Comparative efficacy of prolonged-release melatonin versus clonazepam for isolated rapid eye movement sleep behavior disorder.

PURPOSE: Clonazepam and melatonin are recommended as first-line treatments for isolated rapid eye movement (REM) sleep behavior disorder (iRBD). This study aimed to compare their efficacy and safety in REM sleep without atonia (RWA) and RBD-related symptoms. METHODS: This prospective, open-label, randomized trial included patients with video-polysomnography-confirmed iRBD. The patients were randomly assigned to receive either clonazepam 0.5 mg or prolonged-release (PR) melatonin 2 mg 30 min before bedtime for 4 weeks. The primary outcome was changes in RWA on follow-up polysomnography (PSG). Secondary endpoints were changes in other PSG parameters, clinical global improvement-impression scale (CGI-I) scores, and sleep questionnaire scores. The safety endpoint was adverse events. RESULTS: Of 40 patients with probable RBD considered, 34 were enrolled in the study and randomized. Visual scoring parameters of RWA indices were reduced, and automatic scoring parameters tended to be improved after clonazepam treatment but not after PR melatonin treatment. The proportion of N2 sleep was increased, and N3 and REM sleep were decreased only in the clonazepam group. The clonazepam group tended to answer "much or very much improvement" on the CGI-I more frequently than the PR melatonin group (p = 0.068). Daytime sleepiness and insomnia symptoms were reduced after PR melatonin but not after clonazepam. Depressive symptoms increased after clonazepam. Four of the patients (13.3%) reported mild to moderate adverse events, which were similar between the two groups. CONCLUSION: Four weeks of clonazepam, but not PR melatonin, improved RWA. RBD symptom improvement tended to be better after clonazepam than PR melatonin in exchange for increased depressive symptoms and daytime sleepiness. CLINICALTRIALS: gov identifier: NCT03255642 (first submitted August 21, 2017).

Correlation between craniofacial changes and respiratory improvement after nasomaxillary skeletal expansion in pediatric obstructive sleep apnea patients.

PURPOSE: The aim of this study was to investigate the correlation between the changes in respiratory function and dimensions of the nasomaxillary complex (NMC) and upper airway (UA) compartments after nasomaxillary skeletal expansion (NMSE) treatment for pediatric patients with obstructive sleep apnea (OSA). METHODS: Nonobese OSA patients (mean age, 13.6 ± 2.9 years; mean body mass index, 18.1 ± 3.0 kg/m2); mean apnea-hypopnea index (AHI, 7.0 ± 5.4 events/h) presenting with transverse nasomaxillary constriction were evaluated before and after NMSE using cone-beam computed tomography (CBCT), home sleep test, and modified pediatric sleep questionnaire (m-PSQ). Paired t tests were performed to examine the treatment-related changes in all the parameters, and a multiple regression analysis adjusted for age and sagittal and vertical skeletal patterns was conducted to determine the dimensional parameters to affect the functional improvement. RESULTS: Among 26 patients, NMSE treatment significantly increased NMC dimensions at all tested levels and all UA compartments in CBCT, except glossopharyngeal airway. Concurrently, AHI, oxygen desaturation index, the lowest oxygen saturation (LSaO2), flow limitation (FL), snoring, and m-PSQ were significantly improved. AHI reduction was correlated with UA enlargement with no correlation with NMC expansion, whereas FL reduction was affected by NMC expansion. The minimal cross-sectional area was the most predictive of functional improvement, presenting correlations with AHI, LSaO2, and m-PSQ. CONCLUSION: NMSE can be a good treatment for pediatric OSA patients when applied to enhance the nasal and pharyngeal airway patencies beyond the NMC, ultimately to improve pharyngeal collapsibility as well as nasal airflow.

Sex differences in seizure effects on social anxiety in persons with epilepsy.

