Epilepsy & Behavior 56 (2016) 123–130
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Review
Psychiatric comorbidity in psychogenic nonepileptic seizures compared with epilepsy William Diprose a,⁎, Frederick Sundram b, David B. Menkes b,c a b c
Whangarei Hospital, Private Bag 9742, Whangarei 0148, New Zealand Department of Psychological Medicine, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand Waikato Clinical Campus, Private Bag 3200, Hamilton 3240, New Zealand
a r t i c l e
i n f o
Article history: Received 18 November 2015 Revised 15 December 2015 Accepted 23 December 2015 Available online xxxx Keywords: PNES Conversion disorder Posttraumatic stress disorder Anxiety disorder Personality disorder Depression
a b s t r a c t Objectives: Psychogenic nonepileptic seizures (PNESs) are closely linked with psychological distress, but their etiology is not well-understood. We reviewed psychiatric comorbidity in PNESs and epileptic seizures (ESs) with an aim to assist understanding, diagnosis, and management of PNESs. Methods: A search of Web of Science, MEDLINE (PubMed), PsycINFO, and Scopus identified 32 relevant studies on the prevalence of psychiatric comorbidity in PNESs. We used meta-analysis to compare psychiatric comorbidity between PNESs and ESs. Results: Samples with PNESs had high rates of psychiatric comorbidity overall (53–100%), notably including posttraumatic stress disorder (PTSD), depression, and personality and anxiety disorders. Compared with ESs, samples with PNESs had more psychiatric comorbidity overall (RR: 1.30, 95% CI: 1.14–1.48, p b 0.0001) with significantly elevated risks found for PTSD, personality disorder, and anxiety but not depression. Conclusions: Psychiatric disorders are more common in PNESs than ESs. Because of methodological limitations of available studies, causality cannot be established; prospective longitudinal designs are required. © 2015 Elsevier Inc. All rights reserved.
1. Introduction The International League Against Epilepsy defines an epileptic seizure (ES) as a transient occurrence of signs and/or symptoms due to abnormal, excessive, or synchronous neuronal activity in the brain [1]. Conversely, psychogenic nonepileptic seizures (PNESs) are episodes that superficially resemble ESs but lack any electrophysiological evidence of abnormal neuronal activity [2]. Up to 40% of patients in tertiary epilepsy centers have seizures that are attributable to PNESs [3], while estimates of population prevalence vary widely between 2/100,000 and 33/100,000 [4]. Since being first described by the Egyptians in 1900 BCE [5], PNESs have been associated with psychological distress [6]. Janet, Charcot, and Freud all linked PNESs to psychosocial stressors in some way, with the latter's psychological constructs of conversion and dissociation continuing to underpin PNES theories today [6]. Although these concepts remain largely unchanged, the range of terminology is considerable, with PNES being the preferred term and more historical terms such as hysteroepilepsy and pseudoseizure considered pejorative [7]. Given psychosocial contributors, it is unsurprising that people with PNESs have high rates of psychiatric comorbidity. Available evidence
⁎ Corresponding author. Tel.: +64 210720040. E-mail address:
[email protected] (W. Diprose).
http://dx.doi.org/10.1016/j.yebeh.2015.12.037 1525-5050/© 2015 Elsevier Inc. All rights reserved.
indicates that adults with PNESs have poorer prognosis than those with ESs, with 40% of patients with PNESs and 60–80% of patients with ESs achieving seizure-free remission within 5 years of diagnosis [8]. Importantly, psychiatric comorbidity is associated with worse outcomes in both PNESs and ESs [9,10]. Asadi-Pooya and Sperling recently reviewed the literature regarding the diagnosis, incidence, demographics, prognosis, and mortality associated with PNESs; however, they did not examine rates of psychiatric comorbidity [11]. Other authors have identified PNES comorbidity with particular psychiatric disorders but did not consider psychiatric diagnosis more generally. For example, Fiszman et al. [12] critically reviewed the relationship between posttraumatic stress disorder (PTSD) and PNESs but not other psychiatric disorders. Accordingly, the aim of this review was to synthesize the results of studies that investigate the prevalence of psychiatric comorbidity in PNESs and, where possible, compare this with groups with ESs. As far as we could ascertain, this topic is yet to be reviewed in the literature. 2. Method Searches were carried out on 13 December 2015 using Web of Science, MEDLINE (PubMed), PsycINFO, and Scopus with the following terms in the abstract field: (comorbid* OR co-morbid* OR psychiatric profile OR depression OR mood disorder OR PTSD OR posttraumatic stress disorder OR post-traumatic stress disorder OR anxiety disorder OR personality disorder) AND (hysterical seizures OR conversion seizures OR
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Fig. 1. Identifying studies.
