Multiple sclerosis: an animated, cited guide

This page needs JavaScript for its animations. The outline and key answers are below, and every claim in the full version carries a numbered citation.

Not medical advice. MS Companion is an educational synthesis of published literature. It does not replace a clinician.

What is in it

What MS is Who gets it, the numbers, and where in the nervous system it strikes.
Myelin and demyelination How signals jump along a myelinated nerve fibre, and what a lesion does to them.
The immune attack T cells, B cells and the blood-brain barrier, step by step.
Genes and risk factors HLA-DRB1*15:01, Epstein-Barr virus, vitamin D, smoking and teenage obesity.
Relapse and remission over time Relapsing, secondary progressive and primary progressive MS on one timeline.
A relapse, week by week Onset, steroids and recovery, and how a pseudo-relapse differs.
Measuring disability: EDSS The 0 to 10 scale and what confirmed worsening means.
McDonald criteria calculator Dissemination in space and time, CSF, and the 2017 and 2024 rules.
The differential NMOSD, MOGAD and other conditions that look like MS.
How the drugs work Where each disease-modifying therapy acts.
The DMT ladder Escalation, early high-efficacy treatment and stopping in later life.
Safety and monitoring PML and the JCV index, infections, vaccines and rebound.
Toward a cure Remyelination, BTK inhibitors, stem-cell transplantation and EBV.
Symptoms and rehabilitation Fatigue, spasticity, bladder, walking, mood and cognition.
Living with MS Pregnancy, work, heat, exercise and planning.
Nursing care Assessment, giving the medicines, monitoring and teaching.
History and people From Carswell and Charcot to the 2024 criteria.
Flashcards, quiz and glossary Revision for students.
Sources Every reference behind the app.

Part 3 · Diagnosis

McDonald criteria calculator

Place MS-type lesions on a schematic brain, spinal cord and optic nerves, add CSF and other results, then watch the 2017 or 2024 McDonald criteria build a verdict step by step.

A learning aid, not a diagnosis. It applies the published rules to the boxes you tick. It cannot diagnose anyone. The last step, "no better explanation", always needs a clinician's judgement after a full workup, so a positive result here reads "criteria met (if no better explanation)". Rules: Thompson et al., Lancet Neurol 2018;17(2):162-173 ⁴⁶² and Montalban et al., Lancet Neurol 2025;24(10):850-865 ³²⁵. The 2024 paper was paywalled to our research, so its Figures 2 and 3 were read from the official IACCTMS slide deck that reproduces them.

Criteria

Load a case

Steps

Lesion details for

gold ring: enhances with gadolinium (Gd+)dashed ring: new on the follow-up scandark line through a lesion: central vein signdark edge: paramagnetic rim

Schematic composite, not to scale and not a real scan. Abbreviations in the steps: PV periventricular, JC cortical/juxtacortical, IT infratentorial, SC spinal cord, ON optic nerve, WM white matter. Deep white-matter lesions are drawn because many people have them, but they are not a DIS site.

Everything else the criteria ask about

Clinical picture

Attacks

Objective clinical evidence of

Clear-cut historical evidence of an earlier attack in a different place (2017 table, row 2; 2024 counts it as clinical dissemination in space) A later attack implicated a different CNS site (clinical dissemination in space)

An attack means symptoms with corroborating objective findings, lasting at least 24 hours, without fever or infection ⁴⁴³. Accepting attacks without objective evidence was a leading cause of misdiagnosis ⁴⁴¹.

At least 12 months of disability progression from onset, independent of relapses

Cerebrospinal fluid 2 or more CSF-restricted oligoclonal bands (OCB) κ-FLC index

κ-FLC index = (CSF κ-FLC ÷ serum κ-FLC) ÷ (CSF albumin ÷ serum albumin). Positive CSF in 2024 means OCB or an index ≥6.1; each laboratory should verify that cut-off ^114,254. The 2017 criteria use OCB only ⁴⁶².

Optic nerve evidence (2024) OCT inter-eye difference, pRNFL (μm) OCT inter-eye difference, GCIPL (μm) Abnormal full-field VEP: P100 delayed or a significant difference between the eyes

With rigorous quality control, an inter-eye difference of ≥6 μm in peripapillary RNFL or ≥4 μm in GCIPL supports optic nerve involvement; an MRI optic nerve lesion also counts (place it on the map). Any of these needs no better explanation for the optic nerve finding ^218,416.