PURPOSE: We investigated sex differences in the effect of seizures on social anxiety in persons with epilepsy. METHOD: In this cross-sectional multicenter study, social anxiety was measured using the short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). SPS-6 scores ≥ 9 and SIAS-6 scores ≥ 12 were considered to indicate social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9, Stigma Scale-Revised, and Family Adaptation-Partnership-Growth-Affection-Resolve scale were also completed. A logistic regression analysis with an interaction term was used to analyze the data. RESULTS: Out of 285 participants, a SPS-6 score ≥ 9 and a SIAS-6 score ≥ 12 were noted in 62 (21.8%) and 36 (12.6%) of participants, respectively. There was no difference in the prevalence of social anxiety between men and women. Intractable seizures and lack of seizure freedom were associated with a SPS-6 score ≥ 9 and a SIAS-6 score ≥ 12, but statistical significance was lost in the adjusted models. However, intractable seizures and lack of seizure freedom significantly interacted with sex for a SPS-6 score ≥ 9 (p = 0.018) and a SIAS-6 score ≥ 12 (p = 0.048) in both the separate and adjusted models. Specifically, intractable seizures tended to be positively associated with SPS-6 scores ≥ 9 than non-intractable seizures in men only (odds ratio = 2.602, p = 0.068), whereas lack of seizure freedom tended to be negatively associated with SIAS-6 scores ≥ 12 than seizure freedom in women only (odds ratio = 4.804, p = 0.053). CONCLUSION: We found significant sex differences in seizure effects on social anxiety. Intractable seizures were associated with social phobia in men, whereas lack of seizure freedom in the last year was associated with social interaction anxiety in women.

Survey on Antiepileptic Drug Therapy in Patients with Drug Resistant Epilepsy.

BACKGROUND AND PURPOSE: Individualized anti-epileptic drug (AED) selection in patient with epilepsy is crucial. However, there is no unified opinion in treating patients with drug resistant epilepsy (DRE). This survey aimed to make a consolidate consensus with epileptologists' perspectives of the treatment for Korean DRE patients by survey responses. METHODS: The survey was conducted with Korean epilepsy experts who have experience prescribing AEDs via e-mail. Survey questionnaires consisted of six items regarding prescription patterns and practical questions in treating patients with DRE in Korea. The research period was from February 2021 to March 2021. RESULTS: The survey response rate was 83.3% (90/108). Most (77.8%) of the responders are neurologists. The proportion of patients whose seizures were not controlled by the second AED was 26.9%. The proportion of patients who had taken five or more AEDs is 13.9%, and those who are currently taking five or more AEDs are 7.3%, of which 54.5% and 37.9% reported positive effects on additional AED, respectively. The majority (91.1%) of respondents answered that the mechanism of action was the top priority factor when adding AED. Regarding data priority, responders considered that expert opinion should have the top priority, followed by clinical experiences, reimbursement guidelines and clinical evidence. Responders gave 64.9 points (range from 0 to 100) about overall satisfaction on reimbursement system of Health Insurance Review and Assessment Service for AED. CONCLUSIONS: This study on AED therapy for DRE patients is the first nationwide trial in Korean epilepsy experts. In five drug failure, the top priorities on AED selection are mechanism of action and expert opinion. These findings might help to achieve consensus and recognize the insight on optimal therapy of AED in DRE.

Respiratory and sleep characteristics based on frequency distribution of craniofacial skeletal patterns in Korean adult patients with obstructive sleep apnea.

OBJECTIVE: To investigate the frequency distribution of various craniofacial skeletal patterns in a large Korean adult obstructive sleep apnea (OSA) population, and to find a relationship between craniofacial risks and respiratory and sleep characteristics. METHODS: A total of 1226 OSA patients (mean age of 44.9±13.3 years) were included in this retrospective cross-sectional study. All subjects were evaluated for gender and age using fourteen polysomnographic, five cephalometric, two comorbid variables, and three self-reported indexes. Frequency analysis was used to screen the distribution of main skeletal patterns and subtypes. Intergroup comparisons were performed using independent t-test, chi-square test or analysis of variance. Univariable regression analysis was done to find a relationship between skeletal risks and OSA characteristics. RESULTS: The frequency distribution of skeletal patterns was as follows: sagittally 57.2%, 32.3%, and 10.5% of Class II, Class I, and Cass III; vertically 54.0%, 26.7%, and 19.3% of hyperdivergent, normodivergent, and hypodivergent type, respectively. Polysomnographic, symptomatic, and comorbid variables showed no differences among patients with different skeletal patterns. Conversely, skeletal variables showed no differences according to OSA severity. The prevalence of highly risky skeletal pattern of hyperdivergent Class II was more likely to be females (OR 4.52, P < .01) and less obese (OR 3.21, P < .01), irrelevant to OSA and sleep characteristics. CONCLUSION: Characteristic frequency distributions of skeletal patterns and subtypes were observed in adult OSA patients however, no statistical association was found between the skeletal patterns and OSA characteristics due to the large interindividual variation.

