Multiple system atrophy with amyloid-ß-predominant Alzheimer's disease neuropathologic change.

Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency and mostly comprise primary age-related tauopathy or low levels of Alzheimer's disease-related neuropathologic change. Therefore, the concomitant presence of different misfolded proteins in the same brain region is less likely in multiple system atrophy. During the neuropathological evaluation of 21 consecutive multiple system atrophy cases, we identified four cases exhibiting an unusual discrepancy between high Thal amyloid-ß phase and low transentorhinal Braak neurofibrillary tangle stage. We mapped α-synuclein pathology, measured the size and number of glial cytoplasmic inclusions and compared the amyloid-ß peptides between multiple system atrophy and Alzheimer's disease. In addition, we performed α-synuclein seeding assay from the affected putamen samples. We performed genetic testing for APOE, MAPT, PSEN1, PSEN2 and APP. We refer to the four multiple system atrophy cases with discrepancy between amyloid-ß and tau pathology as 'amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy' to distinguish these from multiple system atrophy with primary age-related tauopathy or multiple system atrophy with typical Alzheimer's disease neuropathologic change. As most multiple system atrophy cases with mixed pathologies reported in the literature, these cases did not show a peculiar clinical or MRI profile. Three amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy cases were available for genetic testing, and all carried the APOE ɛ4 allele. The extent and severity of neuronal loss and α-synuclein pathology were not different compared with typical multiple system atrophy cases. Analysis of amyloid-ß peptides revealed more premature amyloid-ß plaques in amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy compared with Alzheimer's disease. α-Synuclein seeding amplification assay showed differences in the kinetics in two cases. This study highlights a rare mixed pathology variant of multiple system atrophy in which there is an anatomical meeting point of amyloid-ß and α-synuclein, i.e. the striatum or cerebellum. Since biomarkers are entering clinical practice, these cases will be recognized, and the clinicians have to be informed that the prognosis is not necessarily different than in pure multiple system atrophy cases but that the effect of potential α-synuclein-based therapies might be influenced by the co-presence of amyloid-ß in regions where α-synuclein also aggregates. We propose that mixed pathologies should be interpreted not only based on differences in the clinical phenotype but also on whether protein depositions regionally overlap, potentially leading to a different response to α-synuclein-targeted therapies.

Revisiting the relevance of Hirano bodies in neurodegenerative diseases.

AIMS: Hirano bodies (HBs) are eosinophilic pathological structures with two morphological phenotypes commonly found in the hippocampal CA1 region in Alzheimer's disease (AD). This study evaluated the prevalence and distribution of HBs in AD and other neurodegenerative diseases. METHODS: This cross-sectional study systematically evaluated HBs in a cohort of 193 cases with major neurodegenerative diseases, including AD (n = 91), Lewy body disease (LBD, n = 87), progressive supranuclear palsy (PSP, n = 36), multiple system atrophy (MSA, n = 14) and controls (n = 26). The prevalence, number and morphology of HBs in the stratum lacunosum (HBL) and CA1 pyramidal cell layer were examined. In addition, we investigated the presence of HBs in five additional hippocampal subregions. RESULTS: The morphological types of HBs in CA1 were divided into three, including a newly discovered type, and were evaluated separately, with their morphology confirmed in three dimensions: (1) classic rod-shaped HB (CHB), (2) balloon-shaped HB (BHB) and the newly described (3) string-shaped HB (SHB). The prevalence of each HB type differed between disease groups: Compared with controls, for CHB in AD, AD + LBD, PSP and corticobasal degeneration, for BHB in AD + LBD and PSP, and SHB in AD + LBD and PSP were significantly increased. Regression analysis showed that CHBs were independently associated with higher Braak NFT stage, BHBs with LBD and TDP-43 pathology, SHBs with higher Braak NFT stage, PSP and argyrophilic grain disease and HBLs with MSA. CONCLUSIONS: This study demonstrates that HBs are associated with diverse neurodegenerative diseases and shows that morphological types appear distinctively in various conditions.

