Epilepsy & Behavior 17 (2010) 228–235

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Epilepsy & Behavior

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When do psychogenic nonepileptic seizures occur on a video/EEG telemetry unit?

Ione O.C. Woollacott a,*, Catherine Scott b,c, David R. Fish b,c, Shelagh M. Smith b,c, Matthew C. Walker c

a Faculty of Medicine and Dentistry, University of Bristol, Bristol, UKb Department of Neurophysiology, National Hospital for Neurology and Neurosurgery, London, UKc Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK

a r t i c l e i n f o

Article history:Received 28 May 2009Revised 2 November 2009Accepted 1 December 2009Available online 4 January 2010

Keywords:Epileptic seizuresPsychogenic nonepileptic seizuresVideo/EEG monitoringEvent diagnosisAdmissions

1525-5050/$ - see front matter � 2009 Elsevier Inc. Adoi:10.1016/j.yebeh.2009.12.002

* Corresponding author. Address: Faculty of MedicinBristol, 69 St. Michael’s Hill, Bristol BS2 8DZ, UK.

E-mail addresses: iw4509@bristol.ac.uk, ioneocw@mwalker@ion.ucl.ac.uk (M.C. Walker).

a b s t r a c t

To maximize the efficiency of diagnostic video/EEG telemetry, we retrospectively studied the occurrenceof clinical events during admission in 254 patients. One hundred fifty-nine patients had psychogenic non-epileptic seizures (PNES) and 95 had epileptic seizures (ES). Twenty-five with PNES and none with ES hadan event before or during electrode placement (P < 0.0001). In the remaining 229, the initial eventoccurred within 48 hours of electrode placement in 98.5% patients with PNES and 100.0% of patients withES. Time to occurrence of initial event did not differ between groups (P = 0.69). 17.1% patients with PNESand 51.6% with ES had events between 12 AM and 6 AM (P = 0.001). In conclusion, during diagnosticvideo/EEG telemetry, most patients who experience PNES or ES have diagnostic, typical events within2 days. Although time to initial event after electrode placement does not differ between diagnoses, eventsprior to or during placement are most likely PNES and events at night are most likely ES.

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1. Introduction

A significant proportion of patients presenting to tertiaryspecialist neurological referral centers for investigation of seizuredisorders have psychogenic nonepileptic seizures (PNES), definedas ‘‘episodes of altered movement, sensation or experience similarto epilepsy, but caused by a psychological process and not associatedwith abnormal electrical discharges in the brain” [1]. Twenty-fourpercent of patients referred with ‘‘refractory epilepsy” have a diag-nosis of PNES [2], and 23% of patients with supposed ‘‘refractory sta-tus epilepticus” have pseudo-status [3]. A delayed diagnosis of PNESresults in uncertainty, poorer outcomes, unnecessary prescription ofantiepileptic drugs (AEDs) [4], and even unnecessary interventions,such as intubation in the case of prolonged events misdiagnosed asstatus epilepticus [1]. Currently, the average delay from onset ofPNES to correct diagnosis is 7 years [4], and the health and costimplications incurred during this delay are significant [5]; therefore,it is imperative that efforts are made to expedite a correct diagnosisin these patients. Despite a wealth of research into the typical clinicalfeatures of PNES, in many patients it is still difficult to determinefrom history alone whether they are experiencing PNES, epilepticseizures (ES), both, or some other organic or psychiatric paroxysmalevent. It is in these cases that admission to a videotelemetry unit for

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gmail.com (I.O.C. Woollacott),

diagnostic video/EEG telemetry is most useful; this investigation re-mains the gold standard for seizure disorder diagnosis [6].

Extensive research exists concerning the clinical features of sei-zures that may be used to differentiate between PNES and ES[1,5,6]. However, less research is available regarding the relevanceof the timing of events that occur during diagnostic video/EEGtelemetry. Several studies have examined the diagnostic yield ofand techniques used during outpatient video/EEG monitoring aim-ing to capture PNES or ES [7–9], but few have extended this analysisto inpatient admissions. The time to occurrence (TTO) of an initialtypical, diagnostic PNES or ES experienced by patients during inpa-tient video/EEG investigation has been examined in several studies[10–15], but only some of these have discussed how we might mod-ify admission protocols based on these observations [12–14]. Inaddition, the few studies examining whether the TTO of initial PNESonset differs from the TTO of initial ES onset have produced contra-dictory results [12,13].

Results from early studies suggested that an initial PNES or EStends to occur early on during admission. PNES are more frequentin the first 2 days of monitoring [11], and of 33 patients (16 withPNES and 17 with ES), 69% had their initial PNES and 29% their ini-tial ES within a 6-hour recording session [10]. Twenty percent ofpatients with PNES had an event within 60 minutes of initiatingrecording [15], and 37.5% of ES occurred within a 6-hour monitor-ing period [14]. However, these studies either included fewpatients with PNES [10,11,15] or analyzed presurgical rather thandiagnostic patients with epilepsy [14]. Two larger studies haveexamined the time to first event in patients with PNES or ESadmitted for diagnostic video/EEG telemetry [12,13]. Parra et al.

