Multiple sclerosis

• Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which the immune system damages myelin and, over time, the nerve fibres underneath it.
• The typical patient is a young adult who develops episodes of focal neurological deficit, each lasting days to weeks and each followed by partial recovery.
• Diagnosis now rests on showing both that lesions are widespread in space and that they have occurred at more than one time, combined with cerebrospinal fluid (CSF) findings such as oligoclonal bands.
• Magnetic resonance imaging (MRI) is the single most important diagnostic test; CSF analysis supports it.
• An acute relapse that affects function is treated with high-dose methylprednisolone; long-term control means starting a disease-modifying therapy (DMT) early, guided by NICE NG220, the AAN 2018 guideline (reaffirmed 2024) and the ECTRIMS/EAN 2018 guideline.

By the end of this page you should be able to:

1. Define MS and list the recognised phenotypes and how they differ.
2. Explain how MS develops from an environmental trigger in a genetically susceptible person to a demyelinating plaque.
3. Recognise the common presentations in the patient's own words and the signs you should elicit.
4. Apply the 2017 McDonald criteria, including dissemination in space, dissemination in time and the oligoclonal band substitution.
5. Interpret the MRI and CSF findings that support or refute the diagnosis.
6. Treat an acute relapse with the correct steroid dose and route.
7. Choose, dose and monitor a disease-modifying therapy using the current guidelines.
8. Manage the common symptoms, complications and special situations, including pregnancy.

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS), that is the brain, spinal cord and optic nerves, in which inflammatory lesions destroy myelin and injure axons. It runs a relapsing or progressive course and produces neurological deficit that may partly or fully recover.

MS is the most common inflammatory disease of the CNS in young adults. It is not directly inherited in a simple way, but susceptibility is strongly influenced by genes, especially variants in the major histocompatibility complex (MHC) class II region, acting together with environmental factors.

MS is classified clinically into phenotypes defined by how the disease behaves over time. Understanding the phenotype matters, because it guides both prognosis and the choice of DMT.

The historical and still widely used phenotypes are four ^[3]:

• Clinically isolated syndrome (CIS): a single first episode of neurological symptoms caused by inflammatory demyelination, in someone not known to have MS who has not yet met the criterion of dissemination in time.
• Relapsing-remitting MS (RRMS): clearly defined attacks of new or worsening symptoms, followed by periods of partial or complete recovery and no progression between relapses.
• Secondary progressive MS (SPMS): an initial relapsing-remitting course followed by steady worsening of disability, with or without superimposed relapses.
• Primary progressive MS (PPMS): steady worsening from onset, usually without relapses or remissions.

A later refinement groups the same phenotypes into "active" or "not active" on the basis of clinical relapses, new or enlarging MRI lesions, or both. ^[3] Younger patients more often have relapses; older patients more often have progressive phenotypes. ^[3]

MS affects more than 2 million people worldwide and more than 900,000 people in the United States. ^[3] Women are affected about three times as often as men. ^[7] It is predominantly a disease of young adults; the most common presenting age is under 50. ^[1]

• Global pattern. Prevalence is highest in temperate zones and increases with latitude in both hemispheres, although migrants tend to keep the risk of the area where they spent childhood up to puberty.
• Survival. Prevalence is rising partly because people with MS now live longer with the disease.
• Ethnicity. MS occurs in all ethnic groups, but the risk varies; much of this variation is explained by the distribution of susceptibility genes and of environmental factors.

MS is not usually fatal within a short time, but it is a leading cause of non-traumatic disability in young adults.

Susceptibility is polygenic. The strongest and best replicated association is with the HLA-DRB1*15:01 allele, which is consistently enriched in people with MS. ^[7] Many additional loci outside the HLA region also contribute, but each adds only a small effect.

Environmental risk factors that are well established include ^[7]:

• Epstein-Barr virus (EBV) infection. EBV infects more than 90% of adults. The association with MS is remarkably strong: EBV is regarded as a necessary but not sufficient cause. Symptoms of primary EBV infection in adolescence (infectious mononucleosis) increase risk further. ^[7]
• Cigarette smoking. Active and passive smoking both increase susceptibility and speed disability progression; NICE NG220 advises people with MS not to smoke because it increases progression of disability. ^[1]
• Vitamin D and sunlight. Low vitamin D and low sun exposure in childhood and adolescence increase risk.
• Obesity in early life. A higher body mass index in childhood and adolescence is associated with increased risk.
• Latitude and childhood migration. The risk of the area lived in to puberty tends to persist after migration.

