Epilepsy & Behavior 45 (2015) 35–38
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Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Psychiatric disorders as “hidden” contraindications for presurgical VEEG in patients with refractory epilepsy: A retrospective cohort study in a tertiary center Gerardo Maria de Araujo Filho a,⁎, Ana Eliza Romano Furlan a, Ana Elisa Sa Antunes Ribeiro a, Lucia Helena Neves Marques b a b
Department of Psychiatry and Medical Psychology, Faculdade de Medicina de São José do Rio Preto (FAMERP), São Paulo, Brazil Department of Neurological Sciences, Faculdade de Medicina de São José do Rio Preto (FAMERP), São Paulo, Brazil
a r t i c l e
i n f o
Article history: Received 18 November 2014 Revised 20 February 2015 Accepted 21 February 2015 Available online 21 March 2015 Keywords: Refractory epilepsy Psychiatric evaluation VEEG monitoring Psychiatric issues
a b s t r a c t Given the high frequency of psychiatric disorders (PDs) observed among patients with epilepsy, studies have highlighted the necessity of psychiatric evaluation for these patients, especially for those with refractory temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS) who are surgical candidates. Current evidence highlights the safety of video-electroencephalography (VEEG) as a means of investigation in patients with TLE-MTS and PDs. However, the presence of such disorders has still been seen as a contraindication for presurgical evaluation with VEEG in some epilepsy centers mainly because of the risk of negative behavioral events. The present retrospective cohort study performed in a Brazilian tertiary epilepsy center aimed to identify whether the presence of a PD remains a contraindication for presurgical VEEG. Clinical, sociodemographic, and psychiatric data from 41 patients who underwent VEEG as part of their presurgical evaluation were compared to data from 32 patients with refractory TLE-MTS who had not undergone VEEG. Psychiatric diagnoses were determined using the DSM-IV and ILAE criteria. Psychiatric disorders were diagnosed in 34 patients (46.6%). Major depressive disorder was the most frequent PD and was observed in 22 patients (30.1%). Anxiety disorders were observed in 14 patients (19.2%). Of the 41 patients (56.2%) who underwent presurgical VEEG, only 12 (29.2%) were found to have a PD during the presurgical psychiatric evaluation compared to 22 of the 32 (68.7%) who did not undergo VEEG (p = 0.001; RR = 2.35). The present findings suggest that the presence of a PD alone should not be a contraindication for VEEG monitoring and epilepsy surgery. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Studies in the literature have observed a prevalence rate of comorbid psychiatric disorders (PDs_ of 20-40% in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS), which rises to 70% in groups with refractory forms of epilepsy [1–6]. Mood disorders are the most common (24–74%), followed by anxiety (10–25%), psychotic disorders (2–9%), and personality disorders (1–2%) [2–5]. Given the high prevalence of presurgical PDs in this population, the psychiatric outcomes of such patients have become of particular interest to researchers [3,4]. Moreover, the correlation between the presence of presurgical PDs and poorer postsurgical seizure outcomes in patients with refractory epilepsy who underwent surgery has been increasingly recognized [5–10].
Given the high frequency of psychiatric comorbidity observed among patients with refractory TLE-MTS, studies have also highlighted the necessity of careful psychiatric evaluation as part of the presurgical and postsurgical protocols in tertiary epilepsy centers [1–6]. Despite recent studies indicating that the sole presence of a PD would not be a risk factor for evaluation with video-electroencephalography (VEEG), the presence of a PD has remained a relative contraindication for presurgical VEEG in some epilepsy centers mainly because of the risk of negative behavioral events, such as aggressiveness, attempted suicide, or psychomotor agitation [11,12]. The present retrospective cohort study aimed to determine whether PDs have remained a “hidden” contraindication for presurgical VEEG in a Brazilian tertiary epilepsy center with a psychiatrist as a member of the team. 2. Methods
⁎ Corresponding author at: Faculdade de Medicina de São José do Rio Preto, Av. Brigadeiro Faria Lima, 5416, São José do Rio Preto, São Paulo CEP: 15090-000, Brazil. Fax: +55 17 3201 5734. E-mail address: fi[email protected] (G.M. de Araujo Filho).
http://dx.doi.org/10.1016/j.yebeh.2015.02.026 1525-5050/© 2015 Elsevier Inc. All rights reserved.
