Epilepsy & Behavior 19 (2010) 32–35

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Epilepsy & Behavior

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Latency to first psychogenic nonepileptic seizure upon admission to inpatient EEGmonitoring: Evidence for semiological differences

Margaret W. Perrin a, Sanjiv K. Sahoo a, Howard P. Goodkin a,b,⁎a Department of Neurology, University of Virginia Healthsystem, Charlottesville, VA, USAb Department of Pediatrics, University of Virginia Healthsystem, Charlottesville, VA, USA

⁎ Corresponding author. PO Box 800394, Charlottesvil982 1726.

E-mail address: Hpg9v@virginia.edu (H.P. Goodkin).

1525-5050/$ – see front matter © 2010 Elsevier Inc. Aldoi:10.1016/j.yebeh.2010.06.006

a b s t r a c t

a r t i c l e i n f o

Article history:Received 8 April 2010Received in revised form 4 June 2010Accepted 5 June 2010Available online 2 August 2010

Keywords:Epilepsy monitoring unitPsychogenic nonepileptic seizureSeizure latencySeizure semiologyVideo/EEG monitoring

Two hundred sixteen consecutive patients diagnosed with psychogenic nonepileptic seizures (PNES)admitted to the epilepsy monitoring unit at our institution over a 4.5-year period were retrospectivelyidentified. PNES were classified into four semiological subcategories: major motor (n=123), minor motor(n=38), akinetic (n=32), and subjective/experiential (n=23). The median latency to first PNES for theentire population was 7 hours (range: b1 to 207 hours), confirming previous observations that the latency tofirst PNES on admission is often b24 hours. The novel observation is that latency to first PNES was dependenton type. The median latency to first PNES was significantly prolonged in both the minor motor(median=21 hours) and subjective/experiential (median=22 hours) groups as compared with the majormotor (median=5 hours) and akinetic (median=4 hours) groups. Thus, patients with one of these twosubtypes may require longer admissions to capture the event of interest and confirm the diagnosis.

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1. Introduction

Psychogenic nonepileptic seizures (PNES) are sudden alterationsin behavior that are the result of a psychological process and not anepileptic mechanism [1,2]. The clinical manifestations of these eventscan range from violent, thrashing behaviors to trembling to staringand immobility to experiential complaints. As these behaviors overlapthose associated with epileptic seizures, it is often necessary to admitpatients with PNES to an inpatient video/EEG monitoring unit (EMU)for diagnostic evaluation. It is important to differentiate PNES fromepilepsy as the treatment varies between these two medicalconditions.

It has previously been demonstrated that the latency to the firstspontaneous PNES following admission to an EMU is typically lessthan 24 hours [3,4]. However, according to a recent report, aproportion of first spontaneous PNES occur after 72 hours ofmonitoring [5]. These prior studies grouped all patients with PNESinto a single group. The effect of PNES semiology on latency was notinvestigated. The purpose of this study was to determine if latency tofirst PNES during an admission to an EMU varies by semiology.

2. Methods

This retrospective review was approved by the University ofVirginia's institutional review board.

2.1. Patient selection

All patients, older than 18 years of age (n=645), admitted to theF.E. Dreifuss EMU at the University of Virginia over a 4.5-year periodwere retrospectively placed into the following categories based onreview of the daily EMU reports and discharge summaries: epilepticseizures (n=338), PNES (n=216), physiological nonepilepticevents (e.g., myoclonus, tremor, transient ischemic attack, restlessleg syndrome, and migraine headache; n=26), and nondiagnosticadmission (n=65). The epileptic seizure group includes 41 patientswho had events that could not definitely be differentiated fromsimple partial seizures during the admission. In all cases of PNES, theEMU report specifically stated that the event occurred in the absenceof an ictal or postictal EEG change.

The 216 patients who had at least one unprovoked PNES (patientswith PNES) and the 65 patients with nondiagnostic admissions formthe basis of this report.

2.2. PNES semiological classification

The daily EMU reports of the 216 patients with PNES werereviewed to characterize the semiological presentation. These reportswere prepared after complete review of continuous simultaneousvideo and EEG data obtained digitally (Grass-Telefactor, AstroMed,Inc) by neurologists with additional fellowship training in epilepsywith board certification in clinical neurophysiology (American Boardof Psychiatry and Neurology), electroencephalography (AmericanBoard of Electroencephalography), or both.

Table 2

33M.W. Perrin et al. / Epilepsy & Behavior 19 (2010) 32–35

During monitoring, electrodes were placed according to the 10–20International Electrode System. Sphenoidal electrodes were not used;however, T1 and T2 electrodes were placed.

Patients were observed continuously by a monitor attendant whoreported all suspicious clinical and electrographic events. In addition,the patient, patient's family/friends, and nurses were able to markevents of interest for review.

