Quantitative Network Comparisons of REM Sleep Without Atonia Across the α-Synucleinopathy Spectrum: A Systematic Review.

Purpose: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by REM sleep without atonia (RWA) and is regarded as the prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). RWA is also associated with neurodegeneration driven by α-synucleinopathy. However, the level of RWA across the α-synucleinopathy spectrum remains elusive. We aimed to rate the percentage of RWA across the α-synucleinopathy spectrum, encompassing prodromal and overt phenotypes. Methods: A systematic search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases. We included cohort, cross-sectional, and case-control studies comparing the RWA percentage during REM sleep evaluated by tonic chin activity (RWA%-T) or by phasic chin activity (RWA%-P) across the α-synucleinopathy spectrum. Bayesian network meta-analysis was used to combine both direct and indirect evidence regarding the group differences in the RWA%-T and RWA%-P. The surface under the cumulative ranking curve was used to estimate the ranked probability. Results: Fifteen articles met the inclusion criteria. The investigations included 204 iRBD, 295 PD with RBD (PDwtRBD), 187 PD without RBD (PDwoRBD), 42 MSAwtRBD, 9 DLBwtRBD patients, and 246 controls. MSAwtRBD ranked first in RWA%-T, whereas iRBD ranked first in RWA%-P. RWA% in PDwoRBD patients was comparable to that in the controls and was lower than that in PDwtRBD patients. Conclusion: Overt phenotypes such as MSAwtRBD and PDwtRBD ranked high in RWA%-T, whereas iRBD, a prodromal type, ranked highest in RWA%-P. Taken together, our data suggest that the percentage of neurodegeneration in RBD patients may be associated with RWA%-T rather than RWA%-P. Prospero Registration Number: CRD42021276445.

Felt stigma proportion in people living with epilepsy: A systematic review.

PURPOSE: Numerous inventories to identify felt stigma (FS) in people living with epilepsy (PLWE) have been developed. Past studies have mainly focused on the relationship between FS scores and clinical factors, making it challenging to delineate FS proportions and compare FS between groups. We aimed to integrate FS proportions in PLWE and compare them by continent. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, and Scopus. Among the identified studies, we chose the ones providing an FS proportion measured by Jacoby's Stigma Scale (JSS) and its revised version (JSS-R) in PLWE. We applied the random-effects model. RESULTS: A total of 63 datasets from 47 studies were included. There were 29,924 PLWE, with 14,323 of them experiencing FS. The overall FS proportion was 48.4%. Of these datasets, 51 used JSS, and 12 used JSS-R. The FS proportions were 44.9% for the former and 62.1% for the latter, with significant heterogeneity. In the intercontinental comparison with 51 datasets employing JSS, the difference in FS proportions was insignificant: 51.2% in Africa, 47.2% in Europe, 35.4% in Asia, and 28.8% in the Middle East. Furthermore, the meta-regression revealed that the year of each primary study did not influence the FS proportion. CONCLUSION: Among PLWE, FS proportions depended on the choice of a measurement tool. When measured using JSS, the FS proportion was 44.9%, while it was 62.1% when evaluated with JSS-R. Even though the FS proportions were integrated differently, no substantial differences were observed between continents.

Impact of the Occurrence While Sleeping of First Unprovoked Seizure on Seizure Recurrence: A Systematic Review.

BACKGROUND AND PURPOSE: The impact of the occurrence while sleeping of first unprovoked seizure (FUS) on seizure recurrence in people with FUS is currently unclear. This uncertainty makes it challenging for physicians to determine whether to apply antiseizure medications (ASMs) to people with FUS while sleeping (FUS-S). This study aimed to determine the impact of the occurrence while sleeping of FUS. METHODS: We searched the MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus electronic databases. Among retrieved studies, we selected those that provided information on the number of people with FUS, and relapsed people among these in each instance of FUS-S and FUS when waking (FUS-W). We used a random-effects model for meta-analyses. RESULTS: Of the 3,582 identified studies, 13 were eligible for systematic review. Seven of these 13 studies were deemed adequate for inclusion in a meta-analysis since they provided information at the time point of 2 years follow-up after FUS. The seven studies were of high quality regarding their risk of bias. When combining these 7 studies, the total sample comprised 1,659 people, of which 626 had FUS-S and 1,033 had FUS-W. The relative risk of seizure recurrence between FUS-S and FUS-W was 1.627. The seizure recurrence rates (SRRs) were 59.8% and 36.5% in the FUS-S and FUS-W groups, respectively. CONCLUSIONS: We verified that the SRR was higher among people with FUS-S than FUS-W. After 2 years of follow-up, the SRR in people with FUS-S was about 60%. It is preferable to initiate an ASM for people with FUS-S. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021266191.

