Neurovascular networks in epilepsy: Correlating ictal blood perfusion with intracranial electrophysiology.

Perfusion patterns observed in Subtraction Ictal SPECT Co-registered to MRI (SISCOM) assist in focus localization and surgical planning for patients with medically intractable focal epilepsy. While the localizing value of SISCOM has been widely investigated, its relationship to the underlying electrophysiology has not been extensively studied and is therefore not well understood. In the present study, we set to investigate this relationship in a cohort of 70 consecutive patients who underwent ictal and interictal SPECT studies and subsequent stereo-electroencephalography (SEEG) monitoring for localization of the epileptogenic focus and surgical intervention. Seizures recorded during SEEG evaluation (SEEG seizures) were matched to semiologically-similar seizures during the preoperative ictal SPECT evaluation (SPECT seizures) by comparing the semiological changes in the course of each seizure. The spectral changes of the ictal SEEG with respect to interictal ones over 7 traditional frequency bands (0.1 to 150Hz) were analyzed at each SEEG site. Neurovascular (SEEG/SPECT) relations were assessed by comparing the estimated spectral power density changes of the SEEG at each site with the perfusion changes (SISCOM z-scores) estimated from the acquired SISCOM map at that site. Across patients, a significant correlation (p<0.05) was observed between spectral changes during the SEEG seizure and SISCOM perfusion z-scores. Brain sites with high perfusion z-score exhibited higher increased SEEG power in theta to ripple frequency bands with concurrent suppression in delta and theta frequency bands compared to regions with lower perfusion z-score. The dynamics of the correlation of SISCOM perfusion and SEEG spectral power from ictal onset to seizure end and immediate postictal period were also derived. Forty-six (46) of the 70 patients underwent resective epilepsy surgery. SISCOM z-score and power increase in beta to ripple frequency bands were significantly higher in resected than non-resected sites in the patients who were seizure-free following surgery. This study provides for the first time concrete evidence that both hyper-perfusion and hypo-perfusion patterns observed in SISCOM maps have strong electrophysiological underpinnings, and that integration of the information from SISCOM and SEEG can shed light on the location and dynamics of the underlying epileptic brain networks, and thus advance our anatomo-electro-clinical understanding and approaches to targeted diagnostic and therapeutic interventions.

The effect of injection time on rates of epileptogenic zone localization using SISCOM and STATISCOM.

BACKGROUND: The identification of hyperperfusion on ictal single-photon emission computed tomography (SPECT) scan is a technique for the localization of the epileptogenic zone (EZ) in patients with focal epilepsy undergoing presurgical evaluation. The accuracy of this technique has been improved by subtraction from an interictal image and coregistration with magnetic resonance imaging (MRI) (subtraction ictal SPECT coregistered to MRI (SISCOM)), and subsequently by the development of Statistical Ictal SPECT Co-registered to MRI (STATISCOM) which is reported to further improve localization accuracy by statistically accounting for random variation between images. However, the use of ictal SPECT is limited by the necessity for rapid injection of the radiotracer. The purpose of this study was to investigate the effect of tracer injection time on EZ localization rates using both STATISCOM and SISCOM. METHODS: Consecutive patients with drug-resistant focal epilepsy who had an ictal SPECT scan while admitted to the video-electroencephalography (EEG) monitoring unit at the Royal Melbourne Hospital, Victoria, Australia, and a subsequent interictal scan, between 2009 and 2017 were included. The information collected included age, sex, seizure type, epilepsy diagnosis, and injection time. Statistical Ictal SPECT Co-registered to MRI and SISCOM images were generated and reviewed by two blinded reviewers. The rates of potential localization of the EZ, and the agreement with the EEG, were determined for each scan. Localization rates were compared between ictal scans with different radiotracer injection time windows (<30 s, 30-45 s, 45-60 s, 60-90 s, 90-120 s, >120 s). RESULTS: Seventy patients (male = 32, 16-67 years) were included in the study. Overall agreement between the primary raters was moderate for STATISCOM (k = 0.44) and SISCOM (k = 0.57). The ability of SPECT to localize the potential EZ was 69% (48/70) for STATISCOM and 59% (41/70) for SISCOM. Injection time was not associated with the rate of localizing the potential EZ for STATISCOM (p = 0.64), whereas for SISCOM there was a trend that shorter injection times were associated with better ability to localize the potential EZ (p = 0.06). Agreement between SPECT and video-EEG data was 54% (38/70) for STATISCOM and 39% (27/70) for SISCOM. Statistical Ictal SPECT Co-registered to MRI did not show any difference of agreement across injection time groups (p = 0.42) whereas SISCOM showed better agreement with video-EEG data in the earlier injection time groups (p = 0.02). No differences in agreement between SPECT and video-EEG data were seen between patients with and without MRI lesions for either STATISCOM or SISCOM. Statistical Ictal SPECT Co-registered to MRI showed significantly better agreement for temporal than extratemporal seizures, with no difference of agreement between early (<45 s) and late (>45 s) injections. CONCLUSION: Statistical Ictal SPECT Co-registered to MRI showed overall higher agreement rates with EZ localization by video-EEG than SISCOM, which was not affected by the injection times. Statistical Ictal SPECT Co-registered to MRI may provide localizing information for "late" injections where visual reads and SISCOM are inconclusive.

