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Can semiology predict psychogenic nonepileptic seizures a prospective study.

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Can Semiology Predict Psychogenic
Nonepileptic Seizures? A Prospective
Tanvir U. Syed, MD, MPH,1 W. Curt LaFrance, Jr., MD, MPH,2,3 Emine S. Kahriman, MD,1
Saba N. Hasan, MD,1 Vijayalakshmi Rajasekaran, MD,4 Deepak Gulati, MD,1
Samip Borad, MD,5 Asim Shahid, MD,1 Guadalupe Fernandez-Baca, MD,1
Naiara Garcia, MD,1 Matthias Pawlowski, MD,6 Tobias Loddenkemper, MD,7
Shahram Amina, MD,1 and Mohamad Z. Koubeissi, MD1
Objective: Reducing health and economic burdens from diagnostic delay of psychogenic nonepileptic seizures
(PNES) requires prompt referral for video electroencephalography (VEEG) monitoring, the diagnostic gold standard.
Practitioners make VEEG referrals when semiology suggests PNES, although few semiological signs are supported by
well-designed studies, and most VEEG studies neglect to concurrently measure how accurately seizure witnesses can
ascertain semiology. In this study, we estimate the value of eyewitness-reported and video-documented semiology
for predicting PNES, and we measure accuracy of eyewitness reports.
Methods: We prospectively interviewed eyewitnesses of seizures in patients referred for VEEG monitoring, to inquire
about 48 putative PNES and ES signs. Multiple, EEG-blinded, epileptologists independently evaluated seizure videos
and documented the presence/absence of signs. We used generalized estimating equations to identify reliable
video-documented PNES and ES signs, and we compared eyewitness reports with video findings to assess how
accurately signs are reported. We used logistic regression to determine whether eyewitness reports could predict
VEEG-ascertained seizure type.
Results: We analyzed 120 seizures (36 PNES, 84 ES) from 35 consecutive subjects. Of 45 video-documented signs,
only 3 PNES signs (‘‘preserved awareness,’’ ‘‘eye flutter,’’ and ‘‘bystanders can intensify or alleviate’’) and 3 ES signs
(‘‘abrupt onset,’’ ‘‘eye-opening/widening,’’ and postictal ‘‘confusion/sleep’’) were significant and reliable indicators of
seizure type. Eyewitness reports of these 6 signs were inaccurate and not statistically different from guessing.
Consequentially, eyewitness reports of signs did not predict VEEG-ascertained diagnosis. We validated our findings
in a second, prospective cohort of 36 consecutive subjects.
Interpretation: We identified 6 semiological signs that reliably distinguish PNES and ES, and found that eyewitness
reports of these signs are unreliable. We offer suggestions to improve the accuracy of eyewitness reports.
ANN NEUROL 2011;69:997–1004
sychogenic nonepileptic seizures (PNES) are commonly mistaken for epilepsy (ES), resulting in diagnostic delay for 7 to 10 years,1 on average, and imposing
health and economic burdens at individual and population levels. Misdiagnosed PNES patients are unnecessarily
prescribed multiple high-dose antiepileptic medications
(AEDs) with potential for adverse effects and teratogenicity, and patients with prolonged attacks are needlessly in-
tubated for pharmacological sedation.2,3 Early diagnosis
of PNES can lower out-of-pocket and systemwide costs
by reducing the need for emergency room visits, hospitalizations, repeated diagnostic testing, and AEDs.4
Reducing diagnostic delay requires early referral for
prolonged video electroencephalography (VEEG) monitoring, the standard-of-care5 and the accepted gold
standard for diagnosing PNES.6 Limitations of VEEG
View this article online at DOI: 10.1002/ana.22345
Received Sep 12, 2010, and in revised form Nov , 2010. Accepted for publication Nov 22, 2010.
