Ictal Perfusion Research Articles

Novel noninvasive identification of patient-specific epileptic networks in focal epilepsies: Linking single-photon emission computed tomography perfusion during seizures with resting-state magnetoencephalography dynamics.

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.

EEG Driven Autonomous Injection System For An Epileptic Neuroimaging Application.

Seizure episodes are frequently observed for adults and children suffering from medically refractory epilepsy and the events remain debilitating unless treated with a more comprehensive approach. Ictal perfusion studies with single-photon emission computed tomography (SPECT) is one of the non invasive imaging modality that has been extensively used to adequately localize the seizure focus. Current practices include the tracer injection within a short time interval at the onset of seizure to generate desirable SPECT scan quality with accurate information on foci region. However, the onset of a seizure is a highly unpredictable event and also with added subclinical events, the overall procedure makes it difficult to administer the tracer manually within the ideal time frame.Hence a complete autonomous injection of radioactive tracer element without manual intervention is expected to offer a highly accurate epileptical focus region and aids in further management of the patient. Electroencephalogram (EEG) physiological signals in the preictal phase contain sufficient indicators to predict the seizure event. The proposed injection system works on the seizure prediction model from the EEG signals to release the dosage, making the system completely autonomous in action. The accuracy of the prediction model based on the publicly available seizure embedded EEG datasets was designed to achieve 94% accuracy, and the model was deployed on an edge system. The syringe based injection system was characterized to emulate dosage release action with minimum volumetric error, and low injection time, on predicting seizure Ictal event from the EEG signal. The proposed system is a step towards developing an autonomous injection system for epileptic neuroimaging applications in hospital settings.Clinical relevance- Autonomous injection of tracer dosage for obtaining accurate and high quality Ictal SPECT scan results is preferred over the manual operation in clinical and hospital residential settings as a part of pre-surgical evaluations. The EEG signal based early prediction of seizure ensures adequate time for radioactive tracer element to reach the brain cells and eventually helps to accurately localize the onset region of seizure in the brain. The EEG driven automated injection system for the noninvasive Ictal SPECT method is clinically important as a pre-surgical evaluation in MRI negative or discordant cases for further surgical actions.

Predicting the Outcome of Epilepsy Surgery by Covariance Pattern Analysis of Ictal Perfusion SPECT.

Previous studies on the utility of specific perfusion patterns in ictal brain perfusion SPECT for predicting the outcome of temporal lobe epilepsy surgery used qualitative visual pattern classification, semiquantitative region-of-interest analysis, or conventional univariate voxel-based testing, which are limited by intra- and interrater variability or low sensitivity to capture functional interactions among brain regions. The present study performed covariance pattern analysis of ictal perfusion SPECT using the scaled subprofile model for unbiased identification of predictive covariance patterns. Methods: The study retrospectively included 18 responders to temporal lobe epilepsy surgery (Engel I-A at 12 mo follow-up) and 18 nonresponders (≥Engel I-B). Ictal SPECT images were analyzed with the scaled subprofile model masked to group membership for unbiased identification of the 16 covariance patterns explaining the highest proportion of variance in the whole dataset. Individual expression scores of the covariance patterns were evaluated for predicting seizure freedom after temporal lobe surgery by receiver-operating-characteristic analysis. Kaplan-Meier analysis including all available follow-up data (up to 60 mo after surgery) was also performed. Results: Among the 16 covariance patterns only 1 showed a different expression between responders and nonresponders (P = 0.03). This favorable ictal perfusion pattern resembled the typical ictal perfusion pattern in temporomesial epilepsy. The expression score of the pattern provided an area of 0.744 (95% CI, 0.577-0.911, P = 0.004) under the receiver-operating-characteristic curve. Kaplan-Meier analysis revealed a statistical trend toward longer seizure freedom in patients with positive expression score (P = 0.06). The median estimated seizure-free time was 48 mo in patients with positive expression score versus 6 mo in patients with negative expression score. Conclusion: The expression of the favorable ictal perfusion pattern identified by covariance analysis of ictal brain perfusion SPECT provides independent (from demographic and clinical variables) information for the prediction of seizure freedom after temporal lobe epilepsy surgery. The expression of this pattern is easily computed for new ictal SPECT images and, therefore, might be used to support the decision for or against temporal lobe surgery in clinical patient care.

