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Identification of three distinct groups of patients with both epilepsy and psychogenic nonepileptic seizures
Epilepsy & Behavior 22 (2011) 318–323
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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Identification of three distinct groups of patients with both epilepsy and psychogenic nonepileptic seizures A. Magaudda ⁎, S.C. Gugliotta, R. Tallarico, T. Buccheri, R. Alfa, A. Laganà Epilepsy Center, Neuroscience Department, University of Messina, Messina, Italy
a r t i c l e
i n f o
Article history: Received 30 May 2011 Revised 27 June 2011 Accepted 5 July 2011 Available online 15 August 2011 Keywords: Psychogenic nonepileptic seizures Epileptic seizures Mixed psychogenic nonepileptic seizures Pure psychogenic nonepileptic seizures Etiology Conversion disorder Dissociative disorders Reinforced behavior pattern
a b s t r a c t Psychogenic nonepileptic seizures (PNES) can be observed in patients with or without epilepsy (mixed and pure PNES). Patients with mixed PNES are usually considered to be a homogeneous group characterized by the coexistent epilepsy. Our study found that patients with mixed PNES were not homogeneous, but could be divided into three groups based on epilepsy type, mental level, comorbid psychiatric disorders, and history of traumatic experiences. Group 1 patients have pharmacoresistant epilepsy, normal cognition, and comorbid anxiety and/or depressive disorders. Here, PNES etiology is the epilepsy-related problems. In group 2 patients, the epilepsy is associated with mental retardation and dependent personality traits. PNES etiology is represented by the reduction or cessation of seizures. The PNES allow patients to continue receiving attention from caregivers. Group 3 patients have epilepsy, normal cognition, comorbid cluster B personality disorders and anxiety disorders, and psychic trauma. Here, PNES etiology is not related to the epilepsy, but to the psychic trauma. © 2011 Elsevier Inc. All rights reserved.
1. Introduction Psychogenic nonepileptic seizures (PNES) are episodes of paroxysmal impairment of self-control associated with a range of motor, sensory, and mental manifestations that represent an experiential or behavioral response to emotional or social distress [1]. There is a vast amount of literature dealing with PNES that has been comprehensively reexamined in two recent reviews [1,2]. The true rate of PNES in the general population is not known. Some authors report figures of 1.5–3/100,000 per year, but these would appear to be underestimates, in part due to bias caused by misdiagnosis. Indeed, 5–20% of the patients diagnosed with epilepsy have PNES. PNES can be found in patients affected by epilepsy, either ongoing or in remission (mixed PNES), and incidence ranges from 5 to 60% according to various studies [3–12]. Psychogenic nonepileptic seizures are more common in females. They are thought to be sustained by conversion or dissociative mechanisms. In most patients, the PNES represent the expression of an intrapsychic conflict and their purpose is to reduce anxiety (primary gain). PNES can also be useful in attaining a secondary gain (avoiding unpleasant activities or eliciting a positive response from the environment). In some patients, particularly those with mental retardation or borderline intellectual functioning, PNES appear to manifest a reinforced behavior pattern (RBP) that has developed over time ⁎ Corresponding author. Fax: + 39 0902212301. E-mail address: [email protected] (A. Magaudda). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.07.005
within the context of the person's relationships with care providers. Often, these patients have unconsciously learned to produce seizurelike episodes that allow them to control the environment and the patient is paradoxically reinforced in this behavior by caregivers. As such, PNES do not represent any underlying psychological conflict in these patients [13]. The comorbid psychiatric disorders most frequently diagnosed in patients with PNES are: (Axis I) Major Depressive Disorder, Dysthymic Disorder [14–17], Generalized Anxiety Disorder (GAD), Panic Disorder with or without Agoraphobia, Posttraumatic Stress Disorder (PTSD) [18–20], and Psychotic Disorder; (Axis II) Cluster B Personality Disorders (Borderline Personality Disorder [BPD] and Histrionic Personality Disorder [HPD)] and Cluster C Dependent Personality Disorder (DPD) [21–28]. Reuber and Elger [29] maintain that PNES etiology is expressed by a number of factors that determine their appearance, continuation, and outcome as follows: (1) predisposing factors (trauma, family dysfunction, personality, psychopathology, illness perceptions and coping styles, cognitive factors, neurobiological factors); (2) precipitating factors (stress and dilemmas, triggers for seizure recurrence); (3) perpetuating factors (health care contacts, social/financial illness gain). Bodde et al. [2] proposed a different model organized on five levels: 1. Psychological etiology comprises sexual abuse and other traumatic experiences. 2. Vulnerability refers to factors that predispose a person to develop psychosomatic symptoms like PNES, for example, personality
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factors, gender, neuropsychological impairments, and age. Many authors have pointed to the specific vulnerability of patients with PNES in terms of both their emotional “makeup” and their neuropsychological functioning. Physical factors may also play a role here. 3. Shaping factors can specifically shape the symptoms in the direction or form of “seizures,” in contrast to, for example, movement disorders or “headache-like symptoms.” One shaping factor could be a family relative with epileptic seizures (symptom modeling) or a history of epilepsy. 4. Triggering factors create circumstances or situations that provoke PNES such as factors that refer to primary gain. Psychological mechanisms that transform an emotional state into a seizure can also play a part in these triggering factors, for example, dissociation and somatization. Such factors explain why seizures occur on a specific day or in a cluster or why there is a period of remission. This differentiates PNES from conversion states, which are more or less permanently present. 