Risk of encephalitis and meningitis after COVID-19 vaccination in South Korea: a self-controlled case series analysis.

BACKGROUND: Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, we sought to evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population. METHODS: We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from the Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With day 0 defined as the date of vaccination, risk window was defined as days 1-28 and the control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type. RESULTS: From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08-1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03-2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (IRR 1.03; 95% CI 0.91-1.16). CONCLUSIONS: Our findings suggest an overall increased risk of encephalitis after COVID-19 vaccination. However, the absolute risk was small and should not impede COVID-19 vaccine confidence. No significant association was found between the risk of meningitis and COVID-19 vaccination.

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).

Working memory deficits in patients with idiopathic restless legs syndrome are associated with abnormal theta-band neural synchrony.

Cognitive impairment, particularly prefrontal function, has been reported in patients with restless legs syndrome. However, working memory performance in patients with restless legs syndrome remains uncertain. The present study aimed to examine working memory performance in patients with restless legs syndrome by investigating electroencephalography theta-band oscillations within task-relevant brain regions and the synchronization among oscillations during a working memory task. Twelve female idiopathic patients with restless legs syndrome and 12 female healthy controls participated in this study. Nineteen-channel electroencephalography data were recorded while participants performed a Sternberg working memory task. We analysed event-related theta-band activity and interregional theta-band phase synchrony during the memory retrieval phase. The spatial pattern of theta-band phase synchrony was quantified using graph theory measures, including the clustering coefficient, characteristic path length, and small-world propensity. Considerable increases in theta-band activity and theta-band phase synchrony were observed at 600-700 ms in controls and at 650-750 ms in restless legs syndrome subjects after the probe item was presented. During this period, induced theta-band activity showed lower with borderline significance in the restless legs syndrome subjects than in the controls regardless of channel location (F4,88  = 3.92, p = .06). Theta-band phase synchrony between the frontal and posterior regions was significantly reduced in the restless legs syndrome subjects. Inefficiency in both global and local networks in the restless legs syndrome subjects was revealed by the decreased small-world propensity (t22  = 2.26, p = .03). Small-world propensity was negatively correlated with restless legs syndrome severity (r = -.65, p = .02). Our findings suggest that patients with restless legs syndrome have multiple deficits in cognitive processes, including attentional allocation, evaluation of incoming stimuli, and memory manipulation of encoded information during a working memory task. Abnormal local theta-band neural synchrony and global theta-band neural synchrony may underlie the neurophysiological mechanism of the working memory dysfunction associated with restless legs syndrome.

Effects of perampanel on cognition and quantitative electroencephalography in patients with epilepsy.

Antiepileptic drugs are well known for their effects on cognition and electrophysiologic changes. However, perampanel is yet to be evaluated for its effects on cognitive function and electroencephalography (EEG). The purpose of the present study was to identify the effect of perampanel on neuropsychological (NP) tests and quantitative EEG (QEEG) and their relationship with the level of the drug in blood. Seventeen patients with epilepsy were enrolled in the study. Electroencephalographic recordings were obtained, and NP tests were conducted before perampanel intake and 6 months after treatment. The relative frequency band power, peak alpha frequency, and NP test scores were compared before and after drug administration. The serum concentration of perampanel was correlated with the QEEG changes. Delayed recall of the Rey Complex Figure showed significant improvement (20.03 vs. 22.94; P = 0.004) following perampanel administration. Other cognitive function tests showed no significant differences before and after drug administration. Theta frequency band power increased in all brain regions (P = 0.001-0.01), and alpha frequency power decreased in all brain regions (P = 0.006-0.03). The theta/alpha ratio, which represents background EEG slowing, increased in all brain areas (P = 0.003-0.02). The peak frequency of the alpha rhythm decreased after perampanel intake (t = 2.45, P = 0.03). Difference of relative alpha power in the central region positively correlated with the blood level of perampanel (r = 0.53, P = 0.03). Perampanel induced electrophysiological slowing, but cognitive decline was not observed. Because the controls were not compared in the study, the results of cognitive function tests should be interpreted conservatively. Background EEG slowing correlated with the serum concentration of perampanel. Our results show the effect of perampanel on cognitive function and background EEG in adult patients with epilepsy.

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.

Treatment of epilepsy in adults: Expert opinion in South Korea.

