Abstracts

Rationale: Metabolic imaging studies, such as positron emission tomography (PET), allow for an assessment of physiological functioning of the brain and [¹⁸F]fluoro-2-deoxyglucose (FDG) - PET is now a commonly used technique in pre-surgical epilepsy evaluations. Focal inter-ictal decreases in glucose consumption are often but inconsistently concordant with the ictal onset area and the underlying mechanisms are poorly understood. The current study tests the hypothesis that areas of glucose hypometabolism, determined by FDG-PET, are associated with mitochondrial dysfunction in patients with medically intractable epilepsy associated with isolated focal cortical dysplasia (FCD). Methods: Measures of electron transport chain (ETC) functioning and mitochondrial abnormalities (ETC complex biochemistry, Akt1, GFAP) were assessed in surgical resection specimens that had hypometabolic abnormalities and those that were normal on FDG-PET. Determination of FDG-PET abnormalities was made based on co-registration of statistical parametric mapping (SPM) results with post-surgical images (Figure 1). Seizure outcome for each patient at 24 months was classified based upon the system proposed by the ILAE. Results: 22 patients (11 males, 11 females; mean age at the time of surgery 10.5 ± 4.4 years), with pathologically confirmed FCD, were included in this retrospective review. Complex IV function was found to be significantly reduced in areas of hypometabolism (p = 0.014) while there was a trend towards a significant reduction in complexes II and III function in areas of hypometabolism (p=0.08, p=0.059, respectively) (Figure 2). These decreases were independent of cortical dysplasia severity (p=0.321) and other clinical epilepsy measures. In addition, no difference in long term seizure outcome was found between the patients with PET normal and PET hypometabolic resection specimens. However, the odds of attaining an ILAE outcome of 1 or 2 (seizure free with our without auras) was much greater if the resection included low Complex IV functioning of less than 8.0 (OR=24, 95% CI 2-282). Conclusions: The most important finding from our study is that there is a significant decrease in Complex IV activity within regions of glucose hypometabolism. This finding is unrelated to the duration of epilepsy, frequency of seizures, or the degree of FCD severity. This study suggests an association among glucose hypometabolism, reduced mitochondrial complex IV functioning, and the seizure onset zone which is independent of the degree of cortical dysplasia.