Abstracts

Rationale: Malformations of cortical development (MCD) are a heterogeneous group of lesions that share in common a strong association with epilepsy. Although the boundless evidences of structural and metabolic abnormalities in the aberrant lesions of MCD, recent studies have started looking into the associated abnormalities in the normal appearing parenchyma (NAP) of these patients. Intracellular pH is an important parameter of brain bionergetics and electrophysiological status in neurons and glia, and there is a large body of evidence pointing to neurometabolic disturbances as key factors in epileptogenesis. The goal of this study was to evaluate the intracellular hydrogen-ion potential (pH) in the NAP of patients with MCD and epilepsy. Methods: Three-dimensional phosphorus magnetic resonance spectroscopy (31P-MRS) at 3.0 Tesla was performed in 37 MCD patients and in 31 matched-control subjects. The patients were assigned into three main MCD subgroups: hemimegalencephaly/cortical dysplasia (n = 10); heterotopia (n = 14); schizencephaly/polymicrogyria (n = 13). Voxels (12.5 cm3) were selected in five homologous regions containing NAP: right putamen; left putamen; frontoparietal parasagittal cortex; right centrum semiovale; and left centrum semiovale. Robust methods of quantification were applied, and the intracellular pH was calculated with the chemical shifts of inorganic phosphate (Pi) relative to phosphocreatine (PCr). Results: In comparison to controls and assuming a p value < 0.05, MCD patients presented acidosis in the frontoparietal parasagittal cortex, right centrum semiovale, and left centrum semiovale (Table 1). Dunnet and Dunn tests demonstrated that the differences in pH values remained statistically significant in all MCD subgroups (Figure 1). Conclusions: Hydrogen ions play a remarkable role in the maintenance of electrophysiological status and in the regulation of several mitochondrial reactions. The present study demonstrates widespread acidosis in the NAP, and reinforces the idea that MCD visible lesions are only the tip of the iceberg. This issue may be of particular importance in patients who are candidates for lesion resection. The NAP could be a secondary target for medical interventions, and understanding the biochemical abnormalities that occur beyond the visible lesions may facilitate this approach.