No Evidence to Favor 99mTc-HMPAO or 99mTc-ECD for Ictal Brain Perfusion SPECT for Identification of the Seizure Onset Zone.

Ictal brain perfusion SPECT with the tracer 99mTc-HMPAO or 99mTc-ECD is widely used for identification of the epileptic seizure onset zone (SOZ) in presurgical evaluation if standard pointers are uncertain or inconsistent. For both tracers, there are theoretical arguments to favor it over the other for this task. The aim of this study was to compare the performance of ictal brain perfusion SPECT between 99mTc-HMPAO and 99mTc-ECD in a rather large patient sample. The study retrospectively included 196 patients from clinical routine in whom ictal perfusion SPECT had been performed with stabilized 99mTc-HMPAO (n = 110) or 99mTc-ECD (n = 86). Lateralization and localization of the SOZ were obtained by the consensus of 2 independent readers based on visual inspection of the SPECT images. The 99mTc-HMPAO group and the 99mTc-ECD group were well matched with respect to age, sex, age at first seizure, duration of disease, seizure frequency, history of previous brain surgery, and findings of presurgical MRI. The proportion of lateralizing ictal SPECT did not differ significantly between 99mTc-HMPAO and 99mTc-ECD (65.5% vs 72.1%, P = 0.36). Sensitivity of ictal perfusion SPECT (independent of the tracer) for correct localization of the SOZ in 62 patients with temporal lobe epilepsy and at least worthwhile improvement (Engel scale ≤ III) 12 months after temporal epilepsy surgery was 63%. This study does not provide evidence to favor 99mTc-HMPAO or 99mTc-ECD for identification of the SOZ by ictal perfusion SPECT.

Ictal hypoperfusion and iron deposition in the symptomatogenic zone of epilepsia partialis continua – A case report

Ictal hypoperfusion and iron deposition in the symptomatogenic zone of epilepsia partialis continua – A case report

Surgical Outcome in Extratemporal Epilepsies Based on Multimodal Pre-Surgical Evaluation and Sequential Intraoperative Electrocorticography

Objective: to present the postsurgical outcome of extratemporal epilepsy (ExTLE) patients submitted to preoperative multimodal evaluation and intraoperative sequential electrocorticography (ECoG). Subjects and methods: thirty-four pharmaco-resistant patients with lesional and non-lesional ExTLE underwent comprehensive pre-surgical evaluation including multimodal neuroimaging such as ictal and interictal perfusion single photon emission computed tomography (SPECT) scans, subtraction of ictal and interictal SPECT co-registered with magnetic resonance imaging (SISCOM) and electroencephalography (EEG) source imaging (ESI) of ictal epileptic activity. Surgical procedures were tailored by sequential intraoperative ECoG, and absolute spike frequency (ASF) was calculated in the pre- and post-resection ECoG. Postoperative clinical outcome assessment for each patient was carried out one year after surgery using Engel scores. Results: frontal and occipital resection were the most common surgical techniques applied. In addition, surgical resection encroaching upon eloquent cortex was accomplished in 41% of the ExTLE patients. Pre-surgical magnetic resonance imaging (MRI) did not indicate a distinct lesion in 47% of the cases. In the latter number of subjects, SISCOM and ESI of ictal epileptic activity made it possible to estimate the epileptogenic zone. After one- year follow up, 55.8% of the patients was categorized as Engel class I–II. In this study, there was no difference in the clinical outcome between lesional and non lesional ExTLE patients. About 43.7% of patients without lesion were also seizure- free, p = 0.15 (Fischer exact test). Patients with satisfactory seizure outcome showed lower absolute spike frequency in the pre-resection intraoperative ECoG than those with unsatisfactory seizure outcome, (Mann– Whitney U test, p = 0.005). Conclusions: this study has shown that multimodal pre-surgical evaluation based, particularly, on data from SISCOM and ESI alongside sequential intraoperative ECoG, allow seizure control to be achieved in patients with pharmacoresistant ExTLE epilepsy.