Address correspondence to Dr Syed, Lakeside 3200, 11100 Euclid Ave., Cleveland, OH 44106. E-mail:
From the 1Epilepsy Center, Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH; Departments of 2Neurology and
Comprehensive Epilepsy Program, and 3Psychiatry and Human Behavior, Rhode Island Hospital, Brown Medical School, Providence, RI; 4Department of
Neurology, West Virginia University, Morgantown, WV; 5Department of Neurology, Virginia Commonwealth University Health System, Richmond, VA;
Department of Neurology, University of Münster, Münster, Germany; 7Children’s Hospital Boston, Harvard Medical School, Boston, MA.
C 2011 American Neurological Association
of Neurology
include that it is expensive and is not readily available at
many centers. Practitioners refer patients when clues
obtained during history-taking raise the index of suspicion for PNES. Among these clues are a plethora of
semiological signs (eg, pelvic thrusting) that have been
suggested to distinguish PNES from ES1,7; however,
most semiological signs lack evidence-based support of
their association with PNES.8,9 Only a minority of
VEEG studies that measure association between videodocumented semiology and PNES concurrently investigate whether seizure witnesses can accurately recall the
presence or absence of specific semiological signs, prior
to VEEG.10
In this study, we prospectively assess whether eyewitness reports of seizure semiology can predict PNES,
prior to VEEG. Additionally, we use blinded, independent, epileptologist multirater review of seizure videos to
ascertain which video-documented semiological signs distinguish PNES and ES. Finally, we compare seizure witness testimonies with seizure video findings to investigate
how accurately seizure witnesses report semiology during
Patients and Methods
subjects (or caregivers) and participating seizure witnesses provided verbal and written informed consent prior to
For study purposes, we evaluated subjects’ AMU records and
prepared video clips of VEEG-recorded PNES or ES. Video
clips began 1 minute prior to seizure onset and ended 5
minutes after seizure offset, as marked by the treating epileptologist during AMU stay. If subjects had more than 5 recorded
seizures during AMU stay, we prepared video clips of the 5 longest seizures, and for subjects with more than 1 seizure phenotype we prepared at least 1 video clip of each phenotype. Based
on systematic review of PNES literature published before January 2009, we listed 48 semiological signs (Fig 1) reported to
potentially distinguish PNES and ES. Two additional epileptologists, blinded to diagnosis and EEG tracings, independently
reviewed the seizure videos, and for each seizure, documented
presence or absence of the listed semiological signs. Blinded
epileptologists documented signs as ‘‘unknown’’ if presence or
absence was unclear in seizure videos. If the 2 blinded epileptologists disagreed about a sign in a seizure video, a third blinded
epileptologist reviewed the video and broke the tie. As part of
clinical routine, AMU nurses examined subjects during and after seizures according to a written protocol that assesses levelof-awareness, memory, receptive and expressive language, and
motor function.
Beginning October 2009 we prospectively enrolled consecutive
seizure patients scheduled for inpatient VEEG monitoring in
the adult epilepsy monitoring unit (AMU) at University Hospitals Case Medical Center, an academic institution. Study enrollment was limited to patients having VEEG-recorded PNES or
ES during AMU stay, confirmed (by history) to represent their
habitual events. For this study, we used VEEG-based diagnosis
as the gold standard against which diagnostic yield of individual
semiological signs would be measured. Specifically, consistent
with clinical convention we classified VEEG-recorded events
during AMU stay as ES if the treating epileptologist documented the presence of an ictal epileptiform correlate on electroencephalogram (EEG) tracings. We classified remaining (ie,
EEG-negative) VEEG-recorded events as PNES if semiology
and EEG/electrocardiogram (ECG) findings could not be
explained by physiologic etiologies (eg, syncope, migraine, and
positional vertigo). We excluded EEG-negative sensory events
(eg, tingling, numbness) since normal scalp EEG tracings may
not have definitively ruled out subtle epileptiform activity in
these cases.11 Consequentially, we excluded EEG-confirmed epileptic auras, to prevent bias from overrepresenting isolated
sensory events as epileptic. Post hoc, we recruited 2 additional
epileptologists to assess interrater reliability of VEEG interpretation in our study, and to estimate the degree to which epileptologist classification of EEG findings in our study depended
on information gathered from seizure videos (refer to Supporting Information for methodological details). The university
institutional review board approved the study, and all enrolled
Eyewitness Interview
After conferring with subjects and their family members or
caregivers, we selected for each subject an adult ‘‘seizure witness’’
who could best describe the semiology of the subject’s seizures.
