Distinct features of B cell receptors in neuromyelitis optica spectrum disorder among CNS inflammatory demyelinating diseases.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. METHODS: From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. RESULTS: Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. CONCLUSIONS: NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual's lifetime.

Seizure outcome in medically treated patients with adult-onset epilepsy and cerebral cavernous malformation.

PURPOSE: We evaluated long-term seizure outcomes of antiseizure medications (ASMs) and risk factors for drug resistance in patients with adult-onset epilepsy associated with cerebral cavernous malformation (CCM). MATERIALS AND METHODS: This retrospective observational study included patients newly diagnosed with adult-onset focal epilepsy associated with CCM. Patients received individualized treatments with ASMs. All patients were followed-up for at least 2 years. The main outcome measure was terminal 2 year seizure freedom (2-YSF). RESULTS: Forty eight subjects (28 men and 20 women) were included. Thirty-one (64.6%) subjects achieved a terminal 2-YSF (range 2.0-17.0 years). After treatment with the first drug regimen, 31 (64.6%) subjects achieved 2-YSF, with 23 remaining seizure-free until final follow-up visit. Of the 23 subjects treated with the second drug regimen and the six treated with the third drug regimen, ten (43.5%) and one (16.7%), respectively, achieved a terminal 2-YSF. Stepwise logistic regression analyses showed that terminal 2-YSF was negatively associated with epileptiform discharge on EEG at the time of diagnosis (odds ratio = 0.214, p = 0.047) and tended to be associated with age ≥ 45 years at seizure onset (odds ratio = 4.260, p = 0.056). CONCLUSION: The present study found that 64.6% of CCM patients with adult-onset epilepsy achieved terminal 2-YSF after ASM initiation. Interictal epileptiform discharge on EEG at the time of diagnosis was associated with poor prognosis. Failure to achieve sustained seizure freedom after two ASMs may indicate the need for surgical treatment.

Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis.

It is unclear whether serum proteins can serve as biomarkers to reflect pathological changes and predict recovery in inflammation of optic nerve. We evaluated whether serum proteins could monitor and prognosticate optic neuritis (ON). We prospectively recruited consecutive patients with recent ON, classified as ON with anti-aquaporin-4 antibody (AQP4-ON), ON with anti-myelin oligodendrocyte glycoprotein antibody (MOG-ON), and double-seronegative ON (DSN-ON). Using ultrasensitive single-molecule array assays, we measured serum neurofilament light chain and glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF). We analyzed the markers according to disease group, state, severity, and prognosis. We enrolled 60 patients with recent ON (15 AQP4-ON; 14 MOG-ON; 31 DSN-ON). At baseline, AQP4-ON group had significantly higher serum GFAP levels than did other groups. In AQP4-ON group, serum GFAP levels were significantly higher in the attack state than in the remission state and correlated with poor visual acuity. As a prognostic indicator, serum BDNF levels were positively correlated with follow-up visual function in the AQP4-ON group (r = 0.726, p = 0.027). Serum GFAP reflected disease status and severity, while serum BDNF was identified as a prognostic biomarker in AQP4-ON. Serum biomarkers are potentially helpful for patients with ON, particularly those with AQP4-ON.

Disease characteristics of idiopathic transverse myelitis with serum neuronal and astroglial damage biomarkers.

Despite its close association with CNS inflammatory demyelinating disorders (CIDDs), pathogenic characteristics of idiopathic transverse myelitis (ITM) remain largely unknown. Here, we investigated serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) in patients with ITM to unravel the disease characteristics of ITM. We prospectively recruited 70 patients with ITM, 62 with AQP4 + NMOSD and 85 with RRMS-including 31 patients with acute TM attacks-along with 30 HCs. We measured sNfL and sGFAP levels using single-molecular arrays and compared these levels per lesion volume between the disease groups during attacks. Compared to HCs, ITM patients showed higher sNfL and sGFAP during acute attacks (sNfL: p < 0.001, sGFAP: p = 0.024), while those in remission (sNfL: p = 0.944, sGFAP: p > 0.999) did not, regardless of lesion extents and presence of multiple attacks. ITM patients demonstrated lower sGFAP/volume (p = 0.011) during acute attacks and lower sGFAP (p < 0.001) in remission compared to AQP4 + NMOSD patients. These findings suggest that both neuronal and astroglial damages occur in patients with acute ITM attacks at a similar level to those with RRMS, distinct from AQP4 + NMOSD. However, active neuroinflammatory process was not remarkable during remission in this cohort.

