Multimodal mapping of regional brain vulnerability to focal cortical dysplasia.

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

Diffusion tensor imaging-based pontine damage as a degeneration marker in synucleinopathy.

The pons is one of the earliest affected regions in patients with synucleinopathies. We aimed to investigate the diagnostic value of measuring pontine damage using diffusion tensor imaging (DTI) in these patients. We enrolled 49 patients with Parkinson's disease (PD), 16 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), 23 patients with multiple system atrophy (MSA), and 39 healthy controls in this study. All the participants underwent high-resolution T1-weighted imaging and DTI. Mean diffusivity (MD) and fraction anisotropy (FA) values in the pons were calculated to characterize structural damage. The discriminatory power of pontine MD and FA values to differentiate patients with synucleinopathies from healthy controls was examined using receiver operating characteristics (ROC) analyses. Compared to healthy controls, patients with PD, iRBD, and MSA had increased MD values and decreased FA values in the pons, although no correlation was observed between these DTI measures and disease severity. The ROC analyses showed that MD values in the pons had a fair discriminatory power to differentiate healthy controls from patients with PD (area under the curve [AUC], 0.813), iRBD (AUC, 0.779), and MSA (AUC, 0.951). The AUC for pontine FA values was smaller than that for pontine MD values when differentiating healthy controls from patients with PD (AUC, 0.713; p = 0.054) and iRBD (AUC, 0.686; p = 0.045). Our results suggest that MD values in the pons may be a useful marker of brain stem neurodegeneration in patients with synucleinopathies.

Cerebral Infarction Observed on Brain MRI in Unconscious Out-of-Hospital Cardiac Arrest Survivors: A Pilot Study.

BACKGROUND: Cumulative evidence regarding the use of brain magnetic resonance imaging (MRI) for predicting prognosis of unconscious out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM) is available. Theoretically, these patients are at a high risk of developing cerebral infarction. However, there is a paucity of reports regarding the characteristics of cerebral infarction in this population. Thus, we performed a pilot study to identify the characteristics and risk factors of cerebral infarction and to evaluate whether this infarction is associated with clinical outcomes. METHODS: A single-center, retrospective, registry-based cohort study was conducted at Severance Hospital, a tertiary center. Unconscious OHCA survivors were registered and treated with TTM between September 2011 and December 2015. We included patients who underwent brain MRI in the first week after the return of spontaneous circulation. We excluded patients who underwent any endovascular interventions to focus on "procedure-unrelated" cerebral infarctions. We assessed hypoxic-ischemic encephalopathy (HIE) and procedure-unrelated cerebral infarction separately on MRI. Patients were categorized into the following groups based on MRI findings: HIE (-)/infarction (-), infarction-only, and HIE (+) groups. Conventional vascular risk factors showing p < 0.05 in univariate analyses were entered into multivariate logistic regression. We also evaluated if the presence of this procedure-unrelated cerebral infarction lesion or HIE was associated with a poor clinical outcome at discharge, defined as a cerebral performance category of 3-5. RESULTS: Among 71 unconscious OHCA survivors who completed TTM, underwent MRI, and who did not undergo endovascular interventions, 14 (19.7%) patients had procedure-unrelated cerebral infarction based on MRI. Advancing age [odds ratio (OR) 1.11] and atrial fibrillation (OR 5.78) were independently associated with the occurrence of procedure-unrelated cerebral infarction (both p < 0.05). There were more patients with poor clinical outcomes at discharge in the HIE (+) group (88.1%) than in the infarction-only (30.0%) or HIE (-)/infarction (-) group (15.8%) (p < 0.001). HIE (+) (OR 38.69, p < 0.001) was independently associated with poor clinical outcomes at discharge, whereas infarction-only was not (p > 0.05), compared to HIE (-)/infarction (-). CONCLUSIONS: In this pilot study, procedure-unrelated cerebral infarction was noted in approximately one-fifth of unconscious OHCA survivors who were treated with TTM and underwent MRI. Older age and atrial fibrillation might be associated with the occurrence of procedure-unrelated cerebral infarction, and cerebral infarction was not considered to be associated with clinical outcomes at discharge. Considering that the strict exclusion criteria in this pilot study resulted in a highly selected sample with a relatively small size, further work is needed to verify our findings.