Comparison of rapid eye movement without atonia quantification methods to diagnose rapid eye movement sleep behavior disorder: a systematic review.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep without atonia (RWA) is essential for diagnosing REM sleep behavior disorder (RBD). Manual and automatic quantifications of RWA that use different criteria have been validated. This study compared the RWA quantification methods for diagnosing RBD. METHODS: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were systemically searched for studies published from inception to December 2021. The inclusion criteria were cohort, cross-sectional, and case-control studies assessing the sensitivity and specificity of RWA quantification methods. Pooled estimates of the sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were determined. Risk of bias and certainty of evidence was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool and the Grading of Recommendations, Assessment, Development, and Evaluations framework, respectively. RESULTS: Fourteen articles including 402 patients with RBD met the inclusion criteria. Manual methods evaluating any chin and phasic flexor digitorum superficialis (FDS) activity had the highest DOR (138.8, 95% CI = 21.8% to 881.7%) and AUC (0.9686). The automatic REM atonia index (RAI) showed similar or higher sensitivity (89.1%, 95% CI = 84.6% to 92.7%) but a lower specificity (73.5%), DOR (43.1), and AUC (0.9369) than the manual techniques. CONCLUSIONS: In this meta-analysis, manual RWA quantification that employed chin or phasic FDS activity had the best RBD diagnostic performance. The automatic RAI method may be useful for screening patients with RBD. The results should be interpreted carefully because of the high risk of bias in patient selection and significant heterogeneity among the studies. PROSPERO REGISTRATION NUMBER: CRD42021276445.

Reflex and Spontaneous Movements in Pediatric Patients with Brain Death.

BACKGROUND: Reflex and spontaneous movements are not uncommon in brain death patients. However, most studies have been conducted in adults, while reports in infants and children are rare. Thus, we aimed to evaluate the frequency and characteristics of these movements in pediatric patients declared as brain death. METHODS: Records of pediatric patients who were diagnosed as brain death from 15 hospitals in the Yeongnam region, South Korea, between January 2013 and September 2016 were analyzed. All body movements in patients who met the criteria for brain death as established by the Korea Medical Association were assessed by medical doctors and trained organ transplant coordinators. The frequency and characteristics of these movements were identified. Additionally, the demographic and clinical factors of the brain death patients with and without these movements were compared. RESULTS: A total of 31 patients who met the criteria for brain death were enrolled. Seven patients (22.6%) showed either reflex or spontaneous movements; six of them (85.7%) showed reflex movements only, and one patient (14.3%) showed both types of movements. The most common types of reflex movements were the flexor/extensor plantar response and isolated finger jerk. Four of seven patients (57.1%) showed a single movement pattern, while three (42.9%) showed two different movement patterns. CONCLUSION: It is essential for physicians who perform pediatric brain death examinations to recognize the frequency and characteristics of reflex and spontaneous movements, and this article may help in the accurate and prompt diagnosis of brain death.

Factors Affecting the Time Taken to Determine Brain Death in Patients with Impending Brain Death.

BACKGROUND AND PURPOSE: The increased demand for donor organs has made it crucial to keep the organs of patients with impending brain death (PWIBDs) suitable for transplantation during the process of determining brain death. This study aimed to identify the time taken to determine brain death (TT-BD) in PWIBDs and the associated influencing factors. METHODS: This study analyzed data collected by the Korean Organ Donation Agency from 15 hospitals in the Yeongnam region of South Korea. There were 414 PWIBDs eligible for inclusion in this study. The data consisted of the TT-BD for PWIBDs and the potential variables influencing the TT-BD. RESULTS: The mean age of the 414 PWIBDs was 48.9 years, and 120 of them were female (29.0%). The mean TT-BD was 8.5 days. The presence of spontaneous movements (SMs) and craniotomy significantly affected the TT-BD. The mean TT-BDs were 13.9 and 8.2 days in the PWIBDs with and without SMs, respectively, and 9.8 and 8.0 days in the PWIBDs with and without craniotomy, respectively. CONCLUSIONS: The SMs in PWIBDs and a craniotomy performed immediately before starting the process of determining brain death seem to be related to lengthening the TT-BD.

