EpilepsyCIEDNCT03533374
Validation of Criteria for Identification of Epileptiform Discharges in EEG Recordings of Patients With Epilepsy
An observational study of Epilepsy and Non-Epileptic Seizure, run by Sándor Beniczky.
Trial summary
Electroencephalography (EEG) records electric activity of the brain using electrodes placed on the scalp. EEG is an important tool in the diagnostic work-up of patients with epilepsy. Specific types of sharp EEG discharges (epileptiform discharges) are associated with patients with epilepsy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Epilepsy, Non-Epileptic Seizure
- What is being tested?
- Electroencephalogram (EEG) and visual evaluation
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2012to 1 Jan 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patient with epilepsy and patient with non-epileptic seizures (paroxysmal episodes)
Who may be able to join
- Patients who underwent long-term video-EEG monitoring
- Patients who had at least one habitual episode (seizure) recorded on video and EEG.
- Patients with sharp transients.
- For patients with epilepsy: the interictal (epileptiform) sharp transients are concordant with the ictal recording
Who cannot join
- Patients with both epileptic seizures and non-epileptic seizures (paroxysmal episodes).
About this study
Official title: Clinical Validation of Criteria for Identification of Epileptiform Electroencephalography Discharges in Sensor Space and Source Space
Electroencephalography (EEG) records electric activity of the brain using electrodes placed on the scalp. EEG is an important tool in the diagnostic work-up of patients with epilepsy. Specific types of sharp EEG discharges (epileptiform discharges) are associated with patients with epilepsy.
The International Federation of Clinical Neurophysiology (IFCN) has recently published a set of six operational criteria for identifying epileptiform discharges. At least four criteria need to be present in order to classify a discharge as epileptiform. These criteria are largely based on expert opinion and have not been validated yet. It is not clear what the sensitivity and specificity of these criteria are, and which combination of these criteria are optimal. Each criterion is based on visual assessment. However, it is not known what the inter-rater agreement of these criteria are.
Read more
EEG is traditionally inspected in sensor space, i.e. in the recording channels. Advances in signal analysis made possible reconstructing the electric currents in the regions of the brain generating them, and displaying the signals in the source space, instead of the sensor space.
The objectives of this study are: to determine the inter-rater agreement of the IFCN criteria by visual analysis in sensor space, to determine the combination of criteria with the best accuracy (sensitivity and specificity) and assess the accuracy of evaluating the discharges in source space.
The raters will analyze EEG recordings from 100 patients, from two groups: consecutive patients with epilepsy and consecutive patients with non-epileptic paroxysmal episodes. EEG was recorded during long-term video-EEG monitoring. As reference standard, the investigators used the evaluation of the patients´ habitual clinical episode. The performance of the criteria in sensor-space and the analysis in source space will be compared with the unrestricted expert scorings.
Read the detailed description
Epilepsy affects 50 million people of all ages. It is the most common neurologic disorder across the lifespan, and has been found to be associated with an increased risk of mortality compared to the general population.
EEG is an important tool in the diagnostic work-up of patients with suspected epilepsy. The presence of epileptiform EEG discharges (EDs) confirm the diagnosis and provides important information that helps in classifying epilepsy.
EDs are visually identified by experts with training in reading EEG. Although EDs were defined in the previous edition of the IFCN glossary of terms, that definition was conceptual, and the inter-rater agreement for identifying EDs was only moderate. Recently, the IFCN suggested the following operational definition for EDs: Transients distinguishable from background activity with a characteristic morphology; EDs have to fulfill at least 4 of the following 6 criteria:
- Di- or tri-phasic waves with sharp or spiky morphology (i.e. pointed peak).
- Different wave-duration than the ongoing background activity: either shorter or longer.
- Asymmetry of the waveform: a sharply rising ascending phase and a more slowly decaying descending phase, or vice versa.
- The transient is followed by an associated slow after-wave.
- The background activity surrounding epileptiform discharges is disrupted by the presence of the epileptiform discharges.
- Distribution of the negative and positive potentials on the scalp suggests a source of the signal in the brain, corresponding to a radial, oblique or tangential orientation of the source. This is best assessed by inspecting voltage maps constructed using common-average reference.
However, these criteria are largely based on expert opinion. Data from clinical validation studies are lacking, thus it is not known what the sensitivity and specificity of these methods are. The threshold of four fulfilled criteria was arbitrary, and it is not sure whether it yields the optimal accuracy (sensitivity and specificity). Furthermore, since each criterion is based on visual evaluation, it is not known whether all experts would reach the same conclusion.
The IFCN criteria were developed for identifying EDs using the traditional way of inspecting EEG, in the channels of the recording electrodes (sensor space). However, advances in signal analysis made possible to reproduce the electric currents in the brain regions, using a spatial filtering method (source space).
