Epilepsy & Behavior 75 (2017) 143–145

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Epilepsy & Behavior

journal homepage: www.elsevier.com/locate/yebeh

Delay in diagnosis of psychogenic nonepileptic seizures in adults:

A post hoc study☆
Ali A. Asadi-Pooya a,b,⁎, Jennifer Tinker a
a
Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA
b
Neurosciences Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: The aim of the current post hoc study was to investigate factors associated with delay in diagnosis of
Received 19 May 2017 adult patients with psychogenic nonepileptic seizures (PNES).
Revised 13 July 2017 Methods: We retrospectively investigated all patients with PNES admitted to the epilepsy-monitoring unit at the
Accepted 2 August 2017 Jefferson Comprehensive Epilepsy Center from 2012 through 2016. We identified the median time to diagnosis of
Available online xxxx
PNES and divided the patients into two groups. We studied factors associated with delay in diagnosis of PNES.
Results: In all, 49 patients (39 women and 10 men) were studied. Mean age at the time of admission was 40 ±
Keywords:
Delay
16 years and at the onset of the seizures was 34 ± 16 years. Disease duration was 5.6 ± 8.2 years. The median
Diagnosis for time to diagnosis was 3 years. Patients with early diagnosis (before 3 years after seizure onset) (21 patients)
Epilepsy and patients with late diagnosis (delay of 3 years or more from onset) (28 patients) were compared. Only history
PNES of head trauma had significant association with the delay in diagnosis: 2 of 19 patients (7%) with an early diag-
Psychogenic nosis and 11 of 28 patients (39%) with a late diagnosis reported head trauma (P = 0.02).
Video-EEG Conclusion: Delay in diagnosis of PNES is common, and some factors (e.g., history of head trauma) may contribute
to this delay. It is important that physicians involved in the management of seizures appreciate the importance of
making an early and definitive diagnosis of PNES.
© 2017 Elsevier Inc. All rights reserved.

1. Introduction
Psychogenic nonepileptic seizures (PNES) are relatively common
occurrences in epilepsy centers [1]. Although PNES are the most com-
mon and important differential diagnoses of epilepsy, misdiagnosis
and delay in diagnosis are common. Symptoms in PNES often overlap
with other conditions and may be attributed to more than one condition
in a single patient, or different physicians may offer different diagnoses
to the same patient. As a result, patients with PNES are at risk of iatro-
genic harm, as they are more likely to receive unnecessary treatments
(e.g., antiepileptic drugs) and even hospital admissions [2–4]. Early
and definitive diagnosis of PNES has prognostic significance with regard
to outcome because it can lead to appropriate therapy [1,5].
A few prior studies investigated factors that preclude early diag-
nosis of PNES, and these studies reported conflicting results [3,6,7].
Identifying factors that delay diagnosis may have significant clinical
implications in formulating appropriate management plans. The aim
☆ The authors conducted the statistical analyses.
⁎ Corresponding author at: Department of Neurology, 901 Walnut Street, Suite 435,
Philadelphia, PA 19107, United States.
E-mail addresses: aliasadipooya@yahoo.com (A.A. Asadi-Pooya),
jennifer.tinker@jefferson.edu (J. Tinker).
of the current post hoc study was to investigate factors potentially asso-
ciated with delay in diagnosis of adult patients with PNES.
2. Patients and methods
The original data from which the current post hoc analyses were
derived were published previously [8]. We retrospectively investigated
all patients with PNES admitted to the epilepsy monitoring unit at the
Jefferson Comprehensive Epilepsy Center from 2012 through 2016.
Patients included in this study had a confirmed diagnosis of PNES de-
termined by clinical assessment and long-term video-EEG monitoring
with ictal recording of their spontaneous seizures. We excluded pa-
tients with comorbid epilepsy, abnormal EEG, or insufficient data. We
excluded the patients with abnormal EEG to make sure that none of
the patients included in the study had epilepsy despite the fact that
some patients with PNES may have abnormal EEG (e.g., as a genetic
trait) without having epilepsy. We extracted all of the relevant clinical
and demographic data from their medical records. We classified the
seizures into four distinct classes: (1) generalized motor, (2) akinetic,
(3) subjective symptoms (e.g., pain, sensory phenomena, nausea,
and vague feelings that might have made the impression of having
epileptic seizures), and (4) focal motor seizures. All studied patients
were administered psychological self-report inventories (i.e., Beck
Depression Inventory and Beck Anxiety Inventory), as well as questions

http://dx.doi.org/10.1016/j.yebeh.2017.08.005
1525-5050/© 2017 Elsevier Inc. All rights reserved.
144 A.A. Asadi-Pooya, J. Tinker / Epilepsy & Behavior 75 (2017) 143–145

