Blinded study: prospectively defined high frequency oscillations predict seizure outcome in individual patients

AbstractBackgroundInterictal high frequency oscillations (HFO) are discussed as biomarkers for epileptogenic brain tissue that should be resected in epilepsy surgery to achieve seizure freedom. The prospective classification of tissue sampled by individual electrode contacts remains a challenge. We have developed an automated, prospective definition of clinically relevant HFO in intracranial EEG (iEEG) from MNI Montreal and tested it in iEEG from Zurich. We here validate the algorithm on iEEG recorded in an independent epilepsy center so that HFO analysis was blinded to seizure outcome.MethodsWe selected consecutive patients from Geneva University Hospitals who underwent resective epilepsy surgery with postsurgical follow-up > 12 months. We analyzed long-term iEEG recordings during non-rapid eye movement (NREM) sleep that we segmented into intervals of 5 min. HFOs were defined in the ripple (80-250 Hz) and the fast ripple (FR, 250-500 Hz) frequency band. Contacts with the highest rate of ripples co-occurring with FR (FRandR) designated the HFO area. If the HFO area was not fully resected and the patient suffered from recurrent seizures (ILAE 2-6), this was classified as a true positive (TP) prediction.ResultsWe included iEEG recordings from 16 patients (median age 32 y, range [18-53]) with stereotactic depth electrodes and/or with subdural electrode grids (median follow-up 27 mo, range [12-55]). The HFO area had high test-retest reliability across intervals (median dwell time 95%). We excluded two patients with dwell time < 50% from further analysis.The HFO area was fully included in the resected volume in 2/4 patients who achieved postoperative seizure freedom (ILAE 1, specificity 50%) and was not fully included in 9/10 patients with recurrent seizures (ILAE > 1, sensitivity 90%), leading to an accuracy of 79%.ConclusionsWe validated the automated procedure to delineate the clinical relevant HFO area in individual patients of an independently recorded dataset and achieved the same good accuracy as in our previous studies.SignificanceThe reproducibility of our results across datasets is promising for a multicienter study testing the clinical application of HFO detection to guide epilepsy surgery.

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Blinded study: prospectively defined high frequency oscillations predict seizure outcome in individual patients

Brain Communications ◽

10.1093/braincomms/fcab209 ◽

2021 ◽

Author(s):

Vasileios Dimakopoulos ◽

Pierre Mégevand ◽

Ece Boran ◽

Shahan Momjian ◽

Margitta Seeck ◽

...

Keyword(s):

Epilepsy Surgery ◽

High Frequency ◽

Dwell Time ◽

Seizure Outcome ◽

Seizure Freedom ◽

Intracranial Eeg ◽

Retest Reliability ◽

High Frequency Oscillations ◽

Test Retest Reliability

Abstract Interictal high frequency oscillations are discussed as biomarkers for epileptogenic brain tissue that should be resected in epilepsy surgery to achieve seizure freedom. The prospective classification of tissue sampled by individual electrode contacts remains a challenge. We have developed an automated, prospective definition of clinically relevant high frequency oscillations in intracranial EEG from Montreal and tested it in recordings from Zurich. We here validated the algorithm on intracranial EEG that was recorded in an independent epilepsy centre so that the analysis was blinded to seizure outcome. We selected consecutive patients who underwent resective epilepsy surgery in Geneva with postsurgical follow-up > 12 months. We analysed long-term recordings during sleep that we segmented into intervals of 5 minutes. High frequency oscillations were defined in the ripple (80-250 Hz) and the fast ripple (250-500 Hz) frequency bands. Contacts with the highest rate of ripples co-occurring with fast ripples designated the relevant area. As a validity criterion, we calculated the test-retest reliability of the high frequency oscillations area between the 5 min intervals (dwell time ≥50%). If the area was not fully resected and the patient suffered from recurrent seizures, this was classified as a true positive prediction. We included recordings from 16 patients (median age 32 years, range 18-53 years) with stereotactic depth electrodes and/or with subdural electrode grids (median follow-up 27 months, range 12-55 months). For each patient, we included several 5 min intervals (median 17 intervals). The relevant area had high test-retest reliability across intervals (median dwell time 95%). In two patients, the test-retest reliability was too low (dwell time < 50%) so that outcome prediction was not possible. The area was fully included in the resected volume in 2/4 patients who achieved postoperative seizure freedom (specificity 50%) and was not fully included in 9/10 patients with recurrent seizures (sensitivity 90%), leading to an accuracy of 79%. An additional exploratory analysis suggested that high frequency oscillations were associated with interictal epileptic discharges only in channels within the relevant area and not associated in channels outside the area. We thereby validated the automated procedure to delineate the clinically relevant area in each individual patient of an independently recorded dataset and achieved the same good accuracy as in our previous studies. The reproducibility of our results across datasets is promising for a multicentre study to test the clinical application of high frequency oscillations to guide epilepsy surgery.

