What is the management approach for a patient with T2 hyperintensity in the right side of the splenium of the corpus callosum, suspected to be either sequela of prior trauma (axonal injury) or demyelination?

Management of T2 Hyperintensity in the Splenium of the Corpus Callosum

For an isolated T2 hyperintense lesion in the splenium of the corpus callosum without enhancement and with faint susceptibility, the primary management approach is clinical observation with short-interval follow-up MRI in 4-8 weeks to determine if the lesion is transient and reversible, while simultaneously investigating for underlying metabolic, infectious, or toxic etiologies.

Initial Diagnostic Workup

The first priority is to distinguish between reversible splenial lesions and pathological processes requiring specific treatment:

• Obtain detailed clinical history focusing on recent infections (viral or bacterial), medication changes (particularly antiepileptic drug withdrawal), alcohol use, metabolic disturbances, and any episodes of altered consciousness or seizures 1, 2, 3
• Laboratory evaluation should include complete metabolic panel, vitamin B12 level (deficiency has been associated with splenial lesions), inflammatory markers, and infectious workup if clinically indicated 3
• Review medication history for recent antiepileptic drug changes or withdrawal, as these are common precipitants of reversible splenial lesions 2, 4

Imaging Characteristics That Guide Management

The imaging features you describe suggest a potentially reversible lesion rather than demyelination or chronic traumatic injury:

• Isolated splenial location without additional periventricular, juxtacortical, or infratentorial lesions argues against multiple sclerosis, which requires dissemination in space across at least 2 of 4 characteristic regions 5, 6
• Absence of enhancement excludes active inflammation or blood-brain barrier breakdown, making acute demyelination less likely 5
• Faint susceptibility may represent microhemorrhage from prior trauma, but the T2 hyperintensity pattern is more consistent with cytotoxic or vasogenic edema 4

Short-Term Management Strategy

Follow-up imaging is the cornerstone of management to differentiate reversible from permanent lesions:

• Repeat MRI brain with and without gadolinium in 4-8 weeks to assess for resolution, which would confirm a transient splenial lesion syndrome (RESLES) 1, 2, 4
• Complete resolution within 3 days to 9 months has been documented in reversible splenial lesions, with most resolving within 4-12 weeks 1, 4
• If the lesion persists unchanged beyond 3 months, consider additional imaging including cervical and thoracic spine MRI to evaluate for demyelinating disease 6

Differential Diagnosis Considerations

The clinical context determines which diagnostic pathway to pursue:

For Reversible Splenial Lesion Syndrome (Most Likely):

• Treat underlying precipitant such as infection, metabolic disturbance, or medication-related cause 1, 2, 3
• Expectant management with clinical monitoring, as these lesions typically resolve spontaneously without specific neurological treatment 4
• No specific therapy is required for the lesion itself beyond addressing the underlying cause 1, 4

For Demyelination (Less Likely Given Imaging):

• Requires additional lesions in at least 2 of 4 characteristic MS regions (periventricular, juxtacortical, infratentorial, spinal cord) for diagnosis 5, 6
• Lesions must be ≥3 mm in longest axis to meet MS diagnostic criteria 5, 6
• CSF analysis for oligoclonal bands and elevated IgG index only if MRI demonstrates dissemination in space or new lesions develop on follow-up 6

For Traumatic Axonal Injury (Possible):

• Faint susceptibility suggests microhemorrhage, which could represent remote diffuse axonal injury 5
• Traumatic lesions are typically permanent and do not resolve on follow-up imaging, unlike reversible splenial lesions 4
• Clinical history of significant head trauma is essential for this diagnosis; without clear trauma history, this becomes less likely 5

Long-Term Monitoring Plan

The follow-up strategy depends on lesion behavior:

• If lesion resolves completely: No further imaging required unless new neurological symptoms develop 1, 4
• If lesion persists but remains stable: Repeat MRI at 6 months, then annually for 2 years to ensure stability 5
• If new lesions develop: Pursue full demyelinating disease workup including spine MRI and CSF analysis 6

Critical Pitfalls to Avoid

Common errors in managing splenial lesions include:

• Over-interpreting isolated splenial lesions as MS without meeting dissemination in space criteria (requires lesions in ≥2 characteristic regions) 5, 6
• Initiating disease-modifying therapy for presumed MS based on a single lesion without proper diagnostic criteria being met 6
• Failing to investigate reversible causes such as infection, metabolic disturbance, or medication effects before pursuing extensive demyelinating workup 1, 2, 3
• Not obtaining follow-up imaging to document resolution or progression, which is essential for distinguishing reversible from permanent pathology 4

When to Escalate Workup

Pursue aggressive investigation if:

• New neurological symptoms develop such as vision changes, weakness, sensory deficits, or ataxia suggesting demyelination 6
• Follow-up MRI shows new lesions in characteristic MS locations (periventricular perpendicular to corpus callosum, juxtacortical, infratentorial) 5, 6
• Patient is younger than 50 years without vascular risk factors and lesion persists beyond 3 months, raising concern for demyelinating disease 5
• Lesion demonstrates gadolinium enhancement on follow-up, indicating active inflammation 5, 6