Transient lesions of the splenium of the corpus callosum, mild encephalitis/encephalopathy with reversible splenial lesion (MERS)[1], reversible splenial lesions, and reversible splenial lesion syndrome (RESLES)[2] are some examples of past attempts by the scientific community to characterize these lesions. Today we know that these lesions are not only found in the splenium of the corpus callosum, they are not always reversible and they may have serious implications for the patient.

Many factors can lead to CLOCCs[7,8]:

• Medication (anti-seizure treatment, chemotherapy, corticosteroids, antibiotics)
• Central nervous system malignancy
• Infections
• Hypararachnoid hemorrhage
• Metabolic disorders
• Status epilepticus
• Vaccination
• Posterior reversible encephalopathy syndrome
• Kawasaki disease
• Hemolytic uremic syndrome

All of the above causes ultimately lead to an increase in IL 1, IL 6, and TNF-α resulting in an increase in extracellular glutamate in the brain as well as activation of microglia that can lead to demyelination[4-6,8] Glutamate in turn binds to N-methyl-D-aspartate receptors (NMDA-R) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR), leading to changes in the concentration of intracellular and extracellular sodium, calcium and potassium ions in neurons and glial cells. This results in the influx of water molecules into neurons and astrocytes and the formation of cytotoxic edema [7].

Cytotoxic edema is localized in the region of the corpus callosum as there is greater expression of these receptors than in other parts of the brain. [4,6]

CLOCCS may appear in three forms [7,8]:

• Round or oval lesion in the center of the splenium of the corpus callosum.
• Lesion in the splenium of the corpus callosum extending into the surrounding white matter.
• Lesion extending to the anterior part of the corpus callosum.

On MRI these lesions are depicted as foci with restricted diffusion, increased signal intensity on T2 weighted/FLAIR images, low signal intensity on T1 weighted images, and do not show enhancement post-contrast administration.

Patients with CLOCCS show symptoms related to the underlying cause while only one publication has reported symptoms of hemispheric disconnection presenting with alien hand syndrome. [3]

In terms of the course of CLOCCs, the majority of these lesions have resolved within the one-month follow-up.

The differential diagnosis of CLOCCs includes ischemic lesions, demyelinating lesions as well as tumors such as lymphoma. These lesions tend to be less symmetric than CLOCCs and do not resolve with time. In demyelinating lesions, we usually have other periventricular white matter lesions, while tumors show more aggressive behavior with mass effect.

Presented below are three cases encountered at our medical institution.

Case Ν^ο 1

An 8-year-old boy is admitted to our hospital with fever and altered mental status, a history of upper respiratory tract infection, and oliguria. There is a family history of COVID-19 with elevated antibody titers in the patient.

A brain MRI was performed with the following findings:

Fig 1: A) fluid-attenuated inversion recovery (FLAIR) B) T1 weighted image post-contrast C) Diffusion-weighted imaging (DWI) D)Apparent diffusion coefficient (ADC) map References: Department of Radiology, Papageorgiou General Hospital of Thessaloniki

Fig 2: fluid-attenuated inversion recovery (FLAIR) coronal view References: Department of Radiology, Papageorgiou General Hospital of Thessaloniki

Ιmage of an ovoid lesion in the center of the splenium of the corpus callosum with increased signal in FLAIR sequence, showing no enhancement after contrast administration. The lesion is visualised with diffusion restriction.

Multisystem inflammatory syndrome in children (MIS-c) was suspected and g-globulin and methylprednisolone were administered with remission of symptoms.

A follow-up brain MRI conducted two months later revealed no abnormal signal foci.

Fig 3: A)fluid-attenuated inversion recovery (FLAIR) B) Diffusion-weighted imaging (DWI) References: Department of Radiology, Papageorgiou General Hospital of Thessaloniki

Case Ν^ο 2

A 12.5-year-old female is admitted for seizures. She reports nasal congestion, cough, and fever for the last three days with a positive rapid test for influenza type A.

A brain MRI was performed : 

Fig 4: Α)T2 weighted image B)T1 weighted image post-contrast C) Diffusion-weighted imaging (DWI) D) apparent diffusion coefficient (ADC) map References: Department of Radiology, Papageorgiou General Hospital of Thessaloniki

Presence of a high signal foci in the T2 weighted sequence in the center of the splenium of the corpus callosum which does not show enhancement after contrast administration. The above lesion shows diffusion restriction.

The lesion was interpreted as CLOCCS attributed to Influenza A infection.

Case Ν^ο 3

A 10-year-old boy is admitted to the hospital for possible encephalitis due to a decreased level of consciousness and inability to walk. The lumbar puncture was negative. Right middle lobe pneumonia and Enterobacter sepsis were found during hospitalisation.

A brain MRI was performed:

Fig 5: A) fluid-attenuated inversion recovery (FLAIR) B) T1 weighted image post-contrast C) Diffusion-weighted imaging (DWI) D)Apparent diffusion coefficient (ADC) map References: Department of Radiology, Papageorgiou General Hospital of Thessaloniki

Presence of a high signal foci in the FLAIR sequence in the center of the splenium of the corpus callosum which does not show enhancement after contrast administration. The above lesion shows diffusion restriction.

These findings were attributed to CLOCCs due to pneumonia and sepsis. Intravenous antibiotic treatment was given with improvement of symptoms.

A follow-up brain MRI conducted three months later revealed no abnormal signal foci.

Fig 6: A) fluid-attenuated inversion recovery (FLAIR) C) Diffusion-weighted imaging (DWI) References: Department of Radiology, Papageorgiou General Hospital of Thessaloniki