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A spiking neural network (SNN) for detecting high frequency oscillations (HFOs) in the intraoperative ECoG

Scientific Reports ◽

10.1038/s41598-021-85827-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Karla Burelo ◽

Mohammadali Sharifshazileh ◽

Niklaus Krayenbühl ◽

Georgia Ramantani ◽

Giacomo Indiveri ◽

...

Keyword(s):

Neural Network ◽

Real Time ◽

Epilepsy Surgery ◽

High Frequency ◽

Seizure Outcome ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Spiking Neural Network ◽

High Frequency Oscillations ◽

Neuromorphic Hardware

AbstractTo achieve seizure freedom, epilepsy surgery requires the complete resection of the epileptogenic brain tissue. In intraoperative electrocorticography (ECoG) recordings, high frequency oscillations (HFOs) generated by epileptogenic tissue can be used to tailor the resection margin. However, automatic detection of HFOs in real-time remains an open challenge. Here we present a spiking neural network (SNN) for automatic HFO detection that is optimally suited for neuromorphic hardware implementation. We trained the SNN to detect HFO signals measured from intraoperative ECoG on-line, using an independently labeled dataset (58 min, 16 recordings). We targeted the detection of HFOs in the fast ripple frequency range (250-500 Hz) and compared the network results with the labeled HFO data. We endowed the SNN with a novel artifact rejection mechanism to suppress sharp transients and demonstrate its effectiveness on the ECoG dataset. The HFO rates (median 6.6 HFO/min in pre-resection recordings) detected by this SNN are comparable to those published in the dataset (Spearman’s $$\rho$$ ρ = 0.81). The postsurgical seizure outcome was “predicted” with 100% (CI [63 100%]) accuracy for all 8 patients. These results provide a further step towards the construction of a real-time portable battery-operated HFO detection system that can be used during epilepsy surgery to guide the resection of the epileptogenic zone.

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Is Seizure Surgery an Option for Patients with Very Low IQ?

Epilepsy Currents ◽

10.1111/j.1535-7511.2008.00275.x ◽

2008 ◽

Vol 8 (6) ◽

pp. 150-151 ◽

Cited By ~ 1

Author(s):

Paul Garcia

Keyword(s):

Epilepsy Surgery ◽

Neurological Impairment ◽

Population Based ◽

Seizure Outcome ◽

Seizure Freedom ◽

Histopathological Diagnosis ◽

Counselling Process ◽

Low Iq ◽

Seizure Surgery

Seizure Outcome after Resective Epilepsy Surgery in Patients with Low IQ. Malmgren K, Olsson I, Engman E, Flink R, Rydenhag B. Brain 2008;131(Pt 2):535–542. Epilepsy surgery has been questioned for patients with low IQ, since a low cognitive level is taken to indicate a widespread disturbance of cerebral function with unsatisfactory prognosis following resective surgery. The prevalence of epilepsy in patients with cognitive dysfunction is, however, higher than in the general population and the epilepsy is often more severe and difficult to treat. It is therefore important to try to clarify whether IQ predicts seizure outcome after resective epilepsy surgery. The Swedish National Epilepsy Surgery Register, which includes data on all epilepsy surgery procedures in Sweden since 1990, was analysed for all resective procedures performed 1990–99. Sustained seizure freedom with or without aura at the 2-year follow-up was analysed as a function of pre-operative IQ level categorized as IQ <50, IQ 50–69 and IQ ≥70 and was also adjusted for the following variables: age at epilepsy onset, age at surgery, pre-operative seizure frequency, pre-operative neurological impairment, resection type and histopathological diagnosis. Four hundred and forty-eight patients underwent resective epilepsy surgery in Sweden from 1990 to 1999 and completed the 2-year follow-up: 72 (16%) had IQ <70, (18 with IQ <50 and 54 with IQ 50–69) and 376 IQ ≥70. There were 313 adults and 135 children ≤18 years. Three hundred and twenty-five patients underwent temporal lobe resections (TLR) and 123 underwent various extratemporal resections (XTLR). At the 2-year follow-up, 56% (252/448) of the patients were seizure free: 22% (4/18) in the IQ <50 group, 37% (20/54) in the IQ 50–69 group and 61% (228β76) in the IQ ≥70 group. There was a significant relation between IQ category and seizure freedom [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.27–0.62] and this held also when adjusting for clinical variables [OR 0.58 (95% CI 0.35–0.95)]. In this population-based epilepsy surgery series, IQ level was shown to be an independent predictor of seizure freedom at the 2-year follow-up. However, many of the low-IQ patients benefit from surgery, especially patients with lesions. Low IQ should not exclude patients from resective epilepsy surgery, but is an important prognostic factor to consider in the counselling process.

