Three-dimensional hippocampal atrophy maps distinguish two common temporal lobe seizure-onset patterns.

Intracranial depth electrode recordings indicate that the majority of seizures in patients with temporal lobe epilepsy (TLE) may be segregated into two groups based on electrographic ictal onset patterns (Engel, 1990). Hypersynchronous (HYP) onsets consist of long-lasting (>5-s) trains of low-frequency (<2-Hz), high-amplitude spikes, whereas low-voltage fast (LVF) onsets are characterized by high-frequency, low-amplitude activity (Townsend & Engel, 1991; Spencer et al., 1992a; Velasco et al., 2000; Bragin et al., 2005b). Seizures beginning with HYP onsets are more likely to originate focally in hippocampal regions and are less likely to spread quickly to the contralateral hemisphere. In contrast, LVF onset seizures are more likely to be regional as opposed to focal, tend to propagate quickly to the contralateral hemisphere, and often originate in the neocortex (Lieb et al., 1981; Engel, 1990; Townsend & Engel, 1991; Spanedda et al., 1997; Velasco et al., 2000). These differences in ictal-onset morphology, propagation time, and spatial distribution, as well as differences in voltage-depth profiles (Bragin et al., 2005b) indicate that seizures with HYP onsets arise via different mechanisms than those beginning with LVF onsets. Despite the differences between HYP and LVF seizure onsets, a characteristic common to these onset patterns is the presence of hippocampal sclerosis (HS) and/or hippocampal atrophy (HA) ipsilateral to the epileptogenic region (Townsend & Engel, 1991; Spencer et al., 1992b; Spanedda et al., 1997; Velasco et al., 2000). However, if different mechanisms of seizure generation and propagation underlie the two onset morphologies, distinct patterns of anatomic damage might be expected for each group. Although previous studies used cell counts to quantify the extent of HS in patients with HYP or LVF onsets, histologic analysis has been derived largely from surgically resected tissue rather than autopsy specimens, so only ipsilateral hippocampus is available and often it is incomplete. It has long been known that damage to contralateral structures may be present as well (Margerison & Corsellis, 1966; Mathern et al., 1995b), and thus HA may be present contralaterally and may differ in extent depending on seizure-onset type. To fully characterize the extent of damage associated with each onset morphology, it is necessary to quantify HA in the entire hippocampus bilaterally. Characterization of the spatial distribution of atrophy in HYP and LVF patients may indicate networks involved in seizure genesis. Recently developed noninvasive magnetic resonance imaging (MRI)–based neuroimaging techniques have been shown to be highly sensitive in detecting and mapping local areas of HA throughout the hippocampi of patients with Alzheimer's disease (Thompson et al., 2004; Apostolova et al., 2006; Frisoni et al., 2006), schizophrenia (Narr et al., 2004), autism (Nicolson et al., 2006), depression (Ballmaier et al., 2008), bipolar illness (Bearden et al., 2007), blindness (Lepore et al., 2008), and TLE (Hogan et al., 2004; Lin et al., 2005). Using techniques such as those developed by Thompson et al. (1996, 2004), three-dimensional (3D) hippocampal surface models may be derived from manually traced serial MRI sections, providing detailed maps of local hippocampal thickness measurements. Maps from patients and from healthy control subjects may then be compared, to quantify atrophy and evaluate the distribution of tissue loss associated with a particular patient group. In the present study, patients with medically refractory TLE were assigned to HYP and LVF onset groups based on ictal-onset patterns recorded with intracranial depth electrodes. Surface contour maps of hippocampi ipsilateral and contralateral to ictal onset were generated for patients with TLE and for age- and gender-matched control subjects to determine the extent and distribution of HA in each seizure-onset group. We hypothesized that this approach would reveal distinct atrophy profiles for each seizure-onset pattern.