None of these factors causes MS on its own. The working model is that genetic susceptibility, an EBV-driven B-cell dysregulation, and one or more further environmental insults combine to produce the disease.

MS arises where a susceptible immune system loses tolerance to antigens of the central nervous system, most probably myelin proteins. The process appears to be driven by autoreactive T cells and by B cells.

1. Initiation. An environmental trigger, most plausibly EBV infection acting in a genetically susceptible person, activates autoreactive lymphocytes.
2. Trafficking into the CNS. Activated T and B cells cross the blood-brain barrier and enter perivascular and subpial spaces.
3. Demyelination. These cells and recruited macrophages and microglia attack myelin sheaths, producing an acute inflammatory plaque with relative axonal sparing at first.
4. Recovery and repair. Oligodendrocyte precursor cells remyelinate the lesion, sometimes producing a "shadow plaque"; this is why early deficits may recover.
5. Cumulative damage. Repeated relapses and chronic "smouldering" inflammation eventually exhaust remyelination and cause axonal loss, brain and spinal cord atrophy, and irreversible disability.
6. Progression. In progressive MS the emphasis shifts from focal relapses to diffuse chronic inflammation, microglial activation, oxidative injury, mitochondrial dysfunction and atrophy, rather than new focal lesions. ^[3]

Myelin is therefore both the early target and the early story: symptoms of a relapse map to the tract affected by a new plaque, and recovery maps to remyelination. The burden of silent lesions and atrophy is the later story, and explains why disability can worsen even when relapses have stopped.

Immune mechanisms involve mature B cells beyond their antibody production. Oligoclonal CSF-restricted immunoglobulin G (IgG), intrathecal antibody synthesis and complement deposition in MS lesions all implicate B cells, which is the rationale for the anti-CD20 DMTs. ^[3]

MS can present with surprisingly varied symptoms, because a plaque can form in almost any part of the CNS. The commonest are ^[1]:

• loss or reduction of vision in one eye, with painful eye movements (optic neuritis);
• double vision;
• ascending sensory disturbance or weakness;
• an electric shock sensation travelling down the back and into the limbs on bending the neck forward (Lhermitte's sign);
• progressive difficulties with balance and gait.

NICE NG220 advises clinicians to be alert when the person is often aged under 50 and may also have a history of previous neurological symptoms, symptoms that evolved over more than 24 hours, symptoms that persisted for several days or weeks and then improved, and no fever or infection. ^[1] Fatigue, depression, dizziness or vague sensory symptoms alone should not routinely raise suspicion of MS in the absence of a history or evidence of focal neurological signs. ^[1]

Symptom frequency reported in cohorts includes fatigue in about 60%, cognitive impairment in about 40% and depression in about 27% of people with MS. ^[3] Cognition and mood should therefore be part of every review.

Onset. Relapses typically last days to weeks and then improve over weeks to months. Symptoms may worsen with heat, exertion or fever (Uhthoff phenomenon) and with emotional stress.

Examination. Look for evidence of lesions distributed in more than one CNS site:

• Optic nerves: reduced visual acuity, a relative afferent pupillary defect, and a pale optic disc later.
• Brainstem and cerebellum: internuclear ophthalmoplegia, nystagmus, dysarthria and ataxia.
• Corticospinal tracts: weakness, hyperreflexia, clonus and extensor plantar responses, often asymmetric.
• Sensory pathways: altered vibration, proprioception, fine touch, sometimes a sensory level.
• Gait: ataxia, spasticity, and foot drop.
• Mood and cognition: slowed processing, impaired memory and executive function, depression, anxiety.

A vignette. A 28-year-old woman develops blurred vision in her left eye with pain on moving it. Six weeks later she recovers most of her sight, but two months after that she notices numbness from the waist down and mild unsteadiness on walking. Her MRI shows multiple periventricular and spinal cord lesions. This is the pattern that should make you think of MS: discrete episodes, in different parts of the CNS, in a young adult.

The same patient may look as if they have migraine, stroke, vitamin B12 deficiency, neurosyphilis, cervical spondylosis or a systemic inflammatory disease. The features that separate the common alternatives are set out below. ^[1] adds one procedural point: if a person has an isolated optic neuritis confirmed by an ophthalmologist, refer them to a consultant neurologist for further assessment.

NICE NG220 states that the diagnosis of neuromyelitis optica spectrum disorder should be made by an appropriate specialist using established up-to-date criteria. ^[1]

MRI is the most useful test in MS. It shows lesions that are often clinically silent and allows assessment of dissemination in space and time.

