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Stereotypy of psychogenic nonepileptic seizures
Epilepsy & Behavior 70 (2017) 140–144
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Stereotypy of psychogenic nonepileptic seizures☆,☆☆ Moshe Herskovitz ⁎ Department of Neurology, Rambam Health Care Campus, Haifa, Israel Technion Faculty of Medicine, Haifa, Israel
a r t i c l e
i n f o
Article history: Received 28 November 2016 Revised 3 February 2017 Accepted 9 February 2017 Available online xxxx Keywords: Somatization Neuropsychiatry Psychogenic non epileptic seizures Stereotypy
a b s t r a c t Psychogenic nonepileptic seizures (PNES) are defined as paroxysmal episodes in which epileptic semiology features are manifested, without the characteristic concomitant electrical discharges seen in epileptic seizures. Although many studies have dealt with semiologic classification of PNES, most of the studies did not raise the question of consistency of PNES in the same patient. The aim of this study was to measure the degree of consistency of PNES among individual patients. We retrospectively reviewed medical records and video- EEG records of all adult patients who underwent monitoring in our center from August 1st 2013 to May 31st 2015. Those who were diagnosed with PNES with or without a background of epilepsy were selected for this study. In order to check consistency between seizures, we analyzed patients who had more than one recorded seizure during monitoring. In case of more than 2 recorded seizures, the first two seizures were analyzed. We found 53 patients who had PNES during this period, 29 of them had more than one seizure. All seizures in the same patient were in the same semiology category. In patients with either motor rhythmic or complex motor seizures, we found a main anatomical region involved. The main anatomical region involved was the same in 13 out of 14 patients. Movement frequency was highly similar between the seizures of the same patient, while duration of seizures was significantly different. Despite significant differences in duration between the first and second seizure in patients with PNES, all other aspects tested were highly similar. This shows that recurrent PNES in the same patient are stereotypic. This supports the hypothesis that PNES is probably a dissociative disorder. © 2017 Elsevier Inc. All rights reserved.
1. Introduction Psychogenic nonepileptic seizures (PNESs) are defined as paroxysmal episodes in which epileptic semiology features are manifested without the characteristic concomitant electrical discharges seen in epileptic seizures (ESs) [1]. Many studies have dealt with semiologic classification of PNES, aiming to create a unified nomenclature for describing PNES phenomena [2–4]. However, most of these studies did not focus on the consistency of PNES in the same patient. According to the DSM 5, PNES is considered a sub group of conversion disorders, and according to the ICD 10, PNES is a dissociative disorder [5]. Like other dissociative disorders, PNESs involve reduced awareness to the causality of attacks, and reduced awareness to the surrounding during attacks. Hence, it would be logical to assume that the behavior during the attacks has automatic components and
☆ Disclosure: The author has no disclosures or conflict of interests to report. ☆☆ Author contribution: Moshe Herskovitz MD – Conceptualization of the study, analysis and interpretation of data, and revision of the manuscript. ⁎ Epilepsy Service, Dept of Neurology, Rambam Medical Center, Technion Faculty of Medicine, 1 Efron St., Haifa 31096, Israel. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.yebeh.2017.02.015 1525-5050/© 2017 Elsevier Inc. All rights reserved.
there should be some consistency between attacks in the same patient. Seneviratne et al. [3] classified PNESs into six categories: 1. Rhythmic motor PNES. 2. Hypermotor PNES. 3. Complex motor PNES. 4. Dialeptic PNES 5. Nonepileptic auras. 6. Mixed PNES. The aim of this study was to measure the consistency of semiology between two attacks of PNESs in the same patient. We hypothesized that: 1. Multiple PNES of the same patient will belong to the same PNES category. 2. In patients with rhythmic motor PNES there will be consistency in the frequency of movements between attacks. 3. In patients with complex motor PNESs there will be consistency in the type of behaviors and the sequence of their appearance, from one event to the next.
