Gender differences in prevalence of psychiatric disorders, levels of alexithymia, and coping strategies in patients with refractory mesial temporal epilepsy and comorbid psychogenic nonepileptic seizures

Epilepsy & Behavior 82 (2018) 1–5

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Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh

Gender differences in prevalence of psychiatric disorders, levels of alexithymia, and coping strategies in patients with refractory mesial temporal epilepsy and comorbid psychogenic nonepileptic seizures Amanda Cristian Serafim de Barros, Ana Eliza Romano Furlan, Lucia Helena Neves Marques, Gerardo Maria de Araújo Filho ⁎ Faculdade de Medicina de São José do Rio Preto (FAMERP), Brazil

a r t i c l e

i n f o

Article history: Received 2 January 2018 Revised 25 February 2018 Accepted 25 February 2018 Available online xxxx Keywords: Psychogenic nonepileptic seizures Gender differences Depression Anxiety Quality of life

a b s t r a c t Objective: The objective of this study was to investigate the psychological aspects and psychiatric disorders (PDs) in patients dually diagnosed with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) with psychogenic nonepileptic seizures (PNES) treated in a tertiary center in order to find any gender differences in psychiatric, clinical, and sociodemographic characteristics. Method: Psychiatric assessment was performed through the Diagnostic and Statistical Manual for Psychiatric Disorders — 5th edition (DSM-5). The Brazilian versions of the Medical Outcomes Study 36 (SF-36), Toronto Alexithymia Scale (TAS-20), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Ways of Coping Checklist (WCC) were applied. Results: Of the 47 patients enrolled (25 females; 53.2%), females were significantly more likely to have a history of previous psychiatric treatment (P = 0.02), family history of epilepsy (P = 0.01), and family history of PD (P = 0.03). They also presented earlier onset of PNES (P = 0.01) and higher PNES duration (P = 0.02) compared with males. Major depressive disorder (MDD) was the most frequent PD (24; 51.0%). Females presented more psychiatric diagnoses (P b 0.001), more diagnoses of MDD (P b 0.001), and posttraumatic stress disorder (PTSD) (P b 0.001). Several differences regarding quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies were observed between groups. Conclusions: There are significant gender differences in psychiatric, clinical, and sociodemographic aspects in a group of patients with TLE-MTS and PNES, as well as in quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies. These gender differences suggest that specific approaches might be adopted depending on the patient's gender and, consequently, their distinct psychological/psychiatric profile. © 2018 Elsevier Inc. All rights reserved.

1. Introduction Psychogenic nonepileptic seizures (PNES) are paroxysmal episodes superficially resembling epileptic seizures, but they are not associated with any electrical abnormalities [1–3]. Although PNES are a clinically heterogeneous group, most patients fulfill the diagnostic criteria of a functional neurological symptom (conversion) disorder (Diagnostic and Statistical Manual for Psychiatric Disorders — 5th edition (DSM5)) or of dissociative convulsions (International Classification of Diseases — 10th revision (ICD-10)) [4,5]. Moreover, those patients frequently present other psychiatric disorders (PDs), such as mood and/or anxiety disorders. Patients with PNES represent an important subpopulation for epilepsy specialists because they require and can ⁎ Corresponding author at: Av. Brigadeiro Faria Lima, 5416 – Nova Redentora, São José do Rio Preto, SP 15090-000, Brazil. E-mail address: fi[email protected] (G.M. de Araújo Filho).

https://doi.org/10.1016/j.yebeh.2018.02.026 1525-5050/© 2018 Elsevier Inc. All rights reserved.