functional seizures OR pseudoseizures OR dissociative convulsions OR psychogenic seizures OR psychogenic nonepileptic seizures OR psychogenic non-epileptic seizures OR nonepileptic seizures OR non-epileptic seizures OR nonepileptic attacks OR non-epileptic attacks OR PNES). There was no restriction on year of publication. As outlined in Fig. 1, this search strategy returned 3002 publications. Titles and abstracts were screened, and all studies describing the psychiatric profile of patients with PNESs were provisionally included. Studies were excluded if (i) the study population was less than 18 years old; (ii) videoelectroencephalography (vEEG) monitoring was not used to confirm diagnosis of PNES; (iii) the Diagnostic Statistical Manual of Mental
Disorders (DSM) or the International Classification of Diseases (ICD) were not used for the diagnosis of psychiatric comorbidity; and (iv) there were less than ten participants with PNESs. Studies including participants with intellectual disabilities or psychogenic movement disorders were not excluded. As outlined in Fig. 1, 59 studies met initial inclusion criteria, and 29 of these were excluded: 17 because DSM or ICD criteria were not used; nine because of age; two because of sample size; and one because vEEG was not used. A hand search of the bibliographies of collated articles identified an additional two studies, making a total of 32. We used RevMan [13] to compare rates of psychiatric comorbidity between groups with PNESs and groups with ESs. Studies that
Table 1 Included studies of psychiatric findings in samples with PNESs. Study Author year
Country
2015 2014
Obrien [14] RodriquezUrrutia [14]
Ireland Spain
2013
Alessi [15]
2013
Patidar [16]
No. with Diagnostic PNESs criteria
Compared with ESs
Psychiatric PTSD (%) comorbidity (%)
Depressiona Other psychiatric disorder (%) (%)
Personality disorder (%) 42 15.1
20 53
DSM-IV DSM-IV
No No
53 73.6
NR NR
NR 32.1
Brazil
102
DSM-IV
No
NR
NR
48.0
India
63
DSM-IV
No
NR
NR
90.2
Somatoform/conversion (100) Anxiety (28.3) Other conversion (26.4) Adjustment (20.8) Somatoform disorder (31.4) Anxiety disorder (27.5) Alcoholism or other substance abuse (9.8) Suicide attempts (7.8) Psychosis (6.9) Bipolar disorder (3.9) Anxiety disorder (62.3) Somatoform disorder (27.9) Dissociative disorder (3.3)
9.8
NR
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Table 1 (continued) Compared with ESs
Psychiatric PTSD (%) comorbidity (%)
Depressiona Other psychiatric disorder (%) (%)
DSM-IV
Yes
100 vs. 67.5 22.9 vs. 4.1 (p = 0.003) (p = 0.009)
34.3 vs. 34.7
DSM-III or DSM-IV DSM-IV-TR or DSM-III-R
Yes
76.0 vs. 59.5 58 vs. 13.5 (p = 0.004) 68.6 vs. 62.9 17.1 vs. 5.7
46 vs. 29.7 28.6 vs. 20
MINI-DSM- No IV-TR DSM-IV No DSM-IV-TR PNES vs. mixed PNES vs. ES DSM-IV-TR No
68
20
36
48.7 100 vs. 52
NR NR
43.5 9 vs. 10
79
NR
31
DSM-IV DSM-IV
Yes No
81.2 vs. 76 NR
NR NR
25 vs. 48 48
44
DSM-IV-TR
No
NR
25
72.7
USA Brazil
16 28
DSM-IV-TR DSM-IV
Yes No
NR 53.6
NR 7
NR 36
Hovorka [29]
Czech Republic
56
ICD-10
No
NR
NR
8.9
2006
Alessio [30]
Argentina
24
DSM-IV
88.4 (PNES & mixed)
29 vs. 5
54 vs. 74
2004
Binzer [31]
UK
20
DSM-IV
PNES vs. mixed PNES Yes
55 vs. 25
NR
30 vs. 15
2004
Bailles [32]
Spain
30
DSM-III-R
No
67.7
NR
30
2003
Galimberti [33]
Italy
31
DSM-III-R
Yes
100 vs. 70
NR
13 vs. 45
2003
Dikel [34]
USA
17
DSM-IV
Yes
NR
NR
2003
Kuyk [35]
Netherlands
60
DSM-III-R and DSM-IV
PNES vs. mixed PNES
NR
NR
70.6 vs. 32.4 28.3 vs. 32
2003
Abubakr [36]
USA
23
DSM-IV
No
NR
30
78
Study Author year
Country
No. with Diagnostic PNESs criteria
2013
Scevola [17]
Argentina
35
2012
Salinsky [18]
USA
50
2012
Direk [19]
Turkey
35
2011
Hingray [20]
France
25
2011 2011
Seneviratne [21] Australia Turner [22] Italy