2.1. Procedures All patients were followed in the outpatient clinic of a tertiary center (Epilepsy Section of the Faculdade de Medicina de São José do Rio Preto,
36
G.M. de Araujo Filho et al. / Epilepsy & Behavior 45 (2015) 35–38
São Paulo, Brazil) from January 2013 to November 2014 and underwent psychiatric evaluation. The eligibility criteria included patients who were older than 18, had an electroclinical diagnosis of TLE based on the ILAE classification [13], had been receiving follow-up care with the Epilepsy Center for at least six months, and had been referred for presurgical psychiatric evaluation before VEEG. All patients were seen by the same clinical team. Exclusion criteria included the presence of other clinical or neurological diseases besides epilepsy, cognitive impairments precluding evaluation, and patients who already had VEEG performed before psychiatric evaluation. Any clinical or social factors other than psychiatric evaluations recorded in patients' files that had precluded the use of VEEG were also considered as exclusion criteria. Patients with any PD at the time of psychiatric evaluation that precluded the use of VEEG were excluded, as were those who declined the procedure. Patients with a putative diagnosis of psychogenic nonepileptic seizures (PNES) were not included in the study because this diagnosis must be confirmed using VEEG. The VEEG consisted of 2–6 days of continuous monitoring with 32-channel EEG. Electrodes, including sphenoidal electrodes, were placed on the temporal lobe according to the 10–10 system. Mesial temporal sclerosis was determined to be present if atrophy, increased T2-weighted signal, decreased T1-weighted signal, and disrupted internal hippocampal structure were present and accompanied by observations of amygdala atrophy and/or temporal pole signal changes upon visual inspection of the MRI images. The epileptogenic zone was determined by predominantly ipsilateral interictal epileptiform discharges (80% cutoff) and seizure onset recorded during the prolonged VEEG monitoring. Refractoriness to medical treatment was considered present if seizures persisted after the utilization of at least two firstline medications for partial seizures at the highest tolerated dose for at least 6 months. An initial precipitant injury (IPI) was defined as the occurrence of severe cerebral events that required medical intervention and/or hospitalization during the first year of life before the appearance of epilepsy. Febrile seizures, meningoencephalitis, head trauma, or severe perinatal hypoxia were considered IPIs. 2.2. Psychiatric evaluation A single psychiatrist (GMAF) conducted the clinical interviews using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I criteria [14]. Because each patient could have more than one Axis I psychiatric diagnosis, both the number of patients diagnosed and all comorbid PDs diagnosed were considered in the analysis. The presence of other specific psychiatric diagnoses commonly associated with epilepsy, which are not covered by the DSM-IV but are well described in the literature, such as interictal dysphoric disorder (IDD) and epilepsy psychoses, was evaluated using the ILAE criteria. These criteria were also used to differentiate postictal psychosis (PIP) from
interictal psychosis (IIP) [15]. Data concerning the lifetime history of psychotropic treatment, defined as any past treatment with psychiatric drugs, were collected from patients during the first clinical interview. Information about the familial history of epilepsy and PDs was also obtained from patients through broad questions regarding whether any first-degree relative was in treatment for epilepsy and/or any PD at the time of the clinical interview. 2.3. Statistics Statistical analyses were performed using the version 14.0 of the Statistical Package for Social Sciences software (SPSS 10.0, Chicago, Illinois). Bivariate statistical analyses were performed using the most suitable statistical test for each situation (chi-square (χ2), Fisher's exact test, or Student's t-test for unequal variances). For statistical comparisons, patients were divided into two groups according to the use of VEEG monitoring as an indispensable presurgical evaluation that always occurred (or did not occur) as part of the service routine following psychiatric evaluation. A p-value b 0.05 was considered significant. 3. Results After written informed consent was obtained, the clinical and sociodemographic data of 73 consecutive surgical candidates with refractory TLE-MTS (48 females; 57.8%) who met the eligibility criteria were collected. Patients' clinical and sociodemographic characteristics are shown in Table 1. Mesial temporal sclerosis occurred more frequently on the left side (39 patients; 53.4%). Thirty-one patients (42.5%) had a history of IPI, with febrile seizures the most frequent (12 cases; 38.7%). There were also ten cases of head trauma (32.2%), five of perinatal hypoxia (16.1%), and two of meningoencephalitis (6.4%). Sixty-nine patients (94.5%) were using at least two medications at the time of evaluation. Carbamazepine (CBZ) was the most frequently used AED and was prescribed to 55 patients (75.3%), followed