benefit from the differentiated diagnostic procedures these professionals provide. In addition, since most patients with PNES can be initially misdiagnosed as having epilepsy, specialists need their assistance and knowledge to diagnose PNES and manage the treatment [1,2,6]. It is believed that up to 20 or 30% of patients referred with apparently antiepileptic drug-refractory epilepsy receive a diagnosis of PNES after expert evaluation in tertiary epilepsy centers [1–3,6]. Temporal lobe epilepsy (TLE) is one of the most frequent epilepsy syndromes (ESs) and the most frequent ES found in patients with medically refractory epilepsy, especially among those followed up in tertiary epilepsy centers. Mesial temporal sclerosis (MTS) is the most frequent etiology of TLE observed among those patients. It compromises the primary structures of the limbic system, particularly the hippocampus and amygdala, and is associated with cognitive deficits, PDs, and a lower quality of life [7–10]. Although a number of studies have already found gender differences in sociodemographic, clinical, psychological, and behavioral aspects

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among patients with PNES [7–10], there is a scarcity of data regarding possible gender differences in psychiatric diagnoses, especially in patients with dual diagnoses. The main objective of the present study was to investigate possible gender differences in sociodemographic, clinical, and psychiatric characteristics, as well as the presence and degree of alexithymia, anxiety/depression symptoms, and quality of life in a group of patients dually diagnosed with refractory TLE-MTS with comorbid PNES treated in a tertiary center. 2. Methods 2.1. Patients At the time this study was conducted, 385 patients were being treated in a tertiary epilepsy center (outpatient epilepsy clinic of Faculdade de Medicina de São José do Rio Preto — FAMERP), 97 (25.1%) of whom had PNES. Of these, 47 patients (12.2%) fulfilled the clinical inclusion criteria, which were age 18 to 65 years, dual diagnoses of TLE-MTS and PNES confirmed through video-electroencephalography (VEEG), clear magnetic resonance imaging (MRI) findings consistent with MTS, presence of a psychiatric evaluation performed by one of the authors (GMAF), and having been treated for at least one year at the epilepsy clinic of FAMERP. Exclusion criteria were cognitive impairments preventing them from answering the questionnaires and the presence of epileptic syndromes other than TLE-MTS or only PNES at neurological evaluation. After the study was approved by the local ethics committee, all 47 patients were included. 2.2. Procedures All 47 patients underwent 2–6 days of continuous VEEG monitoring with 32-channel EEG recording. Mesial temporal sclerosis was defined as the presence of atrophy, an increased T2-weighted signal, a decreased T1-weighted signal, and disrupted internal structure of the hippocampus along with atrophy of the amygdala and/or temporal pole signal alteration on visual inspection of MRI pictures. Refractoriness to medical treatment was defined as seizures persisting after the utilization of at least two first-line medications for partial seizures at the highest tolerated doses for at least six months. Initial precipitant injury (IPI) was defined as the occurrence of severe cerebral events in the first year of life before the appearance of epilepsy that required medical intervention and/or hospitalization. Febrile seizures, meningoencephalitis, head trauma, or severe perinatal hypoxia were considered IPI. Data regarding previous psychiatric treatment, family history of epilepsy, family history of PD, age of PNES onset, and PNES duration were collected from patients' files and/or through patient/family information. 2.3. Instruments The enrolled patients underwent standard psychiatric assessment according to DSM-5 criteria [4] and were assessed with the Brazilian versions of the following instruments: a) Medical Outcomes Study 36 (SF-36) [11]: This is a 36-item multidimensional questionnaire grouped into 8 domains: functional capacity, physical aspects, pain, general health, vitality, social aspects, emotional aspects, and mental health. It carries a final score of 0 to 100 (obtained by summing the raw scores), where 0 corresponds to the worst general health condition and 100 corresponds to the best health status; b) Toronto Alexithymia Scale (TAS-20) [12–14]: This is a scale designed to measure the degree of alexithymia, defined as the inability to express distress, and somatization. The instrument examines three main domains: ability to identify and to describe feelings and to distinguish feelings of bodily sensations, ability to daydream, and preference for focusing on external events rather than inner experiences.

