Correlation of motor-auditory cross-modal and auditory unimodal N1 and mismatch responses of schizophrenic patients and normal subjects: an MEG study.

Introduction: It has been suggested that the positive symptoms of schizophrenic patients (hallucinations, delusions, and passivity experience) are caused by dysfunction of their internal and external sensory prediction errors. This is often discussed as related to dysfunction of the forward model that executes self-monitoring. Several reports have suggested that dysfunction of the forward model in schizophrenia causes misattributions of self-generated thoughts and actions to external sources. There is some evidence that the forward model can be measured using the electroencephalography (EEG) and magnetoencephalography (MEG) components such as N1 (m) and mismatch negativity (MMN) (m). The objective in this MEG study is to investigate differences in the N1m and MMNm-like activity generated in motor-auditory cross-modal tasks in normal control (NC) subjects and schizophrenic (SC) patients, and compared that activity with N1m and MMNm in the auditory unimodal task. Methods: The N1m and MMNm/MMNm-like activity were recorded in 15 SC patients and 12 matched NC subjects. The N1m-attenuation effects and peak amplitude of MMNm/MMNm-like activity of the NC and SC groups were compared. Additionally, correlations between MEG measures (N1m suppression rate, MMNm, and MMNm-like activity) and clinical variables (Positive and Negative Syndrome Scale (PANSS) scores and antipsychotic drug (APD) dosages) in SC patients were investigated. Results: It was found that (i) there was no significant difference in N1m-attenuation for the NC and SC groups, and that (ii) MMNm in the unimodal task in the SC group was significantly smaller than that in the NC group. Further, the MMNm-like activity in the cross-modal task was smaller than that of the MMNm in the unimodal task in the NC group, but there was no significant difference in the SC group. The PANSS positive symptoms and general psychopathology score were moderately negatively correlated with the amplitudes of the MMNm-like activity, and the APD dosage was moderately negatively correlated with the N1m suppression rate. However, none of these correlations reached statistical significance. Discussion: The findings suggest that schizophrenic patients perform altered predictive processes differently from healthy subjects in latencies reflecting MMNm, depending on whether they are under forward model generation or not. This may support the hypothesis that schizophrenic patients tend to misattribute their inner experience to external agents, thus leading to the characteristic schizophrenia symptoms.

Psychoses after an antiepileptic drug administration: Frequency, timing, and duration.

OBJECTIVES: To clarify the pathophysiology of psychoses after the new administration of antiepileptic drugs (AED), we analyzed the annual incidence, timing of development, and duration of episodes. METHODS: Psychotic outcomes in the first 6-month period after an AED or non-AED administration in patients with focal epilepsy were exhaustively reviewed in eight Japanese neuropsychiatry institutions. In cases with psychotic episodes, the subtype of psychosis, timing of development, previous history of psychosis, and duration of the episode were evaluated. RESULTS: Between 1981 and 2015, 5018 new drugs (4402 AED and 616 non-AED) were administered to 2067 patients with focal epilepsy. In the first 6-month period, 105 psychotic episodes occurred (81 interictal psychosis [IIP] and 24 postictal psychosis). Furthermore, 55 cases were first episodes and 50 were recurrent episodes. The frequency of psychoses is significantly higher after AED administration (n = 102) compared with non-AED administration (n = 3). Psychosis occurred most frequently in the initial 1-month period after new-AED administration and tended to decrease with increasing time. The estimated annual incidence of all psychoses after a new AED administration was 3.5% (2.0% for first-episode psychosis and 1.8% for first-episode IIP). Duration of psychoses (mean, 38.5 weeks) was equivalent to overall IIP. Duration of IIP did not shorten with discontinuation of newly administered AED. SIGNIFICANCE: Patients with epilepsy exhibit psychosis more frequently after new AED administration than after non-AED administration. This study shows the pathophysiology of psychoses after AED administration with annual incidence, the timing of development, and the duration of PAP, which have rarely been reported.

Quantitative psychopathology of interictal psychosis in epilepsy; interaction between epilepsy-related and psychosis-general effects.