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found that 96.2% of patients with PNES had a spontaneous diagnos-tic event within 48 hours, and that the time to first event was sig-nificantly shorter for PNES than for ES [12], although this studyfocused more on whether induction techniques should be usedduring admission. In a more recent study, Lobello et al. found that88% of 162 patients who had an event during admission had theirfirst event within a similar time scale (2 days), but in contrast theyfound that there was no significant difference in the time to firstevent between PNES and ES [13]. Despite their merits, these andother studies have included patients on first and repeat admissionsin the same sample group, or have pooled data from patientsundergoing variable degrees of AED reduction, and most have ana-lyzed induced rather than spontaneous events during admission.As inconsistencies in number of admissions within patient groups,AED reduction schedules, and induction protocols may all affectoccurrence of events, this may have confounded past results.

We therefore undertook a retrospective study of patientsadmitted to a videotelemetry unit for diagnostic video/EEG telem-etry who experienced at least one typical, diagnostic PNES or ESduring their first admission without induction and, consistent withour policy for these admissions, did not undergo AED reductionprior to or during admission. We aimed to ascertain whether anypatterns in event occurrence might exist that could enhance theefficacy of current inpatient admission protocols, and whetherobservations of the timing of event occurrence might improve dif-ferentiation between PNES and ES in future patients admitted fordiagnostic telemetry.

2. Methods

2.1. Participants

Patients were retrospectively selected from the video/EEGtelemetry unit database at the National Hospital for Neurologyand Neurosurgery, London, UK, which contains medical recordsand video/EEG telemetry reports of all patients who have had vi-deo/EEG telemetry investigation on the unit from 1995 to date.This study was approved by the National Hospital for Neurologyand Neurosurgery and Institute of Neurology Joint Research EthicsCommittee as a retrospective audit. Most patients admitted fordiagnostic video/EEG telemetry have already had a negative rou-tine outpatient EEG, and patients may have one or more of a vari-ety of diagnoses, including paroxysmal sleep disorders, movementdisorders, epilepsy, and PNES. Patients are informed of the in-tended predetermined duration of their admission prior to arrivalat the unit and do not routinely undergo drug reduction prior toor during these admissions. First admissions for diagnostic telem-etry are usually for 2 days, but can vary according to the patientbased on preadmission event information such as event frequency.Repeat admissions are usually for 5 days, but again can vary basedon individual patient characteristics.

A search was performed for all patients who had a first admis-sion for diagnostic video/EEG telemetry between 31 December1999 and 21 July 2008; we excluded patients with known epilepsyadmitted for presurgical evaluation, as these cases have a con-firmed diagnosis and also undergo variable drug reduction. The pa-tient selection process is summarized in Fig. 1.

From a total of 1206 patients we excluded 372 patients whohad no event recorded during their first admission, to avoidincluding patients with varying numbers of admissions in oursample, which may have otherwise confounded results. Thesepatients included a wide variety of complex cases, most ofwhom were patients admitted for analysis of suspected sleepand movement disorders. Of the remaining 834 patients, weidentified 159 patients who had experienced at least one PNES

of a nature typical for that patient during admission, confirmedby clinical features typical of PNES with no EEG evidence of ictalepileptiform activity, and who had no prior history of confirmedES. From these, we excluded 25 patients because the initial eventoccurred prior to or during electrode placement, so there was noEEG confirmation for the event, meaning time to initial eventcould not be analyzed. The remaining 134 patients formed the‘‘PNES group.”

We also identified 95 consecutive patients who had experi-enced at least one ES (of a nature typical for that patient) duringtheir first ever diagnostic admission in the study period withoutthe use of induction techniques, had no previous diagnosis of PNES,and did not experience any PNES during admission. None of the pa-tients had undergone drug reduction prior to or during admission.These 95 patients formed the ‘‘ES group.” In addition, we identifieda separate subgroup of 8 patients who experienced both ES andPNES during their first admission. These patients may exhibit pat-terns of event occurrence different from those of patients with onlyPNES or ES, meriting analysis as a separate study group, but thesample size was too small to perform this analysis adequately, sothese 8 patients were excluded from our study.

2.2. Measures

For each patient, data were extracted from two sources:

1. Telemetry reports, which consist of written descriptions of thetimes, nature, and duration of events occurring during admis-sion transcribed from video evidence, and descriptions of inter-ictal and ictal brain activity and sleep states, interpreted fromEEG recordings.