Each item of the TAS-20 consists of a sentence that can be answered through a five-point Likert self-assessment tool: 1: I strongly disagree, 2: I disagree in part, 3: I do not agree or disagree, 4: I agree in part, and 5: I totally agree. The score indicated by the instrument ranges from 26 to 130. Values lower than 62 do not indicate symptoms of alexithymia, and values higher than 74 indicate the presence of these symptoms. Values between 63 and 73 are inconclusive. c) Hamilton Depression Scale (HAM-D) [15,16]: This quantitatively estimates the level of the patient's depressive symptoms and measures the results of treatments. The most used HAM-D version consists of 17 items. Scores above 25 points are characteristic of severely depressed patients; scores between 18 and 24 points, moderately depressed patients; and scores between 7 and 17 points, patients with mild depression. d) Hamilton Anxiety Scale (HAM-A) [17,18]: This emphasizes the somatic aspects of anxiety and measures aspects such as mood and cognitive and somatic symptoms. The score ranges from 0 to 56. A score of 17 or less indicates mild anxiety severity. A score from 18 to 24 indicates mild to moderate anxiety severity. Scores higher than 25 and 30 indicate moderate and severe anxiety symptoms, respectively; e) Ways of Coping Checklist (WCC) [19,20]: This instrument identifies which types of coping strategies have been used by the individual in relation to specific stressors. The Brazilian version consists of 45 items with eight subscales that express cognition and behaviors to address stressful events. The answers are given on a five-point Likert scale (1 = I never do this, 2 = I do it a little, 3 = I do it sometimes, 4 = I do it a lot, and 5 = I do it always), with a maximum score of 20.

2.4. Statistical analysis The collected data were distributed in the form of mean and standard deviation (discrete variables) or according to their presence or absence (categorical variables). Since multiple comparisons between groups were done, the results obtained were statistically analyzed through analysis of variance (ANOVA) with Bonferroni's post hoc test when necessary. A P value of b 0.05 was considered significant. 3. Results Data from all 47 patients (25 females; 53.2%) were included. Mesial temporal sclerosis occurred more frequently on the left side (29 patients; 61.7%). Twelve patients (25.5%) had a history of IPI, with febrile seizures being the most frequent (seven cases; 14.9%). All patients had used two or more antiepileptic drugs (AEDs); carbamazepine (CBZ) was the most frequent AED, being prescribed to 31 patients (65.9%). Benzodiazepines (BZD), particularly clobazam (CLB), were the most common adjunctive drugs, being prescribed to 23 patients (48.9%). Female patients significantly more often had a history of previous psychiatric treatment (P = 0.02), family history of epilepsy (P = 0.01), and family history of PD (P = 0.03). They also presented earlier onset of PNES (P = 0.01) and higher PNES duration (P = 0.02) compared with males. Clinical and sociodemographic data of patients are shown in Table 1. Since all patients (100%) presented diagnostic criteria for functional neurological symptoms disorder (FNSD) according to DSM-5, this diagnosis was not included in our statistical analysis. Other PDs were observed in all of the 47 patients (100.0%); major depressive disorder (MDD) was the most frequent PD (24 patients; 51.0%), followed by anxiety disorders (22 patients; 46.8%), posttraumatic stress disorder (PTSD) (19 patients; 40.4%), psychotic disorders (five patients; 10.6%), and excoriation disorder (two patients; 4.2%). Female patients presented significantly more psychiatric diagnoses than males (P b 0.001), as well as more diagnoses of MDD (P b 0.001) and PTSD (P b 0.001). Twenty-three

A.C.S. de Barros et al. / Epilepsy & Behavior 82 (2018) 1–5 Table 1 Clinical and demographic data of patients with TLE-MTS with psychogenic nonepileptic seizures. Clinical/demographic data

Female

Male

P

Number of patients (%) Age Age at epilepsy onset (mean ± SD) Age at PNES onset (mean ± SD) Years of epilepsy duration (mean ± SD) Years of PNES duration (mean ± SD) Previous psychiatric treatment (%) Family history of epilepsy (%) Family history of psychiatric disorders (%) MTS lateralization Left Right Most frequently used AEDs (%) Carbamazepine Phenytoin Phenobarbital Topiramate Oxcarbazepine Benzodiazepines Presence and type of IPI (%) No IPI Perinatal hypoxia Febrile seizures Meningoencephalitis

