Abstract
Objective
This study was undertaken to estimate the prevalence and characterize the semiology of co‐occurring functional/dissociative seizures (FDSs) and identify clinical features potentially associated with the development of video‐electroencephalography (video‐EEG)‐diagnosed FDSs in patients with idiopathic generalized epilepsy (IGE).
Methods
In this retrospective single‐center inpatient video‐EEG study, we characterized clinical features of FDSs recorded in patients with IGE aged ≥16 years admitted into our epilepsy monitoring unit between January 2008 and December 2024. We compared clinical characteristics of IGE patients with FDSs to an IGE cohort without FDSs. FDSs were classified as akinetic nonmotor, subjective nonmotor, motor, or mixed FDSs.
Results
Among 123 patients with IGE, 29 (23.5%) had co‐occurring documented FDSs recorded on video‐EEG. Twenty‐eight (96.5%) were females. Median age at admission was 25 years (interquartile range [IQR] = 14). The median length of admission was 5 days (IQR = 3). Twenty‐eight patients (96.5%) had generalized interictal discharges, emerging on the first day of admission in 24 of 28 (85.7%). Epileptic seizures were also captured in 13 patients (44.8%). Twenty‐four patients (82.7%) had multiple FDSs episodes, whereas 19 (65.5%) presented with a single FDSs subtype. Subjective FDSs was the most common subtype (17/29, 58.6%), followed by pure motor (6/29, 20.7%), mixed motor–akinetic (6/29, 20.7%), pure akinetic (5/29, 17.2%), mixed akinetic–subjective (4/29, 13.8%), and mixed motor–subjective (1/29, 3.4%). Among the clinical variables analyzed, female sex was associated with co‐occurring FDSs, although this association did not remain significant after Bonferroni correction.
Significance
Approximately one quarter of patients with IGE who underwent video‐EEG had co‐occurring FDSs. Almost half had epileptic seizures during the same admission. Video‐EEG referral should be considered in patients with suspected drug‐resistant IGE with active seizures or if there is a clinical suspicion of FDSs.
Keywords: antiseizure medication, drug resistance, functional dissociative seizures, idiopathic generalized epilepsy, video‐electroencephalography
Key points.
Approximately one quarter of IGE patients referred to our inpatient video‐EEG unit had co‐occurring FDSs.
The semiology of FDSs in IGE is broad, including subjective, akinetic, pure motor events, or mixed events.
No distinguishing clinical features were identified between IGE patients with or without co‐occurring FDSs.
Video‐EEG should be considered early in the evaluation of IGE patients if FDSs or apparent drug resistance is suspected.
1. INTRODUCTION
Functional/dissociative seizures (FDSs) are a common diagnosis in neurology practice, associated with significant morbidity, and an estimated prevalence of 2–33/100 000 people, comparable with conditions like multiple sclerosis or trigeminal neuralgia. 1 Misdiagnosis of FDSs as epilepsy is common, 2 leading to inappropriate antiseizure medication (ASM) prescription, and delay in appropriate psychological intervention. Although some clinical features identified through history, direct observation, or home video may help differentiate FDSs from epileptic seizures, 3 video‐electroencephalography (video‐EEG) remains the gold standard diagnostic test. 2 Both limited access to video‐EEG and repeated trials of ASM may delay the diagnosis of FDSs by 8.4 years on average. 4 FDSs and epileptic seizures are known to co‐occur, with reported comorbidity rates ranging from 3.6% to 58%. 5 , 6 , 7
Co‐occurring FDSs in patients with idiopathic generalized epilepsy (IGE) have rarely been described in the literature, 8 despite IGE representing 15%–20% of all epilepsies. 9 This may reflect overrepresentation of focal relative to generalized epilepsy in epilepsy monitoring unit (EMU) cohorts, as presurgical evaluation of focal epilepsy is a common reason for admission, 10 , 11 and inpatient video‐EEG monitoring is generally not needed for IGE, because routine EEG or sleep‐deprived EEG is typically sufficient to support diagnosis. 12
In this study, we aimed to estimate the prevalence and characterize the clinical semiology of co‐occurring FDSs in patients with IGE admitted to a tertiary referral EMU, and to compare their clinical features with those of patients with IGE without co‐occurring FDSs.
2. MATERIALS AND METHODS
2.1. Participants and study design
We conducted a retrospective comparative study of patients with IGE with and without co‐occurring FDSs during inpatient video‐EEG monitoring at Beaumont Hospital, Dublin, Ireland, between January 2008 and December 2024. As Beaumont Hospital is an adult center, only patients aged 16 years and older were included in the study.
