Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk during neurodevelopment.

Regulation of microtubule dynamics is required to properly control various steps of neurodevelopment. In this study, we identified granule cell antiserum-positive 14 (Gcap14) as a microtubule plus-end-tracking protein and as a regulator of microtubule dynamics during neurodevelopment. Gcap14 knockout mice exhibited impaired cortical lamination. Gcap14 deficiency resulted in defective neuronal migration. Moreover, nuclear distribution element nudE-like 1 (Ndel1), an interacting partner of Gcap14, effectively corrected the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency. Finally, we found that the Gcap14-Ndel1 complex participates in the functional link between microtubule and actin filament, thereby regulating their crosstalks in the growth cones of cortical neurons. Taken together, we propose that the Gcap14-Ndel1 complex is fundamental for cytoskeletal remodeling during neurodevelopmental processes such as neuronal processes elongation and neuronal migration.

Genome-wide kinase-MAM interactome screening reveals the role of CK2A1 in MAM Ca2+ dynamics linked to DEE66.

The endoplasmic reticulum (ER) and mitochondria form a unique subcellular compartment called mitochondria-associated ER membranes (MAMs). Disruption of MAMs impairs Ca2+ homeostasis, triggering pleiotropic effects in the neuronal system. Genome-wide kinase-MAM interactome screening identifies casein kinase 2 alpha 1 (CK2A1) as a regulator of composition and Ca2+ transport of MAMs. CK2A1-mediated phosphorylation of PACS2 at Ser207/208/213 facilitates MAM localization of the CK2A1-PACS2-PKD2 complex, regulating PKD2-dependent mitochondrial Ca2+ influx. We further reveal that mutations of PACS2 (E209K and E211K) associated with developmental and epileptic encephalopathy-66 (DEE66) impair MAM integrity through the disturbance of PACS2 phosphorylation at Ser207/208/213. This, in turn, causes the reduction of mitochondrial Ca2+ uptake and the dramatic increase of the cytosolic Ca2+ level, thereby, inducing neurotransmitter release at the axon boutons of glutamatergic neurons. In conclusion, our findings suggest a molecular mechanism that MAM alterations induced by pathological PACS2 mutations modulate Ca2+-dependent neurotransmitter release.

Clinical outcomes of etoposide and cytarabine as consolidation in elderly patients with primary CNS lymphoma.

BACKGROUND: A consolidation strategy has not been established for transplant-ineligible elderly patients with primary central nervous system lymphoma (PCNSL). In this study, we aimed to retrospectively evaluate the clinical outcomes of etoposide and cytarabine (EA) as consolidation chemotherapy for transplant-ineligible patients with PCNSL following high-dose methotrexate (MTX)-based induction chemotherapy. MATERIALS AND METHODS: Between 2015 and 2021, newly diagnosed transplant-ineligible patients with PCNSL with diffuse large B-cell lymphoma were consecutively enrolled. All enrolled patients were over 60 years old and received EA consolidation after achieving a complete or partial response following induction chemotherapy. RESULTS: Of the 85 patients who achieved a complete or partial response to MTX-based induction chemotherapy, 51 received EA consolidation chemotherapy. Among the 25 (49.0%, 25/51) patients in partial remission before EA consolidation, 56% (n = 14) achieved complete remission after EA consolidation. The median overall survival and progression-free survival were 43 and 13 months, respectively. Hematological toxicities were most common, and all patients experienced grade 4 neutropenia and thrombocytopenia. Forty-eight patients experienced febrile neutropenia during consolidation chemotherapy, and 4 patients died owing to treatment-related complications. CONCLUSION: EA consolidation chemotherapy for transplant-ineligible, elderly patients with PCNSL improved response rates but showed a high relapse rate and short progression-free survival. The incidences of treatment-related mortality caused by hematologic toxicities and severe infections were very high, even after dose modification. Therefore, the use of EA consolidation should be reconsidered in elderly patients with PCNSL.

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. METHODS: We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. RESULTS: We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. CONCLUSION: Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.

Schizophrenia-associated Mitotic Arrest Deficient-1 (MAD1) regulates the polarity of migrating neurons in the developing neocortex.

