The corpus callosum (CC), as the largest interhemispheric commissure, connects the cortical zones of the left and right hemispheres. The anterior regions of the CC contain axons from the frontal premotor and motor cortices, while the posterior regions contain fibers from the somesthetic, parietal, occipital, and temporal lobes. Cytotoxic lesions of the corpus callosum (CLOCCs) are a rare clinicoradiologic syndrome characterized by transient and reversible lesions of the CC and possibly of the adjacent white matter. CLOCCs have been observed in the context of various diseases, including viral infections. Since CLOCCs were identified as a distinct radiological finding in patients with neuroCOVID, the Chinese researchers in this retrospective study presented the neurological, radiological, and laboratory features of cytotoxic lesions of the corpus callosum in eight COVID-19 patients.
The role of the CC has two main aspects. The first aspect suggests that the CC is associated with functional cortical lateralization at the level of interhemispheric inhibition. The second implies that the CC contributes to brain symmetry, as impairment of the CC leads to intrahemispheric isolation. The authors noted that structural features and blood supply characteristics are the mechanisms that may make the CC susceptible to damage. These features may include a lack of adrenergic receptors, impaired regulation of water and electrolyte homeostasis and ion transport, excitatory amino acid toxicity, oxidative stress damage, or inflammatory infiltration mediated by immune dysregulation. However, neurological symptoms appear to rapidly emerge after infection and then subside. This suggests that disruption of the blood-brain barrier, leading to direct invasion of SARS-CoV-2 virus, is unlikely to be the direct cause of CLOCCs.
Importantly, COVID-19-related CLOCCs are more common in adolescents and young adults. They also have more severe neurological symptoms, such as impaired consciousness, ataxia, hallucinations, dysarthria, and psychotic disorders, as observed in pediatric cases linked to multisystemic inflammatory syndromes. However, it is important to note that all reported cases had complete remission of neurological symptoms. Interestingly, in a previous functional brain magnetic resonance imaging (MRI) study investigating brain activation during working memory tasks in patients with post-COVID neuropsychiatric symptoms, some changes were detected at the level of brain lateralization. Lower activation in two large clusters localized in the left hemisphere and higher activation in the right hemisphere were registered during more difficult tasks in post-COVID patients compared to healthy controls. They also showed poorer performance in the domains of endurance, locomotion, and manual dexterity of the dominant hand, which is controlled by the motor area of the dominant, mostly left hemisphere. https://discovermednews.com/post-covid-syndrome-and-brain-activation-during-the-working-memory-tasks/ Also, the study exploring the association between neuroimaging findings and visuospatial abilities in postCOVID patients found a negative correlation between increased white matter volume in the left and right genu of the corpus callosum, extending to the cingulum bilaterally, and the results of Rey-Osterrieth Complex Figure Test of visuospatial abilities, executive functions, and memory. https://discovermednews.com/visuospatial-deficit-immune-markers-neuroimaging-after-covid-19/
About the study
The study comprised eight patients with COVID-19-related CLOCCs. All patients were evaluated by at least two neurologists. The inclusion criteria were SARS-CoV-2 infection confirmed with positive PCR or antigen testing as well as CLOCC findings on brain MRI. The exclusion criteria included pre-existing lesions or other causes of the CC abnormalities, such as non-COVID-19 infections, acute trauma, pregnancy, epilepsy or antiepileptic medications, chemotherapy, and alcohol intoxication.
All patients underwent a 3-T brain MRI scans. All MRI images were interpreted by at least one radiologist and one neurologist. Laboratory testing included a peripheral blood cell count, inflammatory cytokines, markers of cellular lysis (such as lactate dehydrogenase), coagulation parameters, thyroid hormones, creatine kinase, and electrolytes. Peripheral blood samples were taken within six hours after admission.
Results
254 COVID-19 patients with an average age of 64.4 years (range: 15-96 years) underwent brain MRI scans. CLOCCs were found in eight COVID-19 patients (four males and four females) with an average age of 31.1 years (range: 15-82 years). More than half of these patients were younger than 20 years. Neurological symptoms in all COVID-19 patients diagnosed with CLOCCs developed within three days of COVID-19 onset and included impaired consciousness (5/8), headache (4/8), psychiatric abnormalities (4/8), ataxia (2/8), dysarthria (2/8), pyramidal tract signs (2/8), and visual disturbances (2/8). Two cases had severe COVID-19-related rhabdomyolysis. None of the patients had pre-existing neurological disorders, neurological symptoms, or signs.
Based on the extent of the CC lesions on MRI, patients were categorized into three different types of CLOCCs. Type I lesions, which were localized in the splenium of the CC, were associated with faster recovery. Type II (cases 6 and 7) and III (case 8), involving the peripheral white matter or anterior CC, were associated with more severe neurological symptoms. These results suggest that the location of the CC lesion may influence the clinical presentation and recovery from CLOCCs. Follow-up MRI scans of the brain showed that the CC lesions had resolved within 2 to 3 weeks.
Electroencephalography was also performed in cases 2 and 7, which showed epileptic discharges in case 2 and diffuse slow-wave spikes throughout the brain in case 7.
Laboratory Findings
At the onset of the disease, CRP-lymphocyte ratio was elevated in all cases, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammatory index, and C-reactive protein in 7/8 cases, and IL-6 in 2/4 cases, which gradually decreased as the disease resolved. Importantly, in patients with MRI type II and III of CLOCCs, serum levels of platelet-lymphocyte ratio, systemic immune-inflammation index, CRP, CRP-lymphocyte ratio, and IL-6 were higher than in type I patients. When the CC lesions resolved in all patients, the levels of CRP-lymphocyte ratio subsequently declined, suggesting that this marker may serve as a useful indicator of disease activity.
In addition, hyponatremia was found in type II and III patients, particularly those with adjacent white matter lesions, supporting the hypothesis that electrolyte imbalance may contribute to the pathogenesis of CLOCCs.
The cerebrospinal fluid (CSF) samples collected from five patients showed normal cell count, glucose, and chloride concentrations, and elevated levels of total proteins in one patient. All patients tested positive for the SARS-CoV-2 virus via RT-PCR.
Conclusion
In this study, clinical and radiological findings of eight patients with COVID-19-associated CLOCCs are presented, highlighting the favorable prognosis and the importance of considering CLOCCs in the differential diagnosis of neurological symptoms in neuroCOVID-19 patients. However, the retrospective nature of the study and the small number of patients limit the generalizability of these findings. Given the ongoing threat of SARS-CoV-2 variants, further research is necessary to comprehend the full range of neurological effects of COVID-19 and to define future treatment strategies.
This article was published in Brain and Behavior.
Journal Reference
Wan C, Li M, Yu Y et al. COVID-19-Associated Cytotoxic Lesions of the Corpus Callosum in Chinese Patients: A Retrospective Study. Brain and Behavior, 2025; 15: e70547. (Open Access) https://doi.org/10.1002/brb3.70547
