Summary
Objective
Although a clear correlation has been observed between high‐frequency oscillations (HFOs) and the seizure‐onset zone in distinct lesions, the role of the underlying pathologic ...substrates in the generation of HFOs is not well established. We aimed to investigate HFO correlates of different pathologic substrates in patients with drug‐resistant epilepsy, and to examine the relation of HFOs with the anatomic location of the dysplastic lesion and surrounding tissue in patients with focal cortical dysplasia (FCD).
Methods
We studied consecutive patients with drug‐resistant epilepsy who underwent intracranial electroencephalography (iEEG) investigations with depth electrodes at the Montreal Neurological Institute and Hospital, between November 2004 and May 2013. Inclusion criteria were the following: a focal lesion documented by magnetic resonance imaging (MRI); EEG recording at a 2,000 Hz sampling rate; and seizures starting from depth electrode contacts placed in lesion and perilesional tissue.
Results
Thirty‐seven patients (13 FCD, 12 mesial temporal sclerosis, five cortical atrophy, three polymicrogyria, three nodular heterotopia, and one tuberous sclerosis) were included; 18 were women (median age 34). Ripples and fast ripples were found in all lesion types, except tuberous sclerosis, which showed no fast ripples. There was a significant difference in rates of ripples and fast ripples across different lesions (p < 0.001), with higher rates in FCD, mesial temporal sclerosis, and nodular heterotopia than in atrophy, polymicrogyria, and tuberous sclerosis. Regarding patients with FCD, HFOs rates differed significantly across the three types of tissue (lesional, perilesional, and nonlesional; p < 0.001), being higher within the borders of the MRI‐visible dysplastic lesion, followed by the surrounding area, and rare in the remote cortex.
Significance
Our findings suggest that in patients who are all intractable, the HFO rates vary with different pathologies, and reflect different types of neuronal derangements. Our results also emphasize the potential usefulness of HFOs as an additional method to better define the extent of the epileptogenic dysplastic tissue in FCD.
Objective
We aimed to (1) assess the concordance between various polymicrogyria (PMG) types and the associated epileptogenic zone (EZ), as defined by stereoelectroencephalography (SEEG), and (2) ...determine the postsurgical seizure outcome in PMG‐related drug‐resistant epilepsy.
Methods
We retrospectively analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy.
Results
Mean age at SEEG or surgery was 28.3 years (range, 2–50). PMG was bilateral in 9 (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%) multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty‐eight (48%) patients additionally had schizencephaly, heterotopia, or focal cortical dysplasia. The SEEG‐determined EZ was fully concordant with the PMG in only 8 (16%) cases, partially concordant in 74%, and discordant in 10%. The EZ included remote cortical areas in 21 (43%) cases and was primarily localized in those in 5 (10%), all related to the mesial temporal structures. All but 1 PMG patient with corticectomy or hemispherotomy had a unilateral PMG. At last follow‐up (mean, 4.6 years; range, 1–16), 28 (72%) patients remained seizure free. Shorter epilepsy duration to surgery was an independent predictor of seizure freedom.
Interpretation
PMG‐related drug‐resistant epilepsy warrants a comprehensive presurgical evaluation, including SEEG investigations in most cases, given that the EZ may only partially overlap with the PMG or include solely remote cortical areas. Seizure freedom is feasible in a large proportion of patients. PMG extent should not deter from exploring the possibility of epilepsy surgery. Our data support the early consideration of epilepsy surgery in this patient group. Ann Neurol 2017;82:781–794
Highlights • We analyzed the interictal signature of the two most common temporal lobe seizure-onset patterns. • Despite interindividual variability, both seizure-onset patterns show distinct ...interictal epileptiform discharge morphology. • This suggests that spike morphology is a marker of the underlying mechanisms of seizure generation.
Objective
The integration of high‐frequency oscillations (HFOs; ripples 80–250 Hz, fast ripples 250–500 Hz) in epilepsy evaluation is hampered by physiological HFOs, which cannot be reliably ...differentiated from pathological HFOs. We evaluated whether defining abnormal HFO rates by statistical comparison to region‐specific physiological HFO rates observed in the healthy brain improves identification of the epileptic focus and surgical outcome prediction.
Methods
We detected HFOs in 151 consecutive patients who underwent stereo‐electroencephalography and subsequent resective epilepsy surgery at two tertiary epilepsy centers. We compared how HFOs identified the resection cavity and predicted seizure‐free outcome using two thresholds from the literature (HFO rate > 1/min; 50% of the total number of a patient's HFOs) and three thresholds based on normative rates from the Montreal Neurological Institute Open iEEG Atlas (https://mni‐open‐ieegatlas.research.mcgill.ca/): global Atlas threshold, regional Atlas threshold, and regional + 10% threshold after regional Atlas correction.
