Clinical characteristics, semiology, and comorbidity patterns in non-epileptic seizures (NES): a retrospective comparative study
- 1Neurology Unit, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
- 2S.C.U. Obstetrics and Gynaecology Clinic, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo, ” Trieste, Italy
Abstract
Objectives: Non-epileptic seizures (NES) are paroxysmal events resembling epileptic seizures but not explained by ictal activity. Differential diagnosis may be challenging, particularly because NES and epilepsy can coexist. We aimed to characterize the demographic, clinical, semiological, psychiatric, and instrumental profile of patients with NES, compare patients with NES only with patients with NES epilepsy-only, and assess the robustness of the main associations through sensitivity analyses.
Methods: We conducted a retrospective observational comparative study using a clinical database from our Neurology Unit (2022–2025) including 38 patients with NES and 23 patients with epilepsy without NES. A total of 18 NES patients had comorbid epilepsy; therefore, the primary comparison included mutually exclusive groups: NES-only (n = 20) and epilepsy-only (n = 23). All NES patients were retained for descriptive analyses. Between-group comparisons used exact or non-parametric tests with Benjamini–Hochberg false-discovery-rate (BH-FDR) correction. Sensitivity analyses restricted NES-only patients to those with database-recorded video-EEG confirmation and used Firth penalized logistic regression adjusted for age and sex.
Results: Among 38 patients with NES, 94.7% had documented psychological/psychiatric comorbidity, mainly anxiety (50.0%) and depression (28.9%). Positive motor phenomena were documented in 73.7%, neurological examination inconsistency/incongruity in 85.7% of evaluable patients, and video-EEG confirmation in 73.7%. Psychological/psychiatric comorbidity was significantly more frequent in NES-only than epilepsy-only patients (90.0% vs. 13.0%; exact OR 50.40, 95% CI 7.29–670.28; BH-FDR p < 0.001), as was anxiety (45.0% vs. 4.3%; BH-FDR p = 0.014). Broad seizure-semiology domains were not significantly different after multiplicity correction. Among imaged patients, abnormal MRI findings were more frequent in epilepsy-only patients (12/18 vs. 0/10; BH-FDR p = 0.006), although MRI ascertainment differed between groups. The psychiatric-comorbidity association persisted in sensitivity analyses.
Conclusion: NES showed substantial clinical heterogeneity and frequently coexisted with epilepsy. Psychological/psychiatric comorbidity was markedly more frequent in NES-only than epilepsy-only patients and remained robust in sensitivity analyses, although differential ascertainment limits interpretation. Broad seizure manifestations alone did not distinguish the groups after multiplicity correction. Instrumental findings should be considered descriptive rather than NES biomarkers. These findings support explicit stratification for comorbid epilepsy and standardized prospective assessment of psychiatric and semiological features.
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BibTeX
@article{caruso2026clinical,
title = {{Clinical characteristics, semiology, and comorbidity patterns in non-epileptic seizures (NES): a retrospective comparative study}},
author = {Paola Caruso and Magda Quagliotto and Yvonne Radin and Stefania Pavan and Paolo Manganotti and Alberto Benussi},
journal = {Frontiers in Psychology},
year = {2026},
month = oct,
doi = {10.3389/fpsyg.2026.1982723},
url = {https://doi.org/10.3389/fpsyg.2026.1982723},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical characteristics, semiology, and comorbidity patterns in non-epileptic seizures (NES): a retrospective comparative study
AU - Paola Caruso
AU - Magda Quagliotto
AU - Yvonne Radin
AU - Stefania Pavan
AU - Paolo Manganotti
AU - Alberto Benussi
PY - 2026
DA - 2026/10/22
JO - Frontiers in Psychology
DO - 10.3389/fpsyg.2026.1982723
UR - https://doi.org/10.3389/fpsyg.2026.1982723
AB - Objectives: Non-epileptic seizures (NES) are paroxysmal events resembling epileptic seizures but not explained by ictal activity. Differential diagnosis may be challenging, particularly because NES and epilepsy can coexist. We aimed to characterize the demographic, clinical, semiological, psychiatric, and instrumental profile of patients with NES, compare patients with NES only with patients with NES epilepsy-only, and assess the robustness of the main associations through sensitivity analyses. Methods: We conducted a retrospective observational comparative study using a clinical database from our Neurology Unit (2022–2025) including 38 patients with NES and 23 patients with epilepsy without NES. A total of 18 NES patients had comorbid epilepsy; therefore, the primary comparison included mutually exclusive groups: NES-only (n = 20) and epilepsy-only (n = 23). All NES patients were retained for descriptive analyses. Between-group comparisons used exact or non-parametric tests with Benjamini–Hochberg false-discovery-rate (BH-FDR) correction. Sensitivity analyses restricted NES-only patients to those with database-recorded video-EEG confirmation and used Firth penalized logistic regression adjusted for age and sex. Results: Among 38 patients with NES, 94.7% had documented psychological/psychiatric comorbidity, mainly anxiety (50.0%) and depression (28.9%). Positive motor phenomena were documented in 73.7%, neurological examination inconsistency/incongruity in 85.7% of evaluable patients, and video-EEG confirmation in 73.7%. Psychological/psychiatric comorbidity was significantly more frequent in NES-only than epilepsy-only patients (90.0% vs. 13.0%; exact OR 50.40, 95% CI 7.29–670.28; BH-FDR p < 0.001), as was anxiety (45.0% vs. 4.3%; BH-FDR p = 0.014). Broad seizure-semiology domains were not significantly different after multiplicity correction. Among imaged patients, abnormal MRI findings were more frequent in epilepsy-only patients (12/18 vs. 0/10; BH-FDR p = 0.006), although MRI ascertainment differed between groups. The psychiatric-comorbidity association persisted in sensitivity analyses. Conclusion: NES showed substantial clinical heterogeneity and frequently coexisted with epilepsy. Psychological/psychiatric comorbidity was markedly more frequent in NES-only than epilepsy-only patients and remained robust in sensitivity analyses, although differential ascertainment limits interpretation. Broad seizure manifestations alone did not distinguish the groups after multiplicity correction. Instrumental findings should be considered descriptive rather than NES biomarkers. These findings support explicit stratification for comorbid epilepsy and standardized prospective assessment of psychiatric and semiological features.
SN - 1664-1078
ER -