Predictive value of metabolic and perfusion changes outside the seizure onset zone for postoperative outcome in patients with refractory focal epilepsy.

The value of functional molecular changes outside the seizure onset zone as independent predictive factors of surgical outcome has been scarcely evaluated. The aim of this retrospective study was to evaluate relative metabolic and perfusion changes outside the seizure onset zone as predictors of postoperative outcome in patients with unifocal refractory focal epilepsy. Eighty-six unifocal epilepsy patients who underwent 18F-FDG PET prior to surgery were included. Ictal and interictal perfusion SPECT was available in 65 patients. Good postoperative outcome was defined as the International League against Epilepsy class 1. Using univariate statistical analysis, the predictive ability of volume-of-interest based relative metabolism/perfusion for outcome classification was quantified by AUC ROC-curve, using composite, unilateral cortical (frontal, orbitofrontal, temporal, parietal, occipital) and central volumes-of-interest. The results were cross-validated, and a false discovery rate (FDR) correction was applied. As a secondary objective, a subgroup analysis was performed on temporal lobe epilepsy patients (N = 64). Increased relative ictal perfusion in the contralateral central volume-of-interest was significantly associated with the good surgical outcome both in the total population (AUC 0.79, pFDR = 0.009) and the temporal lobe epilepsy subgroup (AUC 0.80, pFDR = 0.028). No other significant associations between functional molecular changes and postoperative outcome were found. Increased relative ictal perfusion in the contralateral central region significantly predicted outcome after epilepsy surgery in patients with refractory focal epilepsy. We postulate that these relative perfusion changes could be an expression of better preoperative neuronal network integration and centralization in the contralateral central structures, which is suggested to be associated with better postoperative outcome.

Non-invasive Seizure Localization with Ictal Single-Photon Emission Computed Tomography is Impacted by Preictal/Early Ictal Network Dynamics.

More than one third of children with epilepsy have medically intractable seizures. Promising therapies, including targeted neurostimulation and surgery, depend on accurate localization of the epileptogenic zone. Ictal perfusion Single-Photon Emission Computed Tomography (SPECT) can localize the seizure focus noninvasively, with comparable accuracy to that of invasive EEG. However, multiple factors including seizure dynamics may affect its spatial specificity. Using subtracted ictal from interictal SPECT and scalp EEG from 118 pediatric epilepsy patients (40 of whom had surgery after the SPECT studies), information theoretic measures of association and advanced statistical models, this study investigated the impact of preictal and ictal brain network dynamics on SPECT focality. Network dynamics significantly impacted the SPECT localization ~30 s before to ~45 s following ictal onset. Distributed early ictal connectivity changes, indicative of a rapidly evolving seizure, were negatively associated with SPECT focality. Spatially localized connectivity changes later in the seizure, indicating slower seizure propagation, were positively associated with SPECT focality. In the first ~60 s of the seizure, significantly higher network connectivity was estimated in an area overlapping with the area of hyperperfusion. Finally, ~75% of patients with Engel class 1a/1b outcomes had SPECTs that were concordant with the resected area. Slowly evolving seizures are more likely to be accurately imaged with SPECT, and the identified focus may overlap with brain regions where significant topological changes occur. Measures of preictal/early ictal network dynamics may help optimize the SPECT localization, leading to improved surgical and neurostimulation outcomes in refractory epilepsy.

Positron emission tomography imaging of cerebral glucose metabolism and type 1 cannabinoid receptor availability during temporal lobe epileptogenesis in the amygdala kindling model in rhesus monkeys.

We investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis. Because it is rarely possible to study epileptogenesis in humans, we applied the electrical amygdala kindling model in nonhuman primates to image longitudinal changes in type 1 cannabinoid receptor (CB1R) binding and cerebral glucose metabolism. Two rhesus monkeys received [18 F]-MK-9470 and fluorodeoxyglucose-positron emission tomography ([18 F]-FDG -PET) scans in each of the 4 kindling stages to quantify relative changes over time of CB1R binding and cerebral glucose metabolism in vivo. We constructed z-score images relative to a control group (n = 8), and considered only those changes measured in both kindled animals by calculating the binary conjunction image per kindling stage. The seizure-onset zone exhibited an increased CB1R binding and a decreased glucose metabolism, which both aggravated gradually in extent and intensity throughout kindling. The ipsilateral thalamus and insula showed hypometabolism that coincided with an increase and a decrease in CB1R binding, respectively. These changes also became gradually more severe throughout kindling and overlapped with ictal perfusion changes during the final stage of amygdala kindling, with hyperperfusion in the ipsilateral thalamus and hypoperfusion in the ipsilateral insula. The observed changes in CB1R binding may reflect a combination of a protective mechanism of neurons against seizure activity that becomes stronger over time to combat more severe seizures, and on the other hand, a process of epileptogenesis that facilitates seizure activity and generalization, depending on the cell type involved in those specific regions. This study provides unique evidence that the CB1R is dynamically and progressively involved from the start of mesial temporal lobe epileptogenesis.

Connectivity in ictal single photon emission computed tomography perfusion: a cortico-cortical evoked potential study.

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.

Utility of gray-matter segmentation of ictal-Interictal perfusion SPECT and interictal 18F-FDG-PET in medically refractory epilepsy

PurposeWe present a method of gray-matter segmentation of functional neuroimaging for localization of seizure onset zone (SOZ) in epilepsy surgery. 18F-FDG-PET hypometabolism and ictal SPECT hyperperfusion may correspond to SOZ. We hypothesize that limiting functional images to gray matter improves identification of small, subtle, or obscure cortical volumes of 18F-FDG-PET hypometabolism and eliminates hyperperfused seizure propagation pathways within white matter in ictal perfusion SPECT. MethodsTwenty-five adult and pediatric patients age 2–48 years with epilepsy surgery evaluations consisting of MRI, 18F-FDG-PET, ictal and interictal perfusion SPECT, and intracranial EEG (iEEG) monitoring were selected. MRI gray matter segmentation was used to identify cortical regions in coregistered 18F-FDG-PET and Ictal-Interictal SPECT Analysis by SPM (ISAS) as volumes of interest (VOI). VOIs in 18F-FDG-PET and SPECT perfusion clusters were compared to iEEG localization. The level of VOI concordance between two modalities was recorded as the same subgyrus (highest concordance), gyrus, sublobe, lobe, hemisphere, or no concordance. ResultsWith segmentation, 84% (21/25) of cases had at least one area identified on 18F-FDG-PET scan concordant with iEEG SOZ at sublobar or higher levels, and 72% (18/25) of cases had subgyral concordance with iEEG SOZ. Without segmentation, 60% (15/25) of cases had at least one area in 18F-FDG-PET scan concordant with iEEG SOZ at sublobar or higher levels, and 32% (8/25) with subgyral concordance. 83% (10/12) of seizure free patients had subgyral concordance on segmented 18F-FDG-PET. Both segmented and nonsegmented ictal-interictal SPECT perfusion clusters had 56% (14/25) of cases with at least sublobar concordance. Subgyral concordance was achieved by 28% (7/25) of segmented and 20% (5/25) of nonsegmented SPECTs. DiscussionSegmented 18F-FDG-PET scans frequently result in high correspondence to iEEG onset zones with localizations exactly concordant with iEEG SOZ- more than twice as often as without segmentation. Segmentation allows for the identification of small or subtle areas of hypometabolism that are often unappreciated or are obscured by normally hypometabolic white matter. Segmentation of ictal-interictal SPECT clusters did not significantly increase localization with iEEG SOZ over nonsegmented clusters.

