Spectrum of Ictal-Interictal Continuum: The Significance of 2HELPS2B Score and Background Suppression.

PURPOSE: The aims of this study were to identify (1) the spectrum of ictal-interictal continuum (IIC) using the two dimensions of 2HELPS2B score and background suppression and (2) the response to subsequent anti-seizure drugs depends on the spectrum of IIC. METHODS: The study prospectively enrolled 62 patients with IIC on EEG. The diagnosis of nonconvulsive status epilepticus was attempted with Salzburg criteria as well as clinical and neuroimaging data. IICs were dichotomized into patients with nonconvulsive status epilepticus and coma-IIC. The 2HELPS2B score was evaluated as the original proposal. The suppression ratio was analyzed with Persyst software. RESULTS: Forty-seven cases (75.8%) were nonconvulsive status epilepticus-IIC and 15 cases (24.2%) were coma-IIC. Multivariate analysis revealed that the 2HELPS2B score was the only significant variable dichotomizing the spectrum of IIC (odds ratio, 3.0; 95% confidence interval, 1.06-8.6; P = 0.03 for nonconvulsive status epilepticus-IIC). In addition, the suppression ratio was significantly negatively correlated with 2HELPS2B scores (Spearman coefficient = -0.37, P = 0.004 for left hemisphere and Spearman coefficient = -0.3, P = 0.02 for right hemisphere). Furthermore, patients with higher 2HELPS2B score (74% [14/19] in ≥2 points vs. 44% [14/32] in <2 points, P = 0.03 by χ 2 test) and lower suppression ratio (62% [23/37] in ≤2.18 vs. 35% [6/17] in >2.18, P = 0.06 by χ 2 test) seemed to be more responsive to subsequent anti-seizure drug. CONCLUSIONS: The 2HELPS2B score and background suppression can be used to distinguish the spectrum of IIC and thereby predict the response to subsequent anti-seizure drug.

Minimally Invasive Skin Transcriptome Extraction Using a Dermal Biomarker Patch.

INTRODUCTION: Advances in the scientific understanding of the skin and characteristic genomic dermal signatures continue to develop rapidly. Nonetheless, skin diagnosis remains predicated on a subjective visual examination, frequently followed by biopsy and histology. These procedures often are not sufficiently sensitive, and in the case of many inflammatory diseases, biopsies are not justified, creating a situation where high-quality samples can be difficult to obtain. The wealth of molecular information available and the pace at which new data are acquired suggest that methods for minimally invasive biomarker collection could dramatically alter our understanding of skin disease and positively impact treatment paradigms. METHODS: A chemical method was optimized to covalently modify custom dermal patches with single-stranded DNA that could bind to messenger RNA. These patches were applied to ex vivo skin samples and penetration evaluated by histological methods. Patches were then applied to both the skin of normal human subjects (lower arm) as well as lesional skin of psoriasis patients, and the transcriptome captured (N = 7; 33 unique samples). Standard RNA-Seq processing was performed to assess the gene detection rate and assessments made of the reproducibility of the extraction procedure as well as the overlap with matched punch biopsy samples from the same patient. RESULTS: We have developed a dermal biomarker patch (DBP) designed to be minimally invasive and extract the dermal transcriptome. Using this platform, we have demonstrated successful molecular analysis from healthy human skin and psoriatic lesions, replicating the molecular information captured with punch biopsy. CONCLUSION: This DBP enables an unprecedented ability to monitor the molecular "fingerprint" of the skin over time or with various interventions, and generate previously inaccessible rich datasets. Furthermore, use of the DBP could be favored by patients relative to biopsy by limiting pain resulting from biopsy procedures. Given the large dynamic range observed in psoriatic skin, analysis of complex phenotypes is now possible, and the power of machine-learning methods can be brought to bear on dermatologic disease.

Alterations in the metabolic networks of temporal lobe epilepsy patients: A graph theoretical analysis using FDG-PET.