Factors associated with stigma and depressive symptoms in family members of patients with epilepsy.

PURPOSE: Literature regarding family stigma related to epilepsy is scarce. This study investigated the prevalence of family stigma and depressive symptoms and the associated factors among the family members of patients with epilepsy. METHODS: In a cross-sectional study, Stigma Scale-Revised score ≥ 4 and Patient Health Questionnaire-9 score ≥ 10 were considered indicative of moderate-to-severe stigma and depressive symptoms, respectively. Stepwise logistic regression analyses were performed. RESULTS: Of the 482 family members, a mean age was 47.1 ±â€¯9.4 years, and 73.4% were female. Of the patients, a mean age was 25.5 ±â€¯16.7 years, and 45.0% were female. Idiopathic generalized epilepsy and focal epilepsy were noted in 22.4% and 65.6% of patients, respectively. Family stigma and depressive symptoms were noted in 10.0% and 11.2% of family members, respectively. Family stigma was significantly associated with high seizure frequency and being a sibling or offspring of a patient independent of their depressive symptoms. By contrast, depressive symptoms in family members were significantly associated with polytherapy, being parents of a patient, and neurological comorbidities independent of family stigma. In a subset of patients and their family, patients had higher proportion of stigma and depressive symptoms than their family. Depressive symptoms and stigma among patients were significantly correlated with those among parents, but not spouse. CONCLUSION: Family stigma is common in families with epilepsy and is closely related to depressive symptoms. Frequent seizures, polytherapy, neurological comorbidities, and the relationship to a patient may be factors that are independently associated with family stigma and depressive symptoms in family members.

Does the new Korean term for epilepsy reduce the stigma for Korean adults with epilepsy?

PURPOSE: The purpose of this study was to evaluate differences in stigma, disclosure management of epilepsy, and knowledge about epilepsy between patients with epilepsy who recognized and did not recognize the new Korean term for epilepsy. METHODS: This was a cross-sectional, multicenter study. The Stigma Scale-Revised, the Disclosure Management Scale, the Patient Health Questionnaire-9, and a questionnaire assessing knowledge about epilepsy were used. The set of questionnaires had two versions, using either the old or new name for epilepsy. Multivariate logistic regression analyses were used. RESULTS: A total of 341 patients with epilepsy and 509 family members were recruited. Approximately 62% of patients felt some degree of epilepsy-related stigma. Mild stigma, severe concealment of epilepsy diagnosis, and increased knowledge about epilepsy were independently identified as factors associated with recognition of the new term in patients. Recognition of the new term was more prevalent in patients and family members with higher education, female family members, and family members having patients with younger age at seizure onset and shorter duration of epilepsy. There were no significant differences between the two types of questionnaires. About 81% of patients and 93% of family members had a positive attitude about renaming epilepsy. CONCLUSION: The use of the new Korean term for epilepsy (cerebroelectric disorder) increased knowledge about epilepsy but did not reduce stigma and concealment of epilepsy diagnosis in Korean adults with epilepsy. Higher education may be an important factor for knowing the new term in patients and family members.

Factors associated with social anxiety in South Korean adults with epilepsy.