Acute large-vessel occlusion due to an infected thrombus formation induced by invasive sphenoid sinus aspergillosis: illustrative case.

BACKGROUND: The authors describe a rare case of acute large-vessel occlusion due to an infected thrombus formation that was induced by invasive sphenoid sinus aspergillosis. OBSERVATIONS: An 82-year-old man with a history of immunoglobulin G4-related disease and long-term use of steroids and immunosuppressants was admitted to the authors' hospital with severe right hemiparesis. Cerebral angiography revealed occlusion of the left internal carotid artery (ICA). He underwent thrombectomy, resulting in successful recanalization. However, severe stenosis was evident in the left ICA cavernous segment. Pathological analysis of the retrieved thrombus identified Aspergillus. Postoperative magnetic resonance imaging revealed sinusitis in the left sphenoid sinus as a possible source of the infection. The patient's general condition deteriorated during the course of hospitalization due to refractory aspiration pneumonia, and he died 46 days after thrombectomy. Pathological autopsy and histopathological investigation of the left ICA and the left sphenoid sinus showed that Aspergillus had invaded the wall of the left ICA from the adjacent sphenoid sinus. These findings indicate a diagnosis of acute large-vessel occlusion due to infected thrombus formation induced by invasive sphenoid sinus aspergillosis. LESSONS: Pathological analysis of a retrieved thrombus appears useful for identifying rare stroke etiologies such as fungal infection.

Molecular Behavior of α-Synuclein Is Associated with Membrane Transport, Lipid Metabolism, and Ubiquitin-Proteasome Pathways in Lewy Body Disease.

Lewy body diseases (LBDs) feature α-synuclein (α-syn)-containing Lewy bodies, with misfolded α-syn potentially propagating as seeds. Using a seeding amplification assay, we previously reported distinct α-syn seeding in LBD cases based on the area under seeding curves. This study revealed that LBD cases showing different α-syn seeding kinetics have distinct proteomics profiles, emphasizing disruptions in mitochondria and lipid metabolism in high-seeder cases. Though the mechanisms underlying LBD development are intricate, the factors influencing α-syn seeding activity remain elusive. To address this and complement our previous findings, we conducted targeted transcriptome analyses in the substantia nigra using the nanoString nCounter assay together with histopathological evaluations in high (n = 4) and low (n = 3) nigral α-syn seeders. Neuropathological findings (particularly the substantia nigra) were consistent between these groups and were characterized by neocortical LBD associated with Alzheimer's disease neuropathologic change. Among the 1811 genes assessed, we identified the top 20 upregulated and downregulated genes and pathways in α-syn high seeders compared with low seeders. Notably, alterations were observed in genes and pathways related to transmembrane transporters, lipid metabolism, and the ubiquitin-proteasome system in the high α-syn seeders. In conclusion, our findings suggest that the molecular behavior of α-syn is the driving force in the neurodegenerative process affecting the substantia nigra through these identified pathways. These insights highlight their potential as therapeutic targets for attenuating LBD progression.

Successful carotid stenting of a carotid arterial dissection after straightening the tortuosity using an inflated balloon guiding catheter and the delivery wire of an anchored stent retriever.

The authors present a patient with carotid dissection in a tortuous arterial segment who successfully underwent carotid artery stenting (CAS) by straightening the tortuosity using an inflated balloon guiding catheter (BGC) and a stent retriever (SR). A 56-year-old man was transferred to our institute with right hemiparesis and a National Institutes of Health Stroke Scale score of 9. Magnetic resonance imaging showed left internal carotid artery (ICA) occlusion and ischemic change in the parietal lobe. Emergent angiography revealed tapered extracranial ICA occlusion sugg carotid artery dissection (CAD). CAS was attempted for CAD due to a mismatch of the motor area on clinical imaging. However, several attempts to navigate the stent delivery system over a guidewire failed. Therefore, we deployed a Trevo NXT ProVue SR (3 × 32 mm) in the middle cerebral artery, inflated a BGC, and then pulled on both to straighten the tortuous carotid artery, which resulted in successful navigation of the stent delivery system. The patient's symptoms improved after the recanalization. This case demonstrates the utility of a technique for navigation of a stent delivery system through a tortuous carotid artery in which the tortuosity is straightened by pulling on an inflated BGC and the delivery wire of the SR.

