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Ictal SPECT injected during the pre-generalization period, with CBF increases including but not limited to the correct localization. Patient had right temporal neocortical epilepsy confirmed by intracranial EEG (Patient 12, Table 1, see also Supplementary Table 1). ( A ) Three dimensional rendering. ( B ) Coronal views with results superimposed on the SPM MRI template. Ictal SPECT scan was background subtracted using the patient’s interictal SPECT, and the difference was then compared with a database of normal SPECT pairs using ISAS (see Methods section). CBF increases are shown as warm colours, and decreases are shown as cool colours; colour bars indicate t -values. The most significant hyperperfusion cluster was localized to the right temporal and occipital lobes (cluster-level significance P 5 0.0001 corrected for multiple comparisons, Z -score of most significant voxel = 6.48, cluster size, k = 29 663 voxels). Extent threshold, k = 125 voxels (voxel dimensions 2 Â 2 Â 2 mm), voxel-level height threshold, P = 0.01.
Source publication
Partial seizures produce increased cerebral blood flow in the region of seizure onset. These regional cerebral blood flow increases can be detected by single photon emission computed tomography (ictal SPECT), providing a useful clinical tool for seizure localization. However, when partial seizures secondarily generalize, there are often questions o...
Contexts in source publication
Context 1
... should be noted that some studies reported good localization of seizure onset based on post-ictal CBF decreases (Devous et al ., 1998; O’Brien et al ., 1999), which could reflect differences in analysis methods. Although post-ictal CBF decreases may have questionable value for localizing the lobe of seizure onset, we recently found that the hemisphere with greatest overall post-ictal CBF decreases usually corresponds to the side of seizure onset (McNally et al ., 2005). Post-ictal CBF decreases in partial seizures without secondary generalization can thus be useful to at least lateralize the side of seizures onset. We were therefore interested in whether the side of overall greatest hypoperfusion would be useful for lateralizing the side of onset of partial seizures with secondary generalization. We found that for SPECT injections in the pre-generalization phase, the side of greater hypoperfusion was ipsilateral or contralateral to the side of onset with about equal frequency, and was therefore not clinically useful for lateralization (five ipsilateral and four contralateral, Table 3). Interestingly, for seizures injected during the generalization phase, hypoperfusion was greater in the hemisphere contralateral to seizure onset in 90% (9 of 10) of patients with known side of seizure onset (Table 3). For postictal injections, hypoperfusion remained greater in the hemisphere contralateral to onset in most cases (71%; 17 of 24 patients, Table 4). This was especially true for patients injected within 15 s of seizure end, where 100% (seven of seven) showed greater hypoperfusion contralateral to onset (Patients 25–32 in Tables 2 and 4). These findings suggest that while CBF decreases are not useful for localizing the lobe of seizure onset, CBF decreases during and shortly after generalization are usually greatest in the hemisphere contralateral to the side of onset. It is of interest that this is opposite to the pattern seen following partial seizures without generalization, where overall hypoperfusion is usually greatest in the hemisphere ipsilateral to side of onset (McNally et al ., 2005). Examples of CBF decreases during partial seizures with secondary generalization are shown in Figs 1–3. In the example shown during the pre-generalization period, CBF decreases were seen in multiple bilateral brain regions (Fig. 1), similar to those reported previously for temporal lobe seizures without generalization (Van Paesschen et al ., 2003; Blumenfeld et al ., 2004). In the ...
Context 2
... cases the single region of ictal CBF increase correctly localized seizure onset (Table 1). This compares favourably with partial seizures, where we recently found using the same methods that if a single unambiguous region of ictal CBF increase was found, it was correct in 10/10 patients (100%) meeting these criteria (McNally et al ., 2005). In the other six patients with a single unambiguous CBF increase (Patients 8, 11, 17, 18, 21, 23), the precise localization was not known. However, as already dis- cussed, the CBF increases correctly identified at least the hemisphere of onset in all of these patients in which the side of onset was known (Patients 8, 17, 18, 23). An example of an ictal SPECT injected during the pre- generalization period is shown in Fig. 1. In this patient (Patient 12, Table 1), ictal–interictal SPECT analysed using ...