PURPOSE: The aim of this study was to examine social anxiety in South Korean adults with epilepsy and to identify associated factors. METHOD: This was a cross-sectional, multicenter study in South Korea. Social anxiety was assessed using short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). The SPS-6 scores ≥9 and SIAS-6 scores ≥12 were considered indicative of social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9 (PHQ-9); Stigma Scale-Revised (SS-R); Disclosure Management Scale; Family Adaptation, Partnership, Growth, Affection, Resolve (F-APGAR) scale; and a questionnaire assessing knowledge about epilepsy were also used. RESULTS: Of a total of 219 patients with epilepsy, 21% and 11% had SPS-6 scores ≥9 and SIAS-6 scores ≥12, respectively. In logistic regression analysis, SPS-6 scores ≥9 were independently associated with SS-R scores of 4-9 (odds ratio [OR]: 8.626, 95% confidence interval [CI]: 2.515-29.587, p = .001), SS-R scores 1-3 (OR: 5.496, 95% CI: 1.757-17.197, p = .003), and PHQ-9 scores ≥10 (OR: 4.092, 95% CI: 1.823-9.185, p = .001). In contrast, SIAS-6 scores ≥12 were related only to PHQ-9 scores ≥10 (OR: 8.740, 95% CI: 3.237-23.599, p < .001). Belonging to a dysfunctional family and lack of knowledge about epilepsy tended to be associated with social phobia (p = .071) and social interaction anxiety (p = .090), respectively. Epilepsy-related variables were not related to social anxiety. CONCLUSION: Social anxiety is not rare in patients with epilepsy. In this study, social phobia was associated with perceived stigma and depressive symptoms, whereas social interaction anxiety was related only to depressive symptoms in patients with epilepsy.

Comparison of cardiac autonomic activity between positional and nonpositional obstructive sleep apnea using heart rate variability.

OBJECTIVES: Patients with obstructive sleep apnea (OSA) experience sympathetic hyperactivation during sleep, which is associated with increased cardiovascular risk factors. However, the difference in cardiac autonomic activity in OSA patients according to position dependency has not been evaluated. This study aimed to evaluate the differences between positional OSA (pOSA) and nonpositional OSA (npOSA) using heart rate variability (HRV) analysis. METHODS: This was a single-center cross-sectional study. Twenty-eight patients with npOSA and 28 age-, sex-, and AHI-matched patients with pOSA underwent standard polysomnography. A five-minute R-R interval from stable waking conditions before bedtime was collected from each subject and analyzed for HRV. RESULTS: Patients with pOSA had lower body-mass index (BMI, 25.8 ± 2.9 vs 28.9 ± 3.7 kg/m2, p = 0.001), shorter apnea duration (24.1 ± 7.1 vs 30.3 ± 12.7 s, p = 0.028) and higher minimum oxygen saturation (78.2 ± 7.1 vs 71.5 ± 11.4%, p = 0.011) than those with npOSA. HRV analysis showed higher parasympathetic activity in pOSA patients than in npOSA patients, including a higher square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD, 31.3 ± 29.0 vs 18.6 ± 9.2, p = 0.032), percentage of pairs of adjacent NN intervals that differ by more than 50 ms (pNN50%, 10.7 ± 17.1 vs 3.3 ± 6.5, p = 0.024), and high-frequency (HF) power (534.7 ± 986.8 vs 146.7 ± 150.5, p = 0.026). The group difference was insignificant after adjusting for age and BMI. The log-transformed supine/nonsupine AHI ratio was the sole independent predictor of HRV parameters. CONCLUSION: The waking HRV was higher in pOSA patients than in npOSA patients due to the lower BMI of pOSA patients. The difference was especially apparent in parasympathetic indices. Higher parasympathetic activity in pOSA may suggest a lower risk for cardiovascular morbidity and mortality.

Sleep hygiene-related conditions in patients with mild to moderate obstructive sleep apnea.

OBJECTIVE: Sleep hygiene-related conditions are factors that affect the symptoms experienced by patients with obstructive sleep apnea (OSA). However, very few studies have investigated the association between sleep hygiene and sleep symptoms, especially in patients with mild or moderate OSA. This study evaluated the relationship between factors related to sleep hygiene and clinical symptoms in patients with mild to moderate OSA. METHODS: One hundred and seventy-four patients who visited the Sleep Breathing Disorder Center at a tertiary academic center to evaluate suspected OSA were included. All patients underwent standard polysomnography (PSG) and the Epworth sleepiness scale (ESS) and questionnaires related to daytime and nighttime symptoms and sleep hygiene. Medical records were reviewed for demographic, clinical, and PSG parameters. Correlation analysis between sleep hygiene-related conditions and clinical symptoms in patients with mild to moderate OSA was performed. RESULTS: The correlation analysis between the nine categories of sleep hygiene and the three categories of clinical symptoms showed that, in the case of inadequate temperature and humidity conditions, the three categories of clinical symptoms were more severe (daytime symptoms r=0.382, nighttime symptoms r=0.568, ESS score r=0.321). Drinking alcohol before sleep (daytime symptoms r=0.457, nighttime symptoms r=0.649, ESS score r=0.301) and emotional excitement or arousal (daytime symptoms r=0.378, nighttime symptoms r=0.545, ESS score r=0.341) were correlated with greater severity of each of the clinical symptoms (p<0.05). CONCLUSION: Among the factors of sleep hygiene-related conditions, inadequate temperature and humidity, drinking alcohol before sleep, and emotional excitement or arousal were associated with symptoms of mild to moderate OSA. This study supports the hypothesis that patients with mild to moderate OSA can experience symptom relief if they are trained to correct lifestyle habits to maintain adequate sleep hygiene-related conditions.