Nuclear medicine in pediatric refractory epilepsy

The nuclear medicine procedures 99mTc-ECD SPECT and 18F-FDG PET play an important diagnostic role in children with refractory seizures. In select patients, surgical removal of epileptogenic cortex is a therapeutic option. Magnetic resonance imaging (MRI) is the principal imaging method used to identify which patients would benefit from the surgery. However, there are cases when MRI does not detect an abnormality (MRI-negative epilepsy). Under these, and other circumstances, functional nuclear medicine studies are helpful in the workup of these patients. A combination of nuclear medicine procedures with MRI and CT depicts functional–anatomic relationships and assists in the non-invasive localization of epileptogenic cortex. Information derived from these procedures is valuable in the selection of candidates for surgical resection. Timing of tracer administration in relation to imaging and monitoring the state of brain activation are essential for accurate interpretation. Ictal and interictal perfusion single photon computed tomography (SPECT), with digital subtraction and registration to MRI can define the region of ictal cortical hyperperfusion more clearly than separate image interpretation. Ictal SPECT is more sensitive than interictal positron emission computed tomography (PET) and interictal PET is more sensitive than interictal SPECT. Interictal SPECT and PET are easier to obtain than ictal SPECT, since they do not require coordination between seizure onset and tracer administration. When surface electrode grids or depth electrodes are planned, anatomic-functional images can assist in their anatomic positioning. The best results are obtained when the planning, execution and interpretation of nuclear medicine procedures are carried out with the support of a well-trained multidisciplinary team familiar with children and refractory seizures.

The effective connectivity of the seizure onset zone and ictal perfusion changes in amygdala kindled rhesus monkeys.

Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded as a circuit-level disorder that cannot be understood outside this context. Better insight into the effective connectivity of the seizure onset zone and the manner in which seizure activity spreads could lead to specifically-tailored therapies for epilepsy.We applied the electrical amygdala kindling model in two rhesus monkeys until these animals displayed consistent stage IV seizures. At this stage, we investigated the effective connectivity of the amygdala by means of electrical microstimulation during fMRI (EM-fMRI). In addition, we imaged changes in perfusion during a seizure using ictal SPECT perfusion imaging. The spatial overlap between the connectivity network and the ictal perfusion network was assessed both at the regional level, by calculating Dice coefficients using anatomically defined regions of interest, and at the voxel level.The kindled amygdala was extensively connected to bilateral cortical and subcortical structures, which in many cases were connected multisynaptically to the amygdala. At the regional level, the spatial extents of many of these fMRI activations and deactivations corresponded to the respective increases and decreases in perfusion imaged during a stage IV seizure. At the voxel level, however, some regions showed residual seizure-specific activity (not overlapping with the EM-fMRI activations) or fMRI-specific activation (not overlapping with the ictal SPECT activations), indicating that frequently, only a part of a region anatomically connected to the seizure onset zone participated in seizure propagation.Thus, EM-fMRI in the amygdala of electrically-kindled monkeys reveals widespread areas that are often connected multisynaptically to the seizure focus. Seizure activity appears to spread, to a large extent, via these connected areas.

Ictal perfusion changes associated with seizure progression in the amygdala kindling model in the rhesus monkey.

Amygdala kindling is a widely used animal model for studying mesial temporal lobe epileptogenesis. In the macaque monkey, electrical amygdala kindling develops slowly and provides an opportunity for investigating ictal perfusion changes during epileptogenesis. Two rhesus monkeys were electrically kindled through chronically implanted electrodes in the right amygdala over a period of 16 and 17 months. Ictal perfusion single photon emission computed tomography (SPECT) imaging was performed during each of the four predefined clinical stages. Afterdischarge duration increased slowly over 477 days for monkey K and 515 days for monkey S (18 ± 8 s in stage I; 52 ± 13 s in stage IV). During this time, the animals progressed through four clinical stages ranging from interrupting ongoing behavior to bilateral convulsions. Ictal SPECT perfusion imaging showed well-localized but widely distributed regions of hyperperfusion and hypoperfusion, in both cortical and subcortical structures, at every seizure stage. A large portion of the ictal network was involved in the early stages of epileptogenesis and subsequently expanded over time as seizure severity evolved. Our data indicate that the different mesial temporal lobe seizure types occur within a common network affecting several parts of the brain, and that seizure severity may be determined by seizure-induced epileptogenesis within a bihemispheric network that is implicated from the start of the process.