We conducted structured face-to-face or phone interviews with
seizure witnesses just prior to subjects’ AMU admission to
inquire about occurrence of the listed semiological signs during
any recently observed seizures that they understood to be the
basis for AMU referral. Interviews took place in a private area
away from subjects, and interviewers were physicians with specialty training in epilepsy who attempted to describe semiological signs in language that seizure witnesses could understand.
Interviewers asked seizure witnesses to respond ‘‘present,’’
‘‘absent,’’ or ‘‘don’t know’’ for each semiological sign.
Statistical Analysis
priori criteria to identify video-documented semiological signs
that are clinically and statistically significant for distinguishing
PNES and ES. First, to demonstrate scientific plausibility and
consistency with prior studies, signs must occur more frequently
in their postulated seizure type (defined in the literature; eg,
pelvic thrusting in PNES, eye-opening in ES) than in the alternate seizure type. We used VEEG records and blinded video
documentation of the listed semiological signs to assess frequency of each sign in its postulated seizure type, and we
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FIGURE 1: Flow diagram summarizing analytic procedure to identify ‘‘best’’ video-recorded semiological signs for distinguishing PNES and ES. ES signs are in italics. Circled numerals represent sequential quantitative criteria (see Patients and Methods).
*’’Resistance-to-eye-opening’’ was not tested in 111 (93%) seizures (was not part of AMU clinical protocol), and ‘‘foaming-atthe-mouth’’ and PI Todd’s paralysis never occurred in recorded seizures. yBlinded epileptologists were not able to definitively
ascertain or exclude postictal ‘‘aphasia’’ in 64 (53%) seizure videos. zPI ‘‘confusion’’ and PI ‘‘sleep’’ were analyzed as a single
sign because they are postulated ES signs that cannot co-occur in a seizure. ‘‘Others can influence’’ indicates that actions or
words of bystanders intensify or alleviate seizure. ES 5 epileptic seizure; GEE 5 generalized estimating equations; PI 5 postictal; PNES 5 psychogenic nonepileptic seizures.
calculated sensitivity and specificity at seizure-level for each sign
as an identifier of its postulated seizure type. Second, we
assigned a standard that a sign’s sensitivity or specificity to
postulated seizure type must be at least 80% at subject-level, to
hypothetically be able to rule in or rule out a given seizure type
with at least 80% probability in a population. The second criterion we set also requires that sensitivity and specificity are at
least 50% (ie, chance value), to exclude signs with spuriously
high values from overoccurrence or underoccurrence in the
sample. To assess this criterion, we performed a second calculation of sensitivity and specificity for each semiological sign
using only 1 ‘‘representative’’ seizure per subject, defined as the
subject’s seizure exhibiting the most video-documented semiological signs. Finally, the sign must be statistically significantly
(p < 0.05) associated with its postulated seizure type. We
obtained p values through generalized estimating equations
(GEE)12 that approximate the relative likelihood of PNES
when each semiological sign is present. In seizure-level analysis,
GEE generates more valid p values than traditional methods
(eg, logistic regression) because it protects against inflated statistical strength that results from analyzing multiple seizures in
the same individual as if they were independent.10,13
REPORT SEMIOLOGY?. To estimate how accurately seizure witnesses report semiological signs during history-taking,
we compared seizure witness reports (‘‘present,’’ ‘‘absent,’’ ‘‘don’t
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know’’) of each sign with video-documented presence/absence
of that sign in AMU-recorded seizures. We defined a seizurewitness’s affirmative report of a sign as correct if that sign was
present in at least 1 seizure video of the related subject. We calculated sensitivity and specificity using traditional formulas
(Sens ¼ true-positive [TP]/Videoþ, Spec ¼ true-negative
[TN]/Video), so that values of ‘‘don’t know’’ cells factor into
the denominators of sensitivity and specificity calculations (ie,
Videoþ ¼ TP þ false-negative [FN] þ don’t know
[DK]|Videoþ; Video ¼ TN þ false-positive [FP] þ
DK|Video). We used univariate logistic regression to test statistical significance of associations between eyewitness reports
and video-documented findings. In regression models, we coded
eyewitness reports as 1 for ‘‘present,’’ 0 for ‘‘don’t know,’’ and
1 for ‘‘absent,’’ to indicate that ‘‘present’’ and ‘‘absent’’
responses provide equal and opposite information, whereas
‘‘don’t know’’ response adds no information.