Although large-scale genome-wide association studies (GWAS) have identified an association between MAD1L1 (Mitotic Arrest Deficient-1 Like 1) and the pathology of schizophrenia, the molecular mechanisms underlying this association remain unclear. In the present study, we aimed to address these mechanisms by examining the role of MAD1 (the gene product of MAD1L1) in key neurodevelopmental processes in mice and human organoids. Our findings indicated that MAD1 is highly expressed during active cortical development and that MAD1 deficiency leads to impairments in neuronal migration and neurite outgrowth. We also observed that MAD1 is localized to the Golgi apparatus and regulates vesicular trafficking from the Golgi apparatus to the plasma membrane, which is required for the growth and polarity of migrating neurons. In this process, MAD1 physically interacts and collaborates with the kinesin-like protein KIFC3 (kinesin family member C3) to regulate the morphology of the Golgi apparatus and neuronal polarity, thereby ensuring proper neuronal migration and differentiation. Consequently, our findings indicate that MAD1 is an essential regulator of neuronal development and that alterations in MAD1 may underlie schizophrenia pathobiology.

Crif1 deficiency in dopamine neurons triggers early-onset parkinsonism.

Mitochondrial dysfunction has been implicated in Parkinson's Disease (PD) progression; however, the mitochondrial factors underlying the development of PD symptoms remain unclear. One candidate is CR6-interacting factor1 (CRIF1), which controls translation and membrane insertion of 13 mitochondrial proteins involved in oxidative phosphorylation. Here, we found that CRIF1 mRNA and protein expression were significantly reduced in postmortem brains of elderly PD patients compared to normal controls. To evaluate the effect of Crif1 deficiency, we produced mice lacking the Crif1 gene in dopaminergic neurons (DAT-CRIF1-KO mice). From 5 weeks of age, DAT-CRIF1-KO mice began to show decreased dopamine production with progressive neuronal degeneration in the nigral area. At ~10 weeks of age, they developed PD-like behavioral deficits, including gait abnormalities, rigidity, and resting tremor. L-DOPA, a medication used to treat PD, ameliorated these defects at an early stage, although it was ineffective in older mice. Taken together, the observation that CRIF1 expression is reduced in human PD brains and deletion of CRIF1 in dopaminergic neurons leads to early-onset PD with stepwise PD progression support the conclusion that CRIF1-mediated mitochondrial function is important for the survival of dopaminergic neurons.

A population pharmacokinetic model of methotrexate in Korean patients with haematologic malignancy.

AIMS: This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with haematologic malignancy, identify factors affecting methotrexate PK, and propose an optimal dosage regimen for the Korean population. METHODS: Data were retrospectively collected from 188 patients with acute leukaemia or non-Hodgkin's lymphoma who were admitted to Severance Hospital during the period from November 2005 to January 2016. Using demographic factors and laboratory results as potential covariates for PK parameters, model development was performed using NONMEM and optimal dosing regimens were developed using the final PK model. RESULTS: A two-compartment model incorporating body weight via allometry best described the data, yielding typical parameter values of 25.09 L for central volume of distribution ( V 1 ), 17.65 L for peripheral volume of distribution ( V 2 ), 12.89 L/h for clearance (CL) and 0.655 L/h for inter-compartmental clearance in a 50 kg patient. Covariate analyses showed that, at the weight of 50 kg, CL decreased by 0.11 L/h for each 1-year increase in age above 14 years old and decreased 0.8-fold when serum creatinine level doubled, indicating the importance of age-specific dose individualization in methotrexate treatment. Volume of distribution at steady state derived from PK parameters (= V 1 + V 2 ) was 0.85 L/kg, which was similar to those in the Western or Chinese populations. Optimal doses simulated from the final model successfully produced the PK measures close to the target chosen. CONCLUSIONS: The population PK model and optimal dosage regimens developed in this study can be used as a basis to achieve precision dosing in Korean patients with haematologic malignancy.

3D Bioprinting of Diatom-Laden Living Materials for Water Quality Assessment.

Diatoms have long been used as living biological indicators for the assessment of water quality in lakes and rivers worldwide. While this approach benefits from the great diversity of these unicellular algae, established protocols are time-consuming and require specialized equipment. Here, this work 3D prints diatom-laden hydrogels that can be used as a simple multiplex bio-indicator for water assessment. The hydrogel-based living materials are created with the help of a desktop extrusion-based printer using a suspension of diatoms, cellulose nanocrystals (CNC) and alginate as bio-ink constituents. Rheology and mechanical tests are employed to establish optimum bio-ink formulations, whereas cell culture experiments are utilized to evaluate the proliferation of the entrapped diatoms in the presence of selected water contaminants. Bioprinting of diatom-laden hydrogels is shown to be an enticing approach to generate living materials that can serve as low-cost bio-indicators for water quality assessment.

Root electrotropism in Arabidopsis does not depend on auxin distribution but requires cytokinin biosynthesis.