OBJECTIVE: The aim of this study is to investigate changes in metabolic networks based on fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with drug-resistant temporal lobe epilepsy (TLE) (with and without hippocampal sclerosis [HS]) when compared with healthy controls. METHODS: We retrospectively enrolled 30 patients with drug-resistant temporal lobe epilepsy (17 patients with HS and 13 patients without HS) and 39 healthy controls. All subjects underwent interictal FDG-PET scans, which were analyzed to obtain metabolic connectivity using graph theoretical analysis. We investigated the differences in metabolic connectivity between patients with drug-resistant TLE (with and without HS) and healthy controls. RESULTS: When compared with healthy controls, TLE patients with HS showed alterations of global and local metabolic connectivity. When considering global connectivity, TLE patients with HS had a decreased average degree with increased modularity. When considering local connectivity, TLE patients with HS displayed alterations of betweeness centrality in widespread regions. However, there were no alterations of global metabolic connectivity in TLE patients without HS when compared with healthy controls. In addition, when compared to TLE patients without HS, TLE patients with HS had increased modularity. SIGNIFICANCE: Our study demonstrates more severe alterations in metabolic networks based on FDG-PET in TLE patients with HS than in those without HS and healthy controls. This may represent distinct epileptic networks in TLE patients with HS versus those without HS, although both are drug-resistant focal epilepsy.

A case of a 'rude' but not to be missed manifestation of epilepsy: ictal swearing.

Swearing is described in various neurological conditions such as Tourette syndrome, Lesch-Nyhan syndrome and post stroke or encephalitis. However, swearing as an ictal manifestation or automatism has rarely been reported. We herein describe a case with swearing as a predominant manifestation in focal epilepsy.

Characteristics of Perfusion Computed Tomography Imaging in Patients with Seizures Mimicking Acute Stroke.

INTRODUCTION: Seizures as acute stroke mimics are a diagnostic challenge. OBJECTIVE: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke. METHODS: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group. RESULTS: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan). CONCLUSIONS: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.

Cognitive Intervention with Musical Stimuli Using Digital Devices on Mild Cognitive Impairment: A Pilot Study.

The effect of music therapy on cognitive function has been widely reported; however, its clinical implications remain controversial. Performing therapeutic musical activities in groups using individualized instruments can help overcome the issues of engagement and compliance. We aimed to evaluate the effect of a cognitive intervention with musical stimuli using digital devices on mild cognitive impairment (MCI). In this prospective study, 24 patients with MCI (intervention group, 12; and control group, 12) were enrolled. We developed an electronic device with musical instruments and the Song-based Cognitive Stimulation Therapy protocol (SongCST). Patients in the intervention group underwent a 10-week cognitive intervention involving musical stimuli generated by our device. Effect of the intervention on cognitive function was evaluated by the Mini-Mental State Examination-Dementia Screening (MMSE-DS), Montreal Cognitive Assessment-Korean (MOCA-K), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB). In the intervention group, MMSE-DS and MOCA-K scores improved significantly after the 10-week intervention. The changes in MOCA-K and CDR-SB scores were significantly different between the intervention and control groups. Our study showed that music therapy with digital devices has a positive effect on the executive function and overall disease severity in patients with MCI. Our study can facilitate individualization of music therapy using digital devices in groups.

Development of a predictive scale for cardioembolic stroke using extracted thrombi and angiographic findings.

