The usefulness of subtraction ictal SPECT coregistered to MRI in single- and dual-headed SPECT cameras in partial epilepsy

PURPOSE: To prove the clinical usefulness of SISCOM and compare SISCOM images derived from single- and dual-headed single-photon computed tomography (SPECT) cameras for localization of partial epileptic seizures. METHODS: We retrospectively studied 38 partial epilepsy patients, using subtraction SPECT coregistered to magnetic resonance imaging (MRI; SISCOM). SPECT imaging of the first 15 patients was performed by single-headed camera, and the next 23 patients by dual-headed camera. Side-by-side ictal-interictal SPECT evaluation and SISCOM images were blindly reviewed and classified as either localizing to one of 16 sites or nonlocalizing. A third reviewer evaluated cases of disagreement between primary reviewers. Results were compared with seizure localization by any of the following three traditional techniques: surgical outcome, invasive, and noninvasive video-EEG monitoring. The results from the single- and dual-headed SPECT cameras were compared. RESULTS: Reviewers localized areas of hyperperfusion with SISCOM images more often than with side-by-side SPECT evaluation (71.0 vs. 47.4%; p = 0.01). When we compared results of SPECT evaluation with traditional techniques, SISCOM showed greater concordance than side-by-side SPECT evaluation (60.53 vs. 36.84%; p = 0.006). There were no differences in localization between images derived from single- and dual-headed cameras. Concordance of seizure localization, compared with traditional techniques, also was not different between these groups [kappa = 0.38, 95% confidence interval (CI), 0.18-0.58] vs. kappa = 0.63, 95% CI (0.45-0.81)]. CONCLUSIONS: SISCOM is a worthwhile technique for preoperative evaluation in partial epilepsy patients and improves the sensitivity and specificity of seizure localization of SPECT images derived from both single- and dual-headed SPECT cameras.     

Prospective use of subtraction ictal SPECT coregistered to MRI (SISCOM) in presurgical evaluation of epilepsy

Purpose: In patients with drug‐refractory focal epilepsy, nonlesional magnetic resonance imaging (MRI) or discordant data of presurgical standard investigations leads to failure generating a sufficient hypothesis for electrode implantation or epilepsy surgery. The seizure‐onset zone can be further investigated by subtraction ictal single‐photon emission computed tomography (SPECT) coregistered to MRI (SISCOM). This is an observational study of a large consecutive cohort of patients undergoing prospective SISCOM to generate hypothesis for electrode implantation or site of epilepsy surgery. Methods: One hundred seventy‐five consecutive patients undergoing presurgical evaluation with either nonlesional MRI or discordant data of standard investigations preventing the generation of hypothesis for seizure onset were evaluated with SISCOM. Results were compared to gold standard for seizure onset detection, either electrocorticography (ECoG) and/or postoperative outcome. Key Findings: One hundred thirty patients had successful SPECT injection. Hypothesis for electrode implantation/site of surgery was generated in 74 patients. Forty patients had gold standard comparison. Twenty‐eight patients underwent resective surgery. SISCOM was concordant to site of surgery in 82%. An additional 12 patients underwent invasive EEG monitoring but were not suitable for surgery. SISCOM was concordant multifocal in 75%. Two years postsurgical follow‐up of 26 patients showed favorable outcome in 22 (Engel class I and class II). Significance: SISCOM is a highly valuable diagnostic tool to localize the seizure‐onset zone in nonlesional and extratemporal epilepsies. Outcome in this patient group was unexpectedly good, even in patients with nonlesional MRI. The high correlation with ECoG and site of successful surgery is a strong indicator that outcome prediction in this patient group should be adapted accordingly, which may encourage more patients to undergo electrode implantation and subsequent successful surgery. Statistical analysis showed that SISCOM with shorter duration of seizures, focal seizures, and lesional MRI was more likely to generate implantation hypothesis.     

