Reassessment of the DTI-ALPS index in focal epilepsy

Recent evidence highlights the limited specificity of diffusion tensor imaging (DTI) along perivascular spaces (ALPS) as a noninvasive glymphatic biomarker because microstructural tract degeneration and crossing-fiber geometry confound it. We aimed to reassess the interpretation of the DTI-ALPS index in people with focal epilepsy.

Seventy-nine people with drug-resistant focal epilepsy (PWFE) underwent comprehensive presurgical work-up and 3-T magnetic resonance imaging (MRI). Etiologies included MRI-negative epilepsy, malformations of cortical development, temporal lobe epilepsy, and low-grade epilepsy-associated tumors. DTI preprocessing was conducted using QSIPrep with automated region-of-interest (ROI) placement. Linear regression models and Wilcoxon signed-rank tests were used to assess group differences and associations with clinical variables. Twenty-five age- and sex-matched healthy controls were included for comparison.

Seventy-nine patients (28.6 years ± 11.3 [mean ± standard deviation]; 47 men, 32 women) and 25 healthy controls (mean age, 26.7 years ± 4.2; 11 men, 14 women) were evaluated. DTI-ALPS findings were more abnormal in lesions in proximity to the ROI (p = 0.014), implicating local white matter disruption as a modifier, which was further corroborated by reduced postoperative values. No associations were identified with disease duration, sex, or normalized gray-or white matter volumes.

Our results demonstrate a distance-dependent correlation of DTI-ALPS values to the seizure onset zone in focal epilepsy, whilst no significant associations to disease duration or normalized brain volumes were found. Together, these findings suggest that local disruption of fiber tracts may act as important modifiers of this measure and warrant caution in the interpretation of the DTI-ALPS index.

Question Microstructural changes may significantly confound the interpretation of the DTI-ALPS index as a surrogate parameter for glymphatic system dysfunction in epilepsy. Findings No significant differences in the DTI-ALPS index were observed comparing PWFE with healthy controls; however, lesion proximity and post-operative status significantly alter the metric. Relevance statement Local white-matter disruption and microstructural architecture may significantly alter the DTI-ALPS index; therefore, caution is warranted when interpreting the index as a glymphatic biomarker in focal epilepsy.