Neuropathology of patients with preclinical or early clinical Alzheimer's disease with pathogenic PSEN1_p. L392V: Comparison of advanced siblings.

INTRODUCTION: Neuropathological investigation of presymptomatic or early symptomatic presenilin-1 (PSEN1) mutation carriers in familial Alzheimer's disease (AD) is extremely scarce. METHODS: We report the autopsy findings of brothers with familial AD. Case 1 is a 45-year-old man without obvious cognitive impairment, who committed suicide. Case 2 is a 57-year-old older brother of Case 1 with advanced AD symptoms, who died of hypothermia during wondering. RESULTS: In both cases, abundant amyloid plaques positive for amyloid ß (Aß) were found throughout the brain. Progression of neuronal loss and increasing amount and extension of neurofibrillary tangle pathology were evident in Case 2. Genetic investigation revealed a PSEN1_p. L392V mutation in both cases. DISCUSSION: The present study shows a possible neuropathological boundary between symptomatic and preclinical AD with pathogenic PSEN1 mutation. Additional clinicopathological investigation for familial AD-related mutation carriers may be significant to explore the association between familial AD and suicide.

Sudden unexpected death of a young adult due to subarachnoid hemorrhage associated with polyarteritis nodosa: Clinicopathological appearance and literature review.

A 28-year-old male was found dead in his bedroom. There were no anomalies in his birth and medical history, and there was no family history of sudden unexpected death (SUD). Autopsy showed subarachnoid hemorrhage (SAH) with basilar top inflammatory pseudoaneurysm rupture accompanied by fibrinoid necrosis in the aneurysm wall. Active and healed arteritides in small- to medium-sized arteries were identified in the brain, heart, and systemic connective tissue, which was consistent with polyarteritis nodosa (PAN). Furthermore, pneumatosis cystoides intestinalis was observed in the ascending colon. Hepatitis B virus infection and antineutrophil nuclear antibodies were negative. Genetic investigation using whole-exome sequencing showed no mutations among autoinflammatory-related genes, including UBA1, MEFV, and ADA2. SAH due to rupture of a pseudoaneurysm formed by PAN was considered as the cause of death in the present case. Although myocardial ischemia linked to coronary arteritis is a recognized trigger for SUD in PAN, our study showed that rupture of inflammatory pseudoaneurysm in the cerebral artery can also cause SUD in younger subjects with PAN, even if prodromal symptoms are not evident before death.

The molecular spectrum of amyloid-beta (Aß) in neurodegenerative diseases beyond Alzheimer's disease.

This study investigated the molecular spectrum of amyloid-beta (Aß) in neurodegenerative diseases beyond Alzheimer's disease (AD). We analyzed Aß deposition in the temporal cortex and striatum in 116 autopsies, including Lewy body disease (LBD; N = 51), multiple system atrophy (MSA; N = 10), frontotemporal lobar degeneration-TDP-43 (FTLD-TDP; N = 16), and progressive supranuclear palsy (PSP; N = 39). The LBD group exhibited the most Aß deposition in the temporal cortex and striatum (90/76%, respectively), followed by PSP (69/28%), FTLD-TDP (50/25%), and the MSA group (50/10%). We conducted immunohistochemical analysis using antibodies targeting eight Aß epitopes in the LBD and PSP groups. Immunohistochemical findings were evaluated semi-quantitatively and quantitatively using digital pathology. Females with LBD exhibited significantly more severe Aß deposition, particularly Aß42 and Aß43 , along with significantly more severe tau pathology. Furthermore, a quantitative analysis of all Aß peptides in the LBD group revealed an association with the APOE-ε4 genotypes. No significant differences were observed between males and females in the PSP group. Finally, we compared striatal Aß deposition in cases with LBD (N = 15), AD without α-synuclein pathology (N = 6), and PSP (N = 5). There were no differences in the pan-Aß antibody (6F/3D)-immunolabeled deposition burden among the three groups, but the deposition burden of peptides with high aggregation capacity, especially Aß43 , was significantly higher in the AD and LBD groups than in the PSP group. Furthermore, considerable heterogeneity was observed in the composition of Aß peptides on a case-by-case basis in the AD and LBD groups, whereas it was relatively uniform in the PSP group. Cluster analysis further supported these findings. Our data suggest that the type of concomitant proteinopathies influences the spectrum of Aß deposition, impacted also by sex and APOE genotypes.