by phenobarbital (PB) (35; 47.9%), valproate (15; 20.5%), topiramate (TPM) (10; 13.7%), oxcarbazepine (OXC) (7; 9.6%), and phenytoin (PHT) (7; 9.6%). Benzodiazepines (BZDs), particularly clobazam (CLB), were the most common adjunctive drugs and were prescribed to 26 patients (35.6%). Among the 73 patients, Axis I psychiatric diagnoses were observed in 34 (56.6%). Major depressive disorder (MDD), which included all diagnoses of depression within the present cohort, was the most common PD and was diagnosed in 22 patients (30.1%). Fourteen patients (19.2%) had anxiety disorders, all of them presenting generalized anxiety disorder (GAD). Psychotic disorders were observed in seven patients (9.6%), all of which had IIP. Somatoform disorders (excluding the nonconfirmed presence of PNES) were observed in five patients (6.8%). Fourteen patients fulfilled the criteria for two Axis I disorders. Interictal dysphoric disorder
Table 1 Clinical and demographic data of patients with refractory epilepsy who did or did not undergo video-electroencephalography. Clinical/demographic data
Total
VEEG
Non-VEEG
p
Number of patients (%) Female gender (%) Age (mean ± SD) Age at epilepsy onset (mean ± SD) Epilepsy duration (mean ± SD) Lifetime psychiatric treatment (%) Family history of epilepsy (%) Family history of PD (%) Presence of IPI (%) Patients with PDs (%)
73 (100) 42 (57.5) 41.4 ± 12.10 13.9 ± 13.32 26.1 ± 13.32 34 (46.5) 22 (30.1) 13 (17.8) 31 (42.5) 34 (46.6)
41 (56.2) 20 (48.7) 41.0 ± 12.57 12.0 ± 9.17 28.4 ± 13.50 10 (24.3) 12 (29.2) 4 (9.7) 19 (46.3) 12 (29.2)
32 (43.8) 22 (68.7) 42.4 ± 12.66 16.8 ± 13.31 25.1 ± 14.30 24 (75.0) 10 (31.2) 9 (28.1) 12 (37.5) 22 (68.7)
– 0.22a 0.42b 0.37b 0.61b 0.02⁎,a
IPI: initial precipitant injury, PDs: psychiatric disorders, and SD: standard deviation. ⁎ p b 0.05. a Chi-square. b Student's t-test. c Fisher's exact test.
0.93a 0.03⁎,c 0.55a 0.001⁎,a
G.M. de Araujo Filho et al. / Epilepsy & Behavior 45 (2015) 35–38
was diagnosed in eight patients (10.9%), and six of them (75%) also presented an Axis I PD. This diagnosis, however, was not included in the statistics because its criteria are not included in the DSM-IV. Of the 73 patients included in the study, 41 (56.2%) underwent presurgical VEEG. Of those, only 12 patients (29.2%) were diagnosed with a PD during the presurgical psychiatric evaluation; nine presented with MDD and three, with IIP. In contrast, of the 32 patients who did not undergo VEEG, 22 (68.7%) presented with a PD (p = 0.001). In addition, a relative risk (RR) of 2.35 was observed, indicating that patients who were not diagnosed with a PD during a previous psychiatric evaluation were approximately 2.35 times more likely to undergo VEEG. Patients who did not undergo VEEG were also more likely to have had a history of PD (p = 0.02) and more likely to have a history of lifetime psychiatric treatment (p = 0.03). A comparison of the clinical and sociodemographic characteristics of both groups is shown in Table 1, and the diagnosed PDs are shown in Fig. 1.
4. Discussion The aim of this retrospective cohort study was to verify whether PDs have remained a “hidden” contraindication for presurgical VEEG in patients with refractory epilepsy (TLE-MTS) in a Brazilian tertiary center with a psychiatrist as a member of the team. Such verification is important for highlighting the need for more information regarding the possible risks involved in VEEG evaluation, and consequently the surgical procedure, in this population. The present study observed a significantly higher prevalence rate of PDs among patients who did not undergo VEEG compared to those with the same clinical and sociodemographic conditions who underwent such a procedure. As noted earlier, the available literature indicates a PD prevalence rate of 20–40% in patients with epilepsy, although it can be as high as 70% in refractory forms of the condition, particularly TLE-MTS [2–6]. Irrespective of some form of methodological bias, such as the selection of patients or the types of research instruments utilized, this elevated prevalence has highlighted the importance of psychiatric evaluation for these patients [16–20]. Such evaluation would be especially important for patients who are candidates for epilepsy surgery given the relatively higher risk of postsurgical PDs [5,6,16–20]. Recent studies have also shown a correlation between the risk of a poorer postsurgical seizure outcome and some presurgical clinical and sociodemographic characteristics, such as lifetime psychiatric history (particularly of major depressive disorder), presurgical history of secondarily generalized tonic–clonic seizures, duration of seizure disorder, extent of the resection of the mesial temporal structures, and the presence of neuropathologic abnormalities [17–20]. The most frequently discussed hypothesis in the literature is that presurgical PDs, and particularly MDD, could be
VEEG