The inclusion criteria were as follows: (1) patients diagnosed with IGE in the EMU showing a normal background and interictal 3–5.5‐Hz generalized spike‐ or polyspike‐wave discharges (GSWD/GPSWDs), who had co‐occurring FDSs during admission; (2) patients with a previously supportive electroclinical diagnosis of IGE, who did not exhibit interictal 3–5.5‐Hz GSWD/GPSWDs but had co‐occurring FDSs during admission; or (3) patients with an initial diagnosis of focal or unclassified epilepsy whose diagnosis was later revised to IGE and had co‐occurring FDSs during inpatient video‐EEG monitoring. Patients with epilepsy with eyelid myoclonia, in the absence of epileptic encephalopathy, were also included.
The exclusion criteria were as follows: (1) patients without an electroclinical IGE diagnosis; (2) an EEG with prominent and persisting focal discharges, persistent focal slowing, or abnormal background; (3) neuroimaging findings consistent with focal epilepsy; (4) moderate to severe intellectual disability; (5) other evidence supporting a diagnosis of epileptic encephalopathy or focal epilepsy; or (6) FDSs diagnosis without video‐EEG confirmation.
2.2. Data collection and outcome measures
Our epilepsy‐specific Electronic Patient Record (EPR) was interrogated searching the keywords “idiopathic generalized epilepsy”, “idiopathic generalized epilepsy: not otherwise specified”, “generalized tonic‐clonic seizures only”, “generalized convulsions only”, “juvenile absence epilepsy”, and “juvenile myoclonic epilepsy”. After prescreening all IGE patients in our database, only patients who were admitted to the EMU were included. We individually screened all video‐EEG reports, and cases were included only if FDSs had been confirmed by a board‐certified consultant epileptologist/clinical neurophysiologist. Baseline clinical and neurophysiological data were obtained from the EPR, paper‐based medical notes, initial referral letters, and EEG software data. Prior to 2024, referrals to our EMU were unstructured and submitted as free‐text requests. From 2024 onward, referrals were standardized and stratified as either presurgical evaluation or diagnostic admissions.
FDSs were initially diagnosed by a consultant neurophysiologist and the attending consultant neurologist during admission (G.M., P.W.W., R.D.K., and N.D.). For the purpose of this study, we employed the FDSs classification proposed by Asadi‐Pooya, which differentiates FDSs into three main categories: motor seizures, nonmotor seizures, and mixed events (Figure 1). 13 All events were subsequently classified independently by another consultant neurophysiologist (N.M.). Diagnosis of IGE during video‐EEG was based on the diagnostic confidence criteria proposed by Koutroumanidis and colleagues, as part of the International League Against Epilepsy (ILAE) Neurophysiology Task Force, including the following: confirmatory of clinical diagnosis (confirmed IGE), high diagnostic certainty (probable IGE), and lower diagnostic certainty (possible IGE). 14 Epileptic seizures were classified into absence seizures, myoclonic seizures, and generalized tonic–clonic seizures (GTCSs) based on the latest ILAE classification. 15 Data collection, curation, and analysis were completed between January 2025 and April 2026. For patients referred with suspected FDSs, preadmission diagnostic classification was assigned according to the diagnostic certainty criteria proposed by LaFrance and colleagues, on behalf of the ILAE Nonepileptic Seizures Task Force, categorizing FDSs as possible, probable, clinically established, or documented based on the history, witnessed event, and EEG findings. 2
FIGURE 1.
Classification of functional/dissociative seizures proposed by Asadi‐Pooya. Reproduced and adapted with permission from Elsevier, license No. 6186970751013.
2.3. Inpatient video‐EEG protocol
All patients underwent continuous scalp video‐EEG monitoring. Natus NicoletOne EEG system was used for admissions from 2008 to 2013, whereas Natus NeuroWorks EEG software was used thereafter. Electrodes were placed using the standard International 10–20 electrode placement system with an additional electrocardiogram channel. Video‐EEG recordings were reviewed daily. All patients had a handheld push‐button in case of clinical or subclinical events. ASM reduction and other activation methods such as photic stimulation and/or hyperventilation were performed on an individual basis when considered appropriate by the attending physician without a standardized protocol.
2.4. Statistical analysis
We conducted a comparative analysis of clinical features between patients with and without FDSs using IBM SPSS Statistics (version 30), with statistical significance set at p < .05. The Mann–Whitney U‐test was used to compare continuous variables, including age at seizure onset, age at video‐EEG monitoring, length of admission, number of ASMs trialed prior to admission, and ASMs at admission and discharge, with a Bonferroni‐adjusted significance threshold of p < .008 applied to account for multiple comparisons. Pearson chi‐squared test was used to analyze categorical variables, including sex, psychiatric comorbidity, and the occurrence of epileptic seizures during video‐EEG monitoring, with a Bonferroni‐adjusted significance threshold of p < .017.
