Reversible Splenial Lesions of the Corpus Callosum: Radiologic Clues and Differential Diagnosis

 In neuroimaging, discovering a focal signal abnormality in the splenium of the corpus callosum often raises concern for significant structural or demyelinating pathology. However, radiologic findings must always be interpreted alongside clinical course. Transient lesions confined to the splenium—frequently referred to as MERS (Mild Encephalitis/Encephalopathy with a Reversible Isolated Splenial Lesion)—represent a unique neuro-radiological entity that requires careful recognition.

Understanding the Radiological Sign 

On brain MRI, MERS manifests as a well-circumscribed area of restricted diffusion on Diffusion-Weighted Imaging (DWI) with corresponding hypointensity on Apparent Diffusion Coefficient (ADC) maps in the splenium. The splenium forms the thick posterior portion of the corpus callosum, responsible for interhemispheric communication between parietal, temporal, and occipital regions.

Despite its strategic location, transient splenial hyperintensity is remarkably subtle in its clinical impact. Classic callosal syndromes—including visual apraxia, agraphia, or interhemispheric disconnection signs—are consistently absent. Instead, patients usually present with transient altered sensorium, confusion, delirium, or seizures that improve rapidly alongside the resolution of the radiological lesion.

Broad Differential Diagnosis of Splenial Hyperintensity

When encountering a restricted diffusion pattern in the splenium, clinicians must consider a diverse differential:

• Infectious and Post-Infectious States: Systemic viral infections are among the most common triggers. Triggers include Influenza, Measles, Adenovirus, Mumps, Varicella Zoster, Rotavirus, and acute Hepatitis A. Bacterial etiologies (such as Salmonella or Legionella) and mycobacterial infections (like tuberculous meningitis) can also trigger similar reactions.

• Seizure Activity and Medication Effects: Prolonged focal status epilepticus or abrupt withdrawal of anti-seizure medications can induce transient cytotoxic edema in the splenium.

• Demyelinating and Vascular Conditions: Multiple Sclerosis (MS), Acute Disseminated Encephalomyelitis (ADEM), and Posterior Reversible Encephalopathy Syndrome (PRES) must be ruled out.

• Toxic and Metabolic Disturbances: Toxic encephalopathies, Marchiafava-Bignami disease (often associated with severe alcohol use disorder), and Hemolytic Uremic Syndrome (HUS) are important considerations.

Pathophysiological Insights The primary mechanism behind MERS is transient intramyelinic edema. Systemic inflammation leads to an influx of inflammatory cytokines. This cytokine surge disrupts fluid dynamics within the myelin sheath, causing localized cellular swelling rather than permanent neuronal injury or necrosis. Consequently, as the underlying systemic process resolves, the cytotoxic edema subsides, leading to complete radiologic and clinical clearance.

Clinical Management Strategy

When encountering an isolated splenial lesion on MRI in the context of mild encephalopathy:

• Conduct a thorough systemic workup, including liver enzymes, renal parameters, and viral panels.

• Avoid aggressive invasive interventions unless driven by clear central nervous system signs.

• Schedule follow-up neuroimaging after the acute illness resolves to confirm complete resolution of the splenial lesion.