Table 1 having major depression, behavioral impulsivity, and posttraumatic

Demographic and clinical variables among patients with PNES with regard to delay in stress disorder [9]. Traumatic brain injury often presents with a
diagnosis.
constellation of symptoms that are common to the general population,
Factor Patients with Patients with P value and misattribution of symptoms is common. Given the risk of posttrau-
early diagnosis late diagnosis matic epilepsy following brain injury, misdiagnosis due to physician
(21 patients) (28 patients)
bias and misattribution of symptoms by patients may complicate
Gender (female:male) 16:5 23:5 0.7 new-onset presentation of PNES. These factors may explain the
Age (years) 37 ± 18 42 ± 14 0.2
delay in diagnosis of patients with PNES who had history of TBI, but
Age at onset (years) 36 ± 18 33 ± 14 0.5
Number of seizure classes 7:14 14:14 0.3 further exploration of the interaction between PNES and TBI would be
(1 seizure class:more classes) enlightening.
History of head traumaa 2 11 0.02 Other studies have also investigated factors potentially associated
Family history of seizuresa 6 11 0.2 with a delay in diagnosis of PNES. A prior study of 53 children with
History of substance abuse 4 4 0.7
History of alcohol abuse 1 1 0.4
PNES [3] found that earlier age at seizure onset and a history of psycho-
History of physical abuse 6 11 0.5 logical abuse were associated with delayed diagnosis. Other factors
History of sex abuse 5 12 0.2 (e.g., sexual abuse, physical abuse, gender, PNES semiology, family
Full scale IQ 97 ± 18 90 ± 17 0.2 history of epilepsy, EEG abnormalities, and presence and type of psychi-
Beck Anxiety Inventory 18 ± 12 20 ± 13 0.6
atric disorders) had no correlation with a delay in diagnosis of PNES. In
Beck Depression Inventory 15 ± 13 17 ± 10 0.6
another study, the number of antiepileptic drugs (AEDs) tried was asso-
a
Two patients had missing data. ciated with a longer delay until diagnosis [10]. In one study [7], delay to
diagnosis was studied in 313 patients with PNES. On average, patients
were diagnosed 7.2 ± 9.3 years after seizure onset. Longer delays
were associated with younger age, interictal epileptiform abnormalities
about some of the known risk factors for PNES, including a history of in the EEG, and anticonvulsant treatment. Other patient factors (e.g., sex
sexual abuse or physical abuse, a history of head trauma, and a family and semiology of seizures) were not associated with the delay to
history of seizures during their admission. We identified the median diagnosis. The authors concluded that physician factors contributed to
time for delay in diagnosis of PNES and divided the patients into two delays in diagnosis of PNES [7]. In our study, age was not associated
groups accordingly. We studied factors potentially associated with with a delay in diagnosis. We cannot comment on the association of
delay in diagnosis of PNES using Pearson Chi-Square and t-test. P values interictal epileptiform abnormalities in the EEG and AED treatment
less than 0.05 were considered significant. The Thomas Jefferson with the delay in diagnosis of PNES, as in this post hoc study we could
University Institutional Review Board approved this retrospective not investigate these factors. However, we had the same observation
record review and study. that most patients' factors were not associated with a delay in diagnosis
of PNES, and we agree that physician factors probably play a major role
3. Results in this phenomenon.
Our study had some limitations. This was a retrospective post hoc
Forty-nine patients (39 women and 10 men) were studied. Mean study, and patient data came from a single institution. The patients en-
age of the patients was 40 ± 16 years. Mean age at the onset of the rolled in this study may not be representative of all patients with PNES.
seizures was 34 ± 16 years, and the disease duration before diagnosis These results cannot be applied or extended to PNES with epilepsy be-
was 5.6 ± 8.2 years (minimum: b 1 week; maximum: 40 years). The cause patients with epilepsy were not included in this study. The sample
mean length of long-term video-EEG monitoring was 4 ± 2.2 days size was limited. Finally, we did not investigate other possible risk
(minimum: 1 day; maximum: 9 days). The median for time to diagnosis factors for PNES (other than sexual abuse, physical abuse, history of
was 3 years (5 patients were diagnosed at year 3). Therefore, we divided head trauma, and family history of seizures) or delay in its diagnosis
the patients into two groups: patients with early diagnosis, defined as (e.g., EEG abnormalities and AED use) in this study.
within 3 years after seizure onset (21 patients), and patients with late Delay in diagnosis of PNES is common, and some factors (e.g., history
