Clinical significance of ictal magnetoencephalography in patients undergoing epilepsy surgery.

OBJECTIVE: The significance of ictal magnetoencephalography (MEG) is not well appreciated. We evaluated the relationships between ictal MEG, MRI, intracranial electroencephalography (ICEEG), surgery and postoperative seizure outcome. METHODS: A total of 45 patients (46 cases) with ictal MEG who underwent epilepsy surgery was included. We examined the localization of each modality, surgical resection area and seizure freedom after surgery. RESULTS: Twenty-one (45.7%) out of 46 cases were seizure-free at more than 6 months follow-up. Median duration of postoperative follow-up was 16.5 months. The patients in whom ictal, interictal single equivalent current dipole (SECD) and MRI lesion localization were completely included in the resection had a higher chance of being seizure-free significantly (p < 0.05). Concordance between ictal and interictal SECD localizations was significantly associated with seizure-freedom. Concordance between MRI lesion and ictal SECD, concordance between ictal ICEEG and ictal and interictal SECD, as well as concordance between ictal ICEEG and MRI lesion were significantly associated with seizure freedom. CONCLUSIONS: Ictal MEG can contribute useful information for delineating the resection area in epilepsy surgery. SIGNIFICANCE: Resection should include ictal, interictal SECDs and MRI lesion localization, when feasible. Concordant ictal and interictal SECDs on MEG can be a favorable predictor of seizure freedom.

High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome.

Down syndrome is the phenotypic consequence of trisomy 21, with clinical presentation including both neurodevelopmental and neurodegenerative components. Although the intellectual disability typically displayed by individuals with Down syndrome is generally global, it also involves disproportionate deficits in hippocampally-mediated cognitive processes. Hippocampal dysfunction may also relate to Alzheimer's disease-type pathology, which can appear in as early as the first decade of life and becomes universal by age 40. Using 7-tesla MRI of the brain, we present an assessment of the structure and function of the hippocampus in 34 individuals with Down syndrome (mean age 24.5 years ± 6.5) and 27 age- and sex-matched typically developing healthy controls. In addition to increased whole-brain mean cortical thickness and lateral ventricle volumes (P < 1.0 × 10-4), individuals with Down syndrome showed selective volume reductions in bilateral hippocampal subfields cornu Ammonis field 1, dentate gyrus, and tail (P < 0.005). In the group with Down syndrome, bilateral hippocampi showed widespread reductions in the strength of functional connectivity, predominately to frontal regions (P < 0.02). Age was not related to hippocampal volumes or functional connectivity measures in either group, but both groups showed similar relationships of age to whole-brain volume measures (P < 0.05). Finally, we performed an exploratory analysis of a subgroup of individuals with Down syndrome with both imaging and neuropsychological assessments. This analysis indicated that measures of spatial memory were related to mean cortical thickness, total grey matter volume and right hemisphere hippocampal subfield volumes (P < 0.02). This work provides a first demonstration of the usefulness of high-field MRI to detect subtle differences in structure and function of the hippocampus in individuals with Down syndrome, and suggests the potential for development of MRI-derived measures as surrogate markers of drug efficacy in pharmacological studies designed to investigate enhancement of cognitive function.

Radiological and Clinical Value of 7T MRI for Evaluating 3T-Visible Lesions in Pharmacoresistant Focal Epilepsies.