We analyzed the histopathological findings of the clots obtained from patients with acute ischemic stroke by mechanical thrombectomy. We then developed a clinical scoring system for predicting pathogenic causes in patients with undetermined ischemic stroke using these histopathological and the angiographic findings during endovascular treatment. Only cases with the occlusion of the intracranial internal carotid artery or the proximal part of the middle cerebral artery were included in this study. Histopathologic findings of clots were compared and analyzed using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST; large artery atherosclerosis, cardioembolic, and undetermined groups) and angiographic occlusion type (AOT; branching-site occlusion and truncal-type occlusion groups) classification systems. Fifty-two patients had enough clots extracted by mechanical thrombectomy for full histopathologic examination. There was no significant within-group difference in the fraction of components in the thrombi for either the TOAST or AOT system; however, the platelet distribution patterns were different. The large artery atherosclerotic group and truncal-type occlusion group had mostly peripheral patterns, whereas the cardioembolic group, undetermined group and branching-site occlusion group had mostly clustering patterns (p = 0.02 in TOAST classification; p = 0.007 in AOT classification). Patients with scores of 3 or 4 on our new scale had a sensitivity of 93.5% and a specificity of 100% for cardioembolic stroke. The BOCS2 scale, developed using a combination of the TOAST and AOT classification systems, may be helpful as an adjunctive diagnostic tool for identifying cases caused by cardiogenic embolism in patients with undetermined ischemic stroke.

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.

Thalamic nuclei volumes and network in juvenile myoclonic epilepsy.

OBJECTIVE: The aim of this study was to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with juvenile myoclonic epilepsy (JME) compared to healthy controls. METHODS: We enrolled 50 patients with JME and 42 healthy controls. We obtained structural volumes of the individual thalamic nuclei based on T1-weighted imaging and performed intrinsic thalamic network analysis using graph theoretical analysis. We analyzed the differences of thalamic nuclei volumes and intrinsic thalamic networks between the patients with JME and healthy controls. RESULTS: In the patients with JME, there were significant alterations of thalamic nuclei volumes compared to healthy controls. Right laterodorsal and left suprageniculate nuclei volumes were significantly increased (0.0019% vs 0.0014%, P < .0001; 0.0011% vs 0.0008%, P = .0006, respectively), whereas left ventral posterolateral, left ventromedial, and left pulvinar inferior nuclei volumes (0.0572% vs 0.0664%, P = .0001; 0.0013% vs 0.0015%, P = .0002; 0.0120% vs 0.0140%, P < .0001, respectively) were decreased in the patients with JME. Furthermore, the intrinsic thalamic network of the patients with JME was significantly different from that of the healthy controls. The modularity in the patients with JME was significantly increased over that in healthy controls (0.0785 vs 0.0212, P = .039). CONCLUSION: We found that there were significant alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with JME compared to healthy controls. These findings might contribute to the underlying pathogenesis of in JME.

Antiepileptic Drug Therapy in Patients with Drug-Resistant Epilepsy.

Antiepileptic drug (AED) therapy starts with an accurate diagnosis of epilepsy and is followed by sequential drug trials. Seizure freedom is largely achieved by the first two drug trials; thus, epilepsy that cannot be controlled after appropriately conducted trials of the first two drugs is defined as drug-resistant epilepsy (DRE). It is still unclear which mode of pharmacotherapy, among monotherapy and polytherapy, shows better outcomes in cases of DRE. However, in a recent large hospital cohort study over past two decades, combination therapy was associated with a progressive increase in seizure-free rate than monotherapy in DRE. The benefits of polytherapy in the management of DRE might be related to the recent introduction of many new AEDs with different and novel mechanisms of action and better pharmacokinetic and tolerability profiles. These new AEDs were introduced to the market after they have proven their superiority over placebos in randomized controlled trials (RCTs) on add-on therapy in patients with DRE. Therefore, polytherapy including these new AEDs in the regimen is the approved mode of treatment for cases of DRE; this has prompted physicians to try various combinations of polytherapy to optimize the clinical outcomes. In addition, the significant discrepancies in AED responder rates between RCTs and real-world practice may support the importance of judicious use of new drugs in polytherapy by experienced epileptologists. Most experts now agree to the concept of "rational polytherapy" consisting of mechanistic combinations of AEDs exerting synergistic interactions and to the importance of continuing trials of different rational polytherapy regimens to improve the outcome of the core population of epilepsy patients in the long term.

