Prospective multicenter cohort study of possible psychogenic nonepileptic seizure cases-Results at 1-year follow-up examinations.

OBJECTIVE: The primary purpose of this prospective multicenter study was to examine clinical and demographic feature differences according to the diagnostic level of psychogenic nonepileptic seizures (PNES) and then clarify whether prognosis may also differ accordingly. METHODS: Two hundred forty-two consecutive patients strongly suspected of having PNES attacks were invited to participate, of whom 52 did not consent or contact was lost. At the 1-year follow-up examination, PNES diagnosis was reconsidered in nine patients. In 96 patients, the diagnostic level remained the same (P-group), with that in 43 considered to be clinically established (CE-group) and in 42 documented (D-group). The Qolie-10 and NDDI-E questionnaires were examined at both the study entry and the follow-up examination. RESULTS: Multiple regression analysis of quality of life (QoL) score (n = 173; R2  = 0.374; F = 7.349; P < 0.001) revealed NDDI-E score (t = -6.402; P < 0.001), age of PNES onset (t = -3.026; P = 0.003), and ethnic minority status (t = 3.068; P = 0.003) as significant contributors. At entry, the P-group showed the lowest PNES attack frequency (P < 0.000), the lowest rate of antiseizure, antidepressant, and antipsychotic medication (P < 0.000; P = 0.031; P = 0.013, respectively), and the lowest proportion of psychosis (P = 0.046). At follow-up, PNES attack frequency (P < 0.000), number of admittances to emergency room (P < 0.000), and scores for QoL (P < 0.000) as well as depression (P = 0.004) were found to be significantly improved together with other collateral indicators, such as rate of antiseizure medication prescription (P = 0.001) and psychiatric symptoms (P = 0.03). Multiple regression analysis of a sample limited to patients with intellectual disability (ID) (n = 44; R2  = 0.366; F = 4.493; P = 0.002) revealed continued psychotherapy at follow-up (t = 2.610, P = 0.013) and successful reduction in antiseizure medication (t = 2.868; P = 0.007) as positively related with improved QoL. SIGNIFICANCE: Clinical and the socio-psychological constellation of possible, clinically established, and documented PNES were found to differ greatly. Unexpectedly, significant effects of the continuous psychotherapeutic intervention were confirmed in PNES patients with ID.

PNES around the world: Where we are now and how we can close the diagnosis and treatment gaps-an ILAE PNES Task Force report.

An international consensus clinical practice statement issued in 2011 ranked psychogenic nonepileptic seizures (PNES) among the top three neuropsychiatric problems. An ILAE PNES Task Force was founded and initially charged with summarizing the current state of the art in terms of diagnosis and treatment, resulting in two publications. The first described different levels of diagnostic certainty. The second summarized current knowledge of management approaches. The present paper summarizes an international workshop of the ILAE PNES Task Force that focused on the current understanding and management of PNES around the world. We initially provide a knowledge update about the etiology, epidemiology, and prognosis of PNES-in adults and in special patient groups, such as children, older adults, and those with intellectual disability. We then explore clinical management pathways and obstacles to optimal care for this disorder around the world by focusing on a number of countries with different cultural backgrounds and at very different stages of social and economic development (United Kingdom, U.S.A., Zambia, Georgia, China, and Japan). Although evidence-based methods for the diagnosis and treatment of PNES have now been described, and much is known about the biopsychosocial underpinnings of this disorder, this paper describes gaps in care (not only in less developed countries) that result in patients with PNES not having adequate access to healthcare provisions. A range of challenges requiring solutions tailored to different healthcare systems emerges. Continued attention to PNES by the ILAE and other national and international neurologic, psychiatric, and health organizations, along with ongoing international collaboration, should ensure that patients with PNES do not lose out as healthcare services evolve around the world.

Psychogenic non-epileptic seizure in patients with intellectual disability with special focus on choice of therapeutic intervention.