Obstructive sleep apnea may reduce a diagnostic accuracy of video-polysomnography for idiopathic REM sleep behavior disorder.

BACKGROUND: Severe obstructive sleep apnea (OSA) in patients with rapid eye movement (REM) sleep behavior disorder (RBD) may result in frequent fragmentation of REM sleep and consequently lead to a false negative diagnosis of RBD on a video-polysomnography (video-PSG). Thus, we determined whether OSA has the negative impact on video-PSG diagnostic accuracy for RBD. METHODS: Patients with clinically diagnosed idiopathic RBD were included. RBD was confirmed if a video-PSG demonstrated complex motor behavior during REM sleep or REM sleep without atonia (RWA). Motor behavior was measured using the RBD Severity Scale. Cohen's kappa coefficient was calculated for qualitative assessment of RWA. A stepwise logistic regression analysis was performed. RESULTS: Of a total 254 patients included, a diagnosis of RBD was confirmed by a video-PSG in 221 patients (87.0%). RWA, vocalization, and axial or proximal muscle movements in REM sleep were noted in 86.6%, 58.3%, and 35.9%, respectively. A video-PSG diagnosis of RBD was less likely associated with severe OSA (odds ratio [OR] 0.284, p = 0.010) and moderate OSA (OR 0.404, p = 0.071) whereas was more likely associated with longer REM sleep time (OR 1.036, p < 0.001). In 43 patients who underwent a continuous positive airway pressure (CPAP) titration study, a diagnosis of RBD was more common on a CPAP titration study (88.4%) than on a first video-PSG (65.1%) (p = 0.013). Twelve (27.9%) of 43 CPAP patients were diagnosed with RBD according only to CPAP titration study. CONCLUSIONS: OSA that requires CPAP may reduce a diagnostic accuracy for RBD by a video-PSG. False negative results were probably due to frequent electromyographic artifacts and/or severe sleep disruption from apneic events during REM sleep.

Sex Differences in Excessive Daytime Sleepiness Among Patients With Obstructive Sleep Apnea.

BACKGROUND AND PURPOSE: To identify sex differences in daytime sleepiness associated with apnea severity and periodic limb movements during sleep (PLMS) in subjects with obstructive sleep apnea (OSA). METHODS: This study used the Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Sleep Hygiene Index (SHI) in logistic regression analyses with interaction terms. Severe OSA, excessive daytime sleepiness (EDS), and PLMS were defined as an apnea-hypopnea index of ≥30, an ESS score of ≥11, and a periodic limb movements index of >15, respectively. RESULTS: The 1,624 subjects with OSA (males, 79.1%) comprised 45.3%, 38.2%, and 16.4% with severe OSA, EDS, and PLMS, respectively. Multiple logistic regression without interaction terms showed that sex, severe OSA, and PLMS were not significantly associated with EDS. However, significant interactions were noted between sex and severe OSA and PLMS in EDS in both crude and adjusted models (all p values<0.05). In the adjusted model, severe OSA was associated with EDS in males (p=0.009) but not in females. PLMS were more likely to be associated with EDS in females (p=0.013), whereas PLMS were less likely to be associated with EDS in males (p=0.041). The models were adjusted by the BDI score, SHI, and presence of medical comorbidities. CONCLUSIONS: There are significant sex differences in subjective daytime sleepiness in subjects with severe OSA and PLMS. Severe OSA and PLMS may influence daytime sleepiness more in males and females, respectively.

Validation of items on the NDDIE and PHQ-9 associated with suicidal ideation during suicidality screening in patients with epilepsy.