epiphenomena of a more diffuse cerebral disease and may consequently be associated with poorer seizure control [5,6,8,16–20]. In the present study, a high prevalence rate of PDs was observed, which is in accordance with studies that measured the prevalence of PDs in patients with refractory epilepsy, particularly TLE-MTS [2–6]. In addition, the types of PDs observed were similar to those observed in the literature [2–6,21–23]. When the group of patients with refractory TLE-MTS who underwent VEEG, an indispensable investigational tool for surgical purposes in tertiary epilepsy centers, was compared to patients with the same clinical and sociodemographic conditions who did not undergo the procedure, significant differences in the presence of PDs were found. Although the literature has highlighted the risk of negative behavioral events in patients with epilepsy and PDs, recent studies have not observed significant differences regarding the presence of such events when patients with PDs diagnosed prior to VEEG evaluation were compared to patients without these conditions, even in patients with psychoses [11,12]. Moreover, differences regarding a poorer postsurgical seizure outcome were not observed when patients with presurgical PDs were compared to those without PDs in these studies, highlighting the need for additional studies to investigate this issue [11,12]. The present study has important limitations. We could not evaluate the prevalence of PDs that are not covered by the diagnostic criteria utilized in this study (DSM-IV and ILAE), such as attention-deficit hyperactivity disorder (ADHD), which is often observed among patients with epilepsy [24]. Moreover, only categorical criteria were utilized and no dimensional instruments applied, so we could not assess the presence of mild psychopathological changes in this population. Because of possible incomplete and/or unreliable data, unidentified causes that may have precluded the use of VEEG, including a potentially higher rate of decline of VEEG among patients with PDs, could not be detected. Because it is part of the routine of our center, we could not accurately assess whether VEEG was equally encouraged for both groups before and/or after psychiatric evaluation by clinicians. Finally, our findings demonstrate a correlation between patients with PDs in the non-VEEG group, which does not necessitate a cause–effect relationship. However, although based on a relatively small number of patients and conducted in a single epilepsy center, the present findings address the recurrent issue that, despite patients with presurgical PDs being thought to be at a greater risk of poorer psychiatric and seizure postsurgical outcomes, the sole presence of a PD should not be considered a contraindication for presurgical evaluation (including VEEG) in tertiary centers. Therefore, because of the elevated prevalence of PDs in patients with refractory epilepsy, neurologists and psychiatrists should improve their communication to share knowledge regarding PDs in epilepsy. In addition, there is a growing need for careful psychiatric evaluation to be included as part of the presurgical and postsurgical protocols, especially in
non-VEEG
Total
25 20 15 10 5 0 Mood disorders
Anxiety disorders
37
Somatoform Psychoses disorders
Interictal dysphoric disorder
Fig. 1. Psychiatric diagnoses of patients with refractory epilepsy in a tertiary center. VEEG: video-electroencephalogram.
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tertiary epilepsy centers. Because many questions still remain, continued investigation is highly recommended [5,6]. Acknowledgments This work was supported by CNPq (443742/2014-6) from Brazil. Conflicts of interest The authors confirm that they do not have any financial or personal relationships with other persons or organizations that could inappropriately influence their work. Moreover, they confirm that they have no additional conflicts of interest to disclose. References [1] Pintor L, Bailles E, Fernández-Egea E, Sánchez-Gistau V, Torres X, Carreño M, et al. Psychiatric disorders in temporal lobe epilepsy patients over the first year after surgical treatment. Seizure 2007;16:218–25. [2] Tellez-Zenteno JF, Wiebe S. Prevalence of psychiatric disorders in patients with epilepsy: what we think we know and what we know. In: Kanner AM, Schachter S, editors. Psychiatric controversies in epilepsy. San Diego: Academic Press; 2008. p. 1–18. [3] Gaitatzis A, Trimble MR, Sander JW. The psychiatric comorbidity of epilepsy. Acta Neurol Scand 2004;110:207–20. [4] Devinsky O. Psychiatric comorbidity in patients with epilepsy: implications for diagnosis and treatment. Epilepsy Behav 2003;4:2–10. [5] De Araujo Filho GM, Rosa VP, Lin K, Caboclo LO, Sakamoto AC, Yacubian EMT. Psychiatric comorbidity in epilepsy: a study comparing patients with mesial temporal sclerosis and juvenile myoclonic epilepsy. Epilepsy Behav 2008;13:196–201. [6] De Araujo Filho GM, Mazetto L, Macedo JS, Caboclo LO, Yacubian EMT. Psychiatric comorbidity in patients with two prototypes of focal versus generalized epilepsy syndromes. Seizure 2011;20:383–6. [7] Swinkels WAM, Boas WE, Kuyk J, van Dyck R, Spinhoven P. Interictal depression, personality traits and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE. Epilepsia 2006;47:2092–103. [8] Anhoury S, Brown RJ, Krishnamoorthy ES, Trimble MR. Psychiatric outcome following temporal lobectomy: a predictive study. Epilepsia 2000;41:1608–15.