Volume change in amygdala enlargement as a prognostic factor in patients with temporal lobe epilepsy: A longitudinal study.

OBJECTIVE: Considering the clinical heterogeneity of temporal lobe epilepsy with amygdala enlargement (TLE-AE), identifying distinct prognostic subgroups of TLE-AE has clinical implications. Until now, baseline volume of the enlarged amygdala (EAV) has consistently failed to predict prognosis in TLE-AE. Based on studies suggesting that patients responsive to antiepileptic drugs (AEDs) exhibit remission of AE on follow-up imaging, we investigated whether reduction rate of EAV is predictive of long-term prognosis in TLE-AE. METHODS: Sixty-one consecutive patients with two separate magnetic resonance imaging (MRI) scans were enrolled. To utilize longitudinally measured biomarkers in prediction, the period beyond the first MRI acquisition was split into two periods: the "observation window" (period between the two MRIs) and "prediction window" (follow-up period beyond the second MRI). Patients were classified according to their AED responsiveness during the observation window, and AED-responsive patients were further subdivided by initial seizure frequency: (a) AED-responsive patients presenting with low-frequency seizures (<5 seizures/3 mo; Group A, n = 25), (b) high-frequency seizures (≥5 seizures/3 mo; Group B, n = 23), and (c) patients with poor initial treatment response (Group C, n = 13). Multivariate logistic regression models were constructed for identification of prognostic factors. Along with factors obtained at baseline, factors derived from the observation window (annual percentage change of EAV [APCEAV] and initial AED responsiveness) were also considered as potential predictors. RESULTS: Favorable initial treatment response and faster volume reduction rate (APCEAV ≤ -5.0%/y) were identified as factors predictive of achieving overall seizure freedom. Among the AED-responsive patients, Group A (low-frequency seizures) showed slower remission of AE and higher rate of seizure recurrence, whereas Group B (high-frequency seizures) exhibited faster remission of AE and lower rate of seizure recurrence. SIGNIFICANCE: Faster recuperation of AE in patients with initial high-frequency seizures may be indicative of seizure-induced changes. As volume reduction rate serves as a prognostic marker in TLE-AE, short-term MRI follow-up may be useful in prognostication.

A case of dyskinesia after levetiracetam administration.

BACKGROUND: Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported. CASE PRESENTATION: A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs. DISCUSSION AND CONCLUSIONS: To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.

Subcortical shape analysis of progressive mild cognitive impairment in Parkinson's disease.

BACKGROUND: Cortical neural correlates of ongoing cognitive decline in Parkinson's disease (PD) have been suggested; however, the role of subcortical structures in longitudinal change of cognitive dysfunction in PD has not been fully investigated. Here, we used automatic analysis to explore subcortical brain structures in patients with PD with mild cognitive impairment that converts into PD with dementia. METHODS: One hundred eighty-two patients with PD with mild cognitive impairment were classified as PD with mild cognitive impairment converters (n = 74) or nonconverters (n = 108), depending on whether they were subsequently diagnosed with dementia in PD. We used surface-based analysis to compare atrophic changes of subcortical brain structures between PD with mild cognitive impairment converters and nonconverters. RESULTS: PD with mild cognitive impairment converters had lower cognitive composite scores in the attention and frontal executive domains than did nonconverters. Subcortical shape analysis revealed that PD with mild cognitive impairment converters had smaller local shape volumes than did nonconverters in the bilateral thalamus, right caudate, and right hippocampus. Logistic regression analysis showed that local shape volumes in the bilateral thalamus and right caudate were significant independent predictors of PD with mild cognitive impairment converters. In the PD with mild cognitive impairment converter group, thalamic local shape volume was associated with semantic fluency and attentional composite score. CONCLUSIONS: The present data suggest that the local shape volumes of deep subcortical structures, especially in the caudate and thalamus, may serve as important predictors of the development of dementia in patients with PD. © 2017 International Parkinson and Movement Disorder Society.