39 22
2011
Bora [23]
Turkey
67
2011 2010
Strutt [24] Jones [25]
USA Australia
2010
Baslet [26]
USA
2009 2008
Harden [27] Marchetti [28]
2007
33 221
Yes
Personality disorder (%)
N1 Axis I psychiatric disorder (77.1 vs. 22.4, p = 0.002) Anxiety disorder (40 vs. 16.3) Somatization disorder (5.7 vs. 0) Bipolar disorder (5.7 vs. 0) Malingering (5.7 vs. 0) Psychotic disorder (2.9 vs. 20.4) Eating disorder (2.9 vs. 0) Expressed as odds ratios GAD (17.1 vs. 5.7) OCD (8.6 vs. 17.1) Panic disorder (5.7 vs. 0) Social phobia (5.7 vs. 2.9) Specific phobia (2.9 vs. 5.7) Anxiety disorder (56) Agoraphobia (44) NR Conversion disorder (13.6) Dissociative disorder NOS (9) Anxiety disorder (4.5) Somatoform disorder (4.5) GAD (15) Psychotic disorder (5) Anxiety (9.4 vs. 4) Anxiety (14.9) Substance use (11.8) Somatoform (8.6) Psychosis (6.8) Substance abuse (29.5) Somatoform disorder (22.7) Dissociative disorder (20.5) Panic disorder (18.2) GAD (9.1) Mania (9.1) Psychosis (2.3) NR Conversion disorder (63) Somatization (19) Dissociative NOS (7) Undifferentiated somatoform (4) Anxiety disorder (30.4) Somatization disorder (5.4) Munchhausen syndrome (3.6) Schizoaffective disorder (1.8) Eating disorder (1.8) Malingering (1.8) Somatoform disorder (37.5 vs. 26) Anxiety disorder (25 vs. 10.5) Psychosis (0 vs. 21) NR Conversion disorder (100) Dissociative disorder (50) Somatoform other than conversion (29.3) Anxiety disorder (16.6) Somatoform disorder (67 vs. 0) Anxiety disorder (16 vs. 9) Psychotic disorder (9 vs. 0) Dissociative disorder (3 vs. 0)
NR Anxiety disorder (38.3 vs. 48) Somatoform disorder (18.3 vs. 40, p = 0.035)
Malingering (22)
71.4 vs. 55.1
36 vs. 10.8 (p = 0.01) 74.3 vs. 34.3 (p = 0.001)
24 NR 18 (PNES), 40 (mixed), 5 (ES) 10 NR 5.4
Cluster B (15.9) Cluster C (9.1)
81.3 vs. 75 20
44.6
71 vs. 68
65 vs. 25 (p b 0.05) 60
Cluster A (0 vs. 0) Cluster B (28 vs. 16) Cluster C (0 vs. 22) NR Cluster A (23 vs. 40) Cluster B (18.3 vs. 24) Cluster C (18.3 vs. 40, p = 0.035) NR
(continued on next page)
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Table 1 (continued) Compared with ESs
Psychiatric PTSD (%) comorbidity (%)
Depressiona Other psychiatric disorder (%) (%)
Personality disorder (%)
DSM-IV
No
96
35
57
NR
17
DSM-IV
No
NR
NR
NR
Krishnamoorthy UK [39]
10
ICD-10 and DSM-III-R
Yes
70 vs. 57
NR
Depression (50 vs. 40)
1999
Kanner [40]
USA
45
DSM-III-R
No
96
NR
38
1996
Bowman and Markhand [41]
USA
45
DSM-III-TR
No
NR
49
64
1996
USA
14
DSM-III-R
Yes
71 vs. 51
36 vs. 15
36 vs. 26
1994
Arnold and Privitera [42] Snyder [43]
USA
20
DSM-III-R
No
70
NR
45
1993
Bowman [44]
USA
27
DSM-III-R
No
NR
40
85
Study Author year
Country
No. with Diagnostic PNESs criteria
2002
Mokleby [37]
Norway
23
2001
Silva [38]
Argentina
2001
GAD (39) Bipolar disorder (22) Phobic anxiety disorder (13) OCD (9) Conversion disorder (52.9) Anxiety disorder (22) Dissociative disorder (11) Psychotic disorder (5.8) Panic, anxiety or phobia (50 vs. 17.1) Psychotic disorder (10 vs. 2.9)
Dissociative disorder (22) Somatoform disorder (22) Adjustment reaction (13) Dissociative disorder (91) Somatoform disorder (89) Nonseizure conversion disorder (82) Anxiety disorder (47) Alcohol dependence (28 vs. 15) Panic disorder (21 vs. 11) Panic disorder (70) Somatoform (25) Substance use (15) Psychotic disorder (15) Eating disorder (5) Simple phobia (5) Social phobia (5) Any dissociative disorder (84)
NR
Cluster A (0 vs. 17.1) Cluster B (0 vs. 2.9) Cluster C (0 vs. 17.1) 45
62
36 vs. 18 NR
NR
NR = not reported. BOLD = statistically significant. a All reported as “depression” in this table; however, terms included affective disorder, depression, major depression, and depressive disorder.
