Epilepsy Watch After Vascular Events: Frequency, Outcomes, and Risk Markers

NCT ID: NCT06922734

Last Updated: 2026-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

602 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-11-01

Study Completion Date

2026-12-31

Brief Summary

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This research aims to determine the frequency of seizures in patients following a stroke, identify risk factors associated with post-stroke seizures, and characterize EEG changes linked to these seizures. Unexplored alterations in the aperiodic component of the EEG in post-stroke patients could potentially serve as novel biological markers for epilepsy after stroke.

Detailed Description

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This study included patients with stroke or post-stroke seizures who were admitted to the Neurology Division at the University Medical Centre Maribor, Slovenia, over a 12-month period. The anticipated number of patients was approximately 600-650. Inclusion criteria encompassed acute stroke or seizure occurring at any point after the stroke. Stroke classification was based on the World Health Organization (WHO) criteria, while post-stroke seizures and epilepsy were defined according to the International League Against Epilepsy (ILAE) definitions and classifications.

All participants provided written informed consent after being thoroughly informed about the study. The study was pre-approved by the Medical Ethics Committee of the Republic of Slovenia (Approval No. 48/08/14 and Approval No. 0120-302/2024-2711-3). Patients who did not meet the inclusion criteria or could not undergo diagnostic procedures as outlined in the research protocol were excluded based on principles of good clinical practice.

During the 12-month study period, demographic, imaging, laboratory, and neurophysiological data were prospectively collected from all hospitalized stroke patients.

Data Collection

Patient history was utilized to gather information on neurological impairments, seizure onset, and risk factors for cerebrovascular diseases. For patients who experienced seizures, the interval between stroke onset and seizure occurrence (in days) was calculated to distinguish early from late post-stroke seizures.

Vital signs, including blood pressure, pulse, height, weight, and body mass index (BMI), were recorded. Neurological impairment was assessed on admission and discharge through clinical examinations and standardized scales, including the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS).

Laboratory and Diagnostic Assessments

Within 24 hours of admission, blood samples were collected to measure urea, creatinine, electrolytes, uric acid, cholesterol, triglycerides, liver enzymes, blood glucose, cystatin C, high-sensitivity C-reactive protein (hsCRP), red blood cell count, hemoglobin concentration, and urine analysis.

Within 72 hours of admission, imaging diagnostics (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] of the brain) and functional diagnostics (electroencephalography \[EEG\]) were performed. The study population consisted of patients with ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, and other rare cerebrovascular diseases (CVD).

Patient Grouping

Clinical Seizure Data and Timing of Onset Post-Stroke:

Patients were classified into three groups:

No seizures after stroke ("no EPI")

Early seizures (within 7 days post-stroke; "early EPI")

Late seizures (more than 7 days post-stroke; "late EPI")

EEG-Based Grouping:

Patients were additionally grouped based on EEG results:

EEG+/EPI+: Epileptiform EEG changes with seizures

EEG+/EPI-: Epileptiform EEG changes without seizures

EEG-/EPI-: No epileptiform EEG changes and no seizures

KON: Control group of healthy individuals

Planned Analyses

Demographic Analysis:

Data on gender, age, cerebrovascular risk factors, stroke type, functional impairment (assessed by NIHSS and mRS), seizure prevalence, and EEG changes were analyzed for all participants. Subgroup demographic analyses were performed based on clinical and EEG data.

EEG Analysis:

Standard visual EEG analysis included the evaluation of spectral frequency bands and the identification of focal or generalized epileptiform abnormalities. Preprocessing involved removing segments with noise, saturation, or absence of EEG activity. Ocular artifacts, including blink-related components, were identified using independent component analysis, and the EEG signals were reconstructed without these artifacts.

Using spectral parameterization (SPECPARAM 2.0 in Python), power spectral density was calculated for each patient. Aperiodic components were analyzed by extracting the exponent and offset from each frequency spectrum. Welch's t-tests were used to compare these parameters between groups. Additionally, standardized low-resolution brain electromagnetic tomography (sLORETA) was employed for signal source localization, micro-EEG potential analysis, and network distribution assessment.

Statistical Data Analysis

Descriptive Statistics:

Basic descriptive metrics, including mean, standard deviation, median, minimum, maximum, and quartiles, were calculated for each variable to assess within-group distributions. Frequencies and relative frequencies were determined for categorical variables, with emphasis on the prevalence rates within the "no EPI," "early EPI," and "late EPI" groups. Results were presented in frequency tables.