Efficient foraging by plant roots relies on the ability to sense multiple physical and chemical cues in soil and to reorient growth accordingly (tropism). Root tropisms range from sensing gravity (gravitropism), light (phototropism), water (hydrotropism), touch (thigmotropism), and more. Electrotropism, also known as galvanotropism, is the phenomenon of aligning growth with external electric fields and currents. Although root electrotropism has been observed in a few species since the end of the 19th century, its molecular and physical mechanisms remain elusive, limiting its comparison with the more well-defined sensing pathways in plants. Here, we provide a quantitative and molecular characterization of root electrotropism in the model system Arabidopsis (Arabidopsis thaliana), showing that it does not depend on an asymmetric distribution of the plant hormone auxin, but instead requires the biosynthesis of a second hormone, cytokinin. We also show that the dose-response kinetics of the early steps of root electrotropism follows a power law analogous to the one observed in some physiological reactions in animals. Future studies involving more extensive molecular and quantitative characterization of root electrotropism would represent a step toward a better understanding of signal integration in plants and would also serve as an independent outgroup for comparative analysis of electroreception in animals and fungi.

Hydrometrocolpos: a Contemporary Review of the Last 5 Years.

PURPOSE OF REVIEW: The goal of this review is to provide a comprehensive overview of hydrometrocolpos, covering disease etiology, pathophysiology, clinical presentation, and diagnostic and management techniques, and known outcomes. RECENT FINDINGS: This narrative review presents the literature on hydrometrocolpos in the pediatric population from the past 5 years. We highlight the 69 reported cases of hydrometrocolpos and classify them based on type of obstruction or associated anomaly, discuss new diagnostic algorithms based on imaging, and present novel and underutilized surgical techniques for definitive management. Hydrometrocolpos, a condition characterized by retained fluid causing a distended vagina and uterus in the setting of a distal vaginal outflow obstruction, has a wide range of presentation severity based on the type of obstruction. Whether hydrometrocolpos is due to an isolated condition like imperforate hymen, a complex abnormality like cloacal malformation, or a part of a large congenital syndrome, the mainstay of treatment is decompression of the dilated vagina and surgical correction of the outflow obstruction. Imaging-based diagnostic algorithms and new treatment techniques reported in the literature, as well as longitudinal and patient-reported outcome research, can improve the lives of children affected by this condition.

Behavioral Management of Children With Autism in the Emergency Department.

ABSTRACT: Autism spectrum disorder (ASD) is characterized by impaired social communication in conjunction with patterned behaviors. Often associated with emotional dysregulation, irritability, aggression, depression, and suicidality, ASD youth frequently present to the emergency department for behavioral and mental health evaluation. Psychiatric comorbidities, agitation, and depression are commonly encountered. During these visits, practitioners must thoughtfully consider organic etiologies for presenting symptoms, formulate plans to address risk of agitation, and understand how to effectively formulate disposition options in this patient population.

Clinical characteristics of periodic limb movements during sleep categorized by continuous positive airway pressure titration polysomnography in patients with obstructive sleep apnea.

PURPOSE: The presence of periodic limb movements during sleep (PLMS) varies among patients with obstructive sleep apnea (OSA) undergoing treatment with continuous positive airway pressure (CPAP). The factors associated with this variation are unknown. METHODS: PLMS were defined as a periodic leg movements index of > 15/h. Patients with OSA and PLMS were categorized into four groups depending on diagnostic and CPAP titration polysomnography (PSG). A multinomial logistic regression analysis was performed using a non-PLMS group as the reference category. RESULTS: This study included 861 patients with OSA who underwent a full-night CPAP titration PSG. The proportions of the subjects with PLMS on both PSGs (persistent PLMS), those with CPAP-emergent PLMS, and those with CPAP-resolved PLMS were 12.9%, 9.2%, and 3.9%, respectively. Compared with the non-PLMS group, the persistent group was more likely to be of older age and male sex and has a higher body mass index and restless legs syndrome (RLS). Patients in the CPAP-emergent group were also older and more likely to have RLS as well as more severe apnea. Patients in the CPAP-resolved group were more likely to be women, of older age, have a higher body mass index, but less severe apnea. CONCLUSIONS: PLMS elicited by CPAP are more likely to occur in older patients with more severe sleep apnea and comorbid RLS, whereas OSA patients in which PLMS resolve after CPAP are more likely to be women and have milder sleep apnea. Persistent PLMS share clinical characteristics with PLMS in general population.

Periodic limb movements during sleep are associated with poor health-related quality of life in patients with obstructive sleep apnea.