2. Methods We retrospectively reviewed medical records and video-EEG records of all adult patients who underwent monitoring in our center from August 1st 2013 to May 31st 2015. Those who were diagnosed with PNES, with or without a background of epilepsy, were selected for this study. Long-term video-EEG monitoring LTVEM was performed using a 22-channel digital video-EEG system with the electrodes arranged according to a modified 10–20 system. During the admission,
M. Herskovitz Epilepsy & Behavior 70 (2017) 140–144
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all patients were managed by a neurologist with subspecialty training in epileptology. A diagnosis of epilepsy was made either by interictal epileptiform discharges or by the recording of epileptic seizures during previous or current LTVEM. No induction methods except for AED withdrawal were used during LTVEM. The video monitoring sessions lasted 4–14 days. Patients were admitted for one of three reasons: 1. Investigation (spell classification). 2. Treatment adjustment. 3. Presurgical evaluation. Nonepileptic paroxysmal events mimicking epileptic seizures include: syncope, REM sleep behavior disorders, restless leg syndrome, and panic attacks etc. Diagnosis of PNES was made by an epileptologist, based on clinical interview and the absence of electrographic paroxysmal changes during, after or prior to a typical event [6]. All PNESs occurred spontaneously. The semiology of each clinical event was visually analyzed. All PNESs were classified into six different categories, adopted from [3]: (1) rhythmic motor PNES characterized by rhythmic tremor or rigor-like movements, (2) hypermotor PNES characterized by violent movements, (3) complex motor PNES characterized by complex movements such as flexion, extension, abduction, adduction, rotation, with or without clonic-like and myoclonic-like components of varying combinations and anatomic distribution, (4) dialeptic PNES characterized by unresponsiveness without motor manifestations, (5) nonepileptic auras characterized by subjective sensations without any external manifestations, marked in the LTVEM records as “seizure button presses” and, (6) mixed PNES where combinations of above seizure types were seen. In order to check consistency between different PNESs of the same patient, we analyzed patients who had more than one recorded PNESs during monitoring. In 16 out of 29 patients, only 2 seizures were recorded. In case of more than 2 recorded PNESs, the first two were analyzed, in order to make a uniform comparison for all patients. We analyzed the PNESs through five axes:
more patients were treated with AEDs for suspected epilepsy prior to the LTVEM. Regarding PNES distribution: 6 patients had a nonepileptic aura, 9 patients had a dialeptic PNES, 7 patients had rhythmic motor PNES, and 7 patients had complex motor PNES. The first and second PNES events of the same patient belonged to the same PNES category in all patients. In 14 patients, there were motor manifestations during events (either motor rhythmic or complex motor). In all of those patients, we found that during the PNES there was an anatomical region which was active the longest during the seizure, which hence was defined as the main anatomical region involved. Fig. 2 summarizes the distribution of the main anatomical region involved in those patients. In 13 out of those 14 patients, the same main anatomical region was involved in the first and the second PNES of the same patient. Table 1 summarizes the anatomical regions involved in the PNES, the sequence of their involvement during the PNES, and the duration of PNES. In 9 out of the 14 patients, the same anatomical regions were involved in both PNESs. In 7 out of the 14 patients, the same sequence of anatomical region involvement was observed in both PNESs. Regarding movement frequency: In 12 patients, a rhythmic movement was observed. Movement frequency was calculated only for the main anatomical region involved. In 5 patients the frequency of the main anatomical region involved was calculated by EEG artifact and in 7 patients by video analysis. In those patients, the mean movement frequency of the main anatomical region involved was not significantly different between the first and second PNES (3.35 ± 1.76 vs. 3.6 ± 1.7 Hz - P = 0.724). Information regarding length of PNESs was unclear in 7 patients. In the remaining 22 patients, the length of PNES was significantly different between the first and second PNES (8.7 ± 8.9 vs. 23.5 ± 21.7 min - p b 0.05).
1. Type of PNES: adopted from [3].
4. Discussion
2. Anatomical regions involved during the PNES. 3. Sequence of the PNES: the order of appearance of the anatomical regions involved in the PNES. 4. Frequency of movements: calculated using either EEG movement artifact, or using video analysis (Fig. 1a–b) in case of no movement artifact. 5. Duration of PNES. Descriptive statistics were used to analyze axes 1–3. Two tailed t tests were calculated for axes 4–5. Statistical analysis was conducted using SPSS 13 for windows. All data gathering was approved by our institutional review board. 3. Results Between August 1st 2013 and May 31st 2015, 195 LTVEM were preformed. Fifty-three patients were diagnosed with PNESs during this period. Twenty-nine of them had more than one seizure and were included in the final analysis. The mean age of the patients was 31 ± 14 years. There were 15 women and 14 men. The mean monitoring duration was 4.06 ± 2 days and the mean number of events was 3.8 ± 1.3. The median number of events was 2. The mean duration of “seizures disorder” was 6.2 years ± 5.9 (1 week–21 years) with a median duration of 4.5 years. (In one patient there were missing data regarding “seizures disorder” duration). Eight patients had a comorbidity of epilepsy. In 2 patients, a right temporal seizure was recorded in a previous LTVEM and the other 6 patients had generalized interictal epileptiform discharges. All of these patients were treated with antiepileptic drugs (AEDs). Eleven
There were several main findings in our study: 1. The first and the second PNES in an individual patient during LTVEM were consistent In terms of behavior and motor manifestations. 2. In patients with PNES and motor manifestations, there was a main anatomical region involved, which was consistent across both PNES in most patients (13 out of 14 patients). 3. In patients with PNES and non motor events, the behavior and the subjective feelings were constant across both seizures of the same patient (belonging to the same PNES semiological category). 4. The PNESs were different across patients in terms of anatomical regions involved, behavior, and subjective feelings. 5. Duration of PNESs was not consistent between both PNESs of the same patient. PNESs is classified according to the DSM V as a conversion disorder and according to the ICD 10 as a dissociative disorder. Dissociative disorders are characterized by a disruption of the normal integration of consciousness, memory, identity, emotion, perception, body representation, motor control, or behavior. Dissociative symptoms can potentially disrupt every area of psychological functioning [7]. Somatoform dissociation involves the loss of integration of somatic experiences, functions, and responses [8]. Dissociation is considered a defense mechanism helping the individual in coping with traumatizing events. Often, PNESs follow stressful or traumatic events which can result in dissociation of mental organization [9]. Since PNES (like an ES) is a symptom and not a disease or syndrome, it can be caused by heterogenic etiologies. It would be reasonable to assume that there is no one model which could explain the origin of PNES in all patients [10,11]. Until recently, there were four main models which dealt with the mechanism of PNES: Model 1 [12] “PNES as activation of dissociated material”- PNES results from dissociated memories or mental functions caused by a
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M. Herskovitz Epilepsy & Behavior 70 (2017) 140–144
Fig. 1. Movement frequency analysis techniques. Picture 1a PNES- head shaking back and forth and loss of contact. EEG artifact in the occipital region. 1b PNES - right leg shaking ± hands involvement. Time scale: 1 paper = 0.5 s,Video single frame duration = Δ(Mark 2–Mark 1) = 34 ms. Movement cycle- peak knee elevation to peak knee elevation = Δ(Mark 8–Mark 1) = 210 ms. Mark 9- beginning of a new cycle. Frequency substracted by using frequency calculating tool of Neurofax viewer QP-112AK ver 7-21.