• Lesion characteristics (Jankowska criteria summary). MS-typical lesions are ovoid or round, at least 3 mm in the long axis, often perpendicular to the lateral ventricles (Dawson fingers), and located in characteristic areas: periventricular (abutting the ventricles), juxtacortical or cortical, infratentorial, and spinal cord. Gadolinium may produce open-ring or closed-ring enhancement while a lesion is active. ^[2]
• Dissemination in space (DIS). At least one T2 lesion in at least two of the four regions listed above. In the 2017 McDonald criteria symptomatic and asymptomatic lesions both count, and juxtacortical lesions include cortical lesions. ^[2]
• Dissemination in time (DIT). Either (i) a new T2 or gadolinium-enhancing lesion on a follow-up MRI compared with a baseline scan, regardless of when that follow-up was done, or (ii) simultaneous presence of gadolinium-enhancing and non-enhancing lesions. ^[2]
• Spinal cord MRI is valuable in diagnosis and in people with brown flags or atypical features; asymptomatic cord lesions are common in MS.
• Gadolinium should be used when the diagnosis is uncertain or when activity needs to be documented; repeated administration should be justified.

CSF supports the diagnosis and can substitute for proof of DIT under the 2017 McDonald criteria.

• Oligoclonal bands (OCB). The presence of at least two IgG bands, found in CSF but not in simultaneously drawn serum, detected by agarose isoelectric focusing with immunoblotting. ^[2]
• Frequency. OCB are found in about 95% of clinically definite MS and in 68 to 83% of CIS. ^[2]
• Specificity. OCB specificity in MS is about 94% against non-inflammatory CNS disease, falling to about 64% when other inflammatory CNS diseases are considered. ^[2]
• Intrathecal IgG synthesis and IgG index accompany OCB.
• Cell count. A mild lymphocytic pleocytosis is compatible with MS; atypical features should redirect the differential.
• Atypical CSF findings (marked pleocytosis, neutrophils, very high protein, low glucose, positive cultures or serology) point away from MS.

No blood test diagnoses MS. Tests are used to exclude mimics and to screen before treatment:

• Full blood count, renal and liver function, thyroid function, vitamin B12 (and methylmalonic acid if needed), HbA1c and lipids.
• Infections as clinically indicated: HIV, syphilis, hepatitis B and C, and others.
• Autoimmune serology where relevant (for example ANA, anti-AQP4, anti-MOG).
• Visual evoked potentials can demonstrate subclinical demyelination when MRI is equivocal, but are not routinely required.
• Pre-treatment: for DMTs as specified in product information (for example HIV/hepatitis screening, varicella immunity, pregnancy testing, anti-JCV antibody for natalizumab).

The 2017 revision of the McDonald criteria is the standard taught to students and still in everyday use, even though newer revisions exist. ^[1] NICE NG220 recommends that MS be diagnosed using the 2024 revised McDonald criteria (the recommendation in NG220 is dated 2022 and amended 2026); the 2017 version remains the version most exams and older literature quote. ^[1] The 2017 criteria improved sensitivity (83% versus 66%) at the cost of lower specificity (39% versus 60%) compared with the 2010 criteria, and allowed earlier diagnosis. ^[2]

The 2017 criteria are built on two concepts. ^[2]

• Dissemination in space (DIS). At least one T2 lesion in at least two of four areas: periventricular; juxtacortical or cortical; infratentorial; spinal cord. Symptomatic and asymptomatic lesions both count. A symptomatic brainstem or spinal cord lesion is not excluded, unlike in 2010.
• Dissemination in time (DIT). One of three:
  1. a new T2 and/or gadolinium-enhancing lesion on follow-up MRI compared with a previous scan, regardless of interval;
  2. simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any single time point;
  3. CSF-specific oligoclonal bands, in the absence of other CSF findings atypical of MS, in place of DIT.
• Clinical attack. An episode of objective signs of focal or multifocal CNS demyelination, lasting at least 24 hours and without symptoms of infection. ^[2]

A new qualification in 2017 is that the presence of OCB can substitute for DIT in a patient with a CIS who meets DIS. This qualification had the biggest impact on speed of diagnosis: median time to diagnosis fell from about 13 months under the 2010 criteria to about 3.2 months with OCB and 11.4 months without OCB. ^[2]

About one third of people with CIS do not develop further neurological dysfunction, which is why "definite MS" should not be diagnosed on the first attack alone unless DIS and a permitted form of DIT or OCB substitution are satisfied. ^[2]

• Expanded Disability Status Scale (EDSS). An ordinal scale from 0 (normal) to 10 (death from MS) used in trials and in clinic. It is insensitive to fatigue and cognition and should not be the only outcome measure.
• MS Functional Composite and patient-reported outcomes capture walking speed, dexterity and cognition and are increasingly used alongside EDSS.