OBJECTIVE: There is a historical debate whether psychopathology of epilepsy psychosis is unique to epilepsy or common to other psychoses. However, a large comprehensive studies on this issue are scarce. To clarify the characteristics of interictal psychosis (IIP), we evaluated psychopathology quantitatively. METHODS: This study included 150 patients with IIP (epilepsy+/psychosis+), 187 patients with schizophrenia (SC: epilepsy-/psychosis+), 182 patients with epilepsy (EP: epilepsy+/psychosis-), and 172 non-clinical individuals (NC: epilepsy-/psychosis-). The IIP group comprised 127 chronic and 23 brief psychoses. Age, sex, and years of education, onset and duration of psychosis, and onset and duration of epilepsy were matched among the groups. The psychopathology was evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS), which comprises three symptom factors namely negative symptoms (NS), positive symptoms (PS), and anxiety-depressive symptoms (ADS). RESULTS: For overall 16-BPRS and NS factor scores, there were significant interactions between epilepsy-related (epilepsy+/-) and psychosis-general (psychosis+/-) effects. The EP exhibited higher scores than did the NC, whereas the IIP exhibited lower scores than did the SC. For PS and ADS factor scores, the IIP and SC exhibited a significant psychosis-general effect. Chronic IIP was associated with more serious psychopathologies than was brief IIP. However, limited with chronic IIP, there was a significant interaction between epilepsy-related and psychosis-general effects on the overall 16-BPRS and NS factor scores. CONCLUSION: These findings demonstrate the first large quantitative evidence on the unique psychopathology of IIP which has been only narratively described. The psychopathology is associated with the interaction between epilepsy-related and psychosis-general effects.

The self-stigma of patients with epilepsy in Japan: A qualitative approach.

The mental health of patients with epilepsy represents a substantial public health concern in Japan. For instance, the Japanese term for epilepsy, "tenkan", has the negative meaning of "mad" and "a violent temperament that is apt to be infatuated". Although epilepsy is now understood as a disease caused by abnormal neuronal activity in the brain, discrimination and stigma against people with epilepsy remain deeply rooted in Japanese culture. Understandably, this stigma can have a serious impact on the psychology and behavior of individuals with epilepsy. To our knowledge, no studies have clarified the formation process or examined the treatment of self-stigma in patients with epilepsy in Japan. Characterizing coping strategies and examining methods for reducing self-stigma will increase our understanding of the experiences of patients and facilitate effective psychiatric rehabilitation. Accordingly, the purpose of our study was to investigate the quality and degree of cognition regarding self-stigma and to examine coping strategies in patients with epilepsy living in the community. The participants were psychiatric outpatients aged 20-65 years who had been diagnosed with epilepsy and visited our psychiatric outpatient clinic between October 1 and December 31, 2016. We conducted semi-structured interviews with 20 patients who consented to participate. For data analysis, we used the content analysis method proposed. Our study revealed details of self-stigma in patients with epilepsy. Patients and their families are often aware of the presence of this self-stigma, and many do not know how to address it. In this study, we qualitatively examined self-stigma in patients with epilepsy on the basis of patient narratives. Per our findings, we would like to examine intervention methods for reducing self-stigma in patients with epilepsy.

Individual vulnerabilities to psychosis after antiepileptic drug administration.

BACKGROUND: Psychosis often develops after the administration of antiepileptic drugs (AEDs) in patients with epilepsy. However, the individual vulnerability and clinical condition of such patients have been rarely scrutinised. We investigated the effect of individually consistent (trait-dependent) and inconsistent (state-dependent) characteristics. METHODS: The individual characteristics, clinical states and psychotic outcome of patients from eight adult epilepsy clinics were retrospectively reviewed over 6-month periods after a new drug (AED or non-AED) administration between 1981 and 2015. RESULTS: A total of 5018 new drugs (4402 AEDs and 616 non-AEDs) were used in 2015 patients with focal epilepsy. Subsequently, 105 psychotic episodes (81 interictal and 24 postictal) occurred in 89 patients. Twelve patients exhibited multiple episodes after different AED administrations. Trait-dependent characteristics (early onset of epilepsy, known presumed causes of epilepsy, lower intellectual function and a family history of psychosis) were significantly associated with the patients who exhibited psychosis. Absence of family history of epilepsy was also associated with psychosis but not significantly. Subsequent logistic regression analysis with a model incorporating family history of psychosis and epilepsy, and intellectual function was the most appropriate (p=0.000). State-dependent characteristics, including previous psychotic history and epilepsy-related variables (longer duration of epilepsy, AED administration, higher seizure frequency and concomitant use of AEDs) were significantly associated with psychotic episodes. Subsequent analysis found that a model including AED administration and previous psychotic history was the most appropriate (p=0.000). CONCLUSION: Psychosis occurring after new AED administration was related to the individual vulnerability to psychosis and intractability of epilepsy.

