Seizure-related stress and arousal responses mediate a relationship between anxiety trait and state in epilepsy.

BACKGROUND: Epilepsy causes substantial psychological distress and anxiety, primarily due to seizures. However, the impact of stress responses and changes in arousal and their association with anxiety patterns in patients with epilepsy (PWE) remains unclear. This study aimed to investigate the relationships among seizures, stress and arousal characteristics, and trait and state anxiety characteristics in PWE. METHODS: Our sample consisted of 159 outpatients with epilepsy recruited from five institutions in Japan in 2020. Participants completed the State-Trait Anxiety Inventory-Form JYZ (STAI) and the Japanese-Stress Arousal Check List (J-SACL). We analyzed the correlations between inventory scores and clinical information. Using principal component analysis (PCA), we derived epilepsy-specific stress/arousal characteristics, which accounted for high arousal and low-stress levels, termed epilepsy-specific stress or arousal response (ESAR), from the J-SACL scores. We conducted a mediation analysis to assess the mediating role of ESAR in the relationship between traits and state anxiety. RESULTS: We found significant correlations between J-SACL stress and arousal factors (r = -0.845, p < 0.001), ESAR and seizure frequency (r = -0.29, p < 0.001), ESAR and trait anxiety scores on the STAI (r = -0.77, p < 0.0001), and ESAR and state anxiety scores on the STAI (r = -0.60, p < 0.0001). Mediation analysis supported by the Monte Carlo method revealed that ESAR significantly mediated the association between trait and state anxiety. CONCLUSIONS: These findings elucidate the epilepsy-specific stress and arousal characteristics and their roles in mediating traits and state anxiety. These results may reflect the long-term clinical course and unique emotion recognition tendencies in epilepsy.

[Pregnancy and Childbirth in Women With Epilepsy].

Women with epilepsy (WWE) need effective and safe treatment during the childbearing age. Administration of antiseizure medications to WWE during pregnancy may be associated with risks to the fetus, including major congenital malformations and negative developmental outcomes. Therefore, preconception care is essential for WWE. Multidisciplinary approaches with interprofessional collaboration are important to support WWE during pregnancy and childbirth; however, such collaboration may be complicated and difficult. Moreover, the prevalence of perinatal depression among WWE is higher than that in the general population. Health care professionals should determine factors associated with perinatal mental health concerns among WWE. Previous meta-analysis have reported that perinatal mental health disorders were associated with a three-fold higher risk of child maltreatment. Therefore, perinatal mental health care is important for WWE.

Classification of transient epileptic amnesia attacks: Two types of amnestic seizures, the pure amnesia type and partial amnesia type.

Aim: Transient epileptic amnesia (TEA) is a type of mesial temporal lobe epilepsy characterized by recurrent amnesia attacks. In 1998, Zeman et al. proposed the following diagnostic criteria for TEA: (1) recurrent, witnessed episodes of amnesia (TEA attacks); (2) other cognitive functions remain intact during attacks; and (3) evidence of epilepsy. It was also reported that patients with TEA often demonstrate two other types of memory symptoms: accelerated long-term forgetting (ALF) and autobiographical amnesia (AbA). Both ALF and AbA are persistent memory disorders, but transient epileptic seizures are not. Methods: We encountered two cases of TEA associated with two types of amnesia attacks. Therefore, we reviewed TEA cases in the literature to clarify the type of TEA attacks that occurred. Results: Based on the extracted TEA cases, including our two cases, we found that there are two main types of TEA attacks, and we discussed their clinical features. Conclusion: We propose two main types of TEA attacks; that is, pure amnesia-type and partial amnesia-type seizures. Furthermore, we also propose that topographical amnesia mainly manifests as a type of amnesia attack, rather than as a chronic memory disturbance, such as ALF or AbA.

Efficacy of antimicrobial therapy for bovine acute Klebsiella pneumoniae mastitis.