Objective: The recent FDA approval of the first 7T MRI scanner for clinical diagnostic use in October 2017 will likely increase the utilization of 7T for epilepsy presurgical evaluation. This study aims at accessing the radiological and clinical value of 7T in patients with pharmacoresistant focal epilepsy and 3T-visible lesions. Methods: Patients with pharmacoresistant focal epilepsy were included if they had a lesion on pre-operative standard-of-care 3T MRI and also a 7T research MRI. An epilepsy protocol was used for the acquisition of the 7T MRI. Prospective visual analysis of 7T MRI was performed by an experienced board-certified neuroradiologist and communicated to the patient management team. The clinical significance of the additional 7T findings was assessed by intracranial EEG (ICEEG) ictal onset, surgical resection, post-operative seizure outcome and histopathology. A subset of lesions were demarked with arrows for subsequent, retrospective comparison between 3T and 7T by 7 neuroradiologists using a set of quantitative scales: lesion presence, conspicuity, boundary, gray-white tissue contrast, artifacts, and the most helpful sequence for diagnosis. Conger's kappa for multiple raters was performed for chance-adjusted agreement statistics. Results: A total of 47 patients were included, with the main pathology types of focal cortical dysplasia (FCD), hippocampal sclerosis, periventricular nodular heterotopia (PVNH), tumor and polymicrogyria (PMG). 7T detected additional smaller lesions in 19% (9/47) of patients, who had extensive abnormalities such as PMG and PVNH; however, these additional findings were not necessarily epileptogenic. 3T-7T comparison by the neuroradiologist team showed that lesion conspicuity and lesion boundary were significantly better at 7T (p < 0.001), particularly for FCD, PVNH and PMG. Chance-adjusted agreement was within the fair range for lesion presence, conspicuity and boundary. Gray-white contrast was significantly improved at 7T (p < 0.001). Significantly more artifacts were encountered at 7T (p < 0.001). Significance: For patients with 3T-visible lesions, 7T MRI may better elucidate the extent of multifocal abnormalities such as PVNH and PMG, providing potential targets to improve ICEEG implantation. Patients with FCD, PVNH and PMG would likely benefit the most from 7T due to improved lesion conspicuity and boundary. Pathologies in the antero-inferior temporal regions likely benefit less due to artifacts.

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.

High-resolution functional connectivity of the default mode network in young adults with down syndrome.

Studies of resting-state functional connectivity MRI in Alzheimer's disease suggest that disease stage plays a role in functional changes of the default mode network. Individuals with the genetic disorder Down syndrome show an increased incidence of early-onset Alzheimer's-type dementia, along with early and nearly universal neuropathologic changes of Alzheimer's disease. The present study examined high-resolution functional connectivity of the default mode network in 11 young adults with Down syndrome that showed no measurable symptoms of dementia and 11 age- and sex-matched neurotypical controls. We focused on within-network connectivity of the default mode network, measured from both anterior and posterior aspects of the cingulate cortex. Sixty-eight percent of connections to the posterior cingulate and 26% to the anterior cingulate showed reduced strength in the group with Down syndrome (p < 0.01). The Down syndrome group showed increased connectivity strength from the anterior cingulate to the bilateral inferior frontal gyri and right putamen (p < 0.005). In an exploratory analysis, connectivity in the group with Down syndrome showed regional relationships to plasma measures of inflammatory markers and t-tau. In non-demented adults with Down syndrome, functional connectivity within the default mode network may be analogous to changes reported in preclinical Alzheimer's disease, and warrants further investigation as a measure of dementia risk.

Localization value of subclinical seizures on scalp video-EEG in epilepsy presurgical evaluation.

OBJECTIVE: To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. METHODS: We included 123 consecutive patients who had SCSs and CSs during scalp-VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. RESULTS: Sixty-nine patients (56.1%) had seizure-free outcome at 1-year follow-up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1-year (P = .020) and 2-year follow-up (P = .040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%. SIGNIFICANCE: Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.

Development of high-resolution 3D MR fingerprinting for detection and characterization of epileptic lesions.