5. The aforementioned factors are specifically important in the development of PNES, whereas prolongation factors are important in explaining why the seizures persist and why PNES may become a chronic disorder. Thus, these factors provide a profile of PNES frequency and resistance to therapy. Examples of modulating factors are the patient's coping strategy and secondary gain aspects. Those with PNES have also been found to have underlying organic deficiencies, such as neuropsychological deficits [30,31], slight neurological dysfunctions [32], brain trauma in 20–30% of cases [8,18,33], chronic pain or fibromyalgia [34], and toxicity resulting from antiepileptic drugs (AEDs) [35] with a mechanism similar to that of the PNES that arise after anesthesia [36]. Patients with PNES often have a history of multiple medical pathologies or of a single chronic disease [30,37–42]. Epilepsy is a chronic physical condition with serious psychosocial implications and is normally regarded as the main etiology in patients with mixed PNES in which epileptic seizures act as a shaping factor (symptom modeling). However, patients with mixed PNES have different types of epilepsy (AED-responsive or -pharmacoresistant, epileptic encephalopathies with mental retardation and neurological deficit) or may have had epilepsy in the past. The different types of epilepsy in association with different comorbid psychiatric disorders and the presence or absence of other factors (sexual abuse or other traumatic experiences) could provoke PNES through different pathogenetic mechanisms. The majority of studies include not only patients with PNES alone (pure PNES), but also patients with both PNES and ES (mixed PNES). Some studies have compared groups of patients with mixed PNES with groups of patients with epilepsy alone [43,44] or patients with mixed PNES, those with pure PNES, and those with epilepsy alone [28,45]. Some studies have evaluated the differences between patients with pure PNES and those with mixed PNES [46–49]. However, to the best of our knowledge, no studies have focused exclusively on patients with mixed PNES. Such patients are generally viewed as a single homogeneous group characterized by the co-presence of ES and PNES. The aim of our study was to evaluate if the aforementioned factors (type of epilepsy, cognition, comorbid psychiatric disorders, and history of traumatic experiences) could provide a means to differentiate between patients affected by mixed PNES and thereby classify them into subgroups. 2. Methods One hundred thirty patients affected by PNES were observed at the Epilepsy Center of the University of Messina (Messina, Italy) from 1986 to 2010. Sufficient information was available for 89 of these
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patients; 20 (22.47%) of them were diagnosed with mixed PNES and were included in our study. Patients had undergone an epileptological and psychiatric evaluation and the PNES diagnosis was made after video/EEG monitoring. The recorded attack was then shown to caregivers to ascertain that its semiology coincided with that of the seizures the patient usually experienced. The following factors were taken into account for each patient: type of epilepsy, age at ES onset and PNES onset; ES and PNES semiology; neurological examination (NE); cognition (IQ); comorbid psychiatric disorders and general medical conditions; history of traumatic experiences (sexual or physical abuse, bereavement, etc.); PNES etiology; ES and PNES outcome. We classified PNES on the basis of their similarity to ES semiology as follows: convulsive generalizedlike (clonic, tonic–clonic, hypermotor); akinetic; falling attacks (syncope-like); partial complex-like; simple partial-like (with somatosensory or focal motor or autonomic symptoms or psychic symptoms, such as fear, anxiety, and anger) (Table 1).
3. Results 3.1. Demographic and medical history data The study population comprised 20 patients, 18 females and 2 males. Mean age at last follow-up was 36.2 years (SD 11.81). Mean age at ES and PNES onset was 11.65 years (SD 6.72) and 23.45 years (SD 11.04), respectively; thus, the mean time between ES onset and PNES onset was 11.8 years. The average delay before PNES diagnosis was 7.95 years (SD 8.06). Mean duration of PNES illness was 12.85 years (SD 8.59). We classified patients into three groups on the basis of the different types of epilepsy, cognition, comorbid psychiatric disorders, and history of traumatic experiences. 3.2. Group 1: Six patients, five females and one male Mean age at last follow-up was 37.17 years (SD 8.56). Mean age at ES and PNES onset was 15.33 years (SD 8.98) and 25.83 years (SD 10.19), respectively. Mean time between ES onset and PNES onset was 10.5 years. Average delay before PNES diagnosis was 3.17 years (SD 4.02). Mean duration of PNES illness was 11.33 years (SD 10.73). All patients had normal IQ and NE (Table 2). Epilepsy diagnosis was symptomatic focal epilepsy (SFE) in five patients and cryptogenic generalized epilepsy (CGE) in one patient. Five had pharmacoresistant seizures. ES semiology was complex partial (CP) in five patients, with secondary generalization (SG) in one patient, and generalized tonic–clonic (GTC) in one patient. Semiology of PNES was similar to that of ES (CP-like) in four patients; two patients, one with SGCP and one with GTC epileptic seizures, had convulsive generalized-like (CG-like) PNES. Comorbid psychiatric disorders were: Generalized Anxiety Disorder (GAD) in three patients, associated with Dependent Personality Disorder (DPD) in one case; Dysthymic Disorder (DD) in three patients, associated with GAD in one patient and with Personality Disorder Not Otherwise Specified (PD NOS) in another case. Therefore, in this group,
Table 1 Classification of psychogenic nonepileptic seizures. Convulsive generalized-like Akinetic Falling attacks Partial complex-like Simple partial-like
Clonic, tonic–clonic, hypermotor Syncope-like With somatosensory or focal motor or autonomic symptoms or psychic symptoms, such as fear, anxiety, and anger
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Table 2 General characteristics of the Group 1 patientsa. Patient
Sex
Age
Epileptic syndrome
Age at ES onset
Age at PNES onset
ES type
PNES type
Neurological examination
Cognition
Psychiatric comorbidity
General medical conditions
Etiology of PNES
1
F
27
SFE
14
25
CP
CP-like
Normal
Normal
GAD
Epilepsy
2
2
F
49
SFE
4
20
CP
CP-like
Normal
Normal
Epilepsy
29
3
F
45
SFE
18
43
CP
CP-like
Normal
Normal
4
F
30
SFE
14
20
SGCP
CG-like
Normal
Normal
5
F
34
SFE
11
15
CP
CP-like
Normal
Normal
GAD DPD DD GAD DD Personality Disorder NOS GAD
Cardiopathy Migraine Obesity Tension headaches Obesity Obesity
6
M
38
CGE
31
32
GTC
CG-like
Normal
Normal
DD
Hypertension Obesity Migraine Hypertension Dyslipidemia Obesity
Epilepsy Psychic trauma Epilepsy Dysthymia Epilepsy Epilepsy Work problems
Mean duration of PNES (years)
2 10
19 6
a SFE, Symptomatic focal epilepsy; CGE, cryptogenic generalized epilepsy; CP, complex partial; GTC, generalized tonic–clonic; SG, secondarily generalized; CP-like, complex partial-like; CG-like, convulsive generalized-like; GAD, Generalized Anxiety Disorder; DPD, Dependent Personality Disorder; DD, Dysthymic Disorder; NOS, Not Otherwise Specified.