Atrophy of the pedunculopontine nucleus region in patients with sleep-predominant seizures: A voxel-based morphometry study.

Non-rapid eye movement (NREM) sleep increases interictal epileptiform discharges and frequency of seizures, whereas REM sleep suppresses them. The pedunculopontine nucleus (PPN), one of the REM sleep-modulating structures, is postulated to have a potent antiepileptogenic role. We asked if patients with sleep-predominant seizures (SPS) show volume changes in the region of the PPN compared to those with seizures occurring during awake state only (nSPS). The volume of the PPN region was assessed in patients with SPS, those with nSPS, and healthy volunteers, through voxel-based morphometry and automated, nonbiased region of interest (ROI) analysis of T1 magnetic resonance (MR) images. The volume of PPN region was statistically smaller in patients with SPS (n = 33) than in those with nSPS (n = 40) and healthy controls (n = 30) after controlling for covariates. These results suggest that a structural change in the PPN may be associated with sleep-predominant timing of seizure occurrence. Our findings might help understand the intervening pathomechanism that lies between the human sleep-wake cycle and epilepsy.

Mammillary Body Atrophy in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: We aimed to determine 1) the frequency of mammillary body (MB) atrophy in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), 2) the clinical significance of MB atrophy, and 3) the association between MB atrophy and volume changes in other subcortical limbic structures. METHODS: We enrolled 69 patients with pathologically confirmed TLE with HS, who underwent a standard anterior temporal lobectomy, as well as 40 healthy controls. We used the FreeSurfer deep-learning tool of U-Net to obtain the volumes of the subcortical limbic structures, including the MB, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens. MB atrophy was considered to be present when the MB volume was decreased relative to the healthy controls. RESULTS: MB atrophy was present in 18 (26.1%) of the 69 patients with TLE and HS. Among the clinical characteristics, the mean age at seizure onset was higher (25.5 vs. 15.9 years, p=0.027) and the median duration of epilepsy was shorter (149 vs. 295 months, p=0.003) in patients with than without MB atrophy. The basal forebrain (0.0185% vs. 0.0221%, p=0.004) and septal nuclei (0.0062% vs. 0.0075%, p=0.003) in the ipsilateral hemisphere of HS were smaller in the patients with MB atrophy. CONCLUSIONS: We observed ipsilateral MB atrophy in about one-quarter of patients with TLE and HS. The severity of subcortical limbic structure abnormalities was greater in patients without MB atrophy. These findings suggest that MB atrophy in TLE with HS is not rare, but it has little clinical significance.

Metabolic network is related to surgical outcome in temporal lobe epilepsy with hippocampal sclerosis: A brain FDG-PET study.

BACKGROUND AND PURPOSE: The aim of this study was to investigate differences in metabolic networks based on preoperative fluorodeoxyglucose (FDG)-positron emission tomography (PET) in temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) between patients with complete seizure-free (SF) and those with noncomplete seizure-free (non-SF) after anterior temporal lobectomy. METHODS: This study was retrospectively performed at a tertiary hospital. We recruited pathologically confirmed 75 TLE patients with HS who underwent preoperative FDG-PET. All patients underwent a standard anterior temporal lobectomy. The surgical outcome was evaluated at least 12 months after surgery, and we divided the subjects into patients with SF (International League Against Epilepsy [ILAE] class I) and those with non-SF (ILAE class II-VI). We evaluated the metabolic network using graph theoretical analysis based on FDG-PET. We investigated the differences in network measures between the two groups. RESULTS: Of the 75 TLE patients with HS, 32 patients (42.6%) had SF, whereas 43 patients (57.3%) had non-SF. There were significant differences in global metabolic networks according to surgical outcomes. The patients with SF had a lower assortative coefficient than those with non-SF (-0.020 vs. -0.009, p = .044). We also found widespread regional differences in local metabolic networks according to surgical outcomes. CONCLUSION: Our study demonstrates significant differences in preoperative metabolic networks based on FDG-PET in TLE patients with HS according to surgical outcomes. This work introduces a metabolic network based on FDG-PET and can be used as a potential tool for predicting surgical outcome in TLE patients with HS.