[9] Kanner AM. Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms and treatment. Biol Psychiatry 2003;54:388–98. [10] Kanner AM. Should a psychiatric evaluation be included in every pre-surgical work-up? In: Kanner AM, Schachter S, editors. Psychiatric controversies in epilepsy. San Diego: Academic Press; 2008. p. 239–54. [11] Conceição PO, De Araujo Filho GM, Mazetto L, Alonso NB, Yacubian EMT. Safety of video-EEG monitoring and surgical outcome in patients with mesial temporal sclerosis and psychosis of epilepsy. Seizure 2012;21:583–7. [12] Conceição PO, De Araujo Filho GM, Nascimento PP, Mazetto L, Alonso NB, Yacubian EMT. Are psychiatric disorders exclusion criteria for video-EEG monitoring and epilepsy surgery in patients with mesial temporal sclerosis? Epilepsy Behav 2013;27: 310–4. [13] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99. [14] American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders DSM — IV (text revision). 4th ed.; 2004 [Washington]. [15] 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. [16] Macrodimitris S, Sherman EMS, Forde S, Tellez-Zenteno JF, Metcalfe A, HernandezRonquilho L, et al. Psychiatric outcomes of epilepsy surgery: a systematic review. Epilepsia 2011;52:880–90. [17] Jones R, Rickards H, Cavanna AE. The prevalence of psychiatric disorders in epilepsy: a critical review of the evidence. Funct Neurol 2010;25:191–4. [18] Altshuler L, Rausch R, DeIrahim S, Kay J, Crandall P. Temporal lobe epilepsy, temporal lobectomy and major depression. J Neuropsychiatry Clin Neurosci 1999;11:436–43. [19] Reuber M, Andersen B, Elger CE, Helmstaedter C. Depression and anxiety before and after temporal lobe epilepsy surgery. Seizure 2004;13:129–35. [20] Devinsky O, Barr WB, Vicrey BG, Berg AT, Bazil CW, Pacia SV, et al. Changes in depression and anxiety after resective surgery for epilepsy. Neurology 2005;65: 1744–52. [21] De Araujo Filho GM, Caboclo LOSF. Anxiety and mood disorders in psychogenic nonepileptic seizures. J Epilepsy Clin Neurophysiol 2007;13(4):28–31. [22] Benbadis SR, Agrawal V, Tatum WO. How many patients with psychogenic nonepileptic seizures also have epilepsy? Neurology 2001;57:915–7. [23] Benbadis SR, Hauser A. An estimate of the prevalence of psychogenic nonepileptic seizures. Seizure 2000;9:280–1. [24] Gonzales-Heidrich J, Dodds A, Whitney J, MacMillan C, Waber D, Faraone SV, et al. Psychiatric disorders and behavioral characteristics of pediatric patients with both epilepsy and attention-deficit hyperactivity disorder. Epilepsy Behav 2007;10: 384–8.
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Psychiatric disorders as “hidden” contraindications for presurgical VEEG in patients with refractory epilepsy: A retrospective cohort study in a tertiary center Gerardo Maria de Araujo Filho a,⁎, Ana Eliza Romano Furlan a, Ana Elisa Sa Antunes Ribeiro a, Lucia Helena Neves Marques b a b
Department of Psychiatry and Medical Psychology, Faculdade de Medicina de São José do Rio Preto (FAMERP), São Paulo, Brazil Department of Neurological Sciences, Faculdade de Medicina de São José do Rio Preto (FAMERP), São Paulo, Brazil
a r t i c l e
i n f o
Article history: Received 18 November 2014 Revised 20 February 2015 Accepted 21 February 2015 Available online 21 March 2015 Keywords: Refractory epilepsy Psychiatric evaluation VEEG monitoring Psychiatric issues
a b s t r a c t Given the high frequency of psychiatric disorders (PDs) observed among patients with epilepsy, studies have highlighted the necessity of psychiatric evaluation for these patients, especially for those with refractory temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS) who are surgical candidates. Current evidence highlights the safety of video-electroencephalography (VEEG) as a means of investigation in patients with TLE-MTS and PDs. However, the presence of such disorders has still been seen as a contraindication for presurgical evaluation with VEEG in some epilepsy centers mainly because of the risk of negative behavioral events. The present retrospective cohort study performed in a Brazilian tertiary epilepsy center aimed to identify whether the presence of a PD remains a contraindication for presurgical VEEG. Clinical, sociodemographic, and psychiatric data from 41 patients who underwent VEEG as part of their presurgical evaluation were compared to data from 32 patients with refractory TLE-MTS who had not undergone VEEG. Psychiatric diagnoses were determined using the DSM-IV and ILAE criteria. Psychiatric disorders were diagnosed in 34 patients (46.6%). Major depressive disorder was the most frequent PD and was observed in 22 patients (30.1%). Anxiety disorders were observed in 14 patients (19.2%). Of the 41 patients (56.2%) who underwent presurgical VEEG, only 12 (29.2%) were found to have a PD during the presurgical psychiatric evaluation compared to 22 of the 32 (68.7%) who did not undergo VEEG (p = 0.001; RR = 2.35). The present findings suggest that the presence of a PD alone should not be a contraindication for VEEG monitoring and epilepsy surgery. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Studies in the literature have observed a prevalence rate of comorbid psychiatric disorders (PDs_ of 20-40% in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS), which rises to 70% in groups with refractory forms of epilepsy [1–6]. Mood disorders are the most common (24–74%), followed by anxiety (10–25%), psychotic disorders (2–9%), and personality disorders (1–2%) [2–5]. Given the high prevalence of presurgical PDs in this population, the psychiatric outcomes of such patients have become of particular interest to researchers [3,4]. Moreover, the correlation between the presence of presurgical PDs and poorer postsurgical seizure outcomes in patients with refractory epilepsy who underwent surgery has been increasingly recognized [5–10].
