Multiple sclerosis diagnostic study of choice
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Basir Gill, M.B.B.S, M.D.[2]
Overview
Magnetic resonance imaging (MRI) is the imaging study of choice and the principal paraclinical investigation for suspected multiple sclerosis (MS). However, there is no single standalone confirmatory test for MS. Diagnosis requires integration of the clinical history and neurological examination, characteristic MRI findings, and, when indicated, cerebrospinal fluid (CSF) analysis, while establishing that there is no better explanation for the findings.[1][2]
The current diagnostic framework is provided by the 2024 revised McDonald criteria, published in 2025. It applies across the lifespan, including pediatric and late-life presentations, and permits a diagnosis of MS in selected patients with incidental MRI abnormalities or symptoms that do not constitute a typical demyelinating attack when sufficient additional evidence is present.[1]
Diagnostic Study of Choice
Study of choice
MRI is the imaging modality of choice because it provides the highest sensitivity for detecting demyelinating lesions in the brain, spinal cord, and optic nerve, demonstrates dissemination in space and time, assesses active inflammation, and helps identify alternative diagnoses. MRI findings must be interpreted in the appropriate clinical context and should not be regarded as diagnostic merely because nonspecific white-matter lesions are present.[3][4]
Investigations:
- For the initial evaluation of suspected MS, diagnostic MRI should cover the brain and the whole spinal cord. In adults with suspected central nervous system demyelination, the American College of Radiology rates MRI of the brain and MRI of the cervical and thoracic spine without and with intravenous contrast as usually appropriate.[3][4]
- A standardized MS brain MRI protocol should be used. Three-dimensional T2-weighted fluid-attenuated inversion recovery (FLAIR) is the core brain sequence. The protocol should also permit assessment of T2-hyperintense lesions and, when gadolinium is administered, enhancing lesions. Gadolinium-based contrast should be used judiciously for a defined diagnostic purpose.[5][3]
- Susceptibility-sensitive sequences should be included when feasible to assess the central vein sign (CVS) and paramagnetic rim lesions (PRLs), particularly when conventional clinical and MRI findings are insufficient or when greater diagnostic specificity is required.[3]
- When acute optic neuritis or other optic-nerve involvement is suspected, dedicated orbital MRI with fat-suppressed T2-weighted or short-tau inversion recovery sequences should be obtained; post-gadolinium fat-suppressed T1-weighted imaging may be added when contrast is used. Dedicated orbital imaging is not required in every routine MS examination.[3]
- CT is substantially less sensitive than MRI for demyelinating lesions and is not the preferred examination for establishing an MS diagnosis.[4]
MRI findings supporting the diagnosis
MRI findings that support MS include:
- One or more lesions with morphology and signal characteristics typical of inflammatory demyelination in at least two of five MS-typical anatomical locations, thereby demonstrating dissemination in space (DIS):
- Periventricular
- Cortical or juxtacortical
- Infratentorial
- Spinal cord
- Optic nerve
- Dissemination in time (DIT), demonstrated on MRI by either:
- The simultaneous presence of gadolinium-enhancing and nonenhancing lesions; or
- A new T2-hyperintense or gadolinium-enhancing lesion on follow-up MRI compared with a previous scan.
- A positive central vein sign using the adult Select 6 method: at least 6 CVS-positive white-matter lesions, or a majority of lesions demonstrating CVS when fewer than 10 eligible lesions are present.
- One or more PRLs in the limited diagnostic pathways specified by the 2024 revised McDonald criteria.