Intrinsic Thalamic Network in Temporal Lobe Epilepsy With Hippocampal Sclerosis According to Surgical Outcomes.

Background: The aim of this study was to identify the differences of intrinsic amygdala, hippocampal, or thalamic networks according to surgical outcomes in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS). Methods: We enrolled 69 pathologically confirmed TLE patients with HS. All patients had pre-operative three-dimensional T1-weighted MRI using a 3.0 T scanner. We obtained the structural volumes of the amygdala nuclei, hippocampal subfields, and thalamic nuclei. Then, we investigated the intrinsic networks based on volumes of these structures using structural covariance and graph theoretical analysis. Results: Of the 69 TLE patients with HS, 21 patients (42.1%) had poor surgical outcomes, whereas 40 patients (57.9%) had good surgical outcomes. The volumes in the amygdala nuclei, hippocampal subfields, and thalamic nuclei were not different according to surgical outcome. In addition, the intrinsic amygdala and hippocampal networks were not different between the patients with poor and good surgical outcomes. However, there was a significant difference in the intrinsic thalamic network in the ipsilateral hemisphere between them. The eccentricity and small-worldness index were significantly increased, whereas the characteristic path length was decreased in the patients with poor surgical outcomes compared to those with good surgical outcomes. Conclusion: We successfully demonstrated significant differences in the intrinsic thalamic network in the ipsilateral hemisphere between TLE patients with HS with poor and good surgical outcomes. This result suggests that the pre-operative intrinsic thalamic network can be related with surgical outcomes in TLE patients with HS.

Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia.

BACKGROUND AND OBJECTIVE: To test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD). METHODS: We used clinically acquired 3-dimensional (3D) T1-weighted and 3D fluid-attenuated inversion recovery MRI of 148 patients (median age 23 years [range 2-55 years]; 47% female) with histologically verified FCD at 9 centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed MRI-negative in 51% of patients, in whom intracranial EEG determined the focus. For risk stratification, the CNN incorporated bayesian uncertainty estimation as a measure of confidence. To evaluate performance, detection maps were compared to expert FCD manual labels. Sensitivity was tested in an independent cohort of 23 cases with FCD (13 ± 10 years). Applying the algorithm to 42 healthy controls and 89 controls with temporal lobe epilepsy disease tested specificity. RESULTS: Overall sensitivity was 93% (137 of 148 FCD detected) using a leave-one-site-out cross-validation, with an average of 6 false positives per patient. Sensitivity in MRI-negative FCD was 85%. In 73% of patients, the FCD was among the clusters with the highest confidence; in half, it ranked the highest. Sensitivity in the independent cohort was 83% (19 of 23; average of 5 false positives per patient). Specificity was 89% in healthy and disease controls. DISCUSSION: This first multicenter-validated deep learning detection algorithm yields the highest sensitivity to date in MRI-negative FCD. By pairing predictions with risk stratification, this classifier may assist clinicians in adjusting hypotheses relative to other tests, increasing diagnostic confidence. Moreover, generalizability across age and MRI hardware makes this approach ideal for presurgical evaluation of MRI-negative epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that deep learning on multimodal MRI accurately identifies FCD in patients with epilepsy initially diagnosed as MRI negative.

Nasal pain as an aura: Amygdala origin?

PURPOSE: Nasal pain, as an epileptic aura, has been poorly recognized. This study aims to demonstrate clinical features of patients with epilepsy who have nasal pain as an aura. METHODS: We retrospectively investigated consecutive patients who visited the epilepsy clinic of tertiary hospital from April 2000 to September 2019. All included patients underwent epilepsy-dedicated, high-resolution magnetic resonance imaging (MRI) examinations. All MRI studies were analyzed by visual inspection. RESULTS: Seven patients who presented nasal pain as an aura, were identified. Four patients reported nasal pain as the first aura. Four patients had right amygdala enlargement (isolated amygdala enlargement in three patients; amygdala enlargement in addition to hippocampal sclerosis in one patient), and one patient with compression of an internal carotid-posterior communicating artery aneurysm to right amygdala on brain MRI. Interictal epileptiform or ictal discharges on EEG were found in the right temporal region in five patients. In all four patients with amygdala enlargement, amygdala enlargement was ipsilateral to EEG anomalies. In all patients, nasal pain was accompanied by ictal semiological features, such as autonomic, olfactory, abdominal, or psychic auras, and focal impaired awareness seizures, which are typically associated with mesial temporal lobe epilepsy. CONCLUSIONS: Our findings suggest that nasal pain can occur as an epileptic aura in patients with temporal lobe epilepsy with probable involvement of the amygdala.