PURPOSE: This study was performed to validate individual items on the Neurological Disorders Depression Inventory for Epilepsy (NDDIE) and the Patient Health Questionnaire-9 (PHQ-9), as well as their total scores, during suicidality screening of patients with epilepsy (PWE). METHODS: PWE were assessed with the Mini International Neuropsychiatric Interview (MINI), the NDDIE, and the PHQ-9. Moderate to high suicidality, as assessed by the Suicidality Module of the MINI, was considered the standard measurement. Each item and overall scores for the NDDIE and PHQ-9 were evaluated by receiver operating characteristic (ROC) curve analyses. The optimal cutoff criteria were identified as those with the highest Youden index. RESULTS: Of the 213 participants, 20 (9.4%) had moderate to high suicidality. Item 4 on the NIDDE and item 9 on the PHQ-9, representing suicidal ideation, showed the best psychometric properties for suicidality. A cutoff of >1 for item 4 on the NDDIE showed an area under the ROC curve (AUC) of 0.853, a sensitivity of 90.0%, and a specificity of 72.0%. A cutoff >0 for item 9 on the PHQ-9 showed an AUC of 0.851, a sensitivity of 90.0%, and a specificity of 74.6%. The specificities and positive predictive values of item 4 on the NDDIE and item 9 on the PHQ-9 were higher in patients with depression than those in the overall patient population. CONCLUSION: Item 4 of NDDIE and Item 9 of PHQ-9 showed value in screening for suicidality. Use of these items may rapidly identify suicidality among PWE.

Cleft size and type are associated with development of epilepsy and poor seizure control in patients with schizencephaly.

PURPOSE: To investigate the relationship between the anatomical features of schizencephaly and characteristics of epilepsy. METHODS: We retrospectively evaluated patients diagnosed with schizencephaly using brain magnetic resonance imaging. Seizure outcomes were evaluated as drug-resistant epilepsy and frequent seizures (more than once a month) during the previous year. Development of epilepsy, seizure outcomes, and clinical variables were compared according to the anatomical features of schizencephaly, such as cleft type, size, bilaterality, presence of cortical dysplasia, and temporal lobe involvement. RESULTS: Of the 76 patients with schizencephaly-related epilepsy, 28 (36.8%) had open lip clefts, and 13 (17.1%) had bilateral clefts. The development of epilepsy was related to a larger cleft size and the presence of cortical dysplasia. The patients with medium-to-large clefts were younger at seizure onset than those with small clefts (9.7±7.8 vs. 20.8±10.4 years). Among the 64 patients whose outcomes were evaluated, 31 (48.4%) had drug-resistant epilepsy, and 21 (32.8%) met our definition of frequent seizures. In the univariate analysis, open lip, larger clefts, and the presence of cortical dysplasia were associated with poor seizure outcomes. Even after adjustment for covariates, open lip clefts were significantly related to drug-resistant epilepsy (odds ratio=13.036, P=0.001) and frequent seizures (odds ratio=7.682, P=0.008). CONCLUSION: Open lip clefts were associated with poor seizure outcomes. Further, a larger cleft was related to an earlier development of epilepsy. The anatomical features of schizencephaly should be considered in the treatment of epilepsy.

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.

Nocturnal stridor in multiple system atrophy: Video-polysomnography and clinical features.