Short repetition time diffusion-weighted imaging improves visualization of prostate cancer.

PURPOSE: This study aimed to assess whether short repetition time (TR) diffusion-weighted imaging (DWI) could improve diffusion contrast in patients with prostate cancer (PCa) compared with long TR (conventional) reference standard DWI. MATERIALS AND METHODS: Our Institutional Review Board approved this retrospective study and waived the need for informed consent. Twenty-five patients with suspected PCa underwent multiparametric magnetic resonance imaging (mp-MRI) using a 3.0-T system. DWI was performed with TR of 1850 ms (short) and 6000 ms (long) with b-values of 0, 1000, and 2000s/mm2. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), visual score, apparent diffusion coefficient (ADC), and diagnostic performance were compared between short and long TR DWI for both b-values. The statistical tests included paired t-test for SNR and CNR; Wilcoxon signed-rank test for VA; Pearson's correlation and Bland-Altman plot analysis for ADC; and McNemar test and receiver operating characteristic analysis and Delong test for diagnostic performance. RESULTS: Regarding b1000, CNR and visual score were significantly higher in short TR compared with long TR (P = .003 and P = .002, respectively), without significant difference in SNR (P = .21). Considering b2000, there was no significant difference in visual score between short and long TR (P = .07). However, SNR and CNR in long TR were higher (P = .01 and P = .04, respectively). ADC showed significant correlations, without apparent bias for ADC between short and long TR for both b-values. For diagnostic performance of DWI between short and long TR for both b-values, one out of five readers noted a significant difference, with the short TR for both b-values demonstrating superior performance. CONCLUSIONS: Our data showed that the short TR DWI1000 may provide better image quality than did the long TR DWI1000 and may improve visualization and diagnostic performance of PCa for readers.

Randomized phase I/II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma.

AIM: We evaluated the safety and efficacy of vascular endothelial growth factor receptor (VEGFR)-targeted peptide vaccines for the immunization of patients with unresectable hepatocellular carcinoma (HCC) who had responded to transarterial chemoembolization. METHODS: Twenty-two patients were randomized 1:1 to receive VEGFR-targeted peptides or placebo. The primary end-point was the safety assessment of the immunization. The secondary end-points were evaluation of immunological responses and clinical outcomes. RESULTS: No severe adverse events were induced by the study agents. Among the 12 patients in the vaccine group, a VEGFR1-specific cytotoxic T lymphocyte (CTL) response was induced in eight (66.7%) patients and a VEGFR2-specific CTL response was induced in 10 (83.3%). The median progression-free survival (PFS) and overall survival (OS) rates were 4.8 and 52.0 months, respectively, in the vaccine group, and 2.7 and 21.8 months, respectively, in the placebo group. No statistically significant differences were found between the two groups (PFS p = 0.925, OS p = 0.190). When divided into two groups according to immunoreactivity, the median PFS of patients with and without a strong immune response to VEGFR1 were 7.4 and 2.7 months, and that to VEGFR2 were 10.6 and 2.7 months, respectively; there were significant differences according to the immune response. CONCLUSIONS: Immunotherapy with peptide vaccines targeting VEGFR1 and VEGFR2 was well tolerated with no serious adverse events. It also effectively induced peptide-specific CTLs in patients with unresectable HCC.