We classified the PNESs into four subcategories: major motor,minormotor, akinetic, and subjective/experiential.Major motor events(Gröppel cluster 1) [6] were those described as consisting of at leastone of the following positive motor symptoms in the presence orabsence of an altered state of consciousness: thrashing, flailing, pelvicthrusting, nonrhythmic jerking of the extremities, head nodding orhead turning side to side, or bicycling movements.Minor motor events(Gröppel clusters 2 and 3) [6] were those described as consisting ofeither a fall, change in posture, trembling, or automatisms (small-amplitude movements of the face or upper extremities) in the settingof altered consciousness. Akinetic events [7] were those described as abehavioral arrest evolving to staring and unresponsiveness. The finalcategory, subjective/experiential events, were those described asconsisting of an alteration of cognition or awareness associated witha patient's report of a sensory (e.g., dysesthesia, visual hallucination)or emotional (e.g., claustrophobia) experience [8,9].

Latency to the first PNES was calculated as the number of hoursfrom the start time of the recording to the time of PNES onset.Population latencies are presented as Kaplan–Meier survival curves interms of the probability of not having had a PNES versus duration ofmonitoring.

2.3. Statistics

The specific statistical tests used are noted under Results.Statistical significance was accepted at the Pb0.05 level.

3. Results

3.1. Patient demographics

Patient demographics are summarized in Table 1.The cohort of 216 patients with PNES includes 23 (11%) patients

who had a diagnosis of epilepsy at the time of admission. Thediagnosis had been previously confirmed in 8 of these patients viavideo/EEG monitoring. One had a temporal lobectomy for left mesialtemporal lobe epilepsy 3 years prior to admission. These patientswere admitted for characterization of paroxysmal attacks that wererefractory to changes in antiepileptic medications.

Table 1Demographics of PNES and nondiagnostic admission groups.

PNES Nondiagnostic

(n=216) (n=65)

AgeMedian (range) 37 (18–80) 40 (18–78)Mean±SD 37±12.5 42±14

SexMale 56 (26%) 22 (35%)Female 103 (74%) 43 (65%)

Latency, hoursMedian (range) 7(b1–207) —

Mean±SD 15.8±23

Number of eventsMedian (range) 3(1–40) —

Diagnosis of epilepsy at time of admission 23 (11%) 22 (35%)

There were 15 patients with a clinical diagnosis of epilepsy thathad not been confirmed by video/EEG monitoring prior to thisadmission. Nine of these patients were being treated with antiepi-leptic medications at the time of admission. Six were admitted forcharacterization of paroxysmal attacks that differed in semiology fromthe habitual event onwhich the clinical diagnosis of epilepsy had beenmade. Three were admitted for characterization of their habitualevents, which proved to be psychogenic and not epileptic in etiology.The remaining six patients had distant diagnoses of epilepsy thatresolved during childhood.

The nondiagnostic admission group was included in our calcula-tion of PNES latency as the eventual diagnosis of PNES cannot beexcluded in this patient population. Compared with those who had aPNES, individuals in the nondiagnostic admission group were morelikely to have had a diagnosis of epilepsy at the time of admission(Pb0.05, χ2). Although there were trends to more males (PN0.05, χ2)and older age (PN0.05, Kolmogorov–Smirnov (KS) test) within thenondiagnostic admission group, neither of these variables reachedstatistical significance.

3.2. Semiological classification

For these 216 patients, the captured events were categorized aseither major motor (n=123, 57%), minor motor (n=38, 17%),akinetic (n=32, 15%), or subjective/experiential (n=23, 11%). Theage and gender distribution were similar across groups (PN0.05, χ2)(Table 2).

3.3. Latency to first event

The median latency for the entire patient population was 7 hours(Fig. 1). In total, 16% (46/281) had their first event within the firsthour of admission, 61% (171/281) had their first PNES within24 hours, and 71% (199/281) had their first PNES within 48 hours.The longest latency to an unprovoked PNES was 207 hours.

Linear regression analysis was performed using age, gender, andPNES semiology as independent variables in a model with PNESlatency as the dependent variable. Only PNES semiology (Pb0.001)had a significant effect on latency.

Kaplan–Meier survival curves for PNES latency grouped by PNESsemiological classification are illustrated in Fig. 2. The survival curvefor the major motor group is repeated in each graph for comparison.The median and mean latencies to first event for each group are listedin Table 2. The median latency to PNES was prolonged in the minor

Patient demographics of the PNES semiology subcategories.

Major motor Minor motor Akinetic Subjective/experiential

(n=123) (n=38) (n=32) (n=23)

AgeMedian(range)

37(18–80) 31 (19–67) 34(18–67) 37(18–60)

Mean±SD 38±13 35±13 36±10 38±12

SexMale 31 (25%) 12 (29%) 4 (12%) 7 (30%)Female 92 (75%) 27 (71%) 28 (88%) 16 (70%)

Latency, hoursMedian(range)

5(b1–65) 21(b1–105)a 4 (b1–67) 22 (b1–207)a

Mean±SD 10±13 27±29 13±19 28±43

Number of eventsMedian(range)

3(1–40) 3 (1–29) 3 (1–12) 2 (1–17)

a Pb0.05.

Fig. 1. Kaplan–Meier survival curve of latency to first psychogenic nonepileptic seizuresfollowing start of video/EEG recording for all patients independent of semiological type.