BACKGROUND: Conventional MRI can be limited in detecting subtle epileptic lesions or identifying active/epileptic lesions among widespread, multifocal lesions. PURPOSE: We developed a high-resolution 3D MR fingerprinting (MRF) protocol to simultaneously provide quantitative T1 , T2 , proton density, and tissue fraction maps for detection and characterization of epileptic lesions. STUDY TYPE: Prospective. POPULATION: National Institute of Standards and Technology (NIST) / International Society for Magnetic Resonance in Medicine (ISMRM) phantom, five healthy volunteers and 15 patients with medically intractable epilepsy undergoing presurgical evaluation with noninvasive or invasive electroclinical data. FIELD STRENGTH/SEQUENCE: 3D MRF scans and routine clinical epilepsy MR protocols were acquired at 3 T. ASSESSMENT: The accuracy of the T1 and T2 values were first evaluated using the NIST/ISMRM phantom. The repeatability was then estimated with both phantom and volunteers based on the coefficient of variance (CV). For epilepsy patients, all the maps were qualitatively reviewed for lesion detection by three independent reviewers (S.E.J., M.L., I.N.) blinded to clinical data. Region of interest (ROI) analysis was performed on T1 and T2 maps to quantify the multiparametric signal differences between lesion and normal tissues. Findings from qualitative review and quantitative ROI analysis were compared with patients' electroclinical data to assess concordance. STATISTICAL TESTS: Phantom results were compared using R-squared, and patient results were compared using linear regression models. RESULTS: The phantom study showed high accuracy with the standard values, with an R2 of 0.99. The volunteer study showed high repeatability, with an average CV of 4.3% for T1 and T2 in various tissue regions. For the 15 patients, MRF showed additional findings in four patients, with the remaining 11 patients showing findings consistent with conventional MRI. The additional MRF findings were highly concordant with patients' electroclinical presentation. DATA CONCLUSION: The 3D MRF protocol showed potential to identify otherwise inconspicuous epileptogenic lesions from the patients with negative conventional MRI diagnosis, as well as to correlate with different levels of epileptogenicity when widespread lesions were present. LEVEL OF EVIDENCE: 3. Technical Efficacy Stage: 3. J. Magn. Reson. Imaging 2019;49:1333-1346.

Quantitative positron emission tomography-guided magnetic resonance imaging postprocessing in magnetic resonance imaging-negative epilepsies.

OBJECTIVE: Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD. METHODS: We retrospectively included a consecutive cohort of surgical patients who had a negative preoperative MRI by radiology report. MAP was performed on T1-weighted volumetric sequence and QPET was performed on PET/computed tomographic data, both with comparison to scanner-specific normal databases. Concordance between MAP and QPET was assessed at a lobar level, and the significance of concordant QPET-MAP+ abnormalities was confirmed by postresective seizure outcome and histopathology. QPET thresholds of standard deviations (SDs) of -1, -2, -3, and -4 were evaluated to identify the optimal threshold for QPET-MAP analysis. RESULTS: A total of 104 patients were included. When QPET thresholds of SD = -1, -2, and -3 were used, complete resection of the QPET-MAP+ region was significantly associated with seizure-free outcome when compared with the partial resection group (P = 0.023, P < 0.001, P = 0.006) or the no resection group (P = 0.002, P < 0.001, P = 0.001). The SD threshold of -2 showed the best combination of positive rate (55%), sensitivity (0.68), specificity (0.88), positive predictive value (0.88), and negative predictive value (0.69). Surgical pathology of the resected QPET-MAP+ areas revealed mainly FCD type I. Multiple QPET-MAP+ regions were present in 12% of the patients at SD = -2. SIGNIFICANCE: Our study demonstrates a practical and effective approach to combine quantitative analyses of functional (QPET) and structural (MAP) imaging data to improve identification of subtle epileptic abnormalities. This approach can be readily adopted by epilepsy centers to improve postresective seizure outcomes for patients without apparent lesions on MRI.

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. METHODS: We retrospectively included a consecutive cohort of patients who failed prior resective epilepsy surgery, underwent re-evaluation including MEG and ictal SPECT, and had another surgery after the re-evaluation. The relationship between resection and localization from each test was determined, and their association with seizure outcomes was analyzed. RESULTS: A total of 46 patients were included; 21 (46%) were seizure-free at 1-year followup after reoperation. Twenty-seven (58%) had a positive MEG and 31 (67%) had a positive ictal SPECT. The resection of MEG foci was significantly associated with seizure-free outcome (p = 0.002). Overlap of ictal SPECT hyperperfusion zones with resection was significantly associated with seizure-free outcome in the subgroup of patients with injection time ≤20 seconds(p = 0.03), but did not show significant association in the overall cohort (p = 0.46) although all injections were ictal. Patients whose MEG and ictal SPECT were concordant on a sublobar level had a significantly higher chance of seizure freedom (p = 0.05). CONCLUSIONS: MEG alone achieved successful localization in patients with failed epilepsy surgery with a statistical significance. Only ictal SPECT with early injection (≤20 seconds) had good localization value. Sublobar concordance between both tests was significantly associated with seizure freedom. SPECT can provide essential information in MEG-negative cases and vice versa. SIGNIFICANCE: Our results emphasize the importance of considering a multimodal presurgical evaluation including MEG and SPECT in all patients with a previous failed epilepsy surgery.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed.