traumatic event. Model 2 [13] “PNES as a hard-wired response”PNES is an acute dissociative activation of a pre-wired response to a threat or to a state of high arousal. Model 3 [14] “PNES as a physical manifestation of emotional stress”- the emotional stress is converted into PNES. Model 4 [15] “PNES as a learned behavior” – PNES is activated by means of operant conditioning.
One cannot identify a related traumatic event in all patients with PNESs, nor can PNESs be considered a learned behavior in all patients. Therefore, each model can only partly explain the development and the underlying mechanisms of PNESs. The new integrated cognitive model (ICM) by Brown and Reuber [10] suggests a universal explanation for the mechanism of PNES.
M. Herskovitz Epilepsy & Behavior 70 (2017) 140–144
Fig. 2. Distribution of the main anatomical region involved.
According to the ICM, a stimulus normally causes activation of an association memories network. The response to a stimulus depends on the familiarity of it. A familiar stimulus which is already represented in the network causes an automated program execution; this reaction is perceived as voluntary but effortless [16]. If the stimulus is unfamiliar, it is not represented in the association network; hence there is no automated response to it. A secondary attention system is activated determining which hypothesis and responses will be executed. In these circumstances the action is perceived as voluntary and self controlled. According to this model, PNES is an automatic response pattern that doesn't match reality. It is caused by a “rogue representation”, a distorted perception of a previous stimulus. For example, arousal which accompanies anger triggers a PNES. This automatic response is experienced as involuntary and unwanted [17]. According to this model, the development of PNES is influenced by a patient's life experience, memories of seizures experienced or witnessed, and automatic responses to emotion such as anger, fear, or disgust. These features are defined as the scaffold for the PNES [10]. According to the ICM, it is logical that, in an individual patient, different PNESs attack will be similar, but between individuals and between cultures, PNESs may be variable [18,19]. These hypotheses are supported by our findings. As mentioned above, according to the ICM, PNES is considered an automatic response. Automatic behavior is defined as having the capability of starting, operating, moving, etc., independently, without paying attention to the components of the movement [20]. The finding in our study that the behavior during PNES is stereotypic and repeated without variation [21]) in the same patient supports the idea that PNES is an automatic behavior. Automatic movements are common in everyday life and are particularly observed when making simple motor tasks [22].