OBJECTIVE: The aim of this study was to gather the expert opinions of Korean epileptologists regarding the treatment of adult patients with epilepsy. METHODS: A total of 42 neurologists who specialized in epilepsy were surveyed. They completed an online questionnaire describing multiple patient scenarios. Using these scenarios, they evaluated treatment strategies and gave their preference for specific antiepileptic drugs (AEDs) used to treat genetically mediated generalized epilepsy and focal epilepsy. RESULTS: Initial AED monotherapy, followed by a second form of alternative monotherapy or an add-on combination therapy, was the preferred treatment strategy. The experts reached consensus for 87.2% of the items. The most commonly selected AEDs for the initial monotherapy for patients with generalized epilepsy were levetiracetam or valproate. For those with focal epilepsy, levetiracetam, oxcarbazepine, or lamotrigine were the most popular selections. Ethosuximide was the treatment of choice only for patients with generalized epilepsy with prominent absence seizures. Levetiracetam was preferred as an add-on therapy for both generalized and focal epilepsy. For special populations of patients, such as elderly adults or those with comorbid diseases, levetiracetam or lamotrigine was selected as the treatment of choice. CONCLUSION: Most of the survey results were in accordance with the US expert opinion survey published in 2016. This survey can assist clinicians in making clinical decisions when treating individual adult patients with epilepsy.

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.

Anti-LGI1 encephalitis is associated with unique HLA subtypes.

OBJECTIVE: Autoimmune encephalitis (AE), represented by anti-leucine-rich glioma-inactivated 1 (anti-LGI1) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes. METHODS: We compared the HLA genotypes of 11 anti-LGI1 and 17 anti-NMDAR encephalitis patients to the control groups, which consisted of 210 epilepsy patients and 485 healthy Koreans. RESULTS: Anti-LGI1 encephalitis was associated with the DRB1*07:01-DQB1*02:02 haplotype (10 patients; 91%) in HLA class II genes, as well as with B*44:03 (8 patients; 73%) and C*07:06 (7 patients; 64%) in the HLA class I region. The prevalence of these alleles in anti-LGI1 encephalitis was significantly higher than that in the epilepsy controls or healthy controls. By contrast, anti-NMDAR encephalitis was not associated with HLA genotypes. Additional analysis using HLA-peptide binding prediction algorithms and computational docking underpinned the close relationship. INTERPRETATION: This finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.

Increased adverse events associated with antiepileptic drugs in anti-leucine-rich glioma-inactivated protein 1 encephalitis.

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti-LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti-LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti-LGI1 encephalitis.

Clinical manifestations and treatment outcomes of parvovirus B19 encephalitis in immunocompetent adults.

Parvovirus B19 (PVB19) has rarely been identified as a cause of encephalitis in immunocompetent adults, in whom clinical information regarding PVB19 encephalitis has remained unclear. Herein, we report the clinical presentations, laboratory and imaging findings, and treatment outcomes of five immunocompetent adults with PVB19 encephalitis. Although none of the patients showed any distinctive features of PVB19 infection, they showed various clinical manifestations, including one instance of brainstem involvement. Additionally, immunotherapy can be considered an effective approach, especially in immunocompetent adults with PVB19 encephalitis who are resistant to the initial management.

HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption.

OBJECTIVE: Oxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced cADRs have been identified. However, the HLA-related genetic risk factors associated with OXC-induced cADRs are unknown. METHODS: A total of 40 patients who experienced OXC-induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high-resolution HLA genotyping was performed. RESULTS: The HLA-B*40:02 and HLA-DRB1*04:03 alleles were significantly associated with OXC-induced MPE compared with the OXC-tolerant group (odds ratio [OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population (OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA-B*15:01 genetic frequency was significantly lower in the OXC-MPE group compared to the OXC-tolerant group (OR 0.18, p = 0.016) and the Korean population (OR 0.22, p = 0.030). The allele frequencies of well-known HLA-related risk factors for carbamazepine-induced cADRs (HLA-B*15:02, A*31:01 and B*15:11) were not different among the three groups. SIGNIFICANCE: This study is the first to demonstrate an association of HLA-B*40:02 and HLA-DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC-induced MPE. These findings should be confirmed in future studies in different ethnic groups.

Prediction of mortality and functional outcome from status epilepticus and independent external validation of STESS and EMSE scores.