PURPOSE: There have been a number of studies exploring treatments for psychogenic non-epileptic seizure (PNES) but largely neglecting the sizable subgroup of patients with intellectual disability (ID). In the present study, we attempted to demonstrate effects and preferred modes of therapeutic intervention in PNES patients with ID being treated at a Japanese municipal center with a short referral chain. METHODS: We examined 46 PNES patients with ID (ID group) and 106 PNES patients without ID (non-ID group) retrospectively in case charts. In addition to examining basic demographic and clinical data, effects of different therapeutic intervention were examined as a function of decrease or disappearance of PNES attacks in the ID group. RESULTS: Age at the first visit as well as PNES onset was younger in the ID than in the non-ID group (t=2.651, p=0.009; t=3.528, p=0.001, respectively). PNES-free ratio at the last visit tended to be higher in the non-ID group (chi square=3.455; p=0.063). Psychosis was more often encountered in the ID group (chi square=13.443; p=0.001). Although cognitive therapy and pharmaco-therapeutic approaches were quite similarly distributed in both groups, environmental adjustment was often introduced in the ID group (44%) as compared to the non-ID group (15%) (chi square=14.299; p=0.001). Brief weekly visit service is also more often utilized by the patients with ID (54%) than by those without ID (35%) (chi square=5.021, p=0.025). CONCLUSIONS: Optimal treatment approaches in this sizable patient subgroup should be the subject of future prospective studies.

Behavioral disorder in people with an intellectual disability and epilepsy: A report of the Intellectual Disability Task Force of the Neuropsychiatric Commission of ILAE.

The management and needs of people with intellectual disability (ID) and epilepsy are well evidenced; less so, the comorbidity of behavioral disorder in this population. "Behavioral disorder" is defined as behaviors that are difficult or disruptive, including stereotypes, difficult or disruptive behavior, aggressive behavior toward other people, behaviors that lead to injury to self or others, and destruction of property. These have an important link to emotional disturbance. This report, produced by the Intellectual Disability Task Force of the Neuropsychiatric Commission of the ILAE, aims to provide a brief review of some key areas of concern regarding behavioral disorder among this population and proposes a range of research and clinical practice recommendations generated by task force members. The areas covered in this report were identified by experts in the field as being of specific relevance to the broad epilepsy community when considering behavioral disorder in persons with epilepsy and ID; they are not intended to be exhaustive. The practice recommendations are based on the authors' review of the limited research in this field combined with their experience supporting this population. These points are not graded but can be seen as expert opinion guiding future research and clinical practice.

Delusional experience awareness gap between patients and treating doctors - Self-reported EPDS questionnaire.

OBJECTIVES: Although early and rapid recognition of a psychotic trend in patients with epilepsy certainly pay dividends, there is no handy assessment instrument for screening because of multiple intrinsic difficulties such as lack of a standard screener as well as a reliability gap for screeners between help-seeking and general populations. On the other hand, the predominance of positive symptoms at the initial stage of psychosis is a promising aspect of this specific group. The following specific questions were examined. Is there a measurable difference between the assessment of the treating doctor and the real feelings of the patient? How well does the attained score correspond to the clinical diagnosis? METHODS: The self-reported Emotions with Persecutory Delusions Scale (EPDS) questionnaire, previously validated in a general population, was used as the assessment tool for psychotic trend in 79 outpatients with epilepsy. Independent from scoring by the patients, the treating doctors also expressed their impressions about the same patients using the same scoring tool. RESULTS: Stepwise multiple regression analysis of the EPDS scores of both doctors and patients revealed that a clinical diagnosis of psychosis was the only independent variable significantly related to EPDS score. Also, there was a significant difference between the EPDS scores of the patients and those of the doctors, in favor of the former. SIGNIFICANCE: Clinical diagnosis of psychosis proved to be the most powerful determinant of EPDS score independent from other clinical factors. The awareness gap between doctors and patients based on EPDS score revealed that treating doctors often clearly underestimate the psychotic trend of their patients. Our findings suggest that such simple tests as EPDS, with a narrow focus on attenuated delusional symptoms, may help screen for an early psychotic episode in patients with epilepsy that may otherwise not be diagnosed by their physicians.

[Therapeutic strategy for mental symptoms in people with epilepsy].

Epilepsy has an association with nearly all types of psychiatric problems and psychiatric symptoms are common clinical manifestations seen in epilepsy patients. For example, interictal depression in individuals with epilepsy is more prevalent than in the general population or among patients with other chronic disorders. The high frequency of depression and clinical impact of psychosis in epilepsy have been well documented in recent studies, indicating the importance of diagnosing and treating psychiatric implications in affected patients. This article reviews various psychiatric symptoms such as postictal psychosis, interictal psychosis, depression, psychogenic non-epileptic seizure(PNES), and cognitive dysfunction encountered in patients with epilepsy.

[How to cope with psychiatric illness in patients with epilepsy].