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Citations
... The usefulness of SPECT ictal studies approaches that of [18F]FDG-PET in patients with TLE, and ictal studies are probably superior for extratemporal focus localization [161][162][163]. Partial seizures often show more reliable results than secondarily generalized seizures [164]. False localization is reported in 3-4% of studies, presumably because of seizure propagation, and is more likely to occur with later injection times [107]. ...
This chapter will cover the neuroimaging techniques and their application to the diagnostic work up and management of adults and children with new onset or chronic epilepsy. We will focus on the specific indications and requirements of different imaging techniques for the diagnosis and pre-surgical work up of pharmacoresistant focal epilepsies. We will discuss the sensitivity, specificity and prognostic value of imaging features, benign variants and artefacts, and the possible diagnostic significance of non-epileptogenic lesions. This chapter is intended to be relevant for day-to-day practice in average clinical circumstances, with emphasis on MRI and most commonly used functional neuroimaging techniques.
... The results were similar irrespective of the analysis, that is, two discrete but strongly connected networks can be identified in the interictal state, when informed by the patterns of significant hyperperfusion, and separately significant hypoperfusion, during seizures. The localization value of SPECT studies is considered to be higher with an early ictal injection of the radiotracer (Lee et al., 2011), and with injection during focal seizures that do not evolve to secondary generalization (Varghese et al., 2009). It is important to note that the observed correlations between SPECT and FC were quite robust and were not significantly impacted by early vs. late timing of ictal SPECT injection, secondary generalization versus nongeneralized SPECT seizure, presence of one (uni-focal) versus more than one (multi-focal) SEEG onset regions, and seizure-free versus nonseizurefree outcome. ...
Single-photon emission computed tomography (SPECT) during seizures and magnetoencephalography (MEG) during the interictal state are noninvasive modalities employed in the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy (DRFE). The present study aims to investigate whether there exists a preferentially high MEG functional connectivity (FC) among those regions of the brain that exhibit hyperperfusion or hypoperfusion during seizures. We studied MEG and SPECT data in 30 consecutive DRFE patients who had resective epilepsy surgery. We parcellated each ictal perfusion map into 200 regions of interest (ROIs) and generated ROI time series using source modeling of MEG data. FC between ROIs was quantified using coherence and phase-locking value. We defined a generalized linear model to relate the connectivity of each ROI, ictal perfusion z score, and distance between ROIs. We compared the coefficients relating perfusion z score to FC of each ROI and estimated the connectivity within and between resected and unresected ROIs. We found that perfusion z scores were strongly correlated with the FC of hyper-, and separately, hypoperfused ROIs across patients. High interictal connectivity was observed between hyperperfused brain regions inside and outside the resected area. High connectivity was also observed between regions of ictal hypoperfusion. Importantly, the ictally hypoperfused regions had a low interictal connectivity to regions that became hyperperfused during seizures. We conclude that brain regions exhibiting hyperperfusion during seizures highlight a preferentially connected interictal network, whereas regions of ictal hypoperfusion highlight a separate, discrete and interconnected, interictal network.
... Previous reports in temporal lobe epilepsy showed variable perfusion changes could occur during the postictal phase, except for PSE (22,23), including hypoperfusion contralateral to the focus after secondary generalization [currently described as "focal to bilateral tonic-clonic seizures" (FBTCS)] (22). Thus, if postictal hypoperfusion occurs in the hemisphere contralateral to the stroke lesion in PSE, the phenomenon may lead to pseudo-positive findings on the asymmetry method. ...
... Previous reports in temporal lobe epilepsy showed variable perfusion changes could occur during the postictal phase, except for PSE (22,23), including hypoperfusion contralateral to the focus after secondary generalization [currently described as "focal to bilateral tonic-clonic seizures" (FBTCS)] (22). Thus, if postictal hypoperfusion occurs in the hemisphere contralateral to the stroke lesion in PSE, the phenomenon may lead to pseudo-positive findings on the asymmetry method. ...