2. Medical records in a computerized database, containing demo-graphic information about each patient admitted to the vide-otelemetry unit obtained from patients, family members, andphysicians involved in the patient’s care.

Data were collected for both groups focusing on the variableslisted in Table 1. Although our initial study aims did not encompassdetailed EEG analysis and comparison between groups, we noticedthat several patients with PNES had abnormal interictal EEGrecordings and, therefore, decided to collect data concerning thisvariable in all patients. TTO of initial event was measured in hours,minutes, and seconds (hh:mm:ss) from the moment of completescalp electrode placement, when concurrent video/EEG recordingcommenced. Total video/EEG recording duration (in hours) wasused to represent total admission duration.

All patients underwent a detailed history and neurological exam-ination prior to and on arrival for admission. Standard 10–20 elec-trode placement was used and two chest leads were used for ECGmonitoring. EEG and video were continuously recorded, and pa-tients or observing staff could press an event button to indicate thatan event was occurring. Induction (provocative) techniques such assaline injection were not used in either group. EEG was recorded in areferential montage and then reformatted for review. All video andEEG recordings were reviewed by an EEG technician, and all eventswere reviewed by one of the consultant physicians on the unit(D.R.F., S.M.S., or M.C.W.) as well as by the patient and a witness, suchas a family member, to confirm whether events were typical for thatpatient. When the diagnosis was uncertain, the events and EEGswere reviewed by at least two of the consultant physicians.

2.3. Statistics

Data were compiled and analyzed using Microsoft Excel 2007and GraphPad Prism 5.0. The PNES and ES groups were com-pared using two-tailed Mann–Whitney U tests for medians, as

Fig. 1. Flowchart demonstrating the patient selection process used to form the two study groups: psychogenic nonepileptic seizure (PNES) group (n = 134) and epilepticseizure (ES) group (n = 95). n = number of patients.

Table 1Variables for data extraction for each patient.

Admission and event information EEG findings

Total recording duration (hours) Abnormal or normal interictal EEG presentTime to occurrence of initial event following complete electrode placement (hours, minutes, and seconds) Type of abnormality on interictal EEGTime of day of each recorded event6 AM–12 PM12 PM–6 PM6 PM–12 AM12 AM–6 AMAverage duration of all events recorded during admission (minutes)Total number, type, and origin of events recorded during admission

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all variables were nonparametrically distributed. Fisher’s exactand v2 tests were used to compare proportions for the twogroups. For each test, an a value of P < 0.05 was used forsignificance.

3. Results

3.1. Patient characteristics

Demographics, AED data, and seizure types of patients in thetwo groups are summarized in Table 2. Patients were of similarages in both groups, but in the PNES group there were more fe-males (P = 0.0006) and fewer patients were taking AEDs (patientson at least one AED: PNES = 58.9% vs ES = 72.6%, P = 0.04). Themedian number of AEDs taken by patients with PNES was alsolower than in the ES group (PNES = 1 AED vs ES = 2 AEDs,P < 0.0001). The ES group included both patients with temporallobe epilepsy (n = 40) and patients with extratemporal epilepsy(n = 55); of the latter group 37 patients had seizures localized

to the frontal lobe. Patients had a variety of different seizuretypes, although complex partial seizures were the most commontype in both temporal and extratemporal subgroups.

3.2. Nature of admission and events

Most patients in both groups were admitted, recorded, andobserved for periods of approximately 2 days (Table 3), with pa-tients in the ES group having slightly shorter median totalrecording durations (representative of admission durations) thanthose in the PNES group (ES = 44.0 hours vs PNES = 45.0 hours,P = 0.03). However, total recording duration ranged widely, from3 to 100.5 hours for the PNES group and from 4.0 to 98.0 hoursfor the ES group. As shown in Table 3, patients in the ES groupexperienced more events overall during admission than patientsin the PNES group (ES = 3 vs PNES = 2, P = 0.001), although therange of total number of events was much wider for the PNESgroup (1–40 events) than for the ES group (1–24 events). Eventsrecorded during admission lasted longer for patients in the PNESgroup than for those in the ES group (median duration:

Table 2Demographics of patients in the two groups.

Variable PNES group (N = 134) ES group (N = 95)

Gender (n)Female 103 52Male 31 43

Age (years)Mean ± SEM 34.8 ± 1.1 37.4 ± 1.695% CI 32.7–36.9 34.1–40.6Median 33 34Range 17–69 17–72

Proportion (n) of patients taking P1 AED 58.9% (79) 72.6% (69)

Number of AEDs per patientMean ± SEM 1.4 ± 0.1 2.1 ± 0.195% CI 1.3–1.6 1.8–2.3Median 1 2Range 1–3 1–5

Predominant origin of seizures (n)Temporal lobe n/a 40Extratemporal 55Frontal lobe 37Extratemporal unlocalized 18

Seizure type (n) Temporal (extratemporal)Simple partial only n/a 14 (0)Complex partial only 23 (46)Simple partial and complex partial 2 (2)Secondarily generalized only 0 (6)Complex partial and secondarily generalized 1 (1)

Table 3Event occurrence during admission.

