Teiichi Onuma

Psychoses and epilepsy: are interictal and postictal psychoses distinct clinical entities?

Summary: u2002Purpose: To evaluate further the relevance of designating psychotic episodes as either postictal or interictal, we compared several biologic variables between epilepsy patients with and without psychosis.

Predictive variables of interictal psychosis in epilepsy

Objective: To evaluate which variables predict interictal psychosis in epilepsy. Methods: The authors reviewed the biological backgrounds, clinical characteristics, and EEG findings in 246 patients with epilepsy and interictal psychosis and in 658 control patients with epilepsy and no psychotic history. With a logistic regression approach, the significance of each variable for the development of interictal psychosis was evaluated. Results: There are significant differences in family history of psychosis, age at onset of epilepsy, type of epilepsy, lateralization of epileptiform discharges, and level of intelligence between patients with interictal psychosis and those without it. Subsequent logistic regression analysis with all variables demonstrated that family history of psychosis, age at onset of epilepsy, type of seizures, and level of intelligence significantly correlated with psychosis. Conclusions: A family history of psychosis, earlier age at onset of epilepsy, complex partial seizures or generalized tonic clonic seizures, and borderline intellectual functioning were the most important predictors for development of interictal psychosis.

Frequency and age-related variables in interictal psychoses in localization-related epilepsies

PURPOSEnSeveral studies have described that patients with temporal lobe epilepsy (TLE) develop psychoses more frequently than patients with extra-temporal localization-related epilepsy (LRE). However, few controlled studies have demonstrated an increased susceptibility to psychosis in TLE patients. As one of a series of multi-center studies on psychosis in epilepsy, we investigated whether the frequency of interictal psychosis differs between types of LRE.nnnMETHODSnWe reviewed some biological characteristics of 197 PE patients with interictal psychosis and of 456 LRE patients with no history of psychosis. Type of PE was determined as TLE, frontal lobe epilepsy, parietal lobe epilepsy, occipital lobe epilepsy, and multi-lobar epilepsy/undifferentiated lobar epilepsy by clinical symptoms, EEG findings, and neuroimaging. The frequency of psychosis for each type of LRE was compared. Ages at onset of epilepsy and psychosis and the time interval between onset of each were also analyzed.nnnRESULTSnThere was no significant correlation between psychosis and epilepsy type (P=0.211). Age-related variables also failed to show any significant differences between LRE types (age at onset of epilepsy, P=0.369; age at onset of psychosis, P=0.852; the time interval, P=0.893).nnnCONCLUSIONSnPatients with LREs as well as with TLE are susceptible to interictal psychosis. The mean ages at onset of symptoms and the interval between onset of epilepsy and onset of psychosis that we observed suggest that patients with LREs, regardless of focus, may share similar processes in the development of psychiatric symptoms.

Intellectual Disability and Psychotic Disorders of Adult Epilepsy

Summary:u2002 Purpose: To investigate the prevalence, psychopathology, and cognitive functions associated with psychotic disorders among adult epilepsy patients with intellectual disability (ID) based on a multicenter study in Japan.

Proposal for a New Five-Axis Classification Scheme for Psychoses of Epilepsy

Based on an overview of the literature and a multicenter study in Japan, we propose a new five-axis classification scheme for psychoses of epilepsy: (1) epilepsy variables, (2) psychopathology variables, (3) ictus/EEG variables, (4) precipitating factors of psychoses, (5) organic background. A total of 128 patients, 63 males and 65 females, with epilepsy and psychoses were recruited from five treatment centers. A wide heterogeneity of psychoses of epilepsy was demonstrated and categorization by a single axis was shown to be inadequate. Cluster analysis revealed four subgroups characterized by their psychopathology, temporal relationship to seizure occurrence, and EEG changes during psychoses. By comparing with the control epileptic group without psychoses, higher rates of mild intelligence disturbance and abnormal findings by brain imaging were proven among the psychotic group. The scheme involves a dimensional representation of individual patients to capture the complexity of their clinical background and to relay clinical information accurately and systematically. It is believed to hold direct therapeutic implications and to contribute to promoting research by enabling accumulation of a large number of patients on a multicenter basis.