PURPOSE: The clinical significance of the comorbidity of periodic limb movements during sleep (PLMS) in sleep-disordered breathing remains unclear. This study aimed to determine whether or not the presence of PLMS is related to depressed mood and poor quality of life in subjects with obstructive sleep apnea (OSA). METHODS: We defined PLMS as a periodic leg movement index of > 15/h. Scores for the Medical Outcomes Study Short Form Health Survey and Beck Depression Inventory were assessed with multiple logistic or linear regression analyses. RESULTS: Of 1370 subjects with OSA, a prevalence of PLMS was 14.1%. Older age, men, and obesity were positively associated with PLMS. PLMS occurred in 17%, 15%, and 12% of mild, moderate, and severe subjects with OSA, respectively. Severe OSA was less likely to be associated with PLMS than mild OSA. PLMS negatively correlated with physical and mental component summary scores of the health survey but not with Beck Depression Inventory scores after controlling for confounding variables. PLMS were significantly associated with poor sleep architecture on polysomnography. However, the relationship between PLMS and disturbed sleep was no longer significant after adjusting for age. CONCLUSIONS: Health-related quality of life, including physical and mental health but not depressive symptoms, was worse in subjects with OSA and PLMS than in those without PLMS.

Identifying pediatric emergency department visits for aggression using administrative claims data.

OBJECTIVE: Violence and aggressive behaviors among youth are a leading cause of Emergency Department (ED) mental health (MH) encounters. A consistent method is needed for public health research, to identify ED encounters associated with aggression. The aim of this study was to develop such a screening procedure. DATA SOURCES: Electronic records and administrative claims data related to MH related ED encounters at one of Pediatric Health Information System (PHIS) Children's Hospitals in the United States from January 1, 2019 to December 31, 2019. STUDY DESIGN: The authors selected a combination of ICD-10 codes to screen MH ED encounters for aggression; and then conducted a chart review to compare characteristics of groups that screened positive vs. screened negative, and groups with confirmed vs. without confirmed aggression. DATA EXTRACTION METHOD: Unique ED encounters associated with a MH related ICD-10 code from a one-year period at the study institution were extracted (n = 3092 MH ED encounters). Encounters with any aggression-associated codes were identified as "screen-positive" (N = 349). From the remaining "screen-negative" encounters, 352 unique encounters were randomly selected as a comparison group. Both groups were chart reviewed to investigate the accuracy of the screening method. MAIN FINDING: Chart review confirmed aggression in 287 of 349 screen-positive and 48 of 352 select screen-negative, chart-reviewed encounters. Additional codes were added, with a goal of finding the combination of codes with the highest accuracy. The resulting screen had sensitivity, specificity, positive and negative predictive values of 0.901, 0.817, 0.818, and 0.864, respectively. PRINCIPAL CONCLUSIONS: This paper presents a screening method for identifying ED encounters related to aggression. A replication study will be necessary to validate the method prior to applying to large claims data. If validated, it will support future research on this important population.

Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein.

The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson's disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of α-syn and explored its molecular mechanism using in vitro and in vivo model systems. We demonstrate that neuronal ApoE deficiency attenuates both α-syn uptake and release by downregulating LRP-1 and LDLR expression and enhancing chaperone-mediated autophagy activity, respectively, thereby contributing to α-syn propagation. In addition, we observed that α-syn propagation was attenuated in ApoE knockout mice injected with pre-formed mouse α-syn fibrils. This study will help our understanding of the molecular mechanisms underlying α-syn propagation.

Clinical characteristics and prognostic factors of acquired haemophilia A in Korea.

INTRODUCTION: Acquired haemophilia A (AHA) treatment involves the haemostatic treatment for acute haemorrhage and immunosuppressive therapy (IST) to eradicate FVIII inhibitory antibodies. AIM: We assessed the clinical features of AHA and analysed treatment outcomes in Korea. We further identified prognostic factors affecting treatment outcomes. METHODS: Medical records of 55 patients with AHA from 18 institutions were reviewed retrospectively. Logistic and Cox regression analyses were performed to elucidate clinical factors affecting the achievement of complete remission (CR). The primary endpoint was time to CR after IST, and secondary endpoints were time to haemostasis, the achievement of CR, and overall survival (OS). RESULTS: Among the 55 patients, 50 (91%) had bleeding symptoms. Bleeding was severe in 74% of patients. Thirty-six (72%) patients received haemostatic therapy. Of the 42 patients who received IST, 23 (52%) received steroid alone, with a 52% response rate, and 10 (25%) received a combination of steroid and cyclophosphamide, with an 83% response rate. Five (16%) patients relapsed after a median duration of 220 days. There were eight deaths. In the Cox regression analysis, the FVIII inhibitor titre ≥ 20 BU/mL was the only significant prognostic factor affecting time to CR and haemostasis. No significant difference was observed in OS based on the inhibitor titre. CONCLUSION: The present study demonstrated the demographic data of AHA in Korea and showed that FVIII inhibitory antibody titre was a predictor of time to achieve CR after IST.