25 (53.2) 34.9 ± 10.3 10.5 ± 2.1 14.2 ± 4.7 24.3 ± 11.2 20.2 ± 9.8 15 (60.0) 16 (64.0) 11 (44.0)

22 (46.8) 34.2 ± 12.7 11.1 ± 2.5 19.5 ± 3.7 23.7 ± 13.0 15.4 ± 10.6 8 (36.3) 7 (31.8) 5 (22.7)

– 0.62 0.63 0.01⁎ 0.84 0.02⁎ 0.02⁎ 0.01⁎ 0.03⁎

15 (60.0) 10 (40.0)

14 (63.6) 8 (36.3)

0.73 0.67

17 (68.0) 10 (40.0) 8 (32.0) 6 (24.0) 4 (16.0) 13 (52.0)

14 (63.6) 9 (40.9) 5 (22.7) 4 (18.1) 3 (13.6) 10 (45.4)

0.74 0.98 0.64 0.74 0.64 0.63

18 (72.0) 1 4 (16.0) 2 (8.0)

17 (77.2) 0 3 (13.6) 2 (9.0)

0.62 – 0.88 0.82

AED: antiepileptic drug; IPI: initial precipitant injury; MTS: mesial temporal sclerosis; PNES: psychogenic nonepileptic seizures; SD: standard deviation; TLE: temporal lobe epilepsy. ⁎ P b 0.05.

patients (48.9%) presented two or more PDs beyond FNSD, and females were overrepresented among them (P b 0.001). Nearly all patients diagnosed with PTSD (18; 94.7%) experienced a trauma of a sexual type. Psychiatric diagnoses of patients are shown in Fig. 1. Table 2 describes the results obtained in the instruments applied to patients. Comparing the scores of both groups on SF-36, female patients presented a significant reduction of functional capacity (P = 0.03) and emotional aspects (P = 0.02), whereas males presented a significant reduction on physical aspects (P = 0.03). On TAS-20, females presented significantly higher scores of alexithymia (P = 0.02), despite high scores in the group of males. Females also presented higher scores on HAM-D (P b 0.001), whereas males presented higher scores in all three dimensions of HAM-A (anxious cognition, P = 0.02; anxious mood, P = 0.04; and physical symptoms, P = 0.02). We also observed statistically significant differences regarding the coping strategies on WCC: females

3

presented higher levels of searching for social (P = 0.04) and religious support (P = 0.04).

4. Discussion The main objective of the present study was to investigate possible gender differences in sociodemographic, clinical, and psychiatric characteristics, as well as the presence and degree of alexithymia, anxiety/ depression symptoms, and quality of life in a group of patients dually diagnosed with TLE-MTS and PNES treated in a tertiary center. Compared with males, female patients more often presented a history of previous psychiatric treatment, family history of epilepsy, and family history of PD. Female patients also presented more PD than males, particularly MDD and PTSD. In addition, several differences regarding quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies between sexes were observed. The sociodemographic characteristics of our cohort were quite different from previous studies of PNES whose participants were disproportionately female [1–6,21–24]. The larger proportion of males observed in this study could be a consequence of more restrictive inclusion criteria or the fact that ours is a national referral center for epilepsy treatment and consequently receives a high number of patients of both genders, characteristics that made the present study feasible. Nevertheless, the proportion of patients with PNES found in our tertiary center was similar to prior data in the literature [1–3]. A high proportion of patients with a dual diagnosis of TLE-MTS and PNES was observed, which could be a consequence of both factors listed above. To our knowledge, this is the first study that verified the frequency of such a specific subgroup among patients with PNES treated in tertiary centers [1–3,21–24]. Studies have observed a 20–40% prevalence of PD in patients with TLE-MTS, rising to 70% in patients with refractory forms. Mood disorders have been the most common PD diagnosed (24–74%), followed by anxiety disorders (10–25%), psychoses (2–9%), and personality disorders (1–2%) [25–27]. There was an elevated frequency of PD in the present study, corroborating the frequency and types of psychiatric comorbidities disclosed in other studies involving TLE-MTS populations [7–10]. Moreover, compared with males, female patients had significantly more psychiatric diagnoses, mainly MDD, and PTSD, confirming previous studies that have examined PNES and gender in terms of these variables [7–10,21–24]. To our knowledge, this is the first study that compared genders in these variables in patients with TLE-MTS and PNES.