HLAs associated with perampanel-induced psychiatric adverse effects in a Korean population.

Perampanel (PER) is a new-generation antiepileptic drug that has an occasional but significant shortcoming, psychiatric adverse effects (PAEs). Recently, antiepileptic drug-related adverse reactions, such as skin rash and even PAEs, have been discovered to be correlated with certain human leukocyte antigen (HLA) types. Thus, we aimed to analyze specific HLA alleles as risk factors for PER-PAEs. We prospectively enrolled 17 patients with epilepsy who were prescribed PER between May 2016 and Jul 2018 at Seoul National University Hospital and developed PAEs while taking PER. Their HLA types were analyzed compared to those of 19 patients in the PAE-tolerant group and the general Korean population. In silico docking was performed with two different computational programs, AutoDock Vina and SwissDock, to theoretically evaluate the binding affinity of PER in the grooves of the specific HLA alleles. The HLA-DQB1*06:01, DRB1*08:03, and B*54:01 alleles were significantly associated with the patients who developed PER-PAEs compared with the general Korean population (odds ratio [OR] 3.94, p = 0.008, OR 9.24, p = 0.037, and OR 3.25, p = 0.041, respectively). As a haplotype, the combination of the three alleles was significantly more frequent in the PER-PAE group than in both the PER-tolerant group and the general Korean population. DQB1*06:01 and B*54:01 also demonstrated higher docking scores with PER than other alleles. This is the first study to analyze the association of PER-PAEs with specific HLA genotypes. Our results suggest that an HLA-associated genetic predisposition and a possible immunological mechanism are involved in the occurrence of PER-PAEs.

Reflex and Spontaneous Movements in Adult Patients during the Process of Determining Brain Death in Korea.

BACKGROUND: Brain death is a clinical diagnosis that implies irreversible loss of function of the entire brain, including the brainstem and both hemispheres. Based on previous reports, it is not rare for reflex and spontaneous movements to occur in patients during the process of determining brain death. However, reports of the frequency and common types of these movements vary from study to study. Thus, we evaluated adult patients with impending brain death in Korea to determine the frequency and characteristics of reflex and spontaneous movements. METHODS: Brain dead patients who were admitted to 15 hospitals in the Yeongnam region (Southeast) of Korea were recruited prospectively from January 2013 to September 2016. All patients met the criteria for brain death as established by the Korea Medical Association. All body movements occurred during the process of diagnosing brain death and were assessed by physicians and trained organ transplant coordinators. The frequency and characteristics of these movements were identified and the demographic and clinical factors of impending brain dead patients with and without these movements were compared. RESULTS: A total of 436 patients who met the criteria for brain death were enrolled during the study period. Of these patients, 74 (17.0%) exhibited either reflex or spontaneous movements. Of this subset, 45 (60.8%) exhibited reflex movements only, 18 (24.3%) exhibited spontaneous movements only, and 11 (14.9%) exhibited both reflex and spontaneous movements. The most common reflex movements were the flexor/extensor plantar response and spinal myoclonus. Of the 74 patients, 52 (70.3%) exhibited one movement of the same pattern and 22 (29.7%) exhibited two or more different movement patterns. In addition, 45 (60.8%) exhibited these movements only on a limited area of the body with the leg being most common (n = 26, 57.8%). Patients with hypoxic brain damage and a higher systolic blood pressure exhibited significantly more reflex or spontaneous movements. CONCLUSION: Movements associated with brain dead patients are not rare and thus an awareness of these movements is important to brain death diagnosis. Physicians who perform brain death examinations should understand the frequency and characteristics of these movements to reduce delays in determining brain death.