Somatosensory reflex epilepsy: simultaneous video-EEG monitoring and surface EMG.

Somatosensory reflex epilepsy is induced by repetitive cutaneous contact of a circumscribed body area with a tight time-lock between somatosensory stimulation and seizure. We describe the case of a 27-year-old man with seizures induced by repetitive tapping on the sole of the right foot. Simultaneous video-EEG monitoring and surface electromyography was performed during a seizure triggered by repetitive tapping on the right sole aspect using a hammer. Stimulation produced a tingling sensation on the right sole that extended to the right lower leg. This was followed by motor Jacksonian march of the right leg. [Published with video sequence on www.epilepticdisorders.com].

Diagonal Earlobe Crease is a Visible Sign for Cerebral Small Vessel Disease and Amyloid-ß.

We investigated the frequency and clinical significance of diagonal earlobe crease (DELC) in cognitively impaired patients using imaging biomarkers, such as white matter hyperintensities (WMH) on MRI and amyloid-ß (Aß) PET. A total of 471 cognitively impaired patients and 243 cognitively normal (CN) individuals were included in this study. Compared with CN individuals, cognitively impaired patients had a greater frequency of DELC (OR 1.6, 95% CI 1.1-2.2, P = 0.007). This relationship was more prominent in patients with dementia (OR 1.8, 95% CI 1.2-2.7, P = 0.002) and subcortical vascular cognitive impairment (OR 2.4, 95% CI 1.6-3.6, P < 0.001). Compared with Aß-negative cognitively impaired patients with minimal WMH, Aß-positive patients with moderate to severe WMH were significantly more likely to exhibit DELC (OR 7.3, 95% CI 3.4-16.0, P < 0.001). We suggest that DELC can serve as a useful supportive sign, not only for the presence of cognitive impairment, but also for cerebral small vessel disease (CSVD) and Aß-positivity. The relationship between DELC and Aß-positivity might be explained by the causative role of CSVD in Aß accumulation.

Prevalence of Self-Perceived Snoring and Apnea and Their Association with Daytime Sleepiness in Korean High School Students.

BACKGROUND AND PURPOSE: There has been no nationwide population-based study of the prevalence of self-perceived snoring/apnea in Korean adolescents. The purpose of this study was to estimate prevalence of self-perceived snoring/apnea in Korean high-school students and to evaluate their association with daytime sleepiness. METHODS: An online survey was used to investigate 12,672 students at 75 high schools across the 15 nationwide districts of South Korea. The variables were obtained using a self-reported questionnaire. The students answered questions about self-perceived snoring/apnea during the past 30 days. Daytime sleepiness was measured using a validated Korean version of the Epworth Sleepiness Scale, which was modified for adolescents. Covariates were the sex, school grade, frequency of self-perceived snoring/apnea, body mass index, sleep duration during a school day, and subjective perception of sleep duration. RESULTS: The prevalence of self-perceived snoring/apnea was 22.8% (26.4% for males vs. 18.8% for females, p<0.001) and 9.2% (10.5% for males vs. 7.7% for females, p<0.001). Obesity was significantly associated with self-perceived snoring [odds ratio (OR)=2.18, 95% confidence interval (CI)=1.94-2.46] and apnea (OR=1.57, 95% CI=1.33-1.86). Multivariate analysis showed that any frequency of self-perceived snoring/apnea was significantly associated with excessive daytime sleepiness (EDS). The OR of EDS increased significantly with the frequency of snoring and apnea. Female, sleep duration of <5 hours during a school day, and subjective perceptions of insufficient and considerable sleep durations were also significantly associated with EDS. CONCLUSIONS: The prevalence of self-perceived snoring/apnea was significantly higher in students who were male and obese. Students with self-perceived snoring/apnea exhibited more significant EDS and an increased risk of EDS as the frequency of snoring and apnea increased.