34 M.W. Perrin et al. / Epilepsy & Behavior 19 (2010) 32–35

motor (21 hours) and subjective/experiential (22 hours) groups ascompared with the major motor (5 hours) and akinetic (4 hours)groups (Newman–Keuls, Pb0.05).

Between 48 and 72 hours, 12 initial events were captured (5% of thePNES total): 4 were major motor (3% of total major motor), 4 wereminor motor (10% of total minor motor), 4 were akinetic (12.5% ofakinetic), and 0 were sensory/experiential. After 72 hours, 6 additionalinitial events were captured (2.5% of the PNES total): 4 were in theminor motor group (10% of total minor motor) and 2 in the subjective/experiential group (9% of total subjective/experiential). None of theevents after 72 hours were major motor or akinetic.

4. Discussion

In this study, we confirmed the previous finding [3–5] that thelatency to first unprovoked PNES is relatively short, with themajority ofevents occurringwithin 48 hours. Thenovelfindingwas that the latencyto first event varied with PNES semiology. In this study, the latency toevents classified as either minor motor or subjective/experiential wassignificantly longer than the latency to either major motor or akineticevents.

As Parra and colleagues [3] observed 96.2% of PNES by 48 hours ofmonitoring and no events after 58 hours, they recommended thatinduction protocols bewithheld until after 48 hours of recording. In ourcohort, 5% of the total initial PNES occurred after the 48-hour point and2.5% occurred after 72 hours. In a recent study [5], 25% of PNES occurredon the third day or afterward, and 8% of patients did not have their firstevent until day 7 or later. Semiological classificationwasnot provided ineither of these prior studies. Although our findings support therecommendation for induction protocols at 48 hours in the case of

Fig. 2. Kaplan–Meier survival curves of latency to first psychogenic nonepileptic seizure follcurve for the major motor group is repeated in each graph for comparison. *Pb0.05.

majormotor and akinetic PNES at those centers that choose to use theseprocedures [10,11], our findings suggest that an additional day or moreof monitoring should be considered if the event of interest is consistentwith a minor motor or subjective/experiential event based on theoperational definitions used in this report.

Recent fMRI studies have begun to elucidate those brain regionsthat are activated during conversion disorders [12,13]. However, thepsychopathogenesis of PNES has not yet been elucidated and thebiological significance of our findings of semiology-dependent latencyto first PNES is uncertain at this time. Prior studies investigatingsemiological variation have demonstrated semiological differences inpsychiatric predisposition [14–16] and outcome [17,18]. The presenceof semiological dependence in these variables suggests the possibilitythat different mechanisms underlie the semiological differences inPNES.

Future studies investigating the mechanisms of PNES wouldbenefit from an accurate classification scheme. However, there is, ofyet, no official classification scheme for PNES, and the classification ofPNES has varied by report [6,7,16,17,19–21]. At a minimum, theseschemes have differentiated PNES dominated by major motoractivities such as thrashing, wild head movements, and pelvicthrusting from other PNES. Gröppel et al. [6] used a cluster analysistechnique based on only 28 patients to devise a classification schemethat divided PNES into three groups. However, their system is limitedby the absence of akinetic events and subjective/experiential events,which represent approximately 25% of the events observed in thisstudy and have been frequently observed in other studies of PNES[e.g., 7, 21].

This study had several limitations. The format was a retrospectivechart review and semiological classification was dependent on thedescription available in the EMU reports and discharge summaries.Additional analysis to determine if there were differences inpsychiatric comorbidities or previous trauma could not be pursuedbased on the limited data available in the medical record. Further-more, limited follow-up data were available for both the PNES groupand the nondiagnostic group. We suspect that among the nondiag-nostic group are a large number of patients with epilepsy who did nothappen to have an epileptic seizure during their admission, as well aspeople who may be potentially malingering. Additional prospectivestudies are warranted to better characterize the group of patients whohave nondiagnostic admissions to EMUs.

In summary, this study demonstrated that a large proportion ofpatients with PNES will have their first event within 48 hours ofinpatient video/EEG monitoring, with many occurring within the first24 hours. In general, although 2 days of monitoring are required formost patients, those patients with minor motor or subjective/experiential PNES may require longer admissions to capture theevent of interest and confirm the diagnosis. What is not known is

owing start of video/EEG recording, grouped by semiological classification. The survival

35M.W. Perrin et al. / Epilepsy & Behavior 19 (2010) 32–35

whether these variable clinical presentations are related to differ-ences in the underlying mechanism. Further studies are warranted todetermine not only the correlation of neurological and psychiatriccomorbidites with outcome, but also to begin to elucidate theneuropathogenesis of PNES.

Conflict of interest statement

H.P.G. receives funding from the NIH for projects unrelated to thiswork. He has received a consulting fee from MedIummune, Inc, in thelast 3 years.

Acknowledgments

We thank Dr. Matthew Gurka for his statistical assistance and Dr.Allan Krumholz and Dr. Donna Broshek for their very careful readingof this article and insightful comments.

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