Brain regions associated with periodic leg movements during sleep in restless legs syndrome.

The neural substrates related to periodic leg movements during sleep (PLMS) remain uncertain, and the specific brain regions involved in PLMS have not been evaluated. We investigated the brain regions associated with PLMS and their severity using the electroencephalographic (EEG) source localization method. Polysomnographic data, including electromyographic, electrocardiographic, and 19-channel EEG signals, of 15 patients with restless legs syndrome were analyzed. We first identified the source locations of delta-band (2-4 Hz) spectral power prior to the onset of PLMS using a standardized low-resolution brain electromagnetic tomography method. Next, correlation analysis was conducted between current densities and PLMS index. Delta power initially and most prominently increased before leg movement (LM) onset in the PLMS series. Sources of delta power at -4~-3 seconds were located in the right pericentral, bilateral dorsolateral prefrontal, and cingulate regions. PLMS index was correlated with current densities at the right inferior parietal, temporoparietal junction, and middle frontal regions. In conclusion, our results suggest that the brain regions activated before periodic LM onset or associated with their severity are the large-scale motor network and provide insight into the cortical contribution of PLMS pathomechanism.

Anxiety disorders in outpatient clinics of epilepsy in tertiary care hospitals: A meta-analysis.

BACKGROUND AND PURPOSE: Although anxiety disorders (ADs) occur frequently in people with epilepsy (PWE) and impair quality of life and treatment outcomes, current efforts to categorize and investigate AD subtypes in PWE remain insufficient. Thus, the present meta-analysis aimed to determine the current prevalence rates of any AD type and various AD subtypes in PWE managed by outpatient clinics. METHODS: MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS were searched to identify and select studies that assessed the prevalence of ADs or individual AD subtypes in adult PWE under the routine care of outpatient epilepsy clinics in tertiary hospitals. Only studies that used gold-standard diagnostic tools for assessing ADs were included in this meta-analysis. RESULTS: The database search ultimately identified 15 studies, of which 9 provided current prevalence rates of any type of AD. The pooled estimated prevalence of any AD was 26.1 %. Of the 15 total studies, 13 provided current prevalence rates of generalized anxiety disorder (GAD), revealing an overall estimated prevalence of 18.2 %. In terms of current prevalence rates, GAD was highest, followed by agoraphobia, social phobia, panic disorder, and obsessive-compulsive disorder. CONCLUSIONS: Among PWE managed in the outpatient epilepsy clinics of tertiary care hospitals, the current prevalence of any AD was 26.1 %, and GAD was the most prevalent subtype of AD.

Peripheral Blood Inflammatory Cytokines in Idiopathic REM Sleep Behavior Disorder.

BACKGROUND: Although previous research provides insight into the role of neuroinflammation in idiopathic REM sleep behavior disorder, the association of this disorder with peripheral blood inflammatory markers remains unclear. OBJECTIVE: To investigate inflammatory cytokines in plasma samples in patients with idiopathic rapid eye movement sleep behavior disorder and to explore whether these markers are associated with prodromal symptoms of α-synucleinopathies. METHODS: We collected plasma from patients with polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder without parkinsonism or dementia (n = 54) and from healthy controls (n = 56). The following cytokines were measured: interleukin-1ß, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor-α. The idiopathic REM sleep behavior disorder patients underwent sleep, motor, cognitive, olfactory, and autonomic testing. RESULTS: The anti-inflammatory cytokine, interleukin-10, levels in the idiopathic rapid eye movement sleep behavior disorder group were significantly upregulated compared to the control group (P = 0.022), but this difference did not withstand Bonferroni correction. The other proinflammatory cytokine levels did not differ between the groups. No correlation was found between the cytokine levels and any clinical variable. CONCLUSIONS: Our data do not provide evidence supporting the role of peripheral inflammation in idiopathic rapid eye movement sleep behavior disorder. However, considering the limited statistical power because of the small sample size, further large-scale longitudinal studies with a broader spectrum of cytokines are needed to clarify this issue. © 2019 International Parkinson and Movement Disorder Society.

Impact of a selective cyclooxygenase-2 inhibitor, celecoxib, on cortical excitability and electrophysiological properties of the brain in healthy volunteers: A randomized, double-blind, placebo-controlled study.