INTRODUCTION: Nocturnal stridor, a life-threatening condition linked to respiratory failure and sudden death during sleep, is a serious issue in patients with multiple system atrophy (MSA). However, little is known about polysomnographic findings and clinical features of MSA patients with nocturnal stridor. Hence, we investigated video-polysomnography (VPSG) findings and clinical features associated with nocturnal stridor in patients with MSA. METHODS: We retrospectively analyzed the clinical data of patients with MSA (n = 49) who underwent overnight VPSG for the evaluation of sleep-disordered breathing. The presence of nocturnal stridor was confirmed based on overnight VPSG findings. Clinical data, including VPSG findings and clinical features, were compared between MSA patients with and without nocturnal stridor. RESULTS: Nocturnal stridor was present in 31 (63.3%) patients with MSA. Patients with stridor showed significantly higher apnea-hypopnea, respiratory disturbance, and oxygen desaturation indices than those without stridor (P = 0.024, P = 0.049, and P = 0.006, respectively). Patients with stridor had more severe axial motor features, more impaired activities of daily living, and longer disease duration than those without stridor (P = 0.012, P = 0.036, and P = 0.003, respectively). However, there were no significant between-group differences in sex, age at disease onset, MSA subtype, parkinsonian features, cerebellar ataxia, residual urine volume, or systolic and diastolic blood pressure change. CONCLUSIONS: MSA with nocturnal stridor is related to higher apnea indices in conjunction with higher O2 desaturation index, more severe axial motor features, more impaired activities of daily living, and longer disease duration.

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.

Family cohesion is differently associated with felt stigma depending on enacted stigma in adults with epilepsy.

PURPOSE: There have been little researches examining the role of family functioning on psychological outcomes in the field of adult epilepsy. We determined whether family functioning is correlated with felt stigma in adults with epilepsy. METHODS: In this cross-sectional study, adults with epilepsy and their caregivers were recruited. Data were collected using the Family Adaptability and Cohesion Evaluation Scale (FACES) III, the Family adaptation, partnership, growth, affection, and resolve (APGAR) questionnaire, the Stigma Scale for Epilepsy (SS-E), the modified questionnaire for episodes of discrimination, and the Beck Depression Inventory. Family functioning was measured by the caregivers. RESULTS: A total of 273 adult patients and their primary caregivers were included. Multivariate logistic analyses showed that family cohesion and excellent family functioning were negatively correlated with felt stigma after controlling for confounding variables. Enacted stigma, depressive symptoms, and university education were also significant. Interaction between enacted stigma and family cohesion on felt stigma was significant (p = 0.049). Family cohesion was negatively correlated with felt stigma only in the patients with enacted stigma (p = 0.011). CONCLUSIONS: Family functioning especially family cohesion may have protective effects against development of felt stigma in adults with epilepsy. Such protecting effects against felt stigma may be different according to enacted stigma. This understanding is helpful for developing effective psychosocial interventions to reduce felt stigma in patients with epilepsy.

Insomnia is less prevalent and less severe, independent of depressive symptoms, in patients with epilepsy treated with perampanel as an adjuvant.

PURPOSE: The potential benefit of perampanel for sleep disturbances is unknown. This study determined whether insomnia is less prevalent and less severe in patients with epilepsy (PWE) who take perampanel as an adjuvant. METHODS: This cross-sectional study was conducted in adults with epilepsy. Insomnia in patients treated or not treated with perampanel was diagnosed according to the criteria of the International Classification of Sleep Disorders, the third edition (ICSD-3) and the Insomnia Severity Index (ISI). Patients were also scored on the Epworth Sleepiness Scale (ESS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7), and the groups were compared by stepwise linear or logistic regression analyses. RESULTS: One hundred and twenty-six PWE were included in the study: 31 patients (24.6%) were taking perampanel. Insomnia was diagnosed in 15.9% and 20.6% of all patients according to the ICSD-3 and an ISI score of ≥15, respectively. Agreement between the two diagnostic methods was moderate (Cohen's kappa, 0.470). In a stepwise logistic regression model, insomnia diagnosed by either method was negatively associated with perampanel use (P<0.05) but positively correlated with depressive symptoms, anxiety, and duration of epilepsy. In a stepwise linear regression model, ISI scores correlated negatively with perampanel use (P=0.004) but positively with depressive symptoms (P<0.001) and anxiety (P=0.001). CONCLUSIONS: Insomnia is less prevalent and less severe in PWE treated with perampanel independent of depressive symptoms, which will be helpful for treating PWE and comorbid sleep disturbances.

Severity of idiopathic rapid eye movement sleep behavior disorder correlates with depression and alexithymia.