Automated subfield volumetric analysis of hippocampus in temporal lobe epilepsy using high-resolution T2-weighed MR imaging.

Background and purpose Automated subfield volumetry of hippocampus is desirable for use in temporal lobe epilepsy (TLE), but its utility has not been established. Automatic segmentation of hippocampal subfields (ASHS) and the new version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR imaging are candidates for this volumetry. The aim of this study was to evaluate hippocampal subfields in TLE patients using ASHS as well as the old and new versions of FreeSurfer. Materials and methods We recruited 50 consecutive unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25 without obvious etiology (TLE-nonHS). All patients and 45 healthy controls underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each subfield, normalized z-scores were calculated and compared among groups. Results In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS group, there was no significant volume reduction by either ASHS or FreeSurfer. Conclusions ASHS and the new version of FreeSurfer may have an advantage in compatibility with existing histopathological knowledge in TLE patients with HS compared to the old version of FreeSurfer (ver.5.3), although further investigations with pathological findings and/or surgical outcomes are desirable.

Paranoid‐Hallucinatory State in Patients with Epilepsy: Historical Perspective in Japan

Summary: The major literature on psychosis in patients with epilepsy in Japan is reviewed. A well‐documented case report of postictal psychosis appeared as early as 1908; since then, psychiatrists have been taking an active role in the field of epileptology. Personal observation of a large number of similar cases indicates that most paranoid psychoses in epilepsy are different from schizophrenia in terms of seizure occurrence, time course, and psychiatric symptomatology and may be classified as (a) postictal psychosis, (b) episodic psychosis, (c) chronic schizophrenialike psychosis, (d) psychosis with generalized EEG seizure discharges, and (e) a combination of epilepsy and schizophrenia.

Dissociative experiences in epilepsy: effects of epilepsy-related factors on pathological dissociation.

Psychogenic nonepileptic seizures (PNESs) in patients with epilepsy can be categorized as dissociative disorders. The prevalence of PNESs in patients with epilepsy appears to be much higher than that of dissociative experiences in nonclinical subjects. In order to clarify as to whether epilepsy-related factors were associated with pathological dissociation, we conducted a controlled study with 225 patients with epilepsy and 334 nonclinically matched individuals. All participants completed the Japanese version of the Dissociative Experiences Scale (DES). There was no significant difference in the DES score (DES-S) between the group with epilepsy and the control group. The group with epilepsy showed a significantly higher DES taxon (DES-T; a subset of DES-S and an index of pathological dissociation) than the control group. Thirty-one out of the 225 patients with epilepsy (13.8%) had PNESs. Because of its strong association with the DES-S and DES-T, PNESs can be regarded as a symptom of dissociation. With multiple regression analysis, the patients with a shorter duration of epilepsy, higher seizure frequency, or shorter period in education tend to suffer from pathological dissociation. These findings demonstrate that patients with epilepsy are more prone to experiencing pathological dissociation when having certain clinical factors.

Association of HLA-A*31:01 Screening With the Incidence of Carbamazepine-Induced Cutaneous Adverse Reactions in a Japanese Population

Importance Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated. Objective To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs. Design, Setting, and Participants This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016. Exposures Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. Main Outcomes and Measures Incidence of carbamazepine-induced cADRs. Results Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; Pu2009=u2009.048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; Pu2009<u2009.001). Conclusions and Relevance Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.

A Multi‐Institutional Study on a New Five‐Axial Classification Sys‐ tem for Epileptic Psychoses.

Purpose: The pathophysiology and clinical phenomenology of epileptic psychoses are wide and varied, and an internationally accepted classification system has yet to be established. A multi‐axial classification should be developed to capture the complexity of clinicai situations and to describe the heterogeneity of individuals presenting with the same diagnosis. We propose a new 5‐axial classification system based on a review of the previous literature and evaluate its validity and applicability in Japan by a multi‐institutional design.