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a potentially novel strategy for cognitive enhancement in patients with mild or major neurocognitive disorders. This study aims to assess the safety and efficacy of tDCS during cognitive training on cognitive functioning in patients with mild or major neurocognitive disorders. METHODS: This study was primarily a single arm for safety, secondary a two-arm, parallel, randomized, and sham-controlled trial for potential efficacy. Patients with mild or major neurocognitive disorders were recruited. The participants and raters were blinded to the group assignment. The participants in the active arm received tDCS (anodal; F3, cathodal, Fp2, 2A, 20 min) twice daily for five consecutive days, whereas those in the sham arm received the same amount of sham-tDCS. Calculation and reading tasks were conducted in both arms as a form of cognitive intervention for 20 min during tDCS. The primary outcome was the attrition rate during the trial in the active arm, which is expected to be less than 10%. The secondary outcomes were the between-group differences of adjusted means for several cognitive scales from baseline to post-intervention and follow-up. RESULTS: Twenty patients [nine women (45%)], with a mean (standard deviation) age of 76.1 years participated; nine patients (45%) with minor neurocognitive disorders and 11 (55%) with major neurocognitive disorders were randomized, and 19 of them completed the trial. The attrition rate in the active arm was 0%, with no serious adverse events. Further, in the Intention-to-Treat analysis, patients in the active arm showed no statistically significant improvement compared with those who received the sham in the mean change scores of the mini-mental state examination [0.41; 95% CI (-1.85; 2.67) at day five, 1.08; 95% CI (-1.31; 3.46) at follow-up] and Alzheimer's disease assessment scale - cognition subscale [1.61; 95% CI (-4.2; 0.98) at day 5, 0.36; 95%CI (-3.19; 2.47) at follow-up]. CONCLUSION: These findings suggest that tDCS is safe and tolerable but causes no statistically significant cognitive effects in patients with mild or major neurocognitive disorders. Additional large-scale, well-designed clinical trials are warranted to evaluate the cognitive effects of tDCS as an augmentation to cognitive training. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT03050385.

Increased frequency of psychosis after second-generation antiepileptic drug administration in adults with focal epilepsy.

OBJECTIVE: Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP. METHODS: The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures. RESULTS: Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP. CONCLUSION: Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

Reduced resilience of brain gray matter networks in idiopathic generalized epilepsy: A graph-theoretical analysis.

PURPOSE: The pathophysiology of idiopathic generalized epilepsy (IGE) is still unclear, but graph theory may help to understand it. Here, we examined the graph-theoretical findings of the gray matter network in IGE using anatomical covariance methods. MATERIALS AND METHODS: We recruited 33 patients with IGE and 35 age- and sex-matched healthy controls. Gray matter images were obtained by 3.0-T 3D T1-weighted MRI and were normalized using the voxel-based morphometry tools of Statistical Parametric Mapping 12. The normalized images were subjected to graph-theoretical group comparison using the Graph Analysis Toolbox with two different parcellation schemes. Initially, we used the Automated Anatomical Labeling template, whereas the Hammers Adult atlas was used for the second analysis. RESULTS: The resilience analyses revealed significantly reduced resilience of the IGE gray matter networks to both random failure and targeted attack. No significant between-group differences were found in global network measures, including the clustering coefficient and characteristic path length. The IGE group showed several changes in regional clustering, including an increase mainly in wide areas of the bilateral frontal lobes. The second analysis with another region of interest (ROI) parcellation generated the same results in resilience and global network measures, but the regional clustering results differed between the two parcellation schemes. CONCLUSION: These results may reflect the potentially weak network organization in IGE. Our findings contribute to the accumulation of knowledge on IGE.