Detection and localization of focal cortical dysplasia by voxel-based 3-D MRI analysis

PURPOSE: Focal cortical dysplasia (FCD) is a frequent cause of partial epilepsy. Its diagnosis by visual evaluation of magnetic resonance images (MRIs) remains difficult. The purpose of this study was to apply a novel automated and observer-independent voxel-based technique for the analysis of 3-dimensional (3-D) MRI to detect and localize FCD. METHODS: The technique was based on algorithms of the SPM99 software and included the spatial normalization of 3-D MRI data sets to a common stereotaxic space and the segmentation of cortical grey matter. The resulting data sets represented grey-matter density maps where each voxel encoded the grey-matter concentration at the corresponding position in the original MRI. A normal database was set up by calculating and averaging the grey-matter density maps of 30 healthy volunteers. The MRI data sets of seven epilepsy patients with FCD were evaluated retrospectively for dysplastic lesions by voxelwise subtraction of the mean grey-matter density map of the normal database and searching automatically for local and global maxima in the resulting data set. RESULTS: In all patients, the results of voxel-based 3-D MRI analysis corresponded both to the location of the dysplastic lesions in conventional MRI and to seizure semiology and EEG findings. In one case, surgery was performed, and the diagnosis FCD was supported by histology. CONCLUSIONS: The technique of voxel-based 3-D MRI analysis and comparison with a normal database seems to provide a valuable additional screening tool for the detection of FCD.     

Subtraction SPECT coregistered to MRI in focal malformations of cortical development: localization of the epileptogenic zone in epilepsy surgery candidates

PURPOSE: To determine the extent to which periictal subtraction single-photon emission computed tomography (SPECT) may improve detection and definition of the epileptogenic zone in patients with focal malformations of cortical development (MCDs). METHODS: Subtraction SPECT coregistered to magnetic resonance (MR) images (SISCOM) were constructed for 22 consecutive patients with focal MCDs who underwent periictal SPECT injection (18 ictal and four postictal). In the 17 patients who had epilepsy surgery, concordance between the site of SISCOM localization and site of surgical resection was determined by coregistration of SISCOM images with postoperative MRIs. RESULTS: SISCOM images were localizing in 19 (86%) patients, including eight of the 10 with nonlocalizing MRI. Concordance of SISCOM localization was 91% with MRI localization, 93% with scalp ictal EEG localization, and 100% with intracranial EEG localization. Eight patients whose SISCOM localization was concordant with the surgical resection site had lower postoperative seizure frequency scores (SFSs; p = 0.04) and greater postoperative improvement in SFSs (p = 0.05) than the nine patients whose SISCOM was either nonconcordant or nonlocalizing. On multiple regression analysis, a model combining SISCOM concordance with surgical resection site and extent of MRI lesion resection was predictive of postoperative SFS (R2 = 0.47; p = 0.03). CONCLUSIONS: Periictal subtraction SPECT using the SISCOM technique provides useful information for seizure localization in patients with focal MCDs, even when MRI is nonlocalizing.     

Influence of subtraction ictal SPECT on surgical management in focal epilepsy of indeterminate localization: a prospective study

The impact of functional imaging tests on the decision-making and planning process for epilepsy surgery has never been prospectively assessed. We prospectively evaluated 50 consecutively eligible patients whose noninvasive evaluations showed nonlocalized findings and determined how their SISCOM (subtraction ictal SPECT [single photon emission computed tomography] co-registered to MRI [magnetic resonance imaging]) data altered consensus decisions for epilepsy surgery. At an epilepsy surgery conference where each patient was discussed, consensus decisions were documented after a standardized presentation of data from the noninvasive evaluation (SISCOM findings initially were excluded). Consensus decisions were again documented after presentation of SISCOM data. Consensus decisions changed for 10 of 32 patients (31%) with localizing SISCOM results, whereas the decision changed in only 1 of 18 patients (6%) with nonlocalizing SISCOM results (P<.05). Changes in consensus decisions were as follows: (1) intracranial electrode implantation (IEI) was obviated and resective surgery was recommended (n=2); (2) resective surgery or further evaluation for patients initially not considered surgical candidates (n=2); (3) IEI in patients for whom it was not recommended initially (n=3); (4) increased IEI coverage (n=3); and (5) antiepileptic drug trial or vagal nerve stimulation was recommended instead of IEI (n=1). For some patients whose noninvasive evaluations did not clearly localize a surgical focus, SISCOM data can have a major impact on decisions to recommend resective epilepsy surgery or IEI.     

Micturition induced seizures: ictal EEG and subtraction ictal SPECT findings

We report an 8-year-old girl with seizures induced by micturition. Her seizures were characterized by extension of upper extremities with preserved consciousness. Magnetic resonance imaging and interictal electroencephalograms were normal. Ictal electroencephalogram showed low voltage fast waves without clear focal features followed by frontal dominant rhythmic multiple spikes. Subtraction ictal single photon emission computed tomography revealed a significant increase in blood flow in the mesial frontal area.     