diagnosis, defined as 3 years or more after seizure onset (28 patients). of head trauma) may contribute to this delay. This could have significant
Table 1 shows the demographic and clinical variables among these clinical (e.g., unnecessary interventions and treatment) and social
two groups of patients. Only history of any head trauma (minor or (e.g., stigma, costs, and utilization of resources) implications [1]. Consid-
major) had significant association with the delay in diagnosis; 2 of ering the relatively high prevalence of PNES in neurology clinics, it is im-
19 (7%) patients with an early diagnosis and 11 of 28 (39%) patients portant that physicians involved in the diagnosis and management of
with a late diagnosis reported history of head trauma (P = 0.02) seizures appreciate the importance of making an early and definitive
(2 patients had missing data). No other demographic or clinical factors diagnosis of PNES. Continued medical education may increase the
were significantly associated with delay in diagnosis of PNES in these awareness among healthcare professionals about PNES. To minimize
adult patients. the time from seizure onset to diagnosis of PNES, it is suggested [7]
that (1) patients with atypical seizures are investigated with a video-
4. Discussion EEG monitoring at a specialized center with expertise in making the
differential diagnosis of seizures; (2) therapeutic trials of AEDs are
In the current study, the average time from seizure onset to avoided; (3) the diagnosis of epilepsy is critically reviewed in patients
diagnosis of PNES was 5.6 ± 8.2 years. The mean time to make the diag- who fail to respond to two AEDs or those who develop status epilepticus;
nosis of PNES in previous studies was similarly prolonged, often from 5 (4) a previous diagnostic label of epilepsy is not accepted without
to 7 years but even up to 11 years [1]. We observed that a history of head questioning; and (5) known PNES-associated risk factors are reviewed
trauma was significantly associated with delayed diagnosis of PNES. for diagnostic consideration when treating patients with drug-resistant
Traumatic brain injury (TBI) is a commonly reported PNES-associated or atypical seizures.
factor [1,9]. In one study of 92 patients with PNES, 41 (44.6%) had a his-
tory of TBI [9]. Patients with TBI had more psychological diagnoses, were Acknowledgments
more likely to receive disability, and had a lower global functioning than
patients without TBI but with PNES after adjusting for age and sex. This was an unfunded study. We thank Jennifer Fisher Wilson for
Patients with TBI and PNES had also significantly increased odds for editorial assistance.
 A.A. Asadi-Pooya, J. Tinker / Epilepsy & Behavior 75 (2017) 143–145
Disclosures
Ali A. Asadi-Pooya, M.D., was a consultant for Cerebral Therapeutics,
LLC, and UCB Pharma and received honorarium from Hospital Physician
Board Review Manual and royalty from Oxford University Press
(book publication). Jennifer Tinker, Ph.D., reports no conflict of interest.
References
[1] Asadi-Pooya AA, Sperling MR. Epidemiology of psychogenic non-epileptic seizures.
Epilepsy Behav 2015;46:60–5.
[2] Kerr MP, Mensah S, Besag F, de Toffol B, Ettinger A, Kanemoto K, et al. International
consensus clinical practice statements for the treatment of neuropsychiatric
[10] Kerr WT, Janio EA, Le JM, Hori JM, Patel AB, Gallardo NL, et al. Diagnostic delay in
conditions associated with epilepsy. Epilepsia 2011;52:2133–8.
[3] Valente KD, Alessi R, Vincentiis S, Santos BD, Rzezak P. Risk factors for diagnostic
delay in psychogenic nonepileptic seizures among children and adolescents. Pediatr
Neurol 2017;67:71–7.
145
[4] Asadi-Pooya AA, Emami M, Ashjazadeh N, Nikseresht A, Shariat A, Petramfar P, et al.
Reasons for uncontrolled seizures in adults; the impact of pseudointractability.
Seizure 2013;22:271–4.
[5] Farias ST, Thieman C, Alsaadi TM. Psychogenic nonepileptic seizures: acute change in
event frequency after presentation of the diagnosis. Epilepsy Behav 2003;4:424–9.
[6] Bodde NM, Lazeron RH, Wirken JM, van der Kruijs SJ, Aldenkamp AP, Boon PA.
Patients with psychogenic non-epileptic seizures referred to a tertiary epilepsy
centre: patient characteristics in relation to diagnostic delay. Clin Neurol Neurosurg
2012;114:217–22.
[7] Reuber M, Fernández G, Bauer J, Helmstaedter C, Elger CE. Diagnostic delay in
psychogenic nonepileptic seizures. Neurology 2002;58:493–5.
[8] Asadi-Pooya AA, Tinker J, Fletman EW. How variable are psychogenic nonepileptic
seizures? A retrospective semiological study. J Neurol Sci 2017;377:85–7.
[9] LaFrance Jr WC, Deluca M, Machan JT, Fava JL. Traumatic brain injury and psycho-
genic nonepileptic seizures yield worse outcomes. Epilepsia 2013;54:718–25.
psychogenic seizures and the association with anti-seizure medication trials. Seizure
2016;40:123–6.