The inflammatory response is considered a defence mechanism against physical or infectious insults and is prevalent within the central nervous system. Seizures also result in a robust inflammatory cascade, leading to enhanced activation of excitatory synaptic networks. Ample evidence based on animal models of epilepsy has demonstrated that celecoxib, a highly selective inhibitor of cyclooxygenase-2, has anticonvulsant effects. We aimed to evaluate the impact of celecoxib on the cortical excitability and electrophysiological properties of the brain in healthy humans. Electroencephalography (EEG) or transmagnetic stimulation (TMS) was used to measure neurophysiological activity. Forty healthy volunteers were randomized to 4 groups (n = 10 in each group): 1) celecoxib and EEG, 2) placebo and EEG, 3) celecoxib and TMS, and 4) placebo and TMS. For the EEG study, resting EEG was performed at baseline just before administering 400 mg of celecoxib or placebo and repeated 4 hours after administration. The subjects took 200 mg of celecoxib or placebo twice a day for 7 subsequent days, and a third EEG was conducted 4 hours after the final dose. Power spectra were compared at each time point. For the TMS study, the resting motor threshold (RMT), motor evoked potential (MEP) peak-to-peak amplitude, and cortical silent period (CSP) were measured at baseline and after taking 200 mg of celecoxib or placebo twice a day for 7 days. Celecoxib did not significantly change brain activity in the EEG study. However, the sum of power recorded from all electrodes tended to increase in the celecoxib group only at 4 hours after administration (p = 0.06). In detail, one dose of celecoxib (400 mg) transiently and significantly increased the alpha band power recorded in the frontal and parietal areas as well as in the whole brain (p = 0.049, 0.017, and 0.014, respectively) and the beta frequency in the central and parietal regions (p = 0.013 and 0.005, respectively), whereas the placebo did not. This effect was abolished after 7 days of treatment. In the TMS study, we found no statistically significant change in the RMT, MEP peak-to-peak amplitude or CSP. This evidence suggests that celecoxib transiently alters the electrophysiological properties of the brain but does not suppress neuronal excitability in healthy humans.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

Optimal cutoff score of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) for detecting major depressive disorder: A meta-analysis.

BACKGROUND AND PURPOSE: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a useful inventory for screening major depressive disorder (MDD) in people with epilepsy (PWE). The cutoff score for detecting MDD has been reported with the range of >11 to >16. The aim of this study was to find optimal cutoff score of the NDDI-E for MDD detection by combining the raw data from previous studies. METHODS: We searched MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS to identify proper studies. Original researches, which tested the accuracy of NDDI-E for MDD detection in adult PWE, were recruited. We included the studies in which MDD was diagnosed by a gold standard structural interview, the Mini International Neuropsychiatric Interview (MINI). In addition, we included only the studies providing enough information for meta-analysis: number of PWE with MDD, number of total PWE, and sensitivity (Se) and specificity (Spe) for each cutoff score. After collecting data from included studies, we performed a diagnostic test accuracy (DTA) meta-analysis using bivariate model. RESULTS: We identified 13 validation studies conducted in outpatient epilepsy clinic setting. As summary estimates of test accuracy measures, the Se, Spe, and diagnostic odds ratio (DOR) of NDDI-E for MDD detection were 0.81, 0.84, and 22.48, respectively. The analysis using the multiple thresholds model showed that the NDDI-E score of 13.2 was the best fit for MDD detection. When analyzing only with the seven data sets of the cutoff score >13, the Se, Spe, and DOR were 0.87, 0.80, and 25.72, respectively. CONCLUSIONS: The optimal NDDI-E cutoff score for MDD detection is >13. The information provided by this DTA meta-analysis will be a useful reference for applying NDDI-E in geographic areas where no NDDI-E validation studies have been conducted for their languages.

HLA-A*11:01 is associated with levetiracetam-induced psychiatric adverse events.