Given the high frequency of psychiatric comorbidity observed among patients with refractory TLE-MTS, studies have also highlighted the necessity of careful psychiatric evaluation as part of the presurgical and postsurgical protocols in tertiary epilepsy centers [1–6]. Despite recent studies indicating that the sole presence of a PD would not be a risk factor for evaluation with video-electroencephalography (VEEG), the presence of a PD has remained a relative contraindication for presurgical VEEG in some epilepsy centers mainly because of the risk of negative behavioral events, such as aggressiveness, attempted suicide, or psychomotor agitation [11,12]. The present retrospective cohort study aimed to determine whether PDs have remained a “hidden” contraindication for presurgical VEEG in a Brazilian tertiary epilepsy center with a psychiatrist as a member of the team. 2. Methods
⁎ Corresponding author at: Faculdade de Medicina de São José do Rio Preto, Av. Brigadeiro Faria Lima, 5416, São José do Rio Preto, São Paulo CEP: 15090-000, Brazil. Fax: +55 17 3201 5734. E-mail address: fi[email protected] (G.M. de Araujo Filho).
http://dx.doi.org/10.1016/j.yebeh.2015.02.026 1525-5050/© 2015 Elsevier Inc. All rights reserved.
2.1. Procedures All patients were followed in the outpatient clinic of a tertiary center (Epilepsy Section of the Faculdade de Medicina de São José do Rio Preto,
36
G.M. de Araujo Filho et al. / Epilepsy & Behavior 45 (2015) 35–38
São Paulo, Brazil) from January 2013 to November 2014 and underwent psychiatric evaluation. The eligibility criteria included patients who were older than 18, had an electroclinical diagnosis of TLE based on the ILAE classification [13], had been receiving follow-up care with the Epilepsy Center for at least six months, and had been referred for presurgical psychiatric evaluation before VEEG. All patients were seen by the same clinical team. Exclusion criteria included the presence of other clinical or neurological diseases besides epilepsy, cognitive impairments precluding evaluation, and patients who already had VEEG performed before psychiatric evaluation. Any clinical or social factors other than psychiatric evaluations recorded in patients' files that had precluded the use of VEEG were also considered as exclusion criteria. Patients with any PD at the time of psychiatric evaluation that precluded the use of VEEG were excluded, as were those who declined the procedure. Patients with a putative diagnosis of psychogenic nonepileptic seizures (PNES) were not included in the study because this diagnosis must be confirmed using VEEG. The VEEG consisted of 2–6 days of continuous monitoring with 32-channel EEG. Electrodes, including sphenoidal electrodes, were placed on the temporal lobe according to the 10–10 system. Mesial temporal sclerosis was determined to be present if atrophy, increased T2-weighted signal, decreased T1-weighted signal, and disrupted internal hippocampal structure were present and accompanied by observations of amygdala atrophy and/or temporal pole signal changes upon visual inspection of the MRI images. The epileptogenic zone was determined by predominantly ipsilateral interictal epileptiform discharges (80% cutoff) and seizure onset recorded during the prolonged VEEG monitoring. Refractoriness to medical treatment was considered present if seizures persisted after the utilization of at least two firstline medications for partial seizures at the highest tolerated dose for at least 6 months. An initial precipitant injury (IPI) was defined as the occurrence of severe cerebral events that required medical intervention and/or hospitalization during the first year of life before the appearance of epilepsy. Febrile seizures, meningoencephalitis, head trauma, or severe perinatal hypoxia were considered IPIs. 2.2. Psychiatric evaluation A single psychiatrist (GMAF) conducted the clinical interviews using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I criteria [14]. Because each patient could have more than one Axis I psychiatric diagnosis, both the number of patients diagnosed and all comorbid PDs diagnosed were considered in the analysis. The presence of other specific psychiatric diagnoses commonly associated with epilepsy, which are not covered by the DSM-IV but are well described in the literature, such as interictal dysphoric disorder (IDD) and epilepsy psychoses, was evaluated using the ILAE criteria. These criteria were also used to differentiate postictal psychosis (PIP) from
