Cytotoxic lesions of the corpus callosum: a systematic review

Abstract

Objectives: Cytotoxic lesions of the corpus callosum (CLOCC) are a common magnetic resonance imaging (MRI) finding associated with various systemic diseases including COVID-19. Although an increasing number of such cases is reported in the literature, there is a lack of systematic evidence summarizing the etiology and neuroimaging findings of these lesions. Thus, the aim of this systematic review was to synthesize the applied nomenclature, neuroimaging and clinical features, and differential diagnoses as well as associated disease entities of CLOCC.

Materials and methods: A comprehensive literature search in three biomedical databases identified 441 references, out of which 324 were eligible for a narrative summary including a total of 1353 patients.

Results: Our PRISMA-conform systematic review identifies a broad panel of disease entities which are associated with CLOCC, among them toxic/drug-treatment-associated, infectious (viral, bacterial), vascular, metabolic, traumatic, and neoplastic entities in both adult and pediatric individuals. On MRI, CLOCC show typical high T2 signal, low T1 signal, restricted diffusion, and lack of contrast enhancement. The majority of the lesions were reversible within the follow-up period (median follow-up 3 weeks). Interestingly, even though CLOCC were mostly associated with symptoms of the underlying disease, in exceptional cases, CLOCC were associated with callosal neurological symptoms. Of note, employed nomenclature for CLOCC was highly inconsistent.

Conclusions: Our study provides high-level evidence for clinical and imaging features of CLOCC as well as associated disease entities.

Clinical relevance statement: Our study provides high-level evidence on MRI features of CLOCC as well as a comprehensive list of disease entities potentially associated with CLOCC. Together, this will facilitate rigorous diagnostic workup of suspected CLOCC cases.

Key points: • Cytotoxic lesions of the corpus callosum (CLOCC) are a frequent MRI feature associated with various systemic diseases. • Cytotoxic lesions of the corpus callosum show a highly homogenous MRI presentation and temporal dynamics. • This comprehensive overview will benefit (neuro)radiologists during diagnostic workup.

Keywords: COVID-19; Central nervous system diseases; Corpus callosum; Magnetic resonance imaging; Systematic review.

Fig. 1

Flow chart depicting the study selection process

Fig. 2

Typical structural MRI findings in cytotoxic lesions of the corpus callosum (CLOCC). Pictorial magnetic resonance imaging (MRI) examples of a 38-year-old patient who presents with a typical cytotoxic lesion of the corpus callosum (CLOCC) after head trauma. A DWI B0, oval hyperintensity throughout the splenium and into the adjacent hemispheres (“boomerang sign”). B ADC hypointensity due to restricted diffusion. C T2w-FLAIR, high signal. D T2 slightly hyperintense. E T1 native, pre-gadolinium uptake, shows a slight hypointensity in the region. F T1 post-gadolinium uptake, no enhancement. Abbreviations. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery