Epileptic Seizures Patients Research Articles

Cognitive deficits’ profiles of attention and executive functions in epilepsy versus psychogenic non-epileptic seizure patients: A preliminary cross-sectional study

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures (ES) but lack the associated brain electrical disruptions. Their underlying mechanism remains elusive, even though cognitive deficits are commonly reported in both ES and PNES patients. This preliminary cross-sectional study compared attention and executive functions in 20 patients with ES (ES group) and 18 with PNES or comorbid PNES and ES (PNES group) using the Stroop task and attentional network task (ANT). Both groups exhibited a significant Stroop effect, with no significant differences between them. In the ANT assessment, the ES group had significantly slower reaction times (RTs) in non-tone conditions compared to in-tone conditions (P < 0.05). Meanwhile, the PNES group displayed no significant difference in RTs between these conditions, indicating a more pronounced alerting effect in the ES compared to PNES group. No significant disparities emerged in executive control and orientation between the groups. The findings underscore differences in attentional processing between these groups, emphasizing the clinical significance of understanding these cognitive deficits for accurate diagnosis and tailored neuropsychological rehabilitation.

Epileptic Seizure Detection from Decomposed EEG Signal through 1D and 2D Feature Representation and Convolutional Neural Network

Electroencephalogram (EEG) has emerged as the most favorable source for recognizing brain disorders like epileptic seizure (ES) using deep learning (DL) methods. This study investigated the well-performed EEG-based ES detection method by decomposing EEG signals. Specifically, empirical mode decomposition (EMD) decomposes EEG signals into six intrinsic mode functions (IMFs). Three distinct features, namely, fluctuation index, variance, and ellipse area of the second order difference plot (SODP), were extracted from each of the IMFs. The feature values from all EEG channels were arranged in two composite feature forms: a 1D (i.e., unidimensional) form and a 2D image-like form. For ES recognition, the convolutional neural network (CNN), the most prominent DL model for 2D input, was considered for the 2D feature form, and a 1D version of CNN was employed for the 1D feature form. The experiment was conducted on a benchmark CHB-MIT dataset as well as a dataset prepared from the EEG signals of ES patients from Prince Hospital Khulna (PHK), Bangladesh. The 2D feature-based CNN model outperformed the other 1D feature-based models, showing an accuracy of 99.78% for CHB-MIT and 95.26% for PHK. Furthermore, the cross-dataset evaluations also showed favorable outcomes. Therefore, the proposed method with 2D composite feature form can be a promising ES detection method.

Latency of epileptic and psychogenic nonepileptic seizures.

Due to their semiological similarities, psychogenic nonepileptic seizures (PNESs) can occasionally hardly be differentiated from epileptic seizures (ESs), and long-term video-electroencephalographic monitoring (VEM) is needed for the differential diagnosis. To investigate the time of the first clinical event and its distribution on the days of VEM in ES and PNES patients. In total, a consecutive series of 48 PNES and 51 ES patients matched for gender and age were retrospectively and consecutively evaluated. The time distribution of the seizures during the day was noted. Seizure latency was determined as the time in hours from the start of the video-electroencephalographic recording to the first clinical event. The seizure latency was significantly shorter in PNES patients compared to ES patients (p < 0.001). Seventy-two percent of PNES patients and 49.1% of ES patients had their first seizure in the 24 hours of video-EEG recording (p = 0.023). Recording longer than 48 hours was required for 12.5% of PNES patients and 37.3% of ES patients (p = 0.006). While ESs were almost evenly distributed throughout the day, most PNESs occurred during the evening hours (p = 0.011). We observed that the PNESs appeared earlier than the ESs in the VEM and were concentrated during daylight hours. Although not strictly reliable, seizure latency can contribute to the differential diagnosis of ES and PNES.

The Comparison Between Neuropsychological Features of Psychogenic Non-epileptic Seizures and Epileptic Seizures

Background: Both epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) are often associated with some degree of cognitive impairment. Video electroencephalography (EEG) monitoring is the gold standard for diagnosing PNES. This diagnostic procedure is costly and available in specific tertiary centers. Neuropsychological assessment can provide clues for the differential diagnosis of PNES and ES and help clarify the nature and etiology of these two disorders. Objectives: Therefore, this study aimed to compare the neuropsychological profiles of PNES and ES patients. Methods: In this analytical cross-sectional study, 30 patients with ES and 31 patients with PNES were compared by neuropsychiatric tests, such as the Wechsler Adult Intelligence scale (WAIS), Addenbrooke’s Cognitive examination (ACE), and California Verbal Learning test (CVLT). Results: There was a female predominance in the PNES group (female-to-male ratio = 4.16/1, P = 0.003). In the PNES group, 77.4% of the patients had a psychiatric disorder versus 66.7% of the patients in the ES group; however, the difference was not statistically significant (P = 0.34). The mean score of total intelligence was higher in the PNES group (84.77 ± 16.94), compared to the ES group (83.63 ± 10.04); however, the difference was not significant (P = 0.75). Based on the mean subscale scores, the digit symbol score (WAIS-IV subscale) and memory score (ACE subscale) were significantly higher in the PNES group compared to the ES group (P = 0.037 and 0.032, respectively). Conclusions: This study showed that neuropsychological assessments might not differentiate ES from non-epileptic seizures.

Psychodynamic interpretation of linguistic findings in patients with epileptic and psychogenic non-epileptic seizures: the role of metaphors.

This work points out the main differences in the semantic expressions used by patients with psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES). In reference to the body as a phenomenological entity, in ES the concept of the body-object prevails while in PNES the body, with all its life attributes, predominates. In description of seizures and in similitudes and metaphors used, ES patients focus on the description of the attack, trying to close the "gap" with a big effort, while patients with PNES concentrate on the context and on the presence of bystanders. Patients with PNES are unable to describe their own attack, since this it is not at the core of their distress, but rather the manifestation of something else, which is hiding the extreme anguish associated with experiences of the past that cannot be revealed (expressed). In the case of ES, instead, the ability to talk and the willingness to elaborate on the emotions become useful tools for facing the disease, an entity perhaps unsurmountable but at least manageable, to the benefit of everyone. In general, we can say that the experience of a disease (real or symbolic) deserves constant attention because it gives us the opportunity not only to probe the depth of the emotional experiences but also the psychic structure of the individual in front of us. A cure would not be a cure without considering such fundamental elements. It would become a sterile exercise of prescribing medications without paying attention to the person, which is the best way of preserving dignity in a state of illness.

Proteomic Analysis of patients with Epileptic Seizure and Psychogenic Non-epileptic Seizure; a Cross-Sectional Study.

There is an increasing interest in the use of different biomarkers to help distinguish psychogenic non-epileptic seizure (PNES) from epileptic seizures (ES). This study aimed to evaluate the patterns of differentially expressed serum proteins in ES and PNES cases. In this cross-sectional study, 4 patients with mesial temporal lobe epilepsy and 4 patients with PNES were selected from patients with history of recurrent seizures. Venous blood samples were obtained within 1 hour after seizure and serum proteomes as well as the extent of protein expression were analyzed. 361 proteins were identified; of these, expression of 197 proteins had altered. 110 (55.9%) proteins were down-regulated and 87 (44.1%) were up-regulated in the PNES samples compared to ES samples. The mean pI for deregulated proteins with 1.5 to 3 fold changes were 6.69 ± 1.68 in proteins with increasing expression in ES group and 5.88 ± 1.39 in proteins with increasing expression in PNES group (p = 0.008). The median and interquartile range (IQR) of molecular weight changes in proteins with 1.5 to 3 fold changes were 64 (22.0-86.0) in proteins whose expression had increased in ES group and 39.5 (26.0-61.5) in proteins whose expression had increased in PNES cases (p = 0.05). Several spots with differential expression were observed by comparing patients with ES against the PNES groups, which could be potential biomarkers of the disease. Damage to the blood-brain barrier is the most important difference between the two groups, thus identifying total protein changes offers a key to the future of differentiating ES and PNES patients.

