myelopathy.
Interpretation and limitations
Multiple sclerosis lesions are commonly short and peripheral; a longitudinally extensive central lesion should prompt alternative antibody-mediated, vascular or infectious assessment.
03
Lumbar puncture with oligoclonal bands and, where available, kappa free-light chains
Why
Demonstrate intrathecal immunoglobulin synthesis using validated current criteria markers and test competing inflammatory or infectious disease.
Interpretation and limitations
Cerebrospinal-fluid-restricted oligoclonal bands or a validated positive kappa free-light-chain result can provide current-criteria evidence of intrathecal immunoglobulin synthesis; neither is specific, availability varies, and paired serum plus specialist interpretation remain essential.
04
Aquaporin-4 and MOG antibodies
Why
Investigate phenotypes atypical for ordinary multiple sclerosis before committing to treatment.
Interpretation and limitations
Use validated serum cell-based assays through specialists; low-titre or poorly timed results require expert interpretation because therapies and prognosis differ.
05
Mimic blood screen
Why
Exclude treatable nutritional, infectious, systemic inflammatory and metabolic disease selected from the presentation.
Interpretation and limitations
Common tests include blood count, B12, folate, thyroid, glucose and inflammatory markers, with HIV, syphilis, copper or autoimmune studies guided by phenotype rather than a universal panel.
06
Optical coherence tomography and visual evoked potentials
Why
Provide structural or physiological evidence of optic-pathway injury in selected diagnostic and monitoring questions.
Interpretation and limitations
Retinal nerve-fibre thinning or delayed conduction supports previous optic neuropathy but is not specific; ophthalmic disorders must be excluded.
07
Pre-treatment safety screening
Why
Define infection, immune, vaccination and organ risks before a disease-modifying therapy.
Interpretation and limitations
Requirements vary by agent and may include hepatitis, tuberculosis, varicella immunity, JC-virus status, immunoglobulins, blood count, liver tests, pregnancy testing and baseline MRI.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

NMOSD or MOG-associated disease

Severe bilateral optic neuritis, extensive myelitis or area-postrema symptoms favour antibody-associated disease with different relapse-prevention treatment.

Migraine or small-vessel imaging change

Non-specific white-matter spots without a characteristic clinical syndrome or lesion distribution do not establish MS by themselves.

Compressive or vascular myelopathy

Abrupt onset or mechanical compression on imaging favours infarction or structural cord disease over inflammatory relapse.

Nutritional, infectious or systemic inflammation

Vitamin B12 deficiency, infection, sarcoid and vasculitis can reproduce cord, optic or brain lesions and require targeted contextual testing.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Possible first eventConfirm a typical central syndromeFirst stepA person develops a new focal neurological deficit over hours or days.

1Localise the syndrome to optic nerve, brainstem, cerebellum or spinal cord, document objective signs and seek vascular, compressive, metabolic, infectious and antibody-mediated warning features.
2Arrange neurology review and protocol MRI of brain and relevant spine, adding cerebrospinal fluid and targeted mimic tests when criteria or phenotype require them.
3Avoid diagnosing multiple sclerosis from non-specific MRI spots or a symptom list alone; communicate diagnostic uncertainty and a concrete follow-up plan.

02Suspected relapseSeparate inflammation from pseudo-relapseEstablished multiple sclerosis is accompanied by new or clearly worsened neurological function.

1Record onset, duration, objective deficit and functional impact, then check fever, urinary or respiratory infection, heat exposure, sleep loss and metabolic disturbance.
2Discuss a disabling relapse promptly with the specialist team and offer high-dose methylprednisolone within the recommended window after contraindication and infection review.
3Provide rehabilitation and safety support, explaining that corticosteroids accelerate recovery but do not substitute for reviewing disease-modifying treatment after breakthrough activity.

03Long-term controlChoose disease-modifying therapy by risk and preferenceRelapsing inflammatory disease or active progressive disease meets current treatment criteria.

1Stratify relapse severity, MRI burden, spinal or brainstem involvement and recovery alongside age, comorbidity, infection, cancer and reproductive considerations.
2Compare eligible therapies using current NHS England algorithms, including route, monitoring, vaccine timing, rebound risk and whether early high efficacy fits the person's priorities.
3Establish baseline safety tests, contraception or pregnancy plan and a named specialist monitoring service before the first dose, then measure clinical and MRI activity longitudinally.

04Living with MSTreat symptoms and participationFatigue, spasticity, pain, bladder dysfunction, cognition or mood limits daily life.