Alteration of Ictal and Interictal Perfusion in Patients with Paroxysmal Kinesigenic Dyskinesia

Although previous cerebral blood flow studies have suggested that the basal ganglia or thalamus are involved in the pathogenesis of paroxysmal kinesigenic dyskinesia (PKD), the precise anatomic substrate or pathophysiological networks associated with PKD remain unclear. Here, ictal and interictal single photon emission computed tomography (SPECT) in 2 patients with idiopathic PKD compared to 6 age-matched normal controls and the perfusion findings of subtraction ictal SPECT co-registered to MRI (SISCOM) in 1 patient are reported. The interictal and ictal perfusion changes were different in each of the patients and there were no consistent anatomic substrates observed. 2 patients had significant perfusion changes in the left frontal/temporal cortices compared to controls, whereas the others showed an increased uptake of 99mTc-ethyl cysteinate dimer (ECD) in the left occipital area on subtraction SPECT imaging. The results of this study suggest that the pathophysiology of PKD cannot be simply explained by lesions of the basal ganglia or thalamus, and that other associated areas of the cortex are likely involved in these movement disorders.

Focal hyperperfusion on ictal cerebral perfusion computed tomography in partial seizures mimicking acute stroke

Focal hyperperfusion on ictal cerebral perfusion computed tomography in partial seizures mimicking acute stroke

Brain activation patterns of versive, hypermotor, and bilateral asymmetric tonic seizures

Patients who have seizure onset from different brain regions can produce seizures that appear clinically indistinguishable from one another. These clinically stereotypic manifestations reflect epileptic activation of specific networks. Several studies have shown that ictal perfusion single photon emission computed tomography (SPECT) can reveal propagated ictal activity. We hypothesize that the pattern of hyperperfusion may reflect neuronal networks that generated specific ictal symptomatology. All patients were identified who were injected with (99m)Tc-hexamethyl-propylene-amine-oxime (HMPAO) during versive seizures (n = 5), bilateral asymmetric tonic seizures (BATS; n = 5), and hypermotor seizures (n = 7) in the presurgical epilepsy evaluation between 2001 and 2005. The SPECT ictal–interictal difference image pairs of each subgroup were compared with image pairs of 14 controls using statistical parametric mapping (SPM 2) to identify regions of significant hyperperfusion. Hyperperfused regions with corrected cluster-level significance p < 0.05 were considered significant. We have identified a distinct ictal perfusion pattern in each subgroup. In versive seizure subgroup, prominent hyperperfusion was present in the frontal eye field opposite to the direction of head version. In addition, there was associated caudate and crossed cerebellar hyperperfusion. The BATS subgroup showed pronounced hyperperfusion supplementary sensorimotor area ipsilateral to the epileptogenic region, bilateral basal ganglia, and contralateral cerebellar hemisphere. The hypermotor seizure subgroup demonstrated two clusters of significant hyperperfusion: one involving bilateral frontomesial regions, cingulate gyri, and caudate nuclei, and another involving ipsilateral anteromesial temporal structures, frontoorbital region, insula, and basal ganglia. We have identified distinct hyperperfusion patterns for specific ictal symptomatology. Our findings provide further insight into understanding the anatomic basis of seizure semiology.

Contralateral hyperperfusion and ipsilateral hypoperfusion by ictal SPECT in patients with mesial temporal lobe epilepsy

Ictal Single Proton Emission Computed Tomography (SPECT) has demonstrated high levels of sensitivity in localizing seizures among patients with epilepsy of the mesial temporal lobe (mTLE). However, incorrect information on the lateralization of mTLE has also been reported. In order to investigate the causes of these incorrect localizations, the authors assessed clinical symptoms, as well as the electroencephalography (EEG) and brain SPECT scan data of five patients with mTLE experiencing ictal hyperperfusion of the contralateral temporal lobe. All patients underwent presurgical evaluations, including an interictal and ictal brain SPECT scan. A subtraction ictal SPECT co-registered with Magnetic Resonance Imaging (MRI) procedure or SISCOM was performed. Hyperperfusion (ictal perfusion greater than interictal perfusion) and hypoperfusion (ictal perfusion lower than interictal perfusion), results of SISCOM were analyzed and compared with seizure and ictal EEG pattern patterns. All the five patients had unilateral hippocampal sclerosis, and the radiotracer for the ictal SPECT was injected after the ictal EEG pattern had propagated to the contralateral side. The average delay between the ictal EEG onset and the radiotracer injection was 29.7+/-9.6s. All hyperperfusion SISCOM results revealed hyperperfusion in the contralateral temporal region with a more intense ictal EEG build-up. However, hypoperfusion SISCOM results demonstrated significant hypoperfusion in the epileptogenic temporal lobe of three of the five patients, but no hypoperfusion finding in the other two patients. This study demonstrates that early ictal EEG pattern propagation to the contralateral side in mTLE may be associated with contralateral ictal hyperperfusion with or without ipsilateral temporal hypoperfusion. The authors recommend simultaneous interpretations of ictal SPECT and ictal EEG propagation patterns at the time of the injection of radiotracers.