50

Males

45

Females

Number of patients

40 35 30 25 20 15 10 5 0 Major depressive disorder*

Anxiety disorders

PTSD*

Psychotic disorders

Excoriation disorder

Two or more PD*

Total*

Fig. 1. Gender differences on psychiatric disorders in patients with temporal lobe epilepsy/mesial temporal sclerosis and psychogenic nonepileptic seizures. PD: psychiatric disorders; PTSD: posttraumatic stress disorder; P b 0.05.

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Table 2 Instrument scores of female and male patients with refractory temporal lobe epilepsy and mesial temporal sclerosis with psychogenic nonepileptic seizures. Instrument

SF-36

TAS-20 HAM-D HAM-A

WCC

Variable

Functional capacity Physical aspects Pain General well-being Vitality Social aspects Emotional aspects Mental health Alexithymia/somatization scores Depressive scores Anxious cognition Anxious mood Physical symptoms Problem-focused coping Emotion-focused coping Search for religious support Search for social support

Females

Males

P-value

Minimuma

Maximuma

Median

Mean

SD

Minimuma

Maximuma

Median

Mean

SD

0 0 0 5 20 13 0 12 45 8 8 3 2 2 1 1 2

100 100 100 67 70 100 100 68 77 44 53 18 15 5 4 4 5

65 75 63 45 40 75 33 36 75 18 14 8 5 3 3 3 4

63 67 64 43 42 70 49 39 75 18 17 9 6 3 3 3 4

24 33 27 14 12 26 34 15 2 7 9 5 5 0 0 1 1

25 0 21 15 15 13 0 16 36 6 9 5 1 3 3 2 2

95 100 100 77 65 100 100 68 70 28 64 27 26 4 4 4 5

80 50 74 40 40 69 67 32 65 11 18 11 4 3 3 2 2

73 53 69 40 41 69 63 37 66 13 18 11 5 3 3 2 2

20 34 27 13 13 24 30 13 3 4 5 3 3 0 0 0 1

0.03⁎ 0.03⁎ 0.45 0.32 0.67 0.65 0.02⁎ 0.73 0.02⁎ b0.001⁎ 0.02⁎ 0.04⁎ 0.02⁎ 0.98 0.15 0.04⁎ 0.04⁎

HAM-A: Hamilton Anxiety Scale; HAM-D: Hamilton Depression Scale; SD: standard deviation; SF-36: Medical Outcomes Study 36; TAS-20: Toronto Alexithymia Scale; WCC: Ways of Coping Checklist. ⁎ P b 0.05. a Scores obtained by participants.