Coenzyme Q10 Insufficiency Contributes to the Duration and Frequency of Seizures in Epileptic Patients.

Introduction:Oxidative stress has recently emerged as a possible mechanism in the pathogenesis of epilepsy. Coenzyme Q10 (CoQ10) is a strong endogenous antioxidant that protects cells from lipid oxidation and Reactive Oxygen Species (ROS) production; however, the impact of CoQ10 on seizure characteristics in epileptic patients is unclear.Methods:The current study enrolled patients with Epileptic Seizure (ES) to evaluate their serum concentration of CoQ10 and to investigate whether a relationship exists between CoQ10 levels with the duration, frequency, and type of seizure.Results:A total of 39 patients with epileptic seizures and 35 healthy controls were included in the study. The levels of CoQ10 in ES patients were significantly lower in comparison with healthy controls (11.99±5.93 vs (ng/ml). 16.48±4.20 (ng/ml) P<0.001). We also found that the duration of epilepsy and seizure frequency was negatively correlated with serum CoQ10 levels.Conclusion:These findings indicate that CoQ10 deficiency might substantially contribute to the clinical signs of epileptic patients.

Personality profiles differ between patients with epileptic seizures and patients with psychogenic non-epileptic seizures

PurposePsychogenic non-epileptic seizures (PNES) and epileptic seizures (ES) are often difficult to differentiate, leading to incorrect or delayed diagnosis. The aim of the study was to determine whether patients of these two diagnostic groups possess different personality profiles, and whether they could be used to efficiently screen for PNES in clinical settings. MethodsCollection of data was conducted on 305 patients who completed the NEO-Five Factor Inventory questionnaire during a Video EEG Monitoring admission to the Royal Melbourne Hospital between 2002–2017. Personality differences were investigated using Bayesian linear mixed effects models, with receiver operating characteristic curve analysis computed to evaluate diagnostic accuracy. ResultsThe ‘openness to experience’ domain (BF10 = 21.55, d = −0.43 [95% CI −0.71, −0.17]) and the ‘aesthetic interest’ facet (B10 = 7.98, d= −0.39 [95% CI −0.66, −0.12]) were the only personality factors demonstrating strong evidence for a group difference, with patients with PNES having higher scores compared to the ES group. ES patients had lower scores on these measures compared to the normal population, while PNES patients did not. Both openness to experience and aesthetic interest showed poor sensitivities (53%, 46% respectively) and specificities (69%, 46% respectively) for classifying PNES and ES patients. ConclusionWhile openness and aesthetic interests differ greatly between PNES and ES groups, low sensitivity and specificity suggests their use is limited in a clinical setting. Nevertheless, these findings open up new avenues of research using modern personality models to further understand patients with epilepsy and related presentations.

Suicidal Ideation and Traumatic Exposure Should Not Be Neglected in Epileptic Patients: A Multidimensional Comparison of the Psychiatric Profile of Patients Suffering From Epilepsy and Patients Suffering From Psychogenic Nonepileptic Seizures.

Introduction: Patients with psychogenic nonepileptic seizures (PNESs) have often been exposed to traumatic events, which is a risk factor for suicidal behavior. This would suggest that the severity of suicidal ideation is greater in PNES than in patients suffering only from epileptic seizures (ESs). However, these psychiatric symptoms may be underestimated in the ES population. The specific features or similarities between the psychiatric clinical profiles of these two groups should be elaborated to improve therapeutic management. Our study is the first to compare suicidal ideation, suicide risk, posttraumatic stress disorder (PTSD), and depression disorder simultaneously in both groups, in a tertiary care epilepsy center. Material and methods: We prospectively enrolled patients hospitalized for video-electroencephalography (EEG) monitoring to assess repeated seizures before an ES or a PNES diagnosis was made. During the psychiatric consultation that accompanied the video EEG, we rated the severity of suicidal ideation and depressive symptoms, suicidal risk, traumatic exposure history, and PTSD symptoms. Results: Eighteen subjects were enrolled and diagnosed with PNES, and 42, with ES. The PNES group reported more exposures to traumatic events and more intense PTSD symptoms (median: 17 vs. 27; p = 0.001). The severity of suicidal ideation did not differ significantly between the two groups. Conclusion: It is the severity of PTSD symptoms in PNES patients that differentiates them from ES patients, although exposure to traumatic events is also frequent in ES patients. We demonstrated that suicidal ideation and suicide risk are equally high in the ES and PNES groups. Therefore, both groups require extreme vigilance in terms of suicidal risk.