compared mixed PNESs (ESs and PNESs together) with ESs were excluded.
when the seven studies comparing only pure PNESs with ESs were combined, the increased risk of major depression failed to reach statistical significance (RR: 1.16, 95% CI: 0.88–1.53, p = 0.30).
3. Results 3.3. Anxiety and posttraumatic stress disorder (PTSD) Table 1 summarizes the 32 studies included in the review. 3.1. Psychiatric comorbidity The rates of psychiatric comorbidity ranged between 53% and 100%. All 11 studies comparing pure PNESs with ESs found higher rates of psychiatric comorbidity in the groups with PNESs. However, only one demonstrated a statistically significant difference, with 100% of patients with PNESs and 67.5% of patients with drug-resistant epilepsy having psychiatric comorbidity (p = 0.003) [17]. As shown in Fig. 2, when the relevant studies were combined, the risk of psychiatric comorbidity was significantly higher in the group with PNESs (RR: 1.30, 95% CI: 1.14–1.48, p b 0.0001). 3.2. Depression The majority of studies suggested that depression was the most common psychiatric comorbidity, with rates between 8.9% and 85% [22,23,44]. Some reported rates of any affective disorder, whereas others reported specific diagnoses such as major depressive disorder, dysthymia, and bipolar affective disorder. In the largest cross-sectional study looking at depression and PNESs, 106 of 221 participants (48%) had depression [25]. In most of the studies that compared groups with PNESs and groups with ESs, those with PNES tended to have higher rates of depression [17,18,22,31,34,42]. However, as shown in Fig. 3,
The prevalence of anxiety disorders ranged between 4.5% and 70% (in the latter example, all were panic disorder) [22,43]. Seven studies reported rates of specific anxiety disorders including panic disorder (5.7–70%), agoraphobia (44%), generalized anxiety disorder (9.1–39%), phobic disorder (2.9–13%), obsessive–compulsive disorder (9%), and social phobia (5%). When relevant studies were combined, there was a significantly elevated risk of anxiety in the group with PNESs, as shown in Fig. 4 (RR: 1.82, 95% CI: 1.27–2.61, p = 0.001). Twelve studies investigated the prevalence of PTSD in patients with PNESs and reported a wide range of between 7% and 100% [28,45]. Two studies comparing groups with PNESs and groups with ESs found a significant difference in the prevalence of PTSD between the two groups [17,18,45]. The largest of these studies reported an odds ratio of 20.5 (p = 0.004) for risk of PTSD in PNESs compared with ESs [18]. As shown in Fig. 5, when eligible studies were combined there was a more than threefold risk of PTSD in the group with PNESs (RR: 3.21, 95% CI: 2.09–4.95, p b 0.00001). 3.4. Personality disorders Twenty-four studies examined the rate of personality disorders in patients with PNESs, which ranged between 5.4% and 74.3% [19,25]. Only two studies reported a statistically significant difference in prevalence of personality disorders between PNESs and ESs [31,34]. When the
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Fig. 2. Meta-analysis of eligible studies comparing risk of psychiatric comorbidity (any Axis I diagnosis) between PNES and ES.
relevant studies were combined (Fig. 6), a significantly increased risk of personality disorder in the group with PNESs was apparent (RR: 1.73, 95% CI: 1.38–2.17, p b 0.00001). Where a study specified types of personality disorders, the sample size was generally too small for any meaningful interpretation. Geschwind syndrome, an interictal personality disorder that sometimes occurs in temporal lobe epilepsy, was not mentioned in any of the included studies [46].
3.6. Conversion, dissociation, and somatoform disorders For the purposes of this review, conversion, dissociative, and somatoform disorders were not considered comorbidities. In the current classification systems, DSM-5 [47] and ICD-10 [48], PNES is best defined as a conversion (found under somatic symptom disorder) or dissociative disorder, respectively. This is because PNESs can be viewed as a common clinical expression of the processes of conversion or dissociation. Nevertheless, the rate of conversion and dissociative disorders were reportedly as low as 13.6% and 3.3%, respectively [16,22,44].