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Automatic detection of high frequency oscillations during epilepsy surgery predicts seizure outcome

Clinical Neurophysiology ◽

10.1016/j.clinph.2016.06.009 ◽

2016 ◽

Vol 127 (9) ◽

pp. 3066-3074 ◽

Cited By ~ 41

Author(s):

Tommaso Fedele ◽

Maryse van ’t Klooster ◽

Sergey Burnos ◽

Willemiek Zweiphenning ◽

Nicole van Klink ◽

...

Keyword(s):

Epilepsy Surgery ◽

High Frequency ◽

Automatic Detection ◽

Seizure Outcome ◽

High Frequency Oscillations

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Factors predicting 10-year seizure freedom after temporal lobe resection

Zeitschrift für Epileptologie ◽

10.1007/s10309-019-00302-x ◽

2020 ◽

Vol 33 (1) ◽

pp. 50-61 ◽

Cited By ~ 2

Author(s):

Friedhelm C. Schmitt ◽

H.‑Joachim Meencke

Keyword(s):

Temporal Lobe ◽

Epilepsy Surgery ◽

Univariate Analysis ◽

Class I ◽

Seizure Outcome ◽

Seizure Freedom ◽

Patient Counseling ◽

Long Term Follow Up

Abstract Background Resective surgery is an established and evidence-based treatment approach in pharmacoresistant temporal lobe epilepsy (TLE). Extra-long-term follow-up data are important to allow for good patient counseling. So far, only few trials provide prospective or retrospective data exceeding 5 years. Objective This study aimed to present data of continuous seizure outcome over an extended time period, with a particular focus on patients who remained seizure free for 10 years. Methods We analyzed seizure outcome after epilepsy surgery for TLE in 46 consecutive patients, who were seen on an annual basis for 10 years in a single center (Epilepsy Center Berlin Brandenburg). Factors for remaining seizure free for 10 years were determined by univariate analysis. Results The class I outcome changed each year by 74–78%. Of the patients, 63% remained continuously in Engel class I (48% Engel Class IA for 10 years) for 10 years. Six patients were never seizure free (12.5%). After 10 years, 35% of the patients were cured (i.e., seizure-free without medication). A higher number of antiepileptic drugs and seizures before surgery as well as the indication for invasive presurgical monitoring were associated with “unsuccessful surgery.” Conclusion With almost half of the patients completely seizure free and more than a third “cured,” epilepsy surgery remains the mainstay of therapy for TLE patients. Analysis in larger cohorts with extra-long-term follow-up is needed to assess good prognostic factors and other postsurgical outcome issues such as neuropsychological, psychiatric, and psychosocial outcomes.

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An electronic neuromorphic system for real-time detection of High Frequency Oscillations (HFOs) in intracranial EEG

10.21203/rs.3.rs-83699/v1 ◽

2020 ◽

Author(s):

Mohammadali Sharifhazileh ◽

Karla Burelo ◽

Johannes Sarnthein ◽

Giacomo Indiveri

Keyword(s):