Almost every kind of psychiatric problems are associated with epilepsy such as psychotic states, manic as well as depressive states and anxiety attacks. Overall, the prevalence of psychiatric comorbidities in patients with epilepsy amounts to as high as 20-30% of all cases. Acute and chronic interictal psychoses, as well as postictal psychosis (or more precisely periictal psychosis), comprise 95% of psychosis in patients with epilepsy. Prevalence of depressive states in patients with yet active epilepsy ranges from 20-55%. Prevalence in patients with controlled epilepsy ranges from 3-9%. Depressive states comprise 50-80% of psychiatric co-morbidities in patients with epilepsy. Several studies reported that PNES amounted to as high as 30% among patients considered as candidates for epilepsy surgery due to intractable epilepsy. It is of clinical use that PNES is divided into 3 groups: The first group belongs to PNES without either intellectual disability nor epilepsy; The second group suffers from intellectual disability in addition to PNES; The third group shows both epileptic seizure and PNES. These groups need to be differently treated. After temporal lobectomy for controlling pharmacoresistant TLE, severe but transient depression possibly leading to suicide can appear, especially within the first few months after surgery.

Psychotic illness in patients with epilepsy.

Apart from the rather rare ictal psychotic events, such as non-convulsive status epilepticus, modern epileptic psychoses have been categorized into three main types; chronic and acute interictal psychoses (IIPs) and postictal psychosis (PIP). Together, they comprise 95% of psychoses in patients with epilepsy (PWE). Four major questions, that is, "Is psychosis in PWE a direct consequence of epilepsy or schizophrenia induced by epilepsy?", "Is psychosis in PWE homogeneous or heterogeneous?", "Does psychosis in PWE have symptomatological differences from schizophrenia and related disorders?", "Is psychosis in PWE uniquely associated with temporal lobe epilepsy (TLE)?" are tried to be answered in this review with relevant case presentations. In the final section, we propose a tentative classification of psychotic illness in PWE, with special attention to those who have undergone epilepsy surgery. Psychotic disorders in PWE are often overlooked, mistreated, and consequently lingering on needlessly. While early diagnosis is unanimously supported as a first step to avoid this delay, necessity of switching from antiepileptic drugs with supposedly adverse psychotopic effects. to others is more controversial. To elucidate the riddle of alternative psychosis, we need badly further reliable data.

Screening for major depressive episodes in Japanese patients with epilepsy: validation and translation of the Japanese version of Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

We validated and translated into Japanese the English version of the screening instrument Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to identify major depressive episodes in patients with epilepsy. A total of 159 Japanese subjects with epilepsy underwent a psychiatric structured interview with the Japanese version of the Mini International Neuropsychiatric Interview (M.I.N.I.-J) followed by completion of the Japanese version of NDDI-E (NDDI-E-J). Twelve participants met the M.I.N.I.-J criteria of current major depressive episode. Participants had no difficulties completing the NDDI-E-J. Its Cronbach's alpha coefficient was 0.83 and a cut-off score greater than 16 provided a sensitivity of 0.92, a specificity of 0.89, and a negative predictive value of 0.99. The NDDI-E-J appears to be useful for primary care clinicians to screen for major depressive episodes in epilepsy patients. Routine use of this brief and self-administered instrument in busy clinical settings will likely improve management of depression in Japanese individuals with epilepsy.

Lack of data on depression-like states and antidepressant pharmacotherapy in patients with epilepsy: randomised controlled trials are badly needed.

The prevalence of depression in patients with epilepsy (PWE) is high. To elucidate the nature of depression in PWE, a comparison was made between PWE and patients with idiopathic depression (PWID), applying 3 test batteries: Beck Depression Inventory II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-D) and Buss-Perry Aggression Questionnaire (BAQ). The former 2 rating scales were developed to measure depressive symptoms, while the latter was designed to detect anger and aggressive states. As a result, the group of patients with PWE showed significantly higher BAQ scores in comparison to those with PWID. Further, the BAQ and BDI scores were closely related within a group of PWE, while BAQ and BDI scores were not correlated with each other within a group of PWID. With regard to pharmaceutical therapy, the safety of antidepressants, especially SSRIs, is well established. However, there has been only one randomized controlled trial (RCT) thus far, which failed to show a significant difference in efficacy between placebo and various antidepressants. In contrast, there are two RCTs regarding the efficacy of LTG. The clinical profile of the depressiolytic effects of LTG in PWE may be different from that of antidepressants in patients with idiopathic depression, in that BAQ is more sensitive measure than BDI or CES-D. It is now widely recognized that the failure to treat depression in PWE can result in serious consequences. However, even a fundamental question, such as whether antidepressants are as effective in this population as in PWID, remains to be answered.