3.5. Other psychiatric comorbidity 4. Discussion The occurrence of other psychiatric disorders was not routinely reported in the included studies. Ten studies reported a low (0–15%) prevalence of psychosis in PNESs [30,43]. Five reported the prevalence of alcohol and substance abuse as between 9.8% and 29.5% [15,26]. Neurodevelopmental, neurocognitive, and subthreshold psychiatric disorders were inconsistently reported and not included in the current study.
Based on our review of 32 articles, psychiatric comorbidity is substantial in clinical populations with PNESs, notably when compared to the general population and to controls with epileptic seizures (ESs). In particular, people with PNESs tended to have higher rates of PTSD, anxiety, and personality disorders.
Fig. 3. Meta-analysis of eligible studies comparing risk of major depression between PNES and ES.
Fig. 4. Meta-analysis of eligible studies comparing risk of anxiety disorder between PNES and ES.
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Fig. 5. Meta-analysis of eligible studies comparing risk of PTSD between PNES and ES.
Psychogenic nonepileptic seizure falls under the broader category of medically unexplained physical symptoms (MUPS). Although 50–75% of patients with MUPS also have coexisting depression and anxiety, they often present with somatic symptoms as opposed to psychological distress [49]. As with other physically unexplained symptoms, PNESs provide clinicians the opportunity to evaluate for underlying psychiatric disorders. Given that psychiatric disorders are overrepresented in PNESs, it may suggest a shared etiology between PNESs, PTSD, anxiety, and personality disorders. When comparing PNESs and ESs, PTSD was most strikingly associated with PNESs. Sexual abuse, physical abuse/neglect, and health-related trauma (medical comorbidities) have been identified as commonly associated with PNESs [11]. Indeed, traumatic experiences are a known risk factor for the development of both PNESs and PTSD [12]; however, the causal mechanisms are unknown. Interestingly, cognitive (memory) impairment in PTSD with PNESs resemble that found in PTSD alone [50], suggesting that PNESs may be a common expression of a range of psychopathologies, notably including those arising from psychological trauma. Recent studies have also suggested overlapping brain connectivity alterations in PNESs [51,52] and PTSD [53]. Personality disorders are also strongly linked with PNESs compared to ESs. Studies have shown similar developmental and trauma histories in PNESs and borderline personality disorder, with some authors arguing that the latter is central to the etiology of PNESs [54]. Likewise, anxiety is also overrepresented in samples with PNESs compared with samples with ESs, notably with regard to experiential avoidance, self-reported anxiety [55], and panic symptoms [56]. These data suggest that a range of psychopathologies may underlie PNESs, explaining both the high burden and considerable variation of identified psychiatric disorders in PNESs. Indeed, some authors suggest that it is misleading to refer to psychiatric comorbidities in PNESs [63], as PNESs are likely a common clinical expression of several psychiatric disorders as opposed to discrete nosology [57]. Alternatively, psychiatric comorbidity may not underlie PNESs but rather perpetuate ongoing nonepileptic seizures [58]. In line with this, greater psychiatric comorbidity is associated with poorer outcomes in PNESs
[59], meaning those who have comorbidity are more likely to present to tertiary centers for evaluation and treatment. Regardless of the causal relationship, identification and treatment of psychiatric comorbidity could, in principle, reduce seizure frequency. Currently available treatment options for PNESs include psychological interventions such as cognitive behavioral therapy (CBT), psychodynamic therapy, and group therapy, as well as pharmacological treatment with serotonin reuptake inhibitors [60,61]. To date, the highest quality evidence comes from a multicenter randomized clinical trial that found combined psychotherapy and sertraline-reduced seizure frequency by 59% (p = 0.008) and improved mood and anxiety symptoms in patients with PNESs with significant psychiatric comorbidity [62]. Reducing psychiatric comorbidity may have contributed to reduced seizure frequency in this study. This would suggest that tailoring treatments according to psychiatric comorbidity may be more successful than treating PNESs as a homogenous group. For example, serotonin reuptake inhibitors might be more effective in groups with PNESs with significant depressive or anxiety symptoms, while trauma-focused CBT might be more effective in groups with PNESs with PTSD. To date, a treatment approach tailored to underlying psychiatric comorbidity has not been systematically investigated. There were a number of methodological limitations in the studies examined. The majority were cross-sectional which means the direction of causality between PNESs and psychiatric comorbidity cannot be established. All were hospital-based populations so may not represent the majority of people with PNESs who reside in the community. Some studies reported “lifetime” and some “current” prevalence of psychiatric comorbidity. Although DSM criteria were used in the majority of studies, the detail of reporting varied significantly. Finally, the majority of studies were not case-controlled with a group with epilepsy, which means factors specific to PNESs cannot be identified. Also, our meta-analysis was limited by the small number and size of studies comparing PNESs with ESs. Future research should focus on clarifying the temporal relationship between PNESs and other psychiatric disorders through large
Fig. 6. Meta-analysis of eligible studies comparing risk of personality disorder between PNES and ES.