1Identify reversible contributors such as infection, anaemia, sleep apnoea, depression, medicine sedation, constipation and poor mobility before adding symptom medicines.
2Coordinate specialist nursing, physiotherapy, occupational therapy, continence, neuropsychology, rehabilitation and vocational support around the person's goals.
3Review benefit and harm of each intervention, maintain bone and cardiovascular health and provide relapse, pregnancy, vaccination and emergency contact plans.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Speeds recovery from an inflammatory relapse but does not improve long-term disability outcome from that episode.

Methylprednisolone oral

NICE recommends 0.5 g orally once daily for 5 days for a functionally significant acute relapse, prescribed through an appropriate relapse pathway.

Exclude meaningful infection, discuss mood, sleep, glucose, gastrointestinal and bone risks, and never use lower-dose prolonged steroids as a substitute for this regimen.

Treats severe relapse where the oral pathway is inappropriate or specialist inpatient care is required.

Methylprednisolone intravenous

NICE advises considering 1 g intravenously once daily for 3 to 5 days when oral treatment fails, is not tolerated or admission and monitoring are needed.

Monitor glucose, blood pressure, psychiatric effects, infection and cardiac context; repeated courses should trigger disease-activity and cumulative-risk review.

First-line medicine option for troublesome multiple-sclerosis spasticity when goals are defined.

Baclofen

Start with a low oral dose and increase gradually using the current BNF and specialist spasticity plan, reducing for renal impairment and frailty.

Weakness, sedation and falls can outweigh reduced tone; abrupt withdrawal can cause severe rebound spasticity, delirium or seizures, especially after intrathecal exposure.

Reduces relapses and new MRI inflammatory activity, with some therapies used in eligible active progressive disease.

Disease-modifying therapy

Agent, loading, maintenance and monitoring schedules are selected by an MS specialist from current NICE technology appraisals and NHS England treatment algorithms.

Risks vary widely and include serious infection, malignancy signals, cytopenia, liver injury, cardiac effects, teratogenicity and rebound; agent-specific guidance must replace generic prescribing.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Mobility and spasticity disability

Cord and cerebellar injury causes weakness, stiffness, ataxia, falls and contracture, progressively restricting work and independence.

Visual and sensory impairment

Optic neuritis and central pathway lesions leave reduced vision, neuropathic pain, numbness and impaired proprioception between relapses.

Bladder, bowel and sexual dysfunction

Autonomic cord involvement causes urgency, retention, constipation and sexual difficulty with infection, renal and relationship consequences.

Fatigue, cognition and treatment risk

Fatigue, mood and cognitive change impair participation, while disease-modifying immunotherapy adds infection, malignancy, reproductive and monitoring burdens.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record relapses with date, objective deficit, recovery and steroid use, distinguishing them from infection-triggered fluctuation and gradual progression.
Use scheduled clinical review and protocol MRI to assess new inflammatory activity; do not change treatment from a single ambiguous symptom without correlation.
Follow the chosen disease-modifying agent's blood, liver, kidney, immunoglobulin, infection and cancer-surveillance plan with clear ownership for abnormal results.
Review mobility, falls, spasticity, fatigue, cognition, bladder, bowel, pain, mood, swallowing and work participation at least annually and after major change.
Revisit pregnancy intentions, contraception, breastfeeding, vaccines and infection exposure before treatment changes because washout and rebound risks differ between agents.
Monitor bone health, smoking, exercise, vitamin D sufficiency, cardiovascular risk and social isolation as part of whole-person care rather than attributing all health to MS.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

MRI must match syndrome

A few small subcortical spots in migraine do not equal dissemination; morphology, location and objective neurological history supply the diagnostic meaning.

Heat unmasks old damage

Uhthoff worsening resolves as temperature normalises and does not by itself indicate new inflammation or justify corticosteroids.

Steroids change speed

High-dose methylprednisolone can shorten a relapse but should not be presented as preventing future disability or replacing disease-modifying therapy.

Progression has competitors

Arthritis, deconditioning, medication, sleep disorder and spinal stenosis may worsen gait alongside progressive MS and remain treatable.

Stopping can be active risk

Some high-efficacy medicines carry rebound inflammatory activity after interruption, making pregnancy and switching plans as important as initiation.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing multiple sclerosis from non-specific MRI lesions alone.
02
Calling fever-related worsening a relapse and prescribing steroids immediately.
03
Missing aquaporin-4 or MOG-associated disease in an atypical severe syndrome.
04
Presenting corticosteroids as a treatment that prevents long-term progression.
05
Selecting disease-modifying therapy without pregnancy, vaccination and infection planning.
06
Ignoring bladder, cognition, mood, sexual function and vocational goals.
07
Stopping a disease-modifying agent abruptly without assessing rebound risk.