depressive and anxiety disorders are the main comorbid psychiatric disorders. These patients had several problems linked to epilepsy, such as stigmatization, limitations affecting the performance of different activities, poor social adaptation, difficulty in establishing long-lasting relationships, and employment. Psychogenic nonepileptic seizures ceased in two patients, after PNES diagnosis in one case and after cessation of ES in the other. PNES persisted in three patients with pharmacoresistant epilepsy. We have no information on the PNES outcome in the remaining patient. 3.3. Group 2: Seven patients, six females and one male Mean age at last follow-up was 31.71 years (SD 10.04). Mean age at ES and PNES onset was 9 years (SD 5.2) and 20.14 years (SD 9.56), respectively. Mean time between ES and PNES onset was 11.14 years. Average delay before PNES diagnosis was 6.86 years (SD 5.58). Mean duration of PNES illness was 11.57 years (SD 7.48). All patients had mild mental retardation. Neurological examination was normal in
four patients. Two patients had hemiparesis, and one had cerebellar syndrome and amaurosis (Table 3). Six patients were affected by SFE partially responsive to AEDs. One had been affected by idiopathic generalized epilepsy (IGE) and had not had any seizures for many years. ES semiology was CP in four patients, with SG in three of them; simple partial (SP) with SG in one patient; GTC in one patient; and absence, tonic, and atonic seizures in one patient. Semiology of PNES was similar to that of ES in one patient (CPlike); arc en circle in one patient; akinetic in one patient; myoclonic jerks in one patient; and CG-like in three patients who also had recurrent pseudo-grand mal status. In all patients PNES occurred after cessation (one patient) or reduction in frequency (five patients) of ES. Comorbid psychiatric disorders were: DPD in four patients; Adjustment Disorder (AD) with depressive mood in one patient; Histrionic Personality Disorder (HPD) in one patient; and Psychotic Disorder Not Otherwise Specified (PDNOS) associated with DPD in another case. Therefore, comorbid psychiatric disorders were the main personality disorders. In all patients, RBP represented the pathogenetic mechanism of PNES.
Table 3 General characteristics of the group 2 patientsa. Neurological examination
Cognition Psychiatric comorbidity
General medical conditions
Etiology of PNES
Absence Arc en circle Tonic Atonic SGCP Akinetic
Left hemiparesis
Mild MR
Obesity
Decrease in 20 ES frequency
Normal
Mild MR
Normal
Mild MR
Patient Sex Age Epileptic Age at Age at ES type syndrome ES onset PNES onset
PNES type
1
F
31
SFE
9
11
2
F
31
SFE
13
28
3
F
24
IGE
1
6
GTC
4
F
25
SFE
15
18
SGSP
Myoclonic jerks CG-like
5
F
21
SFE
12
18
SGCP
CG-like
Right hemiparesis
Mild MR
6
F
41
SFE
3
30
SGCP
CG-like
Normal
Mild MR
7
M
49
SFE
10
30
CP
CP-like
Normal
Mild MR
Cerebellar syndrome Mild MR Amaurosis
DPD
AD with depressed mood HPD
Decrease in ES frequency
Mean duration of PNES (years)
3
Obesity
Cessation 18 of ES DPD Obesity Decrease in 7 ES frequency DPD Q-T syndrome Decrease in 3 Obesity ES frequency DPD Obesity Decrease in 11 Hypothyroidism ES frequency Obesity Decrease in 19 Psychotic ES frequency Disorder NOS DPD
a SFE, symptomatic focal epilepsy; IGE, idiopathic generalized epilepsy; CP, complex partial; GTC, generalized tonic–clonic; SP, simple partial; SG, secondarily generalized; CG-like, convulsive generalized-like; CP-like, complex partial-like; MR, mental retardation; DPD, Dependent Personality Disorder; AD, Adjustment Disorder; HPD, Histrionic Personality Disorder; NOS, Not Otherwise Specified.
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Table 4 General characteristics of the group 3 patientsa. Patient Sex Age Epileptic Age at Age at ES syndrome ES onset PNES onset type
PNES type
Neurological Cognition Psychiatric General medical examination comorbidity conditions
Etiology of PNES
1
F
53
SFE
6
44
SGCP
Akinetic
Normal
Normal
DD
Father's death
2
F
37
CGE
12
13
GTC
CG-like
Normal
Normal
HPD
3
F
67
CPE
14
42
SGCP
CP-like
Normal
Normal
GAD
4 5
F F
36 20
BCECTS IGE
6 20
28 18
SGSP GTC
CP-like Akinetic
Normal Normal
Normal Normal
BPD BPD
6 7
F F
30 36
IGE BCECTS
13 7
10 18
GTC SP
CG-like CP-like
Normal Normal
Normal Normal
BPD GAD
Migraine Obesity HCV hepatitis Cardiopathy
Obesity
Rheumatic arthritis
Sexual abuse Daughter's epilepsy Multiple medical conditions Mother's death Miscarriage Job loss Poor adaptation to work Sexual abuse Difficult relationships
Mean duration of PNES (years) 9 24
25 8 2 20 18
a SFE, symptomatic focal epilepsy; CGE, cryptogenic generalized epilepsy; CPE, cryptogenic partial epilepsy; BCECTS, benign childhood epilepsy with centrotemporal spikes; IGE, idiopathic generalized epilepsy; CP, complex partial; GTC, generalized tonic–clonic; SP, simple partial; SG, secondarily generalized; CG-like, convulsive generalized-like; CP-like, complex partial-like; DD, Dysthymic Disorder; HPD, Histrionic Personality Disorder; GAD, Generalized Anxiety Disorder; BPD, Borderline Personality Disorder.
