Clinical Performance Evaluation of an Artificial Intelligence-Powered Amyloid Brain PET Quantification Method.

Purpose: This study assesses the clinical performance of BTXBrain-Amyloid, an artificial intelligence-powered software for quantifying amyloid uptake in brain PET images. Methods: 150 amyloid brain PET images were visually assessed by experts and categorized as negative and positive. Standardized uptake value ratio (SUVR) was calculated with cerebellum grey matter as the reference region, and receiver operating characteristic (ROC) and precision-recall (PR) analysis for BTXBrain-Amyloid were conducted. For comparison, same image processing and analysis was performed using Statistical Parametric Mapping (SPM) program. In addition, to evaluate the spatial normalization (SN) performance, mutual information (MI) between MRI template and spatially normalized PET images was calculated and SPM group analysis was conducted. Results: Both BTXBrain and SPM methods discriminated between negative and positive groups. However, BTXBrain exhibited lower SUVR standard deviation (0.06 and 0.21 for negative and positive, respectively) than SPM method (0.11 and 0.25). In ROC analysis, BTXBrain had an AUC of 0.979, compared to 0.959 for SPM, while PR curves showed an AUC of 0.983 for BTXBrain and 0.949 for SPM. At the optimal cut-off, the sensitivity and specificity were 0.983 and 0.921 for BTXBrain and 0.917 and 0.921 for SPM12, respectively. MI evaluation also favored BTXBrain (0.848 vs. 0.823), indicating improved SN. In SPM group analysis, BTXBrain exhibited higher sensitivity in detecting basal ganglia differences between negative and positive groups. Conclusion: BTXBrain-Amyloid outperformed SPM in clinical performance evaluation, also demonstrating superior SN and improved detection of deep brain differences. These results suggest the potential of BTXBrain-Amyloid as a valuable tool for clinical amyloid PET image evaluation.

Probable secondary hemophagocytic lymphohistiocytosis manifesting as central nervous system lesions after COVID-19 vaccination: a case report.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory disease commonly characterized by histiocyte infiltration in multiple organs, such as the liver, spleen, lymph nodes, bone marrow, and central nervous system. The clinical features of HLH include fever, splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated blood ferritin levels. HLH is categorized as either primary or secondary. Coronavirus disease 2019 (COVID-19) vaccines may occasionally trigger secondary HLH, which is related to hyperinflammatory syndrome. Case presentation: A 58-year-old woman, previously diagnosed with Graves' disease, presented with cognitive decline 2 weeks after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Brain MRI revealed a hyperintense lesion on T2-weighted and fluid-attenuated inversion recovery images in the bilateral subcortical white matter and right periventricular area. Vaccination-associated acute disseminated encephalomyelitis was suspected and methylprednisolone and intravenous immunoglobulin (IVIg) were administered. From the 5th day of IVIg administration, the patient developed fever and pancytopenia. In the findings of bone marrow biopsy, hemophagocytosis was not observed; however, six of the eight diagnostic criteria for HLH-2004 were met, raising the possibility of HLH. Although there was no definitive method to confirm causality, considering the temporal sequence, suspicion arose regarding vaccine-induced HLH. Splenectomy was considered for therapeutic and diagnostic purposes; however, the patient died on the 28th day of hospitalization owing to multiple organ failure. Conclusion: To date, 23 cases of COVID-19 vaccine-related HLH have been reported. Additionally, HLH in COVID-19 patients has been reported in various case reports. To the best of our knowledge, this is the first reported case of central nervous system involvement in HLH related to any type of COVID-19 vaccine. This case suggests that even when there are no systemic symptoms after COVID-19 vaccination, HLH should be considered as a differential diagnosis if brain lesions are suggestive of CNS demyelinating disease.

Modified RCTU Score: A Semi-Quantitative, Visual Tool for Predicting Alzheimer's Conversion from aMCI.