The objective of this study are:
- To determine the inter-rater agreement for the IFCN criteria
- To determine the number of criteria and their combination that yields the highest diagnostic accuracy
- To determine the accuracy of identifying EDs in source space. Raters with experience in clinical EEG will inspect 100 anonymized EEG samples, from consecutive patients with epilepsy and consecutive patients with non-epileptic paroxysmal episodes. All 100 patients have a reference standard for their condition, derived from analysis of their video-EEG recordings of their habitual clinical episode. Patients with both focal and generalized epilepsy, as well as non-epileptic paroxysmal episodes (psychogenic non-epileptic seizures, sleep-disorders, movement disorders, convulsive syncope) are included.
Each EEG sample contains a sharp transient that is either epileptiform or not. EEGs were recoded using the IFCN electrode array of 25 electrodes (including the ones in the inferior temporal chain).
The samples were randomized twice, resulting in two series containing the same set of 100 samples, though with different codes and in different order of presentation. The raters will inspect the two series separately. In the first session the raters will inspect samples in sensor space, using traditional EEG montages (longitudinal and transversal bipolar; common average) and voltage maps. For each sample, they will score the presence or absence of each IFCN criterion. In the second session, the raters will inspect the EEG samples in source space and voltage maps, and will conclude on the presence / absence of EDs.
The performance of these methods will be compared with unrestricted scorings based on the experts´ evaluation.
- Conditions
- Epilepsy, Non-Epileptic Seizure
- Being tested
- Electroencephalogram (EEG) and visual evaluation
- Keywords
- Accuracy, Inter-ictal EEG Discharges, Inter-rater agreement, Long Term Monitoring, Sensitivity, Sharp transients, Specificity, Source Space, Voltage maps
- Medical subject headings
- Epilepsy, Seizures, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electroencephalogram (EEG) and visual evaluationDiagnostic test
Electroencephalogram (EEG) was recorded using Nicolet-One system, and the standard 25-electrode array. Recordings with sharp transients are inspected by experts (physicians).
| Study group | Role | What they receive |
|---|---|---|
| Patients with epileptic seizures | Electroencephalogram (EEG) and visual evaluation
- Electroencephalogram (EEG) was recorded using Nicolet-One system, and the standard 25-electrode array. Recordings with sharp transients are inspected by experts (physicians). Receives: Diagnostic Test: Electroencephalogram (EEG) and visual evaluation | |
| Patients with non-epileptic seizures | Electroencephalogram (EEG) and visual evaluation
- Electroencephalogram (EEG) was recorded using Nicolet-One system, and the standard 25-electrode array. Recordings with sharp transients are inspected by experts (physicians). Receives: Diagnostic Test: Electroencephalogram (EEG) and visual evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inter-rater Agreement of the International Federation of Clinical Neurophysiology (IFCN) Criteria (Cut-off=4) in Sensor Space and of Detection of Epileptiform Discharges (EDs) in Source Space
Inter-rater agreement of IFCN criteria (cut-off=4) in sensor space and of detection of EDs in source space was calculated using Gwet´s Agreemen Coefficient (AC1).
We calculated Gwet's coefficients of agreement AC1 for beyond chance agreement, because, compared with Cohen's Kappa, the Gwet's agreement coefficient is less affected by prevalence and marginal probability and thereby avoids the problem known as the "paradoxes of kappa". Strength of agreement beyond chance was interpreted according to Landis and Koch criteria: poor (<0), slight (0·01-0·20), fair (0·21-0·40), moderate (0·41-0·60), substantial (0·61-0·80), and almost perfect (0·81-1·00).
Measured: 1 year
Sensitivity and Specificity IFCN Criteria (Cut-off=4)
This is a diagnostic study, hence sensitivity and specificity must be calculated from different groups: sensitivity form the group of patients with epilepsy and specificity from the gruoup of patients who do not have epilepsy.
Sensitivity: the percentage of patients with abnormal index test (true positives) among patients with epilepsy.
Specificity: the percentage of patients with normal index test (true negatives) among patients who do not have epilepsy.
Measured: 1 year
The Sensitivity and Specificity of Detecting EDs in Source-space
This is a diagnostic study, hence sensitivity and specificity must be calculated from different groups: sensitivity form the group of patients with epilepsy and specificity from the group of patients who do not have epilepsy.
Sensitivity: the percentage of patients with abnormal index test (true positives) among patients with epilepsy.