Predicting the antiepileptic drug response by brain connectivity in newly diagnosed focal epilepsy.

OBJECTIVE: Growing evidence has suggested that epilepsy is a disease with alterations in brain connectivity. The aim of this study was to investigate whether the changes in brain connectivity can predict the response to an antiepileptic drug (AED) in patients with a newly diagnosed focal epilepsy of unknown etiology. METHODS: This observational study was independently performed at two tertiary hospitals (Group A and B). Thirty-eight patients with newly diagnosed focal epilepsy of unknown etiology were enrolled in Group A and 46 patients in Group B. We divided these patients into two groups according to their seizure control after AED treatment: AED good and poor responders. We defined the AED good responders as those in whom had seizure free for at least the last 6 months while AED poor responders who were not. All of the subjects underwent diffusion tensor imaging, and graph theoretical analysis was applied to reveal the brain connectivity. We investigated the difference in the clinical characteristics and network measurements between the two groups. RESULTS: Of the network measures, the assortativity coefficient in the AED good responders was significantly higher than that in the AED poor responders in both Groups A and B (- 0.0239 vs. - 0.0473, p = 0.0110 in Group A; 0.0173 vs. - 0.0180, p = 0.0024 in Group B). The Kaplan-Meier survival analysis revealed that the time to failure to retain the first AED was significantly longer in the patients with assortative networks (assortativity coefficient > 0) than in those with disassortative networks (assortativity coefficient < 0) in Group B. CONCLUSION: We demonstrated that the assortativity coefficient differed between patients with newly diagnosed focal epilepsy of unknown etiology according to their AED responses, which suggests that the changes in brain connectivity could be a biomarker for predicting the responses to AED.

Visit-to-visit HbA1c and glucose variability and the risks of macrovascular and microvascular events in the general population.

This study evaluate association between glycemic variability and adverse vascular events in nondiabetic middle-aged adults. From 10,020 Ansung-Ansan cohort, Korean Genome, and Epidemiology Study (KoGES) data. 6,462 nondiabetic adults aged <65 years was analyzed. The mean and coefficient of variation (CV) of all biannually recorded HbA1c, fasting blood glucose(FBG), and post 2 hr blood glucose (PBG) were calculated and divided into 3 groups based on tertile of CV at each measurement, respectively. Primary endpoint was composite of Macro (composite of Coronary artery disease, Myocardial infarction, Congestive heart failure or Stroke) and Microvascular event (Creatine Clearance <60 ml/min/1.73 m2). The participants (mean age: 50 years, 50% men) were followed for a median of 9.9 (9.1-10.0) years. The high HbA1c-CV tertile (odds ratio 1.30; 1.01-1.66) was independent risk factor for microvascular events. In contrast, high FBG-CV tertile (2.32; 1.30-4.12) and PBG-CV (1.85; 1.05-3.26) was for macrovascular events. In this 10-year prespective cohort study, higher HbA1c-CV tertile was associated with higher composite of macro- and microvascular events and independent risk factor in non-DM middle-aged participants. In addition, higher tertile of FBG-CV and PBG-CV were risk factors for macrovascular events.

The Effect of Anxiety and Depression on Sleep Quality of Individuals With High Risk for Insomnia: A Population-Based Study.