Lamotrigine improves aggression in patients with temporal lobe epilepsy.

Aggression in patients with temporal lobe epilepsy (TLE) may have phenomenological and neurobiological heterogeneity. In the present study, we targeted patients with TLE who showed aggression and evaluated the effects of lamotrigine on this symptom using the Buss-Perry Aggression Questionnaire (BAQ), which is based on a four-factor model that includes Physical Aggression, Verbal Aggression, Anger, and Hostility. As compared with the healthy control subjects (n=115), patients with TLE (n=21) had significantly higher BAQ Total, Physical Aggression, Anger, and Hostility scores. Ten weeks after initiation of lamotrigine, the BAQ Total and Anger scores of the patients with TLE were significantly improved. However, the patients with TLE in this study did not exhibit depressive symptoms. Our results suggest that lamotrigine mitigates aggression, especially anger, which represents the emotional factor of aggression in the BAQ.

Violence and postictal psychosis: a comparison of postictal psychosis, interictal psychosis, and postictal confusion.

The belief that epilepsy is linked with violent behavior acquired a highly stigmatizing value in the late 19th century on the basis of degenerative theory. This widespread medical view lost general acceptance among experts in the 1990s after several large-scale studies showed that aggressive phenomena can arise during epileptic seizures, but are extremely rare. The concept of postictal psychosis (PIP) shed a new light on this old dispute. With this concept, the significance of the chronological relationship between seizures and violent behaviors in patients with epilepsy is newly stressed, which made a simple "yes" or "no" answer to the question implausible. In this review, we discuss violent behaviors at five chronological points relative to seizures and demonstrate representative cases. As shown in our previous study, well-directed violent attacks occurred during 22.8% of the PIP episodes, 4.8% of the IIP episodes, and 0.7% of the postictal confusions. Compared with the other two situations, proneness to violence stood out in the PIP episodes. Suicidal attempts showed a similar trend. Purposeful, organized violence as a direct manifestation of seizures or ictal automatism is highly exceptional. Violent acts could occur in postictal confusion as an expression of unconscious, vigorous resistance against efforts of surrounding people to prevent the affected individual from roaming or fumbling about. In contrast, some PIP episodes can be highly alarming, especially if a violent act has been previously committed in preceding episodes. Violent acts by patients with epilepsy should be treated differently according to the various pathophysiological backgrounds from which the violence arises.

The cell wall galactomannan antigen from Malassezia furfur and Malassezia pachydermatis contains beta-1,6-linked linear galactofuranosyl residues and its detection has diagnostic potential.

Lipophilic yeasts of the genus Malassezia are associated with several skin diseases, such as pityriasis versicolor, Malassezia folliculitis, seborrhoeic dermatitis and atopic dermatitis, and are also increasingly associated with catheter-related fungaemia. The cell wall components of pathogenic micro-organisms behave as an antigen and/or ligand of the innate immune response. Live cells of Malassezia furfur and Malassezia pachydermatis did not react with an anti-alpha-1,2-mannoside antibody. However, they showed a strong hydrophobicity and reactivity with an anti-beta-1,3-glucan antibody compared to those of C. albicans. The cell wall polysaccharides of M. furfur and M. pachydermatis were isolated and their structures analysed by (1)H and (13)C NMR experiments. Both polysaccharides were shown to be beta-1,6-linked linear galactofuranosyl polymers with a small amount of mannan. The presence of galactomannan on cells of Malassezia species has not been described previously. The galactomannan did not react with an anti-Aspergillus fumigatus monoclonal antibody which has specificity for beta-1,5-linked galactofuranosyl residues. An anti-M. furfur antibody strongly reacted with the galactomannans of M. furfur and M. pachydermatis, but did not react with the galactomannans of Trichophyton rubrum, A. fumigatus or Fonsecaea pedrosoi. The characteristics of the anti-M. furfur antibody suggest that there is potential for diagnosis of Malassezia infections by antigen detection.

Interictal psychoses in comparison with schizophrenia--a prospective study.