Anion gap can differentiate between psychogenic and epileptic seizures in the emergency setting.

Differentiation between psychogenic nonepileptic seizures (PNES) and generalized convulsive epileptic seizures (ES) is important for appropriate triaging in the emergency department (ED). This can be difficult in the ED, as the event is often not witnessed by a medical professional. In the current study, we investigated whether anion gap (AG), bicarbonate, and the Denver Seizure Score (DSS) could differentiate between PNES and ES. Of a total of 1,354 subjects reviewed from a tertiary care medical center, 27 PNES and 27 ES patients were identified based on clinical description and subsequent electroencephalogram. Multivariate logistic regression analysis and receiver operating characteristic curves were used to determine whether there was an association between seizure type and AG, bicarbonate, or DSS (24-bicarbonate + 2 × [AG-12]) when samples were drawn within 24 h of the concerning event. The result showed that sensitivity and negative predictive value dropped markedly for all measures if samples were drawn >2 h after the event; the sensitivity was similar for AG and DSS and higher than for bicarbonate. We propose that AG > 10 (sensitivity of 81.8%, specificity of 100%) in the first 2 h after the event could be used as a potential tool in the ED to help differentiate between PNES and ES.

Increased odds and predictive rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences.

The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases.

Traumatic Brain Injury and Psychogenic Seizures in Veterans

To evaluate a proposed seizure etiology of traumatic brain injury (TBI) as a risk factor for psychogenic nonepileptic seizures (PNESs), the effect of reported TBI severity on the diagnosis of PNES versus epileptic seizures (ESs), and the potential moderating role of posttraumatic stress disorder (PTSD). Veterans with a diagnosis of PNES or ES during epilepsy monitoring at a Veterans Affairs Medical Center. Retrospective review of seizure type, proposed seizure etiology, TBI severity, and PTSD. Both PNES and ES groups were compared for TBI history and severity, and prior diagnosis of PTSD. Traumatic brain injury was the proposed seizure etiology for 57% of 67 PNES patients versus 35% of 54 ES patients (P < .05). It was mild in 87% of PNES patients and 37% of ES patients (P < .001). Posttraumatic stress disorder increased the likelihood of diagnosing PNES versus ES in Veterans with mild TBI as the proposed seizure etiology. Veterans with PNES commonly cite a TBI as the cause for seizures. Mild TBI was strongly associated with PNES versus ES. Posttraumatic stress disorder may moderate the development of PNES in Veterans with a history of mild TBI. Clinicians caring for Veterans with seizures may use these results in selecting patients for early diagnostic evaluation.

How long is long enough? The utility of prolonged inpatient video EEG monitoring

Video EEG monitoring (VEM) is a valuable tool for the diagnosis of epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES). We sought to determine the benefits of prolonged length of stay (LOS). We retrospectively reviewed the records of patients admitted for VEM. We analyzed LOS for ES and PNES patients to determine if there was reduced utility, as evidenced by a significantly higher inconclusive outcome, beyond a certain duration. We calculated receiver operating characteristic (ROC) curves to determine optimal cut off points for LOS based on futility. Patients admitted with presumed PNES were significantly more likely to have an inconclusive admission (31/150, 20.7%) versus all others (58/446, 13%, p=0.033). There was no significant difference in the likelihood of having an inconclusive admission if monitoring was continued for any duration in patients with ES (area under curve, AUC, 0.46). For patients with PNES, a LOS ≥5 days was associated with an increased risk of the stay being inconclusive (28% versus 12.5%, p=0.026). Although the ROC curve suggested a cut off of 5.5 days, it did not predict outcomes well (AUC 0.52, sensitivity 0.55, specificity 0.5). Based on our data, prolonging VEM appears useful for the proper classification and localization of ES.