Using dual single-photon emission computed tomography (SPECT) scanning, we recently found the postictal-interictal (P-I) subtraction method frequently detects prolonged postictal hyperperfusion in poststroke epilepsy (PSE) and thus may be valuable for auxiliary diagnosis. This study aimed to determine if the asymmetry method can localize hyperperfusion to reflect epileptic activity in PSE using a single postictal SPECT scan. Sixty-four patients with PSE who had undergone perfusion SPECT two times (postictal and interictal) were enrolled. We formulated a novel asymmetry method (subtraction analysis of reversed postictal SPECT from postictal SPECT, co-registered to magnetic resonance imaging) to identify paradoxical asymmetric increase, defined as a higher perfusion area adjacent to stroke lesions compared to the contralateral side. The postictal hyperperfusion area and detection rates were determined by the asymmetry and P-I subtraction methods independently. We subsequently calculated the sensitivity and specificity of the asymmetry method, compared to the gold standard P-I subtraction method. We also evaluated lateralization concordance between the asymmetry method and other clinical findings. Among 64 patients (median age, 75 years), prolonged postictal hyperperfusion was detected in 43 (67%) by the asymmetry, and 54 (84%) the P-I, method. The asymmetry method had high sensitivity (80%) and specificity (100%) in detecting postictal hyperperfusion, showing high lateralization concordance with seizure semiology (97%) and epileptiform electroencephalography findings (interictal/ictal epileptiform discharges or periodic discharges) (100%). The present study demonstrated the advantages of the objective asymmetry method for detecting prolonged hyperperfusion through using one postictal SPECT scan in PSE.
... Thus, ictal SPECT and ASL MRI can, at best, detect the hemodynamic changes associated with the entire propagation path of the seizure, with localization of the onset zone depending on the timing between seizure onset and dye injection (for SPECT), the interval between seizure and MRI (for ASL MRI), and the presence of secondary generalization. 11 This information can however be used to guide placement of invasive electrical recordings, which would be capable of refining the seizure onset zone using signatures of an epileptic focus such as those identified by Lim et al. (e.g., increased preictal interneuron synchronization and decreased preictal gamma power). Ongoing studies with simultaneous measurement of epileptiform neuronal activity and cerebral blood flow, like those highlighted here, will continue to inform the use of (also rapidly advancing) clinical neuroimaging modalities to improve outcomes of patients undergoing surgical resection for the treatment of epilepsy. ...
... Focal epilepsy with FBTCS has been noted to have a larger propagation network than in focal epilepsy without FBTCS 29,30 . Therefore, the question could be raised of whether the increase in RMS CCEPs both near and distant from ictal onset zone in FCD type I could be attributable to a greater percentage of patients having FBTCS. ...
Objective
To determine whether brain connectivity differs between focal cortical dysplasia (FCD) types I and II.
Methods
We compared cortico‐cortical evoked potentials (CCEPs) as measures of effective brain connectivity in 25 FCD patients with drug‐resistant focal epilepsy who underwent intracranial evaluation with stereo‐electroencephalography (SEEG). We analyzed the amplitude and latency of CCEP responses following ictal‐onset single‐pulse electrical stimulation (iSPES).
Results
In comparison to FCD type II, patients with type I demonstrated significantly larger responses in the electrodes near the ictal‐onset zone (<50 mm). These findings persisted when controlling for the location of the epileptogenic zone, as noted in patients with temporal lobe epilepsies, as well as controlling for seizure type, as noted in patients with focal to bilateral tonic‐clonic seizures (FBTCS). In type II, the root mean square (RMS) of CCEP responses dropped substantially from the early segment (10–60 ms) to the middle and late segments (60–600 ms). The middle and late CCEP latency segments showed the largest differences between FCD types I and II.
Significance
Focal cortical dysplasia type I may have a greater degree of cortical hyperexcitability as compared with FCD type II. In addition, FCD type II displays a more restrictive area of hyperexcitability in both temporal and spatial domains. In patients with FBTCS and type I FCD, the increased amplitudes of RMS in the middle and late CCEP periods appear consistent with the cortico‐thalamo‐cortical network involvement of FBTCS. The notable differences in degree and extent of hyperexcitability may contribute to the different postsurgical seizure outcomes noted between these two pathological substrates.
... Moreover, traditional side-by-side visual inspection and interpretation of interictal and ictal SPECT can be technically challenging. More sophisticated techniques, such as subtraction ictal SPECT co-registered with MRI (SISCOM), (Varghese et al., 2009;Desai et al., 2013), statistical parametric mapping (SPM), (McNally et al., 2005) and stratifying differences on ictal/interictal subtraction SPECT images based on pixel values, (Koo et al., 2003) can be used to improve the clinical utility of ictal SPECT in localizing the seizure-onset zone, especially in nonlesional and extratemporal epilepsies (von Oertzen et al., 2011). At centers where these tools are not available, proper utilization of SPECT may be limited. ...
