Differences in iron content between gray matter heterotopia and normal gray matter

Gray matter heterotopia (GMH) is a common etiology of epilepsy. However, the precise pathophysiological mechanisms driving epileptogenesis remain unclear. Iron deposition has been postulated as a potential modulator of neuronal excitability in epilepsy. Leveraging the unique advantage of enhanced T2*-weighted magnetic resonance angiography (ESWAN) sequence in quantitatively assessing cerebral iron content, this study aimed to assess differences in iron deposition between GMH and normal gray matter (NGM), and to explore the potential pathophysiology of GMH-related epilepsy.

Patients diagnosed with GMH between January 2020 and April 2025 were screened according to inclusion and exclusion criteria. A total of 78 patients with 105 GMH lesions were ultimately enrolled. Phase and magnitude images were acquired based on the ESWAN. Regions of interest (ROIs) were manually delineated by two observers. The consistency of measurements between observers was assessed using the intraclass correlation coefficient (ICC). ROIs were placed at the center of the GMH lesions and in NGM at the ipsilateral level, with the typically located NGM serving as a reference. Corresponding quantitative parameters were subsequently obtained. Paired sample t-tests were used to compare the quantitative parameters between GMH and NGM.

A total of 78 patients with GMH (43 males and 35 females) were included in this study, with a mean age of 27.5 years (range, 17-38 years). Among them, 27 cases presented with bilateral lesions and 51 cases with unilateral lesions. Based on the location of the lesions, periventricular nodular heterotopia (PVNH) was the most common type (62 cases) followed by band heterotopia (BH) (11 cases) and subcortical nodular heterotopia (5 cases). Paired samples t-tests revealed significantly lower phase values in GMH compared to NGM in the right (adjusted P=0.028) and left (adjusted P=0.002) hemispheres. Similarly, magnitude values were significantly lower in GMH (right: adjusted P=0.003; left: adjusted P=0.013).

ESWAN initially untangled the differences in iron deposition between GMH and NGM.