Psychogenic nonepileptic seizures ceased or decreased in frequency after diagnosis in three patients and persisted in four others. 3.4. Group 3: Seven females Mean age at last follow-up was 39.86 years (SD 15.49). Mean age at ES and PNES onset was 11.14 years (SD 5.18) and 24.71 years (SD 13.7) respectively. Mean time between ES onset and PNES onset was 13.57 years. Average delay before PNES diagnosis was 13.14 years (SD 10.27). Mean duration of PNES illness was 15.14 years (SD 8.84). All patients had normal IQ and neurological examination (Table 4). One patient had SFE; one patient had CGE; one patient had cryptogenic partial epilepsy (CPE); two patients had been affected by benign childhood epilepsy with centrotemporal spikes (BCECTS); two patients had had IGE. Types of ES were CP with SG in two patients; GTC in three patients; and SP in two patients, with SG in one case. Semiology of PNES was similar to that of ES in three patients, but different in the other four (CP-like in two patients and akinetic in two others). One patient had recurrent convulsive generalized pseudostatus. All patients in this group had suffered psychic trauma: sexual abuse (two patients), parent's death (two patients), job loss (one patient), difficult relationships (one patient), poor adaptation to work (one patient). Thus, psychic trauma can be considered the etiology of PNES. This is particularly true in two patients whose PNES appeared before ES. Comorbid psychiatric disorders were: Borderline Personality Disorder (BPD) in three patients; HPD in one case; GAD in two patients; and DD in one patient. PNES ceased or decreased in frequency in four patients: after diagnosis in one case, after psychotherapy in another, and after antidepressant medication in the other two. PNES persisted in two patients, one of whom committed suicide. 4. Discussion Our study has focused specifically on patients with mixed PNES. We were able to divide these patients into three separate groups on the basis of epilepsy type, cognition, comorbid psychiatric disorders, and history of trauma. Although there is a great deal of literature dealing with PNES, many of the studies include both patients with mixed PNES and patients with pure PNES and make no distinction between them. Some studies have compared groups of patients with mixed PNES with groups of patients with epilepsy alone [43,44] or patients with mixed PNES, those with pure PNES, and those with epilepsy alone [28,45]. One study used the
Minnesota Multiphasic Personality Inventory (MMPI) to determine any differences in psychological profile among 32 patients with mixed PNES, 38 with pure PNES, and 36 with epilepsy alone. The results revealed that patients with PNES, both pure and mixed, had similar personality profiles that differed from those of patients with only epilepsy. Patients with PNES scored higher on the Hs (Hypochondria) and Hy (Hysteria) Scales compared with Scale D (Depression), on which patients with epilepsy alone scored higher [45]. A number of studies have evaluated the differences between patients with pure PNES and those with mixed PNES [46–49]. In one study conducted on 25 patients with mixed PNES and 85 with pure PNES, the authors identified several significant differences between the two groups. Patients with mixed PNES were younger at diagnosis (by video/EEG), had a longer follow-up period, had a longer delay in diagnosis, and were less susceptible to induction techniques; a higher percentage had been treated with AEDs, and a lower proportion had had a reduction in AEDs. Thus, no significant differences emerged with respect to age, gender, social level, family history of epilepsy, age at PNES onset, and semiology of PNES. Moreover, 16 of the 25 patients with mixed PNES had PNES similar to ES; the remaining 9 patients had PNES with different semiology [49]. As for the psychiatric profiles for the two groups (mixed and pure PNES), some authors report that personality disorders are more frequently diagnosed in patients with mixed PNES, whereas anxiety disorders and somatoform disorders prevail for patients with pure PNES [44]. Overall, differences between patients with pure PNES and those with mixed PNES have been highlighted, but there are no studies in the literature that have investigated exclusively patients with mixed PNES, who have been considered to be a homogeneous group characterized by the coexistent epilepsy. However, patients with mixed PNES have different types of epilepsy and different comorbid psychiatric disorders, may be intellectually impaired or have a normal IQ, and may or may not have a history of psychic trauma. The different types of epilepsy in association with different comorbid psychiatric disorders and the presence or absence of other factors (sexual abuse and other traumatic experiences) could lead to PNES through different pathogenetic mechanisms. Here we propose a classification of patients with mixed PNES based on epilepsy type, cognition, comorbid psychiatric disorders, and history of traumatic experiences. All these factors can be objectively detected. The main features of group 1 are pharmacoresistant SFE with CP seizures with experiential phenomena, normal cognition, and anxiety and/or depressive disorders. These patients had several problems linked to epilepsy, such as stigmatization, limitations affecting the
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performance of different activities, poor social adaptation, difficulty in establishing long-lasting relationships, and employment. Therefore, the etiology of PNES is the negative perception of epilepsy and problems linked to this illness. In the majority of these patients, the psychic symptoms (fear, anxiety, etc.) of ES were reproduced during PNES and made differential diagnosis relatively difficult. In this group the prognosis for the PNES was closely linked to how their epilepsy evolved. As these patients were normal intellectually, cognitive-behavioral psychotherapy combined with pharmacological treatment (where indicated for comorbid psychiatric disorders) would appear to be the most suitable treatment strategy. Group 2 comprises patients with mental retardation, affective immaturity, dependent personality traits, and early onset of the physical condition of which the ES were a symptom. The prevailing etiology of PNES in group 2 subjects is the cessation or decrease in frequency of ES. These patients had early-onset epilepsy and thus received a great deal of attention from caregivers. Hence, the PNES experienced by these patients do not constitute a conversion disorder sustained by an intrapsychic conflict; rather, they represent behavior that is unconsciously learned and used to retain the secondary gains deriving from their role as an ill person and to have control over their immediate surroundings. Given that the decrease in frequency or cessation of ES would mean the loss of these advantages, the PNES represent a substitute symptom. Family members would discontinue their role as caregivers were the ES to lessen or disappear, and then this would reinforce the mechanism that triggered the PNES. This pathogenetic mechanism was described by Gates and Erdahl in 1993 as a reinforced behavior pattern [13]. Treatment choices are more limited as psychotherapy must be ruled out because of the mental retardation of subjects and anxiolytic or antidepressant drugs are not useful because these patients do not have anxiety or depressive disorders. The main type of comorbid psychiatric disorder is DPD. In such cases, certain deconditioning techniques may be useful (e.g., “if you stop having PNES then you will be rewarded”). It is extremely important to teach caregivers how to distinguish PNES from ES, not to be alarmed by them, and not to reinforce the patient's role as a sick person. Group 3 comprises patients with non-pharmacoresistant epilepsy, ongoing or in remission, who have experienced one or more traumatic life events (abuse, bereavement, etc.). The most frequent comorbid psychiatric disorders in this group are personality disorders (Cluster B) and anxiety disorders. Here, it is not the epilepsy that constitutes the main etiology of PNES, but the experience of traumatic life events, as in patients with pure PNES. The timing of PNES onset is closely linked to the traumatic event. In these patients, epilepsy acts as a form of “symptom modeling.” Understandably, the easiest means of conversion for these patients, who have experienced ES, is to reproduce symptoms similar to those of their ES, especially if they are experiential symptoms. PNES outcome is not connected to changes in the epileptic condition, but to resolution or continuation of the intrapsychic conflict produced by psychic trauma. The main methodological limitation of our study is that our classification has not been tested independently by physicians not involved in the study to validate that the criteria proposed by us are sufficient to differentiate the three groups of patients with mixed PNES. This would be a means to test whether our categorization can be replicated or to detect whether there is more overlap between these groups than we have reported. This could be done in a subsequent study. Despite this limitation, our study provides a novel classification of patients with mixed PNES that can be tested further. The identification of different subgroups of patients with mixed PNES provides a useful tool to guide choice of the most appropriate strategy for treatment.