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Voxel-based morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative epilepsies.

OBJECTIVE: In the presurgical workup of magnetic resonance imaging (MRI)-negative (MRI(-) or "nonlesional") pharmacoresistant focal epilepsy (PFE) patients, discovering a previously undetected lesion can drastically change the evaluation and likely improve surgical outcome. Our study utilizes a voxel-based MRI postprocessing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle abnormalities in a consecutive cohort of MRI(-) surgical candidates. METHODS: Included in this retrospective study was a consecutive cohort of 150 MRI(-) surgical patients. MAP was performed on T1-weighted MRI, with comparison to a scanner-specific normal database. Review and analysis of MAP were performed blinded to patients' clinical information. The pertinence of MAP(+) areas was confirmed by surgical outcome and pathology. RESULTS: MAP showed a 43% positive rate, sensitivity of 0.9, and specificity of 0.67. Overall, patients with the MAP(+) region completely resected had the best seizure outcomes, followed by the MAP(-) patients, and patients who had no/partial resection of the MAP(+) region had the worst outcome (p < 0.001). Subgroup analysis revealed that visually identified subtle findings are more likely correct if also MAP(+) . False-positive rate in 52 normal controls was 2%. Surgical pathology of the resected MAP(+) areas contained mainly non-balloon-cell focal cortical dysplasia (FCD). Multiple MAP(+) regions were present in 7% of patients. INTERPRETATION: MAP can be a practical and valuable tool to: (1) guide the search for subtle MRI abnormalities and (2) confirm visually identified questionable abnormalities in patients with PFE due to suspected FCD. A MAP(+) region, when concordant with the patient's electroclinical presentation, should provide a legitimate target for surgical exploration.

Analyzing reliability of seizure diagnosis based on semiology.

This study aimed to determine the accuracy of seizure diagnosis by semiological analysis and to assess the factors that affect diagnostic reliability. A total of 150 video clips of seizures from 50 patients (each with three seizures of the same type) were observed by eight epileptologists, 12 neurologists, and 20 physicians (internists). The videos included 37 series of epileptic seizures, eight series of physiologic nonepileptic events (PNEEs), and five series of psychogenic nonepileptic seizures (PNESs). After observing each video, the doctors chose the diagnosis of epileptic seizures or nonepileptic events for the patient; if the latter was chosen, they further chose the diagnosis of PNESs or PNEEs. The overall diagnostic accuracy rate for epileptic seizures and nonepileptic events increased from 0.614 to 0.660 after observations of all three seizures (p < 0.001). The diagnostic sensitivity and specificity of epileptic seizures were 0.770 and 0.808, respectively, for the epileptologists. These values were significantly higher than those for the neurologists (0.660 and 0.699) and physicians (0.588 and 0.658). A wide range of diagnostic accuracy was found across the various seizures types. An accuracy rate of 0.895 for generalized tonic-clonic seizures was the highest, followed by 0.800 for dialeptic seizures and then 0.760 for automotor seizures. The accuracy rates for myoclonic seizures (0.530), hypermotor seizures (0.481), gelastic/dacrystic seizures (0.438), and PNESs (0.430) were poor. The reliability of semiological diagnosis of seizures is greatly affected by the seizure type as well as the doctor's experience. Although the overall reliability is limited, it can be improved by observing more seizures.

The correlation of magnetoencephalography to intracranial EEG in localizing the epileptogenic zone: a study of the surgical resection outcome.