interictal psychosis (IIP) [15]. Data concerning the lifetime history of psychotropic treatment, defined as any past treatment with psychiatric drugs, were collected from patients during the first clinical interview. Information about the familial history of epilepsy and PDs was also obtained from patients through broad questions regarding whether any first-degree relative was in treatment for epilepsy and/or any PD at the time of the clinical interview. 2.3. Statistics Statistical analyses were performed using the version 14.0 of the Statistical Package for Social Sciences software (SPSS 10.0, Chicago, Illinois). Bivariate statistical analyses were performed using the most suitable statistical test for each situation (chi-square (χ2), Fisher's exact test, or Student's t-test for unequal variances). For statistical comparisons, patients were divided into two groups according to the use of VEEG monitoring as an indispensable presurgical evaluation that always occurred (or did not occur) as part of the service routine following psychiatric evaluation. A p-value b 0.05 was considered significant. 3. Results After written informed consent was obtained, the clinical and sociodemographic data of 73 consecutive surgical candidates with refractory TLE-MTS (48 females; 57.8%) who met the eligibility criteria were collected. Patients' clinical and sociodemographic characteristics are shown in Table 1. Mesial temporal sclerosis occurred more frequently on the left side (39 patients; 53.4%). Thirty-one patients (42.5%) had a history of IPI, with febrile seizures the most frequent (12 cases; 38.7%). There were also ten cases of head trauma (32.2%), five of perinatal hypoxia (16.1%), and two of meningoencephalitis (6.4%). Sixty-nine patients (94.5%) were using at least two medications at the time of evaluation. Carbamazepine (CBZ) was the most frequently used AED and was prescribed to 55 patients (75.3%), followed by phenobarbital (PB) (35; 47.9%), valproate (15; 20.5%), topiramate (TPM) (10; 13.7%), oxcarbazepine (OXC) (7; 9.6%), and phenytoin (PHT) (7; 9.6%). Benzodiazepines (BZDs), particularly clobazam (CLB), were the most common adjunctive drugs and were prescribed to 26 patients (35.6%). Among the 73 patients, Axis I psychiatric diagnoses were observed in 34 (56.6%). Major depressive disorder (MDD), which included all diagnoses of depression within the present cohort, was the most common PD and was diagnosed in 22 patients (30.1%). Fourteen patients (19.2%) had anxiety disorders, all of them presenting generalized anxiety disorder (GAD). Psychotic disorders were observed in seven patients (9.6%), all of which had IIP. Somatoform disorders (excluding the nonconfirmed presence of PNES) were observed in five patients (6.8%). Fourteen patients fulfilled the criteria for two Axis I disorders. Interictal dysphoric disorder
Table 1 Clinical and demographic data of patients with refractory epilepsy who did or did not undergo video-electroencephalography. Clinical/demographic data
Total
VEEG
Non-VEEG
p
Number of patients (%) Female gender (%) Age (mean ± SD) Age at epilepsy onset (mean ± SD) Epilepsy duration (mean ± SD) Lifetime psychiatric treatment (%) Family history of epilepsy (%) Family history of PD (%) Presence of IPI (%) Patients with PDs (%)
73 (100) 42 (57.5) 41.4 ± 12.10 13.9 ± 13.32 26.1 ± 13.32 34 (46.5) 22 (30.1) 13 (17.8) 31 (42.5) 34 (46.6)
41 (56.2) 20 (48.7) 41.0 ± 12.57 12.0 ± 9.17 28.4 ± 13.50 10 (24.3) 12 (29.2) 4 (9.7) 19 (46.3) 12 (29.2)
32 (43.8) 22 (68.7) 42.4 ± 12.66 16.8 ± 13.31 25.1 ± 14.30 24 (75.0) 10 (31.2) 9 (28.1) 12 (37.5) 22 (68.7)
– 0.22a 0.42b 0.37b 0.61b 0.02⁎,a
IPI: initial precipitant injury, PDs: psychiatric disorders, and SD: standard deviation. ⁎ p b 0.05. a Chi-square. b Student's t-test. c Fisher's exact test.
0.93a 0.03⁎,c 0.55a 0.001⁎,a
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was diagnosed in eight patients (10.9%), and six of them (75%) also presented an Axis I PD. This diagnosis, however, was not included in the statistics because its criteria are not included in the DSM-IV. Of the 73 patients included in the study, 41 (56.2%) underwent presurgical VEEG. Of those, only 12 patients (29.2%) were diagnosed with a PD during the presurgical psychiatric evaluation; nine presented with MDD and three, with IIP. In contrast, of the 32 patients who did not undergo VEEG, 22 (68.7%) presented with a PD (p = 0.001). In addition, a relative risk (RR) of 2.35 was observed, indicating that patients who were not diagnosed with a PD during a previous psychiatric evaluation were approximately 2.35 times more likely to undergo VEEG. Patients who did not undergo VEEG were also more likely to have had a history of PD (p = 0.02) and more likely to have a history of lifetime psychiatric treatment (p = 0.03). A comparison of the clinical and sociodemographic characteristics of both groups is shown in Table 1, and the diagnosed PDs are shown in Fig. 1.
4. Discussion The aim of this retrospective cohort study was to verify whether PDs have remained a “hidden” contraindication for presurgical VEEG in patients with refractory epilepsy (TLE-MTS) in a Brazilian tertiary center with a psychiatrist as a member of the team. Such verification is important for highlighting the need for more information regarding the possible risks involved in VEEG evaluation, and consequently the surgical procedure, in this population. The present study observed a significantly higher prevalence rate of PDs among patients who did not undergo VEEG compared to those with the same clinical and sociodemographic conditions who underwent such a procedure. As noted earlier, the available literature indicates a PD prevalence rate of 20–40% in patients with epilepsy, although it can be as high as 70% in refractory forms of the condition, particularly TLE-MTS [2–6]. Irrespective of some form of methodological bias, such as the selection of patients or the types of research instruments utilized, this elevated prevalence has highlighted the importance of psychiatric evaluation for these patients [16–20]. Such evaluation would be especially important for patients who are candidates for epilepsy surgery given the relatively higher risk of postsurgical PDs [5,6,16–20]. Recent studies have also shown a correlation between the risk of a poorer postsurgical seizure outcome and some presurgical clinical and sociodemographic characteristics, such as lifetime psychiatric history (particularly of major depressive disorder), presurgical history of secondarily generalized tonic–clonic seizures, duration of seizure disorder, extent of the resection of the mesial temporal structures, and the presence of neuropathologic abnormalities [17–20]. The most frequently discussed hypothesis in the literature is that presurgical PDs, and particularly MDD, could be
VEEG
epiphenomena of a more diffuse cerebral disease and may consequently be associated with poorer seizure control [5,6,8,16–20]. In the present study, a high prevalence rate of PDs was observed, which is in accordance with studies that measured the prevalence of PDs in patients with refractory epilepsy, particularly TLE-MTS [2–6]. In addition, the types of PDs observed were similar to those observed in the literature [2–6,21–23]. When the group of patients with refractory TLE-MTS who underwent VEEG, an indispensable investigational tool for surgical purposes in tertiary epilepsy centers, was compared to patients with the same clinical and sociodemographic conditions who did not undergo the procedure, significant differences in the presence of PDs were found. Although the literature has highlighted the risk of negative behavioral events in patients with epilepsy and PDs, recent studies have not observed significant differences regarding the presence of such events when patients with PDs diagnosed prior to VEEG evaluation were compared to patients without these conditions, even in patients with psychoses [11,12]. Moreover, differences regarding a poorer postsurgical seizure outcome were not observed when patients with presurgical PDs were compared to those without PDs in these studies, highlighting the need for additional studies to investigate this issue [11,12]. The present study has important limitations. We could not evaluate the prevalence of PDs that are not covered by the diagnostic criteria utilized in this study (DSM-IV and ILAE), such as attention-deficit hyperactivity disorder (ADHD), which is often observed among patients with epilepsy [24]. Moreover, only categorical criteria were utilized and no dimensional instruments applied, so we could not assess the presence of mild psychopathological changes in this population. Because of possible incomplete and/or unreliable data, unidentified causes that may have precluded the use of VEEG, including a potentially higher rate of decline of VEEG among patients with PDs, could not be detected. Because it is part of the routine of our center, we could not accurately assess whether VEEG was equally encouraged for both groups before and/or after psychiatric evaluation by clinicians. Finally, our findings demonstrate a correlation between patients with PDs in the non-VEEG group, which does not necessitate a cause–effect relationship. However, although based on a relatively small number of patients and conducted in a single epilepsy center, the present findings address the recurrent issue that, despite patients with presurgical PDs being thought to be at a greater risk of poorer psychiatric and seizure postsurgical outcomes, the sole presence of a PD should not be considered a contraindication for presurgical evaluation (including VEEG) in tertiary centers. Therefore, because of the elevated prevalence of PDs in patients with refractory epilepsy, neurologists and psychiatrists should improve their communication to share knowledge regarding PDs in epilepsy. In addition, there is a growing need for careful psychiatric evaluation to be included as part of the presurgical and postsurgical protocols, especially in
non-VEEG
Total
25 20 15 10 5 0 Mood disorders
Anxiety disorders
37
Somatoform Psychoses disorders
Interictal dysphoric disorder
Fig. 1. Psychiatric diagnoses of patients with refractory epilepsy in a tertiary center. VEEG: video-electroencephalogram.
38
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