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Modern monitoring of multiple sclerosis cannot rely on a single measurement. The clinician integrates the clinical picture, magnetic resonance imaging, cerebrospinal fluid findings, blood biomarkers and the patient’s functional course over time.
These tools answer different questions: how well the diagnosis is supported, whether inflammatory activity persists, whether nervous-system damage is accumulating, whether treatment is effective, and whether signs of gradual progression are emerging.
A biomarker is an objectively measurable indicator of a biological process that helps answer a specific clinical question.
Helps confirm that central nervous system involvement is consistent with multiple sclerosis and distinguish it from disorders with a similar clinical or MRI appearance.
Helps detect new inflammatory injury, including disease activity that is not accompanied by new symptoms.
Some biomarkers are associated with a later risk of accumulating neurological disability or disease progression.
Changes in biomarkers may complement clinical assessment and MRI when monitoring treatment effectiveness.
| Biomarker | What it reflects | Diagnosis | Activity | Progression | Use |
|---|---|---|---|---|---|
| New or enlarging T2/FLAIR lesions | New focal inflammatory activity | Yes | Yes | Limited | Routine |
| Gadolinium-enhancing lesions | Recent blood–brain barrier disruption | Yes | Yes | Not directly | When clinically indicated |
| Central vein sign (CVS) | Characteristic perivenular lesion architecture | Yes | No | Not established | Specialized MRI |
| Paramagnetic rim lesions (PRL) | Chronic inflammation at the lesion edge | Yes, in selected situations | Chronic activity | Promising | Specialized MRI |
| Oligoclonal bands (OCB) | Intrathecal immunoglobulin synthesis | Yes | No | Limited | Routine |
| Kappa free light chains (κ-FLC) | Intrathecal immunoglobulin response | Yes | Not a primary activity marker | Under study | Included in the 2024 McDonald criteria |
| Neurofilament light chain (NfL) | Neuroaxonal injury | No | Additional marker | Has prognostic value | Gradually entering clinical practice |
| Glial fibrillary acidic protein (GFAP) | Astroglial activation | No | Limited | Promising marker | Not yet routine |
| MSDA test | Multi-protein disease activity profile | No | Additional assessment | Not validated as a stand-alone progression test | Specialized commercial test |
| Slowly expanding lesions (SEL) | Gradual enlargement of some chronic lesions | No | Chronic activity | Promising marker | Mainly research |
| Brain and spinal cord atrophy | Accumulated structural tissue loss | No | Not directly | Yes, at group level | Individual interpretation is limited |
| Optical coherence tomography (OCT) | Retinal and visual pathway injury | Used to document optic nerve involvement | Limited | Has prognostic value | Clinically available |
The 2024 revision of the McDonald criteria expanded the options for objective confirmation of multiple sclerosis. Alongside conventional MRI findings, specific imaging and CSF biomarkers now have a more prominent role.
Typical lesion location and morphology remain central. In selected clinical situations, the central vein sign (CVS) and paramagnetic rim lesions (PRL) may provide additional diagnostic specificity.
Oligoclonal bands (OCB) and kappa free light chains (κ-FLC) help document intrathecal immunoglobulin synthesis.
MRI remains the main objective imaging method in MS. Interpretation now includes not only the number of lesions, but also their location, structure, evolution and signs of chronic activity.
New lesions or enlargement of existing lesions remain among the main indicators of ongoing focal inflammatory activity.
Reflects the characteristic location of an MS lesion around a small vein and may help distinguish demyelinating lesions from some nonspecific white-matter abnormalities.
May reflect persistent chronic inflammation at the edge of an older lesion. They have diagnostic value and are actively studied as a possible marker of less favorable disease biology.
Detected through quantitative analysis of serial MRI and reflect gradual enlargement of a subset of chronic lesions.
Loss of brain or spinal cord volume is associated with accumulated tissue damage, but individual assessment requires standardized acquisition and specialized image processing.
Cortical involvement is an important part of MS pathology, but small cortical lesions are less visible on standard MRI protocols.
CSF-restricted IgG oligoclonal bands reflect local immunoglobulin production within the central nervous system and remain highly important for MS diagnosis.
Once the diagnosis is established, repeating OCB testing to monitor disease activity is usually unnecessary.
Kappa free light chains also reflect an intrathecal immunoglobulin response. Their advantage is that they can be measured quantitatively and with automated laboratory methods.
In the 2024 McDonald criteria, κ-FLC acquired a diagnostic role alongside oligoclonal bands.
The major advantage of blood biomarkers is the possibility of repeated measurement without an invasive procedure. This makes them particularly attractive for longitudinal monitoring in MS.
NfL reflects neuroaxonal injury. Increased levels may accompany relapses, new MRI activity and other forms of nervous-system damage.
NfL is not specific to MS, so every result requires clinical interpretation.
GFAP is a structural protein of astrocytes and is being studied particularly in relation to gradual progression, PIRA and progressive forms of MS.
It is not yet a stand-alone clinical test for diagnosing progression.
This multi-protein serum assay measures 18 protein biomarkers and uses an algorithm to calculate an integrated disease activity score.
MSDA may complement MRI and clinical assessment, but it does not replace them.
The absence of relapses does not always mean that the disease is completely inactive. New inflammatory injury may remain clinically silent.
New or enlarging T2/FLAIR lesions remain the best-established imaging sign of new focal disease activity.
These indicate recent blood–brain barrier disruption and identify active inflammation during a limited time window.
Increased NfL may accompany new neuroaxonal injury and can add information to clinical assessment and MRI.
A new relapse or a new gadolinium-enhancing lesion is relatively easy to link to an acute inflammatory event. It is much harder to measure slow accumulation of damage that may occur without relapses and without new conventional T2 lesions.
This is why biomarkers of progression independent of relapse activity (PIRA) and chronic active tissue injury are being studied so intensively.
May reflect astroglial activation and, in several studies, is associated with subsequent disability accumulation.
May serve as an imaging sign of persistent chronic activity within previously formed lesions.
Reflect gradual long-term evolution of some chronic lesions, but currently require specialized quantitative MRI processing.
Associated with accumulated structural damage, but small changes are difficult to interpret reliably in an individual patient.
Closely associated with motor disability and progression, but quantitative assessment is not yet a standard component of routine monitoring.
Retinal layer thinning may reflect neuroaxonal injury and has prognostic value, but OCT is not used as a stand-alone criterion for changing therapy.
When monitoring treatment, the key is not one isolated test result but concordance across several sources of information.
Relapses, new symptoms, neurological examination and functional changes are assessed over time.
New or enlarging lesions remain one of the most important objective signs of persistent focal inflammatory activity.
Serial NfL and, in selected situations, MSDA or other markers may complement clinical and imaging assessment.
People with MS often undergo regular laboratory monitoring, but many of these tests do not measure MS activity itself. Their main role is to make treatment safer.
Used to assess risk of progressive multifocal leukoencephalopathy during natalizumab treatment, not to assess MS activity.
Important for safety monitoring with several DMTs, including fumarates, S1P modulators and cladribine.
Particularly relevant during long-term B-cell-depleting therapy and in patients with recurrent infections.
May reflect the biological effect of anti-CD20 therapy, but are not a direct marker of MS activity.
Used for treatment safety with selected therapies rather than for assessing MS progression.
Hepatitis B, tuberculosis, varicella-zoster immunity and other infection-related tests may be required for safe treatment selection.
Beyond NfL and GFAP, many proteins, chemokines, cytokines and molecular profiles are being studied. For most, it is not yet clear how a result should change the treatment of an individual patient.
C-X-C motif chemokine ligand 13 is involved in B-cell trafficking and intrathecal immune activity and is studied particularly in CSF.
Chitinase-3-like protein 1 is associated with glial and innate immune activation and is being studied as a possible marker of chronic tissue injury and progression.
Proteomic approaches can measure many proteins simultaneously and generate integrated profiles of disease activity. MSDA is one of the first commercial examples of this strategy.
Studies gene activity and RNA profiles associated with immune activation and MS course.
Examines small molecules and metabolic pathways that may accompany inflammation, tissue injury and repair.
A particularly promising approach is to combine clinical data, MRI, blood biomarkers, CSF and digital measures into a single individualized risk model.
Multiple sclerosis includes several parallel biological processes: acute inflammation, axonal injury, chronic activity within older lesions, glial responses and gradual loss of nervous tissue. No single measurement can fully describe all of these processes.
New T2/FLAIR lesions, gadolinium-enhancing lesions, clinical relapses and neurofilament light chain.
Paramagnetic rim lesions, slowly expanding lesions, GFAP and other emerging markers.
Atrophy, optical coherence tomography, neurological examination and longitudinal functional change.
The clinical presentation, typical and atypical MRI findings, CSF results and alternative diagnoses need to be assessed together.
The key questions are whether this is true breakthrough activity, whether MRI studies were compared appropriately and whether there is enough evidence to change treatment.
PIRA, spinal cord involvement, functional change, symptomatic causes of deterioration and possible progressive disease all need to be considered.
The important question is not only whether the value is outside a reference range, but what it means in the context of age, MRI findings, clinical course and current treatment.