Striatal parvalbumin interneurons, not cholinergic interneurons, are activated in a mouse model of cerebellar dystonia.

Dystonia is supposed to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted the established cerebellar dystonia mice model by injecting ouabain to examine the contribution of the cerebellum. Initially, we examined whether the entopeduncular nucleus (EPN), substantia nigra pars reticulata (SNr), globus pallidus externus (GPe), and striatal neurons were activated in the model. Next, we examined whether dopamine D1 receptor agonists (D1 agonist) and dopamine D2 receptor antagonists (D2 antagonist) or selective ablation of striatal parvalbumin (PV) interneurons could modulate their involuntary movements. The cerebellar dystonia mice had a higher number of c-fos-positive cells in the EPN, SNr, and GPe, as well as a higher positive ratio of c-fos in striatal PV interneurons than the control mice. Furthermore, systemic administration of combined D1 agonist and D2 antagonist and selective ablation of striatal PV interneurons relieved their involuntary movements. Abnormalities in the motor loop of the basal ganglia could be crucially involved in cerebellar dystonia, and modulating PV interneurons might provide a novel treatment strategy.

Optimal timing of SARS-CoV-2 vaccination prior to cardiovascular surgery under cardiopulmonary bypass.

BACKGROUND: mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became common. We investigated the optimal timing for inoculation against SARS-COV-2 in the candidates for cardiac surgery under cardiopulmonary bypass (CPB). METHODS: In 100 patients with preoperative vaccination, who underwent CPB surgery between July 2021 and February 2022, the IgG against the receptor binding domain (RBD-IgG), with a threshold of >100 binding antibody unit (BAU)/mL for adequate immunity, was measured. RESULTS: The vaccines, including 87 BNT162b2 (Pfizer/BioNTech) and 13 mRNA-1273 (Moderna), were inoculated at 98.8 ± 59.4 days before surgery. The median RBD-IgG titers before surgery, 1 day after surgery, and 1 month after surgery were 166.8, 100.0, and 84.0 BAU/mL, respectively. The standby interval (SBI) from the vaccination to the surgery showed a significantly negative correlations with the RBD-IgG titer before the surgery (p < 0.001). A cut-off SBI for RBD-IgG >100 BAU/mL before surgery was <81 days with a sensitivity of 76%, specificity of 62%, and area under ROC value of 0.73 (p = 0.03). The patients with SBI <81 days (n = 48) had significantly higher RBD-IgG (>100 BAU/mL) than those with SBI ⩾81 days (n = 52) at all perioperative periods. CONCLUSIONS: Although 40% of the RBD-IgG titers reduce 1 day after CPB surgery, the patients who received the SARS-COV-2 vaccination within an 81-day window prior to the surgery maintained a desirable RBD-IgG level, even up to 1 month after surgery. It may be important to schedule the surgery no later than 81 days after the vaccination.

Nonconvulsive status epilepticus in patients with acute subarachnoid hemorrhage is associated with negative arterial spin labeling on peri-ictal magnetic resonance images.

Purpose: Non-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase. Methods: Based on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics. Results: In 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %). Conclusion: Normal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness.

Contributing factors to heparin resistance during cardiopulmonary bypass.

Since the risk factors for heparin resistance (HR) before cardiopulmonary bypass (CPB) have not been fully clarified, this study investigated the contributing factors for HR after the initial unfractionated heparin (UFH) dose of 500 IU/kg. We retrospectively analyzed the data of 371 patients who underwent CPB surgery, with the initial UFH dose of 500 IU/kg, between May 2017 and December 2021. We defined HR as the failure to achieve activated clotting time (ACT) of > 480 s after the initial UFH dose of 500 IU/kg. HR was observed in 36 patients (9.7%) (HR group), while HR was not observed in 335 patients (control group). The HR group included significantly more patients with preoperative use of UFH, with significantly higher white blood cell counts, fibrinogen, fibrinogen degradation products, D-dimer, and C-reactive protein, and lower hemoglobin and albumin. The multivariable logistic regression analysis identified albumin (OR: 3.09, 95% CI 1.3504-7.0845, p = 0.0075) and fibrinogen (OR: 0.99, 95% CI 0.9869-0.9963, p = 0.0003) as independent predictors for HR. Using the Youden index, the cutoffs of albumin and fibrinogen were calculated as 3.8 g/dL and 303 mg/dL, respectively. The receiver operating characteristic curves showed the predictive performance of albumin (area under the curve (AUC): 0.78, sensitivity: 65%, specificity: 81%) and fibrinogen (AUC: 0.77, sensitivity: 56%, specificity: 88%). The incidence of HR after the initial UFH dose of 500 IU/kg was 9.7%. The preoperative albumin < 3.8 g/dL and fibrinogen > 303 mg/dL were independent predictors for HR.