Pisa syndrome associated with mirtazapine: a case report.

BACKGROUND: Mirtazapine is a noradrenergic and specific serotonergic antidepressant; its pharmacological profile indicates a low risk for dopaminergic adverse effects. To date, there has been only a single case report of Pisa syndrome associated with mirtazapine. CASE PRESENTATION: The authors report a case involving a 79-year-old woman with bipolar disorder, in whom Pisa syndrome occurred after introduction of mirtazapine, and completely disappeared 3 days after suspension of the drug. CONCLUSIONS: Aspects of this particular case suggest that Pisa syndrome is a possible side effect of Mirtazapine.

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; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .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.

Brain morphological and microstructural features in cryptogenic late-onset temporal lobe epilepsy: a structural and diffusion MRI study.

PURPOSE: Although epilepsy in the elderly has attracted attention recently, there are few systematic studies of neuroimaging in such patients. In this study, we used structural MRI and diffusion tensor imaging (DTI) to investigate the morphological and microstructural features of the brain in late-onset temporal lobe epilepsy (TLE). METHODS: We recruited patients with TLE and an age of onset > 50 years (late-TLE group) and age- and sex-matched healthy volunteers (control group). 3-Tesla MRI scans, including 3D T1-weighted images and 15-direction DTI, showed normal findings on visual assessment in both groups. We used Statistical Parametric Mapping 12 (SPM12) for gray and white matter structural normalization and comparison and used Tract-Based Spatial Statistics (TBSS) for fractional anisotropy and mean diffusivity comparisons of DTI. In both methods, p < 0.05 (family-wise error) was considered statistically significant. RESULTS: In total, 30 patients with late-onset TLE (mean ± SD age, 66.8 ± 8.4; mean ± SD age of onset, 63.0 ± 7.6 years) and 40 healthy controls (mean ± SD age, 66.6 ± 8.5 years) were enrolled. The late-onset TLE group showed significant gray matter volume increases in the bilateral amygdala and anterior hippocampus and significantly reduced mean diffusivity in the left temporofrontal lobe, internal capsule, and brainstem. No significant changes were evident in white matter volume or fractional anisotropy. CONCLUSIONS: Our findings may reflect some characteristics or mechanisms of cryptogenic TLE in the elderly, such as inflammatory processes.

Seizure activity and individual vulnerability on first-episode interictal psychosis in epilepsy.

OBJECTIVE: Despite a theoretical consensus that interictal psychosis (IIP) is related to various epilepsy-related factors, the impact of seizure activity on development of IIP remains inconclusive. This is the first controlled study using quantitative seizure-activity measures at the onset of IIP. METHODS: One hundred and eighty-one patients with epilepsy who exhibited first-episode IIP (IIP group) and 427 patients with epilepsy without psychotic episodes (control group) were enrolled. The control group was matched for age, epilepsy type, and duration of epilepsy. The two seizure-activity indices (seizure frequency at the time of onset of first-episode IIP and the number of seizures before the onset of IIP) were evaluated and compared between the IIP and control groups. Logistic regression analysis was used for extracting risk variables to develop first-episode IIP. RESULTS: The sum of previous seizures was greater in the IIP than in control groups. This was particularly the case in the patients with partial epilepsies (PE). Higher seizure frequency in the patients with PE was associated with the development of first-episode IIP while no association was found in the whole cohort or in the patients with generalized epilepsies (GE). Subsequent multivariate analysis revealed the sum of previous seizures and family history of psychosis as risk variables to first-episode IIP. CONCLUSIONS: The accumulation of seizure-related damages and family history of psychosis is associated with the onset of IIP episodes, particularly in the patients with PE. Seizure activity and individual vulnerability to psychosis are likely to be interacted for as the development of IIP in patients with epilepsy.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. RESULTS: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. CONCLUSION: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. TRIAL REGISTRATION: UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

White matter abnormalities in patients with temporal lobe epilepsy and amygdala enlargement: Comparison with hippocampal sclerosis and healthy subjects.