Variable PNES group (N = 134) ES group (N = 95) P

Total recording duration (hours)Mean ± SEM 44.8 ± 1.6 39.4 ± 1.7 0.03a

95% CI 41.6–48.1 36.0–42.7Median 45.0 44.0Range 3.0–100.5 4.0–98.0

Total number of events recorded during admissionMean ± SEM 3.4 ± 0.4 4.7 ± 0.5 <0.0001a

95% CI 2.6–4.2 4.1–5.9Median 2 3Range 1–40 1–24

Average duration of all events recorded during admission (minutes)Mean ± SEM 10.9 ± 1.1 1.2 ± 0.1 <0.0001a

95% CI 8.6–13.1 0.9–1.5Median 5.4 1.0Range 0.08–65.0 0.03–7.0

Time to occurrence of initial event after complete electrode placement (hours)Mean ± SEM 11.5 ± 1.1 10.8 ± 1.1 0.6995% CI 9.3–13.7 8.6–12.9Median 6.1 7.0Range 0.17–77.5 0.13–44.2

Proportion (n) of patients with initial event occurrence624 h after electrode placement 89.6% (120) 85.3% (81) 0.41648 h after electrode placement 98.5% (132) 100.0% (95) 0.51

Time frame of event occurrence (proportion of patients experiencing an event)6 AM–12 PM 55.2% 53.7% 0.001b

12 PM–6 PM 64.1% 55.8%6 PM–12 AM 41.8% 53.7%12 AM–6 AM 17.1% 51.6%

a Significant difference between PNES and ES groups at P < 0.05 using Mann–Whitney U test for medians.b Significant difference between PNES and ES groups at P < 0.05 for 12 AM–6 AM period only. For all other time periods, no significant difference between groups (P > 0.05).

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PNES = 5.4 minutes [range 5.0 seconds–65.0 minutes] vs ES = 1.0minutes [range 2.0 seconds–7.0 minutes], P < 0.0001).

3.3. Event occurrence

Of 159 patients diagnosed with PNES during their first admis-sion, we excluded 25 patients (15.7%) because their initial typi-

cal event occurred prior to or during electrode placement,hence insufficient concurrent video and EEG data were availableto confirm this event as a PNES. Twelve of these patients expe-rienced their first event prior to electrode placement, 10 duringelectrode placement, and 3 both prior to and during placement.Nevertheless, a diagnosis of PNES was made in all 25 patientsbased on further events during admission with clinical features

Fig. 3. Time to occurrence of first psychogenic nonepileptic seizure (PNES),measured as time in hours following complete electrode placement, plotted againstduration of first admission (total recording duration, in hours).

Fig. 4. Time to occurrence of first epileptic seizure (ES), measured as time in hoursfollowing complete electrode placement, plotted against duration of first admission(total recording duration, in hours).

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typical of PNES on video and no ictal or interictal epileptiformEEG activity. In comparison, all 95 patients diagnosed with ESduring their first admission experienced their initial event aftercomplete electrode placement, with none experiencing seizuresprior to full video/EEG recording (P < 0.0001).

In the remaining 229 patients, the TTO of initial event follow-ing complete electrode placement was similar in both groups(median TTO: PNES = 6.1 hours vs ES = 7.0 hours, P = 0.69) (Ta-ble 3). The majority of patients in both groups had experiencedtheir initial typical, diagnostic event within 24 hours of electrodeplacement (89.6% of patients in PNES group vs 85.3% of patientsin ES group, P = 0.41), independent of the duration of theiradmission (measured as total recording duration) and withoutthe use of induction techniques. The proportions of patientswho experienced their initial event within 48 hours of electrodeplacement were 98.5% for the PNES group and 100.0% for the ESgroup (P = 0.51). Fig. 2 illustrates the cumulative distribution ofTTO of initial event for both groups, demonstrating how only asmall proportion of patients in both groups experienced theirinitial event beyond 24 hours, and especially beyond 48 hours,after complete electrode placement. This is the case even for pa-tients with PNES for whom it was thought necessary to have aprolonged admission and extensive recording durations (60, 70,or even 100 hours), as shown in Fig. 3, and also for patients withES (Fig. 4).