The purpose of this retrospective study was to assess the efficacy of antimicrobial therapy for bovine acute Klebsiella pneumoniae mastitis. We evaluated data from cattle in Ehime, Japan, with naturally occurring acute mastitis due to K. pneumoniae (n=208) or Escherichia coli (n=201). Survival was significantly shorter in cattle with acute K. pneumoniae mastitis (median, 76 days) compared with the disease caused by E. coli (median 464 days). In 2004-2008, because both species were highly susceptible to cefazolin, cases of K. pneumoniae and E. coli mastitis were treated solely with cefazolin, yielding clinical cure rates of 52.8% for K. pneumoniae and 86.0% for E. coli. However, since 2009, the efficacy of treatment of K. pneumoniae mastitis with cefazolin alone has decreased. When cefazolin administered on the first disease day led to clinical improvement, treatment with cefazolin was continued. However, when cefazolin administered on the first disease day failed to yield clinical improvement, the antibiotic was switched to a fluoroquinolone on the second day, resulting in cure rates of 76.7% for K. pneumoniae and 80.0% for E. coli. These findings suggest that, when the first-line drug (e.g., cefazolin) is ineffective, promptly changing to a second-line drug (e.g., a fluoroquinolone) increases the cure rate for bovine K. pneumoniae mastitis.

Low prevalence of SARS-CoV-2 specific antibodies among endoscopists and their assistants in a university hospital in Tochigi prefecture-A single-center study.

Objectives: Gastrointestinal endoscopic procedures have a risk to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through aerosols. Little information is available on the seroprevalence of SARS-CoV-2 antibodies among healthcare workers (HCWs) in endoscopy units. Thus, the seroprevalence was examined in HCWs who do and do not participate in gastrointestinal endoscopy. Methods: A total of 382 HCWs at Jichi Medical University Hospital were enrolled in this study through March 2021. Among 382 HCWs, 63 are in the endoscopy unit. Serum antibody levels against SARS-CoV-2 were determined by immunochromatography, chemiluminescent immunoassay (CLIA), electric CLIA (ECLIA), and chemiluminescence microparticle immunoassay (CMIA). HCWs in the endoscopy unit underwent testing up to three times. We defined antibody-positive as when at least one test was positive. Results: The seroprevalence of SARS-CoV-2 antibodies in 63 HCWs in the endoscopy unit was 0%-1.9%, 0%-1.7%, and 0%-1.7% during the first (Ap-May 2020), second (Jun-Nov 2020), and third intervals (Dec 2020-Mar 2021), respectively. This seroprevalence was comparable to that of other HCWs not involved with gastrointestinal endoscopy. Two HCWs in the endoscopy unit were positive for antibodies: one was ECLIA-positive and the another was CMIA-positive. The ECLIA-positive HCW was PCR negative and converted to negative for the second and third tests. Another HCW was CMIA-positive at all three evaluations and the titers were unchanged. No HCWs in the endoscopy unit contracted a SARS-CoV-2 infection. Conclusions: The seroprevalence of SARS-CoV-2 antibodies was low among HCWs in the endoscopy unit through March 2021 (UMIN000039997).

A proposal for a new clinical entity: transient epileptic amnesia complex syndrome (TEACS).

Transient epileptic amnesia (TEA) is a special type of temporal lobe epilepsy, the main symptom of which is recurrent amnesia attacks. In the late 1990s, Zeman et al. developed the following diagnostic criteria for TEA: (i) recurrent, witnessed episodes of amnesia; (ii) other cognitive functions remain intact during attacks; and (iii) evidence of epilepsy. It was subsequently reported that patients with TEA almost always demonstrate two other types of memory symptoms: accelerated long-term forgetting (ALF) and autobiographical amnesia (AbA). As a result, it has been recognised that TEA causes at least three characteristic types of amnesia, that is, amnesia attacks, ALF, and AbA. In this report, we present two clinical cases, in which the patients showed symptoms of ALF and/or AbA without suffering any type of epileptic seizure, including amnesia attacks, for a long time. We discuss a syndrome associated with TEA, particularly the relationship between TEA and ALF/AbA, based on our two cases and a review of the literature. In addition, we propose a new clinical entity, which we named 'transient epileptic amnesia complex syndrome (TEACS)' and will help to ensure that physicians recognise the existence of such cases and do not overlook this condition. Furthermore, the following diagnostic criteria for TEACS are proposed. (i) The patient is middle-aged to elderly at onset and has no history of epilepsy. (ii) ALF and/or AbA have been definitively diagnosed. (iii) The ALF and/or AbA precede TEA attacks and/or other epileptic seizures. (iv) Except for the ALF/AbA, the patient's cognitive functions are confirmed to be intact via clinical examinations. (v) There is evidence for a diagnosis of epilepsy. Such evidence can include: (i) wake or sleep electroencephalography; or (ii) a clear response to anti-epileptic drugs. Furthermore, we describe our hypotheses regarding the pathogenesis of ALF/AbA and discuss the relationships between TEACS and other epileptic amnesia-related syndromes.

Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE). METHODS: Phase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523) in patients with IGE and PGTCS taking 1-3 concomitant antiepileptic drugs. Primary outcome was time to second PGTCS during 24-week treatment. RESULTS: 242 patients were randomised and received ≥1 dose of trial medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history of generalised-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median treatment duration with lacosamide/placebo was 143/65 days. Risk of developing a second PGTCS during 24-week treatment was significantly lower with lacosamide than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 to 0.774; p<0.001; n=118/n=121). Median time to second PGTCS could not be estimated for lacosamide (>50% of patients did not experience a second PGTCS) and was 77.0 days for placebo. Kaplan-Meier estimated freedom from PGTCS at end of the 24-week treatment period (day 166) for lacosamide/placebo was 31.3%/17.2% (difference 14.1%; p=0.011). More patients on lacosamide than placebo had ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from baseline in PGTCS frequency/28 days, or observed freedom from PGTCS during treatment (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) patients on lacosamide had treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No patients died during the trial. CONCLUSIONS: Lacosamide was efficacious and generally safe as adjunctive treatment for uncontrolled PGTCS in patients with IGE.

Characterization of acne patients carrying clindamycin-resistant Cutibacterium acnes: A Japanese multicenter study.

Use of antimicrobials for acne treatment is correlated with an increased occurrence of antimicrobial-resistant Cutibacterium acnes. To clarify the role of antimicrobial use on the resistance and to investigate the characteristics of resistant strains, we conducted a multicenter study in dermatological clinics frequently visited by new patients with acne vulgaris. We collected specimens in 264 acne patients and tested 164 C. acnes strains isolated from 164 patients visiting 13 dermatological clinics. Antimicrobial susceptibility testing showed that the rates of resistance for tetracyclines, macrolides and clindamycin were significantly higher in C. acnes strains isolated from patients using antimicrobials for acne treatment than patients not using them. In particular, clindamycin-resistant strains were frequently isolated from patients with older median age (≥24 years) and severe/moderate acne. After investigating the resistance mechanism of 15 high-level clindamycin-resistant strains, the transposable clindamycin resistance genes, erm(X) or erm(50), were detected in 14 strains. Using single-locus sequence typing for C. acnes, the strains with erm(X) or multidrug resistance plasmid pTZC1 coding erm(50) and tetracycline resistance gene tet(W) were classified into clade F, which were specifically isolated from Japanese patients with acne, except for one strain. Our data showed that patients' information, such as antimicrobial use, age and acne severity, are valuable in estimating whether a patient carries antimicrobial-resistant C. acnes. Additionally, our results suggest that the clade F strains have a high risk of acquiring multidrug resistance.

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.

Utility of Preoperative Multidetector-Row Computed Tomographic Angiography after Sublingual Nitroglycerin with Three-Dimensional Reconstruction in Planning of the Anterolateral Thigh Flap.

The utility of nitroglycerin is well established in coronary angiography but less so in other surgical fields. In this study, the authors investigated the utility of preoperative computed tomographic angiography after sublingual nitroglycerin followed by three-dimensional visualization for selecting suitable perforators in planning the free anterolateral thigh flap. The authors performed preoperative computed tomographic angiography following sublingual nitroglycerin (after screening for contraindications) in patients for whom reconstructive surgery with the free anterolateral thigh flap was planned. Data were reconstructed three-dimensionally, mapping location and course of source arteries and perforators. Suitable perforators were selected, and flap design was planned. The characteristics of perforators were analyzed statistically. Of 14 patients for whom surgery was planned, two had contraindications to nitroglycerin and underwent computed tomographic angiography alone. Nitroglycerin allowed for the visualization of more peripheral branches. The Hounsfield units at the deep fascia of perforators selected for surgery were significantly higher than for those not selected (p = 0.003). The distance from the intermuscular septum to the selected perforators was significantly shorter than the distance to nonselected perforators (p = 0.017). There were no adverse events, and all flaps survived. Sublingual nitroglycerin before computed tomographic angiography was safe and increased the visibility of perforators, enabling preoperative planning of flap design based on the three-dimensionally-reconstructed image. The authors highly recommend this procedure. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, IV.

Discriminating chorea-acanthocytosis from Huntington's disease with single-case voxel-based morphometry analysis.