PURPOSE: Cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have increasingly been reported. However, the white matter (WM) abnormalities of TLE patients with AE remain poorly investigated. Here we explored macrostructural and microstructural WM abnormalities in TLE patients with AE compared to normal controls and TLE patients with hippocampal sclerosis (HS). MATERIAL AND METHODS: We selected 17 patients with unilateral TLE with AE (TLE-AE) based on automated amygdala volumetry using FreeSurfer software, and 34 healthy controls and 35 patients with unilateral TLE with HS (TLE-HS) were also recruited. Subsequently, differences in gray matter (GM) and WM volumes and fractional anisotropy (FA) among the three groups were analyzed using SPM8 software. RESULTS: The volume analysis of GM obtained results that are consistent with the structural characteristics of TLE with AE and with HS (i.e. amygdala increase in the TLE-AE, and mesial temporal atrophy in the TLE-HS). In the volume of WM, only the TLE-HS patients had WM reductions mainly in the ipsilateral temporal lobe. Compared to the controls, the TLE-AE group showed a significant FA decrease in the ipsilateral anterior cingulum and the corpus callosum, whereas an extended FA decrease in the whole cerebrum was observed in the TLE-HS group. CONCLUSION: Our findings regarding the WM of TLE patients with AE may reflect characteristic pathophysiology such as the anatomical and functional connection between the amygdala and medial prefrontal cortex, and our results may thus provide insights into TLE with AE.

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.

Impaired cerebral blood flow networks in temporal lobe epilepsy with hippocampal sclerosis: A graph theoretical approach.

Graph theory is an emerging method to investigate brain networks. Altered cerebral blood flow (CBF) has frequently been reported in temporal lobe epilepsy (TLE), but graph theoretical findings of CBF are poorly understood. Here, we explored graph theoretical networks of CBF in TLE using arterial spin labeling imaging. We recruited patients with TLE and unilateral hippocampal sclerosis (HS) (19 patients with left TLE, and 21 with right TLE) and 20 gender- and age-matched healthy control subjects. We obtained all participants' CBF maps using pseudo-continuous arterial spin labeling and analyzed them using the Graph Analysis Toolbox (GAT) software program. As a result, compared to the controls, the patients with left TLE showed a significantly low clustering coefficient (p=0.024), local efficiency (p=0.001), global efficiency (p=0.010), and high transitivity (p=0.015), whereas the patients with right TLE showed significantly high assortativity (p=0.046) and transitivity (p=0.011). The group with right TLE also had high characteristic path length values (p=0.085), low global efficiency (p=0.078), and low resilience to targeted attack (p=0.101) at a trend level. Lower normalized clustering coefficient (p=0.081) in the left TLE and higher normalized characteristic path length (p=0.089) in the right TLE were found also at a trend level. Both the patients with left and right TLE showed significantly decreased clustering in similar areas, i.e., the cingulate gyri, precuneus, and occipital lobe. Our findings revealed differing left-right network metrics in which an inefficient CBF network in left TLE and vulnerability to irritation in right TLE are suggested. The left-right common finding of regional decreased clustering might reflect impaired default-mode networks in TLE.

Graph Theoretical Analysis of Structural Neuroimaging in Temporal Lobe Epilepsy with and without Psychosis.

