MS Diagnostic Workup
The comprehensive workup for suspected MS requires brain MRI with gadolinium (minimum 1.5T, preferably 3.0T), spinal cord MRI, CSF analysis with oligoclonal bands, and blood tests to exclude mimics, all interpreted by a specialist familiar with MS and its differential diagnoses. 1, 2
Clinical Assessment Requirements
Objective neurological examination findings are mandatory—historical symptoms alone cannot establish MS diagnosis. 1 The examination must document:
- Attack definition: Neurological disturbance lasting ≥24 hours, excluding pseudoattacks from fever or infection 1, 2
- Temporal separation: At least 30 days between onset of separate attacks 1, 2
- Age considerations: Criteria apply best to patients 18-50 years, though can be used in pediatric cases with special attention under age 11 1, 3
Brain MRI Protocol (Mandatory)
Perform on minimum 1.5T scanner (preferably 3.0T) with standardized protocol not exceeding 25-30 minutes. 4, 1, 2 Required sequences include:
- Axial T1-weighted sequences before and after gadolinium contrast (single dose 0.1 mmol/kg, minimum 5-minute delay post-injection) 4
- Axial T2-weighted and proton-density (or T2-FLAIR) sequences 4, 1
- Sagittal 2D or isotropic 3D T2-FLAIR sequences 4, 1, 2
MRI criteria for dissemination in space require lesions in ≥2 of 4 characteristic CNS regions: periventricular, cortical/juxtacortical, infratentorial, and spinal cord. 1, 2
Dissemination in time is demonstrated by simultaneous gadolinium-enhancing and non-enhancing lesions on a single MRI, or new T2/enhancing lesions on follow-up imaging (minimum 3 months after clinical event). 1, 2
Spinal Cord MRI (Mandatory Even Without Spinal Symptoms)
Spinal cord MRI is required because 30-40% of clinically isolated syndrome patients have asymptomatic cord lesions. 4, 1 This is particularly critical when:
- Brain MRI is inconclusive or shows only one lesion 4
- Clinical presentation includes spinal cord symptoms 4
- Brain MRI shows nonspecific findings (perivascular lesions, aging effects, migraine-related changes) 4
- Primary progressive MS is suspected 4
Standardized spinal cord protocol includes:
- Sagittal sequences: Dual-echo (proton-density and T2-weighted) conventional/fast spin-echo, STIR, and contrast-enhanced T1-weighted spin-echo if T2 lesions present 4, 1
- Optional axial sequences: 2D/3D T2-weighted fast spin-echo, contrast-enhanced T1-weighted spin-echo 4
Cerebrospinal Fluid Analysis
Lumbar puncture is indicated when imaging criteria are not fully satisfied, clinical presentation is atypical, or progressive onset without relapses (primary progressive MS). 1, 2, 3 Key CSF findings include:
- Oligoclonal bands (IgG-specific) 1, 2, 3
- Elevated IgG index 1, 2
- Albumino-cytological dissociation 1, 2
Laboratory Studies to Exclude Mimics
Essential blood tests must be performed to rule out alternative diagnoses:
- Complete blood count and comprehensive metabolic panel 1, 2
- Anti-aquaporin-4 (AQP4) antibodies to exclude neuromyelitis optica spectrum disorder 1, 2, 3
- Consider ANA and antiphospholipid antibodies if clinically indicated 3
- Vitamin B12 levels to exclude deficiency 2
Additional Paraclinical Tests
Visual evoked potentials (VEP) should be considered when:
- Suspected optic nerve involvement is present 2, 3
- MRI access is limited 2, 3
- Atypical presentations require additional evidence 1, 3
Fat-suppressed MRI of optic nerves may be useful in atypical cases to rule out alternative diagnoses. 2
Critical Differential Diagnoses to Exclude
No diagnosis of MS can be made if there is a better explanation for clinical and paraclinical abnormalities. 2, 3 Must exclude:
- Neuromyelitis optica spectrum disorder (via AQP4 antibodies) 1, 2, 3
- Cerebrovascular disease (multifocal ischemia/infarction in young adults) 2, 3
- Infectious diseases (HTLV1, Lyme disease) 3
- Inflammatory conditions (sarcoidosis, Behçet's disease) 2
- Vitamin B12 deficiency 2
- Spinal cord compression 2
Diagnostic Pitfalls and Special Populations
In pediatric cases under age 11, look for at least one T1 hypointense lesion ("black hole") and one periventricular lesion to distinguish MS from monophasic demyelination. 1, 3
In patients older than 50 years or with vascular risk factors, apply more stringent criteria (higher number of periventricular lesions required). 3
Bilateral sudden hearing loss or sudden focal neurologic symptoms (headache, confusion, diplopia, dysarthria) may indicate conditions other than MS and require prompt alternative evaluation. 3
Specialist Requirement
Diagnosis must be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments—neurology consultation is essential for definitive diagnosis and treatment initiation. 2, 3 Diagnosis should not be made solely on MRI results; at least one clinical event consistent with acute demyelination remains the cornerstone. 3, 5