IS THERE A LINK BETWEEN NON-EPILEPTIC ATTACK DISORDERS (NEAD) AND PERSONALITY DISORDERS (PD)? – A SYSTEMATIC REVIEW

ObjectiveThis systematic review determined whether there are specific types of Personality disorders (PD) cluster(s) and/or specific PD disorder(s) that is more likely to occur in people with Non-epileptic attack disorders...

Patient and caregiver quality of life in psychogenic non-epileptic seizures compared to epileptic seizures

PurposeLittle is known about the effect of psychogenic non epileptic seizures (PNES) to caregiver quality of life (QOL), particularly as it compares to epileptic seizures (ES). We sought to characterize this effect and identify its determinants. MethodsThe study population comprised of 126 ES and 33 PNES patients who underwent video EEG monitoring along with 48 and 18 caregivers respectively who accompanied them to their investigations. Patients completed questionnaires providing demographic, disease-related, cognitive, psychiatric, sleep and QOL information on admission, prior to their diagnosis being clarified. Their caregivers completed questionnaires providing demographic, disease burden and generic QOL information. Paraclinical data were also gathered. Regression analysis was used to identify patient and caregiver related determinants of patient and caregiver QOL. ResultsQOL scores were significantly worse for PNES than ES patients and were mainly linked to depression levels. PNES and ES caregivers had comparable demographic characteristics and QOL scores. ES caregiver QOL was better in employed caregivers with lower burden scores for the physical component summary (PCS) and worse in female caregivers of depressed patients with higher burden scores for the mental component summary (MCS). Caregiver burden score was the strongest correlate of PNES caregiver MCS QOL score. ConclusionCaregiver QOL in PNES does not differ from caregiver QOL in ES, while patient QOL is worse in PNES. Caregiver burden emerges as a consistent correlate of caregiver QOL both in ES and PNES. These findings advocate for consideration of caregiver burden and QOL in PNES in clinical practice and for future research paradigms.

MMPI-2 profiles: Fibromyalgia Patients Compared to Epileptic and Non-Epileptic Seizure Patients

We compared MMPI-2 profiles of Gulf War veterans with fibromyalgia (FM) to epileptic seizure (ES) patients, psychogenic non-epileptic seizure (PNES) patients, and Gulf War veteran healthy controls. Both PNES and FM are medically unexplained conditions. In previous MMPI-2 research PNES patients were shown to have significantly higher Hs and Hy clinical scales than ES patients. In the present research the FM group had significantly higher Hs and Hy scale scores than both the ES group and the healthy control group. There was no significant difference between the FM and PNES Hs scale scores; however, the FM Hy scale score was significantly lower than the PNES Hy scale score. Present findings indicate a high level of psychological distress in the FM group.

Burns in Epilepsy: Seven Years of Experience from the Hallym Burn Center in Korea

The objective of this retrospective epidemiological study was to identify the characteristics of burn injuries of seizure disorder patients in Korea, with the goal of developing programs to prevent or reduce the frequency and morbidity of such injuries. We reviewed the medical records of 34 acutely burned, epileptic-seizure patients who were admitted to a single regional burn center unit during the 7 years between January 1997 and April 2003, all of whom had been burned during an epileptic seizure. The most commonly associated seizure type was generalized tonic-clonic, followed by absence and complex partial. Females predominated in all age groups. There were more seizures in the morning hours between 3 and 10 am. The mean age was 43 +/- 16 years. Seizures occurred at home, while the patient was conducting daily household chores. Scalding was the most common injury, leaving small-but-deep wounds that required a mean hospital stay of 37 +/- 27 days. Typically, upper limbs and trunk were affected. To implement a successful burns injury-prevention program, patients with epilepsy should be better recognized as a high-risk group. Specific passive as well as active recommendations are suggested based on the epidemiologic features of seizure disorder patients in Korea.