PURPOSE: Psychosis is one of the most important psychiatric comorbidities in temporal lobe epilepsy (TLE), and its pathophysiology still remains unsolved. We aimed to explore the connectivity differences of structural neuroimaging between TLE with and without psychosis using a graph theoretical analysis, which is an emerging mathematical method to investigate network connections in the brain as a small-world system. MATERIALS AND METHODS: We recruited 11 TLE patients with unilateral hippocampal sclerosis (HS) presenting psychosis or having a history of psychosis (TLE-P group). As controls, 15 TLE patients with unilateral HS without any history of psychotic episodes were also recruited (TLE-N group). For graph theoretical analysis, the normalized gray matter images of both groups were subjected to Graph Analysis Toolbox (GAT). As secondary analyses, each group was compared to 14 age- and gender-matched healthy subjects. RESULTS: The hub node locations were found predominantly in the ipsilateral hemisphere in the TLE-N group, and mainly on the contralateral side in the TLE-P group. The TLE-P group showed significantly higher characteristic path length, transitivity, lower global efficiency, and resilience to random or targeted attack than those of the TLE-N group. The regional comparison in betweenness centrality revealed significantly decreased connectivity in the contralateral temporal lobe, ipsilateral middle frontal gyrus, and bilateral postcentral gyri in the TLE-P group. The healthy subjects showed well-balanced nodes/edges distributions, similar metrics to TLE-N group except for higher small-worldness/modularity/assortativity, and various differences of regional betweenness/clustering. CONCLUSION: In TLE with psychosis, graph theoretical analysis of structural imaging revealed disrupted connectivity in the contralateral hemisphere. The network metrics suggested that the existence of psychosis can bring vulnerability and decreased efficiency of the whole-brain network. The sharp differences in structural networks between morphologically homogeneous groups are remarkable and may contribute to a better understanding of psychosis in TLE.

A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness.

Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs). Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC) complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.

Effect of electroconvulsive therapy on gray matter volume in major depressive disorder.

BACKGROUND: Although the clinical efficacy of electroconvulsive therapy (ECT) is well established, the underlying mechanisms of action remain elusive. The aim of this study was to elucidate structural changes of the brain following ECT in patients with major depressive disorder (MDD). METHOD: Fifteen patients with MDD underwent magnetic resonance imaging scanning before and after ECT. Their gray matter volumes were compared between pre- and post-ECT. RESULTS: There were significant volume increases after ECT in the bilateral medial temporal cortices, inferior temporal cortices, and right anterior cingulate. Further, the increase ratio was correlated with the clinical improvement measured by the Hamilton Depression Rating scale. LIMITATION: All subjects were treated with antidepressants that could have a neurotoxic or neuroprotective effect on the brain. CONCLUSIONS: We found that there were significant increases of gray matter volume in medial temporal lobes following ECT, suggesting that a neurotrophic effect of ECT could play a role in its therapeutic effect.

Evaluation of amygdala pathology using (11)C-methionine positron emission tomography/computed tomography in patients with temporal lobe epilepsy and amygdala enlargement.

OBJECTIVE: The association between amygdala enlargement (AE) and temporal lobe epilepsy (TLE) has increasingly been reported. However, the pathology of AE remains poorly understood. The purpose of this study was to explore AE pathology using (11)C-methionine (Met) positron emission tomography (PET)/computed tomography (CT) in patients who have TLE with AE. MATERIALS AND METHODS: Twenty-six TLE patients with AE and 18 TLE patients without AE underwent (11)C-Met PET/CT and magnetic resonance imaging (MRI). (11)C-Met uptake in amygdala was evaluated by both visual inspection and semi-quantitative measurement. MRI was assessed visually and semi-quantitatively for AE. Laterality index (LI) was obtained by comparing the amygdala volumes of ipsilateral and contralateral sides. The clinical course and histopathological findings of all patients were also analyzed. RESULTS: On (11)C-Met PET/CT images, visual examination detected increased uptake in the enlarged amygdala in 7 of 26 (27%) TLE patients with AE, and the results were confirmed by semi-quantitative analysis. Among six TLE patients with AE who underwent surgery, histopathology revealed neoplasms (low grade astrocytoma and gangliocytoma) in two patients and focal cortical dysplasia in one patient with increased (11)C-Met uptake, but non-neoplastic lesions (focal cortical dysplasia, vacuolar degeneration, and hamartoma) in all three patients with no increased (11)C-Met uptake. On MRI, volume of the affected amygdala was significantly larger compared to the contralateral amygdala. LI was significantly higher in the group with AE than in the group without AE. CONCLUSIONS: This study revealed that some TLE patients with AE showed increased (11)C-Met uptake in the enlarged amygdala. (11)C-Met PET/CT is potentially useful for the evaluation of AE pathology, and may provide beneficial information for appropriate decision-making.