Subtraction ictal SPECT co-registered to MRI (SISCOM) patterns in children with temporal lobe epilepsy.

OBJECTIVE: We evaluated SISCOM patterns and their relationship with surgical outcome in children with temporal lobe epilepsy (TLE) who had undergone a temporal lobe surgery. METHODS: This was an observational study evaluating SISCOM patterns in 40 children with TLE. We classified SISCOM patterns into 4 categories; (i) unilateral anteromesial and/or anterolateral temporal pattern; (ii) unilateral anteromesial and/or anterolateral temporal plus posterior extension pattern; (iii) bilateral anteromesial and/or anterolateral temporal pattern; and (iv) atypical pattern. Determinants of SISCOM pattern and correlation between postoperative outcomes and SISCOM patterns were evaluated. RESULTS: Pattern (i), (ii), (iii), and (iv) were identified in 10 (25%), 14 (35%), 0 (0%), and 16 (40%) patients, respectively. There was no significant correlation between patterns and postoperative outcomes. SISCOM patterns significantly associated with the presence of hippocampal sclerosis and type of focal cortical dysplasia (p-value = 0.048 and 0.036, respectively). Patients with HS had 5 times the odds of having unilateral temporal pattern, compared to patients with other neuropathology (OR = 5, 95% CI 0.92 to 27.08). Patients with FCD type 2 had 9.71 times the odds of having atypical pattern, compared to patients with other types of FCD (OR = 9.71, 95% CI 0.92 to 103.04). Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes (p-value = 0.018 and 0.013, respectively). CONCLUSION: Three SISCOM patterns were seen. Patients with HS had increased odds of having unilateral temporal pattern while patients with FCD type 2 had increased odds of having atypical pattern. However, there was no significant correlation between SISCOM patterns and postoperative outcomes. Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcome. SIGNIFICANCE: This study shows that the distribution of SISCOM patterns and their relationship with postoperative outcomes in children with TLE are different from adult population. Besides, SISCOM may add only limited diagnostic and prognostic information in children with drug-resistant TLE undergoing epilepsy surgery. Further evaluation to identify patient populations that may benefit from SISCOM is desirable.

MNI SISCOM: an Open-Source Tool for Computing Subtraction Ictal Single-Photon Emission CT Coregistered to MRI.

Subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) is a well-established technique for quantitative analysis of ictal vs interictal SPECT images that can contribute to the identification of the seizure onset zone in patients with drug-resistant epilepsy. However, there is presently a lack of user-friendly free and open-source software to compute SISCOM results from raw SPECT and MRI images. We aimed to develop a simple graphical desktop application for computing SISCOM. MNI SISCOM is a new free and open-source software application for computing SISCOM and producing practical MRI/SPECT/SISCOM image panels for review and reporting. The graphical interface allows any user to quickly and easily obtain SISCOM images with minimal user interaction. Additionally, MNI SISCOM provides command line and Python interfaces for users who would like to integrate these features into their own scripts and pipelines. MNI SISCOM is freely available for download from: https://github.com/jeremymoreau/mnisiscom .

A Novel Noninvasive Approach Based on SPECT and EEG for the Location of the Epileptogenic Zone in Pharmacoresistant Non-Lesional Epilepsy.

Background and objectives: The aim of this study is to propose a methodology that combines non-invasive functional modalities electroencephalography (EEG) and single photon emission computed tomography (SPECT) to estimate the location of the epileptogenic zone (EZ) for the presurgical evaluation of patients with drug-resistant non-lesional epilepsy. Materials and Methods: This methodology consists of: (i) Estimation of ictal EEG source imaging (ESI); (ii) application of the subtraction of ictal and interictal SPECT co-registered with MRI (SISCOM) methodology; and (iii) estimation of ESI but using the output of the SISCOM as a priori information for the estimation of the sources. The methodology was implemented in a case series as an example of the application of this novel approach for the presurgical evaluation. A gold standard and a coincidence analysis based on measures of sensitivity and specificity were used as a preliminary assessment of the proposed methodology to localize EZ. Results: In patients with good postoperative evolution, the estimated EZ presented a spatial coincidence with the resection site represented by high values of sensitivity and specificity. For the patient with poor postoperative evolution, the methodology showed a partial incoherence between the estimated EZ and the resection site. In cases of multifocal epilepsy, the method proposed spatially extensive epileptogenic zones. Conclusions: The results of the case series provide preliminary evidence of the methodology's potential to epileptogenic zone localization in non-lesion drug-resistant epilepsy. The novelty of the article consists in estimating the sources of ictal EEG using SISCOM result as a prior for the inverse solution. Future studies are necessary in order to validate the described methodology. The results constitute a starting point for further studies in order to support the clinical reliability of the proposed methodology and advocate for their implementation in the presurgical evaluation of patients with intractable non-lesional epilepsy.

PISCOM: a new procedure for epilepsy combining ictal SPECT and interictal PET.

PURPOSE: We present a modified version of the SISCOM procedure that uses interictal PET instead of interictal SPECT for seizure onset zone localization. We called this new nuclear imaging processing technique PISCOM (PET interictal subtracted ictal SPECT coregistered with MRI). METHODS: We retrospectively studied 23 patients (age range 4-61 years) with medically refractory epilepsy who had undergone MRI, ictal SPECT, interictal SPECT and interictal FDG PET and who had been seizure-free for at least 2 years after surgical treatment. FDG PET images were reprocessed (rFDG PET) to assimilate SPECT features for image subtraction. Interictal SPECT and rFDG PET were compared using statistical parametric mapping (SPM). PISCOM and SISCOM images were evaluated visually and using an automated volume of interest-based analysis. The results of the two studies were compared with each other and with the known surgical resection site. RESULTS: SPM showed no significant differences in cortical activity between SPECT and rFDG PET images. PISCOM and SISCOM showed equivalent results in 17 of 23 patients (74%). The seizure onset zone was successfully identified in 19 patients (83%) by PISCOM and in 17 (74%) by SISCOM: in 15 patients (65%) the two techniques showed concordant successful results. The volume of interest-based analysis showed no significant differences between PISCOM and SISCOM in identifying the extension of the seizure onset zone. However, PISCOM showed a lower amount of indeterminate activity due to propagation, background or artefacts. CONCLUSION: Preliminary findings of this initial proof-of-concept study suggest that perfusion and glucose metabolism in the cerebral cortex can be correlated and that PISCOM may be a valid technique for identification of the seizure onset zone. However, further studies are needed to validate these results.