Specificity: the percentage of patients with normal index test (true negatives) among patients who do not have epilepsy.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start1 Jan 2012
- Primary completion1 Jan 2018
- Study completion1 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sándor Beniczky
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Central Denmark Region, Filadelfia Epilepsy Hospital, University Health Network, Toronto, University Hospital Erlangen, Oslo University Hospital
- Responsible party
- Sponsor-investigator, Sándor Beniczky, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03533374
- Sponsor's protocol ID
- CIED
- Acronym
- CIED
- Status last verified
- Jul 2019
- First submitted
- 11 May 2018
- Last updated
- 22 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Validation of Criteria for Identification of Epileptiform Electroencephalography Discharges in Sensor Space and Source Space
- ClinicalTrials.gov ID
- NCT03533374
- Acronym / sponsor ID
- CIED / CIED
- Conditions
- Epilepsy, Non-Epileptic Seizure
- Keywords
- Accuracy, Inter-ictal EEG Discharges, Inter-rater agreement, Long Term Monitoring, Sensitivity, Sharp transients, Specificity, Source Space
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Sándor BeniczkyUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Central Denmark Region, Filadelfia Epilepsy Hospital, University Health Network, Toronto, University Hospital Erlangen, Oslo University Hospital
- Study start
- 1 Jan 2012 (actual)
- Primary completion
- 1 Jan 2018 (actual)
- Study completion
- 1 Jan 2018 (actual)
- First posted
- 23 May 2018 (actual)
- Results
- Posted 22 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Electroencephalography (EEG) records electric activity of the brain using electrodes placed on the scalp. EEG is an important tool in the diagnostic work-up of patients with epilepsy. Specific types of sharp EEG discharges (epileptiform discharges) are associated with patients with epilepsy.
The International Federation of Clinical Neurophysiology (IFCN) has recently published a set of six operational criteria for identifying epileptiform discharges. At least four criteria need to be present in order to classify a discharge as epileptiform. These criteria are largely based on expert opinion and have not been validated yet. It is not clear what the sensitivity and specificity of these criteria are, and which combination of these criteria are optimal. Each criterion is based on visual assessment. However, it is not known what the inter-rater agreement of these criteria are.
EEG is traditionally inspected in sensor space, i.e. in the recording channels. Advances in signal analysis made possible reconstructing the electric currents in the regions of the brain generating them, and displaying the signals in the source space, instead of the sensor space.
The objectives of this study are: to determine the inter-rater agreement of the IFCN criteria by visual analysis in sensor space, to determine the combination of criteria with the best accuracy (sensitivity and specificity) and assess the accuracy of evaluating the discharges in source space.
The raters will analyze EEG recordings from 100 patients, from two groups: consecutive patients with epilepsy and consecutive patients with non-epileptic paroxysmal episodes. EEG was recorded during long-term video-EEG monitoring. As reference standard, the investigators used the evaluation of the patients´ habitual clinical episode. The performance of the criteria in sensor-space and the analysis in source space will be compared with the unrestricted expert scorings.
Detailed description
Epilepsy affects 50 million people of all ages. It is the most common neurologic disorder across the lifespan, and has been found to be associated with an increased risk of mortality compared to the general population.
EEG is an important tool in the diagnostic work-up of patients with suspected epilepsy. The presence of epileptiform EEG discharges (EDs) confirm the diagnosis and provides important information that helps in classifying epilepsy.
EDs are visually identified by experts with training in reading EEG. Although EDs were defined in the previous edition of the IFCN glossary of terms, that definition was conceptual, and the inter-rater agreement for identifying EDs was only moderate. Recently, the IFCN suggested the following operational definition for EDs: Transients distinguishable from background activity with a characteristic morphology; EDs have to fulfill at least 4 of the following 6 criteria:
- Di- or tri-phasic waves with sharp or spiky morphology (i.e. pointed peak).
- Different wave-duration than the ongoing background activity: either shorter or longer.
- Asymmetry of the waveform: a sharply rising ascending phase and a more slowly decaying descending phase, or vice versa.
- The transient is followed by an associated slow after-wave.
- The background activity surrounding epileptiform discharges is disrupted by the presence of the epileptiform discharges.
- Distribution of the negative and positive potentials on the scalp suggests a source of the signal in the brain, corresponding to a radial, oblique or tangential orientation of the source. This is best assessed by inspecting voltage maps constructed using common-average reference.
However, these criteria are largely based on expert opinion. Data from clinical validation studies are lacking, thus it is not known what the sensitivity and specificity of these methods are. The threshold of four fulfilled criteria was arbitrary, and it is not sure whether it yields the optimal accuracy (sensitivity and specificity). Furthermore, since each criterion is based on visual evaluation, it is not known whether all experts would reach the same conclusion.
The IFCN criteria were developed for identifying EDs using the traditional way of inspecting EEG, in the channels of the recording electrodes (sensor space). However, advances in signal analysis made possible to reproduce the electric currents in the brain regions, using a spatial filtering method (source space).