BACKGROUND: Two clinical scoring systems, the status epilepticus severity score (STESS) and the epidemiology-based mortality score in status epilepticus (EMSE), are used to predict mortality in patients with status epilepticus (SE). The aim of this study was to compare the outcome-prediction function of the two scoring systems regarding in-hospital mortality using a multicenter large cohort of adult patients with SE. Moreover, we studied the potential role of these two scoring systems in predicting the functional outcome in patients with SE. METHODS: The SE cohort consisted of patients from the epilepsy centers of eight academic tertiary medical centers in South Korea. The clinical and electroencephalography data for all adult patients with SE from January 2013 to December 2014 were derived from a prospective SE database. The primary outcome variable was defined as in-hospital death. The secondary outcome variable was defined as a poor functional outcome, i.e., a score of 1-3 on the Glasgow Outcome Scale, at discharge. RESULTS: Among the 120 non-hypoxic patients with SE recruited into the study, 16 (13.3%) died in the hospital and 64 (53.3%) were discharged with a poor functional outcome. The receiver-operating characteristic (ROC) curve for prediction of in-hospital death based on the STESS had an area under the curve of 0.673 with an optimal cutoff value for discrimination (best match for both sensitivity (0.56) and specificity (0.70)) that was ≥ 4 points. The two combinations of elements of the EMSE system (EMSE-ALDEg and EMSE-ECLEg) predicted not only in-hospital mortality with the best match for sensitivity (more than 0.6) and specificity (more than 0.6), but also a poor functional outcome with the best match for both sensitivity (>0.7) and specificity (>0.6). STESS did not predict a poor functional outcome (area under the ROC, 0.581; P = 0.23). CONCLUSION: Although the EMSE is a clinical scoring system that focuses on individual mortality, we did not find differences between the EMSE and STESS in the prediction of in-hospital death. The EMSE was useful in predicting poor functional outcome, as it was significantly better than STESS.

Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome.

BACKGROUND: Patients with postural tachycardia syndrome often appear depressive and report diminished quality of life (QOL). In the current study, we first evaluated if the maximal heart rate (HR) increment after standing is associated with the clinical symptoms in patients with excessive orthostatic tachycardia (OT). Next, we investigated the correlations among the symptoms of orthostatic intolerance (OI), depression, and health-related QOL in these patients. Finally we assessed if patients with minimal OI symptoms suffer from depression or diminished QOL. METHODS: We performed a comprehensive questionnaire-based assessment of symptoms in 107 patients with excessive OT with a ≥ 30 beats/min heart rate increment (or ≥ 40 beats/min in individuals aged between 12 and 19) within 10 min after standing up. An existing orthostatic intolerance questionnaire (OIQ), the Beck depression inventory-II (BDI-II), and the 36 Item Short-Form Health Survey were completed prior to any treatment. Correlation analyses among the items of the questionnaires and other parameters were performed. Additionally, patients with minimal OI symptoms were analysed separately. RESULTS: The maximal orthostatic HR increment was not associated with the clinical symptoms. The OI symptoms were significantly correlated with depression and diminished QOL. The BDI-II score demonstrated a positive linear relationship with total OIQ score (r = 0.516), and both physical and mental component summary scales of SF-36 showed a negative linear relationship with total OIQ score (r = -0.542 and r = -0.440, respectively; all p <0.001). Some OI symptoms were more strongly associated with depression, and others were more strongly related to QOL. Chest discomfort and concentration difficulties were the most influential OI symptoms for depression, while nausea and concentration difficulties were the most influential symptoms for physical and mental QOL, respectively. Dizziness and headache were the two most common complaints in patients with mild to moderate OI symptoms. In addition, subjects with minimal OI symptoms also had considerable deterioration in QOL. CONCLUSION: The OI symptoms, but not the maximal HR increment, are significantly correlated with depression and diminished QOL in patients with excessive OT. Therefore, pervasive history taking is important when encountering patients with excessive OT.

Dysregulation of long non-coding RNAs in mouse models of localization-related epilepsy.

Genome-wide profiling has revealed that eukaryotic genomes are transcribed into numerous non-coding RNAs. In particular, long non-coding RNAs (lncRNAs) have been implicated in various human diseases due to their biochemical and functional diversity. Epileptic disorders have been characterized by dysregulation of epigenetic regulatory mechanisms, and recent studies have identified several lncRNAs involved in neural development and network function. However, comprehensive profiling of lncRNAs implicated in chronic epilepsy has been lacking. In this study, microarray analysis was performed to obtain the expression profile of lncRNAs dysregulated in pilocarpine and kainate models, two models of temporal lobe epilepsy commonly used for studying epileptic mechanisms. Total of 4622 lncRNAs were analyzed: 384 lncRNAs were significantly dysregulated in pilocarpine model, and 279 lncRNAs were significantly dysregulated in kainate model compared with control mice (≥3.0-fold, p < 0.05). Among these, 54 and 14 lncRNAs, respectively, had adjacent protein-coding genes whose expressions were also significantly dysregulated (≥2.0-fold, p < 0.05). Majority of these pairs of lncRNAs and adjacent genes shared the same direction of dysregulation. For the selected adjacent gene-lncRNA pairs, significant Gene Ontology terms were embryonic appendage morphogenesis and neuron differentiation. This was the first study to comprehensively identify dysregulated lncRNAs in two different models of chronic epilepsy and will likely provide a novel insight into developing lncRNA therapeutics.