Intractable Epilepsy with Solitary Cerebral Calcification.

Cerebral calcification is a common incidental finding upon brain imaging and its epileptogenicity is often underestimated. Here, we report a case of intractable epilepsy arising in conjunction with a solitary cerebral calcification. A 42-year-old male with intractable epilepsy was admitted to the epilepsy clinic for invasive epilepsy surgery. Brain magnetic resonance imaging revealed a slight high-intensity signal change in the right amygdala and a small, calcified lesion in the right lateral temporal region. The patient underwent invasive monitoring with subdural electrodes. He had five habitual seizures with automatisms and fast activity. These seizures initiated in the right lateral temporal area just above the solitary calcified lesion. Neuropathology of the calcified lesion showed no specific findings apart from a fibrocalcific nodule. Thus, although solitary cerebral calcifications may be an asymptomatic or coincidental finding in some patients, they may also have a highly epileptogenic focus.

The Difference in Heart Rate Change between Temporal and Frontal Lobe Seizures during Peri-ictal Period.

BACKGROUND AND PURPOSE: Heart rate (HR) change is easily seen in seizures. Tachycardia is frequently seen in temporal lobe epilepsy (TLE), rather than extra temporal lobe epilepsy (XTLE). We report the difference in the HR pattern between TLE and frontal lobe epilepsy (FLE) during peri-ictal period. METHODS: The ECG data, collected during EEG monitoring, was used. To compare the HR pattern between FLE and TLE, we investigated the baseline HR, maximum HR, seizure onset to peak HR, HR change, and the time return to baseline. RESULTS: A total of 198 seizures (FLE was 115, TLE was 83) were included in this study. The baseline HR (in TLE, 74.9 ± 17.2 and in FLE, 70.7 ± 11.5 bpm), there was no difference between two groups. But the mean duration of the increased HR was more prolonged in TLE group (93.8 ± 54.9 seconds) than the FLE group(39.0 ± 21.4 seconds) (p < 0.001), the time to peak HR of the TLE group (135.1 ± 19.1 seconds) was higher than FLE group (119.3 ± 19.7 seconds) (p = 0.027), and the HR change of the TLE group (60.0 ± 26.3 bpm) was more prominent than that of the FLE group (22.8 ± 26.2 seconds) (p < 0.001). Furthermore, a longer duration of HR increase was seen in that of the TLE group than FLE group. CONCLUSIONS: The HR change of the TLE group was more prominent and prolonged than that of the FLE group. Therefore, the HR change can be a pattern that differentiates TLE from FLE.

Non-ketotic hyperglycaemia presenting as epilepsia partialis continua.

Epilepsia partialis continua is a rare epileptic syndrome observed in patients with brain structural lesions and metabolic disorders. We report a patient with non-ketotic hyperglycaemia presenting as epilepsia partialis continua with reversible focal brain lesions. An 83-year-old woman visited our hospital due to sudden and repetitive left facial twitching lasting for two days. Initial laboratory data revealed serum glucose, osmolality, and sodium levels of 631 mg/dl, 310 mOsm/l, and 130 mEq/l, respectively. EEG was normal. Brain MRI showed low signal changes in the right frontal subcortical area and high signal changes in the surrounding right frontal cortical areas on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. No seizures recurred after correcting blood glucose levels, hydrating the patient, and infusing valproate (900 mg/day). Follow-up MRI, six months later, showed complete resolution of the signal changes in the right frontal cortical and subcortical areas and no clinical seizures. When considering non-ketotic hyperglycaemia with epilepsia partialis continua in an elderly patient, early diagnosis and administration of the appropriate therapy is very important in order to decrease morbidity.