Susceptibility MRI (2024)

Set "with central vein sign" and "with paramagnetic rim" per site in the lesion details above. Select-6: at least 6 white-matter lesions with a central vein or, if fewer than 10 white-matter lesions are seen, more CVS-positive than CVS-negative lesions. PRL: at least 1 paramagnetic rim lesion ^325,418,443. The official slide deck is internally inconsistent here: one slide applies the majority rule below 6 lesions and another below 10. The published figure says fewer than 10, which this calculator uses ²¹⁸.

The person

Age

Significant vascular risk (high blood pressure, smoking, diabetes, high lipids), known vascular disease, or a headache disorder such as migraine A child whose first event was ADEM (acute disseminated encephalomyelitis)

Step 4 · No better explanation A better explanation is present, or the workup has not excluded one

"No better explanation" means the presentation is typical of MS and nothing clinical or paraclinical suggests another diagnosis, or the workup for those diagnoses is negative ⁴⁴³. A calculator cannot decide this. See The differential.

The same case under 2017 and 2024

Both rule sets run on every change. The highlighted card is the version the map is showing. Apart from some people with primary progressive MS who lack several spinal cord lesions, everyone who meets 2017 also meets 2024, and a diagnosis made under older criteria is not changed by the revision ⁴⁴³.

2024 dissemination in time follows the paper's Figure 3 footnote: "one or more new T2 lesions or one or more gadolinium-positive lesions or a clinical attack" ³²⁵. The companion glossary reads it more strictly, as new T2 lesions over time or enhancing and non-enhancing lesions together on one scan, as in 2017 ⁴⁴³. The sources do not settle this; the verdict tells you when the stricter reading would change the answer.

How well the criteria and tests perform

Where experts disagree

Debated

Diagnosing without dissemination in time

2024 allows a diagnosis on 4–5 sites alone, or with a central vein sign, to speed diagnosis ^325,477. Real-world cohorts found many more diagnoses, specificity of 57.8% against 2017 at follow-up, and low 2017–2024 agreement in one cohort (κ=0.112) ^54,178. The London authors note that their "specificity" counts 2017-negative CIS and RIS as false positives. No long-term prospective validation yet.

Unresolved

Calling RIS multiple sclerosis

About 51% of people with RIS develop clinical symptoms within 10 years ^218,407, and OCB (HR 5.09) and κ-FLC ≥6.1 (HR 2.79) predict it ¹⁴⁸. Critics point to overdiagnosis, the consequences of treatment and labelling, and gaps in implementation ^54,254,418. Letters raising concerns were published with an authors' reply ³²⁶.

Varies by centre

The optic nerve as a fifth site

Adding it raised sensitivity without losing specificity by VEP in one cohort ⁴⁸¹ and gave similar accuracy across MRI, OCT and VEP in another ⁴⁸². Other cohorts found lower specificity, and asymptomatic optic nerve findings in non-optic-neuritis CIS added no patients ^53,139. OCT and VEP thresholds depend on quality control, centre and device ⁴¹⁶.

Threshold choice

Central vein sign and κ-FLC cut-offs

Earlier work used a 40% lesion rule; Select-3 was sensitive but not specific, and 2024 adopted Select-6 ^63,325,467. Published κ-FLC cut-offs range from 2.4 to 20; 6.1 is a weighted mean, and κ-FLC and OCB disagree in about 10%–13% of cases ^114,218.

Exam hook2017: DIS = 2 of 4 areas (PV, cortical/JC, IT, cord); DIT = enhancing + non-enhancing together, or a new lesion, or a second attack; CSF OCB can stand in for DIT; symptomatic lesions count except in the optic nerve; PPMS = 1 year of progression + 2 of 3 (brain, ≥2 cord, OCB). 2024: optic nerve is the 5th site; DIS + positive CSF (OCB or κ-FLC ≥6.1) is enough; one site needs (CSF or DIT) and (CVS or PRL); 4–5 sites alone only after an attack or progression; RIS can qualify with ≥2 sites + CSF, CVS or DIT. ^325,462

In plain wordsTo diagnose MS, doctors look for damage in more than one part of the nervous system, signs that it happened at more than one time (or a spinal fluid test that stands in for that), and then make sure nothing else explains it better. The 2024 rules add new scan and eye tests that can make the answer faster, but the final check still belongs to a person.