Most patients in both groups had events during the period 12PM to 6 PM, with fewer patients experiencing events in all otherperiods (Table 3). For patients in the PNES group, there was a sig-nificant difference in event occurrence between the different peri-ods. In particular, these patients rarely experienced events duringthe night (12 AM–6 AM), but often had events during daytime peri-ods (e.g., 6 AM–12 PM and 6 PM–12 AM) (P < 0.0001). One patienthad one PNES, presumably with arousal, from stage II sleep,although this occurred between 6 PM and 12 AM. In contrast, pa-tients in the ES group often experienced ES at night and had a moreeven distribution of event occurrence across all periods duringadmission (P = 0.95 between periods), although the distributionof events across sleep states was not analyzed for these patients.When the two groups are compared with each other, significantlyfewer patients in the PNES group experienced events from 12 AMto 6 AM (17.1% of patients) than patients in the ES group (51.6% ofpatients) (P = 0.001), emphasizing the infrequency of PNES at night.For all other periods, the proportion of patients experiencing anevent did not significantly differ between the two groups(P > 0.05).

Fig. 2. Cumulative probability plots of time to occurrence (in hours, followingcomplete electrode placement) of first recorded event during admission, forpatients with epileptic seizures (ES) and for patients with psychogenic nonepilepticseizures (PNES).

3.4. EEG findings

Whereas all 95 patients in the ES group had an abnormal inter-ictal EEG recording during admission (with interictal epileptiformactivity on EEG evident in 100.0% of patients), 44 patients (32.8%)who experienced PNES had interictal EEG abnormalities, themajority of which were abnormal theta waves. Recorded interictalEEG abnormalities are summarized in Table 4, which also detailswhether they were recorded during the awake state, sleep state,or both, in each patient. In the PNES group, 3.7% (5 patients) dem-onstrated frank epileptiform activity on interictal EEG. However,these 5 patients had no known prior history of epilepsy, a historyof only one type of event (typical examples of which were recordedduring admission and confirmed to be PNES in all patients), noatypical events during admission, and no events during admissionwith concurrent ictal epileptiform activity on EEG.

4. Discussion

Here we have shown that the majority of patients who have atleast one PNES or ES during their first admission for diagnostic vi-deo/EEG telemetry will have their first typical event, sufficient fordiagnosis and without the use of induction techniques or drugreduction, within 48 hours of initiating full video/EEG recording.Although the TTO of an initial event following complete electrodeplacement does not significantly differ between patients with PNESand those with ES, and hence may not be useful in differentiatingclinically between these two diagnoses, events that occur prior toor during electrode placement are most likely to be PNES. Patientswith PNES were much less likely to experience events at night (be-tween 12 AM and 6 AM) than patients with ES, suggesting thatpatients with frequent events recorded within this period during

Table 4Interictal EEG abnormalities recorded in patients with PNES.

Interictal EEG abnormality Awake state only Sleep state only Awake and sleep states

Theta alone 9 1 —Theta and sharp waves — 1 6Theta and delta 2 1 3Theta and slow waves 1 — —Nonspecific sharp waves alone 1 3 3Nonspecific slow waves alone 1 — 2Slow and sharp waves 1 1 2Encephalopathic — — 1Epileptiform — 2 3

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admission are more likely to have ES (or, perhaps, some other par-oxysmal disorder) than PNES. In addition, a significant proportionof patients with PNES had interictal EEG abnormalities.

Our first aim for this study was to examine the occurrence ofdiagnostic events in patients with PNES or ES during their firstadmission to our videotelemetry unit, to investigate whether wemight enhance the efficacy of future admission protocols. In partic-ular, we aimed to improve on previous studies by analyzing pa-tients without variable degrees of AED reduction and byincluding only patients on their first admission, rather than com-bining patients with different numbers of admissions in the samegroup. From our study of 229 patients on their first admission,none of whom underwent AED reduction prior to or during admis-sion, we found that the majority of patients in our PNES group(89.6%) and ES group (85.3%) experienced their initial, clinicallytypical, diagnostic seizure without the use of induction techniqueswithin 24 hours of electrode placement. These figures rose to 98.5%(PNES group) and 100.0% (ES group) within 48 hours irrespective ofthe total recording duration: even in cases where patients wereadmitted for long periods (e.g., 100 hours), most had their firstPNES or ES within 48 hours. This would suggest, therefore, thatour observations of time to first event are not an artifact of re-stricted admission durations.

Our observations are consistent with corresponding figuresfrom two previous studies, which employed variable AED with-drawal schedules and analyzed groups containing patients on bothfirst and repeat admissions [12,13]. These studies reported that96.2% of patients experience their initial PNES within 48 hours ofadmission [12], and that 87.7% of patients experience either a PNESor ES within the first 2 days of video/EEG monitoring [13]. A recentstudy has also shown that long-term diagnostic video/EEG moni-toring of an average duration of 2.4 days was useful in obtaininga diagnosis in 44% of patients with various paroxysmal events,although diagnostic, classification, and presurgical cases were allincluded [16]. From their observations, Lobello et al. concludedthat there is a low diagnostic yield beyond 2 days of inpatient vi-deo/EEG monitoring in the majority of patients with PNES andthose with epilepsy [13], and our results also provide some evi-dence that 48 hours may be an appropriate duration for firstadmissions for diagnostic video/EEG telemetry, in select patientswith negative outpatient EEGs, where uncertainty remains con-cerning a diagnosis of PNES versus ES.