Accuracy of arterial spin labeling magnetic resonance imaging (MRI) perfusion in detecting the epileptogenic zone in patients with drug-resistant neocortical epilepsy: comparison with electrophysiological data, structural MRI, SISCOM and FDG-PET.

BACKGROUND AND PURPOSE: Locating the epileptogenic zone (EZ) in patients with neocortical epilepsy presents major challenges. Our aim was to assess the accuracy of arterial spin labeling (ASL), an emerging non-invasive magnetic resonance imaging (MRI) perfusion technique, to locate the EZ in patients with drug-resistant neocortical epilepsy. METHODS: Twenty-five consecutive patients with neocortical epilepsy referred to our epilepsy unit for pre-surgical evaluation underwent a standardized assessment including video-electroencephalography (EEG) monitoring, structural MRI, subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) and fluorodeoxyglucose positron emission tomography (FDG-PET) studies. An ASL sequence was included in the MRI studies. Areas of hypoperfusion or hyperperfusion on ASL were classified into 15 anatomic-functional cortical regions; these regional cerebral blood flow maps were compared with the EZ determined by the other tests and the strength of concordance was assessed with the kappa coefficient. RESULTS: Of the 25 patients [16 (64%) women; mean age 32.4 (±13.8) years], 18 (72%) had lesions on structural MRI. ASL abnormalities were seen in 15 (60%) patients (nine hypoperfusion, six hyperperfusion). ASL had a very good concordance with FDG-PET (k = 0.84), a good concordance with structural MRI (k = 0.76), a moderate concordance with video-EEG monitoring (k = 0.53) and a fair concordance with SISCOM (k = 0.28). CONCLUSION: Arterial spin labeling might help to confirm the location and extent of the EZ in the pre-surgical workup of patients with drug-resistant neocortical epilepsy.

SPECT postprocessing for epileptogenic focus localization: SISCOM versus ISAS.

OBJECTIVE: Ictal SPECT can be used as an estimate for the epileptogenic zone in people with focal epilepsy. Subtraction of ictal and interictal SPECT scans reveals the area with significant ictal hyperperfusion. Some methods use a control database to also correct for physiological variance. This control database is ideally scanner specific, but it is not trivial to obtain such a database because of ethical issues. In this study, we used a publicly available control database to compare ictal-interictal SPECT analyzed by SPM (ISAS) with the most commonly used subtraction ictal SPECT co-registered to MRI (SISCOM). METHODS: Ictal and interictal SPECTs of 26 patients (age range: 7-50 years, 15 adults, 11 children) with focal drug resistant epilepsy in workup for epilepsy surgery were retrospectively analyzed using both SISCOM and ISAS. The control database for ISAS was obtained from the ISAS website. Two groups of blinded reviewers determined the location of ictal hyperperfusion in all datasets. Results were compared between subtraction algorithms and with the resected area (if available) or the suspected epileptogenic zone. The number of significant clusters and the locations of maximum hyperperfusion were compared between algorithms. RESULTS: The location of ISAS and SISCOM hyperperfusion was the same in 14 patients (54%). ISAS localized in 6 patients where SISCOM did not. Compared to the resected area or suspected epileptogenic zone, SISCOM correctly localized in 55%, while ISAS did in 65% (not significantly different). ISAS shows significantly less clusters than SISCOM. The maximum hyperperfusion was in the reviewer's location in 65% for ISAS and 38% for SISCOM. SIGNIFICANCE: ISAS using a publicly available control database gives comparable or better results than SISCOM. ISAS results are easier to interpret than SISCOM results. We show that ISAS is a reliable alternative for SISCOM, which could easily be implemented in epilepsy surgery clinics. PLAIN LANGUAGE SUMMARY: We explored the effectiveness of ISAS as an alternative to the widely used SISCOM for assessing SPECT scans in epilepsy surgery candidates. Utilizing a publicly available control database, we compared the two methods in 26 patients. The results indicate that ISAS might offer increased accuracy and interpretability, making it a promising option, especially for centers without access to a specific control dataset.