PREDICT DIAGNOSIS?. To assess whether seizure witness
reports of semiological signs can predict diagnosis of PNES (or
ES), we compared seizure witness reports (‘‘present,’’ ‘‘absent,’’
‘‘don’t know’’) of each sign with presence of VEEG-recorded
PNES (or ES, depending on semiological sign) during AMU
stay. Just as in calculation of eyewitness report accuracy (see
above), we determined sensitivity and specificity using traditional formulas to account for values in ‘‘don’t know’’ cells. We
of Neurology
FIGURE 2: Subject-level sensitivity and specificity of video-documented signs for identification of PNES. Values are derived
from original cohort, except for the 4 PNES signs that were tested in the validation cohort. *p < 0.05 according to seizure-level
analysis (generalized estimating equations) in original and validation cohorts. PNES 5 psychogenic nonepileptic seizures; Sens
5 sensitivity; Spec 5 specificity.
used univariate logistic regression to test statistical significance
of eyewitness reports as predictors of PNES. We estimated
34 total subjects necessary to be able to assess with 80%
power and 0.05 probability of Type I error whether eyewitness reports of a semiological sign could correctly diagnose
seizure type at the subject-level in at least 80% of subjects
(equivalent to diagnosis-weighted average of sensitivity and
All statistical analyses were performed using Stata 11.0
(Statacorp, College Station, TX).
FIGURE 3: Subject-level sensitivity and specificity of video-documented signs for identification of ES. Values are derived from
original cohort, except for the 4 ES signs that were tested in the validation cohort. *p < 0.05 according to seizure-level analysis
(generalized estimating equations) in original and validation cohorts. ES 5 epileptic seizure; Sens 5 sensitivity; Spec 5
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From October to December 2009, 48 patients were
admitted to the AMU and were offered participation in
the study. Four patients with ES did not consent (3 encephalopathic without accompanying caregiver, 1 declined
participation), 1 patient with ES could not identify a seizure witness, 7 consenting patients did not have habitual
seizures during their AMU stay, and 1 patient’s events
were related to cardiac arrhythmia, leaving 35 enrolled
subjects with 120 VEEG-recorded seizures for analysis in
this study. Thirty-six PNES were recorded from 12 subjects, and 84 ES (2 primary-generalized, 18 secondarygeneralized) were recorded from the remaining 23 subjects. Three subjects with PNES had interictal epileptiform activity on EEG tracings during AMU stay (2 with
corresponding cortical lesions on brain magnetic resonance imaging [MRI]); however, we included these subjects in the PNES group because they did not exhibit
frank ES during AMU stay, and their clinical history
indicated recent-onset seizures of distinct semiology as
the reason for AMU admission. There were no subjects
with concurrently recorded PNES and ES during AMU
stay. The kappa statistic for interrater reliability of VEEG
diagnosis was 0.94 (95% confidence interval [CI], 0.77–
1.00) at subject-level, indicating ‘‘excellent’’ agreement,14
and epileptologist VEEG-classification depended on information gathered from seizure videos in 2.9% (1) of
subjects. PNES and ES subjects were similar in age
(PNES: median, 39; range, 19–55 years; ES: median, 36;
range, 19–65 years; p ¼ 0.84, Mann-Whitney test), but
a higher percentage of PNES subjects were women
(PNES, 83%; ES, 48%; p ¼ 0.04, chi-square), and median disease duration was longer in ES subjects (PNES:
11 years; interquartile range [IQR], 0.2–17; ES: 16 years,
IQR, 0.5–30; p ¼ 0.03, Mann-Whitney test).