Sex-specific relationship of cardiometabolic syndrome with lower cortical thickness.

OBJECTIVE: To investigate whether cardiometabolic factors were associated with age-related differences in cortical thickness in relation to sex. METHODS: In this cross-sectional study, we enrolled 1,322 cognitively normal elderly (≥65 years old) individuals (774 [58.5%] men, 548 [41.5%] women). We measured cortical thickness using a surface-based analysis. We analyzed the associations of cardiometabolic risk factors with cortical thickness using multivariate linear regression models after adjusting for possible confounders and interactions with age. RESULT: Among women, hypertension (ß = -1.119 to -0.024, p < 0.05) and diabetes mellitus (ß = -0.920, p = 0.03) were independently associated with lower mean cortical thickness. In addition, there was an interaction effect between obesity (body mass index [BMI] ≥27.5 kg/m2) and age on cortical thickness in women (ß = -0.324 to -0.010, p < 0.05), suggesting that age-related differences in cortical thickness were more prominent in obese women compared to women with normal weight. Moreover, low education level (<6 years) was correlated with lower mean cortical thickness (ß = -0.053 to -0.046, p < 0.05). Conversely, among men, only being underweight (BMI ≤18.5 kg/m2, ß = -2.656 to -0.073, p < 0.05) was associated with lower cortical thickness. CONCLUSIONS: Our findings suggest that cortical thickness is more vulnerable to cardiometabolic risk factors in women than in men. Therefore, sex-specific prevention strategies may be needed to protect against accelerated brain aging.

Effect of 12-week home-based cognitive training on cognitive function and brain metabolism in patients with amnestic mild cognitive impairment.

PURPOSE: We assessed the effect of home-based cognitive intervention (HCI) on cognitive function along with brain metabolism by 18F-FDG PET in patients with amnestic MCI (aMCI). PATIENTS AND METHODS: Fifty-seven patients with aMCI from three hospitals were randomized (30 HCI, 27 control). For 12 weeks, subjects received HCI. Thirty-two subjects (15 HCI, 17 control) underwent brain 18-F-FDG-PET imaging at baseline and at 12 and 24 weeks. RESULTS: The HCI group showed significant improvement in the scores of the Controlled Oral Word Association Test (COWAT) 12 and at 24 weeks. Significant brain metabolic changes by 18F-FDG PET were not observed. CONCLUSION: The current study suggests that HCI was effective in improving general cognition along with frontal executive function in patients with aMCI.

Clinical opinion: Earlier employment of polytherapy in sequential pharmacotherapy of epilepsy.

Modern pharmacotherapy for epilepsy consists of orderly, sequential drug trials, in which antiepileptic drugs (AEDs) are chosen under the concept of individual patient-oriented (or - tailored) pharmacotherapy. Although monotherapy has been established as the preferred mode of AEDs therapy in both newly diagnosed and drug resistant epilepsies, there are still lack of evidence to favor either monotherapy or polytherapy in epilepsy, which has generated continuing controversies on the preferred mode of pharmacotherapy. However, each mode of pharmacotherapy may have both advantages and disadvantages, which are different and variable related to individual case scenario. We conducted a brief comparative overview between monotherapy and polytherapy to provide clues for earlier employment of polytherapy in each steps of sequential drug trials. Previous claims about the advantages of monotherapy over polytherapy are not supported but gradually losing its ground by the introduction of a large number of drugs carrying pharmacological advantages for combination therapy. Current evidence stresses the importance of combining drugs having synergistic interactions for better outcome of polytherapy, which has not been considered in previous clinical investigations comparing monotherapy and polytherapy. It is likely that a significant improvement in the outcome of current AEDs therapy is feasible by earlier employment of polytherapy as well as identification of combination drug regimens carrying synergistic interactions. At present, lamotrigine(LTG) and valproate(VPA) combination regimen is the only well documented synergistic regimen, but there are a long-list of candidate regimens requiring future trials in appropriate designs.