The principles are to treat relapses that affect the person's ability to carry out usual tasks, as early as possible, and to avoid treating minor deficits that would recover anyway.

NICE NG220 defines a relapse as new or worsening symptoms lasting more than 24 hours, in the absence of infection or any other cause, after a stable period of at least one month, and advises not to routinely diagnose a relapse if symptoms persist for more than 3 months. ^[1]

• Assess promptly, and offer treatment within 14 days of symptom onset. ^[1]
• Treatment. Offer oral methylprednisolone 0.5 g daily for 5 days. ^[1]
• Alternative. Consider intravenous methylprednisolone 1 g daily for 3 to 5 days when oral steroids have failed or are not tolerated, or when the person needs admission to hospital for a severe relapse or monitoring of conditions such as diabetes or depression. ^[1]
• Dose floor. Do not prescribe steroids at lower doses than methylprednisolone 0.5 g daily for 5 days to treat an acute relapse. ^[1]
• No maintenance steroid. Single courses do not alter the long-term course; maintenance oral steroids are not recommended.
• Plasma exchange is not routine for MS relapse but may be considered for severe steroid-refractory attacks in specialist centres.

The central concept of modern MS care is "treat to target": start a DMT early in anyone with relapsing disease, monitor for disease activity, and switch if activity continues.

Guideline landscape.

• NICE NG220 (published 2022, DMT section updated with technology appraisals to 2026) recommends, for active relapsing-remitting MS: cladribine, ublituximab, diroximel fumarate, ponesimod, ofatumumab, peginterferon beta-1a, ocrelizumab, glatiramer acetate, interferon beta-1a, interferon beta-1b (Extavia) and dimethyl fumarate; teriflunomide is included in the same technology appraisal list. NICE recommends interferon beta-1b (Betaferon) is not recommended for relapsing-remitting MS, and ozanimod is not recommended for active relapsing-remitting MS. For highly active disease on treatment, NICE lists natalizumab (subcutaneous originator and intravenous biosimilar), ublituximab, cladribine, alemtuzumab, ponesimod, ofatumumab, ocrelizumab and fingolimod. ^[1]
• AAN 2018 guideline (reaffirmed 2024). Thirty recommendations were developed: 17 on starting, 10 on switching and 3 on stopping DMTs. They cover counselling about therapy, individualisation by safety and route, annual or REMS-based monitoring, and discontinuation rules. ^[6]
• ECTRIMS/EAN 2018 guideline. Developed with GRADE, from ten PICO questions, taking into account all EMA-approved DMTs at publication, yielding 21 recommendations after three rounds of consensus. ^[5] One commentary on it counts 23 recommendations when consensus statements are included. ^[4]

Dosing of the commonly used DMTs ^[3].

Many DMTs are now available. Non-oral agents require infection screening, vaccination review and (for natalizumab) anti-JCV antibody monitoring throughout treatment. ^[6]

DMT advice from the guidelines in summary:

• Start early rather than late in relapsing disease; counselling should cover risks, benefits, route, adherence and cost. ^[6]
• Treat highly active MS with high-efficacy agents (fingolimod, natalizumab, alemtuzumab, ocrelizumab). ^[6]
• Mitoxantrone should not be used unless the benefit greatly outweighs the risks, because of serious adverse effects. ^[6]
• Switch on breakthrough activity if, over about a year on an effective DMT, there are one or more relapses, two or more unequivocally new MRI-detected lesions, or increased disability, after checking adherence and confounders. ^[6]
• Monitor MRI disease activity from clinical onset. ^[6]
• Switch to lower progressive multifocal leukoencephalopathy (PML) risk agents in JCV-antibody-positive patients on natalizumab, especially when the anti-JCV antibody index is high. ^[6]
• Stopping DMT is reasonable in people with secondary progressive MS who have no relapses or gadolinium-enhancing lesions and who have been non-ambulatory long term, and should always be followed by periodic re-evaluation. ^[6]
• Counsel women about reproductive plans and birth control while on DMT; stop DMT before conception for planned pregnancies unless the risk of MS activity outweighs the risk of the specific drug. ^[6]

Long-term quality of life depends on treating the symptoms and impairments that relapses and progression leave behind.