The impact of diabetic polyneuropathy on toe grip strength in patients with type 2 diabetes mellitus: a cross-sectional study.

Purpose: Type 2 diabetes mellitus (T2DM) and concomitant diabetic polyneuropathy (DPN) induce muscle weakness. Muscle weakness in the foot is associated with foot deformities and falls. However, factors affecting toe grip strength (TGS) are not well known. Therefore, the present study investigated factors related to TGS in patients with T2DM. Methods: This was a cross-sectional study involving 100 patients with T2DM who were hospitalized for the treatment of T2DM and 50 healthy adults. The subjects were divided into three groups: a group of healthy subjects, a group of T2DM patients without DPN, and a group of T2DM patients with DPN. Hierarchical multiple regression analysis was performed with TGS and the TGS-to-weight ratio (TGS/Wt%) as dependent variables and with age, the presence of T2DM, and DPN as independent variables, and sex and BMI as confounders. Results: There were no significant differences in age or sex among the three groups. In the final regression analysis, age and presence of T2DM and DPN were associated in both models with TGS and TGS/Wt% as dependent variables. Conclusion: DPN, T2DM, and age were found to be related to TGS. The findings of this study could contribute to healthcare providers developing foot care and rehabilitation programs for diabetic patients. Trial registration: This study was registered with UMIN-CTR (UMIN000034320) on 1 November 2018.

A case of intracerebral hemorrhage due to cerebral hyperperfusion after stenting for acute cervical carotid artery dissection.

Urgent carotid artery stenting (CAS) is effective for treatment-resistant cervical internal carotid artery dissection (CICAD). We experienced a 37-year-old woman who presented with sudden onset of cervical pain, blurred vision in the right eye, and numbness in the left upper and lower extremities. Due to neurological deterioration resulting from hemodynamic impairment, urgent CAS was performed under general anesthesia. Brain perfusion single-photon emission computed tomography performed immediately after CAS showed increased blood flow in the right hemisphere despite no evidence of hemorrhage or ischemic lesion on brain computed tomography (CT). Systolic blood pressure was therefore strictly controlled below 110 mm Hg perioperatively. However, the day after CAS, a follow-up CT showed intracerebral hemorrhage in the right temporal lobe. Urgent CAS in patients with progressive deterioration of hemodynamic impairment caused by CICAD may induce intracerebral hemorrhage due to cerebral hyperperfusion. Care should be taken to recognize and manage this phenomenon during the perioperative period.

Pancreatic ductal adenocarcinoma with acinar-to-ductal metaplasia-like cancer cells shows increased cellular proliferation.

BACKGROUND/OBJECTIVES: Acinar-to-ductal metaplasia (ADM) has been shown to contribute to the development of pancreatic ductal adenocarcinoma (PDAC) in genetically engineered mouse models, but little is known about whether acinar cell plasticity contributes to carcinogenesis in human PDAC. We aimed to assess whether cancer cells that stain positive for amylase and CK19 (ADM-like cancer cells) are present in human resected PDAC and to investigate their role in tumor progression. METHODS: We immunohistochemically investigated the presence of ADM-like cancer cells, and compared the clinical and histological parameters of PDAC patients with and without ADM-like cancer cells. RESULTS: ADM-like cancer cells were detected in 16 of 60 (26.7%) PDAC specimens. Positive staining for anterior gradient protein 2 (AGR2) was observed in 14 of 16 (87.5%) PDAC specimens with ADM-like cancer cells. On the other hand, the intensity of AGR2 expression (negative, low/moderate or high) was lower in PDAC with ADM-like cancer cells (9/7) than in PDAC without these cells (11/33) (P = 0.032). The presence of ADM-like cancer cells was significantly correlated with increased cell proliferation (P = 0.012) and tended to be associated with MUC1 expression (P = 0.067). CONCLUSIONS: These results indicated that acinar cells may act as the origin of human PDAC, and that their presence may be useful for the stratification of human PDAC to predict prognosis.