Sleep structure in patients with psychogenic nonepileptic seizures

Psychogenic nonepileptic seizures (PNES) are a significant public health problem, occurring in perhaps 25% of patients admitted to epilepsy monitoring units. Additional distinguishing characteristics for these patients would be helpful from both a clinical and a scientific standpoint. This study examines sleep structure by polysomnography in patients with PNES compared with patients with epileptic seizures (ES). ES and PNES were verified by video-EEG monitoring. All patients with PNES were evaluated by a psychiatrist. Eight female patients with PNES were compared with 10 female ES patients in the same age group. Percentage REM sleep was significantly greater for women with PNES (23 ± 1%) than for those with ES (18 ± 1%). There were no differences in other sleep stages, total sleep time, or sleep efficiency. REM latency was less in PNES patients although not significantly. The study suggests that patients with PNES have a sleep architecture similar to that found in major depression, known to be associated with increased REM sleep.

Non-epileptic seizures: delayed diagnosis in patients presenting with electroencephalographic (EEG) or clinical signs of epileptic seizures

The clinical differentiation between epileptic seizures (ES) and non-epileptic seizures (NES) is often difficult and mostly based on the presence or absence of widely recognized features of ES such as tongue biting, falling, incontinence or concomitant epileptic abnormalities in the electroencephalogram (EEG). We retrospectively analysed the records of all patients referred to our Epilepsy Centre for refractory epilepsy and finally diagnosed with NES between 1980 and 1999 ( n= 103), half of them also exhibiting ES. The mean time-lapse between first attack and NES diagnosis was 8.7 ± 1.3 years and 16.5 ± 1.4 years for the NES and NES + ES groups respectively. At least one of the usual signs associated with generalized tonic–clonic seizures (tongue biting, falling or incontinence) was reported by 66% and 60% of patients with NES or NES + ES respectively. Interictal EEG abnormalities were recorded in 16% of NES patients vs. 80% of NES + ES patients. In the NES group, delay before establishing the correct diagnosis was significantly longer when the patients exhibited ≥1 symptom(s) of generalized seizures, or when patients exhibited interictal EEG abnormalities. Upon admission, 72% of NES patients and all NES + ES patients were being treated with antiepileptic drugs (AEDs).We conclude that EEG or clinical abnormalities suggestive of epileptic seizures are common in undiagnosed NES patients. Such diagnostic pitfalls, besides considerably delaying NES diagnosis, also considerably delay appropriate treatment implementation.

Demographic and Seizure Variables, But Not Hypnotizability or Dissociation, Differentiated Psychogenic from Organic Seizures

Early detection and differential diagnosis of psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES) is a major clinical issue in comprehensive epilepsy centers. Using blind conditions with patients with PNES (N= 10) and ES (N= 31) before diagnosis, we tested the hypotheses that individuals with PNES would exhibit significantly greater dissociativity, hypnotizability, absorption, and history of early abuse than ES patients. Although PNES patients tended to show greater dissociative phenomena, only the last of our hypotheses was fully supported. Although absorption did not discriminate between the two diagnostic groups, it was significantly higher among those reporting early abuse. A logistic regression analysis using scores on dissociation, hypnotizability and absorption showed them to be poor predictors of diagnosis; however, other analyses revealed that female gender, reports of multiple trauma incidents lasting months or years, initial seizure onset in late teens or twenties, and daily seizure attacks significantly differentiated PNES from ES patients. Thus, demographic and seizure variables proved to be much better predictors of diagnosis than psychological dimensions often associated with PNES.