The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population.

The use of lamotrigine (LTG) can be limited by the occurrence of cutaneous adverse drug reactions (cADRs) that range from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [OR] 4.09, p = 0.025) and the general Korean population (OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG-MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG-MPE group when compared to the LTG-tolerant group (OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population.

A case of lacosamide-induced hepatotoxicity.

INTRODUCTION: Lacosamide is a novel antiepileptic drug that acts mainly via the selective enhancement of slow inactivation of voltage-gated sodium channels. It has been reported that lacosamide is effective and generally tolerable as an adjuvant treatment in patients with partial seizures. There are few reports regarding liver damage caused by lacosamide. We describe a case of a patient with drug-resistant epilepsy who developed symptomatic hepatotoxicity after lacosamide administration. RESULTS: A 22-year-old female with a 2-year history of temporal lobe epilepsy was admitted to our hospital because of nausea, dizziness, and abnormal liver function tests. Lacosamide was added for further seizure control 9 days before the current presentation. Her liver enzymes were markedly increased: aspartate aminotransferase, 635 U/L; alanine aminotransferase, 697 U/L. Lacosamide was ceased immediately, whereas other medications (zonisamide, clobazam, and tianeptine) were not withdrawn. The level of liver enzymes improved significantly within a few days, and a diagnosis of lacosamide-induced hepatitis was made based on the obvious temporal relationship. CONCLUSION: This case report demonstrates that hepatotoxicity may develop in association with lacosamide therapy. Liver function tests should be prompted in patients with symptoms suggestive of adverse effects after the initiation of lacosamide. Further research is required to identify predisposing factors of lacosamideinduced hepatotoxicity.

Infarct pattern and clinical outcome in acute ischemic stroke following middle cerebral artery occlusion.

BACKGROUND: Cerebral arterial occlusion develops via two distinct mechanisms: thrombosis and embolism. Discrimination between thrombosis and embolism is an important aspect needed for further determining the etiology of stroke in a patient. This study evaluated infarct patterns and outcomes in acute stroke patients with relevant artery occlusions, focusing on features specific to each occlusion mechanism. METHODS: Acute ischemic stroke patients who were consecutively registered in a tertiary hospital between 2002 and 2010 with infarctions in the middle cerebral artery territory and a corresponding M1 occlusion confirmed by magnetic resonance angiography, computed tomography angiography, or conventional angiography were enrolled. Patients with a high-risk cardioembolic source, clear recanalization, concurrent infarct in an arterial territory other than the occlusion site, or no prior occlusion in a previous imaging within 1 month were assigned to the embolic occlusion group, and the remaining patients were assigned to the thrombotic occlusion group. The infarct pattern was categorized into seven groups: scattered, territorial, lenticulostriatal, scattered-territorial, scattered-lenticulostriatal, territorial-lenticulostriatal, and scattered-territorial-lenticulostriatal. Data of stroke recurrence and mortality were collected through electronic medical record and the National Vital Statistics System. RESULTS: Of 114 patients, 54 (47.4%) were classified as having an embolic occlusion. When infarct patterns were compared between the groups, any-scattered infarct pattern was more common in the thrombotic occlusion group (71.2% vs. 40.7%, p = 0.002), and any-territorial infarct pattern was more prevalent in the embolic occlusion group (55.6% vs. 28.8%, p = 0.005). In addition, scattered-without-territorial pattern was higher in the thrombotic occlusion group (OR: 0.25; CI: 0.11-0.57; p = 0.001). Any-territorial infarct pattern was also related to initial stroke severity (NIHSS on admission, OR: 400.98; CI: 2.94-54,741.32; p = 0.017) and poor functional outcome (modified Rankin Scale score ≥4) at discharge (OR: 14.40; CI: 1.37-152.00; p = 0.027) independent of other parameters. However, no association was found between stroke recurrence, mortality and occlusion mechanism. CONCLUSION: This study shows that specific infarct patterns are related to cerebral arterial occlusion mechanisms and are correlated with functional outcome. Otherwise, the results of our study indicates that infarct patterns on DWI might be a clue for determining ischemic stroke etiology on patients with major cerebral artery occlusion.

Safety of tianeptine use in patients with epilepsy.