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longitudinal case-controlled studies. Furthermore, high quality randomized controlled trials should investigate the impact of treating specific psychiatric comorbidities on seizure frequency in PNESs.
Acknowledgments We would like to thank Dr. Martin Salinsky for kindly providing us with supplementary data [18]. Conflict of interest We do not have any conflicts of interest to report in relation to the contents of the manuscript.
References [1] Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46: 470–2. [2] Hubsch C, Baumann C, Hingray C, Gospodaru N, Vignal J-P, Vespignani H, et al. Clinical classification of psychogenic non-epileptic seizures based on video-EEG analysis and automatic clustering. J Neurol Neurosurg Psychiatry 2011;82:955–60. [3] Martin R, Burneo JG, Prasad A, Powell T, Faught E, Knowlton R, et al. Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG. Neurology 2003;61:1791–2. [4] Benbadis SR, Allen Hauser W. An estimate of the prevalence of psychogenic nonepileptic seizures. Seizure 2000;9:280–1. [5] Tasca C, Rapetti M, Carta MG, Fadda B. Women and hysteria in the history of mental health. Clin Pract Epidemiol Ment Health 2012;8:110–9. [6] Dickinson P, Looper KJ. Psychogenic nonepileptic seizures: a current overview. Epilepsia 2012;53:1679–89. [7] Brigo F, Igwe SC, Ausserer H, Nardone R, Tezzon F, Bongiovanni LG, et al. Terminology of psychogenic nonepileptic seizures. Epilepsia 2015;56:e21–5. [8] Durrant J, Rickards H, Cavanna AE. Prognosis and outcome predictors in psychogenic nonepileptic seizures. Epilepsy Res Treat 2011;2011:274736–7. [9] Bodde NMG, Brooks JL, Baker GA, Boon PAJM, Hendriksen JGM, Mulder OG, et al. Psychogenic non-epileptic seizures—definition, etiology, treatment and prognostic issues: a critical review. Seizure 2009;18:543–53. [10] Jacoby A, Baker GA, Steen N, Potts P, Chadwick DW. The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. community study. Epilepsia 1996;37:148–61. [11] Asadi-Pooya AA, Sperling MR. Epidemiology of psychogenic nonepileptic seizures. Epilepsy Behav 2015;46:60–5. [12] Fiszman A, Alves-Leon SV, Nunes RG, D Andrea I, Figueira I. Traumatic events and posttraumatic stress disorder in patients with psychogenic nonepileptic seizures: a critical review. Epilepsy Behav 2004;5:818–25. [13] Collaboration C. Review manager (RevMan) [computer program]. Copenhagen: The Nordic Cochrane Centre; 2011. [14] Rodríguez-Urrutia A, Toledo M, Eiroa-Orosa FJ, Salas-Puig X, Santamarina E, FidelKinori SG, et al. Psychosocial factors and antiepileptic drug use related to delayed diagnosis of refractory psychogenic nonepileptic seizures. Cogn Behav Neurol 2014; 27:199–205. [15] Alessi R, Valente KD. Psychogenic non-epileptic seizures at a tertiary care center in Brazil. Epilepsy Behav 2013;26:91–5. [16] Patidar Y, Gupta M, Khwaja GA, Chowdhury D, Batra A, Dasgupta A. Clinical profile of psychogenic non-epileptic seizures in adults: a study of 63 cases. Ann Indian Acad Neurol 2013;16:157–62. [17] Scévola L, Teitelbaum J, Oddo S, Centurión E, Loidl CF, Kochen S, et al. Psychiatric disorders in patients with psychogenic nonepileptic seizures and drug-resistant epilepsy: a study of an Argentine population. Epilepsy Behav 2013;29:155–60. [18] Salinsky M, Evrard C, Storzbach D, Pugh MJ. Psychiatric comorbidity in veterans with psychogenic seizures. Epilepsy Behav 2012;25:345–9. [19] Direk N, Kulaksizoglu IB, Alpay K, Gurses C. Using personality disorders to distinguish between patients with psychogenic nonepileptic seizures and those with epileptic seizures. Epilepsy Behav 2012;23:138–41. [20] Hingray C, Maillard L, Hubsch C, Vignal JP, Bourgognon F, Laprevote V, et al. Psychogenic nonepileptic seizures: characterization of two distinct patient profiles on the basis of trauma history. Epilepsy Behav 2011;22:532–6. [21] Seneviratne U, Briggs B, Lowenstern D, D'Souza W. The spectrum of psychogenic non-epileptic seizures and comorbidities seen in an epilepsy monitoring unit. J Clin Neurosci 2011;18:361–3. [22] Turner K, Piazzini A, Chiesa V, Barbieri V, Vignoli A, Gardella E, et al. Patients with epilepsy and patients with psychogenic non-epileptic seizures: video-EEG, clinical and neuropsychological evaluation. Seizure 2011;20:706–10. [23] Bora IH, Taskapilioglu O, Seferoglu M, Kotan OV, Bican A, Ozkaya G, et al. Sociodemographics, clinical features, and psychiatric comorbidities of patients with psychogenic nonepileptic seizures: experience at a specialized epilepsy center in Turkey. Seizure 2011;20:458–61.