Neural Network ◽

Real Time ◽

Epilepsy Surgery ◽

High Frequency ◽

Neural Recording ◽

Clinical Applications ◽

Seizure Outcome ◽

Intracranial Eeg ◽

High Frequency Oscillations ◽

Neuromorphic System

Abstract The analysis of biomedical signals for clinical studies and therapeutic applications can benefit from compact and portable devices that can process these signals locally, in real-time, without the need for off-line processing. An example is the recording of intracranial EEG(iEEG) during epilepsy surgery with the detection of High Frequency Oscillations (HFOs, 80-500 Hz), which are a biomarker for the epileptogenic zone. Conventional approaches of HFO detection involve the offline analysis of prerecorded data, often on bulky computers. However, clinical applications during surgery or in long-term intracranial recordings demand a self-sufficient embedded device that is battery-powered to avoid interfering with other electronic equipment in the operation room. Mixed-signal and analog-digital neuromorphic circuits offer the possibility of building compact, embedded, and low-power neural network processing systems that can analyze data on-line and produce results with short latency in real-time. These characteristics are well suited for clinical applications that involve the processing of biomedical signals at (or very close to) the sensor level. In this work, we present a neuromorphic system that combines for the first time a neural recording headstage with a signal-to-spike conversion circuit and a multi-core spiking neural network (SNN) architecture on the same die for recording, processing, and detecting clinically relevant HFOs in iEEG from epilepsy patients. The device was fabricated using a standard 0.18μm CMOS technology node and has a total area of 99 mm2. We demonstrate its application to HFO detection in the iEEG recorded from 9 patients with temporal lobe epilepsy who subsequently underwent epilepsy surgery. The total average power consumption of the chip during the detection task was 614.3 μW. We show how the neuromorphic system can reliably detect HFOs: the system predicts postsurgical seizure outcome with state-of-the-art accuracy, specificity, and sensitivity (78%, 100%, and 33% respectively). This is the first feasibility study towards identifying relevant features in intracranial human data in real-time, on-chip, using event-based processors and spiking neural networks. By providing “neuromorphic intelligence” to neural recording circuits the approach proposed will pave the way for the development of systems that can detect HFO areas directly in the operation room and improve the seizure outcome of epilepsy surgery.

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TP3-2 Epilepsy surgery outcomes in a paediatric population – a single centre 10 year experience

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-abn.57 ◽

2019 ◽

Vol 90 (3) ◽

pp. e18.2-e18

Author(s):

O Pope ◽

A Chadwick ◽

C Pringle ◽

V Josan

Keyword(s):

Epilepsy Surgery ◽

Paediatric Population ◽

Seizure Outcome ◽

Seizure Freedom ◽

Single Centre ◽

Surgical Interventions ◽

Post Surgery ◽

Intractable Seizures ◽

Anti Epileptic Drug

ObjectivesTo analyse the efficacy of epilepsy surgery in reducing the burden of seizures in a paediatric population – a single centre 10 year experience.DesignSingle centre retrospective review of medical records.Subjects74 consecutive paediatric patients who underwent epilepsy surgery between 2008–2017 by one neurosurgeon at a single centre.MethodsSeizure history, pre-operative investigations, surgical interventions, seizure outcomes, complications and long term anti-epileptic drug (AED) use were evaluated. Seizure outcomes at 1 year post surgery to the last available follow up (up to 5 years) were documented and classified using the Engel System. Engel I and II were classified as a good seizure outcome and Engel III and IV were classified as a poor seizure outcome.ResultsThe mean duration of follow up was 41 months. 62.2% of patients achieved seizure freedom (Engel I) at their latest follow up, with 82.4% of patients achieving a good seizure outcome (Engel I/II). 13.5% of patients achieved worthwhile improvement (Engel III) and only 4.1% of patients had no worthwhile improvement in seizure burden (Engel IV). More favourable outcomes were observed in children with temporal lobe epilepsy. Post-surgery AED use was reduced or discontinued in 41.4% of all patients; 41.4% of the 29 patients with AED data at their 5 year follow up were completely free of AEDs.ConclusionsEpilepsy surgery is an efficacious treatment with low morbidity and no mortality that is underutilised in children with medically intractable seizures.

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Can we use intraoperative high‐frequency oscillations to guide tumor‐related epilepsy surgery?

Epilepsia ◽

10.1111/epi.16845 ◽

2021 ◽

Author(s):

Nicole E. C. Klink ◽

Willemiek J. E. M. Zweiphenning ◽

Cyrille H. Ferrier ◽

Peter H. Gosselaar ◽

Kai J. Miller ◽

...