Yield of non-invasive imaging in MRI-negative focal epilepsy.

OBJECTIVE: The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy. METHODS: We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration). RESULTS: 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11). CONCLUSION: If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together.

Brain perfusion SPECT in the presurgical evaluation of epilepsy: is additional ictal SPECT required in case of high-confidence lateralization of the seizure onset zone by interictal SPECT and vice versa?

BACKGROUND: Ictal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT. METHODS: 177 patients (48% females, median age 38y, interquartile range 27-48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: "interictal only" (interictal SPECT and statistical hypoperfusion map), "ictal only" (ictal SPECT and hyperperfusion map), and "full" setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered "lateralizing with high confidence" if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the "full" setting was used as reference standard. RESULTS: The proportion of "lateralizing with high confidence" cases was 4.5/31.6/38.4% in the "interictal only"/"ictal only"/"full" setting. One (12.5%) of the 8 cases that were "lateralizing with high confidence" in the "interictal only" setting lateralized to the wrong hemisphere. Among the 56 cases that were "lateralizing with high confidence" in the "ictal only" setting, 54 (96.4%) were also lateralizing in the "full" setting, all to the same hemisphere. CONCLUSIONS: Starting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended.

Detection of ictal and periictal hyperperfusion with subtraction of ictal-interictal 1.5-Tesla pulsed arterial spin labeling images co-registered to conventional magnetic resonance images (SIACOM).

Background: Our recent report showed that 1.5-T pulsed arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging (1.5-T Pulsed ASL [PASL]), which is widely available in the field of neuroemergency, is useful for detecting ictal hyperperfusion. However, the visualization of intravascular ASL signals, namely, arterial transit artifact (ATA), is more remarkable than that of 3-T pseudocontinuous ASL and is easily confused with focal hyperperfusion. To eliminate ATA and enhance the detectability of (peri) ictal hyperperfusion, we developed the subtraction of ictal-interictal 1.5-T PASL images co-registered to conventional MR images (SIACOM). Methods: We retrospectively analyzed the SIACOM findings in four patients who underwent ASL during both (peri) ictal and interictal states and examined the detectability for (peri) ictal hyperperfusion. Results: In all patients, the ATA of the major arteries was almost eliminated from the subtraction image of the ictal-interictal ASL. In patients 1 and 2 with focal epilepsy, SIACOM revealed a tight anatomical relationship between the epileptogenic lesion and the hyperperfusion area compared with the original ASL image. In patient 3 with situation-related seizures, SIACOM detected minute hyperperfusion at the site coinciding with the abnormal electroencephalogram area. SIACOM of patient 4 with generalized epilepsy diagnosed ATA of the right middle cerebral artery, which was initially thought to be focal hyperperfusion on the original ASL image. Conclusion: Although it is necessary to examine several patients, SIACOM can eliminate most of the depiction of ATA and clearly demonstrate the pathophysiology of each epileptic seizure.

Association of ictal aphasia with hypoperfusion in language areas in temporal lobe epilepsy patients.

Ictal clinical phenomenology, including aphasia, is usually associated with increased regional cerebral perfusion. We present an unusual pattern of ictal cerebral perfusion in three patients with pharmacoresistant, lesional temporal lobe epilepsy and ictal/postictal aphasia studied with prolonged video-EEG, ictal, and interictal SPECT and MRI for pre-surgical evaluation. Subtraction of ictal-interictal SPECT images co-registered with MRI (SISCOM) showed ictal hyperperfusion in the temporal epileptogenic area in all patients. In addition, hypoperfusion of Broca's area in one case, Wernicke's area in other patient, and both areas in the remaining one were observed. Ictal aphasia in these patients may be explained by functional inhibition of a primary language area, driven by the epileptogenic network. This pattern can contribute to understand the pathophysiology of some ictal signs, with an impact on the evaluation of individual surgical risks.