Based on quality of VEEG recordings and periictal
examination of subjects, blinded reviewers were able to
assess 44 out of the 48 listed semiological signs in at least
90% (108) of seizure video clips (Supporting Table 1).
Interrater agreement between the 2 initial video reviewers
was high (kappa > 0.87) for all signs except postictal
‘‘aphasia’’ (kappa ¼ 0.58) and ‘‘postictal muscle-soreness’’
(kappa ¼ 0.57). There was no significant difference (p ¼
0.23, Mann-Whitney test) in number of seizures analyzed from PNES (median, 3; range, 1–5) vs ES (median, 4; range, 1–5) subjects.
Which Video-Documented Semiological Signs
Distinguish PNES from ES?
Figure 1 shows a flow-diagram that illustrates how the 48
listed semiological signs were ‘‘filtered’’ through sequential
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application of our 3 quantitative criteria in order to identify video-documented signs that ‘‘best’’ distinguish PNES
and ES. Supporting Table 1 (seizure-level), Fig 2, Fig 3,
and Supporting Table 2 (subject-level) show sensitivity and
specificity estimates of individual video-documented
semiological signs for prediction of diagnosis. Out of the
48 listed semiological signs, 4 PNES signs and 4 ES signs
satisfied our 3 criteria in the 35-subject cohort.
Post hoc, we assessed reliability of our findings by
reevaluating these 8 video-documented signs in a second
cohort of 36 consecutive subjects admitted to the AMU
between March and May 2010 (47 admissions; 2 without
consent, 9 undiagnosed; 37 PNES from 20 subjects, 28
ES from 16 subjects). Analysis of the second cohort
(Supporting Table 3) confirmed results for 6 of the 8
signs (see Figs 1 and 4).
How Accurately Do Seizure Witnesses Report
Supporting Table 2 (report accuracy) shows results of
eyewitness report analyses. Most (93%) seizure witnesses
were first-degree relatives or roommates of subjects, who
reported having witnessed a median 18 (IQR, 8–100) of
the related subject’s seizures. More than 80% of seizure
witnesses responded ‘‘yes’’ or ‘‘no’’ to 44 (92%) semiological signs, whereas ‘‘don’t know’’ responses were highest
(26–37%) for ‘‘starts-in-1-limb,’’ ‘‘hand automatisms,’’
‘‘unilateral head-turning,’’ and postictal ‘‘aphasia.’’ Signs
were incorrectly reported by seizure witnesses in 6% to
79% of subjects, and 14 (30%) signs were incorrectly
reported in more than one-half of subjects. Eyewitnesses
most accurately ( >80% correct) reported ictal ‘‘crying/
weeping,’’ ‘‘screaming,’’ ‘‘forced-eye-closure,’’ ‘‘eyes-rolledinto-back-of-head,’’ ‘‘looking-around,’’ and postictal
‘‘vomiting.’’ Notably, the 6 video-documented semiological signs that best distinguished PNES and ES (see
above) were reported incorrectly in 37% to 62% of subjects (see Fig 4, ‘‘WA’’), and reports of these 6 signs were
not significant in logistic regression.
Can Seizure Witness Reports of Semiology Predict Diagnosis?
Eyewitness reports of individual PNES signs predicted diagnosis correctly in 35% to 71% of subjects, whereas
reports of ES signs predicted diagnosis correctly in 32%
to 65% of subjects (Supporting Table 2, ‘‘report dx’’).