This research evaluated the modified RCTU score, derived from amyloid PET scans, for predicting the progression from amnestic Mild Cognitive Impairment (aMCI) to Alzheimer's Disease (AD). aMCI patients underwent baseline evaluations, including amyloid PET. AD conversion was identified through neuropsychological tests after observation. The RCTU was modified by segmenting frontal, parietal, and temporal lobes into left and right, resulting in seven areas. Scores from both modified and conventional RCTU were analyzed and compared. Among 45 patients, 12 progressed to AD (over 17.8 ± 6.8 months). AD converters showed higher scores in modified RCTU scores. Modified RCTU score had strong correlations with amyloid SUVR (r > 0.7). Modified RCTU sum score was the significant covariate of AD conversion. Modified RCTU could determine the asymmetry of amyloid deposits. We demonstrated that symmetric deposits of amyloid showed a higher risk for AD conversion when analyzed using modified RCTU. The modified RCTU score is a promising method for predicting AD conversion, correlating strongly with amyloid SUVR.

Orthodontic tooth extrusion to regenerate missing papilla adjacent to maxillary anterior single implants: A 2- to 7-year retrospective study.

INTRODUCTION: Regeneration of the missing papilla adjacent to single implants in the esthetic zone has always been challenging, despite advances in vertical hard and soft tissue regeneration. Orthodontic tooth extrusion has been shown to effectively gain alveolar bone and gingival tissue. This retrospective study evaluated the effectiveness of orthodontic tooth extrusion on regenerating missing papilla between existing maxillary anterior single implant and its adjacent tooth. METHODS: Patients who underwent orthodontic tooth extrusion to regenerate missing papilla adjacent to a single implant in the esthetic zone were included in this study. The gingival phenotype, orthodontic extrusion movement, proximal bone level, dento-implant papilla level, facial gingival level, mucogingival junction level, and keratinized tissue width, of the extruded tooth were recorded at pre-orthodontic extrusion (T0 ), post-orthodontic extrusion and retention (T1 ), and latest follow-up (T2 ). RESULTS: A total of 17 maxillary single tooth had orthodontic tooth extrusion to regenerate missing papilla adjacent to 14 maxillary anterior single implants in 14 patients. After a mean follow-up time of 48.4 months, implant success rate was 100% (14/14), with none of the orthodontically extruded teeth being extracted. After a mean extrusion and retention period of 14.3 months, a mean orthodontic extrusion movement of 4.62 ± 0.78 mm was noted with a mean proximal bone level gain of 3.54 ± 0.61 mm (77.0% efficacy), dento-implant papilla level gain of 3.98 ± 0.81 mm (86.8% efficacy), and facial gingival tissue gain of 4.27 mm ± 0.55 mm (93.4% efficacy). A mean keratinized tissue width gain of 4.17 ± 0.49 mm with minimal mean mucogingival junction level change of 0.10 ± 0.30 mm were observed. The efficacy of orthodontic eruption movement on dento-implant papilla gain was less in the thin (80.5%) phenotype group when compared with that in the thick (91.5%) phenotype group. CONCLUSIONS: Within the confines of this study, orthodontic extrusion is an effective, noninvasive method in regenerating mid-term stable proximal bone and papilla adjacent to maxillary anterior single implants. CLINICAL SIGNIFICANCE: This retrospective study presents a mid-term result on orthodontic extrusion as a mean to regenerate dento-implant papilla defect. The extended retention period following orthodontic extrusion showed stable and efficacious proximal bone and papilla gain.

Neuromyelitis optica spectrum disorder with herpes simplex viral infection presenting with syndrome of inappropriate antidiuretic hormone: A case report.

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disease that causes lesions in areas with abundant aquaporin-4 (AQP4) channels, including the hypothalamus. Hypothalamic lesions can disrupt antidiuretic hormone regulation, resulting in hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH). Various factors can trigger NMOSD, including viral infections. We report the case of a young female patient who presented with hyponatremia due to SIADH and was found to have bilateral hypothalamic lesions along with positive serum herpes simplex virus immunoglobulin M. PATIENT CONCERNS: An 18-year old female patient presented with fever and nausea that had persisted for 5 days. Three days after hospitalization, the patient complained of blurred vision, hiccups, and excessive daytime sleepiness. DIAGNOSIS: The patient hyponatremia was attributed to SIADH. Magnetic resonance imaging revealed bilateral lesions in the hypothalamus, and serum laboratory tests were positive for herpes simplex virus immunoglobulin M. On the 15th day of admission, the anti-AQP4 antibody test result was positive, leading to the diagnosis of NMOSD. INTERVENTIONS: On the initial suspicion of herpes encephalitis, treatment with acyclovir was initiated. However, upon the confirmation of after anti-AQP4 antibody, the patient was additionally treated with a high-dose intravenous steroid for 5 days. OUTCOMES: The patient fever, nausea, visual disturbances, and other complaints improved within 1 week of initiating steroid treatment. LESSONS: In young patients presenting with hyponatremia and suspected SIADH accompanied by neurological abnormalities, it is crucial to differentiate central nervous system diseases, including NMOSD, which can involve lesions in AQP4-abundant areas, such as the hypothalamus.