BACKGROUND: Depression and alexithymia often accompany early stages of Parkinson's disease (PD). However, these symptoms in idiopathic rapid eye movement sleep behavior disorder (iRBD) remain incompletely understood. The aim of this study was to compare depression and alexithymia between iRBD patients and healthy controls, and to evaluate the association between clinical RBD severity and severity of depression and alexithymia. METHODS: Polysomnography-confirmed iRBD patients (n = 86) and healthy controls (n = 74) were enrolled. Clinical RBD severity was assessed using the RBD questionnaire-Hong Kong (RBDQ-HK). Depression and alexithymia were evaluated by the Beck Depression Inventory (BDI) and the 20-item Toronto Alexithymia Scale (TAS-20), respectively. Multivariate linear regression analysis was performed with adjustments for several covariates to determine the correlations between RBD severity and severity of depression and alexithymia. RESULTS: BDI scores were significantly higher in the iRBD group (10.6 ± 7.3) than in healthy controls (8.2 ± 6.0, p = 0.024). Higher total RBDQ-HK scores were associated with more severe depression in iRBD patients, even after controlling for confounding variables. iRBD patients exhibited significantly higher TAS-20 scores (45.7 ± 10.4) than healthy controls (42.1 ± 9.8, p = 0.026). Total RBDQ-HK scores were positively correlated with TAS-20 scores independent of BDI scores. CONCLUSIONS: Patients with iRBD were more depressed and had more severe alexithymia than healthy controls. Notably, as the clinical severity of RBD increased, both depression and alexithymia worsened.

The timelines of MRI findings related to outcomes in adult patients with new-onset refractory status epilepticus.

OBJECTIVE: To identify the timelines of magnetic resonance imaging (MRI) abnormalities and their relationships with the clinical outcomes of patients with new-onset refractory status epilepticus (NORSE). METHODS: This retrospective observational study enrolled patients with NORSE who were admitted from March 2008 to July 2018. MRI abnormalities were analyzed visually with the readers blinded to the clinical characteristics of the patients. Poor functional outcome was defined as a Glasgow Outcome Scale score ≤ 3 at discharge. Subsequent pharmacoresistant epilepsy was defined as seizures not controlled by two or more anti-seizure medications 6 months after discharge. RESULTS: Among 39 patients with NORSE, 32 (82.1%) exhibited an MRI abnormality. The most common abnormalities were persisting mesial temporal lobe signal abnormality (51.3%); initial diffuse leptomeningeal enhancement within 16 days from seizure onset (15/35, 42.9%); and hippocampal atrophy, which started to appear 26 days after seizure onset (15/26, 57.7%). Only three patients had claustrum abnormalities. Patients with insular involvement had longer treatment delay than those without (24.0 vs 5.5 hours, respectively, P = .02). Duration of status epilepticus (SE) tended to have a linear association with hippocampal atrophy (P = .055). Patients with diffuse leptomeningeal enhancement were more likely to have a poor functional outcome and to develop subsequent pharmacoresistant epilepsy than those without this finding (93.3% vs 15.0%, P < .001; 75.0% vs 22.2%, P = .004, respectively); the results were significant even after adjusting for age, sex, and duration of SE. Hippocampal atrophy and diffuse cortical atrophy were also significantly associated with poor functional outcomes (P = .001 and P = .002, respectively), and patients with these conditions were more likely to develop subsequent pharmacoresistant epilepsy than those without these conditions, after adjusting for age and sex (P = .035 and P = .048, respectively), but not after adjusting for duration of SE. SIGNIFICANCE: Initial diffuse leptomeningeal enhancement and later hippocampal atrophy were associated with a poor functional outcome and subsequent pharmacoresistant epilepsy.

Clinical factors associated with suicide risk independent of depression in persons with epilepsy.