Presurgical evaluation of drug-resistant paediatric focal epilepsy with PISCOM compared to SISCOM and FDG-PET.

PURPOSE: Children with drug-resistant focal epilepsy have a compromised quality of life. Epilepsy surgery can control or significantly reduce the seizures. We assessed and compared the usefulness of PISCOM, a new nuclear imaging processing technique, with SISCOM and 18F-FDG PET (FDG-PET) in pre-surgical evaluation of paediatric drug-resistant focal epilepsy. METHODS: Twenty-two children with pharmcorefractory epilepsy, mainly extratemporal, who had undergone pre-surgical assessment including SISCOM and FDG-PET and with postsurgical favorable outcome (Engel class I or II) for at least two years, were included in this proof-of-concept study. All abnormalities observed in SISCOM, FDG-PET and PISCOM were compared with each other and with the known epileptogenic zone (EZ) based on surgical treatment, histopathologic and surgical outcome results. Global interobserver agreement, Cohen's Kappa coeficient and PABAK statistic were calculated for each technique. RESULTS: PISCOM concordance with the known EZ was significantly higher than SISCOM (p<0.05), and no statistically differences were found with FDG-PET. PISCOM showed successful identification in 19 of 22 cases (86%), successful concordant with FDG-PET in 17 (77%), and SISCOM in 11 (50%). If we consider PISCOM and FDG-PET results together, both techniques successfully localized the known EZ in all cases. The measures of agreement between two experts in nuclear medicine were higher in PISCOM than in SISCOM and FDG-PET. CONCLUSION: PISCOM could provide complementary presurgical information in drug-resistant paediatric focal epilepsy, particularly in cases in which FDG-PET is doubtful or negative, replacing SISCOM and sparing the use of interictal SPECT.

How to inject ictal SPECT? From manual to automated injection.

BACKGROUND: Successful surgery depends on the accurate localization of epileptogenic zone before surgery. Ictal SPECT is the only imaging modality that allows identification of the ictal onset zone by measuring the regional cerebral blood flow at the time of injection. The main limitation of ictal SPECT in epilepsy is the complex methodology of the tracer injection during a seizure. To overcome this limitation, we present the main features of the first automated injector for ictal SPECT (epijet, LemerPax; La Chapelle -sur-Erdre; France). In this study we compared traditional manual injection with automated injection for ictal SPECT in 122 patients with drug-resistant epilepsy. METHODS: The study included 55 consecutive prospective patients with drug-resistant epilepsy undergoing injection with the automated injector. The control group was our retrospective database of a historic pool of 67 patients, injected manually from 2014 to 2016. Calculated annual exposure/radioactive dose for operators was measured. Injection time, seizure focus localization with ictal SPECT, as well as repeated hospitalizations related to inconclusive findings of the SPECT were compared in these two groups of patients. RESULTS: There were no differences in the average injection time with epijet (13 s) compared with the traditional manual injection (14 s). The seizure focus was successfully localized with ictal SPECT with epijet in 44/55 (80 %) patients and with manual injection in 46/67 (68 %) patients (p = 0.097). Repeated studies were required in 9/67 (23 %) patients in the manual injection group compared to 3 patients (7%) in the epijet group (p = 0.141). Calculated annual exposure/dose for operators of 0.39 mSv/year and administered dose error inferior to 5% are other advantages of epijet. CONCLUSION: The first results using epijet are promising in adjustment of the injection dose, reducing the rate of radiation exposure for patients and nurses, maintaining the same injection time and allowing high SPECT accuracy. These preliminary results support the use of an automated injection system to inject radioactive ictal SPECT doses in epilepsy units.