3. RESULTS
3.1. Baseline demographics of patients with IGE and co‐occurring FDSs
Of 443 patients with IGE in our epilepsy‐specific EPR, 123 (27.7%) were admitted to the EMU. We identified 29 patients (23.5%) who had FDSs during admission, of whom twenty‐eight were females (97%). Baseline clinical characteristics are summarized in Table 1. The median age at seizure onset was 14 years (interquartile range [IQR] = 6), and the median age at admission was 25 years (IQR = 14). The median interval between seizure onset and video‐EEG monitoring was 10 years (IQR = 15). Eighteen patients (62%) had a psychiatric comorbidity documented in the initial referral.
TABLE 1.
Baseline demographics of patients with IGE and co‐occurring functional/dissociative seizures, N = 29.
| Clinical features | Results |
|---|---|
| Female, n (%) | 28 (97) |
| Age at seizure onset, median (IQR) | 14 (6) |
| Age at admission, median (IQR) | 25 (14) |
| Years of delay between seizure onset and admission, median (IQR) | 10 (15) |
| History of psychiatric comorbidity, n (%) | 18 (62) |
| Major depressive disorder | 12 |
| Generalized anxiety disorder | 3 |
| Attention‐deficit/hyperactivity disorder | 2 |
| Posttraumatic stress disorder | 1 |
| Borderline personality disorder | 1 |
| Anorexia nervosa | 1 |
| Suicidal attempt | 3 |
| Diagnosis at initial referral, n (%) | |
| IGE | 21 (72) |
| FE | 4 (14) |
| Unclassified [FE vs. IGE] | 4 (14) |
| Baseline number of ASMs at admission, median (IQR) | 2 (2) |
| Number of ASMs at admission, n (%) | |
| 0 ASMs | 2 (7) |
| 1 ASM | 7 (24) |
| 2 ASMs | 11 (38) |
| 3 ASMs | 6 (21) |
| 4 or more ASMs | 3 (10) |
| Previously trialed ASMs before admission, median (IQR) | 2 (4) |
| ASM number trialed before admission, n (%) | |
| 0 ASMs | 4 (14) |
| 1 ASM | 5 (17) |
| 2 ASMs | 6 (21) |
| 3 ASMs | 4 (14) |
| 4 or more ASMs | 10 (34) |
Abbreviations: ASM, antiseizure medications FE, focal epilepsy; IGE, idiopathic generalized epilepsy; IQR, interquartile range.
The median number of ASMs at admission was two (IQR = 2), most commonly lamotrigine (55%), followed by levetiracetam (31%) and zonisamide (31%). The median number of previously trialed ASMs was 2 (IQR = 4), and the most frequently trialed ASMs were valproate (52%), levetiracetam (38%), and lamotrigine (35%). Two patients were not taking ASMs on admission, based on their preferences.
Upon admission to our EMU, 21 patients (72%) had a diagnosis of possible, probable, or confirmed IGE and were referred for diagnostic clarification. Among the 21 patients, EEG reports were available for review in 17. Thirteen showed normal background and interictal 3–5.5‐Hz GSWD/GPSWDs without clinical seizures, supporting a diagnosis of probable IGE. In the remaining four, EEG demonstrated interictal 3–5.5‐Hz GSWD/GPSWDs along with clinical events: absence seizures in two patients, a GTCS in one, and absence status epilepticus in another. For the other four patients, EEG data or reports were unavailable, and a diagnosis of possible IGE was made. Four patients (14%) were initially diagnosed with focal epilepsy by their referring physician; three were referred for presurgical evaluation and one for diagnostic clarification. The remaining four (14%) had unclassified epilepsy and were referred for diagnostic clarification. Among these eight patients, two had normal findings on both routine and sleep‐deprived EEGs. Three had noninformative routine EEGs showing only occasional temporal theta activity, and one demonstrated a brief burst of left frontal spikes. For the remaining two patients, EEG data were not available in the referral. Only one patient (3%) had a documented FDSs during routine EEG prior to referral, whereas in two patients, the referring clinician suspected a diagnosis of FDSs (7%).
3.2. Inpatient video‐EEG findings in patients with co‐occurring FDSs
Clinical and electrographic findings in the 29 patients with documented FDSs are summarized in Table 2. The median length of admission was 5 days (IQR = 3). GSWD/GPSWDs were identified in 28 patients (97%), without evidence of secondary bilateral synchrony. Among the 28 patients, GSWD/GPSWDs were present from the first day in 24 cases (86%), whereas in the remaining four (14%), GSWD/GPSWDs emerged later during the admission. In 21 patients (75%), 3–4‐Hz GSWDs was the predominant interictal abnormality, whereas in seven patients (25%), 4–5.5‐Hz GPSWDs was most frequently observed. The remaining patient had a normal EEG during admission despite ASM reduction and was classified as probable IGE, supported by a prior routine EEG showing a normal background with occasional brief bursts of 3–4‐Hz GSWDs without clinical correlate.
