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

Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-7169, USA.
Epilepsia (Impact Factor: 4.57). 12/2008; 50(6):1361-70. DOI: 10.1111/j.1528-1167.2008.01881.x
Source: PubMed


Current evidence suggests that the mechanisms underlying depth electrode-recorded seizures beginning with hypersynchronous (HYP) onset patterns are functionally distinct from those giving rise to low-voltage fast (LVF) onset seizures. However, both groups have been associated with hippocampal atrophy (HA), indicating a need to clarify the anatomic correlates of each ictal onset type. We used three-dimensional (3D) hippocampal mapping to quantify HA and determine whether each onset group exhibited a unique distribution of atrophy consistent with the functional differences that distinguish the two onset morphologies.
Sixteen nonconsecutive patients with medically refractory epilepsy were assigned to HYP or LVF groups according to ictal onset patterns recorded with intracranial depth electrodes. Using preimplant magnetic resonance imaging (MRI), levels of volumetrically defined HA were determined by comparison with matched controls, and the distribution of local atrophy was mapped onto 3D hippocampal surface models.
HYP and LVF groups exhibited significant and equivalent levels of HA ipsilateral to seizure onset. Patients with LVF onset seizures also showed significant contralateral volume reductions. On ipsilateral contour maps HYP patients exhibited an atrophy pattern consistent with classical hippocampal sclerosis (HS), whereas LVF atrophy was distributed more laterally and diffusely. Contralateral LVF maps also showed regions of subicular atrophy.
The HS-like distribution of atrophy and the restriction of HA to the ipsilateral hippocampus in HYP patients are consistent with focal hippocampal onsets, and suggest a mechanism utilizing intrahippocampal circuitry. In contrast, the bilateral distribution of nonspecific atrophy in the LVF group may reflect mechanisms involving both hippocampal and extrahippocampal networks.

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Available from: Gil D Hoftman, Oct 04, 2015
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    • "LVF seizures start with a positive or negative going spike followed by low-amplitude, high-frequency activity, whereas HYP seizures are characterized at onset by the occurrence of focal periodic spiking. Imaging studies have suggested that these two seizure onset patterns are linked to distinct underlying pathologies; patients with HYP seizures are indeed more likely to show focal onset and greater neuronal loss in the hippocampus than those showing LVF seizures that are often associated with more diffuse lesions (Ogren et al. 2009; Velasco et al. 2000). We recently discovered in the pilocarpine model of temporal lobe epilepsy (TLE) that these two patterns of seizure onset are associated with distinct patterns of occurrence of high-frequency oscillations (HFOs) (Lévesque et al. 2012). "
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    ABSTRACT: Low-voltage fast- (LVF) and hypersynchronous- (HYP) seizure onset patterns can be recognized in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples (80-200 Hz) and fast ripples (250-500 Hz) have been linked to each pattern, with ripples predominating during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the contribution of neural networks with distinct transmitter signaling characteristics. Here, we tested this hypothesis by analysing the seizure activity induced with the K(+) channel blocker 4-aminopyridine (4AP, 4-5 mg/kg, i.p.) - which enhances both glutamatergic and GABAergic transmission - or the GABAA receptor antagonist picrotoxin (3-5 mg/kg, i.p.); rats were implanted with electrodes in the hippocampus, the entorhinal cortex and the subiculum. We found that LVF-onset occurred in 82% of 4AP-induced seizures while seizures following picrotoxin were always HYP. In addition, HFO analysis revealed that 4AP-induced LVF seizures were associated to higher ripple rates compared to fast ripples (p<0.05), whereas picrotoxin-induced seizures contained higher rates of fast ripples compared to ripples (p<0.05). These results support the hypothesis that two distinct patterns of seizure onset result from different pathophysiological mechanisms. Copyright © 2015, Journal of Neurophysiology.
    Journal of Neurophysiology 02/2015; 113(7):jn.00031.2015. DOI:10.1152/jn.00031.2015 · 2.89 Impact Factor
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    • "Author's personal copy Engel, 2002; Staba et al., 2004). By contrast, other HFOs (200–600 Hz, originally termed " fast ripples " ) localize to brain regions capable of generating spontaneous seizures (Bragin, Engel, Wilson, Fried, & Mathern, 1999; Jacobs et al., 2008; Staba et al., 2002; Worrell et al., 2008), and rates of their occurrence have been linked with the severity of morphological alterations associated with HS in MTLE (Ogren, Wilson, et al., 2009; Figure 5.3 Three-dimensional surface contour maps depicting hippocampal atrophy in patients with unilateral hypersynchronous (HYP) or low voltage fast (LVF) ictal EEG onset. (A) In the hippocampus ipsilateral to seizure onset, patients with HYP onsets had significant atrophy (colored white and red (white and light gray in print version)) in several areas that included dentate gyrus (DG), subfields CA3 and CA1, and to lesser extent CA2 (shaded blue (dark gray in print version)). "
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    ABSTRACT: Limbic epilepsy refers to a condition that consists of epileptic seizures that originate in or preferentially involve the limbic system. The majority of cases are medically refractory, necessitating surgical resection when possible. However, even resection of structures thought to be responsible for seizure generation may not leave a patient seizure free. While mesial temporal lobe limbic structures are centrally involved, there is growing evidence that the epileptogenic network consists of a broader area, involving structures outside of the temporal lobe and the limbic system. Information on structural, functional, and metabolic connectivity in patients with limbic epilepsy is available from a large body of studies employing methods such as MRI, EEG, MEG, fMRI, PET, and SPECT scanning, implicating the involvement of various brain regions in the epileptogenic network. To date, there are no consistent and conclusive findings to define the exact boundaries of this network, but it is possible that in the future studies of network connectivity in the individual patient may allow more tailored treatment and prognosis in terms of surgical resection.
    International Review of Neurobiology 08/2014; 114C:89-120. DOI:10.1016/B978-0-12-418693-4.00005-4 · 1.92 Impact Factor
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    • "characteristics are reminiscent of the hypersynchronous onset and of the low-voltage, fast activity onset patterns, respectively, that have been reported to occur in vivo in both epileptic patients (Velasco et al., 2000; Ogren et al., 2009) and animal models (Bragin et al., 1999, 2005; Lévesque et al., 2012, 2013). Overall, these in vitro data indicate that the perirhinal cortex may be more prone to generate ictal discharges as compared with the entorhinal cortex. "
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    ABSTRACT: The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.
    Frontiers in Cellular Neuroscience 08/2013; 7:130. DOI:10.3389/fncel.2013.00130 · 4.29 Impact Factor
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