Abstract PURPOSE To determine the impact of subventricular zone (SVZ) invasion on neurocognitive dysfunction in diffuse glioma patients. MATERIALS AND METHODS We collected neuropsychological assessments of treatment-naïve WHO grade 2-4 diffuse glioma patients between 2017 to 2023. The Chi-square test determined the odds ratio (OR), and multiple linear regression identified factors related to cognitive deficits using Python 3.11.4. RESULTS Of the 129 patients, 64 exhibited SVZ invasion (SVZ+) while 65 were SVZ-. Groups were matched for WHO grading. SVZ+ was associated with more defective domains than SVZ- in both lower grade (WHO grade 2,3, 3.2 ± 2.1 vs. 2.1 ± 1.9, p=0.019) and high grade (WHO grade 4, 4.9 ± 1.6 vs. 3.6 ± 2.2, p=0.019) tumors. In lower grade gliomas, SVZ+ increased risks of language (OR 7.500, p<0.001) and visual learning impairments (OR 4.375, p=0.014). In high grade gliomas, SVZ+ rendered greater language (OR 8.556, p=0.003) and auditory learning vulnerability (OR 3.850, p=0.039). In right hemispheric tumors, SVZ+ lesions conferred worse executive (OR 6.667, p=0.006) and language function (OR 9.063, p=0.017); in left hemispheric tumors, SVZ+ lesions increased language (OR 3.125, p=0.012) and auditory learning (OR 2.889, p=0.024) impairment. Frontal horn of SVZ+ was related to working memory decline, and body part of SVZ+ was related to emotional deficits. Age and WHO grade 4 were associate with more defective domains in the SVZ+ group. In the SVZ- group, parietal lobe tumor was associate with more defective domains, while high education, temporal lobe, and WHO grade 2 were associate with fewer defective domains. CONCLUSION SVZ invasion impacts pre-operative neurocognitive function regardless of lesion laterality and WHO grade. Distinct SVZ sub-regions are linked to specific cognitive impairments. These findings highlight the need for precise tumor mapping involving the SVZ to evaluate neurocognitive outcomes and consider preventive or rehabilitative interventions.
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