The objective of this study are:
- To determine the inter-rater agreement for the IFCN criteria
- To determine the number of criteria and their combination that yields the highest diagnostic accuracy
- To determine the accuracy of identifying EDs in source space. Raters with experience in clinical EEG will inspect 100 anonymized EEG samples, from consecutive patients with epilepsy and consecutive patients with non-epileptic paroxysmal episodes. All 100 patients have a reference standard for their condition, derived from analysis of their video-EEG recordings of their habitual clinical episode. Patients with both focal and generalized epilepsy, as well as non-epileptic paroxysmal episodes (psychogenic non-epileptic seizures, sleep-disorders, movement disorders, convulsive syncope) are included.
Each EEG sample contains a sharp transient that is either epileptiform or not. EEGs were recoded using the IFCN electrode array of 25 electrodes (including the ones in the inferior temporal chain).
The samples were randomized twice, resulting in two series containing the same set of 100 samples, though with different codes and in different order of presentation. The raters will inspect the two series separately. In the first session the raters will inspect samples in sensor space, using traditional EEG montages (longitudinal and transversal bipolar; common average) and voltage maps. For each sample, they will score the presence or absence of each IFCN criterion. In the second session, the raters will inspect the EEG samples in source space and voltage maps, and will conclude on the presence / absence of EDs.
The performance of these methods will be compared with unrestricted scorings based on the experts´ evaluation.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with epileptic seizures | – | Diagnostic Test: Electroencephalogram (EEG) and visual evaluationElectroencephalogram (EEG) and visual evaluation - Electroencephalogram (EEG) was recorded using Nicolet-One system, and the standard 25-electrode array. Recordings with sharp transients are inspected by experts (physicians). |
| Patients with non-epileptic seizures | – | Diagnostic Test: Electroencephalogram (EEG) and visual evaluationElectroencephalogram (EEG) and visual evaluation - Electroencephalogram (EEG) was recorded using Nicolet-One system, and the standard 25-electrode array. Recordings with sharp transients are inspected by experts (physicians). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patient with epilepsy and patient with non-epileptic seizures (paroxysmal episodes)
Key inclusion criteria (4 listed)
- Patients who underwent long-term video-EEG monitoring
- Patients who had at least one habitual episode (seizure) recorded on video and EEG.
- Patients with sharp transients.
- For patients with epilepsy: the interictal (epileptiform) sharp transients are concordant with the ictal recording
Key exclusion criteria (1 listed)
- Patients with both epileptic seizures and non-epileptic seizures (paroxysmal episodes).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Electroencephalogram (EEG) and visual evaluationElectroencephalogram (EEG) was recorded using Nicolet-One system, and the standard 25-electrode array. Recordings with sharp transients are inspected by experts (physicians). | Diagnostic test | Patients with epileptic seizures, Patients with non-epileptic seizures |
Primary outcome
Inter-rater Agreement of the International Federation of Clinical Neurophysiology (IFCN) Criteria (Cut-off=4) in Sensor Space and of Detection of Epileptiform Discharges (EDs) in Source Space
Time frame: 1 year
Inter-rater agreement of IFCN criteria (cut-off=4) in sensor space and of detection of EDs in source space was calculated using Gwet´s Agreemen Coefficient (AC1). We calculated Gwet's coefficients of agreement AC1 for beyond chance agreement, because, compared with Cohen's Kappa, the Gwet's agreement coefficient is less affected by prevalence and marginal probability and thereby avoids the problem known as the "paradoxes of kappa". Strength of agreement beyond chance was interpreted according to Landis and Koch criteria: poor (<0), slight (0·01-0·20), fair (0·21-0·40), moderate (0·41-0·60), substantial (0·61-0·80), and almost perfect (0·81-1·00).
Sensitivity and Specificity IFCN Criteria (Cut-off=4)
Time frame: 1 year
This is a diagnostic study, hence sensitivity and specificity must be calculated from different groups: sensitivity form the group of patients with epilepsy and specificity from the gruoup of patients who do not have epilepsy. Sensitivity: the percentage of patients with abnormal index test (true positives) among patients with epilepsy. Specificity: the percentage of patients with normal index test (true negatives) among patients who do not have epilepsy.
The Sensitivity and Specificity of Detecting EDs in Source-space
Time frame: 1 year
This is a diagnostic study, hence sensitivity and specificity must be calculated from different groups: sensitivity form the group of patients with epilepsy and specificity from the group of patients who do not have epilepsy. Sensitivity: the percentage of patients with abnormal index test (true positives) among patients with epilepsy. Specificity: the percentage of patients with normal index test (true negatives) among patients who do not have epilepsy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Epilepsy
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy and Non-Epileptic Seizure, run by Sándor Beniczky.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inter-rater Agreement of the International Federation of Clinical Neurophysiology (IFCN) Criteria (Cut-off=4) in Sensor Space and of Detection of Epileptiform Discharges (EDs) in Source Space (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2020.