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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Identification of three distinct groups of patients with both epilepsy and psychogenic nonepileptic seizures A. Magaudda ⁎, S.C. Gugliotta, R. Tallarico, T. Buccheri, R. Alfa, A. Laganà Epilepsy Center, Neuroscience Department, University of Messina, Messina, Italy
a r t i c l e
i n f o
Article history: Received 30 May 2011 Revised 27 June 2011 Accepted 5 July 2011 Available online 15 August 2011 Keywords: Psychogenic nonepileptic seizures Epileptic seizures Mixed psychogenic nonepileptic seizures Pure psychogenic nonepileptic seizures Etiology Conversion disorder Dissociative disorders Reinforced behavior pattern
a b s t r a c t Psychogenic nonepileptic seizures (PNES) can be observed in patients with or without epilepsy (mixed and pure PNES). Patients with mixed PNES are usually considered to be a homogeneous group characterized by the coexistent epilepsy. Our study found that patients with mixed PNES were not homogeneous, but could be divided into three groups based on epilepsy type, mental level, comorbid psychiatric disorders, and history of traumatic experiences. Group 1 patients have pharmacoresistant epilepsy, normal cognition, and comorbid anxiety and/or depressive disorders. Here, PNES etiology is the epilepsy-related problems. In group 2 patients, the epilepsy is associated with mental retardation and dependent personality traits. PNES etiology is represented by the reduction or cessation of seizures. The PNES allow patients to continue receiving attention from caregivers. Group 3 patients have epilepsy, normal cognition, comorbid cluster B personality disorders and anxiety disorders, and psychic trauma. Here, PNES etiology is not related to the epilepsy, but to the psychic trauma. © 2011 Elsevier Inc. All rights reserved.
1. Introduction Psychogenic nonepileptic seizures (PNES) are episodes of paroxysmal impairment of self-control associated with a range of motor, sensory, and mental manifestations that represent an experiential or behavioral response to emotional or social distress [1]. There is a vast amount of literature dealing with PNES that has been comprehensively reexamined in two recent reviews [1,2]. The true rate of PNES in the general population is not known. Some authors report figures of 1.5–3/100,000 per year, but these would appear to be underestimates, in part due to bias caused by misdiagnosis. Indeed, 5–20% of the patients diagnosed with epilepsy have PNES. PNES can be found in patients affected by epilepsy, either ongoing or in remission (mixed PNES), and incidence ranges from 5 to 60% according to various studies [3–12]. Psychogenic nonepileptic seizures are more common in females. They are thought to be sustained by conversion or dissociative mechanisms. In most patients, the PNES represent the expression of an intrapsychic conflict and their purpose is to reduce anxiety (primary gain). PNES can also be useful in attaining a secondary gain (avoiding unpleasant activities or eliciting a positive response from the environment). In some patients, particularly those with mental retardation or borderline intellectual functioning, PNES appear to manifest a reinforced behavior pattern (RBP) that has developed over time ⁎ Corresponding author. Fax: + 39 0902212301. E-mail address: [email protected] (A. Magaudda). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.07.005
within the context of the person's relationships with care providers. Often, these patients have unconsciously learned to produce seizurelike episodes that allow them to control the environment and the patient is paradoxically reinforced in this behavior by caregivers. As such, PNES do not represent any underlying psychological conflict in these patients [13]. The comorbid psychiatric disorders most frequently diagnosed in patients with PNES are: (Axis I) Major Depressive Disorder, Dysthymic Disorder [14–17], Generalized Anxiety Disorder (GAD), Panic Disorder with or without Agoraphobia, Posttraumatic Stress Disorder (PTSD) [18–20], and Psychotic Disorder; (Axis II) Cluster B Personality Disorders (Borderline Personality Disorder [BPD] and Histrionic Personality Disorder [HPD)] and Cluster C Dependent Personality Disorder (DPD) [21–28]. Reuber and Elger [29] maintain that PNES etiology is expressed by a number of factors that determine their appearance, continuation, and outcome as follows: (1) predisposing factors (trauma, family dysfunction, personality, psychopathology, illness perceptions and coping styles, cognitive factors, neurobiological factors); (2) precipitating factors (stress and dilemmas, triggers for seizure recurrence); (3) perpetuating factors (health care contacts, social/financial illness gain). Bodde et al. [2] proposed a different model organized on five levels: 1. Psychological etiology comprises sexual abuse and other traumatic experiences. 2. Vulnerability refers to factors that predispose a person to develop psychosomatic symptoms like PNES, for example, personality
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factors, gender, neuropsychological impairments, and age. Many authors have pointed to the specific vulnerability of patients with PNES in terms of both their emotional “makeup” and their neuropsychological functioning. Physical factors may also play a role here. 3. Shaping factors can specifically shape the symptoms in the direction or form of “seizures,” in contrast to, for example, movement disorders or “headache-like symptoms.” One shaping factor could be a family relative with epileptic seizures (symptom modeling) or a history of epilepsy. 4. Triggering factors create circumstances or situations that provoke PNES such as factors that refer to primary gain. Psychological mechanisms that transform an emotional state into a seizure can also play a part in these triggering factors, for example, dissociation and somatization. Such factors explain why seizures occur on a specific day or in a cluster or why there is a period of remission. This differentiates PNES from conversion states, which are more or less permanently present. 