Pivotal Role of Subcortical Structures as a Network Hub in Focal Epilepsy: Evidence from Graph Theoretical Analysis Based on Diffusion-Tensor Imaging.

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.

Alterations of the brain network in idiopathic rapid eye movement sleep behavior disorder: structural connectivity analysis.

PURPOSE: To evaluate and compare structural connectivity using graph theoretical analysis in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy subjects. METHODS: Ten consecutive patients with iRBD were recruited from a single tertiary hospital. All patients had normal brain magnetic resonance imaging results on visual inspection. They did not have any other neurological disorder. Control subjects were also enrolled. All subjects underwent three-dimensional volumetric T1-weighted imaging. Absolute structural volumes were calculated using FreeSurfer image analysis software. Structural volume and connectivity analyses were performed with Brain Analysis using Graph Theory. RESULTS: Compared to healthy controls, patients with iRBD showed significant alterations in cortical and subcortical volumes, showing increased volumes of frontal cortex, thalamus, and caudate nucleus. In addition, patients with iRBD exhibited significantly different structural connectivity compared to healthy controls. In measures of global network, average degree, global efficiency, and local efficiency were decreased whereas characteristic path length was increased in iRBD patients. In measures of local network, there was significant hub reorganization in patients with iRBD. Betweenness centrality of caudate nucleus and frontal cortex was increased in patients with iRBD. CONCLUSIONS: This is the first study to report that structural volume and connectivity in patients with iRBD are significantly different from those in healthy controls. iRBD patients exhibited disrupted topological disorganization of the global brain network and hub reorganization. These alterations are implicated in the pathogenesis of iRBD. They might be potential biomarkers of iRBD.

Vascular factors and neuropathy in lower limb of diabetic patients.

Asymmetric clinical presentation in some patients with diabetic polyneuropathy may result from the different vascular environments in both lower limbs. The aim of the study is to determine the association of neuropathy with vascular factors in each lower limb of diabetic patients. A total of 102 patients (204 lower limbs) given a diagnosis of diabetic polyneuropathy were enrolled. The primary end points are sensory nerve action potential (SNAP) amplitude and conduction velocity (CV) of the sural nerve and independent variables are vascular and nonvascular factors. Vascular factors include mean arterial pressure and pulse pressure at the ankle, ankle-brachial index, and arterial stiffness assessed by pulse wave velocity. Nonvascular factors include age, gender, height, body weight, body mass index, total cholesterol, and hemoglobin A1C. Age, hemoglobin A1C, and ankle pulse pressure were inversely correlated with SNAP amplitude of the sural nerve, while no factors were correlated with CV of the sural nerve. Increased arterial stiffness was significant in the limbs group with abnormal SNAP amplitude of the sural nerve, while increased height was significant in the limbs group with abnormal CV of the sural nerve. Vascular factors were more significantly associated with decreased SNAP amplitude rather than decreased CV of the sural nerve in the nerve conduction study of diabetic patients.

Efficacy, tolerability, and blood concentration of zonisamide in daily clinical practice.

We aimed to evaluate the efficacy, tolerability, and blood concentration of zonisamide (ZNS) used in daily clinical practice. This was a retrospective study performed at a single epilepsy center and included 149 patients with epilepsy. The efficacy and retention of ZNS for 52 weeks, percentage of patients who were seizure free for 26 weeks, and the 5-year retention rate were analyzed. The tolerability was assessed based on treatment-emergent adverse effects (AEs) and the adverse effect profile (AEP). More than 70% (105/149) of patients were on ZNS polytherapy. The mean dose of ZNS was 300 ±â€¯170.6 mg/day, and the antiepileptic drug (AED) load was 2.0 ±â€¯1.1 (median 1.8, range 0.2-5.3). The retention rate for 52 weeks and the percentage of patients who were seizure-free for 26 weeks were 73% and 42%, respectively. The retention rate decreased with time and reached 43% in 5 years. Younger age of onset was a significant variable affecting retention rate for 52 weeks (p = 0.044), whereas fewer concomitant AEDs were significantly associated with being seizure free for 26 weeks (p = 0.0006). AEs were reported in 24% (36/147) of patients. The number, mechanism of action, or drug load of the AEDs did not predict the development of AEs; however, blood concentration of ZNS was significantly higher in patients with AEs (p = 0.0011) than in those without AEs. ZNS is a well-tolerated and effective AED in daily clinical practice, and several clinical factors may predict the efficacy and tolerability of ZNS.