129
[24] Strutt AM, Hill SW, Scott BM, Uber-Zak L, Fogel TG. A comprehensive neuropsychological profile of women with psychogenic nonepileptic seizures. Epilepsy Behav 2011;20:24–8. [25] Jones SG, O'Brien TJ, Adams SJ, Mocellin R, Kilpatrick CJ, Yerra R, et al. Clinical characteristics and outcome in patients with psychogenic nonepileptic seizures. Psychosom Med 2010;72:487–97. [26] Baslet G, Roiko A, Prensky E. Heterogeneity in psychogenic nonepileptic seizures: understanding the role of psychiatric and neurological factors. Epilepsy Behav 2010;17:236–41. [27] Harden CL, Jovine L, Burgut FT, Carey BT, Nikolov BG, Ferrando SJ. A comparison of personality disorder characteristics of patients with nonepileptic psychogenic pseudoseizures with those of patients with epilepsy. Epilepsy Behav 2009;14: 481–3. [28] Marchetti RL, Kurcgant D, Neto JG, Bismark von MA, Marchetti LB, Fiore LA. Psychiatric diagnoses of patients with psychogenic non-epileptic seizures. Seizure 2008; 17:247–53. [29] Hovorka J, Nezádal T, Herman E, Nemcová I, Bajacek M. Psychogenic non-epileptic seizures, prospective clinical experience: diagnosis, clinical features, risk factors, psychiatric comorbidity, treatment outcome. Epileptic Disord 2007;9(Suppl. 1):S52–8. [30] D'Alessio L, Giagante B, Oddo S, Silva WW, Solís P, Consalvo D, et al. Psychiatric disorders in patients with psychogenic non-epileptic seizures, with and without comorbid epilepsy. Seizure 2006;15:333–9. [31] Binzer M, Stone J, Sharpe M. Recent onset pseudoseizures—clues to aetiology. Seizure 2004;13:146–55. [32] Baillés E, Pintor L, Fernandez-Egea E, Torres X, Matrai S, de Pablo J, et al. Psychiatric disorders, trauma, and MMPI profile in a Spanish sample of nonepileptic seizure patients. Gen Hosp Psychiatry 2004;26:310–5. [33] Galimberti CA, Ratti MT, Murelli R, Marchioni E, Manni R, Tartara A. Patients with psychogenic nonepileptic seizures, alone or epilepsy-associated, share a psychological profile distinct from that of epilepsy patients. J Neurol 2003;250:338–46. [34] Dikel TN, Fennell EB, Gilmore RL. Posttraumatic stress disorder, dissociation, and sexual abuse history in epileptic and nonepileptic seizure patients. Epilepsy Behav 2003;4:644–50. [35] Kuyk J, Swinkels WAM, Spinhoven P. Psychopathologies in patients with nonepileptic seizures with and without comorbid epilepsy: how different are they? Epilepsy Behav 2003;4:13–8. [36] Abubakr A, Kablinger A, Caldito G. Psychogenic seizures: clinical features and psychological analysis. Epilepsy Behav 2003;4:241–5. [37] Mökleby K, Blomhoff S, Malt UF, Dahlström A, Tauböll E, Gjerstad L. Psychiatric comorbidity and hostility in patients with psychogenic nonepileptic seizures compared with somatoform disorders and healthy controls. Epilepsia 2002;43:193–8. [38] Silva W, Giagante B, Saizar R, D'Alessio L, Oddo S, Consalvo D, et al. Clinical features and prognosis of nonepileptic seizures in a developing country. Epilepsia 2001;42: 398–401. [39] Krishnamoorthy ES, Brown RJ, Trimble MR. Personality and psychopathology in nonepileptic attack disorder and epilepsy: a prospective study. Epilepsy Behav 2001;2:418–22. [40] Kanner AM, Parra J, Frey M, Stebbins G, Pierre-Louis S, Iriarte J. Psychiatric and neurologic predictors of psychogenic pseudoseizure outcome. Neurology 1999;53: 933–8. [41] Bowman ES, Markand ON. Psychodynamics and psychiatric diagnoses of pseudoseizure subjects. Am J Psychiatry 1996;153:57–63. [42] Arnold LM, Privitera MD. Psychopathology and trauma in epileptic and psychogenic