Introduction: One of the most common sleep disorders, insomnia is a significant public health concern. Several psychiatric disorders, such as anxiety disorders and depression, have shown strong relationships with insomnia. However, the clinical impact of the combination of these two conditions on insomnia severity and sleep quality remains unknown. We investigated the relationship between sleep disturbance and psychiatric comorbidities in subjects with high risk for insomnia. Methods: We analyzed data from a nation-wide cross-sectional survey of Korean adults aged 19 ~ 69 years conducted from November 2011 to January 2012. The survey was performed via face-to-face interviews using a structured questionnaire. We used the insomnia severity index (ISI) to evaluate insomnia and defined respondents with ISI scores of ≥10 were considered to be at high risk for insomnia. To diagnose anxiety and depression, we used the Goldberg anxiety scale (GAS) and Patient Health Questionnaire-9 (PHQ-9), respectively. Results: Of the 2,762 respondents, 290 (10.5%) were classified as subjects with high risk for insomnia; anxiety [odds ratio (OR), 9.8; 95% confidence interval (CI), 7.3-13.1] and depression (OR, 19.7; 95% CI, 13.1-29.6) were more common in this population than in participants without insomnia. Of the participants with insomnia, 152 (52.4%) had neither anxiety nor depression, 63 (21.7%) only had anxiety, 21 (7.2%) only had depression, and 54 (18.6%) had both anxiety and depression. The group with both anxiety and depression was associated with worse scores on sleep-related scales than the other groups [high ISI, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale]. The relationship between outcome measures (ISI and PSQI) and psychiatric problems was significant only when anxiety and depression were present. The PSQI has a significant mediation effect on the relationship between psychiatric comorbidities and insomnia severity. Conclusion: Among the respondents with insomnia, psychiatric comorbidities may have a negative impact on daytime alertness, general sleep quality, and insomnia severity, especially when the two conditions are present at the same time. Clinicians should, therefore, consider psychiatric comorbidities when treating insomnia.

Sirtuin3 Protected Against Neuronal Damage and Cycled into Nucleus in Status Epilepticus Model.

In pathological conditions such as status epilepticus (SE), neuronal cell death can occur due to oxidative stress that is caused by an excessive production and accumulation of reactive oxygen species (ROS). Sirtuin3 (Sirt3) plays an important role in maintaining appropriate ROS levels by regulating manganese superoxide dismutase (MnSOD), which scavenges ROS in mitochondria. Using a SE model, we demonstrated that Sirt3 directly regulated MnSOD activity by deacetylation, which protects hippocampal cells against damage from ROS. Furthermore, we showed that after formation in the nucleus, Sirt3 is primarily located in the mitochondria, where it is activated and exerts its major function. Sirt3 then completed its pathway and moved back into the nucleus. Our data indicate that Sirt3 has an important function in regulating MnSOD, which results in decreased ROS in hippocampal cells. Sirt3 may have potential as an effective therapeutic target in SE conditions that would delay the progression of epileptogenesis.

Relationship Between Sleep Apnea and Coronary Artery Calcium in Patients With Ischemic Stroke.

Study Objectives: Coronary artery disease is considered to be the major cause of death amongst patients with ischemic stroke. The coronary artery calcium (CAC) score is related not only to sleep-disordered breathing, but also with future risk of cardiovascular mortality. We investigated the association between the severity of sleep-disordered breathing and CAC score in patients with ischemic stroke. Methods: We included 32 patients who underwent coronary multichannel computed tomography and polysomnography (within 2 years of the stroke event) amongst the patients admitted to our clinic due to acute ischemic stroke. We investigated vascular risk factors, polysomnography findings, and sleep questionnaire scores, and their relationships with the CAC score. Results: All patients were found to have sleep apnea of any degree, and 23 (72%) had severe sleep apnea. Twenty-three (72%) patients had a positive CAC score. Higher CAC scores were associated with elevated respiratory disturbance index (RDI), apnea index, oxygen desaturation index, and STOP-BANG test scores. Multivariate analysis after adjusting for potential confounding factors revealed independent relationships between the CAC score and the RDI (ß [SE] = 5.3 [2.1], p = 0.01), oxygen desaturation index (ß [SE] = 6.8 [2.8], p = 0.02), and STOP-BANG test score (ß [SE] = 90.3 [37.7], p = 0.02). Conclusion: Our findings indicate a relationship between coronary atherosclerotic burden measured by the CAC score and the severity of sleep apnea. Performing polysomnography could be useful for investigating the severity of hidden coronary artery disease among these patients. BRIEF SUMMARY: Current Knowledge/Study Rationale: The effect of sleep apnea on coronary artery disease in patients with ischemic stroke has not been explored. We investigated the relationship between sleep apnea, its related characteristics and the coronary artery calcium score in patients with stroke.Study Impact: Our findings reveal a close relationship between the atherosclerosis-related burden measured by the coronary artery calcium score and the severity of sleep apnea that persisted after adjusting for confounding variables related to the risk of coronary artery disease. Proper detection and treatment of sleep apnea might mitigate the risk of future coronary events in patients with ischemic stroke.