TABLE 2.
Clinical and electrographic features during inpatient video‐electroencephalography admission of patients with idiopathic generalized epilepsy and co‐occurring functional/dissociative seizures, N = 29.
| Clinical and electrographic findings | Results |
|---|---|
| Length of monitoring, median days (IQR) | 5 (3) |
| ASMs on discharge, median (IQR) | 2 (1) |
| Number of ASMs at discharge, n (%) | |
| 1 ASM | 10 (34) |
| 2 ASMs | 13 (45) |
| 3 ASMs | 6 (21) |
| Generalized IEDs, n (%) | |
| Predominant 3–4‐Hz GSWDs | 21 (75) |
| Predominant 4–5.5‐Hz GPSWDs | 7 (25) |
| Nonlocalizing focal interictal epileptiform discharges, n (%) | 12 (41) |
| PPR, n (%) | 1 (4) |
| Number of patients having at least one epileptic seizure, n (%) | 13 (45) |
| Seizures types during admission | |
| Generalized tonic–clonic seizures | 7 |
| Absence seizures | 4 |
| Myoclonic seizures | 4 |
| Eyelid myoclonia with/without absences | 1 |
Abbreviations: ASM, antiseizure medication; GSWD/GPSWDs, generalized spike–wave discharge/generalized polyspike–wave discharges; IEDs, interictal epileptiform discharges; IQR, Interquartile range; PPR, photoparoxysmal response.
Nonlocalizing focal interictal epileptiform discharges (IEDs) were observed in 12 patients (41%). Photoparoxysmal response (PPR; grade 4) was observed in one patient (4%) of the 27 who were tested. Thirteen patients had at least one epileptic seizure (45%). Seven patients (24%) had at least one GTCS during the admission. Absence seizures were observed in four patients (14%) and myoclonic seizures in four (14%). One patient experienced several episodes of eyelid myoclonia with and without absence seizures (3%). The day of the first epileptic seizure and the outcome diagnosis for each patient after applying the diagnostic certainty criteria are found in Table 3.
TABLE 3.
Inpatient video‐EEG findings.
| Patient | Days of monitoring | ASM reduction | Generalized IEDs from day 1; predominant GSWDs or GPSWDs | Day of the first ES | Day of the first FDSs | ES:FDSs ratio | FDSs classification | Diagnostic certainty criteria |
|---|---|---|---|---|---|---|---|---|
| Patient 1 | 5 | Yes | Yes; GSWDs | 4 | 3 | 1 GTCS:3 FDSs | Subjective | Confirmed unclassified IGE |
| Patient 2 | 4 | No | Yes; GSWDs | 1 | 1 | >10 absence seizures:16 FDSs | Akinetic | Confirmed JAE |
| Patient 3 | 4 | Yes | No; Day 2; GPSWDs | 3 | 2 | 2 GTCSs:2 FDSs | Subjective | Confirmed IGE (probable JME) |
| Patient 4 | 8 | Yes | Yes: GSWDs | 6 | 1 | 1 GTCS:24 FDSs | Subjective | Confirmed unclassified IGE |
| Akinetic | ||||||||
| Patient 5 | 5 | No | Yes; GPSWDs | 2 | 3 | >10 myoclonic seizures:>5 FDSs | Subjective | Confirmed JME |
| Patient 6 | 8 | Yes | Yes; GPSWDs | 7 | 2 | 1 GTCS, >10 myoclonic seizures:1 FDS | Mixed: motor and akinetic | Confirmed JME |
| Patient 7 | 7 | Yes | Yes; GSWDs | 2 | 1 | 13 absence seizures:8 FDSs | Subjective | Confirmed JAE |
| Patient 8 | 6 | Yes | Yes; GPSWDs | 6 | 1 | >10 myoclonic seizures:2 FDSs | Subjective | Confirmed JME |
| Mixed: motor and akinetic | ||||||||
| Patient 9 | 8 | Yes | Yes; GPSWDs | 4 | 1 | 1 GTCS, >10 myoclonic seizures:7 FDSs | Subjective | Confirmed JME |
| Akinetic | ||||||||
| Patient 10 | 5 | Yes | Yes: GSWDs | 1 | 1 | 15 absence seizures:5 FDSs | Mixed: akinetic and motor | Confirmed JAE |
| Akinetic | ||||||||
| Patient 11 | 10 | Yes | No; Day 2, GPSWDs | 5 | 2 | 2 eyelid myoclonia with absence, multiple episodes of eyelid myoclonia without absence:12 FDSs | Mixed: motor and akinetic | Confirmed EEM |
| Subjective | ||||||||
| Patient 12 | 4 | Yes | Yes; GSWDs | n/a | 2 | 0 ESs:5 FDSs | Motor | Probable unclassified IGE |