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However, even complicated tasks, such as playing a musical instrument, can become automatic after practicing. Wu et al. [23] have shown that by learning and practicing sequences of movements, the movement becomes automatic when done in dissociative mode. In their study the subjects were asked to focus primarily on another cognitive task while continuing the movement sequence and the automatic movements remained highly accurate and stereotypic. The importance of practice and experience for creating PNES automatic response (corresponding with Model 4 and ICM) may be reflected by our finding that in most of our patients the PNES disorder was chronic. To further investigate the relation between the duration of PNES disorder and the degree of stereotypy, studies on acute PNES are necessary. In summary, in a healthy person, an automated behavior and even a stereotypic behavior could be elicited by an emotional trigger. A basic example would be laughing or crying. Those basic reactions remain in a normal range due to three main factors. The first factor is coupling between a trigger and a reaction: a person laughs due to a funny trigger or cries because he is sad. The second factor is the self awareness of the coupling between the trigger and the reaction. The awareness leads to the third factor which is self control of the reaction. Not in every social situation will we laugh or cry. The ICM corresponds with Freud's hypothesis on hysteria, that in a person with PNES, the coupling between the emotional trigger and the automatic behavior is abnormal. Since the coupling is abnormal, there is no awareness of the connection between the emotional state and the automatic behavior- the PNES. Due to that, there is lack of control [10,14]. Our experience is that raising the patient's awareness to the source and nature of PNES can ameliorate this condition. Functional MRI studies on functional connectivity in the brains of people with conversion disorders have found a direct link between emotional systems and executive systems [24]. For example, patients with motor conversion exhibit a direct link between the limbic regions and the motor areas [25]. Patients with PNESs exhibit strong functional connectivity between the Insular region and the motor planning regions. These findings suggest a direct connection from regions responsible of emotional processing to motor planning regions, bypassing conscious motor control [26], thereby supporting the ICM and the patients' experience of uncontrolled PNESs. Most studies dealing with clustering of PNES signs and symptoms have either tried to categorize symptoms or to look for typical (stereotypic) symptoms to differentiate between ES and PNES [10, 13,18,19,27,28]. In one study [19], it was shown that the subjective experience of different PNESs in a single patient is variable. They also showed that the attitude to PNES and the perception of PNES are different between the subject and observers. Another study [28] comparing self experience and transient loss of consciousness between groups of patients with syncope, epilepsy, and PNES found that PNES patients as a group had a wider range of symptoms and it was harder to identify
Table 1 The anatomical regions involved and the sequence of their involvement in the PNES. Patient
PNES 1
Duration (min)
PNES 2
Duration (min)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Head → Non responsive Legs → Rt Hand → Head Mouth → Head Body → Legs Rt hand → Shoulder → Hyperventilation → Non responsive Lt Hand → Non responsive Legs–Hands Lt Leg Hands → Legs → Non responsive Head grabbing → Non responsive Rt Leg Head Legs Hands
2.4 10.3 14.4 3.6 4.8 5.2 7.7 19.5 9.9 8.6 23.5 3.8 3 41
Head → Non responsive Legs → Head → Rt Hand Mouth → Head → Rt hand Lt hand → Legs → Body Rt hand → Shoulder → Hyperventilation → Non responsive Lt hand → Non responsive → Rt Leg Legs Lt Leg Falling → Hands → Legs → Non responsive Head grabbing → Non responsive Rt Leg → Hands Head Legs Hands
2.8 15.6 59 4.8 29.2 59 16 61 11.8 20.6 30 61 1.8 57
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M. Herskovitz Epilepsy & Behavior 70 (2017) 140–144
typical PNES symptoms in comparison to patients with syncope or epilepsy (this study, like several studies mentioned above, used the term “stereotypic” in order to describe typical symptoms common to patients with PNES). They did not check consistency between events in the same patient and their observation was based solely on questioners. In a thorough literature search, we did not find any studies which tried to measure the consistency of objective signs from one PNES to another in the same patient. Three studies [2–4] which dealt with PNES categorization mentioned the categorization consistency in the same patient, but it was not their primary goal. In one of those studies [4], it was shown that in 94.4% of patients, PNESs in the same patient were stereotypic. In contrast to this study and to our study, the other studies found that in 82% [3] and 62% [2] of patients, the recurrent PNESs were in the same PNES category. In our study, all PNESs in the same patient fell into the same PNES category. The main strength of our study lies in the fact that consistency between seizures in the same patient was checked by 5 axes and not only by semiology categories. The fact that a patient has shifted from one category to another does not necessarily imply inconsistency between seizures. For example, if in the first PNES one can find only hand shaking and in the next seizure, hand shaking followed by a prolonged unresponsiveness state, then, just by checking categories, the patient has shifted from a rhythmic motor seizure to a mix or dialeptic seizure. By checking other axes, our study was able to show more consistency between seizures. It is important to mention that our study suffers from several limitations which include: 1. Small sample size 2. We just compared the first and second PNES. 3. No second rater was involved. 4. We did not use any automated movement tracking programs. Our measurements of movement frequency resemble those of studies which used EEG muscle artifact [29]. However, in other studies that used an automated accelerometer device, a higher movement frequency was measured (at least in some of the patients) in comparison to the mean movement frequency (3.6 Hz) in our study [30]. It is important to note that we measured only the movement frequency of the main anatomical region involved. The results in our study represent the mean frequency of the main anatomical region involved of all patients with a range of 0.5 Hz–6.65 Hz. Accelerometer measurements as an automated direct measuring method may be more accurate than video or EEG artifact analysis due to the fact that it can monitor the movement continuously. On the other hand, by putting an accelerometer on patients with PNESs, one may create a suggestion of exaggeration of movements. It is important to mention that length of PNES was highly variable between PNESs in the same patient. In our opinion this finding does not weaken the ICM hypothesis because duration and time perception are not associated with a specific sensory motor system [31], hence has less chance to be incorporated in the PNES scaffold. In conclusion, our study showed that recurrent PNESs in the same patient are stereotypic. This supports the idea that PNES is an automatic behavior, done in a dissociative manner. These findings support the hypothesis that PNES is a dissociative disorder.
