The main etiologies of corpus callosum lesions include neoplasm, vascular, trauma, infection, demyelination, and others (3). Consequently, due to this dense white matter tract, only highly aggressive tumors (glioblastoma, lymphoma), typically involve the corpus callosum (Eric C. Bourekas, 2002).

Agenesis of the corpus callosum (Figures 1 and 2) is one of the most common congenital brain malformations. It is characterized by the complete or partial absence of the corpus callosum. This condition is not linked to specific functional or behavioral abnormalities, such as those seen in autism. The primary symptoms of agenesis of the corpus callosum include a reduced ability to transfer sensory-motor information between the brain's hemispheres, delays in cognitive processing, difficulties in analyzing complex data, and challenges in performing unfamiliar tasks (Das & Geetha., 2023).

Glioblastoma

Glioblastoma multiforme originates in the cerebral white matter and accounts for 12–15% of all intracranial tumors, making it the most common primary intra-axial malignancy. Among these tumors, butterfly gliomas (figure 3) are notable for their unique appearance, resembling a "butterfly" in imaging studies. This distinctive shape occurs when the tumor infiltrates the corpus callosum and spreads into both cerebral hemispheres (see Figure 3). Tumors that invade the splenium of the corpus callosum are particularly concerning, as they can severely impair memory and cognitive functions due to the many critical associative pathways that traverse this region. Such involvement complicates surgical resection and is associated with a significantly poorer prognosis (Daulat Singh Kunwar, 2023).

CNS lymphoma

Primary CNS lymphomas usually present as either solitary lesions (60-70%, figure 4) or multiple lesions (30-40%, figure 5) in the periventricular white matter, frequently invading the corpus callosum. On imaging studies, these tumors appear as hyperdense enhancing masses on CT scans and are hypointense on T1-weighted MRI, with iso-to-hypointense characteristics on T2-weighted MRI. They are typically associated with minimal vasogenic edema and rarely exhibit central necrosis. Common symptoms include increased intracranial pressure, focal neurological deficits, and seizures. While glucocorticoids may provide temporary relief, their use before biopsy can obscure the diagnosis in up to 50% of cases. These high-grade tumors have a poor prognosis; surgical resection often leads to a rapid decline in the patient's condition. Although high-dose chemotherapy can reduce tumor size, recurrences are common, and the median survival time is about 30 months. Thus, comprehensive treatment approaches are essential for improving patient outcomes (Gaillard F, 2008).

Vascular etiologies include arterio-venous malformation and infarcts are rare entities.

Arteriovenous malformations of the corpus callosum (Figure 6) present unique challenges due to their higher risk of recurrent hemorrhages compared to superficial AVMs. There is ongoing debate regarding the most effective treatment approach since corpus callosum AVMs can cause mild impairments without significant bleeding. Surgical resection carries serious risks, including the potential for permanent neurological deficits, making the procedure complex. Consequently, there has been a shift toward less invasive treatment options. However, endovascular techniques rarely achieve complete obliteration and may lead to complications. Further research is needed to enhance treatment protocols and improve patient outcomes for corpus callosum AVMs (Aqueel H Pabaney, 2016).

Infarction of the Corpus Callosum

The splenium of the corpus callosum is particularly vulnerable to ischemic lesions with about 46.2% of splenium infarctions affecting both cerebral hemispheres. In contrast, infarctions in the genu and body are often linked to atherosclerosis (Figure 7), while embolism is the primary cause of corpus callosum infarctions. Damage to the corpus callosum can lead to disturbances in higher brain functions. Giroud and Dumas identified two main symptoms: callosal disconnection syndrome (apraxia and alien hand syndrome), and frontal-type gait disorders characterized by a broad base and shuffling steps (Shen Li 1, 2015).

Trauma

Traumatic brain injury (TBI) is a significant economic and social issue worldwide, leading to considerable cognitive, physical, and emotional disabilities. The corpus callosum, a key area often affected by traumatic axonal injury, is frequently associated with high-energy impact trauma and traffic accidents (Figure 8). Its involvement typically indicates a poorer prognosis. Research indicates that damage to the integrity of the corpus callosum after TBI may disrupt connectivity between bilateral frontoparietal neural networks, which are essential for cognitive functions such as working memory, bimanual coordination, and executive processes (Marta Cicuendez, 2016).

The corpus callosum is primarily composed of myelinated axons. As a result, demyelinating processes typically significantly impact it.

Multiple sclerosis (figure 9) is the most common acquired autoimmune demyelinating disease affecting the central nervous system (CNS). More than 80% of patients experience relapsing-remitting symptoms, which may include blurred vision, double vision (diplopia), focal weakness, sensory disturbances, ataxia, or bladder dysfunction. When MS is suspected, an MRI can provide valuable diagnostic insights, particularly through the examination of the inner surface of the corpus callosum (CC). Abnormalities in this region may be found in 55% to 95% of patients with MS (figure 6). Furthermore, progressive atrophy of the corpus callosum occurs in MS and has been linked to increased disability and cognitive dysfunction (Nidhi Garg1).

Transient lesions of corpus callosum

Cytotoxic lesions of the corpus callosum (CLOCCs) involve various conditions that alter signal in the corpus callosum, especially the splenium. These lesions typically arise from a cascade triggered by an initial insult, leading to macrophages releasing inflammatory cytokines (IL-1 and IL-6), recruiting T-cells, breaking down the blood-brain barrier, producing TNF-α, and activating astrocytes. This results in increased extracellular glutamate and subsequent cytotoxic edema. The splenium is particularly affected due to its high density of oligodendrocytes with glutamate-sensitive receptors. CLOCCs are often seen in patients with seizures or metabolic disturbances, but can also result from infections (figures 10 and 11), CNS malignancies, drug toxicity, or trauma (figure 12).  Imaging characteristics include hypointensity on T1-weighted scans, hyperintensity on T2-weighted scans, restricted diffusion, and non-enhancement. Patients typically recover completely on MRI within one month, with significant improvement often within a week following neurological recovery (Gaillard F S. R., 2025).