Facial Mucosal Level Change Following Maxillary Anterior Single Immediate Tooth Replacement in Extraction Sockets With Facial Bone Wall Defects: A 4- to 15-Year Retrospective Study.

An intact extraction socket has been considered a prerequisite for an immediate implant placement and provisionalization (IIPP) procedure. Recent studies, however, have shown successful outcomes when IIPP was performed in sockets with a facial bone wall defect. This retrospective study evaluated the facial implant mucosal stability following IIPP in extraction sockets with a facial bone wall defect in the esthetic zone. The study included 16 cases in 16 patients who received maxillary anterior single IIPP with contour bone graft (C-BG) and contour connective tissue graft (C-CTG) in compromised extraction sockets (V- or U-shaped defect). After a mean follow-up of 6 years, the implant success rate was 100% (16/16). Minimal and non-statistically significant changes were noted in the facial implant mucosal and marginal bone level. Statistically significant changes were observed in facial implant mucosal thickness gain (2.5 mm [1.8 mm to 3.5 mm]) and midfacial bone sounding reduction (6 mm). Within the confines of this study, IIPP with simultaneous C-BG and C-CTG in fresh extraction sockets exhibiting a V- or U-shaped facial bone wall defect can lead to long-term successful outcomes in terms of mucosal stability, contour bone gain, and marginal bone level stability.

Efficacy of a Mobile-Based Multidomain Intervention to Improve Cognitive Function and Health-Related Outcomes Among Older Korean Adults with Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) is a self-reported experience of declining cognitive function showing normal performance in cognitive assessments, which is a known risk factor for dementia. Recent studies highlight the importance of nonpharmacological multidomain interventions that can target multiple risk factors of dementia in older adults. OBJECTIVE: This study investigated the efficacy of the Silvia program, a mobile-based multidomain intervention, to improve cognitive function and health-related outcomes of older adults with SCD. We compare its effects to a conventional paper-based multidomain program on various health indicators related to risk factors of dementia. METHODS: This prospective randomized controlled trial involved 77 older adults with SCD recruited from the Dementia Prevention and Management Center in Gwangju, South Korea during May to October 2022. Participants were randomly assigned to either the mobile- or paper-based group. Interventions were administered for 12 weeks, where pre- and post-assessments were conducted. RESULTS: The K-RBANS total score did not show significant differences between groups. The mobile group showed better improvement in K-PRMQ scores and PSS scores than the paper group. Differences within groups showed that mobile-based interventions significantly improved K-PRMQ, STAI-X-1, PSS, and EQ-5D-5 L scores, while paper-based interventions significantly improved PSS, and EQ-5D-5 L scores. Patient adherence rate was 76.6%. CONCLUSION: Overall, the Silvia program was effective for improving self-reported memory failures, stress, anxiety, and health-related quality of life in older adults with SCD. However, longer periods of administration for more than 12 weeks may be needed to achieve significant improvements in cognitive function by objective measures.

Low concentrations of tricyclic antidepressants stimulate TRPC4 channel activity by acting as an opioid receptor ligand.

Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome. However, the mechanism by which these atypical effects manifest is unclear. Among the proposed mechanisms is the well-known pain-related inhibitory G-protein coupled receptor, namely the opioid receptor (OR). Here, we confirmed that TCA indeed stimulates OR and regulates the gating of TRPC4, a downstream signaling of the Gi-pathway. In an ELISA to quantify the amount of intracellular cAMP, a downstream product of OR/Gi-pathway, treatment with amitriptyline (AMI) showed a decrease in [cAMP]i similar to that of the µOR agonist. Next, we explored the binding site of TCA by modeling the previously revealed ligand-bound structure of µOR. A conserved aspartate residue of ORs was predicted to participate in salt bridge interaction with the amine group of TCAs, and in aspartate-to-arginine mutation, AMI did not decrease the FRET-based binding efficiency between the ORs and Gαi2. As an alternative way to monitor the downstream signaling of Gi-pathway, we evaluated the functional activity of TRPC4 channel, as it is well known to be activated by Gαi. TCAs increased the TRPC4 current through ORs, and TCA-evoked TRPC4 activation was abolished by an inhibitor of Gαi2 or its dominant-negative mutant. As expected, TCA-evoked activation of TRPC4 was not observed in the aspartate mutants of OR. Taken together, OR could be proclaimed as a promising target among numerous binding partners of TCA, and TCA-evoked TRPC4 activation may help to explain the nonopioid analgesic effect of TCA.NEW & NOTEWORTHY Endogenous opioid systems modulate pain perception, but concerns about opioid-related substance misuse limit their use. This study has raised TRPC4 channel as a candidate target for alternative analgesics, tricyclic antidepressants (TCAs). TCAs have been shown to bind to and activate opioid receptors (ORs), leading to downstream signaling pathways involving TRPC4. The functional selectivity and biased agonism of TCA towards TRPC4 in dependence on OR may provide a better understanding of its efficacy or side effects.

Sex differences and risk factors in recurrent ischemic stroke.

Introduction: Recurrent ischemic stroke (RIS) is associated with increased mortality and poor outcomes. Therefore, secondary prevention is critical for reducing the risk of recurrent stroke. Previous studies have found sex differences in risk factors in patients with first-ever stroke; however, the results have been inconsistent for recurrent stroke. Therefore, this study aimed to investigate whether there are significant sex differences in the clinical characteristics and risk factors for recurrent ischemic stroke. Methods: We retrospectively studied 787 patients with recurrent ischemic stroke after first-ever stroke confirmation using magnetic resonance imaging (MRI) after visiting a regional tertiary hospital between 2014 and 2020. Demographic characteristics, laboratory findings, and risk factors were compared between the male and female patients. In addition, multivariate logistic regression was performed to identify the independent factors associated with stroke recurrence in male patients. Results: Among the 787 patients, 466 (59.2%) were males. Males were younger than females (67.6 vs. 71.9 years). Females had higher rates of hypertension, diabetes mellitus, dyslipidemia, and overweight than those of males. However, the alcohol drinking and smoking rate were significantly higher in males than that in females. There were no statistically significant sex-based differences in the laboratory findings. Among males, hypertension, alcohol drinking, smoking and dyslipidemia was a significant risk factor for ischemic stroke recurrence. Conclusion: Hypertension and dyslipidemia were significant risk factors of recurrent ischemic stroke in both genders. Smoking and alcohol drinking were significant risk factors associated with ischemic stroke recurrence in males. Therefore, smoking cessation and alcohol abstinence are recommended after the first stroke to prevent recurrent ischemic stroke especially for males. Diabetes was a significant risk factor of ischemic stroke recurrence in females. More extensive studies are needed to understand the causal relationship of each factors with ischemic stroke recurrence according to sex differences and specification of preventive management is needed.

Characteristics and clinical course of patients referred to the NST.