Levetiracetam (LEV) is effective for focal and generalized epilepsy and is used worldwide because of its relatively few drug interactions and favorable tolerability. However, some psychiatric adverse events (PAEs) have been reported, resulting in drug withdrawal. The pathophysiology of LEV-induced PAE has not yet been elucidated. In this study, we investigated the relationship between PAEs and human leukocyte antigen (HLA) genes. Eleven epilepsy patients, who developed PAEs after the administration of LEV and spontaneously improved after drug withdrawal, were enrolled retrospectively. Genomic DNA from the peripheral blood was extracted, and four-digit allele genotyping of HLA genes was performed. The genotype frequencies of HLA genes were compared to those of 80 patients in which LEV was well tolerated, as well as to 485 individuals from the general Korean population. The frequency of the HLA-A*1101 allele was significantly higher in the LEV-induced PAEs group compared to both the LEV-tolerant group (p = 0.021, OR 4.80, 95% CI 1.30-17.74) and the general Korean population (p = 0.015, OR 4.62, 95% CI 1.38-15.45). This study is the first attempt at investigating the relationship between the HLA system and LEV-induced PAE. The results of this study suggest that the HLA-A*1101 allele could be a risk factor for the development of PAEs.

Major depressive disorder in epilepsy clinics: A meta-analysis.

BACKGROUND AND PURPOSE: Although depression is a frequent psychiatric comorbidity in people with epilepsy (PWE), its prevalence has been underestimated. Comorbid depression has negative impacts on treatment outcomes and quality of life (QOL). It also causes various problems in PWE, such as fatigue, irritability, and suicidality. This meta-analysis was performed to estimate the frequency of major depression disorder (MDD) in clinics managing PWE. METHODS: We searched MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS to identify studies. Hospital-based studies and original research presenting information regarding prevalence of MDD, determined using a gold standard diagnostic tool in adult PWE, were considered for inclusion. The prevalence of depression was examined by meta-analysis. In addition, subgroup analysis was performed based on the continent where the selected studies were conducted, the strictness of selection criteria, and gender. Strict selection criteria were defined as any mention of the use of exclusion criteria. RESULTS: A total of 6607 studies were identified by searching the five databases outlined above. After screening and rescreening, 35 studies were included in the meta-analysis. The total number of PWE was 5434. In the test for heterogeneity of the studies, I2 was 68.014, and the Cochran Q value was 106.296 (p < 0.01). As a pooled estimate, the point prevalence of MDD in PWE was 21.9% with a 95% confidence interval (CI) of 20.8-23.0 in a fixed effects model. In subgroup analyses, continent partly explained the heterogeneity among the selected studies, but the strictness of selection criteria did not. The prevalence of MDD was higher in females than in males (26.4% vs. 16.7%, respectively) with an odds ratio (OR) of 1.805 (95% CI: 1.443-2.258; p < 0.01). CONCLUSIONS: The point prevalence of MDD is estimated at 21.9% among PWE in epilepsy clinics and is higher in females than in males. Based on this relatively high prevalence in PWE, measures are required to identify and resolve MDD. In addition, the female predominance of MDD among PWE indicates a need to pay greater attention to females. Such efforts may reduce the impact of depression in PWE and improve their QOL.

Fatal familial insomnia presenting with agrypnia excitata and very low atonia index level: A case report and literature review.

RATIONALE: Fatal familial insomnia (FFI) is a human prion disease that is characterized by sleep-wake cycle deterioration, loss of slow-wave sleep, and motor overactivation over the daily 24-hour period. PATIENT CONCERNS: Here, we report the case of a 57-year-old man who had an irregular sleep-wake cycle and exhibited frequent movements and vocalizations during sleep. DIAGNOSES: Video-polysomnography showed disrupted sleep structure, rapid alternation between sleep stages, and an absence of sleep spindles and slow-wave sleep. Moreover, body movements persisted throughout the entire sleep period, including rapid eye movement (REM) sleep. The atonia index was very low (<0.025) during REM sleep. Genetic testing revealed a prion protein gene mutation at codon 178, and the patient was diagnosed with FFI. INTERVENTIONS: We tried to treat with amantadine, doxycycline, and immunotherapies, but the disease progressed. OUTCOMES: Sleep disturbance is the most frequent and essential symptom of FFI. LESSONS: FFI is difficult to diagnose due to the low sensitivity of diagnostic tools. Diagnoses can be further supported by better knowledge of typical polysomnographic findings.