• Fatigue. MS-related fatigue may be brought on by heat and by biological, physical and emotional stress; sleep disturbance, pain, spasticity, bladder dysfunction, drug side effects, infections, anaemia, thyroid dysfunction, anxiety and depression are common mimics and should be excluded before treating. ^[1] For people with moderately impaired mobility (EDSS score of 4 or more), consider a combination of supervised aerobic and moderate progressive resistance activity with cognitive behavioural techniques. ^[1]
• Spasticity. Oral baclofen is a first-line treatment; gabapentin is a second-line option if baclofen is not tolerated or does not provide adequate relief. ^[1]
• Walking difficulty. Dalfampridine (fampridine) may improve walking speed in selected patients; review response after a short trial.
• Bladder and bowel dysfunction. Assess regularly; anticholinergics or beta-3 agonists for detrusor overactivity, intermittent self-catheterisation for incomplete emptying, and a bowel programme for constipation.
• Pain. Consider neuropathic pain agents such as gabapentin, pregabalin, amitriptyline and (in some centres) carbamazepine depending on the syndrome.
• Cognition. Cognitive rehabilitation and treatment of mood disorders; cholinesterase inhibitors have inconsistent evidence.
• Depression and anxiety. Screen routinely; treat with antidepressants and psychological therapy; remember that fatigue and depression overlap.
• Annual review. All people with MS should have a comprehensive review of all aspects of care at least once a year, including monitoring for disease activity. ^[1]

• Smoking cessation. Advise all patients not to smoke. ^[1]
• Exercise and physiotherapy. Maintain mobility, strength and balance; fatigue management and energy conservation.
• Occupational therapy and assistive devices for hand function and home adaptation.
• Heat management: cooling strategies, avoiding hot baths, keeping hydrated.
• Diet: no specific diet is proven; a balanced diet and weight management are sensible.
• Vaccination: keep routine vaccines up to date; give inactivated vaccines when appropriate and avoid live vaccines in patients on significant immunosuppression; influenza and (where indicated) pneumococcal and hepatitis B vaccination before starting DMT.
• Follow-up: coordinate between neurology, primary care, rehabilitation and MS specialist nurses.

Pregnancy. Pregnancy does not increase the risk of disease progression; relapses may decrease during pregnancy and may increase 3 to 6 months after childbirth before returning to pre-pregnancy rates. ^[1] DMT use is guided by the agent's reproductive risk. ^[3]:

• Interferons: no increased risk with early exposure; discontinue during pregnancy unless there is evidence of active disease. ^[3]
• Glatiramer acetate: no increased risk with early exposure; can be continued during pregnancy. ^[3]
• Fumaric acid derivatives: discontinue when attempting pregnancy or at a positive pregnancy test; not for use during pregnancy. ^[3]
• Teriflunomide: teratogenic black-box warning; serum level should be below 0.02 mg per litre before attempting conception for women and for men. ^[3]
• S1P receptor modulators (fingolimod, siponimod, ozanimod, ponesimod): risk of congenital malformations; discontinue fingolimod at least 2 months before, siponimod at least 10 days, ozanimod at least 3 months and ponesimod at least 7 days before attempting pregnancy. Consider bridging therapy because discontinuation increases relapse risk. ^[3]
• Cladribine: genotoxicity black-box warning; last dose at least 6 months before attempting pregnancy. ^[3]
• Mitoxantrone: teratogenic black-box warning. ^[3]
• Breastfeeding: most DMTs are not recommended during breastfeeding; decisions need specialist input.

Children. MS can begin before puberty but is rare; pediatric-onset MS tends to be more inflammatory and less degenerative at first, with slower accumulation of disability. DMT choices, dosing and monitoring differ from adults and need a paediatric neurology service.

Older adults. Comorbidities, polypharmacy, infection risk and the rising risk of PML on agents such as natalizumab matter more. Evidence for DMTs above age 55 to 60 is limited; stopping or de-escalating should be considered when disease activity has been absent for years, with follow-up.

Immunocompromised patients. Active or chronic infections, including hepatitis B and C and tuberculosis, need treatment before high-efficacy DMTs; lymphocyte counts and vaccination status should be reviewed.