Clinical outcome following medical treatment of cavernous malformation related epilepsy.

PURPOSE: The study was conducted to assess the long-term outcome of antiepileptic drug (AED) treatment in drug-naïve patients with cavernous malformation (CM) related epilepsy (CRE). METHOD: This is a retrospective, single-center, long-term observational study of 34 patients with previously untreated seizures related to CM. All patients were followed-up for at least two years. Drug resistant epilepsy (DRE) was defined as two or more seizures per year after trial of two appropriate AEDs. Patients who had only one seizure during the previous one year were assigned as "epilepsy with rare seizures (ERSs)". RESULTS: Terminal 1-year seizure remission (1-YTR) was achieved in 22 (64.7%) patients, nine (26.5%) patients were diagnosed as DRE, and three (8.8%) patients were as ERSs. 1-YTR was achieved in 18 (52.9%) patients by the first drug regimen and in additional four (11.8%) patients by the second drug regimen. None of nine patients who failed to first two drug regimens did achieve 1-YTR. The location of CM in the temporal lobe was the only prognostic factor predicting a poor seizure outcome (p=0.012). CONCLUSION: The outcome of AEDs therapy in patients who were presented with new onset of CRE was quite comparable with that of patients with newly diagnosed epilepsy. Failure to achieve seizure-free after adequate trials of two AEDs seems appropriate as the criteria for their referral to surgical treatment. For patients with temporal lobe CRE, earlier presurgical evaluation may be considered justifiable once they failed to an adequate trial of the first drug.

Cognitive and Neuroanatomical Correlates in Early Versus Late Onset Parkinson's Disease Dementia.

BACKGROUND: Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset. OBJECTIVES: The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset. METHODS: A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late-onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance. RESULTS: EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044). CONCLUSIONS: Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD.

Development of epilepsy after posterior reversible encephalopathy syndrome.

PURPOSE: This study was intended to describe the risk of epilepsy subsequent to posterior reversible encephalopathy syndrome (PRES) and the clinical features of post-PRES epilepsy. METHOD: We retrospectively identified all patients with PRES who were admitted to Severance Hospital and consulted with the Department of Neurology between 2001 and 2013 and the subgroup of these patients who subsequently developed epilepsy. We also describe clinical features of patients who were not treated with PRES as inpatients at our center but who presented later with post-PRES epilepsy during the study period. We studied clinical characteristics during the acute symptomatic phase of PRES and after the development of epilepsy. RESULTS: During the study period 102 patients were treated at our center during the acute phase of PRES. Four of these patients (3.9%) subsequently developed epilepsy. Two additional patients with a history of PRES presented to our hospital after the acute phase of their illness with post-PRES epilepsy. During the acute phase, five of six patients had acute symptomatic seizures and four had convulsive or nonconvulsive status epilepticus (SE). Acute phase MRI showed cytotoxic edema in five patients, and follow-up MRI showed focal atrophic changes including hippocampal sclerosis in four. Presumptive epileptogenic foci were located in the left-side temporal, parietal and occipital lobes, corresponding to the regions that showed cytotoxic edema or severe vasogenic edema as well as with the location or lateralization of EEG abnormalities during the acute phase. CONCLUSION: Our findings indicate a small but not insignificant risk for the development of epilepsy after PRES. The presence of cytotoxic edema and severe, acute symptomatic seizures, such as SE suggests irreversible brain damage and may predict the development of epilepsy.