Gender differences in factors associated with resilience for health-related quality of life in persons with epilepsy.

PURPOSE: We determined whether resilience factors such as self-efficacy, stress coping styles, and social support were differentially associated with health-related quality of life (HRQoL) in men and women with epilepsy after controlling for depression, anxiety, and daily-life stress. METHODS: This was a cross-sectional study of 129 adults with epilepsy. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31), Epilepsy Self-Efficacy Scale, Way of Stress Coping Checklist, Social Support Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory, and Daily Hassles Scale were used. Stepwise linear regression analyses were performed. RESULTS: Except for medication effects, there were no gender differences in the QOLIE-31 and its subscales. The medication effects score was higher in men than in women after controlling for BDI scores. The BDI scores were independently associated with the QOLIE-31 score in men and women. Epilepsy self-efficacy was associated with the QOLIE-31 in men, whereas social support was associated with the QOLIE-31 in women. Coping strategies were associated with the QOLIE-31 in neither men nor women. Seizure frequency, daily-life stress, and anxiety were also negatively associated with the QOLIE-31, but only in men. The coefficients of determination were 0.637 and 0.587 in the men's and women's models, respectively. CONCLUSIONS: The influence of self-efficacy and social support on HRQoL differed between men and women with epilepsy even after controlling for psychological distress. These findings could contribute to the development of successful gender-specific psychosocial interventions to improve HRQoL in men and women with epilepsy.

Gender differences in seizure recurrence and antiepileptic drug polytherapy predicting health-related quality of life of persons 1 year after diagnosis of epilepsy.

PURPOSE: The aim of this study was to determine whether gender influences the prediction of health-related quality of life (HRQoL) in persons with newly diagnosed epilepsy (NDE). METHODS: This was a 1-year longitudinal study. Persons with NDE were assessed with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), the Hospital Anxiety Depression Scale (HADS), the Stigma Scale, and the Rosenberg Self-esteem Scale. An analysis of covariance (ANCOVA) with interaction terms was used. RESULTS: Among 134 adults with NDE, there were no gender differences in the scores of the QOLIE-31 and its subscales. A multivariate linear regression analysis showed that the HADS-anxiety scores at diagnosis (p = 0.005) and seizure recurrence after diagnosis (p = 0.050) negatively predicted QOLIE-31 scores in persons with NDE. There were significant effects of the gender interaction with seizure recurrence (F = 8.745, p = 0.004, partial eta2 = 0.066) and antiepileptic drug (AED) polytherapy (F = 6.320, p = 0.013, partial eta2 = 0.049) in the adjusted model. Specifically, seizure recurrence negatively predicted the QOLIE-31 scores only in men. By contrast, AED polytherapy negatively predicted the QOLIE-31 scores only in women. CONCLUSIONS: There are gender differences in certain epilepsy-related factors predicting HRQoL at 1 year in persons with NDE.

Factors associated with alexithymia in adults with epilepsy.

PURPOSE: The relationship between epilepsy and alexithymia, characterized by the inability to feel or express emotion, remains incompletely understood. We investigated alexithymia and its association with epilepsy-related factors in patients with epilepsy (PWE). METHODS: In this cross-sectional study, PWE and healthy control subjects were recruited. Alexithymia was assessed using the Toronto Alexithymia Scale-20 (TAS-20). The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) were also administered to assess depression and anxiety, respectively. Mediation analysis was conducted using a two-stage regression method. RESULTS: Ninety adult PWE and 161 healthy control subjects were included in the study. PWE had significantly higher TAS-20 scores (B = 2.445, p = 0.014) than controls, but the prevalence of alexithymia, defined as TAS-20≥61, did not differ between PWE and control subjects after controlling for confounders (15.6% vs. 6.2%, respectively; p = 0.873). Uncontrolled seizures significantly increased alexithymia through depression (B = 3.536, p = 0.006), and this effect was responsible for 61.2% of the total effect on alexithymia. The direct effects of uncontrolled seizures on alexithymia were not significant. In contrast, AED polytherapy had significant direct effects on alexithymia (B = 4.489, p = 0.037) independent of depression. The indirect effects of AED polytherapy via depression did not reach statistical significance (B = 2.371, p = 0.066). CONCLUSIONS: Alexithymia was more severe, but not more prevalent, in PWE than in healthy controls. AED polytherapy was directly associated with alexithymia, while uncontrolled seizures were indirectly related to alexithymia through depressive symptoms.