None of the eyewitness reports of individual signs
attained significance for predicting diagnosis. Eyewitness
reports of the 6 ‘‘significant’’ video-documented signs (see
above) were nonsensitive and nonspecific predictors of
diagnosis (see Fig 4, ‘‘WD’’).
of Neurology
FIGURE 4: Six most reliable video-documented signs for identification of seizure-type during VEEG. (A) PNES signs. (B) ES
signs. Values derived from subject-level analysis of original cohort (n 5 35). To illustrate, ‘‘abrupt-onset’’ sensitivity estimates
(VID 96, WA 57, WD 48) indicate that ‘‘abrupt-onset’’ was present on video in 96% of ES subjects, was reported ‘‘present’’ by
eyewitnesses in 57% of subjects whose seizure videos exhibited ‘‘abrupt onset’’, and eyewitnesses’ reports of ‘‘abrupt onset’’
correctly identified 48% of ES subjects. ‘‘Preserved awareness’’ is defined as any meaningful communication (verbal or charades) with bystanders, or recall of events during seizure. ES 5 epileptic seizures; PNES 5 psychogenic nonepileptic seizures;
Sn 5 sensitivity; Sp 5 specificity; VEEG 5 video electroencephalography; VID 5 ‘‘video-documented sign’’ vs seizure-type; WA
5 ‘‘eyewitness-report of sign’’ vs ‘‘presence of sign on video’’; WD 5 ‘‘eyewitness-report of sign’’ vs ‘‘VEEG-ascertained seizure-type.’’
We prospectively measured sensitivity and specificity of
45 video-documented semiological signs for distinguishing PNES and ES, and we identified 6 signs that best
differentiated the 2 seizure types during VEEG (see
Fig 4). We found that several ‘‘putative’’ PNES signs and
ES signs8,9 were actually nonsensitive or nonspecific, and
not significantly associated with seizure type (see Fig 1).
Compared to prior VEEG studies of PNES semiology,8,9
we used multiple, independent, EEG-blinded epileptologist video reviewers to assess a large number of signs in a
single cohort, we validated our significant findings in a
second prospective cohort, and we applied quantitative
methods designed to protect against overestimation of
statistical significance that results from analyzing multiple
seizures in a given subject as if they were independent.
In VEEG interpretation, seizure semiology complements EEG data, and may occasionally help expose an
‘‘elusive’’ epileptogenic focus when ictal scalp EEG tracings appear normal (eg, mesial frontal lobe epilepsy).15
However, for reducing diagnostic delay of PNES, the
value of seizure semiology lies in history-taking during
the first outpatient visits, where practitioners can inquire
about PNES early in the course of disease by asking eyewitnesses of patients’ seizures to confirm presence or absence of PNES-specific signs. This implies that semiology
can help reduce diagnostic delay of PNES only to the
extent that eyewitnesses can recall whether or not seizurespecific signs have actually occurred in patients’ seizures.
In this study, we prospectively compared eyewitness
reports with seizure video findings and found that seizure
witnesses were unable to accurately report presence or absence of those video-recorded semiological signs that
were strongly associated with seizure-type (see Fig 4).
These findings explain our final result that eyewitness
reports of seizure semiology, obtained prior to VEEG,
did not accurately predict VEEG-ascertained seizure type.
Our results confirm findings of prior studies10,16
that seizure witnesses provide unreliable accounts of seizure semiology. Our findings suggest (see Fig 4, ‘‘WD’’)
that most seizure witnesses mistakenly ruled out ‘‘preserved-awareness’’ and ‘‘others-can-intensify-or-alleviate’’
(specificity > sensitivity), overreported ‘‘eye-opening/widening’’ and postictal ‘‘confusion/sleep’’ (sensitivity > specificity), and were unaware of rapidity-of-onset and ‘‘eyeflutter’’ (low sensitivity and specificity). We recommend
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Syed et al: Semiology Nonepileptic Seizures
that practitioners ask patients’ family members to carefully observe seizure-onset and patients’ eyes during seizures, as simply knowing ‘‘what to look for’’ may increase
report accuracy. Practitioners may consider instructing
family members how to assess level-of-awareness during
and after a seizure, through verbal commands (eg, such
as ‘‘show me 2 fingers’’) or charades, not unlike the public health strategy of Face-Arms-Speech-Time (F.A.S.T.)