Inferential Statistics:

Parametric tests (for normally distributed data):

Two-group comparisons: t-tests

Multi-group comparisons: ANOVA

Non-parametric tests (for non-normally distributed data):

Two-group comparisons: Mann-Whitney U tests

Multi-group comparisons: Kruskal-Wallis tests

For EEG-based groups, extracted offset and exponent values of aperiodic components were compared using Welch's t-tests. Correlation analyses (Pearson's or Spearman's) were performed based on data distribution. Post-hoc analyses used Dunn's tests for pairwise comparisons when significant differences were identified.

Categorical Data Analysis:

Chi-square tests evaluated differences between categorical variables among patient groups. Fisher's exact test was applied when expected frequencies were too low for the chi-square test.

Survival Analysis:

To examine seizure onset timing, survival analysis was conducted using the time from stroke onset as the time variable. Kaplan-Meier analysis estimated survival curves representing seizure-free intervals, and log-rank (Mantel-Cox) tests were used to compare survival distributions across groups. This analysis helped to identify factors associated with seizure onset timing among stroke patients.

Conditions

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Stroke Seizures EEG Power Spectra Serum Biomarkers CT Scan MR Biomarkers

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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EEG+/EPI+ group

Patients with epileptiform EEG changes and seizures

No interventions assigned to this group

EEG+/EPI- group

Patients with epileptiform EEG changes but no seizures

No interventions assigned to this group

EEG-/EPI-group

Patients without epileptiform EEG changes and no seizures

No interventions assigned to this group

KON group

A control group of comparable healthy individuals

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

Patients were eligible for inclusion if they had experienced an acute stroke or a seizure occurring at any point after a previous stroke.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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IRCCS San Camillo, Venezia, Italy

OTHER

Sponsor Role collaborator

University Medical Centre Maribor

OTHER

Sponsor Role lead

Responsible Party

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Albin Gačnik MD

MD, Senior Consultant Neurologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martin Rakusa, Asoc. Prof.

Role: STUDY_CHAIR

UKC Maribor

Locations

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UKC Maribor

Maribor, , Slovenia

Site Status

Countries

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Slovenia

References

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Bentes C, Rodrigues FB, Sousa D, Duarte GS, Franco AC, Marques R, Nzwalo H, Peralta AR, Ferro JM, Costa J. Frequency of post-stroke electroencephalographic epileptiform activity - a systematic review and meta-analysis of observational studies. Eur Stroke J. 2017 Dec;2(4):361-368. doi: 10.1177/2396987317731004. Epub 2017 Sep 13.

Reference Type BACKGROUND
PMID: 31008328 (View on PubMed)

Tatillo C, Legros B, Depondt C, Rikir E, Naeije G, Jodaitis L, Ligot N, Gaspard N. Prognostic value of early electrographic biomarkers of epileptogenesis in high-risk ischaemic stroke patients. Eur J Neurol. 2024 Jan;31(1):e16074. doi: 10.1111/ene.16074. Epub 2023 Sep 27.

Reference Type BACKGROUND
PMID: 37754551 (View on PubMed)

Tanaka T, Ihara M, Fukuma K, Mishra NK, Koepp MJ, Guekht A, Ikeda A. Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications. Neurology. 2024 Jun 11;102(11):e209450. doi: 10.1212/WNL.0000000000209450. Epub 2024 May 17.

Reference Type BACKGROUND
PMID: 38759128 (View on PubMed)

Pani SM, Saba L, Fraschini M. Clinical applications of EEG power spectra aperiodic component analysis: A mini-review. Clin Neurophysiol. 2022 Nov;143:1-13. doi: 10.1016/j.clinph.2022.08.010. Epub 2022 Aug 28.

Reference Type BACKGROUND
PMID: 36088797 (View on PubMed)

Fukuma K, Tojima M, Tanaka T, Kobayashi K, Kajikawa S, Shimotake A, Kamogawa N, Ikeda S, Ishiyama H, Abe S, Morita Y, Nakaoku Y, Ogata S, Nishimura K, Koga M, Toyoda K, Matsumoto R, Takahashi R, Ikeda A, Ihara M. Periodic discharges plus fast activity on electroencephalogram predict worse outcomes in poststroke epilepsy. Epilepsia. 2023 Dec;64(12):3279-3293. doi: 10.1111/epi.17760. Epub 2023 Oct 30.

Reference Type BACKGROUND
PMID: 37611936 (View on PubMed)

Related Links

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Other Identifiers

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KME št. 0120-302/2024-2711-3

Identifier Type: -

Identifier Source: org_study_id

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