PURPOSE: We determined whether factors related to epilepsy are associated with a risk of suicide independent of depression in persons with epilepsy. METHOD: This cross-sectional study included adults with epilepsy. Suicidality and depression were assessed with the Mini International Neuropsychiatric Interview (MINI). Patients were divided into two age groups (≤ 40 vs. > 40 years). Presence of suicide risk was defined as a MINI suicidality score ≥ 1. A stepwise logistic regression analysis was conducted. RESULTS: A total of 212 participants were recruited (52.4 % men). Suicide risk and depression were noted in 31.6 % and 22.2 % of participants, respectively. An antiepileptic drug load ≥ 1 (odds ratio [OR], 4.093-4.152) was significantly associated with a risk of suicide, independent of depression (OR, 5.794), and a past or family history of psychiatric disorders (OR, 2.677). When stratified by age, pregabalin usage (OR, 13.403) in the younger group and high seizure frequency (≥ 1 per month) (OR, 5.748) in the older group were associated with a risk of suicide independent of current depression. CONCLUSION: The risk of suicide in persons with epilepsy may be associated with epilepsy-related factors such as a high antiepileptic drug load, frequent seizures, and use of pregabalin, independent of depression. Such risk factors may vary depending on the age of the patient.

Sex differences in factors associated with daytime sleepiness and insomnia symptoms in persons with epilepsy.

Clinical factors associated with daytime sleepiness and insomnia in persons with epilepsy (PWE) were examined in this cross-sectional study of 126 participants (men, 50.8%). Excessive daytime sleepiness (EDS; score of ≥11 on the Epworth Sleepiness Scale (ESS)) was noted in 17.5% of participants (mean score, 6.1 ±â€¯4.2), and moderate-to-severe insomnia (Insomnia Severity Index (ISI) scores of ≥15) was noted in 20.6% (mean score, 7.8 ±â€¯6.4). Linear regression analyses revealed that ESS scores were independently associated with obstructive sleep apnea (OSA; snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and gender (STOP-Bang) score of ≥3), an antiepileptic drug (AED) load of >3, depression (Patient Health Questionnaire-9 (PHQ-9) score of ≥10), female sex, and nocturnal seizures. Insomnia Severity Indices were independently associated with depression and anxiety (Generalized Anxiety Disorder-7 (GAD-7) score of ≥7). Notably, significant sex differences were found. Epworth Sleepiness Scale scores were associated with OSA in men but were associated with depression in women. In addition, anxiety was associated with insomnia in women only. Overall, OSA and depression were the most important significant clinical factors associated with daytime sleepiness and insomnia, respectively. However, there were sex differences for the associations between individual factors and sleep disturbances.

Periodic limb movements during sleep may reduce excessive daytime sleepiness in men with obstructive sleep apnea.

PURPOSE: The impact of periodic limb movements during sleep (PLMS) on excessive daytime sleepiness (EDS) is controversial. We investigated the relationship between PLMS and EDS in men with obstructive sleep apnea (OSA). METHODS: This was a cross-sectional study of men with OSA. PLMS parameters were a PLM index (PLMI) > 15 per hour of sleep and a PLM-arousal index (PLMAI) > 5 per hour of sleep. The Epworth Sleepiness Scale (ESS) and the Beck Depression Inventory were used. EDS was defined as an ESS score ≥ 11. Multivariate logistic regression analysis was performed with adjustments for several covariates. RESULTS: Of 1111 men with OSA, 14.0% (n = 156) had a PLMI > 15/h, and 3.7% (n = 41) had a PLMAI > 5/h. EDS was noted in 39.5% (n = 439) of men. Men with a PLMI > 15/h were less likely to have EDS (odd ratio [OR], 0.598; 95% confidence interval [CI], 0.414-0.864; p = 0.006). This association remained significant after controlling for age, body mass index, depressive symptoms, total sleep time, and severity of OSA (OR, 0.675; 95% CI, 0.456-0.999; p = 0.049). Men with a PLMAI > 5/h were less likely to have EDS, but this result did not reach statistical significance (OR, 0.550; 95% CI, 0.273-1.109; p = 0.095). CONCLUSIONS: PLMS defined as PLMI > 15/h are significantly and inversely associated with EDS in men with OSA, even after controlling for several confounding variables.