A Nomogram for Predicting Amyloid PET Positivity in Amnestic Mild Cognitive Impairment.

BACKGROUND: Most clinical trials focus on amyloid-ß positive (Aß+) amnestic mild cognitive impairment (aMCI), but screening failures are high because only a half of patients with aMCI are positive on Aß PET. Therefore, it becomes necessary for clinicians to predict which patients will have Aß biomarker. OBJECTIVE: We aimed to compare clinical factors, neuropsychological (NP) profiles, and apolipoprotein E (APOE) genotype between Aß+ aMCI and Aß-aMCI and to develop a clinically useful prediction model of Aß positivity on PET (PET-Aß+) in aMCI using a nomogram. METHODS: We recruited 523 aMCI patients who underwent Aß PET imaging in a nation-wide multicenter cohort. The results of NP measures were divided into following subgroups: 1) Stage (Early and Late-stage), 2) Modality (Visual, Verbal, and Both), 3) Recognition failure, and 4) Multiplicity (Single and Multiple). A nomogram for PET-Aß+ in aMCI patients was constructed using a logistic regression model. RESULTS: PET-Aß+ had significant associations with NP profiles for several items, including high Clinical Dementia Rating Scale Sum of Boxes score (OR 1.47, p = 0.013) and impaired memory modality (impaired both visual and verbal memories compared with visual only, OR 3.25, p = 0.001). Also, presence of APOEɛ4 (OR 4.14, p < 0.001) was associated with PET-Aß+. These predictors were applied to develop the nomogram, which showed good prediction performance (C-statistics = 0.79). Its prediction performances were 0.77/0.74 in internal/external validation. CONCLUSIONS: The nomogram consisting of NP profiles, especially memory domain, and APOEɛ4 genotype may provide a useful predictive model of PET-Aß+ in patients with aMCI.

Reduction of ipsilateral thalamic volume in temporal lobe epilepsy with hippocampal sclerosis.

The thalamus plays an important role in the modulation of both focal and generalized seizures, but the mechanisms related to seizures may be different among epilepsy syndromes. The aim of this study is to investigate the thalamic atrophy in different epilepsy syndromes. We enrolled a total of 72 patients with epilepsy (22 patients with temporal lobe epilepsy with hippocampal sclerosis, 21 patients with extra-temporal lobe epilepsy, and 29 patients with juvenile myoclonic epilepsy). We analyzed structural volumes of the brain with FreeSurfer 5.1 software, and compared them among subgroups of epilepsy and normal control subjects. Moreover, we quantified correlations between the duration of epilepsy and the structural volumes with age and sex as covariates. The volumes of the ipsilateral hippocampus in temporal lobe epilepsy with hippocampal sclerosis were significantly smaller than those in extra-temporal lobe epilepsy and normal control subjects [analysis of variance (ANOVA), p < 0.001]. Although the volumes of the ipsilateral thalamus were not different from those of normal control subjects, the volumes of the ipsilateral thalamus were negatively correlated with duration of epilepsy in temporal lobe epilepsy with hippocampal sclerosis (r = -0.5, p = 0.02). However, the volumes of interest in extra-temporal lobe epilepsy and juvenile myoclonic epilepsy were not different from those in normal control subjects, and none of these structures were correlated with duration of epilepsy. These findings suggest that the role of the thalamus may be different in thalamo-limbic circuits among epilepsy syndromes.