BACKGROUND AND PURPOSE: Chorea-acanthocytosis is clinically difficult to distinguish from Huntington's disease because these disorders have similar symptoms and MR imaging findings. We evaluated the usefulness of single-case voxel-based morphometry (VBM) analysis for differentiating the two diseases as well as VBM analysis. MATERIALS AND METHODS: We examined five genetically proven chorea-acanthocytosis patients and 11 Huntington's disease patients to detect differences in the gray and white matter atrophic pattern by using single-case VBM analysis in each patient and their clinical findings. We also evaluated VBM analysis for a group comparison in both disease and control groups. RESULTS: The single-case VBM analysis results demonstrated a gray matter volume loss in caudate nucleus in all 16 patients. A characteristic symmetrical white matter volume loss was detected in globus pallidus, putamen, and thalamus on both sides in all the chorea-acanthocytosis patients, but this pattern of atrophy was not seen in any of the Huntington's disease patients. With the VBM analysis, a significant gray matter volume loss was noted in caudate nucleus on both sides in chorea-acanthocytosis patients compared with Huntington's disease patients, and a more extensive white matter volume loss around the basal ganglia and thalamus was observed in chorea-acanthocytosis patients compared to Huntington's disease patients, consistent with the single-case VBM analysis results. Genetic testing identified two novel pathogenic mutations, exon 1 c.16_22delGTGGTCG and exon 55 c.7736-7739delGAGA in a chorea-acanthocytosis patient. CONCLUSIONS: Single-case VBM analysis may be useful to differentiate chorea-acanthocytosis from Huntington's disease with a focus on white matter atrophy.

Multinodular and vacuolating neuronal tumor (MVNT): A presumably incidental and asymptomatic case in an intractable epilepsy patient.

INTRODUCTION: Multinodular and vacuolating neuronal tumor (MVNT) had been initially described as an epilepsy-related brain tumor, but recent studies demonstrated it could be found incidentally in non-epilepsy patients. CASE REPORT: A 33-year-old woman with intractable post-encephalitis epilepsy presented a cluster of multinodular T2 hyperintensity in the left temporal lobe, which was very similar to the characteristics of MVNT. Long-term video electroencephalogram demonstrated that the habitual seizures were originated from bilateral temporal area and the interictal epileptic discharges were seen multifocally, although the lesions with MVNT appearance were localized in the left temporal lobe. It was presumed that the epilepsy in this patient was due to encephalitis in the past, and the link between the lesions and the epilepsy in this patient seemed weak. CONCLUSION: Although MVNT had been considered as an epilepsy-related brain tumor, we suggest it is not necessarily preferable to perform surgical resection of MVNT even on patients with epilepsy, unless epileptic foci are highly related to MVNT.

C-C Motif Chemokine Ligand 15 May Be a Useful Biomarker for Predicting the Prognosis of Patients with Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens. Due to the difficulty of accurately diagnosing CHP, and the poor prognosis associated with the condition, a novel clinical biomarker is urgently needed. OBJECTIVE: To investigate the usefulness of C-C motif chemokine ligand 15 (CCL15), which had been demonstrated to highly express in the lungs of CHP patients, as a clinical biomarker for CHP. METHOD: Immunohistochemical investigations were performed on lung tissue from CHP patients, and CCL15 levels in serum and bronchoalveolar lavage fluid (BALF) were measured via the enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 µg/mL) were significantly higher than those of idiopathic pulmonary fibrosis patients (19.7 ± 1.3 µg/mL, p = 0.01) and healthy subjects (19.5 ± 1.7 µg/mL, p = 0.003). When BALF CCL15 level was divided by BALF albumin (Alb) level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (ß = -0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (ß = -0.41, p = 0.0048), and BALF lymphocyte count (ß = -0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR 1.1, 95% CI 1.03-1.18, p = 0.004). CONCLUSION: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP. CCL15 was highly expressed in the lung tissue of CHP patients, and BALF CCL15/Alb was significantly associated with CHP prognosis.

Novel pathogenic VPS13A gene mutations in Japanese patients with chorea-acanthocytosis.