Results
Using ripples, the regional + 10% threshold performed best for focus identification (77.3% accuracy, 27% sensitivity, 97.1% specificity, 80.6% positive predictive value PPV, 78.2% negative predictive value NPV) and outcome prediction (69.5% accuracy, 58.6% sensitivity, 76.3% specificity, 60.7% PPV, 74.7% NPV). This was an improvement for focus identification (+1.1% accuracy, +17.0% PPV; p < .001) and outcome prediction (+12.0% sensitivity, +1.0% PPV; p = .05) compared to the 50% threshold. The improvement was particularly marked for foci in cortex, where physiological ripples are frequent (outcome: +35.3% sensitivity, +5.3% PPV; p = .014). In these cases, the regional + 10% threshold outperformed fast ripple rate > 1/min (+3.6% accuracy, +26.5% sensitivity, +21.6% PPV; p < .001) and seizure onset zone (+13.5% accuracy, +29.4% sensitivity, +17.0% PPV; p < .05–.01) for outcome prediction. Normalization did not improve the performance of fast ripples.
Significance
Defining abnormal HFO rates by statistical comparison to rates in healthy tissue overcomes an important weakness in the clinical use of ripples. It improves focus identification and outcome prediction compared to standard HFO measures, increasing their clinical applicability.
To assess the utility of EEG-fMRI for epilepsy surgery, we evaluated surgical outcome in relation to the resection of the most significant EEG-fMRI response.
Patients with postoperative neuroimaging ...and follow-up of at least 1 year were included. In EEG-fMRI responses, we defined as primary the cluster with the highest absolute t value located in the cortex and evaluated 3 levels of confidence for the results. The threshold for low confidence was t ≥ 3.1 (
< 0.005); the one for medium confidence corresponded to correction for multiple comparisons with a false discovery rate of 0.05; and a result reached high confidence when the primary cluster was much more significant than the next highest cluster. Concordance with the resection was determined by comparison to postoperative neuroimaging.
We evaluated 106 epilepsy surgeries in 84 patients. An increasing association between concordance and surgical outcome with higher levels of confidence was demonstrated. If the peak response was not resected, the surgical outcome was likely to be poor: for the high confidence level, no patient had a good outcome; for the medium and low levels, only 18% and 28% had a good outcome. The positive predictive value remained low for all confidence levels, indicating that removing the maximum cluster did not ensure seizure freedom.
Resection of the primary EEG-fMRI cluster, especially in high confidence cases, is necessary to obtain a good outcome but not sufficient.
This study provides Class II evidence that failure to resect the primary EEG-fMRI cluster is associated with poorer epilepsy surgery outcomes.
IMPORTANCE: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not ...offered surgery because the seizure-onset zone is less focal than expected or cannot be identified. OBJECTIVE: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. DESIGN, SETTING, AND PARTICIPANTS: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. MAIN OUTCOMES AND MEASURES: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. RESULTS: A total of 128 patients (57 women 44.5%; median range age, 31 13-58 years) were analyzed for score development and 207 patients (97 women 46.9%; median range age, 32 16-70 years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. CONCLUSIONS AND RELEVANCE: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.
•EEG-fMRI is useful to detect epileptic focus for refractory epilepsy, but is not always successful.•Number of interictal epileptic discharges is important factor to obtain significant BOLD ...cluster.•Widespread interictal discharges are more likely to localize the seizure onset zone than focal ones.
We hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI.
157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient.
The number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ.
The number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ.
Widespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.
In this paper we consider the problem of modelling the stage-discharge relationship by curve fitting using the least squares method. Our basic idea is to present new models which are more flexible ...and have the ability to model phenomena with increasing or unchanging carrying capacity. The new models present a generalization of some sigmoid smooth models commonly used in practice. They are characterized by a curvilinear asymptote and may have several inflection points. The use of these models on six real datasets collected from the US Geological Survey's website proves their performance and their ability to model hydrological phenomena.
Editor D. Koutsoyiannis; Associate editor S. Yue
Object
The authors report long-term follow-up seizure outcome in patients who underwent corpus callosotomy during the period 1981–2001 at the Montreal Neurological Institute.
Methods
The records of ...95 patients with a minimum follow-up of 5 years (mean 17.2 years) were retrospectively evaluated with respect to seizure, medication outcomes, and prognostic factors on seizure outcome.
Results
All patients had more than one type of seizure, most frequently drop attacks and generalized tonicclonic seizures. The most disabling seizure type was drop attacks, followed by generalized tonic-clonic seizures. Improvement was noted in several seizure types and was most likely for generalized tonic-clonic seizures (77.3%) and drop attacks (77.2%). Simple partial, generalized tonic, and myoclonic seizures also benefited from anterior callosotomy. The extent of the callosal section was correlated with favorable seizure outcome. The complications were mild and transient and no death was seen.
Conclusions
This study confirms that anterior callosotomy is an effective treatment in intractable generalized seizures that are not amenable to focal resection. When considering this procedure, the treating physician must thoroughly assess the expected benefits, limitations, likelihood of residual seizures, and the risks, and explain them to the patient, his or her family, and other caregivers.
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