| Patient 13 | 5 | Yes | No; Day 3, GSWDs | n/a | 1 | 0 ESs:8 FDSs | Motor | Probable unclassified IGE |
| Subjective | ||||||||
| Patient 14 | 2 | No | Yes; GSWDs | n/a | 2 | 0 ESs:10 FDSs | Mixed: subjective and akinetic | Probable unclassified IGE |
| Motor | ||||||||
| Patient 15 | 8 | Yes | Yes; GSWDs | n/a | 1 | 0 ESs:12 FDSs | Mixed: akinetic and motor | Probable unclassified IGE |
| Patient 16 | 4 | No | Yes; GPSWDs | n/a | 2 | 0 ESs:3 FDSs | Subjective | Probable JME |
| Patient 17 | 6 | Yes | Yes; GSWDs | n/a | 2 | 0 ESs:3 FDSs | Mixed: motor and subjective | Probable unclassified IGE |
| Subjective | ||||||||
| Patient 18 | 8 | Yes | No IEDs | n/a | 4 | 0 ESs:4 FDSs | Subjective | Probable unclassified IGE (diagnosis made with previous routine EEG) a |
| Patient 19 | 5 | n/a b | No; Day 4, GSWDs | n/a | 2 | 0 ESs:3 FDSs | Mixed: akinetic and subjective | Probable unclassified IGE |
| Patient 20 | 4 | No | Yes; GSWDs | n/a | 1 | 0 ESs:11 FDSs | Mixed: akinetic and subjective | Probable unclassified IGE |
| Patient 21 | 3 | No | Yes; GSWDs | n/a | 3 | 0 ESs:1 FDSs | Subjective | Probable unclassified IGE |
| Patient 22 | 5 | Yes | Yes; GSWDs | n/a | 2 | 0 ESs:1 FDSs | Mixed: motor and akinetic | Probable unclassified IGE |
| Patient 23 | 6 | Yes | Yes: GSWDs | n/a | 4 | 0 ESs:1 FDS | Subjective | Probable unclassified IGE |
| Patient 24 | 6 | Yes | Yes; GSWDs | n/a | 4 | 0 ESs:2 FDSs | Subjective | Probable unclassified IGE |
| Patient 25 | 7 | Yes | Yes; GSWDs | n/a | 1 | 0 ESs:2 FDSs | Mixed: subjective and akinetic | Probable unclassified IGE |
| Patient 26 | 2 | No | Yes; GSWDs | n/a | 1 | 0 ESs:1 FDSs | Motor | Probable unclassified IGE |
| Patient 27 | 7 | Yes | Yes; GSWDs | 6 | 2 | 1 GTCS:>5 FDSs | Akinetic | Confirmed unclassified IGE |
| Motor | ||||||||
| Patient 28 | 7 | n/a b | Yes; GSWDs | n/a | 2 | 0 ESs:2 FDSs | Motor | Probable unclassified IGE |
| Subjective | ||||||||
| Patient 29 | 5 | Yes | Yes; GSWDs | 5 | 1 | 1 GTCS:11 FDSs | Subjective | Confirmed unclassified IGE |
Abbreviations: ASM, antiseizure medication; EEG, electroencephalographic; EEM, epilepsy with eyelid myoclonia; ES, epileptic seizure; FDSs, functional (dissociative) seizure; GPSWD, generalized polyspike–wave discharge; GSWD, generalized spike‐wave discharge; GTCS, generalized tonic–clonic seizure; IED, interictal epileptiform discharge; IGE, idiopathic generalized epilepsy; JAE, juvenile absence epilepsy; JME, juvenile myoclonic epilepsy; n/a, not applicable.
Patient was diagnosed with probable IGE on routine EEG.
Patients admitted in the inpatient video‐EEG unit not taking any ASM.
Table 3 includes the FDSs classification, the ratio of epileptic seizures to FDSs, and day of first FDSs. Comprehensive clinical semiology of epileptic seizures and FDSs is provided in Table S1. All patients' episodes were recorded on video, thereby establishing a diagnosis of documented FDSs. Twenty‐four patients (83%) had several FDSs during admission, whereas five patients (17%) had a single FDSs episode. Nineteen patients (66%) presented with a single FDSs subtype, even if multiple semiologies were present within that subtype. Ten patients (35%) were classified as having two or more FDSs subtypes. The distribution of FDS subtypes is outlined in Figure 2. Among the 17 patients with subjective FDSs, 10 experienced only subjective episodes and no other FDSs subtypes. Within the subjective FDSs subgroup, five showed minor positive clinical signs, such as mild tremors of the upper or lower limbs or trunk, or rapid blinking.
FIGURE 2.