[3]
[4]
[5]
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[22] [23]
[24]
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Acknowledgements [29]
Sari Eran Herskovitz is thanked for providing language help and writing assistance. [30]
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Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Stereotypy of psychogenic nonepileptic seizures☆,☆☆ Moshe Herskovitz ⁎ Department of Neurology, Rambam Health Care Campus, Haifa, Israel Technion Faculty of Medicine, Haifa, Israel
a r t i c l e
i n f o
Article history: Received 28 November 2016 Revised 3 February 2017 Accepted 9 February 2017 Available online xxxx Keywords: Somatization Neuropsychiatry Psychogenic non epileptic seizures Stereotypy
a b s t r a c t Psychogenic nonepileptic seizures (PNES) are defined as paroxysmal episodes in which epileptic semiology features are manifested, without the characteristic concomitant electrical discharges seen in epileptic seizures. Although many studies have dealt with semiologic classification of PNES, most of the studies did not raise the question of consistency of PNES in the same patient. The aim of this study was to measure the degree of consistency of PNES among individual patients. We retrospectively reviewed medical records and video- EEG records of all adult patients who underwent monitoring in our center from August 1st 2013 to May 31st 2015. Those who were diagnosed with PNES with or without a background of epilepsy were selected for this study. In order to check consistency between seizures, we analyzed patients who had more than one recorded seizure during monitoring. In case of more than 2 recorded seizures, the first two seizures were analyzed. We found 53 patients who had PNES during this period, 29 of them had more than one seizure. All seizures in the same patient were in the same semiology category. In patients with either motor rhythmic or complex motor seizures, we found a main anatomical region involved. The main anatomical region involved was the same in 13 out of 14 patients. Movement frequency was highly similar between the seizures of the same patient, while duration of seizures was significantly different. Despite significant differences in duration between the first and second seizure in patients with PNES, all other aspects tested were highly similar. This shows that recurrent PNES in the same patient are stereotypic. This supports the hypothesis that PNES is probably a dissociative disorder. © 2017 Elsevier Inc. All rights reserved.
1. Introduction Psychogenic nonepileptic seizures (PNESs) are defined as paroxysmal episodes in which epileptic semiology features are manifested without the characteristic concomitant electrical discharges seen in epileptic seizures (ESs) [1]. Many studies have dealt with semiologic classification of PNES, aiming to create a unified nomenclature for describing PNES phenomena [2–4]. However, most of these studies did not focus on the consistency of PNES in the same patient. According to the DSM 5, PNES is considered a sub group of conversion disorders, and according to the ICD 10, PNES is a dissociative disorder [5]. Like other dissociative disorders, PNESs involve reduced awareness to the causality of attacks, and reduced awareness to the surrounding during attacks. Hence, it would be logical to assume that the behavior during the attacks has automatic components and
☆ Disclosure: The author has no disclosures or conflict of interests to report. ☆☆ Author contribution: Moshe Herskovitz MD – Conceptualization of the study, analysis and interpretation of data, and revision of the manuscript. ⁎ Epilepsy Service, Dept of Neurology, Rambam Medical Center, Technion Faculty of Medicine, 1 Efron St., Haifa 31096, Israel. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.yebeh.2017.02.015 1525-5050/© 2017 Elsevier Inc. All rights reserved.
there should be some consistency between attacks in the same patient. Seneviratne et al. [3] classified PNESs into six categories: 1. Rhythmic motor PNES. 2. Hypermotor PNES. 3. Complex motor PNES. 4. Dialeptic PNES 5. Nonepileptic auras. 6. Mixed PNES. The aim of this study was to measure the consistency of semiology between two attacks of PNESs in the same patient. We hypothesized that: 1. Multiple PNES of the same patient will belong to the same PNES category. 2. In patients with rhythmic motor PNES there will be consistency in the frequency of movements between attacks. 3. In patients with complex motor PNESs there will be consistency in the type of behaviors and the sequence of their appearance, from one event to the next.