PURPOSE: To prospectively investigate the incidence of interictal psychoses of epilepsy patients, and make a comparison between those with interictal psychoses and patients with schizophrenia in respect to their responses to antipsychotic drugs, as well as psychotic states. METHODS: We undertook a two-part prospective investigation. In Part I, the psychotic episodes of 619 epilepsy patients were investigated, while 182 patients with psychotic syndromes were followed in Part II, of whom 59 were diagnosed with schizophrenia and 13 with epilepsy with interictal psychoses. The Positive and Negative Syndrome Scale was used for efficacy assessment. RESULTS: The average annual incidence of interictal psychosis was 0.42% during the 56-month study period. A significant difference was found between patients with schizophrenia and epilepsy patients with interictal psychoses in respect to results on the negative subscale of the PANSS at the initial examination (mean scores of 18.1 and 13.2, respectively, p = 0.004). The response rates one year later for these groups were 27.1% and 53.8%, respectively, which showed a trend of better response to the antipsychotic medication by the epilepsy group (p = 0.098). Initial and maximum doses of antipsychotic drugs used for epilepsy patients with interictal psychoses were significantly lower than those used for patients with schizophrenia (p = 0.008 and p = 0.006, respectively). CONCLUSIONS: Schizophrenia and epileptic psychosis showed different symptom profiles. On average, epilepsy patients with interictal psychoses achieved higher remission rates with lower doses of antipsychotic drugs as compared to patients with schizophrenia in the present 1-year follow-up study.

Duration of postictal psychotic episodes.

PURPOSE: To clarify duration of postictal psychosis (PIP) episodes and identify factors that influence its duration. METHODS: Fifty-eight patients with epilepsy exhibited 151 PIP episodes during a mean follow-up period of 12.8 years. Distribution of the duration of these episodes was determined, and factors potentially affecting were analyzed. Factors analyzed included PIP-related variables (i.e., antecedent seizures and the lucid interval) and patient characteristics (i.e., type of epilepsy, lateralization of EEG abnormalities, and intellectual functioning). RESULTS: The mean duration of the 58 first PIP episodes was 10.5 days, and that of all 151 PIP episodes (including multiple episodes) was 9.2 days. Approximately 95% of the PIP episodes resolved within 1 month. Most PIP-related variables, except for antipsychotic drugs administered, were not associated with duration of the episodes. Several patient characteristics, i.e., history of interictal psychosis, family history of psychosis, and intellectual functioning, were associated with duration of the PIP episodes. CONCLUSIONS: This study showed that most PIP episodes last less than 1 month. PIP episodes appear to be prolonged when individuals have an underlying vulnerability to psychosis. Clinical phenomena that can trigger PIP may not determine the course of the PIP episode.

Postictal autoscopy in a patient with partial epilepsy.

Autoscopy is an experience of seeing oneself in external space, viewed from within one's own physical body. It is a complex psycho-sensorial hallucinatory perception of one's own body image projected into external visual space, with epilepsy one of the common disorders reported to be associated with the experience. A survey of the literature revealed that there are few case reports of postictal autoscopic phenomena. Herein, we report a case of a patient with partial epilepsy who has experienced postictal autoscopy for nearly 30 years. Although the neurological mechanisms that cause autoscopic phenomena are not fully understood, wish-fulfilling fantasies released as a result of a shaken integrity regarding personal bodily image may contribute to the shaping of the symptoms, at least in the case of postictal autoscopy.

A prospective study of postictal psychoses with emphasis on the periictal type.

PURPOSE: To assess prospectively episodes of postictal psychosis. METHODS: We followed 108 consecutive patients with temporal lobe epilepsy, who were divided into three groups: those without psychotic episodes (n=87, N group), those with interictal psychosis (n=13, IIP group), and those with postictal psychosis (n=8, PIP group). The first episode of postictal psychosis, which was defined as a psychotic episode that occurred within 1 week after the end or within 3 days before the beginning of seizure clusters, was assessed with the Brief Psychiatric Rating Scale (BPRS) and Social Dysfunction and Aggression Scale (SDAS) during the observation period. RESULTS: The duration of illness was significantly different between the N and PIP groups (p=0.004) and between the N and IIP groups (p=0.039). The average initial BPRS score (obtained 3.0 days after the end of the seizure cluster) was 19.7, and then decreased to 5.8 after 1 week, and finally normalized at 1.5 after 1 month. A statistically significant decrease in BPRS scores was found between the initial assessment and those obtained after 1 week (p=0.011). Those who had psychotic episodes without a lucid interval tended to have episodes more often than monthly, and experienced additional seizure recurrence even during the psychotic episodes. Two patients exhibited a frank manic phase, and three patients showed excessively aggressive behavior, as determined by the SDAS. CONCLUSIONS: Postictal psychosis should be subdivided into the nuclear type, with an established clinical picture as an indirect aftereffect of seizure activity, and the atypical periictal type, which is a direct manifestation of limbic discharge.