OBJECTIVES: To evaluate the agreement between magnetoencephalography (MEG) and intracranial electroencephalography (ICEEG) results, to determine the characteristics that lead to concordance, and to assess how these factors relate to favorable epilepsy surgery outcome. MATERIALS: This retrospective study reviewed 50 patients who had positive MEG findings and ICEEG recordings between 2008 and 2010. The anatomical concordance between MEG and ICEEG recordings, the features of the MEG focus, and the relationship between the MEG focus and the surgically resected regions were correlated with the epilepsy surgery outcome. RESULTS: Thirty-six of the 50 patients with positive MEG and ICEEG findings underwent epilepsy surgery, and 27 (75%) of the patients had an anatomical concordance of MEG/ICEEG. Among the patients with concordant MEG/ICEEG, the seizure free outcome rate was significantly higher compared to the discordant group [18/27 (66.7%) patients concordant vs. 1/9 (11.1%) patients discordant (p<0.006)]. Nineteen (53%) of the 36 patients had complete resection when the MEG focus overlapped with the resection area, and 15 (79%) of these 19 patients became seizure-free following surgery (p<0.001); 17 (47%) of the 36 patients had an MEG focus that was not completely resected (the MEG foci of 7 patients partially overlapped the resection areas, and 10 patients had MEG foci that were in a different area from the resection area), and 13/17 (76.5%) patients had seizure recurrences (p<0.001). CONCLUSIONS: Both the anatomical concordance of MEG/ICEEG and the complete resection of the MEG foci significantly increased the chance of seizure-free outcomes following epilepsy surgery.

Natural course and predictors of spontaneous seizure remission in idiopathic generalized epilepsy: 7-27 years of follow-up.

The spontaneous course of idiopathic generalized epilepsy (IGE) is still controversial. The aim of this study was both to investigate the long-term spontaneous course and to identify factors that are predictive for epilepsy remission in a small cohort of 15 IGE patients (9 women) who refused antiepileptic drug (AED) treatment and therefore never have been treated with AED. All of them were reevaluated with a review of their medical records and direct face-to-face interview; the mean duration of follow-up was 15.3 years. Five (33.3%) of them had absence epilepsy (absence seizures, ABS), 5 had IGE with generalized tonic-clonic seizures (GTCS), and another 5 had both seizure types (IGE with ABS/GTCS). Rate of epilepsy remission was 53.3% with a mean time of seizure freedom of 13.1 years; rate of remission was highest among absence epilepsy patients (80%), followed by IGE with GTCS (60%) and IGE with ABS/GTCS (20%). The frequency of spontaneous generalized interictal epileptiform discharges in electroencephalography is not associated with the long-term seizure outcome (p=0.201) and per se does not require AED treatment. Furthermore, the occurrence of photoparoxysmal responses (p=0.020) as well as the occurrence of more than 3 GTCS during the course (p=0.029) were identified as significant predictors for a poor long-term seizure outcome which makes AED treatment indispensable in these patients. This study underlines the heterogenity of the group of IGE. AED treatment has no impact on the spontaneous course of IGE with ABS and/or GTCS. Several predictors for the long-term seizure outcome in patients with IGE were identified in this study.

Neuroimaging characteristics of MRI-negative orbitofrontal epilepsy with focus on voxel-based morphometric MRI postprocessing.

PURPOSE: The orbitofrontal (OF) region is one of the least explored regions of the cerebral cortex. There are few studies on patients with electrophysiologically and surgically confirmed OF epilepsy and a negative magnetic resonance imaging (MRI) study. We aimed to examine the neuroimaging characteristics of MRI-negative OF epilepsy with the focus on a voxel-based morphometric MRI postprocessing technique. METHODS: We included six patients with OF epilepsy, who met the following criteria: surgical resection of the OF lobe with/without adjacent cortex, seizure-free for ≥12 months, invasive video-electroencephalography (EEG) monitoring showing ictal onset from the OF area, and preoperative MRI regarded as negative. Patients were investigated in terms of their image postprocessing and functional neuroimaging characteristics, electroclinical characteristics obtained from noninvasive and invasive evaluations, and surgical pathology. MRI postprocessing on T1 -weighted high-resolution scans was implemented with a morphometric analysis program (MAP) in MATLAB. KEY FINDINGS: Single MAP+ abnormalities were found in four patients; three were in the OF region and one in the ipsilateral mesial frontal area. These abnormalities were included in the resection. One patient had bilateral MAP+ abnormalities in the OF region, with the ipsilateral one completely removed. The MAP+ foci were concordant with invasive electrophysiologic data in the majority of MAP+ patients (four of five). The localization value of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and ictal single-photon emission computed tomography (SPECT) is low in this cohort. Surgical pathology included focal cortical dysplasia, remote infarct, Rosenthal fiber formation and gliosis. SIGNIFICANCE: Our study highlights the importance of MRI postprocessing in the process of presurgical evaluation of patients with suspected orbitofrontal epilepsy and "normal" MRI. Using MAP, we were able to positively identify subtle focal abnormalities in the majority of the patients. MAP results need to be interpreted in the context of their electroclinical findings and can provide valuable targets in the process of planning invasive evaluation.