Although PNES disorders are a clinically heterogeneous syndrome, most patients fulfill the diagnostic criteria of a FNSD (DSM-5) or of dissociative convulsions (ICD-10). Moreover, those patients frequently present other psychiatric comorbidities, mainly mood and/or anxiety disorders [1–3]. Only 5% of patients with PNES do not have a comorbid PD [1–3,28,29]. In the present study, all 47 patients presented at least one PD beyond FNSD, and almost half of them presented two or more PD, corroborating prior studies [1–3,21–24,28,29] and reinforcing the high frequency of PD observed in patients with refractory TLE-MTS [7–9]. Therefore, a comprehensive psychiatric assessment undertaken by professionals with the skills required to handle such disorders is highly necessary [29–31]. This recommendation for psychiatric assessment, however, is made acknowledging the reality that psychiatrists are not part of many teams in epilepsy tertiary care centers [29–31]. In two recent surveys that identified current practices on diagnosis and treatment of PNES among Brazilian professionals, it was observed that although participants considered that the psychiatrist was the best professional to address the patients' conditions and to conduct treatment, they had many difficulties referring those patients and did not have a psychiatrist on their tertiary epilepsy care teams [28,29]. They also discussed that this scenario is unfortunately similar to other countries, such as the UK, Chile, and the US [32,33]. This study observed associations between female patients dually diagnosed with TLE-MTS and PNES and some clinical and sociodemographic variables, such as history of previous psychiatric treatment, family history of epilepsy, and family history of PD. Studies that compared the psychological traits between male and female patients with PNES have observed that females presented greater emotional distress, including suicidal behavior, as well as higher rates of physical and sexual abuse and previous psychiatric treatment [21–24]. However, in our particular sample, these associations (with the exception of physical and sexual abuse) could also be linked to clinical refractoriness, failure to diagnose epilepsy earlier, or clinical risk factors for PD in patients with TLE-MTS [7–9]. In addition, females presented an earlier onset of PNES and consequently higher PNES duration compared with males. Despite the fact that those clinical and sociodemographic data were obtained in a retrospective manner through chart review and/or family interview, such information is in accordance with the current literature [21–24]. Regarding psychometric measures, female patients presented significant reductions of functional capacity and on emotional aspects of quality of life whereas males presented significant reduction on physical aspects. Although prior studies have already described high levels of

emotional distress and physical complaints in patients with PNES [21–24], the negative impact of TLE-MTS on quality of life needs to be considered [7–9]. Otherwise, this gender difference could reflect Brazilian cultural aspects in which men are less prone to talk about their feelings, and consequently, emotional issues could appear as physical complaints. Female patients also presented higher levels of alexithymia despite the high scores observed in the male group. Alexithymia, described as a difficulty or inability to describe emotions in a verbal manner, has been considered a core issue in the pathophysiology of PNES, and the treatment proposals for PNES should take this aspect into account [1–3,28–31,34,35]. To our knowledge, this is the first study that measured the levels of alexithymia in a series of patients dually diagnosed with PNES and TLE-MTS, a frequent ES observed in tertiary centers. Females also presented higher depression scores on HAM-D, possibly reflecting the elevated frequency of diagnoses of MDD observed in this study; MDD is a common comorbidity associated with psychological trauma and PTSD. Males presented higher scores in all three dimensions of HAM-A (anxious cognition, anxious mood, and physical symptoms). Prior studies have observed high levels of anxiety traits among men with PNES [21–24]. Statistically significant differences regarding coping strategies between both groups were also observed whereas female patients presented higher levels of searching for social and religious support. A recent study has highlighted a greater use of avoidance as a stress coping strategy among men with PNES [21]. Again, such a difference in coping strategies could also reflect aspects of Brazilian culture, where women are traditionally more likely to seek social and religious support. Taken together, the above data have some important clinical implications. For female patients who presented more PD, higher scores on depression and alexithymia, and a higher prevalence of sexual abuse, treatment approaches might be more intensive, longer, and perhaps trauma-based. On the other hand, given the psychological profile presented by males, such as high anxiety, higher levels of alexithymia, more physical complaints, and a shorter history of PNES, a more traditional cognitive behavioral approach might be indicated. There are, however, important limitations of the present study. Because the data were obtained in a retrospective manner, we were unable to discretely assess psychological trauma types, suicidality, and personality disorders. The results observed should not be generalized to all patients with PNES or even to all patients with a dual diagnosis of PNES and epilepsy, since a specific population having TLE-MTS with