• MRI may be limited. Where unavailable, the diagnosis rests on a compatible clinical course, CSF oligoclonal bands and, if available, evoked potentials.
• Steroids for acute relapse: oral methylprednisolone 0.5 g daily for 5 days is cheap and effective; reserve intravenous regimens for those who cannot take oral treatment. ^[1]
• DMTs may be unavailable or unaffordable; where licensed agents are inaccessible, the AAN 2018 guideline advises considering azathioprine or cladribine for relapsing disease. ^[6]
• Rehabilitation, physiotherapy and bladder care deliver most day-to-day benefit and can be organised locally.
• Referral. Refer for diagnosis and for initiation of high-efficacy therapy; once stable, most follow-up can be shared with primary care.

• Disability and immobility: contractures, pressure injuries, deep vein thrombosis and falls.
• Bladder, bowel and sexual dysfunction, with recurrent urinary tract infection.
• Cognitive change, fatigue and depression, which may be more disabling than motor deficits.
• Chronic pain, including trigeminal neuralgia and pain from spasticity.
• Treatment-related: PML with natalizumab, fingolimod, dimethyl fumarate, ocrelizumab and rituximab (rare); hepatotoxicity and teratogenicity with specific agents; opportunistic infection.
• Prognosis-related: transition from relapsing to secondary progressive disease in a substantial proportion over time if untreated.

MS has a highly variable course. Around one third of people with CIS never develop further neurological dysfunction. ^[2] In those who do convert to MS, the rate of relapse tends to fall and the risk of progression rises with age. Brain and spinal cord atrophy correlate with disability. Early effective treatment and avoidance of smoking improve long-term outcome.

There is no population screening test and no primary prevention of MS. Modifiable actions with evidence behind them:

• Avoid smoking, including passive exposure. ^[1]
• Maintain adequate vitamin D through safe sun exposure and supplementation where appropriate, especially in high-risk groups.
• Manage childhood and adolescent obesity.
• Treat and monitor infection and EBV-related health in the general sense (no specific anti-EBV intervention is established for MS prevention).
• Start DMT promptly once the diagnosis is made.

The table in the Differential diagnosis section sets out the separating features. Two conditions deserve an explicit contrast because they are frequently confused in examinations.

• MS versus Guillain-Barre syndrome. MS is a CNS disease: pyramidal signs, a sensory level, painless optic neuritis and asymmetric deficits are expected, and MRI shows brain or spinal cord lesions. Guillain-Barre syndrome is a peripheral neuropathy: flaccid, areflexic weakness, often ascending and symmetric, with albuminocytological dissociation in the CSF and no CNS lesions on MRI. ^[1]
• MS versus neuromyelitis optica spectrum disorder. Both affect optic nerves and spinal cord; NMOSD causes more severe, often bilateral optic neuritis and longitudinally extensive cord lesions, is associated with AQP4 (or MOG) antibodies, and follows a relapsing course that is not helped by MS DMTs. ^[1]

• MS is a chronic inflammatory disease of the CNS that begins most often in young adults and is about three times as common in women as in men.
• The phenotypes CIS, RRMS, PPMS and SPMS, further described as active or not active, determine both prognosis and treatment.
• Susceptibility combines polygenic risk (HLA-DRB1*15:01) with environmental factors: EBV (a necessary but not sufficient cause), smoking, low vitamin D and obesity.
• Symptoms are episodes in discrete CNS tracts with partial recovery; absence of fever and age under 50 help distinguish MS from infection.
• Diagnosis requires demonstration of dissemination in space and time; CSF-specific oligoclonal bands can substitute for dissemination in time under the 2017 McDonald criteria.
• MS-typical MRI lesions are at least 3 mm and occur in periventricular, juxtacortical or cortical, infratentorial and spinal cord regions.
• Oligoclonal bands are present in about 95% of clinically definite MS and in 68 to 83% of CIS.
• Acute relapses affecting function are treated with methylprednisolone 0.5 g by mouth daily for 5 days, or 1 g intravenously daily for 3 to 5 days when oral treatment fails or hospital care is needed.
• Early DMT is the cornerstone of care; several agents exist, with high-efficacy agents reserved for active disease.
• NICE NG220, the AAN 2018 guideline (reaffirmed 2024) and the ECTRIMS/EAN 2018 guideline are the named sources.
• Stopping DMT is considered only in long-stable secondary progressive disease without activity.
• Pregnancy does not worsen long-term progression; relapses may fall in pregnancy and rise 3 to 6 months after delivery.

Plain-text links only: optic neuritis, acute myelitis, neuroinflammatory disease, Guillain-Barre syndrome, Lambert-Eaton myasthenic syndrome, chronic inflammatory demyelinating polyneuropathy.