Distribution of functional/dissociative seizure subtypes.
Among the 13 patients with epileptic seizures and FDSs recorded during the same admission, FDSs occurred earlier in 10 patients. In one patient, the epileptic seizure occurred first, whereas in the remaining two patients, the first epileptic seizure and FDSs occurred on the same day. In two patients, FDSs occurred during hyperventilation with no evidence of GSWD/GPSWDs activation, whereas in one patient FDSs occurred during photic stimulation with no PPR. In two patients, FDSs began after the termination of epileptic seizures, after a cluster of myoclonic jerks in one patient and after an absence seizure with eyelid myoclonia in another. In one patient, mixed motor and akinetic FDSs were terminated by a typical absence seizure.
Controlled ASM reduction to facilitate seizure provocation was performed in 20 patients (69%). At discharge, the median number of prescribed ASMs was 2 (IQR = 1). Seven patients (24%) had at least one ASM discontinued, four (14%) were discharged on an increased number of ASMs, and four (14%) had modifications to their ASM regimen without a change in the total number. In the remaining 14 patients (48%), the ASM regimen remained unchanged. Detailed information regarding ASM combinations on admission and discharge are found in Table S2.
3.3. Clinical follow‐up 1 year after video‐EEG monitoring
Clinical follow‐up at 1 year or the nearest available follow‐up was available for 25 patients (86%). The median number of ASMs at 1‐year follow‐up was 2 (IQR = 2). Six patients reported being seizure‐free or experiencing a reduction of seizures and/or FDSs, whereas 19 continued to report active seizures and/or FDSs. Twenty‐one (84%) patients were linked with mental health teams. Clinical outcomes for patients with available follow‐up are found in Table S2.
3.4. Comparative analysis
A comparative analysis of clinical variables between individuals with IGE and co‐occurring FDSs (n = 29) and those with IGE without FDSs (n = 94) is presented in Table 4. Female sex was nominally associated with the co‐occurring FDSs group (p = .018), but this did not remain significant after Bonferroni correction. No other variables reached statistical significance.
TABLE 4.
Comparative analysis of patients with and without co‐occurring FDSs.
| Variables | Patients with IGE and with co‐occurring FDSs, n = 29 | Patients with IGE only, n = 94 | p | Bonferroni correction |
|---|---|---|---|---|
| Sex, female, n (%) | 28 (96.5) | 74 (78.7) | .018 a | NS |
| Age at seizure onset, years, median (IQR) | 14 (6) | 13 (9) | .344 | NS |
| Age at video‐EEG monitoring, years, median (IQR) | 25 (14) | 28 (15) | .216 | NS |
| Days of video‐EEG monitoring, median (IQR) | 5 (3) | 6 (4) | .341 | NS |
| Number of ASMs failed prior to video‐EEG monitoring, median (IQR) | 2 (4) | 4 (3) | .224 | NS |
| Number of ASMs prescribed at admission, median (IQR) | 2 (2) | 2 (1) | .043 a | NS |
| Number of ASMs prescribed at discharge, median (IQR) | 2 (1) | 2 (1) | .032 a | NS |
| Psychiatric comorbidity, present, n (%) | 18 (62) | 45 (47.8) | .181 | NS |
| Epileptic seizures during video‐EEG [including absence seizures, myoclonic seizures, and GTCSs], present, n (%) | 13 (44.8) | 48 (51) | .557 | NS |
Abbreviations: ASM, antiseizure medication; EEG, electroencephalographic; FDSs, functional/dissociative seizure; GTCS, generalized tonic–clonic seizure; IGE, idiopathic generalized epilepsy; IQR, interquartile range; NS, nonsignificant.
Statistically significant.
4. DISCUSSION
Our study characterizes the prevalence and semiology of FDSs in EMU‐referred patients with IGE at a tertiary epilepsy center. To our knowledge, this is the largest inpatient video‐EEG study evaluating FDSs in patients with IGE. Within our IGE cohort, approximately one in four patients underwent long‐term video‐EEG monitoring, and among these, approximately one quarter had co‐occurring documented FDSs. FDSs were suspected in approximately 10% of patients based on the initial referral. Our study shows that IGE patients may exhibit a broad spectrum of FDSs semiology, including motor events, nonmotor events with akinetic or subjective symptoms, or mixed motor and nonmotor episodes. Motor and nonmotor FDSs could be misclassified as GTCSs, myoclonic seizures, or absence seizures on clinical grounds, leading to unnecessary treatment and potential iatrogenic harm. Most patients (97%) showed 3–5.5‐Hz GSWD/GPSWDs during the admission, and in 85% of patients, GSWD/GPSWDs emerged on the first day. Nearly half (45%) had epileptic seizures recorded, but FDSs tended to occur earlier during the admission. Seven patients (24%) were discharged on a reduced number of ASMs, and four patients (14%) required changes to their ASM regimen, highlighting the value of video‐EEG not only for diagnostic clarification but also for informing therapeutic management decisions.