Hydration of Alkali Metal and Halide Ions from Static and Dynamic Viewpoints.

Ion hydration in aqueous solutions plays a paramount role in many fields. Despite many studies on ion hydration, the nature of ion hydration is not consistently understood at the molecular level. Combining neutron scattering (NS), wide-angle X-ray scattering (WAXS), and molecular dynamics (MD), we quantify the ionic hydration degree (hydration ability) systematically for a series of alkali metal and halide ions based on static and dynamic hydration numbers. The former is based on the orientational correlation of water molecules bound to an ion derived from the positional information from NS and WAXS. The latter is defined as the mean number of water molecules remaining in the first coordination shell of an ion over a residence time of bound water molecules around the ion from MD. The static and dynamic hydration numbers distinguish hydration from coordination and quantify the ionic hydration degree, which provides a valuable reference for understanding various phenomena in nature.

Comprehensive pathological and genetic investigation of three young adult myotonic dystrophy type 1 patients with sudden unexpected death.

OBJECTIVES: The mechanism and pathological substrate of arrhythmogenic events in dystrophic myopathy type 1 (DM1) have not been fully established, especially for patients without progression of motor and/or cardiac disability. Therefore, we aimed to clarify the pathological appearance and genetic factors, other than CTG repeats in DMPK, associated with sudden cardiac death in patients with DM1. METHODS: A pathological investigation including the cardiac conduction system in the heart and whole-exome sequencing was conducted for three young adults (Patient 1; 25-year-old female, Patient 2; 35-year-old female, Patient 3; 18-year-old male) with DM1 who suffered sudden death. RESULTS: Only Patient 1 showed abnormal electrocardiogram findings before death. The pathological investigation showed severe fibrosis of the atrioventricular conduction system in Patient 1 and severe fatty infiltration in the right ventricle in Patient 2. Several minimal necrotic/inflammatory foci were found in both patients. Patient 3 showed no significant pathological findings. A genetic investigation showed CORIN_p.W813* and MYH2_p. R793* in Patient 1, KCNH2_p. V794D and PLEC_p. A4147T in Patient 2, and SCN5A_p.E428K and SCN3B_ p.V145L in Patient 3 as highly possible pathogenic variants. CONCLUSION AND RELEVANCE: The present study showed varied heart morphology in young adults with DM1 and sudden death. Synergistic effects of various genetic factors other than CTG repeats may increase the risk of sudden cardiac death in DM1 patients, even if signs of cardiac and skeletal muscle involvement are mild. Comprehensive genetic investigations, other than CTG repeat assessment, may be useful to estimate the risk of sudden cardiac death in DM1 patients.

Profile of Nagasaki Islands Study (NaIS): A Population-Based Prospective Cohort Study on Multi-disease.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow-up with them for vital status (death), migration, and occurrence of diseases such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1) -associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014-2016, secondary surveys during 2017-2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed-up; and 3,594 and 3,364 residents (aged 27-96 and 28-98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Using a low-metal-density stent for thrombectomy-resistant vertebrobasilar occlusion due to thrombus migration from a thrombosed vertebral artery aneurysm: illustrative case.

