Single vs. multiple lesions in sporadic cerebral cavernous malformations: the role of developmental venous anomalies

This study evaluated clinical and radiological factors associated with lesion multiplicity in sporadic cerebral cavernous malformations (CCMs), focusing on developmental venous anomalies (DVAs) as potential drivers of lesion multiplicity. Data from 269 patients with sporadic CCMs in a prospective registry were analyzed. Demographic, clinical, and radiological variables were collected, and patients were categorized into single or multiple CCM groups. CCM-DVAs were classified into Type I, II, or III based on angioarchitecture. Comparative analyses and multivariate logistic regression identified predictors of lesion multiplicity. The mean age at diagnosis was 45.5 years (SD 15.9); 41.3% of patients were male. Most patients had a single lesion (92.2%, n = 248), while 7.8% (n = 21) had multiple lesions. Lesions were most commonly supratentorial cortical (40.5%, n = 109), followed by the brainstem (26.8%, n = 72) and supratentorial subcortical (24.2%, n = 65). The mean lesion size was 13.2 mm (SD 7.5). DVAs were present in 51.1% of patients (n = 135), with Type I CCM-DVAs accounting for 51.1%, Type II for 32.6%, and Type III for 16.3%. The mean DVA size was 2.3 mm (SD 1.3), with Type III being the largest (mean: 3.82 mm, SD 1.18). CCM-DVA type was significantly associated with lesion multiplicity, and Type II and III were the strongest independent predictors (p = 0.011 and p < 0.001, respectively). Brainstem CCM lesions were also significant in both univariate and multivariate models (p = 0.044). No significant associations were found with modifiable risk factors. This study is the first to systematically evaluate clinical and radiological factors associated with lesion multiplicity in sporadic CCMs. The findings identify CCM-DVA type and brainstem CCM location as key predictors, underscoring the need for further investigation into the genetic and vascular mechanisms driving lesion formation and progression.