What is the recommended blood test for diagnosing multiple sclerosis (MS)?

Blood Tests for Multiple Sclerosis Diagnosis

There is no specific blood test for diagnosing multiple sclerosis (MS); diagnosis requires evidence of central nervous system lesions disseminated in time and space through a combination of clinical assessment, MRI imaging, and cerebrospinal fluid (CSF) analysis. 1, 2

Diagnostic Approach for MS

• MS diagnosis requires evidence of inflammatory-demyelinating injury within the central nervous system that is disseminated in both time and space, with no better explanation for the clinical presentation 1
• Diagnosis is made through a combination of clinical history, neurological examination, MRI imaging, and exclusion of other diagnostic possibilities 3
• CSF analysis remains an important supportive test, particularly when imaging criteria fall short or in atypical presentations 1

Role of CSF Analysis in MS Diagnosis

• Positive CSF is defined as oligoclonal IgG bands detected by isoelectric focusing that are different from any bands in serum, or elevated IgG index 1
• CSF analysis should include cell count and differential, protein, glucose, lactate, myelin basic protein, and CSF/serum albumin ratio 4
• Lymphocytic pleocytosis should be less than 50/mm³ in MS 1
• Isoelectric focusing with IgG immunoblotting is the preferred method for detecting oligoclonal bands, which is more sensitive than the IgG index 4, 5

When CSF Analysis is Particularly Important

• When MRI findings are insufficient to establish dissemination in time and space 1
• In atypical presentations such as dementia, epilepsy, or aphasia 1, 6
• In patients younger than 10 or older than 59 years 1, 2
• In cases with progressive onset rather than relapsing-remitting pattern 1
• When alternative diagnoses need to be excluded 7, 2

MRI Criteria for MS Diagnosis

• MRI is the preferred imaging modality for diagnosis and monitoring 2
• Dissemination in space requires three of four of the following: one gadolinium-enhancing lesion or nine T2-hyperintense lesions if no gadolinium enhancement, at least one infratentorial lesion, at least one juxtacortical lesion, or at least three periventricular lesions 1
• Dissemination in time can be demonstrated by the presence of gadolinium-enhancing lesion (not at site of original event) or new T2 lesion on follow-up scan 1

Diagnostic Outcomes

• If criteria are fulfilled: diagnosis is MS 1
• If criteria are not completely met: diagnosis is "possible MS" 1
• If criteria are fully explored and not met: diagnosis is "not MS" 1

Important Considerations and Pitfalls

• Alternative diagnoses must always be considered - if tests (MRI, CSF) are negative or atypical, extreme caution should be taken before making an MS diagnosis 1, 2
• The quality of CSF analysis varies between laboratories, and testing should be done with state-of-the-art technology to avoid misdiagnosis 1, 2
• Differential diagnosis includes cerebrovascular disease, infectious diseases (HTLV1, Lyme), paraneoplastic disorders, acute disseminated encephalomyelitis, neuromyelitis optica, and leukodystrophies 1, 2
• Diagnosis should be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments 2

Emerging Biomarkers

• Research is ongoing for potential biomarkers in CSF including T-cell/B-cell patterns, soluble HLA antigens, nitrous oxide metabolites, neurofilament components, tau protein, and chemokines 4
• These potential biomarkers may help predict disease course and treatment response but are not yet part of standard diagnostic protocols 4