Depression is a frequent comorbidity in patients with epilepsy (PWE). However, it is often undertreated because of concerns of seizure exacerbation by antidepressant treatment. The effect of tianeptine on seizure frequency is not known as yet. Thus, we aimed to evaluate the influence of tianeptine on the seizure frequency in PWE. We retrospectively reviewed the medical records of PWE who received tianeptine between January 2006 and June 2013 at the Epilepsy Center of Seoul National University Hospital. Patients were excluded if the dose or type of antiepileptic drugs (AEDs) they took was altered at the start of tianeptine treatment or if the treatment period of tianeptine was <3 months. A total of 74 PWE were enrolled in our study (male: 32, mean age: 41.9±14.5). Sixty-nine patients had localization-related epilepsy, and 5 had idiopathic generalized epilepsy (IGE). Mean seizure frequency during the 3-month period just after tianeptine exposure was compared with the baseline seizure frequency, which showed no change in 69 (93.2%) patients, decrease in 2 (2.7%) patients, and increase in 3 patients (4.1%). The type of epileptic syndrome, the baseline seizure frequency, and the number of coadministered AEDs did not influence the change in seizure frequency after tianeptine prescription. Change in seizure frequency did not differ between the patients given tianeptine as an additive antidepressant and those given tianeptine as a replacement antidepressant. Our data suggest that tianeptine can be prescribed safely to PWE with depression without increasing the seizure frequency regardless of the baseline severity of epilepsy. Tianeptine may be actively considered as a first-choice antidepressant or as an alternative antidepressant in PWE with depression.

Electroencephalographic spectro-spatial covariance patterns related to phenoconversion in isolated rapid eye movement sleep behavior disorder and their longitudinal trajectories in α-synucleinopathies.

STUDY OBJECTIVES: This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD) patients and explore their longitudinal trajectories within α-synucleinopathies. METHODS: We assessed 47 participants, including 35 patients with iRBD and 12 healthy controls (HC), through baseline eye-closed resting EEGs. Patients with iRBD underwent follow-up EEG assessments and 18 patients with iRBD converted (12 to Parkinson's disease (PD), 6 to dementia with Lewy bodies [DLB]) during follow-up. We derived EEG spectro-spatial covariance patterns for PD-RBD and DLB-RBD from converters and HC. Correlations with motor and cognitive function, baseline distinctions among iRBD converters and nonconverters, and longitudinal trajectories were examined. RESULTS: At baseline, converters exhibited higher PD-RBD and DLB-RBD beta2 pattern scores compared to nonconverters (each area under curve [AUC] = 0.7751). The delta and alpha spatial patterns effectively distinguished both PD and DLB converters from HC, with the alpha pattern showing high discriminative power (AUC = 0.9097 for PD-RBD, 0.9306 for DLB-RBD). Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III scores correlated positively with PD-RBD and DLB-RBD delta patterns (Spearman's rho = 0.688, p = 0.00014; rho = 0.539, p = 0.0055, respectively), with age and sex as cofactors. Distinct trajectories emerged during follow-up among PD converters, DLB converters, and iRBD nonconverters. CONCLUSIONS: Unique EEG spectro-spatial patterns specific to PD-RBD and DLB-RBD offer potential as predictive markers for phenoconversion to α-synucleinopathies in iRBD.

EEG-based machine learning models for the prediction of phenoconversion time and subtype in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies and eventually phenoconverts to overt neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Associations of baseline resting-state electroencephalography (EEG) with phenoconversion have been reported. In this study, we aimed to develop machine learning models to predict phenoconversion time and subtype using baseline EEG features in patients with iRBD. METHODS: At baseline, resting-state EEG and neurological assessments were performed on patients with iRBD. Calculated EEG features included spectral power, weighted phase lag index, and Shannon entropy. Three models were used for survival prediction, and four models were used for α-synucleinopathy subtype prediction. The models were externally validated using data from a different institution. RESULTS: A total of 236 iRBD patients were followed up for up to 8 years (mean 3.5 years), and 31 patients converted to α-synucleinopathies (16 PD, 9 DLB, 6 MSA). The best model for survival prediction was the random survival forest model with an integrated Brier score of 0.114 and a concordance index of 0.775. The K-nearest neighbor model was the best model for subtype prediction with an area under the receiver operating characteristic curve of 0.901. Slowing of the EEG was an important feature for both models. CONCLUSIONS: Machine learning models using baseline EEG features can be used to predict phenoconversion time and its subtype in patients with iRBD. Further research including large sample data from many countries is needed to make a more robust model.