for assessment of stroke symptoms.17 Practitioners should
urge eyewitnesses to interact with patients during subsequent seizures to see if, in fact, seizures consistently intensify or subside in response to other people. Finally, acquisition of home video recordings of seizures may lessen
the need to rely on eyewitness reports, and should be
Sample size could not account for lack of statistical
significance (Type II error) in our study unless a sign’s
true sensitivity and specificity were each below 80%,
which we defined a priori as our threshold for clinical
significance. Type I error (chance findings) is also
unlikely because we validated our statistically significant
findings in a second cohort. Nevertheless, future research
should assess validity of the 6 significant signs in larger,
diverse populations. Even though generalized-onset epilepsy was underrepresented in our sample, 21% of ES
seizures exhibited secondary generalization, and we expect
signs that distinguished PNES and ES in our study to
apply to generalized-onset seizures as much as they
applied to the generalized portion of secondarily generalized focal-onset seizures in our study. Our results on eyewitness reports do not apply to patients whose seizures
are unwitnessed, although these patients are less likely to
have PNES.18 We excluded children from our sample
and recommend that pediatric and adult PNES be studied separately, because of differences in disease spectrum
between these 2 age groups.19 Recall bias (or ‘‘suggestion’’), an inherent limitation of interview-based data collection,20 did not likely have a major impact in our
study, as we would have found most eyewitness reports
to be nonspecific and highly sensitive, which was not the
case. Because PNES has no known definitive biomarker,21
VEEG is the accepted diagnostic ‘‘gold’’ standard, and
PNES semiology studies that do not employ VEEG as a
standard are themselves considered substandard.8,9 However, 2 theoretical concerns of using VEEG as the diagnostic ‘‘gold’’ standard in semiology studies are that VEEG is
not without error,6 and may not be entirely independent
of semiology, as its interpretation may partially rely on information gathered from seizure videos. Nevertheless,
interrater reliability of VEEG-diagnosis was high (0.94) in
our study, reflecting a narrow margin of error in seizure
classification,6 and our post hoc assessments indicated that
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interdependence of VEEG diagnosis and seizure videos
was minimal (2.9%) and, thus, had negligible impact on
sensitivity and specificity estimates of individual semiological signs.
In summary, we prospectively identified signs that
distinguish PNES and ES during VEEG, but found
that unreliable eyewitness accounts of semiology can
impede prediction of PNES during history-taking, prior
to VEEG. Practitioners should encourage patients’ family members to play a proactive role in ascertaining seizure semiology, with the goal of recognizing PNES early
in its course and hastening VEEG referral to prevent
misdiagnosis. It is not surprising that only few semiological signs are individually sensitive and specific indicators of PNES or ES, as in clinical practice even
informed specialists contextualize multiple signs to
hypothesize seizure etiology. Relative paucity of sensitive
signs in our study attests to heterogeneity of seizure
phenotypes, in general, with higher degree of variation
in psychogenic disorders. Future research may look into
constellations of semiological signs to predict seizuretype, or investigate effectiveness of patient and practitioner educational material for reducing diagnostic delay
of PNES.
Potential Conflicts of Interest
T.U.S. serves on speakers bureaus for Pfizer, UCB Pharma,
and Boehringer-Ingelheim pharmaceuticals. W.C.L. gave
expert testimony for Healthcare Litigation Support;
receives editor’s royalties for Nonepileptic Seizures, 3rd
ed, Cambridge University Press, 2010; and has grants/
grants pending for research funding from NINDS,
American Epilepsy Society, and Epilepsy Foundation for
treatments of NES. T.L. has been employed by Children’s
Hospital Boston, Neurology Foundation; has grants/
pending grants from American Epilepsy Society, Harvard
Medical School (Harvard Faculty Development Fellowship), and Eisai, Inc.; may own medical stocks within
retirement funds; has been a board member for the
ABRET Long-Term Monitoring Accreditation Board.
None of the other authors have anything to report.
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