Regional Ictal Hyperperfusion in the Contralateral Occipital Area May Be a Poor Prognostic Marker of Anterior Temporal Lobectomy: A SISCOM Analysis of MTLE Cases.

BACKGROUND AND OBJECTIVE: Subtraction of ictal SPECT coregistered to MRI (SISCOM) provides complementary information for detecting the ictal onset zone, especially in patients with MRI-negative focal epilepsy, and provides additional useful information for predicting long-term postresection outcomes. This study sought to investigate the relationship between surgical failure and increased cerebral blood flow (CBF) pattern using SPECT in patients with mesial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS). METHODS: Among 42 subjects who underwent anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) for MTLE-HS, 29 (69.0%) were seizure-free (SF group). Hyperperfusion was compared in 14 ipsilateral and contralateral brain regions in SISCOM images between the two groups. RESULTS: The pattern of ictal hyperperfusion in temporal regions did not vary significantly between the SF and non-seizure-free (NSF) groups. However, CBF increases in the contralateral occipital area was more frequent in the NSF group than in the SF group. Furthermore, ictal hyperperfusion of the ipsilateral occipital and contralateral parietal areas tended to be more frequent in the NSF group. CONCLUSION: The results indicate that poor ATL-AH surgical outcome is associated with a tendency of ictal hyperperfusion of the contralateral occipital cortex based on SISCOM analysis. The pattern of early ictal CBF changes implicating the propagation from temporal to occipital cortices can be considered a marker of poor surgical outcomes of ATL-AH in MTLE-HS patients.

Temporal and spatial changes in cerebral blood flow in neuropsychiatric systemic lupus erythematosus: a subtraction brain spect study.

This study was addressed to evaluate the temporal and spatial changes in regional cerebral blood flow (rCBF) of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Our objective was to correlate the subtracted SPECT coregistered to MRI features (SISCOM) with demographic, clinical and laboratory findings to shed light upon the pathophysiological evolution of the NPSLE. Twenty-six NPSLE patients with MRI and pre- and post-treatment brain SPECT with [99mTc]Tc-ECD. SISCOM features were categorized as improvement, worsening, activation and/or deactivation of rCBF findings. Patients mean age of 43.19 years and 65.38% white were evaluated. The patients mean age at onset of SLE was 26.05 and 42.29 for NPSLE. The mean time between the onset of SLE and first NPSLE symptoms was 05.57 years. The disease has already been initiated as NPSLE in 4 patients. The SLEDAI average score was 31.69 and the SLICC/ACR-DI score was 06.96. The patients underwent an average of 09.23 cyclophosphamide. The SISCOM findings showed functional and pathological states on different brain regions. The rCBF changes were not associated with index scores. There was, however, a trend towards an association between lower SLEDAI scores with improvement and higher SLEDAI with worsening in SISCOM, Also a trend of association between lower SLICC score with improvement, and higher SLICC with worsening. The female gender was predictive of activation and worsening, separately, and deactivation and worsening in a set. Non-white patients were predictive of worsening. The seizure was predictive of deactivation separately, and deactivation and worsening in a set. Finally, normal C3 was a predictor of improvement. The present study showed dynamic brain changes in NPSLE patients. SISCOM technique showed improved rCBF in some brain areas, and worsening, activation and deactivation in others. There were associations between rCBF changes and gender, skin colour and complement C3 and association trends with SLEDAI and SLICC scores.

SPECT activation patterns in psychogenic non-epileptic seizures in temporal lobe epilepsy patients.