Repeated ictal SPECT in partial epilepsy patients: SISCOM analysis

Purpose: Ictal single‐photon emission computerized tomography (SPECT) is often nonlocalized in patients with partial epilepsy. We repeated ictal SPECT in patients with partial epilepsy whose first ictal SPECT was nonlocalized. We also performed subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) to test the localizability of ictal SPECT. Methods: We recruited 69 patients with partial epilepsy (33 male and 36 female, mean plus or minus standard deviation age 29.5 ± 12.2 years), who had a repeated ictal SPECT. Ictal‐interictal SPECT subtractions were performed, and the subtracted SPECTs were coregistered with their brain MRI studies. SISCOM results were considered to be localizing when the results were concordant with the final location of the epileptic focus, as determined by the presurgical evaluation. We compared seizure duration, tracer injection time, interictal and ictal scalp electroencephalography (EEG) patterns, presence and time of secondary generalization, and epilepsy classification between the localized and nonlocalized SISCOM groups. Key Findings: The SISCOM results of the second ictal SPECT were localized in 43 (62.3%) patients and nonlocalized in 26 (37.7%) patients. In the second ictal SPECT, the radiotracer injection time was significantly shorter in the localized group (25.1 ± 8.9 s), as compared to the nonlocalized group (49.2 ± 55.8 s) (p = 0.008). Furthermore, the radiotracer injection time of the second ictal SPECT was significantly shorter than the first ictal SPECT, only in the localized group (36.8 ± 23.8 s in the first and 25.1 ± 8.9 s in the second ictal SPECT in the localized group, p = 0.004). The percent injection time ([(tracer injection time−seizure onset time)/total seizure duration] × 100%) in the second SPECT was significantly shorter in the localized group, as compared to the nonlocalized group (37.9 ± 23.0% in the localized group and 72.3 ± 46.2% in the nonlocalized group, p < 0.001). The localized ictal EEG patterns at the time of injection were more frequent in the localized SISCOM group. The secondary generalization of seizures at the time of injection was more frequent in nonlocalized groups. Significance: Repeated ictal SPECT with SISCOM analysis is helpful for localizing an epileptic focus in patients with partial epilepsy who have a nonlocalized first ictal SPECT. The most important factor for increasing the localizability of repeated ictal SPECT is early injection time and a localizing ictal EEG pattern at the time of radiotracer injection.     

Hot-water epilepsy in an adult: ictal EEG, MRI and SPECT features.

Reflex epilepsy constitutes a rare form of epileptic seizures. We observed a 20-year-old man who presented with seizures induced by immersion in hot water. The trigger stimulus was specific. Contrast CT scan and MRI were all normal, not revealing any structural lesion. Ictal EEG recorded during a hot bath showed focal epileptic discharges in the left temporo-occipital area. Interictal SPECT showed a hypometabolism in the same cerebral region. Neuroimaging studies were rarely performed in this uncommon type of epilepsy. Nevertheless, in our case the result of the SPECT suggests a localized functional disturbance in the emergence of the disorder.     

Spread of ictal activity in focal epilepsy

Purpose: Latencies between seizure onset, propagation of ictal activity, and initial clinical symptoms and signs are critically important for the successful implementation of detection‐based intervention systems in the treatment of epilepsy. This study analyzes intracranial EEG‐recordings for temporal characteristics of ictal spread and its dependence on focus localization. Methods: Intracerebral EEG recordings of 215 seizures from 43 patients with pharmacoresistant focal epilepsy were evaluated based on site of first propagation, latencies between EEG seizure onset, early propagation, and clinical seizure onset. Seizure onset was mesial temporal in 15 patients, neocortical temporal in 15 patients, and frontal in 13 patients. Results: Periods during which ictal activity remained confined to the seizure onset area showed significant differences between the patient groups. Median latencies between electrographic seizure onset and early propagation were significantly longer for patients with mesial temporal (5 s in seizure‐based analysis/10 s in patient‐based analysis) as compared to neocortical temporal (3 s/5 s) and frontal seizure focus (1 s/2 s; p < 0.01). Concordantly, median latencies to onset of clinical symptomatology were significantly longer for patients with mesial temporal (17 s/19 s) as compared to neocortical temporal (11 s/17 s) and frontal seizure focus (4 s in seizure‐based analysis and 6 s in patient‐based analysis; p < 0.01). Conclusions: The speed of propagation of ictal activity and the latencies until initial clinical seizure symptoms differ significantly depending on focus localization. Extended spread often occurred within the time window during which current detection systems operate. This suggests that inclusion criteria of patients suitable for testing the efficacy of detection‐based seizure intervention strategies should be based on focus localization and patient‐individual propagation patterns.     