Objective
Single-photon emission computed tomography (SPECT) is an ancillary noninvasive test commonly used to identify the epileptogenic zone. However, its proper utilization may be limited depending on the resources available at each center. This study aimed to investigate the utility of SPECT in presurgical evaluation of children at our center.
Methods
This was an observational retrospective study in 150 children who were admitted to the Epilepsy Monitoring Unit for presurgical evaluation between 2012 and 2019. The utility of interictal and ictal SPECT in different clinical cohorts was analyzed.
Results
Only interictal SPECT was performed on 87 patients (58 %), while ictal SPECT was performed on 62 (41.3 %), and interictal SPECT alone was considered of low diagnostic value. Ictal SPECT was unremarkable in 27 of 62 patients and abnormal in 35. Ictal SPECT was localized to the temporal lobe in 62.8 % and to the extratemporal lobe in 25.7 % of the patients and lateralized to one hemisphere in 11.4 % of the patients. In the abnormal SPECT group, ictal SPECT was considered unnecessary in 7/35 (20 %) patients with a single lesion and 3/35 (8.5 %) patients with a hemispheric lesion. In the remaining 25 patients, surgery was recommended more frequently than invasive EEG monitoring (IEM) for diffuse lesion cases (P = 0.03), while IEM was recommended more frequently than surgery for MRI-negative cases (P = 0.03), and in this group none of the MRI-negative patients underwent surgery. In our entire cohort, epilepsy surgery was performed on 24.4 % of the patients, 64 % with a single lesion, 7.6 % with a hemispheric lesion, 25.6 % with a diffuse lesion, and only one MRI-negative patient (2.5 %). Surgery was performed in 48.7 % of single lesion cases and 20.5 % of diffuse lesion cases with either unremarkable or no ictal SPECT. Engel class I outcome was achieved in 62 % and class II outcome in 33 % of the patients. In the single lesion etiology, 72 % (18/25) patients achieved excellent outcome and within this group, 22 % (4/18) patients had a positive ictal SPECT whereas 78 % (14/18) patients either did not get an ictal SPECT or it was unremarkable.
Significance
Based on our findings, we suggest carefully selecting patients for SPECT imaging to improve its utility and prevent overutilization and potential harm to children.
... Autonomic signs, particularly drooling/foaming resulting from a lack of swallowing, profuse sweating and excessive salivation, are commonly prominent in secondarily generalized tonic clonic seizures (8); in sGC, however, the absence of autonomic signs is acceptable because an electrocorticography study has suggested that some regions can be spared to some degree, even if a seizure is clinically generalized (17). Given previous suggestions that generalized seizures are not truly generalized (18,19), it is acceptable that the semiology of sGC is clinically heterogeneous and lacks autonomic signs. Therefore, we considered that the absence of autonomic signs during sGC could be an important semiology associated with this specific situation (i.e., the sparing of an area necessary for maintaining consciousness from the seizure activities). ...
We herein report two epilepsy patients with the seizure focus in the non-dominant hemisphere manifesting secondarily generalized convulsion (sGC) with retained awareness characterized by a lack of autonomic signs although GC was complicated by respiratory arrest. Given the semiology and electrophysiological findings, the seizure activity was considered to propagate to the supplementary-motor area and the bilateral primary-motor area, with a clinical manifestation of sGC. The absence of autonomic signs during GC can be a key indicator that the seizure remains in the bilateral suprasylvian area and thus does not involve the region necessary for awareness preservation, which may assist in the diagnosis of this atypical epileptic seizure.
... Secondary generalized seizure (sGS) is a major source of disability in temporal lobe epilepsy (TLE), and it often does not respond to existing drug treatments (Bialer and White, 2010). Up to 70% of patients with partial epilepsy (including TLE) occasionally experience sGS (Forsgren et al., 1996); however, the underlying circuit mechanisms of sGS in TLE have been limited by the challenges of performing electrophysiology/imaging studies or therapeutic interventions in the face of generalized convulsions (Chang and Lowenstein, 2003;Moshé et al., 2015;Varghese et al., 2009). Poor control of those sGSs is the most important risk factor for sudden unexpected death in epilepsy and seizure-related serious injuries ( Bone et al., 2012). ...