2. Methods We retrospectively reviewed medical records and video-EEG records of all adult patients who underwent monitoring in our center from August 1st 2013 to May 31st 2015. Those who were diagnosed with PNES, with or without a background of epilepsy, were selected for this study. Long-term video-EEG monitoring LTVEM was performed using a 22-channel digital video-EEG system with the electrodes arranged according to a modified 10–20 system. During the admission,
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all patients were managed by a neurologist with subspecialty training in epileptology. A diagnosis of epilepsy was made either by interictal epileptiform discharges or by the recording of epileptic seizures during previous or current LTVEM. No induction methods except for AED withdrawal were used during LTVEM. The video monitoring sessions lasted 4–14 days. Patients were admitted for one of three reasons: 1. Investigation (spell classification). 2. Treatment adjustment. 3. Presurgical evaluation. Nonepileptic paroxysmal events mimicking epileptic seizures include: syncope, REM sleep behavior disorders, restless leg syndrome, and panic attacks etc. Diagnosis of PNES was made by an epileptologist, based on clinical interview and the absence of electrographic paroxysmal changes during, after or prior to a typical event [6]. All PNESs occurred spontaneously. The semiology of each clinical event was visually analyzed. All PNESs were classified into six different categories, adopted from [3]: (1) rhythmic motor PNES characterized by rhythmic tremor or rigor-like movements, (2) hypermotor PNES characterized by violent movements, (3) complex motor PNES characterized by complex movements such as flexion, extension, abduction, adduction, rotation, with or without clonic-like and myoclonic-like components of varying combinations and anatomic distribution, (4) dialeptic PNES characterized by unresponsiveness without motor manifestations, (5) nonepileptic auras characterized by subjective sensations without any external manifestations, marked in the LTVEM records as “seizure button presses” and, (6) mixed PNES where combinations of above seizure types were seen. In order to check consistency between different PNESs of the same patient, we analyzed patients who had more than one recorded PNESs during monitoring. In 16 out of 29 patients, only 2 seizures were recorded. In case of more than 2 recorded PNESs, the first two were analyzed, in order to make a uniform comparison for all patients. We analyzed the PNESs through five axes:
more patients were treated with AEDs for suspected epilepsy prior to the LTVEM. Regarding PNES distribution: 6 patients had a nonepileptic aura, 9 patients had a dialeptic PNES, 7 patients had rhythmic motor PNES, and 7 patients had complex motor PNES. The first and second PNES events of the same patient belonged to the same PNES category in all patients. In 14 patients, there were motor manifestations during events (either motor rhythmic or complex motor). In all of those patients, we found that during the PNES there was an anatomical region which was active the longest during the seizure, which hence was defined as the main anatomical region involved. Fig. 2 summarizes the distribution of the main anatomical region involved in those patients. In 13 out of those 14 patients, the same main anatomical region was involved in the first and the second PNES of the same patient. Table 1 summarizes the anatomical regions involved in the PNES, the sequence of their involvement during the PNES, and the duration of PNES. In 9 out of the 14 patients, the same anatomical regions were involved in both PNESs. In 7 out of the 14 patients, the same sequence of anatomical region involvement was observed in both PNESs. Regarding movement frequency: In 12 patients, a rhythmic movement was observed. Movement frequency was calculated only for the main anatomical region involved. In 5 patients the frequency of the main anatomical region involved was calculated by EEG artifact and in 7 patients by video analysis. In those patients, the mean movement frequency of the main anatomical region involved was not significantly different between the first and second PNES (3.35 ± 1.76 vs. 3.6 ± 1.7 Hz - P = 0.724). Information regarding length of PNESs was unclear in 7 patients. In the remaining 22 patients, the length of PNES was significantly different between the first and second PNES (8.7 ± 8.9 vs. 23.5 ± 21.7 min - p b 0.05).
1. Type of PNES: adopted from [3].
4. Discussion
2. Anatomical regions involved during the PNES. 3. Sequence of the PNES: the order of appearance of the anatomical regions involved in the PNES. 4. Frequency of movements: calculated using either EEG movement artifact, or using video analysis (Fig. 1a–b) in case of no movement artifact. 5. Duration of PNES. Descriptive statistics were used to analyze axes 1–3. Two tailed t tests were calculated for axes 4–5. Statistical analysis was conducted using SPSS 13 for windows. All data gathering was approved by our institutional review board. 3. Results Between August 1st 2013 and May 31st 2015, 195 LTVEM were preformed. Fifty-three patients were diagnosed with PNESs during this period. Twenty-nine of them had more than one seizure and were included in the final analysis. The mean age of the patients was 31 ± 14 years. There were 15 women and 14 men. The mean monitoring duration was 4.06 ± 2 days and the mean number of events was 3.8 ± 1.3. The median number of events was 2. The mean duration of “seizures disorder” was 6.2 years ± 5.9 (1 week–21 years) with a median duration of 4.5 years. (In one patient there were missing data regarding “seizures disorder” duration). Eight patients had a comorbidity of epilepsy. In 2 patients, a right temporal seizure was recorded in a previous LTVEM and the other 6 patients had generalized interictal epileptiform discharges. All of these patients were treated with antiepileptic drugs (AEDs). Eleven
There were several main findings in our study: 1. The first and the second PNES in an individual patient during LTVEM were consistent In terms of behavior and motor manifestations. 2. In patients with PNES and motor manifestations, there was a main anatomical region involved, which was consistent across both PNES in most patients (13 out of 14 patients). 3. In patients with PNES and non motor events, the behavior and the subjective feelings were constant across both seizures of the same patient (belonging to the same PNES semiological category). 4. The PNESs were different across patients in terms of anatomical regions involved, behavior, and subjective feelings. 5. Duration of PNESs was not consistent between both PNESs of the same patient. PNESs is classified according to the DSM V as a conversion disorder and according to the ICD 10 as a dissociative disorder. Dissociative disorders are characterized by a disruption of the normal integration of consciousness, memory, identity, emotion, perception, body representation, motor control, or behavior. Dissociative symptoms can potentially disrupt every area of psychological functioning [7]. Somatoform dissociation involves the loss of integration of somatic experiences, functions, and responses [8]. Dissociation is considered a defense mechanism helping the individual in coping with traumatizing events. Often, PNESs follow stressful or traumatic events which can result in dissociation of mental organization [9]. Since PNES (like an ES) is a symptom and not a disease or syndrome, it can be caused by heterogenic etiologies. It would be reasonable to assume that there is no one model which could explain the origin of PNES in all patients [10,11]. Until recently, there were four main models which dealt with the mechanism of PNES: Model 1 [12] “PNES as activation of dissociated material”- PNES results from dissociated memories or mental functions caused by a
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Fig. 1. Movement frequency analysis techniques. Picture 1a PNES- head shaking back and forth and loss of contact. EEG artifact in the occipital region. 1b PNES - right leg shaking ± hands involvement. Time scale: 1 paper = 0.5 s,Video single frame duration = Δ(Mark 2–Mark 1) = 34 ms. Movement cycle- peak knee elevation to peak knee elevation = Δ(Mark 8–Mark 1) = 210 ms. Mark 9- beginning of a new cycle. Frequency substracted by using frequency calculating tool of Neurofax viewer QP-112AK ver 7-21.