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comorbid PNES was studied. However, this could also be considered an important strength of the present study, which has found psychiatric, clinical, and sociodemographic characteristics of this specific subgroup. In addition, it was not possible to determine if there were gender differences in current seizure frequency. We could not diagnose any PD not covered by DSM-5. Finally, although based upon a relatively small number of patients, our findings in this cross-sectional study are concordant with the extant literature and address a relatively homogeneous population of patients dually diagnosed with TLE-MTS and PNES. To conclude, this study found significant gender differences in psychiatric, clinical, and sociodemographic aspects in patients with TLE-MTS and PNES treated in a tertiary center, as well as in quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies. The present study also observed a high prevalence of PD in this group of patients, with significant gender differences that could reflect cultural and biological specificities and highlight the necessity of a comprehensive psychiatric/psychological management of these patients provided by the appropriate professionals. Such differences also reinforce the possibility of different psychological and psychiatric approaches depending on patient's gender and consequently their distinct psychological/psychiatric profile.

[10] [11]

[12] [13] [14] [15] [16]

[17] [18]

[19] [20] [21]

Conflict of interests

[22]

The authors state that they do not have any conflict of interest to disclose.

[23]

Acknowledgments

[24]

This work was supported by the National Council for Scientific and Technological Development (CNPq: 443742/2014-6) and the Medical School of São José do Rio Preto, São Paulo, Brazil (FAMERP: 110400). References [1] Reuber M, Fernández G, Bauer J, Helmstaedter C, Elger CE. Diagnostic delay in psychogenic nonepileptic seizures. Neurology 2002;58:493–5. [2] Brown RJ, Reuber M. Psychological and psychiatric aspects of psychogenic nonepileptic seizures (PNES): a systematic review. Clin Psychol Rev 2016;45:157–82. [3] LaFrance Jr WC, Reuber M, Goldstein LH. Management of psychogenic nonepileptic seizures. Epilepsia 2013;54(Suppl. 1):53–67. [4] American Psychiatric Association. Diagnostic and statistical manual for mental disorders5th ed. ; 2013 [Washington]. [5] World Health Organization. The ICD-10 classification of mental and behavioral disorders. Clinical descriptions and diagnostic guidelines. 10th ed.; 1993 [Genebra]. [6] Reuber M, Fernández G, Helmstaedter C, Bauer J, Quirishi A, Elger CE. Are there physical risk factors for psychogenic nonepileptic seizures in patients with epilepsy? Seizure 2003;12:561–7. [7] De Araujo Filho GM, Mazetto L, da Silva JM, Caboclo LO, Yacubian EM. Psychiatric comorbidity in patients with two prototypes of focal versus generalized epilepsy syndromes. Seizure 2011;20:383–6. [8] De Araujo Filho GM, Mazetto L, Gomes FL, Marinho MM, Tavares IM, Caboclo LO, et al. Pre-surgical predictors for psychiatric disorders following epilepsy surgery in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis. Epilepsy Res 2012;102:86–93. [9] De Araujo Filho GM, Gomes FL, Mazetto L, Marinho MM, Tavares IM, Caboclo LO, et al. Major depressive disorder as a predictor of a worse seizure outcome one

[25] [26]

[27]

[28] [29] [30] [31] [32] [33]

[34]

[35]