seizure patients. Psychosomatics 1996;37:438–43. [43] Snyder SL, Rosenbaum DH, Rowan AJ, Strain JJ. SCID diagnosis of panic disorder in psychogenic seizure patients. J Neuropsychiatry Clin Neurosci 1994;6:261–6. [44] Bowman ES. Etiology and clinical course of pseudoseizures. Psychosomatics 1993; 34:333–42. [45] Rosenberg HJ, Rosenberg SD, Williamson PD, Wolford GL. A comparative study of trauma and posttraumatic stress disorder prevalence in epilepsy patients and psychogenic nonepileptic seizure patients. Epilepsia 2000;41:447–52. [46] Benson DF. The Geschwind syndrome. Adv Neurol 1991;55:411–21. [47] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013. [48] World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines; 1992[Geneva]. [49] Kroenke K. Patients presenting with somatic complaints: epidemiology, psychiatric co-morbidity and management. Int J Methods Psychiatr Res 2003;12:34–43. [50] Myers L, Zeng R, Perrine K, Lancman M, Lancman M. Cognitive differences between patients who have psychogenic nonepileptic seizures (PNESs) and posttraumatic stress disorder (PTSD) and patients who have PNESs without PTSD. Epilepsy Behav 2014;37:82–6. [51] Xue Q, Wang ZY, Xiong XC, Tian CY, Wang YP, Xu P. Altered brain connectivity in patients with psychogenic non-epileptic seizures: a scalp electroencephalography study. J Int Med Res 2013;41:1682–90. [52] Ding J-R, An D, Liao W, Li J, Wu G-R, Xu Q, et al. Altered functional and structural connectivity networks in psychogenic non-epileptic seizures. PLoS One 2013;8:1–10. [53] Du M-Y, Liao W, Lui S, Huang X-Q, Li F, Kuang W-H, et al. Altered functional connectivity in the brain default-mode network of earthquake survivors persists after 2 years despite recovery from anxiety symptoms. Soc Cogn Affect Neurosci 2015; 10:1497–505. [54] Lacey C, Cook M, Salzberg M. The neurologist, psychogenic nonepileptic seizures, and borderline personality disorder. Epilepsy Behav 2007;11:492–8. [55] Dimaro LV, Dawson DL, Roberts NA, Brown I, Moghaddam NG, Reuber M. Anxiety and avoidance in psychogenic nonepileptic seizures: the role of implicit and explicit anxiety. Epilepsy Behav 2014;33:77–86.
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W. Diprose et al. / Epilepsy & Behavior 56 (2016) 123–130
[56] Hendrickson R, Popescu A, Dixit R, Ghearing G, Bagic A. Panic attack symptoms differentiate patients with epilepsy from those with psychogenic nonepileptic spells (PNES). Epilepsy Behav 2014;37:210–4. [57] Gates JR. Nonepileptic seizures: classification, coexistence with epilepsy, diagnosis, therapeutic approaches, and consensus. Epilepsy Behav 2002;3:28–33. [58] Reuber M. The etiology of psychogenic non-epileptic seizures: toward a biopsychosocial model. Neurol Clin 2009;27:909–24. [59] Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav 2003;4:205–16. [60] Martlew J, Pulman J, Marson AG. Psychological and behavioural treatments for adults with non-epileptic attack disorder. The Cochrane Library; 2014.
[61] Haykal MA, Smith B. A therapeutic approach to psychogenic nonepileptic seizures. Curr Treat Options Neurol 2015;17(9):1–10. [62] LaFrance Jr WC, Baird GL, Barry JJ, Blum AS, Frank Webb A, Keitner GI, et al. Multicenter pilot treatment trial for psychogenic nonepileptic seizures. JAMA Psychiatry 2014;71:997–9. [63] Beghi M, Negrini PB, Perin C, Peroni F, Magaudda A, Cerri C, Cornaggia CM. Psychogenic non-epileptic seizures: so-called psychiatric comorbidity and underlying defense mechanisms. Neuropsychiatr Dis Treat 2015;11:2519–27.