Localization of temporal epilepsy foci by subtraction ictal perfusion single photon emission computed tomography is enhanced when using 3D-OSEM iterative reconstruction

Subtraction ictal single photon emission computed tomography (SPECT) images, provided by filtered back-projection (FBP), may exhibit a confusing high level of noise. This study was aimed at assessing an optimized three-dimensional ordered subset expectation maximization (3D-OSEM) iterative reconstruction in this setting. On phantom images, parameters of 3D-OSEM reconstruction were selected as those providing the higher signal/noise ratio but a high enough spatial resolution, equivalent to that of conventional FBP reconstruction (full width at half-maximum = 11 mm). Thereafter, subtraction ictal ethylene cysteine dimer-SPECT coregistered to MRI and reconstructed with either FBP or 3D-OSEM were compared in 21 patients with well-characterized temporal epilepsy foci (subsequent successful surgical treatment). On subtraction images, the use of the selected 3D-OSEM reconstruction (five iterations, 16 subsets and a 9 mm Gauss filter) instead of FBP was associated with: (i) marked reductions in background activity (0.05 ± 0.09 vs. 0.25 ± 0.18 cps, P < 0.001) and in the size of temporal foci (10 ± 7 vs. 14 ± 11 cm, P = 0.01) and (ii) a trend toward higher accuracy in identifying the involved temporal lobes (86 vs. 76%). Localization of temporal epilepsy foci by subtraction ictal SPECT is likely to be enhanced by using 3D-OSEM rather than FBP reconstruction because of marked reductions in background activity and in the size of detected foci.

PET and SPECT in epilepsy: A critical review

Molecular imaging with ictal and interictal single-photon emission computed tomography (SPECT) as well as positron emission tomography (PET) rank among the established functional imaging tests for the presurgical evaluation of epileptic onset zone in patients with intractable partial epilepsy. In temporal lobe epilepsy the sensitivity of these methods was shown to be excellent, in particular if a multimodal platform is used, which combines the functional imaging with the additional morphological information of magnetic resonance imaging (MRI), but was lower in extra temporal lobe epilepsy. Functional imaging with SPECT and PET reflects seizure related changes of cerebral perfusion, glucose-metabolism and neuroreceptor status. In this review the usefulness of SPECT and PET imaging in clinical routine in epilepsy as well as the role of different neuroreceptor PET-tracer, which were used in epilepsy are discussed. The use of perfusion SPECT tracer allows the investigation of ictal activations, but the low temporal resolution of ictal perfusion SPECT often results in the detection of both the ictal onset zone as well as the propagation pathways, an area that has not always need to be resected in order to render a patient seizure free. The additional use of interictal PET with fluorine-18 fluorodeoxyglucose which measures regional cerebral metabolism or interictal perfusion SPECT enhance the informational value of ictal SPECT and were shown to be important tools to better define the ictal onset and surround inhibition zones. In recent years PET imaging of different cerebral neuroreceptor-systems inter alia GABA(A) receptors, serotonin receptors (5-HT(1A)), opioid receptors as well as dopamine receptors was used to investigate the neurochemical basis of epilepsy, the role of these neurotransmitters for the epileptogenesis as well as the spread of epileptic activity during seizures and partially entered in clinical routine. Currently some of these radioligands are also used to investigate new treatment approaches.