Background and aims: The nutrition support team (NST) comprises doctors, nutritionists, pharmacists, and nurses who provide intensive nutritional treatment designed for each patient by evaluating their nutritional status of hospitalized patients. This study aimed to identify the clinical characteristics of patients referred to the NST among those admitted to a tertiary hospital and to understand the factors affecting their clinical course and changes in pressure sore grades. Methods: This study included 1,171 adult patients aged 18 years or older referred to the NST at a tertiary hospital in a metropolitan city between 1 January 2019 and 31 December 2020. Patients were divided into five age groups, neuro department and non-neuro department, those treated in the intensive care unit (ICU), and those not treated in the ICU. Patients were also compared based on the presence of pressure sores at the time of NST referral and changes in pressure sore grades at the first time of NST referral and discharge (improved pressure sores, no change in pressure sores, and aggravated pressure sores). In addition, this study examined the factors affecting changes in pressure sore grades. Results: As age increased, the proportion of both low albumin levels and pressure sores significantly increased (p < 0.001), and the neuro department showed a significantly lower proportion of low albumin levels and pressure sores (p < 0.001). The proportion of patients with pressure sores was higher (64.9%), and this patient group showed significantly higher rates of low albumin levels (p < 0.001) and treatment in the ICU (p < 0.001). The group with aggravated pressure sore grades had a significantly higher proportion of patients in the surgery department (p = 0.009) and those treated in the ICU (p < 0.001). Admission to the surgery department was a factor that aggravated the grade of pressure sores [adjusted odds ratio (aOR) = 1.985, 95% confidence interval (CI) = 1.168-3.371]. When patients were not treated in the ICU, the grade of the pressure sores was less likely to worsen (aOR = 0.364, 95% CI = 0.217-0.609). Conclusion: Pressure sores and low albumin levels are closely related, and the risk of developing and aggravating pressure sores is particularly high in patients in the surgery department and those receiving ICU treatment. Therefore, it is necessary to actively implement NST referral to ensure that overall nutrition, including albumin, is well supplied, especially for patients in the surgery department and treated in the ICU, as they are at high risk of pressure sore development and aggravation. Moreover, since low albumin levels frequently occur in elderly patients, it is necessary to consider including the elderly in the indications for referral to the NST.

Can hippocampal subfield measures supply information that could be used to improve the diagnosis of Alzheimer's disease?

The diagnosis of Alzheimer's disease (AD) needs to be improved. We investigated if hippocampal subfield volume measured by structural imaging, could supply information, so that the diagnosis of AD could be improved. In this study, subjects were classified based on clinical, neuropsychological, and amyloid positivity or negativity using PET scans. Data from 478 elderly Korean subjects grouped as cognitively unimpaired ß-amyloid-negative (NC), cognitively unimpaired ß-amyloid-positive (aAD), mild cognitively impaired ß-amyloid-positive (pAD), mild cognitively impaired-specific variations not due to dementia ß-amyloid-negative (CIND), severe cognitive impairment ß-amyloid-positive (ADD+) and severe cognitive impairment ß-amyloid-negative (ADD-) were used. NC and aAD groups did not show significant volume differences in any subfields. The CIND did not show significant volume differences when compared with either the NC or the aAD (except L-HATA). However, pAD showed significant volume differences in Sub, PrS, ML, Tail, GCMLDG, CA1, CA4, HATA, and CA3 when compared with the NC and aAD. The pAD group also showed significant differences in the hippocampal tail, CA1, CA4, molecular layer, granule cells/molecular layer/dentate gyrus, and CA3 when compared with the CIND group. The ADD- group had significantly larger volumes than the ADD+ group in the bilateral tail, SUB, PrS, and left ML. The results suggest that early amyloid depositions in cognitive normal stages are not accompanied by significant bilateral subfield volume atrophy. There might be intense and accelerated subfield volume atrophy in the later stages associated with the cognitive impairment in the pAD stage, which subsequently could drive the progression to AD dementia. Early subfield volume atrophy associated with the ß-amyloid burden may be characterized by more symmetrical atrophy in CA regions than in other subfields. We conclude that the hippocampal subfield volumetric differences from structural imaging show promise for improving the diagnosis of Alzheimer's disease.

A Single Baseline Amyloid Positron Emission Tomography Could Be Sufficient for Predicting Alzheimer's Disease Conversion in Mild Cognitive Impairment.

OBJECTIVE: Baseline amyloid burden in mild cognitive impairment (MCI) has been linked to conversion to Alzheimer's disease (AD), but the comparison of baseline and longitudinal changes in amyloid burden for predicting AD remains unresolved. The objectives of this study aimed to compare the prognostic ability of baseline and longitudinal changes in amyloid burden in MCI patients. METHODS: Seventy-five individuals with MCI were recruited and examined annually by clinical interviews for a mean follow-up of 24 months (range, 11.6-42.0). [18F]Florbetaben positron emission tomography (PET) scans were performed. T1-weighted 3D volumes were acquired for co-registration, and to define regions of interest. We examined whether baseline and longitudinal amyloid burden changes can improve AD conversion by Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Cox proportional hazards model analysis showed that baseline amyloid burden was significantly associated with increased risk of conversion to AD (hazard ratio [HR]=10.0; 95% confidence interval [CI], 1.15-85.39; p=0.04), but longitudinal amyloid burden changes was not (HR=0.2; 95% CI, 0.02-1.18; p=0.07). When predicting AD, longitudinal amyloid burden changes had better ROC accuracy of 65.2% (95% CI, 48.4-82.0) than baseline amyloid burden of 59.6% (95% CI, 40.3-79.0), without statistical significance in pairwise comparison. CONCLUSION: A single baseline amyloid PET could be sufficient in the prediction of AD conversion in MCI.