5

year after surgery in patients with temporal lobe epilepsy and mesial temporal sclerosis. Seizure 2012;21:619–23. Swinkels WAM, Kuyk J, van Dyck R, Spinhoven PH. Psychiatric comorbidity in epilepsy. Epilepsy Behav 2005;7:37–50. Ciconelli RM, Ferraz MB, Santos W, Meinao I, Quaresma MR. Brazilian–Portuguese version of the SF-36: a reliable and valid quality of life outcome measure. Rev Bras Reumatol 1999;39:143–50. Bagby RM, Parker JD, Taylor GJ. The twenty-item Toronto Alexithymia Scale I. Item selection and cross-validation of the factor structure. J Psychosom Res 1994;38(1):23–32. Bagby RM, Taylor GJ, Parker JD. The twenty-item Toronto Alexithymia Scale II. Convergent, discriminant, and concurrent validity. J Psychosom Res 1994;38(1):33–40. Yoshida EMP. Validity of the Portuguese version of the Toronto Alexithymia ScaleTAS in a sample of inpatients. Psicol Reflex Crit 2007;20:389–96. Hamilton M, White JM. Clinical syndromes in depressive states. Br J Psychiatry 1959; 105:985–98. Freire MA, Figueiredo VLM, Gomide A, Jansen K, Silva RA, Magalhães PVS, et al. Hamilton Depression Scale: study of the psychometric characteristics in a sample from Southern Brazil. J Bras Psiquiatr 2014;63(4):281–9. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959;32: 50–5. Figueiredo VLM, Freire MA, Silva RA, Magalhães PVS, Kapczinsky FP. Hamilton Anxiety Scale: study of the psychometric characteristics in a sample from Southern Brazil. J Bras Psiquiatr 2015;64(2):328–36. Vitaliano PP, Russo J, Carr JE, Maiuro RD, Becker J. The Ways of Coping Checklist: revision and psychometric properties. Multivar Behav Res 1985;20(1):3–26. Seidl EMF, Troccoli BT, Zannon CMLC. Análise Fatorial de Uma Medida de Estratégias de Enfrentamento. Psic Teor Pesq 2001;17(3):225–34. Myers L, Trobliger R, Bortnik K, Lancman M. Are there gender differences in those diagnosed with psychogenic nonepileptic seizures? Epilepsy Behav 2018;78:161–5. Del Bene VA, Renteria MA, Maiman M, Slugh M, Gazzola DM, Nadkarni SS, et al. Increased odds and perspective rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences. Epilepsy Behav 2017;72:43–50. Thomas AA, Preston J, Scott RC, Bujarski KA. Diagnosis of probable psychogenic nonepileptic seizures in the outpatient clinic: does gender matter? Epilepsy Behav 2013;29:295–7. Oto M, Conway P, McGonigal A, Russell AJ, Duncan R. Gender differences in psychogenic non-epileptic seizures. Seizure 2005;14:33–9. Gaitatzis A, Trimble MR, Sander JW. The psychiatric comorbidity of epilepsy. Acta Neurol Scand 2004;110:207–20. Schmitz EB, Moriarty J, Costa DC, Ring HA, Ell PJ, Trimble MR. Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy. J Neurol Neurosurg Psychiatr 1997;62:458–63. Krishnamoorthy ES, Trimble MR, Blumer D. The classification of neuropsychiatric disorders in epilepsy: a proposal by the ILAE commission on psychobiology of epilepsy. Epilepsy Behav 2007;10:349–53. Moore PM, Baker GA. Non-epileptic attack disorder: a psychological perspective. Seizure 1997;6:429–34. WC Jr LaFrance, Devinsky O. The treatment of nonepileptic seizures: historical perspectives and future directions. Epilepsia 2004;45:15–21. McGee MD, Torosian J. Integrating spiritual assessment into a psychiatric inpatient unit. Psychiatry (Edgmont) 2006;3:60–4. Reuber M. The etiology of psychogenic non-epileptic seizures: toward a biopsychosocial model. Neurol Clin 2009;27:909–24. Valente KD, Rzezak P, LaFrance Jr WC. Standard medical care for psychogenic nonepileptic seizures in Brazil. Epilepsy Behav 2015;45:128–35. Valente KD, De Paola L, Palmini A, Faveret E, De Araujo Filho GM, van der Linden H, et al. The approach to patients with psychogenic nonepileptic seizures in epilepsy surgery centers regarding diagnosis, treatment, and education. Epilepsy Behav 2017;68:78–83. Myers L, Matzner B, Lancman M, Perrine K, Lancman M. Prevalence of alexithymia in patients with psychogenic non-epileptic seizures and epileptic seizures and predictors in psychogenic non-epileptic seizures. Epilepsy Behav 2013;26(2):153–7. Bewley J, Murphy PN, Mallows J, Baker GA. Does alexithymia differentiate between patients with nonepileptic seizures, patients with epilepsy, and nonpatient controls? Epilepsy Behav 2005;7:430–7.