Co‐occurring FDSs in people with IGE have rarely been reported, with one study documenting a prevalence of 4%. 8 However, it remains unclear whether the diagnosis of FDSs was made through video‐EEG or based solely on clinical grounds. In an ambulatory video‐EEG study, Hannon and colleagues reported that fewer than 1% of patients with generalized epilepsy had FDSs. 16 This potentially underreported association may be partly explained by the higher likelihood of patients with focal epilepsy being referred for inpatient video‐EEG monitoring, as well as the lower rates of drug resistance observed in IGE. 11 , 17 , 18 In addition, the diagnostic yield of routine EEG in IGE is comparatively high, with a sensitivity of approximately 68% after the first seizure, rising to 92% following a sleep‐deprived EEG, thereby often precluding the need for additional diagnostic investigations. 19
The lack of a formal FDSs classification system has led to the development of several proposed frameworks with moderate reliability. 20 We employed the Asadi‐Pooya classification because its semiological distinction between motor and nonmotor events parallels the colloquial differentiation between “major seizures” and “minor seizures” commonly used to describe GTCSs and absence seizures or myoclonic seizures, respectively. 13 Limiting FDSs to motor phenomena alone may lead to misclassification, with prolonged akinetic episodes mistaken for absence seizures and recurrent subjective events as focal seizures, potentially contributing to overdiagnosis of focal epilepsy. For example, Hannon and colleagues limited the diagnosis of FDSs to motor events, categorizing nonmotor episodes as noncorrelated events; these were reported to be approximately 10 times more frequent than FDSs among patients with generalized epilepsy. 16 Most studies that included nonmotor FDSs correlated the events with video‐EEG, 21 , 22 , 23 , 24 , 25 , 26 , 27 thereby supporting the highest level of diagnostic certainty. 2 , 28 Although interrater reliability has been reported to be higher for subjective FDSs compared to motor FDSs, 20 , 26 subjective events may represent IGE symptomatology, episodes of transient cognitive impairment during periods of active interictal discharges, 29 or “scalp‐negative” focal seizures in cases of combined generalized and focal epilepsy. Therefore, video‐EEG should remain as the gold standard test for diagnosis of FDSs.
Focal seizure symptoms and focal EEG abnormalities are common in IGE. 30 , 31 , 32 , 33 , 34 In a video‐EEG study involving people with IGE, Koren and colleagues found that all patients had focal IEDs and three quarters had focal seizure symptoms. 34 However, no correlation was identified between localization of focal IEDs and the localization or lateralization of focal seizure symptoms, supporting the view that nonlocalizing focal IEDs and focal semiology may be part of the IGE phenotype. 34 Additionally, focal IEDs and focal seizure semiology do not affect the therapeutic response in IGE. 32 Auras preceding GTCSs have been described in IGE, typically occurring in association with a seizure rather than in isolation, suggesting involvement of cortical and subcortical generators within a generalized network. 35 , 36 , 37 In patients with FDSs, auras typically manifest as headache, vertigo, and dizziness. 38 In our study, subjective FDSs were frequently accompanied by positive clinical signs, such as mild tremors in the hands and rapid blinking. FDSs occurred sequentially after a cluster of myoclonic jerks in one patient, and after an absence seizure with eyelid myoclonia in another. A mixed motor and akinetic FDSs was terminated by a typical absence seizure in a patient. We did not observe akinetic or subjective FDSs preceding epileptic seizures, supporting an FDSs diagnosis rather than focal seizures without scalp EEG changes, nor did we identify features suggestive of secondary bilateral synchrony or focal seizures with impaired consciousness and scalp‐positive EEG changes, features that would suggest combined generalized and focal epilepsy. However, given the relatively limited number of video‐EEG studies in IGE compared with those in focal epilepsy, focal seizure semiology in IGE remains underexplored, and further research is warranted.
In our study, female sex was initially found to be significantly associated with IGE and co‐occurring FDSs; however, this association did not remain significant after Bonferroni correction. Whereas a slight female predominance has been reported across most IGE syndromes, 17 83% of IGE patients referred to our unit were female. Sex‐specific disease modifiers have been previously investigated within the IGE spectrum, including catamenial seizures and more frequently reported myoclonic seizures in females. 39 , 40 , 41 Psychiatric comorbidity has also been associated with drug‐resistance in IGE, but without sex predominance. 18 , 42 Although psychiatric comorbidity is relatively common in IGE, we did not find a statistically significant association with co‐occurring FDSs. In clinical practice, co‐occurring FDSs might lead to unnecessary ASM trials and apparent drug resistance. However, we did not identify significant differences between groups in the number of ASMs previously trialed or prescribed at admission. Nonetheless, it is worth noting that our comparison consists solely of EMU‐referred IGE patients, who are more likely to have active seizures and receive polytherapy than those with well‐controlled IGE. In our study, the frequency of epileptic seizures during video‐EEG admission did not differ significantly between patients with and without FDSs (45% vs. 51%, respectively). In most patients, FDSs tended to occur earlier during the admission, aligning with previous research. 5 Although the underlying mechanism remains unclear, it could be hypothesized whether the stressors of being admitted in EMU facilitate FDSs, whereas ASM reduction provokes epileptic seizures at later stage. Nonetheless, this hypothesis requires further investigation through future studies.