The CVS and PRLs increase diagnostic specificity but are not required in every patient and must not be used as isolated proof of MS. Lesion morphology, distribution, clinical compatibility, and exclusion of mimics remain essential.[1][3][2]
Pediatric considerations
- The 2024 revised McDonald framework applies to pediatric-onset MS, but it should not be applied at the time of an initial acute disseminated encephalomyelitis presentation.[1]
- MRI of the brain and spinal cord should be interpreted with particular attention to alternative pediatric demyelinating disorders. Testing for MOG-IgG is required in children younger than 12 years and is advised in older children when features are atypical for MS.[1]
- The adult Select 6 CVS rule has not been sufficiently validated in children. In pediatric patients, CVS is considered positive when more than 50% of eligible lesions demonstrate the sign.[1]
- Evidence is currently insufficient to use PRLs as a diagnostic criterion in pediatric-onset MS.[1]
Radiologically isolated presentations
- A radiologically isolated presentation describes incidentally detected brain or spinal-cord MRI lesions strongly suggestive of inflammatory demyelination in a person without a prior typical MS attack or objective neurological progression. Alternative vascular, migraine-related, infectious, inflammatory, genetic, toxic, metabolic, and structural explanations must be excluded.[6][2]
- Under the 2024 revised McDonald criteria, an asymptomatic person or a person with nonspecific symptoms can meet diagnostic criteria for MS when typical lesions involve at least two of the five anatomical locations and at least one of the following is present: MRI evidence of DIT, positive CSF, or a positive CVS.[1]
- If the criteria for MS are not met, the 2023 revised radiologically isolated syndrome (RIS) criteria should be considered. These criteria permit RIS classification with a lower MRI lesion burden when additional risk features, including a spinal-cord lesion, CSF-restricted oligoclonal bands, or new T2 or gadolinium-enhancing lesions on follow-up MRI, are present in the required combination.[6]
Sequence of Diagnostic Studies
- History and neurological examination, including confirmation that the presentation is compatible with demyelinating disease
- MRI of the brain and whole spinal cord using a standardized MS protocol; dedicated optic-nerve MRI when clinically indicated
- Targeted CSF analysis and laboratory testing when required by the diagnostic pathway or to exclude alternative diagnoses
- Follow-up MRI when the initial evaluation does not establish DIT or when reassessment is clinically indicated
McDonald criteria (2024 revision)
The 2024 revised McDonald criteria integrate clinical presentation, MRI lesion distribution, MRI evidence of DIT, CSF biomarkers, the CVS, and PRLs. The pathways below summarize the principal requirements relevant to an MRI-focused diagnostic evaluation.[1][7]
| Clinical presentation | MRI distribution | Additional evidence required for an MS diagnosis |
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At least 1 of the following:
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Both of the following:
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At least 1 of the following:
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At least 1 of the following:
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For this table:
- DIS indicates dissemination in space.
- DIT indicates dissemination in time, established by a new typical clinical attack or by the MRI findings described above.
- Positive CSF indicates CSF-restricted oligoclonal bands or an elevated CSF kappa free light chain index according to validated laboratory methods.
- Positive CVS indicates a positive central vein sign using the applicable adult or pediatric method.
- PRL indicates a paramagnetic rim lesion identified on an appropriate susceptibility-sensitive MRI sequence.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Montalban X, Lebrun-Frénay C, Oh J, Arrambide G, Moccia M, Amato MP, et al. (October 2025). "Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria". Lancet Neurol. 24 (10): 850–865. doi:10.1016/S1474-4422(25)00270-4. PMID 40975101 Check
|pmid=value (help). - ↑ 2.0 2.1 2.2 Solomon AJ, Arrambide G, Brownlee WJ, Flanagan EP, Amato MP, Amezcua L, et al. (August 2023). "Differential diagnosis of suspected multiple sclerosis: an updated consensus approach". Lancet Neurol. 22 (8): 750–768. doi:10.1016/S1474-4422(23)00148-5. PMID 37479377 Check
|pmid=value (help). - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Barkhof F, Reich DS, Oh J, Rocca MA, Li D, Sati P, et al. (October 2025). "2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis". Lancet Neurol. 24 (10): 866–879. doi:10.1016/S1474-4422(25)00304-7. PMID 40975102 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ 4.0 4.1 4.2 Kalnins A, Lewis LM, Soderlund KA, Austin MJ, Chu S, Hawley DB, et al. (June 2026). "ACR Appropriateness Criteria® Demyelinating Diseases". J. Am. Coll. Radiol. 23 (6): 1183–1214. doi:10.1016/j.jacr.2026.02.003. PMID 41762178 Check
|pmid=value (help). - ↑ Wattjes MP, Ciccarelli O, Reich DS, Banwell B, de Stefano N, Enzinger C, et al. (August 2021). "2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis". Lancet Neurol. 20 (8): 653–670. doi:10.1016/S1474-4422(21)00095-8. PMID 34139157 Check
|pmid=value (help). - ↑ 6.0 6.1 Lebrun-Frénay C, Okuda DT, Siva A, Landes-Chateau C, Azevedo CJ, Mondot L, et al. (August 2023). "The radiologically isolated syndrome: revised diagnostic criteria". Brain. 146 (8): 3431–3443. doi:10.1093/brain/awad073. PMC PMC11004931 Check
|pmc=value (help). PMID 36864688 Check|pmid=value (help). - ↑ Montalban X, Lebrun-Frénay C, Oh J, et al. (November 2025). "Correction to Lancet Neurol 2025; 24: 850–65". Lancet Neurol. 24 (11): e13. doi:10.1016/S1474-4422(25)00355-2.