BACKGROUND: Thrombosed intracranial aneurysms can lead to large vessel occlusion as a result of spontaneous thrombosis. Although mechanical thrombectomy is likely effective, recurrent thromboembolism can occur if the thrombotic source remains untreated. The authors describe a case of recurrent vertebrobasilar artery occlusion due to thrombus migration from a large thrombosed vertebral artery (VA) aneurysm that was successfully treated with mechanical thrombectomy followed by stenting. OBSERVATIONS: A 61-year-old male previously diagnosed with a large, thrombosed VA aneurysm presented with right hypoesthesia. Imaging on admission showed left VA occlusion and an acute ischemic lesion in the left medial medulla. His symptoms worsened, with complete right hemiparesis and tongue deviation occurring 3 hours after admission, and mechanical thrombectomy was performed to recanalize the left-dominant VA. Despite several attempts, reocclusion of the vertebrobasilar system occurred after each mechanical thrombectomy because of repeated thrombus formation in the thrombosed aneurysm. Therefore, a low-metal-density stent was deployed to prevent thrombus migration into the parent artery, which resulted in complete recanalization and rapid improvement of the symptoms. LESSONS: Stenting with a low-metal-density stent for recurrent embolism secondary to thrombus migration from a large thrombosed aneurysm was feasible in the acute stroke setting.

Argyrophilic grain disease is common in older adults and may be a risk factor for suicide: a study of Japanese forensic autopsy cases.

BACKGROUND: Neuropathological diagnosis of argyrophilic grain disease (AGD) is currently based primarily on the combination of argyrophilic grain (AG) visualized using Gallyas-Braak silver staining, phosphorylated tau-positive pretangles, coiled bodies, and ballooned neuron detection. Although AGD is common in patients with dementia and/or prominent psychiatric symptoms, whether it is a distinct neurological disease entity or a by-product of the aging process remains unclear. METHODS: In 1449 serial forensic autopsy cases > 40 years old (823 males and 525 females, aged 40-101 years, mean age 70.0 ± 14.1 years), we examined the frequency and comorbid pathology of AGD cases and investigated the clinical appearance by comparing those with non-AGD cases using the propensity score. RESULTS: Of the 1449 cases, we detected 342 AGD cases (23.6%; mean age 79.7 years; 177 males and 165 females). The AGD frequency and stage increased with age (P < 0.001). Among AGD cases, 80 (23.4%) patients had dementia, and 51 (15.2%) had a history of psychiatric hospital visits. The frequency of suicide and history of psychiatric disorders were significantly higher in AGD cases than in AGD-negative cases, matched for age, sex, and comorbidity pathology, with a relative risk of suicide of 1.72 (1.30-2.26). The frequency of suicide was significantly higher in AGD cases than in non-AGD cases in female but not male cases. The relative risk of suicide increased to 2.27 (1.20-4.30) and 6.50 (1.58-26.76) in AGD patients with Lewy and progressive supranuclear palsy pathology, respectively, and decreased to 0.88 (0.38-2.10) in those with advanced AD pathology. In AGD cases, 23.4% had dementia; however, the difference was not significant after controlling for age, sex, and comorbid pathology. CONCLUSION: Our study demonstrated that AGD is a significant and isolated risk factor for psychiatric hospital visits and suicide completion. In older adults, AGs may contribute to the progression of functional impairment of the limbic system, which leads to psychiatric disorders and suicide attempts.

In situ Raman and X-ray scattering of a single supersaturated aqueous Mg(NO3)2 droplet ultrasonically levitated.

A single liquid droplet in the air generated by ultrasonic levitation provides such analytical advantages as a small sample volume (~ µL) for expensive proteins, container-free condition for deeply supercooling and supersaturation, time-dependent observation, and homogeneous rapid mixing. The investigation of the properties and structure of a droplet at a molecular level is highly needed for understanding the physicochemical behaviors of a droplet and an underlying mechanism of processes in the droplet. We develop in situ Raman and synchrotron X-ray scattering methods of a single liquid droplet of ~ 1 mm size ultrasonically levitated. The composition of a supersaturated Mg(NO3)2 droplet and speciation in the droplet are determined by analyzing the nitrate N-O and the water O-H stretching vibrational Raman bands. The X-ray interference function of an supersaturated Mg(NO3)2 droplet is subjected to an empirical potential structure refinement modeling to reveal the ion solvation, association, and solvent water structure. Furthermore, crystallization of Mg(NO3)2⋅nH2O from a saturated droplet is observed and identified.