What is the diagnosis and recommended treatment for a patient with four small white matter lesions in the cerebral hemispheres that meet the McDonald criteria for Multiple Sclerosis (MS)?

Diagnosis: Multiple Sclerosis with Dissemination in Space

This patient meets the McDonald criteria for Multiple Sclerosis based on the presence of four white matter lesions demonstrating dissemination in space (DIS), though dissemination in time (DIT) has not yet been established on this single MRI. 1, 2, 3

Diagnostic Assessment

Current MRI Findings Analysis

The report describes four white matter lesions with the following distribution:

• Three subcortical lesions in temporal and occipital regions 1
• One periventricular lesion 1

Critical limitation: This does NOT meet the MAGNIMS 2016 criteria for DIS, which requires lesions in at least 2 of 5 CNS locations (≥3 periventricular, ≥1 infratentorial, ≥1 spinal cord, ≥1 optic nerve, ≥1 cortical/juxtacortical). 1 The patient has only ONE periventricular lesion (requires ≥3) and the subcortical lesions' exact relationship to the cortex is unclear from this report. 1

Red Flags Present in This Case

The radiologist's conclusion that these lesions "meet the McDonald criteria for MS DIS" appears premature based on the lesion distribution described. 1 Key concerns:

• Insufficient periventricular lesions: Only 1 periventricular lesion is documented, but ≥3 are required to confirm periventricular involvement for DIS. 1 Single periventricular lesions can occur in up to 30% of migraine patients and healthy individuals. 1

• Subcortical vs. juxtacortical distinction unclear: The report mentions "subcortical" lesions but does not specify if these are truly juxtacortical (directly abutting the cortex with no intervening white matter). 1 This distinction is critical for meeting DIS criteria.

• No infratentorial or spinal cord lesions documented: The cerebellum and brainstem are explicitly described as "without lesions," eliminating these as potential DIS locations. 1

Recommended Diagnostic Workup

Immediate Next Steps

Obtain complete spinal cord MRI (cervical and thoracic) to assess for additional asymptomatic lesions that could establish DIS. 1, 3 Approximately 40% of spinal cord lesions occur in the thoracolumbar region, and spinal cord imaging is particularly valuable when brain MRI does not definitively establish DIS. 1, 3

Perform CSF analysis including oligoclonal bands and IgG index. 4, 5 The presence of CSF-specific oligoclonal bands supports the diagnosis and increases specificity, particularly in cases with borderline MRI findings. 4

Obtain baseline gadolinium-enhanced brain MRI to assess for acute inflammatory activity (enhancing lesions) and establish a reference for future comparison. 2, 4 The presence of both enhancing and non-enhancing lesions simultaneously can establish DIT without waiting for a follow-up scan. 3

Establishing Dissemination in Time

DIT can be demonstrated by: 3

• A new clinical attack occurring ≥30 days after the initial presentation 3
• Simultaneous presence of gadolinium-enhancing and non-enhancing lesions on a single MRI 3
• New T2 lesions on follow-up MRI compared to baseline (minimum 3-month interval recommended) 2, 3

Excluding Alternative Diagnoses

Before confirming MS, exclude: 1, 3, 5

• Neuromyelitis optica spectrum disorder (NMOSD): Test serum anti-AQP4 antibodies, especially given the atypical lesion distribution 1, 4
• Migraine-related white matter changes: Common in young adults, typically smaller and more diffuse 1
• Cerebrovascular disease: Less likely given patient age, but consider vascular risk factors 1
• Systemic autoimmune diseases: Lupus, Sjögren's syndrome can mimic MS 1

Treatment Recommendations

If DIS and DIT Are Confirmed

Initiate disease-modifying therapy (DMT) promptly after establishing definitive MS diagnosis. 4 Nine classes of DMTs are available for relapsing-remitting MS, with efficacy rates ranging from 29-68% reduction in annualized relapse rates. 4

DMT options include: 4

• Interferons
• Glatiramer acetate
• Teriflunomide
• Sphingosine 1-phosphate receptor modulators
• Fumarates
• Cladribine
• Monoclonal antibodies (natalizumab, ocrelizumab, alemtuzumab)

Choice of initial DMT should consider: 4

• Disease activity and severity
• Patient preference regarding route of administration
• Safety profile and monitoring requirements
• Adverse effects including infections, bradycardia, macular edema, and autoimmune complications 4

If DIS/DIT Not Yet Established

Do NOT initiate DMT based solely on this MRI without meeting full diagnostic criteria. 2, 3, 6 MRI findings alone are insufficient for MS diagnosis—at least one clinical event consistent with acute demyelination is essential. 3, 6

Obtain follow-up MRI in 3-6 months to monitor for new lesions that would establish DIT. 2, 3

Critical Pitfalls to Avoid

Do not diagnose MS based solely on MRI findings without appropriate clinical context. 2, 6, 5 The lesions detected with MRI are pathologically nonspecific, and MS diagnosis requires demonstrating dissemination in space and time in the appropriate clinical setting. 6

Do not accept "meets McDonald criteria" from radiology reports without verifying the specific lesion counts and locations. 1 This case illustrates how radiologic interpretation may not align with the strict MAGNIMS criteria requiring ≥3 periventricular lesions. 1

Do not delay appropriate workup waiting for a second clinical attack if MRI criteria can be met with additional imaging (spinal cord) or contrast enhancement. 2, 3

Always confirm "there is no better explanation than MS" for the clinical and radiological picture before finalizing the diagnosis. 2, 3, 5

Monitoring Strategy Once Diagnosis Confirmed

Perform follow-up brain MRI to monitor for: 2

• New or enlarging T2 lesions (subclinical disease activity)
• Gadolinium-enhancing lesions (acute inflammation)
• T1 hypointense "black holes" persisting >6 months (neurodegeneration)