OBJECTIVE: To identify mutations in vacuolar protein sorting 13A (VPS13A) for Japanese patients with suspected chorea-acanthocytosis (ChAc). METHODS: We performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis of the VPS13A gene, and chorein Western blotting of erythrocyte ghosts. As the results of the analysis, 17 patients were molecularly diagnosed with ChAc. In addition, we investigated the distribution of VPS13A gene mutations and clinical symptoms in a total of 39 molecularly diagnosed Japanese patients with ChAc, including 22 previously reported cases. RESULTS: We identified 11 novel pathogenic mutations, including 1 novel CNV. Excluding 5 patients with the unknown symptoms, 97.1% of patients displayed various neuropsychiatric symptoms or forms of cognitive dysfunction during the course of disease. The patients carrying the 2 major mutations representing over half of the mutations, exon 60-61 deletion and exon 37 c.4411C>T (R1471X), were localized in western Japan. CONCLUSIONS: We identified 13 different mutations in VPS13A, including 11 novel mutations, and verified the clinical manifestations in 39 Japanese patients with ChAc.

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.

Alternate-day administration of S-1 for elderly patients with advanced non-small-cell lung carcinoma: A prospective feasibility study.

S-1 is an oral fluoropyrimidine agent used for the treatment of non-small-cell lung cancer (NSCLC). Although S-1 monotherapy has been reported to exhibit lesser hematotoxicity compared with other third-generation chemotherapeutics, digestive toxicity was also frequently observed. Alternate-day administration of S-1 has shown a lower rate of severe digestive toxicity than the daily standard administration in patients with NSCLC. However, the safety of alternate-day S-1 therapy in elderly patients aged 75 years or older has not been investigated. The present study was a multi-center and prospective feasibility study aimed to evaluate the safety of alternate-day S-1 therapy in elderly patients with NSCLC. The patients received S-1 orally twice daily for 4 days (Monday, Wednesday, Friday, and Sunday) every week until disease progression or unacceptable toxicity. The primary endpoint was safety, which was evaluated as the number of grade ≥3 adverse events, and the secondary endpoints were progression-free survival (PFS), 1-year survival, and disease control rate (DCR). A total of 10 patients were enrolled, but 2 patients failed to initiate the treatment protocol. Finally, 8 patients were treated with the study protocol regimen. No grade 3 or higher adverse events were observed. Four (50%) and 1 (12.5%) patient had grade 2 or lower digestive symptoms such as anorexia, diarrhea, or stomatitis and grade 1 lacrimation, respectively. Moreover, 2 (25%), 1 (12.5%), and 1 (12.5%) patients had grade 2 renal dysfunction, grade 2 ileus, and elevated blood bilirubin, respectively. The median PFS was 1.5 months (95% confidence interval: 0.9-1.8), and the 1-year survival rate was 42.9%. The DCR was 12.5%. In conclusion, alternate-day S-1 administration can be a safe treatment regimen for elderly patients with NSCLC, but its therapeutic efficacy and safety for elderly patients with NSCLC should be compared against the standard S-1 administration in a large-scale study.

Nationwide survey in Japan endorsed diagnostic criteria of benign adult familial myoclonus epilepsy.

PURPOSE: Benign adult familial myoclonus epilepsy (BAFME) is an autosomal dominant disease representing tremulous myoclonus or cortical tremor and infrequent generalized seizures. We aimed to delineate detailed epidemiological backgrounds in patients with Japanese BAFME and to establish diagnostic criteria based on clinical and electrophysiological findings. METHODS: After a previous survey on the current nationwide state of myoclonus epilepsy of adults in Japan, we conducted this survey to delineate the clinical characteristics of Japanese BAFME patients, using a questionnaire to obtain details for individual patients. Based on clinical diagnostic criteria, we analyzed demographic and clinical characteristics of 101 BAFME patients in 74 families. RESULTS: BAFME patients were predominantly female and were widely distributed throughout Japan. Ninety-two patients (91.1%) showed signs of cortical tremor and 84 (83.2%) showed epileptic seizures. Epileptic seizures were infrequent in BAFME patients, but 22.6% of patients had more than one seizure per year at the maximum. Three patients (3.0%) showed cerebellar ataxia, eight (7.9%) showed cognitive impairment, and 13 (12.9%) had psychiatric symptoms. Brain MRI was normal in 74% of patients, and the remaining patients had non-specific abnormal findings. Sodium valproate and clonazepam were the primary drugs used for BAFME patients. The older patients showed significantly more severe and higher rates of abnormal electrophysiological results, which were suggestive of cortical hyperexcitability. CONCLUSION: Our study successfully delineated the overall clinical characteristics of Japanese BAFME. The correlation between the genetic, clinical, and electrophysiological results will be very important to further elucidate the pathophysiology and treatment of BAFME in the future.

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.