The pathology of magnetic-resonance-imaging-negative epilepsy.

Patients with magnetic-resonance-imaging (MRI)-negative (or 'nonlesional') pharmacoresistant focal epilepsy are the most challenging group undergoing presurgical evaluation. Few large-scale studies have systematically reviewed the pathological substrates underlying MRI-negative epilepsies. In the current study, histopathological specimens were retrospectively reviewed from MRI-negative epilepsy patients (n=95, mean age=30 years, 50% female subjects). Focal cortical dysplasia cases were classified according to the International League Against Epilepsy (ILAE) and Palmini et al classifications. The most common pathologies found in this MRI-negative cohort included: focal cortical dysplasia (n=43, 45%), gliosis (n=21, 22%), hamartia+gliosis (n=12, 13%), and hippocampal sclerosis (n=9, 9%). The majority of focal cortical dysplasia were ILAE type I (n=37) or Palmini type I (n=39). Seven patients had no identifiable pathological abnormalities. The existence of positive pathology was not significantly associated with age or temporal/extratemporal resection. Follow-up data post surgery was available in 90 patients; 63 (70%) and 57 (63%) attained seizure freedom at 6 and 12 months, respectively. The finding of positive pathology was significantly associated with seizure-free outcome at 6 months (P=0.035), but not at 12 months. In subgroup analysis, the focal cortical dysplasia group was not significantly correlated with seizure-free outcome, as compared with the negative-pathology groups at either 6 or 12 months. Of note, the finding of hippocampal sclerosis had a significant positive correlation with seizure-free outcome when compared with the negative-pathology group (P=0.009 and 0.004 for 6- and 12-month outcome, respectively). Absence of a significant histopathology in the resected surgical specimen did not preclude seizure freedom. In conclusion, our study highlights the heterogeneity of epileptic pathologies in MRI-negative epilepsies, with focal cortical dysplasia being the most common finding. The existence of positive pathology in surgical specimen may be a good indication for short-term good seizure outcome. There is a small subset of cases in which no pathological abnormalities are identified.

Optimizing SPECT SISCOM analysis to localize seizure-onset zone by using varying z scores.

PURPOSE: Subtraction ictal single photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure-free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score. METHODS: Twenty-six patients were identified as having ictal-interictal SPECT images, preoperative and postoperative MRI studies, and having remained seizure free for at least 6 months after temporal or extratemporal surgical resection. SISCOM analysis was performed using preoperative MRI studies, and then blindly reviewed for localization of hyperperfused regions. With the added information from postoperative, coregistered MRI, perfusion patterns were determined. KEY FINDINGS: Using pair-wise comparisons, we found that the optimal z score for SPECT-SISCOM localization of the epileptogenic zone was 1.5, not the commonly used z score of 2. The z score of 1.5 was 84.8% sensitive and 93.8% specific. The z score of 1.5 had a moderate interrater agreement (0.70). When an hourglass configuration hyperperfusion pattern was present, a trend toward correctly localizing the seizure onset region was suggested (100% of the 11 observed occurrences). Nonetheless this trend was not statistically significant, possibly reflecting the small number of occurrences in our study. SIGNIFICANCE: SISCOM is a useful modality in evaluating patients for epilepsy surgery. This study shows that the z score of 1.5 represents a highly sensitive and specific SISCOM threshold that should be examined in conjunction with the traditionally used z score of 2 to enhance the chances of correct localization. Further prospective investigations are needed to confirm this finding in large patient series.