Rapid Regression of Carotid Artery Stenosis Shortly after Intensive Medical Therapy.

Carotid artery stenosis (CAS) is mainly caused by atherosclerosis. Intensive medical therapy is effective in preventing stroke in CAS. To date, there has been no published report of rapid regression of CAS. A woman with untreated hyperlipidemia visited our emergency room with left hemiparesis. She exhibited facial palsy, left hemiparesis, and dysarthria immediately after the visit. Brain magnetic resonance (MR) diffusion-weighted imaging confirmed acute infarction in the right middle cerebral artery (MCA) territory due to severe stenosis of the right internal carotid artery (ICA), which was revealed by MR angiography and carotid duplex ultrasonography. The patient started intensive statin therapy and dual antiplatelet agent therapy. Carotid artery stenting was not performed until hospitalization day 16 due to pleural effusion. On day 16, digital subtraction angiography was performed, and spontaneous regression of severe stenosis was observed. Only mild stenosis with ulcerative plaque was evident. The rapid CAS regression in this case may be caused by M2 macrophage polarization as a result of intensive statin therapy. This rapid regression may also result from reduced foam cell formation by statin and aspirin and thereby increased endogenous thrombolysis. Our patient demonstrated the efficacy of short-term intensive statin and aspirin therapy on atherosclerosis with untreated hyperlipidemia.

Role of ketone bodies in diabetes-induced dementia: sirtuins, insulin resistance, synaptic plasticity, mitochondrial dysfunction, and neurotransmitter.

Patients with type 2 diabetes can have several neuropathologies, such as memory deficits. Recent studies have focused on the association between metabolic imbalance and neuropathological problems, and the associated molecular pathology. Diabetes triggers neuroinflammation, impaired synaptic plasticity, mitochondrial dysfunction, and insulin resistance in the brain. Glucose is a main energy substrate for neurons, but under certain conditions, such as fasting and starvation, ketone bodies can be used as an energy fuel for these cells. Recent evidence has shed new light on the role of ketone bodies in regulating several anti-inflammation cellular pathways and improving glucose metabolism, insulin action, and synaptic plasticity, thereby being neuroprotective. However, very high amount of ketone bodies can be toxic for the brain, such as in ketoacidosis, a dangerous complication that may occur in type 1 diabetes mellitus or alcoholism. Recent findings regarding the relationship between ketone bodies and neuropathogenesis in dementia are reviewed in this article. They suggest that the adequately low amount of ketone bodies can be a potential energy source for the treatment of diabetes-induced dementia neuropathology, considering the multifaceted effects of the ketone bodies in the central nervous system. This review can provide useful information for establishing the therapeutic guidelines of a ketogenic diet for diabetes-induced dementia.

Potential Novel Genes for Late-Onset Alzheimer's Disease in East-Asian Descent Identified by APOE-Stratified Genome-Wide Association Study.

The present study reports two novel genome-wide significant loci for late-onset Alzheimer's disease (LOAD) identified from APOE ε4 non-carrier subjects of East Asian origin. A genome-wide association study of Alzheimer's disease was performed in 2,291 Korean seniors in the discovery phase, from the Gwangju Alzheimer' and Related Dementias (GARD) cohort study. The study was replicated in a Japanese cohort of 1,956 subjects that suggested two novel susceptible SNPs in two genes: LRIG1 and CACNA1A. This study demonstrates that the discovery of AD-associated variants is feasible in non-European ethnic groups using samples comprising fewer subjects from the more homogeneous genetic background.

Pathobiolgy and Management of Alzheimer's Disease.