... Blumenfeld, H., Varghese, G.I., Purcaro, M.J., Motelow, J.E., Enev, M., McNally, K.A., Levin, A.R., Hirsch, L.J., Tikofsky, R., Zubal, I.G., et al. (2009). Cortical and subcortical networks in human secondarily generalized tonicclonic seizures. ...
... SISCOM studies have been more localizable with early ictal SPECT tracer injections ( Lee et al., 2011), SPECT seizures without secondary generalization ( Varghese et al., 2009;von Oertzen et al., 2011) and lesional MRIs (von Oertzen et al., 2011). In our subgroup analysis, none of these factors substantially influenced the proportion of studies with positive significant SISCOM/CCEP correlations, probably because our analysis was not focused on localizing the IOZ, but on detecting connectivity at a larger scale. ...
Subtraction ictal and interictal single photon emission computed tomography can demonstrate complex ictal perfusion patterns. Regions with ictal hyperperfusion are suggested to reflect seizure onset and propagation pathways. The significance of ictal hypoperfusion is not well understood. The aim of this study was to verify whether ictal perfusion changes, both hyper- and hypoperfusion, correspond to electrically connected brain networks. A total of 36 subtraction ictal and interictal perfusion studies were analysed in 31 consecutive medically refractory focal epilepsy patients, evaluated by stereo-electroencephalography that demonstrated a single focal onset. Cortico-cortical evoked potential studies were performed after repetitive electrical stimulation of the ictal onset zone. Evoked responses at electrode contacts outside the stimulation site were used as a measure of connectivity. The evoked responses at these electrodes were compared to ictal perfusion values noted at these locations. In 67% of studies, evoked responses were significantly larger in hyperperfused compared to baseline-perfused areas. The majority of hyperperfused contacts also had significantly increased evoked responses relative to pre-stimulus electroencephalogram. In contrast, baseline-perfused and hypoperfused contacts mainly demonstrated non-significant evoked responses. Finally, positive significant correlations (P < 0.05) were found between perfusion scores and evoked responses in 61% of studies. When the stimulated ictal onset area was hyperperfused, 82% of studies demonstrated positive significant correlations. Following stimulation of hyperperfused areas outside seizure onset, positive significant correlations between perfusion changes and evoked responses could be seen, suggesting bidirectional connectivity. We conclude that strong connectivity was demonstrated between the ictal onset zone and hyperperfused regions, while connectivity was weaker in the direction of baseline-perfused or hypoperfused areas. In trying to understand a patient's epilepsy, one should consider the contribution of all hyperperfused regions, as these are likely not random, but represent an electrically connected epileptic network.
... Secondary generalized seizure (sGS) is a major source of disability in temporal lobe epilepsy (TLE), and it often does not respond to existing drug treatments (Bialer and White, 2010). Up to 70% of patients with partial epilepsy (including TLE) occasionally experience sGS (Forsgren et al., 1996); however, the underlying circuit mechanisms of sGS in TLE have been limited by the challenges of performing electrophysiology/imaging studies or therapeutic interventions in the face of generalized convulsions (Chang and Lowenstein, 2003;Moshé et al., 2015;Varghese et al., 2009). Poor control of those sGSs is the most important risk factor for sudden unexpected death in epilepsy and seizure-related serious injuries (Bone et al., 2012). ...
Secondary generalized seizure (sGS) is a major source of disability in temporal lobe epilepsy (TLE) with unclear cellular/circuit mechanisms. Here we found that clinical TLE patients with sGS showed reduced volume specifically in the subiculum compared with those without sGS. Further, using optogenetics and extracellular electrophysiological recording in mouse models, we found that photoactivation of subicular GABAergic neurons retarded sGS acquisition by inhibiting the firing of pyramidal neurons. Once sGS had been stably acquired, photoactivation of GABAergic neurons aggravated sGS expression via depolarized GABAergic signaling. Subicular parvalbumin, but not somatostatin subtype GABAergic, neurons were easily depolarized in sGS expression. Finally, photostimulation of subicular pyramidal neurons genetically targeted with proton pump Arch, rather than chloride pump NpHR3.0, alleviated sGS expression. These results demonstrated that depolarized GABAergic signaling in subicular microcircuit mediates sGS in TLE. This may be of therapeutic interest in understanding the pathological neuronal circuitry underlying sGS.