5. The aforementioned factors are specifically important in the development of PNES, whereas prolongation factors are important in explaining why the seizures persist and why PNES may become a chronic disorder. Thus, these factors provide a profile of PNES frequency and resistance to therapy. Examples of modulating factors are the patient's coping strategy and secondary gain aspects. Those with PNES have also been found to have underlying organic deficiencies, such as neuropsychological deficits [30,31], slight neurological dysfunctions [32], brain trauma in 20–30% of cases [8,18,33], chronic pain or fibromyalgia [34], and toxicity resulting from antiepileptic drugs (AEDs) [35] with a mechanism similar to that of the PNES that arise after anesthesia [36]. Patients with PNES often have a history of multiple medical pathologies or of a single chronic disease [30,37–42]. Epilepsy is a chronic physical condition with serious psychosocial implications and is normally regarded as the main etiology in patients with mixed PNES in which epileptic seizures act as a shaping factor (symptom modeling). However, patients with mixed PNES have different types of epilepsy (AED-responsive or -pharmacoresistant, epileptic encephalopathies with mental retardation and neurological deficit) or may have had epilepsy in the past. The different types of epilepsy in association with different comorbid psychiatric disorders and the presence or absence of other factors (sexual abuse or other traumatic experiences) could provoke PNES through different pathogenetic mechanisms. The majority of studies include not only patients with PNES alone (pure PNES), but also patients with both PNES and ES (mixed PNES). Some studies have compared groups of patients with mixed PNES with groups of patients with epilepsy alone [43,44] or patients with mixed PNES, those with pure PNES, and those with epilepsy alone [28,45]. Some studies have evaluated the differences between patients with pure PNES and those with mixed PNES [46–49]. However, to the best of our knowledge, no studies have focused exclusively on patients with mixed PNES. Such patients are generally viewed as a single homogeneous group characterized by the co-presence of ES and PNES. The aim of our study was to evaluate if the aforementioned factors (type of epilepsy, cognition, comorbid psychiatric disorders, and history of traumatic experiences) could provide a means to differentiate between patients affected by mixed PNES and thereby classify them into subgroups. 2. Methods One hundred thirty patients affected by PNES were observed at the Epilepsy Center of the University of Messina (Messina, Italy) from 1986 to 2010. Sufficient information was available for 89 of these
319
patients; 20 (22.47%) of them were diagnosed with mixed PNES and were included in our study. Patients had undergone an epileptological and psychiatric evaluation and the PNES diagnosis was made after video/EEG monitoring. The recorded attack was then shown to caregivers to ascertain that its semiology coincided with that of the seizures the patient usually experienced. The following factors were taken into account for each patient: type of epilepsy, age at ES onset and PNES onset; ES and PNES semiology; neurological examination (NE); cognition (IQ); comorbid psychiatric disorders and general medical conditions; history of traumatic experiences (sexual or physical abuse, bereavement, etc.); PNES etiology; ES and PNES outcome. We classified PNES on the basis of their similarity to ES semiology as follows: convulsive generalizedlike (clonic, tonic–clonic, hypermotor); akinetic; falling attacks (syncope-like); partial complex-like; simple partial-like (with somatosensory or focal motor or autonomic symptoms or psychic symptoms, such as fear, anxiety, and anger) (Table 1).
3. Results 3.1. Demographic and medical history data The study population comprised 20 patients, 18 females and 2 males. Mean age at last follow-up was 36.2 years (SD 11.81). Mean age at ES and PNES onset was 11.65 years (SD 6.72) and 23.45 years (SD 11.04), respectively; thus, the mean time between ES onset and PNES onset was 11.8 years. The average delay before PNES diagnosis was 7.95 years (SD 8.06). Mean duration of PNES illness was 12.85 years (SD 8.59). We classified patients into three groups on the basis of the different types of epilepsy, cognition, comorbid psychiatric disorders, and history of traumatic experiences. 3.2. Group 1: Six patients, five females and one male Mean age at last follow-up was 37.17 years (SD 8.56). Mean age at ES and PNES onset was 15.33 years (SD 8.98) and 25.83 years (SD 10.19), respectively. Mean time between ES onset and PNES onset was 10.5 years. Average delay before PNES diagnosis was 3.17 years (SD 4.02). Mean duration of PNES illness was 11.33 years (SD 10.73). All patients had normal IQ and NE (Table 2). Epilepsy diagnosis was symptomatic focal epilepsy (SFE) in five patients and cryptogenic generalized epilepsy (CGE) in one patient. Five had pharmacoresistant seizures. ES semiology was complex partial (CP) in five patients, with secondary generalization (SG) in one patient, and generalized tonic–clonic (GTC) in one patient. Semiology of PNES was similar to that of ES (CP-like) in four patients; two patients, one with SGCP and one with GTC epileptic seizures, had convulsive generalized-like (CG-like) PNES. Comorbid psychiatric disorders were: Generalized Anxiety Disorder (GAD) in three patients, associated with Dependent Personality Disorder (DPD) in one case; Dysthymic Disorder (DD) in three patients, associated with GAD in one patient and with Personality Disorder Not Otherwise Specified (PD NOS) in another case. Therefore, in this group,
Table 1 Classification of psychogenic nonepileptic seizures. Convulsive generalized-like Akinetic Falling attacks Partial complex-like Simple partial-like
Clonic, tonic–clonic, hypermotor Syncope-like With somatosensory or focal motor or autonomic symptoms or psychic symptoms, such as fear, anxiety, and anger
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Table 2 General characteristics of the Group 1 patientsa. Patient
Sex
Age
Epileptic syndrome
Age at ES onset
Age at PNES onset
ES type
PNES type
Neurological examination
Cognition
Psychiatric comorbidity
General medical conditions
Etiology of PNES
1
F
27
SFE
14
25
CP
CP-like
Normal
Normal
GAD
Epilepsy
2
2
F
49
SFE
4
20
CP
CP-like
Normal
Normal
Epilepsy
29
3
F
45
SFE
18
43
CP
CP-like
Normal
Normal
4
F
30
SFE
14
20
SGCP
CG-like
Normal
Normal
5
F
34
SFE
11
15
CP
CP-like
Normal
Normal
GAD DPD DD GAD DD Personality Disorder NOS GAD
Cardiopathy Migraine Obesity Tension headaches Obesity Obesity
6
M
38
CGE
31
32
GTC
CG-like
Normal
Normal
DD
Hypertension Obesity Migraine Hypertension Dyslipidemia Obesity
Epilepsy Psychic trauma Epilepsy Dysthymia Epilepsy Epilepsy Work problems
Mean duration of PNES (years)
2 10
19 6
a SFE, Symptomatic focal epilepsy; CGE, cryptogenic generalized epilepsy; CP, complex partial; GTC, generalized tonic–clonic; SG, secondarily generalized; CP-like, complex partial-like; CG-like, convulsive generalized-like; GAD, Generalized Anxiety Disorder; DPD, Dependent Personality Disorder; DD, Dysthymic Disorder; NOS, Not Otherwise Specified.