Amyloid and tau protein abnormalities have been identified as the main causes of Alzheimer's disease but exact mechanisms remain to be revealed. Especially, amyloid beta and tau protein coupling and neuroinflammatory and neurovascular contributions to Alzheimer disease are quite mysterious. Many animal models and basic biological research are trying to solve these puzzles. Known as aging processes, autophagy, mitochondrial degeneration with generation of reactive oxygen species, and age-related epigenetic modifications are also known to be associated with development of Alzheimer's disease. Environmental factors such as bacterial and viral infections, heavy metal ions, diet, sleep, stress, and gut microbiota are also risk factors of Alzheimer's disease. Future development of preventive and therapeutic modalities may be dependent on the pathobiology of Alzheimer's disease.

Aconitine Neurotoxicity According to Administration Methods.

We evaluated the toxic effects of aconitine on the human nervous system and its associated factors, and the general clinical characteristics of patients who visited the emergency room due to aconitine intoxication between 2008 and 2017. We also analyzed the differences related to aconitine processing and administration methods (oral pill, boiled in water, and alcohol-soaked), and the clinical characteristics of consciousness deterioration and neurological symptoms. Of the 41 patients who visited the hospital due to aconitine intoxication, 23 (56.1%) were female, and most were older. Aconitine was mainly used for pain control (28 patients, 68.3%) and taken as oral pills (19 patients, 46%). The patients showed a single symptom or a combination of symptoms; neurological symptoms were the most common (21 patients). All patients who took aconitine after processing with alcohol showed neurological symptoms and a higher prevalence of consciousness deterioration. Neurological symptoms occurred most frequently in patients with aconitine intoxication. Although aconitine intoxication presents with various symptoms, its prognosis may vary with the processing method and prevalence of consciousness deterioration during the early stages. Therefore, the administration method and accompanying symptoms should be comprehensively investigated in patients who have taken aconitine to facilitate prompt and effective treatment and better prognoses.

Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota.

Resveratrol is a natural polyphenol that has anti-aging and anti-inflammatory properties against stress condition. It is reported that resveratrol has beneficial functions in various metabolic and central nervous system (CNS) diseases, such as obesity, diabetes, depression, and dementia. Recently, many researchers have emphasized the connection between the brain and gut, called the gut-brain axis, for treating both CNS neuropathologies and gastrointestinal diseases. Based on previous findings, resveratrol is involved in glucagon-like peptide 1 (GLP-1) secreted by intestine L cells, the patterns of microbiome in the intestine, the 5-hydroxytryptamine (5-HT) level, and CNS inflammation. Here, we review recent evidences concerning the relevance and regulatory function of resveratrol in the gut-brain axis from various perspectives. Here, we highlight the necessity for further study on resveratrol's specific mechanism in the gut-brain axis. We present the potential of resveratrol as a natural therapeutic substance for treating both neuropathology and gastrointestinal dysfunction.

Follow-Up of Brain Single-Photon Emission Computed Tomography (SPECT) and Magnetic Resonance Imaging (MRI) in a Case of Seizure Caused by Osmotic Demyelination Syndrome.

BACKGROUND Osmotic demyelination syndrome (ODS) is an uncommon neurological disorder. Until the mid-1980s, the mortality rate was 90-100%, but more than half of patients now have a good prognosis. Early suspicion of ODS is important. However, radiologic findings of ODS are variable and scintigraphy findings have not been reported. CASE REPORT A 38-year-old man with alcohol abuse history was admitted due to electrolyte imbalance. On the 10th day of his hospital stay, he had a generalized tonic-clonic seizure. Brain perfusion SPECT showed asymmetrically hyperperfused and hypoperfused lesions. Brain MRI revealed diffuse T2 hyperintensity with mild diffusion restriction in the pons and hyperperfused lesions on brain SPECT. He was treated based on the diagnosis of hyponatremia and osmotic demyelination. After treatment, the asymmetric hyperperfusion was decreased. MRI showed that the cortical hyperintensity had resolved, with encephalomalacic change shown in the pons. CONCLUSIONS To the best of our knowledge, this is the first report showing changes in brain perfusion SPECT and MRI in an ODS patient with a seizure. This case report may be helpful to neurologists, radiologists, and nuclear physicians.

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases.

The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.