MS Trial Atlas, Diagnostic criteria
What is the McDonald criteria and who is McDonald?
The McDonald criteria are the framework clinicians use to diagnose multiple sclerosis, bringing together the clinical history, examination, MRI and, when appropriate, cerebrospinal fluid findings.
Two foundational concepts are dissemination in space—evidence of disease in different central nervous system locations—and dissemination in time—evidence of disease activity at different times. Successive editions have changed how these are demonstrated; newer pathways can permit diagnosis without separate evidence of dissemination in time. There must be no better explanation for the findings.
Professor W. Ian McDonald (1933–2006) was a neurologist and MS researcher at Queen Square, London. He chaired the international panel behind the 2001 criteria. They carry his name, but their development and subsequent revisions represent the collective work of international expert panels.
Newest to oldest. These educational summaries explain the key changes; the original papers contain the full diagnostic pathways and exceptions. Trial links retain the edition used in that study.
A broader framework, with more specific biomarkers
Unifies relapsing and progressive presentations and introduces additional routes to diagnosis, including selected people without a typical clinical attack.
- Space
- The optic nerve joins periventricular, cortical/juxtacortical, infratentorial and spinal cord regions. Typical lesions in two of five regions establish dissemination in space; in progressive disease, two spinal cord lesions can suffice.
- Time & CSF
- Dissemination in time is no longer mandatory in every pathway. For typical presentations, involvement of four or five regions can suffice; dissemination in space plus positive cerebrospinal fluid (CSF) is another route. A validated kappa free-light-chain index can substitute for CSF-restricted oligoclonal bands.
- New evidence
- The central vein sign and paramagnetic rim lesions support specific diagnostic pathways. Selected radiologically isolated presentations may qualify with additional evidence. Progressive onset still requires at least 12 months of progression.
- Interpretation
- Biomarkers are not interchangeable across every pathway. Additional safeguards apply to older adults and vascular comorbidity; exclude better explanations.
The Lancet Neurology, 2025, 24:850–865
DOI 10.1016/S1474-4422(25)00270-4CSF can replace evidence of dissemination in time
Allows earlier diagnosis after a typical clinically isolated syndrome when dissemination in space and CSF-restricted oligoclonal bands are present.
- Space
- At least one T2 lesion in two of four regions: periventricular, cortical/juxtacortical, infratentorial or spinal cord. Cortical lesions now count alongside juxtacortical lesions; symptomatic lesions can contribute.
- Time & CSF
- A new T2 or enhancing lesion on follow-up, or simultaneous enhancing and non-enhancing lesions, can establish dissemination in time. In a typical clinically isolated syndrome with dissemination in space, CSF-restricted oligoclonal bands can replace that requirement.
- Progressive onset
- One year of progression plus two of: at least one typical brain lesion; at least two spinal cord lesions; or CSF-restricted oligoclonal bands.
- Interpretation
- Intended primarily for typical clinically isolated syndromes, with no better explanation. Positive oligoclonal bands alone do not establish MS.
The Lancet Neurology, 2018, 17:162–173
DOI 10.1016/S1474-4422(17)30470-2Simpler MRI rules; diagnosis on a single scan
Simplifies lesion-location requirements and permits MRI evidence of dissemination in space and time at the first assessment in appropriate patients.
- Space
- At least one T2 lesion in two of four regions: periventricular, juxtacortical, infratentorial or spinal cord. In brainstem or spinal cord syndromes, lesions in the symptomatic region are excluded from this MRI count.
- Time
- Simultaneous asymptomatic gadolinium-enhancing and non-enhancing lesions can establish dissemination in time. Alternatively, a new T2 or enhancing lesion on follow-up suffices, regardless of the timing of the baseline scan.
- Progressive onset
- One year of progression plus two of: at least one T2 lesion in a characteristic brain region; at least two spinal cord T2 lesions; or positive CSF (oligoclonal bands and/or elevated IgG index).
- Interpretation
- CSF does not yet replace dissemination in time after a typical first attack. Clinical context and exclusion of alternative diagnoses remain essential.
Annals of Neurology, 2011, 69:292–302
DOI 10.1002/ana.22366More flexible follow-up MRI and progressive criteria
Clarifies spinal cord imaging, relaxes the timing rules for new T2 lesions and simplifies the primary progressive pathway.
- Space
- Retains the original three-of-four brain MRI rule. Clarifies that cord lesions can contribute to the total T2 count, substitute for infratentorial lesions, and provide enhancing-lesion evidence.
- Time
- A new T2 lesion compared with a reference scan obtained at least 30 days after symptom onset can establish dissemination in time. Another route is enhancement at least three months after onset, outside the site responsible for the initial event.
- Progressive onset
- One year of progression plus two of: positive brain MRI (nine T2 lesions, or at least four with positive visual evoked potentials); at least two focal cord lesions; or positive CSF. CSF is therefore no longer obligatory in every progressive case.
- Interpretation
- This remains a more complex MRI framework than the later two-of-four-region rule; trial references to 2005 should retain that historical meaning.
Annals of Neurology, 2005, 58:840–846
DOI 10.1002/ana.20703MRI enters the diagnostic framework
Combines clinical attacks and objective findings with MRI to demonstrate lesions separated in space and time, enabling diagnosis before a second attack in selected patients.
- Space
- The brain MRI rule requires three of four features: one enhancing lesion or nine T2 lesions; one infratentorial lesion; one juxtacortical lesion; and three periventricular lesions. An alternative combines at least two MS-consistent lesions with positive CSF.
- Time
- MRI timing is tied to the first event: enhancement at least three months later, outside the initial symptomatic site, or new lesions on appropriately timed serial scans. A further clinical attack can also demonstrate dissemination in time.
- Progressive onset
- Requires positive CSF, specified MRI/visual-evoked-potential evidence of dissemination in space, and dissemination in time through MRI or one year of continued progression.
- Interpretation
- The original edition establishes the framework rather than the simpler thresholds familiar today. Clinical presentation determines which additional evidence is needed, always with no better explanation.
Annals of Neurology, 2001, 50:121–127
DOI 10.1002/ana.1032