depressive and anxiety disorders are the main comorbid psychiatric disorders. These patients had several problems linked to epilepsy, such as stigmatization, limitations affecting the performance of different activities, poor social adaptation, difficulty in establishing long-lasting relationships, and employment. Psychogenic nonepileptic seizures ceased in two patients, after PNES diagnosis in one case and after cessation of ES in the other. PNES persisted in three patients with pharmacoresistant epilepsy. We have no information on the PNES outcome in the remaining patient. 3.3. Group 2: Seven patients, six females and one male Mean age at last follow-up was 31.71 years (SD 10.04). Mean age at ES and PNES onset was 9 years (SD 5.2) and 20.14 years (SD 9.56), respectively. Mean time between ES and PNES onset was 11.14 years. Average delay before PNES diagnosis was 6.86 years (SD 5.58). Mean duration of PNES illness was 11.57 years (SD 7.48). All patients had mild mental retardation. Neurological examination was normal in
four patients. Two patients had hemiparesis, and one had cerebellar syndrome and amaurosis (Table 3). Six patients were affected by SFE partially responsive to AEDs. One had been affected by idiopathic generalized epilepsy (IGE) and had not had any seizures for many years. ES semiology was CP in four patients, with SG in three of them; simple partial (SP) with SG in one patient; GTC in one patient; and absence, tonic, and atonic seizures in one patient. Semiology of PNES was similar to that of ES in one patient (CPlike); arc en circle in one patient; akinetic in one patient; myoclonic jerks in one patient; and CG-like in three patients who also had recurrent pseudo-grand mal status. In all patients PNES occurred after cessation (one patient) or reduction in frequency (five patients) of ES. Comorbid psychiatric disorders were: DPD in four patients; Adjustment Disorder (AD) with depressive mood in one patient; Histrionic Personality Disorder (HPD) in one patient; and Psychotic Disorder Not Otherwise Specified (PDNOS) associated with DPD in another case. Therefore, comorbid psychiatric disorders were the main personality disorders. In all patients, RBP represented the pathogenetic mechanism of PNES.
Table 3 General characteristics of the group 2 patientsa. Neurological examination
Cognition Psychiatric comorbidity
General medical conditions
Etiology of PNES
Absence Arc en circle Tonic Atonic SGCP Akinetic
Left hemiparesis
Mild MR
Obesity
Decrease in 20 ES frequency
Normal
Mild MR
Normal
Mild MR
Patient Sex Age Epileptic Age at Age at ES type syndrome ES onset PNES onset
PNES type
1
F
31
SFE
9
11
2
F
31
SFE
13
28
3
F
24
IGE
1
6
GTC
4
F
25
SFE
15
18
SGSP
Myoclonic jerks CG-like
5
F
21
SFE
12
18
SGCP
CG-like
Right hemiparesis
Mild MR
6
F
41
SFE
3
30
SGCP
CG-like
Normal
Mild MR
7
M
49
SFE
10
30
CP
CP-like
Normal
Mild MR
Cerebellar syndrome Mild MR Amaurosis
DPD
AD with depressed mood HPD
Decrease in ES frequency
Mean duration of PNES (years)
3
Obesity
Cessation 18 of ES DPD Obesity Decrease in 7 ES frequency DPD Q-T syndrome Decrease in 3 Obesity ES frequency DPD Obesity Decrease in 11 Hypothyroidism ES frequency Obesity Decrease in 19 Psychotic ES frequency Disorder NOS DPD
a SFE, symptomatic focal epilepsy; IGE, idiopathic generalized epilepsy; CP, complex partial; GTC, generalized tonic–clonic; SP, simple partial; SG, secondarily generalized; CG-like, convulsive generalized-like; CP-like, complex partial-like; MR, mental retardation; DPD, Dependent Personality Disorder; AD, Adjustment Disorder; HPD, Histrionic Personality Disorder; NOS, Not Otherwise Specified.
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Table 4 General characteristics of the group 3 patientsa. Patient Sex Age Epileptic Age at Age at ES syndrome ES onset PNES onset type
PNES type
Neurological Cognition Psychiatric General medical examination comorbidity conditions
Etiology of PNES
1
F
53
SFE
6
44
SGCP
Akinetic
Normal
Normal
DD
Father's death
2
F
37
CGE
12
13
GTC
CG-like
Normal
Normal
HPD
3
F
67
CPE
14
42
SGCP
CP-like
Normal
Normal
GAD
4 5
F F
36 20
BCECTS IGE
6 20
28 18
SGSP GTC
CP-like Akinetic
Normal Normal
Normal Normal
BPD BPD
6 7
F F
30 36
IGE BCECTS
13 7
10 18
GTC SP
CG-like CP-like
Normal Normal
Normal Normal
BPD GAD
Migraine Obesity HCV hepatitis Cardiopathy
Obesity
Rheumatic arthritis
Sexual abuse Daughter's epilepsy Multiple medical conditions Mother's death Miscarriage Job loss Poor adaptation to work Sexual abuse Difficult relationships
Mean duration of PNES (years) 9 24
25 8 2 20 18
a SFE, symptomatic focal epilepsy; CGE, cryptogenic generalized epilepsy; CPE, cryptogenic partial epilepsy; BCECTS, benign childhood epilepsy with centrotemporal spikes; IGE, idiopathic generalized epilepsy; CP, complex partial; GTC, generalized tonic–clonic; SP, simple partial; SG, secondarily generalized; CG-like, convulsive generalized-like; CP-like, complex partial-like; DD, Dysthymic Disorder; HPD, Histrionic Personality Disorder; GAD, Generalized Anxiety Disorder; BPD, Borderline Personality Disorder.