Keyword(s):

Epilepsy Surgery ◽

High Frequency ◽

High Frequency Oscillations

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The influence of lesion volume, perilesion resection volume, and completeness of resection on seizure outcome after resective epilepsy surgery for cortical dysplasia in children

Journal of Neurosurgery Pediatrics ◽

10.3171/2014.10.peds14282 ◽

2015 ◽

Vol 15 (6) ◽

pp. 644-650 ◽

Cited By ~ 30

Author(s):

Chima O. Oluigbo ◽

Jichuan Wang ◽

Matthew T. Whitehead ◽

Suresh Magge ◽

John S. Myseros ◽

...

Keyword(s):

Epilepsy Surgery ◽

Seizure Control ◽

Brain Mri ◽

Age At Onset ◽

Cortical Dysplasia ◽

Complete Resection ◽

Seizure Outcome ◽

Seizure Freedom ◽

Lesion Volume ◽

Resection Volume

OBJECT Focal cortical dysplasia (FCD) is one of the most common causes of intractable epilepsy leading to surgery in children. The predictors of seizure freedom after surgical management for FCD are still unclear. The objective of this study was to perform a volumetric analysis of factors shown on the preresection and postresection brain MRI scans of patients who had undergone resective epilepsy surgery for cortical dysplasia and to determine the influence of these factors on seizure outcome. METHODS The authors reviewed the medical records and brain images of 43 consecutive patients with focal MRI-documented abnormalities and a pathological diagnosis of FCD who had undergone surgical treatment for refractory epilepsy. Preoperative lesion volume and postoperative resection volume were calculated by manual segmentation using OsiriX PRO software. RESULTS Forty-three patients underwent first-time surgery for resection of an FCD. The age range of these patients at the time of surgery ranged from 2 months to 21.8 years (mean age 7.3 years). The median duration of follow-up was 20 months. The mean age at onset was 31.6 months (range 1 day to 168 months). Complete resection of the area of an FCD, as adjudged from the postoperative brain MR images, was significantly associated with seizure control (p = 0.0005). The odds of having good seizure control among those who underwent complete resection were about 6 times higher than those among the patients who did not undergo complete resection. Seizure control was not significantly associated with lesion volume (p = 0.46) or perilesion resection volume (p = 0.86). CONCLUSIONS The completeness of FCD resection in children is a significant predictor of seizure freedom. Neither lesion volume nor the further resection of perilesional tissue is predictive of seizure freedom.

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The proportion of seizure onset zone contacts resected is not associated with outcome following SEEG-guided resective epilepsy surgery in children

10.1101/2021.09.18.21263722 ◽

2021 ◽

Author(s):

Mehdi Khan ◽

Aswin Chari ◽

Kiran Seunarine ◽

Christin Eltze ◽

Friederike Moeller ◽

...

Keyword(s):

Epilepsy Surgery ◽

Univariate Analysis ◽

Seizure Outcome ◽

Epileptogenic Zone ◽

Imaging Data ◽

Seizure Onset ◽

Binary Logistic Regression Model ◽

Primary Analysis ◽

Seizure Onset Zone

AbstractPurposeChildren undergoing stereoelectroencephalography (SEEG)-guided epilepsy surgery represent a complex cohort. We aimed to determine whether the proportion of putative seizure onset zone (SOZ) contacts resected associates with seizure outcome in a cohort of children undergoing SEEG-guided resective epilepsy surgery.MethodsPatients who underwent SEEG-guided resective surgery over a six-year period were included. The proportion of SOZ contacts resected was determined by co-registration of pre- and post-operative imaging. Seizure outcomes were classified as seizure free (SF, Engel class I) or not seizure-free (NSF, Engel class II-IV) at last clinical follow-up.ResultsOf 94 patients undergoing SEEG, 29 underwent subsequent focal resection of whom 22 had sufficient imaging data to be included in the primary analysis (median age at surgery of 10 years, range 5-18). Fifteen (68.2%) were SF and 7 (31.8%) NSF at median follow-up of 19.5 months (range 12-46). On univariate analysis, histopathology, was the only significant factor associated with SF (p<0.05). The percentage of defined SOZ contacts resected ranged from 25-100% and was not associated with SF (p=0.89). In a binary logistic regression model, it was highly likely that histology was the only independent predictor of outcome, although the interpretation was limited by pseudo-complete separation of the data.ConclusionHistopathology is a significant predictor of surgical outcomes in children undergoing SEEG-guided resective epilepsy surgery. The percentage of SOZ contacts resected was not associated with SF. Factors such as spatial organisation of the epileptogenic zone, neurophysiological biomarkers and the prospective identification of pathological tissue may therefore play an important role.

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