Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most common form of medically intractable epilepsy, with the most common pathologic finding being mesial temporal sclerosis (MTS). Lateralization of the epileptogenic focus is critical to successful epilepsy surgery. Whether clinically meaningful differences exist in the epileptic networks involved in complex partial seizures which is dependent on laterality of the hemisphere of origin is currently unknown. Methods: This study compares the ictal SPECT perfusion patterns in subjects with lateralized TLE who had pathologically confirmed MTS and Engel class I postsurgical outcome to ensure correct lateralization (n = 20 left TLE, n = 18 right TLE). A SPM analysis of ictal SPECT images was used to isolate hypoperfusion differences between the right and left TLE. We used these laterality of seizure-focus-dependent hypoperfusion differences to create an anterior-to-posterior hypoperfusion asymmetry index (API) and evaluated lateralization accuracy in various support vector machine (SVM) classifier algorithms in ictal, interictal, and subtraction SPECT analyses. In order to characterize the networks involved in the hypoperfusion differences observed, we used task-free fMRI to investigate the functional anatomy of the anterior and posterior limbic networks (ALN and PLN) of normal controls. We then evaluated whether normal limbic network connectivity was predictive of ictal SPECT perfusion in TLE. Results: We observed significant differences in perfusion between right and left MTS (FDR p < 0.001). This consists of greater frontal lobe hypoperfusion (Figure 1a) associated with thalamus, midbrain, and brainstem hyperperfusion in left MTS and a greater parietal lobe hypoperfusion (Figure 1b) associated with basal ganglia and right middle temporal hyperperfusion in right MTS. The accuracy of various SVM classifier models indicate that API adds lateralizing value to traditional ictal and interictal measures of right-left hyperperfusion asymmetry, but not to ictal-interictal subtraction analyses. The normal functional anatomy of the ALN and PLN (Figure 1c) is predictive of the ictal SPECT perfusion changes seen in MTS. PLN connectivity was most predicative of ictal perfusion in left MTS (r = 3.8, p = 3.1E-05) (Figure 2a) while ALN connectivity was most predictive of ictal perfusion in right MTS (r = 3.8, p = 3.3E-05) (Figure 2b). Conclusions: There are differences in the large-scale epileptic network effects of TLE depending on the laterality of origin, which are clinically meaningful. We also found that limbic network connectivity was predictive of ictal SPECT perfusion patterns. Right-sided foci preferentially affect anterior limbic circuitry, while left-sided foci preferentially affect posterior limbic circuitry. Understanding the laterality dependent differences in epileptic networks will not only facilitate clinical localization, but will also have important implications for targeted surgical interventions aimed at indirectly modifying epileptic networks (e.g. vagal nerve stimulation and deep brain stimulation).