INTRODUCTION: The diagnosis of psychogenic non-epileptic seizures (PNES) can often be challenging. When video-electroencephalography (EEG) is not conclusive, single-photon emission computed tomography (SPECT) can be useful by quantifying changes in regional cerebral blood flow (rCBF). METHODS: We conducted a retrospective case-control study in adult patients with pharmacoresistant temporal lobe epilepsy (TLE). Those patients with an ictal SPECT obtained during an event finally diagnosed as PNES were included as cases (PNES+). The control group consisted of patients with TLE without PNES (PNES-). Clinical episodes were analysed and classified according to PNES subtypes. Subtraction ictal SPECT coregistered to MRI (SISCOM) analysis was performed for the detection of areas with significant changes in perfusion compared to individual interictal studies. Group comparisons in SPM12 included paired t-tests of ictal vs. interictal studies in each group of temporal lobe seizures and PNES events. RESULTS: Ten patients with TLE and PNES were included. We found no patterns of regional hyperperfusion typical of TLE seizures during the PNES events. In two of these cases, an ictal SPECT during a confirmed epileptic seizure was also obtained, showing antero-mesial temporal lobe hyperperfusion. Group comparisons between ictal and interictal SPECTs showed increased rCBF in the temporal lobe with reduced perfusion in the default mode network areas and cerebellum during temporal lobe seizures in PNES- patients and decreased perfusion restricted to the posterior parietal cortex without significant rCBF increases in PNES events. CONCLUSIONS: Ictal SPECT can be a helpful tool to characterize rCBF changes in PNES and for differential diagnosis with seizures in TLE patients.

Surgical strategy for refractory epilepsy secondary to porencephaly: ictal SPECT may obviate the need for intracranial electroencephalography. Patient series.

BACKGROUND: Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors aimed to determine whether noninvasive evaluations are sufficient in these patients. OBSERVATIONS: Eleven patients were included in this study. The porencephalic cyst was in the left middle cerebral artery (MCA) area in 9 patients, the left posterior cerebral artery area in 1 patient, and the bilateral MCA area in 1 patient. Interictal electroencephalography (EEG) revealed multiregional, bilateral, interictal epileptiform discharges in 5 of 11 patients. In 6 of 10 patients whose seizures were recorded, the ictal EEG was nonlateralizing. Nine patients underwent ictal single-photon emission computed tomography (SPECT), which revealed lateralized hyperperfusion in 8 of 9 cases. Fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for identifying the functional deficit zone. No patient had intracranial EEG. The procedure performed was hemispherotomy in 7 patients, posterior quadrant disconnection in 3 patients, and occipital disconnection in 1 patient. A favorable seizure outcome was achieved in 10 of 11 patients without the onset of new neurological deficits. LESSONS: Ictal SPECT was useful for confirming the side of seizure origin when electroclinical findings were inconclusive. Thorough noninvasive evaluations, including FDG-PET and ictal SPECT, enabled curative surgery without intracranial EEG. Seizure and functional outcomes were favorable.

Distinct dual cortico-cortical networks successfully identified between supplemental and primary motor areas during intracranial EEG for drug-resistant frontal lobe epilepsy.

We present a case of drug-resistant focal motor seizures in which separate cortico-cortical epileptic networks within the supplementary motor area (SMA) proper and primary motor area (PMA) were proven by ictal high-frequency oscillation (HFO) and cortico-cortical evoked potential (CCEP). A 12-year-old girl presented with two types seizures: type A, tonic extension and subsequent clonic movements of the right arm; and type B, tonic and clonic movements of the right leg. MRI was normal and karyotype genetic analysis revealed 46,X,t(X;14)(q13;p12). She underwent placement of chronic subdural electrodes over the left hemisphere. We recorded a total of nine seizures during 10 days of epilepsy monitoring. Type A seizures started from the lower part of the left SMA proper and early spread to the hand motor area of the PMA. Type B seizures started from the upper part of the SMA proper and early spread to the leg motor area of the PMA. CCEPs of both SMA proper and PMA activated two identical routes for evoked potentials correlating with separate pathways. Corticectomy of the left SMA proper and PMA achieved seizure-free without hemiparesis. Within a small homunculus of the SMA proper, separate epileptic networks were proven and validated by seizure semiology, ictal HFO, and CCEP.

Utility of single-photon emission computed tomography (SPECT) in presurgical evaluation of children: A single-center experience.

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.