Psychogenic nonepileptic seizures ceased or decreased in frequency after diagnosis in three patients and persisted in four others. 3.4. Group 3: Seven females Mean age at last follow-up was 39.86 years (SD 15.49). Mean age at ES and PNES onset was 11.14 years (SD 5.18) and 24.71 years (SD 13.7) respectively. Mean time between ES onset and PNES onset was 13.57 years. Average delay before PNES diagnosis was 13.14 years (SD 10.27). Mean duration of PNES illness was 15.14 years (SD 8.84). All patients had normal IQ and neurological examination (Table 4). One patient had SFE; one patient had CGE; one patient had cryptogenic partial epilepsy (CPE); two patients had been affected by benign childhood epilepsy with centrotemporal spikes (BCECTS); two patients had had IGE. Types of ES were CP with SG in two patients; GTC in three patients; and SP in two patients, with SG in one case. Semiology of PNES was similar to that of ES in three patients, but different in the other four (CP-like in two patients and akinetic in two others). One patient had recurrent convulsive generalized pseudostatus. All patients in this group had suffered psychic trauma: sexual abuse (two patients), parent's death (two patients), job loss (one patient), difficult relationships (one patient), poor adaptation to work (one patient). Thus, psychic trauma can be considered the etiology of PNES. This is particularly true in two patients whose PNES appeared before ES. Comorbid psychiatric disorders were: Borderline Personality Disorder (BPD) in three patients; HPD in one case; GAD in two patients; and DD in one patient. PNES ceased or decreased in frequency in four patients: after diagnosis in one case, after psychotherapy in another, and after antidepressant medication in the other two. PNES persisted in two patients, one of whom committed suicide. 4. Discussion Our study has focused specifically on patients with mixed PNES. We were able to divide these patients into three separate groups on the basis of epilepsy type, cognition, comorbid psychiatric disorders, and history of trauma. Although there is a great deal of literature dealing with PNES, many of the studies include both patients with mixed PNES and patients with pure PNES and make no distinction between them. Some studies have compared groups of patients with mixed PNES with groups of patients with epilepsy alone [43,44] or patients with mixed PNES, those with pure PNES, and those with epilepsy alone [28,45]. One study used the
Minnesota Multiphasic Personality Inventory (MMPI) to determine any differences in psychological profile among 32 patients with mixed PNES, 38 with pure PNES, and 36 with epilepsy alone. The results revealed that patients with PNES, both pure and mixed, had similar personality profiles that differed from those of patients with only epilepsy. Patients with PNES scored higher on the Hs (Hypochondria) and Hy (Hysteria) Scales compared with Scale D (Depression), on which patients with epilepsy alone scored higher [45]. A number of studies have evaluated the differences between patients with pure PNES and those with mixed PNES [46–49]. In one study conducted on 25 patients with mixed PNES and 85 with pure PNES, the authors identified several significant differences between the two groups. Patients with mixed PNES were younger at diagnosis (by video/EEG), had a longer follow-up period, had a longer delay in diagnosis, and were less susceptible to induction techniques; a higher percentage had been treated with AEDs, and a lower proportion had had a reduction in AEDs. Thus, no significant differences emerged with respect to age, gender, social level, family history of epilepsy, age at PNES onset, and semiology of PNES. Moreover, 16 of the 25 patients with mixed PNES had PNES similar to ES; the remaining 9 patients had PNES with different semiology [49]. As for the psychiatric profiles for the two groups (mixed and pure PNES), some authors report that personality disorders are more frequently diagnosed in patients with mixed PNES, whereas anxiety disorders and somatoform disorders prevail for patients with pure PNES [44]. Overall, differences between patients with pure PNES and those with mixed PNES have been highlighted, but there are no studies in the literature that have investigated exclusively patients with mixed PNES, who have been considered to be a homogeneous group characterized by the coexistent epilepsy. However, patients with mixed PNES have different types of epilepsy and different comorbid psychiatric disorders, may be intellectually impaired or have a normal IQ, and may or may not have a history of psychic trauma. The different types of epilepsy in association with different comorbid psychiatric disorders and the presence or absence of other factors (sexual abuse and other traumatic experiences) could lead to PNES through different pathogenetic mechanisms. Here we propose a classification of patients with mixed PNES based on epilepsy type, cognition, comorbid psychiatric disorders, and history of traumatic experiences. All these factors can be objectively detected. The main features of group 1 are pharmacoresistant SFE with CP seizures with experiential phenomena, normal cognition, and anxiety and/or depressive disorders. These patients had several problems linked to epilepsy, such as stigmatization, limitations affecting the
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performance of different activities, poor social adaptation, difficulty in establishing long-lasting relationships, and employment. Therefore, the etiology of PNES is the negative perception of epilepsy and problems linked to this illness. In the majority of these patients, the psychic symptoms (fear, anxiety, etc.) of ES were reproduced during PNES and made differential diagnosis relatively difficult. In this group the prognosis for the PNES was closely linked to how their epilepsy evolved. As these patients were normal intellectually, cognitive-behavioral psychotherapy combined with pharmacological treatment (where indicated for comorbid psychiatric disorders) would appear to be the most suitable treatment strategy. Group 2 comprises patients with mental retardation, affective immaturity, dependent personality traits, and early onset of the physical condition of which the ES were a symptom. The prevailing etiology of PNES in group 2 subjects is the cessation or decrease in frequency of ES. These patients had early-onset epilepsy and thus received a great deal of attention from caregivers. Hence, the PNES experienced by these patients do not constitute a conversion disorder sustained by an intrapsychic conflict; rather, they represent behavior that is unconsciously learned and used to retain the secondary gains deriving from their role as an ill person and to have control over their immediate surroundings. Given that the decrease in frequency or cessation of ES would mean the loss of these advantages, the PNES represent a substitute symptom. Family members would discontinue their role as caregivers were the ES to lessen or disappear, and then this would reinforce the mechanism that triggered the PNES. This pathogenetic mechanism was described by Gates and Erdahl in 1993 as a reinforced behavior pattern [13]. Treatment choices are more limited as psychotherapy must be ruled out because of the mental retardation of subjects and anxiolytic or antidepressant drugs are not useful because these patients do not have anxiety or depressive disorders. The main type of comorbid psychiatric disorder is DPD. In such cases, certain deconditioning techniques may be useful (e.g., “if you stop having PNES then you will be rewarded”). It is extremely important to teach caregivers how to distinguish PNES from ES, not to be alarmed by them, and not to reinforce the patient's role as a sick person. Group 3 comprises patients with non-pharmacoresistant epilepsy, ongoing or in remission, who have experienced one or more traumatic life events (abuse, bereavement, etc.). The most frequent comorbid psychiatric disorders in this group are personality disorders (Cluster B) and anxiety disorders. Here, it is not the epilepsy that constitutes the main etiology of PNES, but the experience of traumatic life events, as in patients with pure PNES. The timing of PNES onset is closely linked to the traumatic event. In these patients, epilepsy acts as a form of “symptom modeling.” Understandably, the easiest means of conversion for these patients, who have experienced ES, is to reproduce symptoms similar to those of their ES, especially if they are experiential symptoms. PNES outcome is not connected to changes in the epileptic condition, but to resolution or continuation of the intrapsychic conflict produced by psychic trauma. The main methodological limitation of our study is that our classification has not been tested independently by physicians not involved in the study to validate that the criteria proposed by us are sufficient to differentiate the three groups of patients with mixed PNES. This would be a means to test whether our categorization can be replicated or to detect whether there is more overlap between these groups than we have reported. This could be done in a subsequent study. Despite this limitation, our study provides a novel classification of patients with mixed PNES that can be tested further. The identification of different subgroups of patients with mixed PNES provides a useful tool to guide choice of the most appropriate strategy for treatment.
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