Correlation of ictal EEG and SPECT studies in patients of intractable epilepsy with normal MRI

Identification of the epileptic focus is the most important requirement for a successful surgical outcome in intractable epilepsy. Patients with normal MRI on high-resolution imaging pose a significant challenge in this regard. We tried to identify the epileptic focus using interictal / ictal SPECT and ictal EEG patterns in 14 patients with normal MRI. Rhythmic ictal onset activity helped to identify a single focus in 10 patients (71.43%). Inter ictal SPECT detected a focus corresponding to ictal EEG in 6 out of 10 patients (60%) in whom the test was performed. Ictal SPECT done in 5 patients correctly identified the focus in all patients (100%). Our data indicate that it is possible to obtain localization in patients with normal MRI using a combination of ictal EEG patterns and an ictal SPECT study.     

The usefulness of subtraction ictal SPECT and ictal near-infrared spectroscopic topography in patients with West syndrome

The recent findings on subtraction ictal SPECT and ictal near-infrared spectroscopic topography in patients with West syndrome were summarized and its availability for presurgical evaluation was discussed. The subtraction ictal SPECT study in patients with West syndrome demonstrated the cortical epileptic region and subcortical involvement, which may consist of epilepsy networks related to the spasms. Moreover, subtraction ictal SPECT may have predictive power for short-term seizure outcome. Patients with a symmetric hyperperfusion pattern are predicted to have a better seizure outcome, whereas patients with asymmetric hyperperfusion pattern may develop poor seizure control. Importantly, asymmetric MRI findings had no predictive power for seizure outcome. Multichannel near-infrared spectroscopic topography applied to the patients with West syndrome detected an increase in regional cerebral blood volume in multiple areas which were activated either simultaneously or sequentially during spasms. Topographic changes in cerebral blood volume were closely correlated with spasm phenotype, suggesting that the cortex is involved in the generation of spasms. In conclusion, subtraction ictal SPECT may be considered as a useful tool for presurgical evaluation of patients with West syndrome and investigation of the pathophysiology of spasms. The ictal near-infrared spectroscopic topography should be more investigated to see if this is useful tool for presurgical evaluation.     

Comparison of ictal SPECT and interictal PET in the presurgical evaluation of temporal lobe epilepsy

We retrospectively compared ictal technetium 99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) and interictal ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) in 35 patients with well-lateralized temporal lobe epilepsy (TLE). Based on SPECT scans the two observers correctly lateralized seizure foci with certainty in 89% of patients; interobserver agreement was excellent. Both observers incorrectly lateralized the seizure focus on two SPECT scans; one error was explained by rapid electroencephalographic spread to the contralateral side and for the other patient, isotope was injected during a brief aura. Based on PET scans, observers correctly lateralized the foci with certainty in 63% and with lesser confidence in 83%; four incorrect lateralizations were made by one observer and none by the other. PET interobserver disagreement was explained by differences between observers in weighting the relative hypometabolism in medial and lateral temporal regions. The detection rate for PET was lower in the absence of structural imaging abnormalities (60 vs 87%). PET yielded correct lateralizations in the 2 patients for whom SPECT interpretation was difficult. We conclude that both ictal SPECT and interictal PET are sensitive methods for the lateralization of TLE, but SPECT can be interpreted with greater certainty and is more sensitive when magnetic resonance imaging findings are negative. False lateralization is rare with ictal SPECT and can be explained when interpreted in conjunction with electroclinical data. Both investigations have complementary roles when localization is difficult.     

Impact of radiotracer injection latency and seizure duration on subtraction ictal SPECT co-registered to MRI (SISCOM) performance in children

Objective

We evaluated the impact of radiotracer injection latency and post-injection seizure duration on subtraction ictal SPECT co-registered to MRI (SISCOM) test performance in identifying the epileptogenic zone (EZ) in children with drug-resistant epilepsy who had undergone a resective epilepsy surgery.

Magnetoencephalography and ictal SPECT in patients with failed epilepsy surgery

Objective

Selected patients with intractable focal epilepsy who have failed a previous epilepsy surgery can become seizure-free with reoperation. Preoperative evaluation is exceedingly challenging in this cohort. We aim to investigate the diagnostic value of two noninvasive approaches, magnetoencephalography (MEG) and ictal single-photon emission computed tomography (SPECT), in patients with failed epilepsy surgery.

Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy

Purpose: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. Methods: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. Key Findings: Fifty‐three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1–60 years). Twenty‐seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty‐three patients had surgical resection and >2 years of follow‐up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. Significance: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.     

Ictal SPECT analysis in epilepsy: subtraction and statistical parametric mapping techniques

Seizures are associated with an increase in regional cerebral blood flow (rCBF). In partial seizures the increased blood flow closely corresponds with the site of seizure origin. Using tracers that accumulate and remain "fixed" in different areas of the brain proportional to rCBF at the time of injection, ictal SPECT is now an important tool for localization of seizures in a presurgical evaluation. However, the best methods for interpretation of partial seizure-induced changes in rCBF remain unclear. Numerous computer-aided tools have been used to increase objectivity and accuracy of ictal SPECT analysis. This review examines the uses of ictal-interictal subtraction methods and statistical parametric mapping (SPM) to enhance interpretation and utility of ictal SPECT. The review covers the evolution of advanced ictal SPECT imaging analysis techniques and the authors' clinical experience with the use of subtraction and SPM methods. The authors discuss the impact of ictal SPECT subtraction or difference imaging methods and the initial evidence for proof-of-principle that SPM can be used to provide objective, accurate analysis of ictal SPECT scans in patients with temporal and extratemporal lobe epilepsy. The limitations of both methodologies are discussed, and suggestions for further study of validation, improvement, and routine clinical implementation of advanced analysis methods are provided.     

Enhanced visualization of blurred gray-white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis

PURPOSE: Focal cortical dysplasia (FCD), a frequent cause of partial epilepsy, is often associated with blurring of the gray-white matter junction in magnetic resonance images (MRI). To improve the recognition and delineation of FCD we developed a novel voxel-based image post-processing method for enhanced visualization of blurred gray-white matter junctions. METHODS: Using standard algorithms of statistical parametric mapping software (SPM99) a T1-weighted MRI volume data set is normalized and segmented. The distribution of gray and white matter is analyzed on a voxelwise basis and compared with a normal database. Based on this analysis, a three-dimensional feature map is created which highlights brain areas with blurred gray-white matter transition. This method was applied to the MRI data of 25 epilepsy patients with histologically proven FCD. RESULTS: In 18/25 patients the new feature maps clearly showed that the dysplastic lesions were accompanied by blurring of the gray-white matter junction. Combined with a formerly published method of voxel-based 3D MRI analysis, 21/25 FCD lesions were shown to be associated with either blurring or abnormal extension of gray matter beyond the normal cortical ribbon, including four cases with lesions not or incompletely recognized on conventional MRI. CONCLUSIONS: The MRI post-processing presented here improves the visualization of FCD and may increase the diagnostic yield of MRI. Thereby, it provides a valuable additional diagnostic tool in the presurgical evaluation of epilepsy patients.     

The localizing value of ictal EEG in focal epilepsy.

OBJECTIVE: To investigate the lateralization and localization of ictal EEG in focal epilepsy. METHODS: A total of 486 ictal EEG of 72 patients with focal epilepsy arising from the mesial temporal, neocortical temporal, mesial frontal, dorsolateral frontal, parietal, and occipital regions were analyzed. RESULTS: Surface ictal EEG was adequately localized in 72% of cases, more often in temporal than extratemporal epilepsy. Localized ictal onsets were seen in 57% of seizures and were most common in mesial temporal lobe epilepsy (MTLE), lateral frontal lobe epilepsy (LFLE), and parietal lobe epilepsy, whereas lateralized onsets predominated in neocortical temporal lobe epilepsy and generalized onsets in mesial frontal lobe epilepsy (MFLE) and occipital lobe epilepsy. Approximately two-thirds of seizures were localized, 22% generalized, 4% lateralized, and 6% mislocalized/lateralized. False localization/lateralization occurred in 28% of occipital and 16% of parietal seizures. Rhythmic temporal theta at ictal onset was seen exclusively in temporal lobe seizures, whereas localized repetitive epileptiform activity was highly predictive of LFLE. Seizures arising from the lateral convexity and mesial regions were differentiated by a high incidence of repetitive epileptiform activity at ictal onset in the former and rhythmic theta activity in the latter. CONCLUSIONS: With the exception of mesial frontal lobe epilepsy, ictal recordings are very useful in the localization/lateralization of focal seizures. Some patterns are highly accurate in localizing the epileptogenic lobe. One limitation of ictal EEG is the potential for false localization/lateralization in occipital and parietal lobe epilepsies.