traumatic event. Model 2 [13] “PNES as a hard-wired response”PNES is an acute dissociative activation of a pre-wired response to a threat or to a state of high arousal. Model 3 [14] “PNES as a physical manifestation of emotional stress”- the emotional stress is converted into PNES. Model 4 [15] “PNES as a learned behavior” – PNES is activated by means of operant conditioning.
One cannot identify a related traumatic event in all patients with PNESs, nor can PNESs be considered a learned behavior in all patients. Therefore, each model can only partly explain the development and the underlying mechanisms of PNESs. The new integrated cognitive model (ICM) by Brown and Reuber [10] suggests a universal explanation for the mechanism of PNES.
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Fig. 2. Distribution of the main anatomical region involved.
According to the ICM, a stimulus normally causes activation of an association memories network. The response to a stimulus depends on the familiarity of it. A familiar stimulus which is already represented in the network causes an automated program execution; this reaction is perceived as voluntary but effortless [16]. If the stimulus is unfamiliar, it is not represented in the association network; hence there is no automated response to it. A secondary attention system is activated determining which hypothesis and responses will be executed. In these circumstances the action is perceived as voluntary and self controlled. According to this model, PNES is an automatic response pattern that doesn't match reality. It is caused by a “rogue representation”, a distorted perception of a previous stimulus. For example, arousal which accompanies anger triggers a PNES. This automatic response is experienced as involuntary and unwanted [17]. According to this model, the development of PNES is influenced by a patient's life experience, memories of seizures experienced or witnessed, and automatic responses to emotion such as anger, fear, or disgust. These features are defined as the scaffold for the PNES [10]. According to the ICM, it is logical that, in an individual patient, different PNESs attack will be similar, but between individuals and between cultures, PNESs may be variable [18,19]. These hypotheses are supported by our findings. As mentioned above, according to the ICM, PNES is considered an automatic response. Automatic behavior is defined as having the capability of starting, operating, moving, etc., independently, without paying attention to the components of the movement [20]. The finding in our study that the behavior during PNES is stereotypic and repeated without variation [21]) in the same patient supports the idea that PNES is an automatic behavior. Automatic movements are common in everyday life and are particularly observed when making simple motor tasks [22].