Our study has several limitations. First, the sample size remains relatively small, and the single‐center nature might limit the generalizability of our findings. Our study is retrospective, introducing a sampling bias. We were unable to estimate the prevalence of FDSs across the entire IGE cohort, as fewer than one quarter of patients with IGE underwent video‐EEG monitoring. Because our cohort consisted exclusively of patients referred to the EMU—who are more likely to be drug‐resistant—our findings may overestimate the frequency of FDSs in individuals with well‐controlled IGE. Females with IGE may be overrepresented in our study, possibly due to the restrictions on ASMs for childbearing women. Due to the retrospective design and referrals from multiple centers, we were unable to comprehensively track the FDSs onset and outcomes for all patients. Furthermore, our unstandardized, free‐text referral system prevented identification of patients initially referred with suspected FDSs who were not subsequently captured during video‐EEG monitoring, potentially affecting prevalence estimates. In the absence of a formal standardized classification of FDSs, we employed the Asadi‐Pooya proposal, which may overestimate subjective events without EEG correlates. Interpretation by the clinical neurophysiologist also introduces inherent subjectivity. Future prospective video‐EEG studies including people with focal epilepsy and developmental and epileptic encephalopathies are required to clarify the prevalence and characteristics of co‐occurring FDSs and to refine FDSs classification across epilepsy syndromes.
In conclusion, our study describes a notable co‐occurrence of FDSs in patients with IGE undergoing inpatient video‐EEG at a large tertiary epilepsy center. Approximately one quarter of IGE patients monitored had co‐occurring documented FDSs. Most patients had generalized interictal abnormalities during the first day of admission, and 45% had epileptic seizures during the admission. The semiology of FDSs is varied, including akinetic, subjective, motor, or mixed clinical features. Our series highlights the value of video‐EEG in this cohort, as gold standard for accurate diagnosis of both epileptic seizures and FDSs, as well as to guide the therapeutic management in IGE.
AUTHOR CONTRIBUTIONS
Javier Peña‐Ceballos designed the study, collected data, undertook and interpreted analyses, and drafted the manuscript. Kishen Radhakrishna collected data and drafted the manuscript. Clodagh O'Keeffe undertook, interpreted analysis, and reviewed the manuscript. Mohamed Ali, Tenzin Choekyi, and Alma O'Donnell collected data and reviewed the manuscript drafts. Tudor Munteanu, Patrick B. Moloney, Hany El Naggar, Gerard Mullins, Peter Widdess‐Walsh, Ronan D. Kilbride, and Norman Delanty supervised patient follow‐up and reviewed the manuscript drafts. Nuala McNicholas designed and led the study, contributed to methodology, and reviewed manuscript drafts.
CONFLICT OF INTEREST STATEMENT
J.P.‐C. has served as a speaker for and received travel expenses from Angelini Pharma, Jazz Pharmaceuticals, and LivaNova. Tenzin Choekyi has received travel expenses from Jazz Pharmaceuticals. T.M. has served as a speaker for and received travel expenses from Angelini Pharma. P.B.M. served as a speaker for and/or received travel expenses from Angelini Pharma, UCB Pharma, and Jazz Pharmaceuticals. Over the past 3 years, N.D. has served as a paid advisor and/or speaker for Actio Biosciences, Angelini Pharma, Eisai, LivaNova, Neuraxpharm, UNEEG Medical, and Jazz Pharmaceuticals. The rest of the authors declare no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Supporting information
Table S1. Clinical information and semiology of patients with idiopathic generalized epilepsy and co‐occurring functional/dissociative seizures during inpatient video‐electroencephalography admission.
Table S2. Clinical follow‐up at 1 year.
ACKNOWLEDGMENTS
We would like to thank the Clinical Neurophysiology and Nursing teams of the Epilepsy Monitoring Unit at Beaumont Hospital for their expertise and exceptional care of patients.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Clinical information and semiology of patients with idiopathic generalized epilepsy and co‐occurring functional/dissociative seizures during inpatient video‐electroencephalography admission.
Table S2. Clinical follow‐up at 1 year.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.