We do not, however, suggest that limiting first admissions fordiagnostic video/EEG telemetry to 48 hours is appropriate for allpatients, as several limitations of our study precluded completeanalysis of all types of patients admitted to the unit. First, we didnot study patients with ES and concurrent PNES or patients withsleep or movement disorders: for these and for other patients witha range of different event types, longer admission durations may benecessary to capture all various typical events and exclude otherdiagnoses. It is also imperative that all events captured duringrecording are confirmed as typical for the patient by an appropriate

witness (as was the case in our study), in case recording ceaseswithout recording any of the patient’s typical events, or capturesatypical events, and hence fails to reveal another coexisting diag-nosis or leads to misdiagnosis.

Another limitation is that we did not examine the TTO of initialevent of 372 patients on repeat admissions, who failed to have anevent on their first admission (30.8% of all those admitted duringthe study period). This means that a significant proportion of pa-tients did not have an event during their first admission. Of these372 patients, 187 were not readmitted, so their final diagnosis re-mained unclear and 71 had at least one repeat admission, of whom19 went on to be diagnosed with PNES, 13 with ES, and 39 with an-other diagnosis such as a sleep or movement disorder. We did notexplore why these patients did not have an event or if these pa-tients have characteristics different from those of patients in ourstudy. Because of these limitations we cannot predict whetherand which patients will have an event during their first admissionor comment on the sensitivity of this investigation for the diagno-sis of PNES. Indeed, some patients (particularly those with infre-quent events) will be unlikely to or will fail to have typicalevents during admissions of 48 hours or longer. In their study of199 patients undergoing inpatient video/EEG monitoring for amedian of 3 days, Lobello et al. noted that patients who did haveES were more likely to have an abnormal baseline EEG than thosewithout ES or other events during admission, and that patientswho did have PNES were more likely to be female and have a focalneurological deficit than those without PNES or other events dur-ing admission [13]. However, the likelihood of having an eventduring admission depends on many individual patient factors,including preadmission event frequency, event triggers, degree ofdrug reduction, and use of induction protocols, which must all betaken into account for patients during preadmission assessment,so that first or repeat admissions can be tailored accordingly.

Prolonged outpatient video/EEG monitoring has been proposedas an alternative to inpatient monitoring for patients requiringbehavioral event characterization, and several studies have foundthis procedure, with or without suggestion or induction tech-niques, to be clinically effective for making diagnoses[8,9,13,17,18]. Outpatient monitoring durations evaluated foreffectiveness have ranged from 40–50 minutes, which captureddiagnostic events in 50.3% of patients [8], to 1–2 hours, which cap-tured diagnostic events in 80% [17], and allowed a diagnosis ofPNES in 66% of patients (although 69% of patients underwentinduction) [9], to 1–5 days, which captured events in 73% of pa-tients [18]. As well as appearing clinically efficacious in the diagno-sis of PNES and ES, outpatient video/EEG may also obviate the needfor inpatient monitoring for some patients [8], which in itselfwould be financially advantageous, would reduce the burden andwaiting times for inpatient monitoring, and overall may expediteaccurate diagnosis, which has been shown to improve outcomesin some patients [19]. However, not yet certain are what the opti-mal duration for prolonged outpatient video/EEG monitoring is and

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for which patients this investigation is most suitable. Proposedsuitable candidates for outpatient rather than inpatient monitoringinclude patients with frequent events, one rather than severalevent types, clear event triggers, who are amenable to the use ofsuggestion or induction techniques, and who can undergo this pro-cedure at centers with ‘‘appropriate clinical and electrophysiolog-ical expertise” [8]. Those who fail to have events during thisprocedure or who are otherwise unsuitable for outpatient monitor-ing are more suitable for inpatient diagnostic video/EEG monitor-ing such as that undertaken in our unit.