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However, even complicated tasks, such as playing a musical instrument, can become automatic after practicing. Wu et al. [23] have shown that by learning and practicing sequences of movements, the movement becomes automatic when done in dissociative mode. In their study the subjects were asked to focus primarily on another cognitive task while continuing the movement sequence and the automatic movements remained highly accurate and stereotypic. The importance of practice and experience for creating PNES automatic response (corresponding with Model 4 and ICM) may be reflected by our finding that in most of our patients the PNES disorder was chronic. To further investigate the relation between the duration of PNES disorder and the degree of stereotypy, studies on acute PNES are necessary. In summary, in a healthy person, an automated behavior and even a stereotypic behavior could be elicited by an emotional trigger. A basic example would be laughing or crying. Those basic reactions remain in a normal range due to three main factors. The first factor is coupling between a trigger and a reaction: a person laughs due to a funny trigger or cries because he is sad. The second factor is the self awareness of the coupling between the trigger and the reaction. The awareness leads to the third factor which is self control of the reaction. Not in every social situation will we laugh or cry. The ICM corresponds with Freud's hypothesis on hysteria, that in a person with PNES, the coupling between the emotional trigger and the automatic behavior is abnormal. Since the coupling is abnormal, there is no awareness of the connection between the emotional state and the automatic behavior- the PNES. Due to that, there is lack of control [10,14]. Our experience is that raising the patient's awareness to the source and nature of PNES can ameliorate this condition. Functional MRI studies on functional connectivity in the brains of people with conversion disorders have found a direct link between emotional systems and executive systems [24]. For example, patients with motor conversion exhibit a direct link between the limbic regions and the motor areas [25]. Patients with PNESs exhibit strong functional connectivity between the Insular region and the motor planning regions. These findings suggest a direct connection from regions responsible of emotional processing to motor planning regions, bypassing conscious motor control [26], thereby supporting the ICM and the patients' experience of uncontrolled PNESs. Most studies dealing with clustering of PNES signs and symptoms have either tried to categorize symptoms or to look for typical (stereotypic) symptoms to differentiate between ES and PNES [10, 13,18,19,27,28]. In one study [19], it was shown that the subjective experience of different PNESs in a single patient is variable. They also showed that the attitude to PNES and the perception of PNES are different between the subject and observers. Another study [28] comparing self experience and transient loss of consciousness between groups of patients with syncope, epilepsy, and PNES found that PNES patients as a group had a wider range of symptoms and it was harder to identify
Table 1 The anatomical regions involved and the sequence of their involvement in the PNES. Patient
PNES 1
Duration (min)
PNES 2
Duration (min)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Head → Non responsive Legs → Rt Hand → Head Mouth → Head Body → Legs Rt hand → Shoulder → Hyperventilation → Non responsive Lt Hand → Non responsive Legs–Hands Lt Leg Hands → Legs → Non responsive Head grabbing → Non responsive Rt Leg Head Legs Hands
2.4 10.3 14.4 3.6 4.8 5.2 7.7 19.5 9.9 8.6 23.5 3.8 3 41
Head → Non responsive Legs → Head → Rt Hand Mouth → Head → Rt hand Lt hand → Legs → Body Rt hand → Shoulder → Hyperventilation → Non responsive Lt hand → Non responsive → Rt Leg Legs Lt Leg Falling → Hands → Legs → Non responsive Head grabbing → Non responsive Rt Leg → Hands Head Legs Hands
2.8 15.6 59 4.8 29.2 59 16 61 11.8 20.6 30 61 1.8 57
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typical PNES symptoms in comparison to patients with syncope or epilepsy (this study, like several studies mentioned above, used the term “stereotypic” in order to describe typical symptoms common to patients with PNES). They did not check consistency between events in the same patient and their observation was based solely on questioners. In a thorough literature search, we did not find any studies which tried to measure the consistency of objective signs from one PNES to another in the same patient. Three studies [2–4] which dealt with PNES categorization mentioned the categorization consistency in the same patient, but it was not their primary goal. In one of those studies [4], it was shown that in 94.4% of patients, PNESs in the same patient were stereotypic. In contrast to this study and to our study, the other studies found that in 82% [3] and 62% [2] of patients, the recurrent PNESs were in the same PNES category. In our study, all PNESs in the same patient fell into the same PNES category. The main strength of our study lies in the fact that consistency between seizures in the same patient was checked by 5 axes and not only by semiology categories. The fact that a patient has shifted from one category to another does not necessarily imply inconsistency between seizures. For example, if in the first PNES one can find only hand shaking and in the next seizure, hand shaking followed by a prolonged unresponsiveness state, then, just by checking categories, the patient has shifted from a rhythmic motor seizure to a mix or dialeptic seizure. By checking other axes, our study was able to show more consistency between seizures. It is important to mention that our study suffers from several limitations which include: 1. Small sample size 2. We just compared the first and second PNES. 3. No second rater was involved. 4. We did not use any automated movement tracking programs. Our measurements of movement frequency resemble those of studies which used EEG muscle artifact [29]. However, in other studies that used an automated accelerometer device, a higher movement frequency was measured (at least in some of the patients) in comparison to the mean movement frequency (3.6 Hz) in our study [30]. It is important to note that we measured only the movement frequency of the main anatomical region involved. The results in our study represent the mean frequency of the main anatomical region involved of all patients with a range of 0.5 Hz–6.65 Hz. Accelerometer measurements as an automated direct measuring method may be more accurate than video or EEG artifact analysis due to the fact that it can monitor the movement continuously. On the other hand, by putting an accelerometer on patients with PNESs, one may create a suggestion of exaggeration of movements. It is important to mention that length of PNES was highly variable between PNESs in the same patient. In our opinion this finding does not weaken the ICM hypothesis because duration and time perception are not associated with a specific sensory motor system [31], hence has less chance to be incorporated in the PNES scaffold. In conclusion, our study showed that recurrent PNESs in the same patient are stereotypic. This supports the idea that PNES is an automatic behavior, done in a dissociative manner. These findings support the hypothesis that PNES is a dissociative disorder.
[3]
[4]
[5]
[6] [7] [8]
[9]
[10]
[11]
[12] [13] [14] [15] [16]
[17] [18] [19]
[20] [21]
[22] [23]
[24]
[25]
[26]
[27]
[28]
Acknowledgements [29]
Sari Eran Herskovitz is thanked for providing language help and writing assistance. [30]
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