Our second aim was to investigate whether observations of thetiming of event occurrence during inpatient admissions for diag-nostic video/EEG telemetry might improve clinical differentiationbetween PNES and ES in future patients admitted for this investi-gation. The significant difference in recorded event duration be-tween PNES (median = 5.4 minutes) and ES (median = 1.0minute) in our study suggests that events that last longer than 5minutes during admission are more likely to be PNES than ES. Thisis consistent with findings from previous studies examining bothreported and recorded event durations [13,20,21], supporting thenotion that event duration may be useful in differentiating be-tween these two disorders. However, we were also interested inwhether the time to initial event during admission is clinically use-ful in this regard. We observed a median time to first PNES of 6.1hours (mean = 11.5 hours ± 1.1 SEM) and a median time to firstES of 7.0 hours (mean = 10.8 hours ± 1.1 SEM). These values areshorter than those in a study on patients undergoing presurgicalvideo/EEG monitoring, where the mean time to first ES was 25.7hours [14], and shorter than those found by Parra et al., wherethe mean time to first diagnostic event was 15.0 hours for PNESand 28.6 hours for ES [12], and by Lobello et al., where the mediantime to first event was 1.0 day (mean = 1.6 days) [13]. However,the TTO of initial event in both of the groups in our study rangedwidely: initial PNES occurred from only 10.2 minutes to just over3 days (77.5 hours) after electrode placement, and initial ES oc-curred from only 7.8 minutes to just under 2 days (44.2 hours)after electrode placement. This variety illustrates that each patienthas an individual pattern of event occurrence, but despite this westill found that the majority of events occurred within 2 days. Wefound no significant difference (P = 0.69) between TTO of an initialES and TTO of an initial PNES, consistent with Lobello et al. [13],but not with Parra et al., who observed that the average TTO ofan initial ES was almost twice as long as that for the initial PNES[12]. These differences may perhaps be explained by different pa-tient populations and differing use of AED withdrawal or inductionprotocols, but it nevertheless emphasizes that the TTO of an initialevent appears to be an unreliable diagnostic tool.

We excluded 25 patients from the PNES group (15.7% of all 159patients who had PNES during their first admission) who experi-enced their initial PNES either before or during electrode placement.This phenomenon was not observed for any of the 95 patients in theES group. Another study of 196 patients during long-term video/EEGmonitoring [22] found that patients with PNES were much morelikely to have an event without video evidence supporting EEGrecording (‘‘off camera”) than those with ES. Patients with PNESmay be more likely to have events in the absence of full video/EEGmonitoring for several reasons. Previous research has indicated thatpatients with PNES are often highly responsive to suggestion tech-niques [7], and indeed, the buildup to or performance of the EEG pro-cedure itself may have an element of suggestion, which couldprovoke events in these patients [9]. Inpatient monitoring may alsolead to high levels of anxiety in some patients, which may provokeevents either during periods of extremely close observation (whilein direct interaction with a health professional such as during elec-trode placement) or during periods of relief from direct observation,such as when ‘‘off camera” or when electrodes are disconnected. The

reasons behind these phenomena may be particular to each patient,but this tendency for PNES to occur without full video/EEG recordingor prior to or during electrode placement during admission may beuseful as a diagnostic indicator.

Although nocturnal events and events occurring during sleepwere traditionally thought to be associated with epilepsy or sleepdisorders rather than PNES, several studies have documented thatPNES can arise both during ‘‘pseudo-sleep” (where the patient ap-pears asleep but has an EEG consistent with wakefulness) [23,24]and from actual sleep states [25] during admission. Moreover, thereis a poor correlation between a history of events occurring duringsleep given during outpatient assessment and a diagnosis of epilepsyrather than PNES [23]. Past research has tended to focus on circadianrather than diurnal patterns in event occurrence in patients withPNES or ES within the clinical history and during admission to a vide-otelemetry unit. However, time of day of event occurrence may berecorded more easily and interpreted more objectively by both pa-tients and physicians than circadian patterns of events, particularlycompared with events arising ‘‘from sleep,” in both outpatient andinpatient settings. We therefore examined the time of day of eventoccurrence in patients with PNES or ES admitted for diagnostic vi-deo/EEG telemetry to determine if any diurnal patterns existed thatmight allow easier differentiation between these two diagnoses. Amuch smaller proportion of patients with PNES (17.1%) had eventsduring nighttime (12 AM–6 AM) than patients with ES (51.6%). PNESand ES tended to occur most often from 12 PM to 6 PM, but similarproportions of patients from both groups had events during thisand all other periods (apart from 12 AM–6 AM). Although we didnot intend to focus on whether events arose from sleep versus awakestates in this study, it was noted that one patient with PNES had anevent arising from stage II sleep between 6 PM and 12 AM. A previousstudy of 1116 events in 188 patients also observed that only a smallproportion (6%) of PNES occurred during the 12 AM–6 AM period,whereas 20% of complex partial seizures and 26% of frontal lobe com-plex partial seizures occurred during this period, although in thatstudy PNES never arose from sleep [26]. Another study of presurgicalpatients observed that most (37.5%) ES occurred between 12 AM and6 AM during video/EEG monitoring, although only 20% of seizuresactually arose from sleep during this period [14]. These results sug-gest that during admission for diagnostic video/EEG telemetry, pa-tients with events occurring between 12 AM and 6 AM are morelikely to have epilepsy than PNES; hence time of day of event occur-rence may be useful as a diagnostic differentiator in the inpatientsetting. It may also prove useful and interesting if patients were torecord this parameter routinely prior to outpatient appointmentsand were then followed up with video/EEG investigation, to confirmdiagnosis if necessary. It could then be established whether a historyof events occurring during this ‘‘nighttime” period is a more reliablediagnostic indicator of epilepsy than a history of events actually‘‘arising from sleep,” in the outpatient setting.

We found incidentally that a large proportion (32.8%) of pa-tients with PNES had abnormalities on interictal EEG, most com-monly theta activity (17.9%) or nonspecific sharp waves (13.4%).Abnormal theta activity occurred most often in the awake (non-drowsy) state, whereas nonspecific sharp waves occurred usuallyonly during sleep or during both awake and sleep states. Frank epi-leptiform abnormalities were also seen in 3.7% (5 patients) withPNES only, either while asleep (2 patients) or both when awakeand asleep (3 patients). Several studies have examined interictalEEG abnormalities in patients with PNES, and interictal EEG abnor-malities, including theta activity and sharp transients [27] andeven benign ‘‘epileptiform” spikes following sleep deprivation[28], have also been observed during sleep in healthy controls.Reuber et al. found that 53.8% of 130 patients with PNES aloneand 10.0% of 50 healthy controls had nonspecific interictal EEGabnormalities (theta or delta waves), but 12.8% of patients with

I.O.C. Woollacott et al. / Epilepsy & Behavior 17 (2010) 228–235 235

PNES and 2.0% of controls had frank epileptiform abnormalities[29]. In a more recent study, 11.4% of 44 patients with PNES exhib-ited interictal theta activity during drowsiness and sleep and inter-ictal sharp transients during sleep [25]. Figures differ betweenstudies and from those in our study, perhaps because of variationsin definitions of EEG abnormalities and differing inclusion andexclusion criteria. Benbadis and Tatum found that 32% of patientswith PNES had been described as having an ‘‘epileptiform” outpa-tient EEG, but when 15 of these were reviewed by the authors,none of the abnormalities were truly epileptiform [30]; they there-fore warn against the tendency to ‘‘overread” EEGs in such pa-tients, and our figures may represent a more cautious approachto EEG interpretation. Despite several studies of the prevalence ofinterictal abnormalities in patients with PNES, the precise physio-logical mechanisms and implications of these abnormalities in pa-tients with PNES remain uncertain. However, these resultsemphasize that interictal EEG abnormalities may occur in a signif-icant proportion of patients with PNES alone, and therefore, EEGsmust be interpreted with care to avoid over- or misdiagnosis ofepilepsy.

In conclusion, our study has extended past research on PNESand ES occurring during inpatient diagnostic video/EEG telemetryby making several findings pertinent to both admission protocolsand the clinical diagnosis of PNES versus epilepsy. In addition,we have improved on previous studies in these areas by focusingonly on patients without AED reduction and those presenting forthe first time for this investigation, thereby reducing the confound-ing effect of factors such as number of admissions and variable de-grees of drug reduction on event occurrence. Our observations ofboth event occurrence during admission and admission durationssubstantiate the unreliability of using the time to first event fol-lowing complete electrode placement for clinical differentiationbetween PNES and ES, and corroborate suggestions of the low diag-nostic yield of inpatient admissions for diagnostic video/EEGtelemetry beyond 2 days of monitoring. However, we maintainthat some patients may require longer or repeat admissions to cap-ture typical events and exclude other diagnoses, and we emphasizethat caution must be employed when interpreting EEGs in patientswith paroxysmal events, to avoid ‘‘overreading” of interictal abnor-malities and misdiagnosis of epilepsy, particularly in patients withPNES. We also provide evidence, to our knowledge for the firsttime, that events occurring prior to or during electrode placementare significantly more likely to be PNES than ES and that diurnalpatterns of event occurrence during admission may be useful indifferentiating between PNES and ES in some patients. We hopethat the results of this study, together with future research, willcontribute toward enabling better and more prompt diagnosis ofPNES and ES and will ultimately improve the outcome of patientsin both the inpatient and outpatient settings.

Ethical approval

We confirm that we have read the Journal’s position on issuesinvolved in ethical publication and affirm that this report is consis-tent with these guidelines.

Conflict of interest statement

We state that there are no conflicts of interest.

Acknowledgments

We thank Dr. Samden Lhatoo, Consultant Neurologist, FrenchayHospital, Bristol, for his comments on this study.

This work was undertaken at UCLH/UCL, which receives a pro-portion of funding from the Department of Health’s NIHR Biomed-ical Research Centres funding scheme.

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