Comparison between Off-Pump and On-Pump Beating Heart Coronary Artery Bypass Grafting.

BACKGROUND: Although coronary artery bypass grafting (CABG) is performed via three different techniques, conventional, on-pump beating heart CABG (ONBHCAB), or off-pump CABG (OPCAB), data are limited to compare ONBHCAB with OPCAB. METHODS: We retrospectively investigated the postoperative cardiac biomarkers, creatine kinase-MB (CK-MB), and troponin I (cTnI), and early and late outcomes in 806 patients undergoing isolated ONBHCAB or OPCAB between February 2008 and September 2022. To eliminate the bias between different groups, propensity score matching was conducted to validate the findings. RESULTS: After matching, the number of each study group totaled 270 patients. In both complete and matched cohorts, early outcomes, including morbidities and mortalities, were similar. However, cTnI and CK-MB levels were significantly higher after ONBHCAB than after OPCAB with median peak cTnI of 9.85 versus 4.60 ng/mL and median peak CK-MB of 48.45 versus 17.10 ng/mL in the matched cohort, which were quite low, below the threshold for values defining perioperative myocardial infarction. At follow-up of 73 ± 45 months, the overall actuarial survival rates were similar between the ONBHCAB and OPCAB patients (86 vs. 87% at 5 years and 64 vs. 68% at 10 years, respectively, in the matched cohort). CONCLUSION: ONBHCAB may be a comparable alternative to OPCAB with similar early and late outcomes, despite higher elevation of postoperative cardiac biomarkers. ONBHCAB provides more efficient hemodynamic support, providing a better surgical visual field, than OPCAB while reducing the risk of incomplete revascularization.

Coexistence of anterior choroidal artery and posterior cerebral artery retia mirabilia presenting with subarachnoid hemorrhage: illustrative case.

BACKGROUND: A rete mirabile is a rare vascular anomaly, with posterior cerebral artery (PCA) involvement being especially rare. Its pathogenesis has been speculated as a remnant of "distal annexation" between the primitive anterior choroidal artery (AchA) and the PCA at this site, but the exact mechanisms remain unclear. OBSERVATIONS: A 29-year-old man presented with subarachnoid hemorrhage. Arteriovenous malformation in the medial temporal lobe was initially suspected, but an arteriovenous shunt was not detected. First, conservative treatment was administered; however, rebleeding occurred 1 month later. Carotid angiography revealed a network-like cluster of blood vessels at the choroidal point of the AchA, suggesting a rete mirabile; these vessel clusters led to the persistent temporo-occipital branch of the AchA. Furthermore, an aneurysm was detected at the junction between the rete mirabile and the persistent temporo-occipital branch of the AchA. Additionally, vertebral angiography demonstrated a rete mirabile at the P2 segment. These findings suggested the coexistence of AchA and PCA retia mirabilia. Consequently, the aneurysm was clipped using a subtemporal approach to prevent re-rupture, and the postoperative course was uneventful. LESSONS: This first report of coexisting AchA and PCA retia mirabilia supports the remnant of distal annexation between the primitive AchA and the PCA as the reason for rete formation at this site.

Fecal Occult Blood Screening before Cardiac Surgery.

BACKGROUND: Concerns of gastrointestinal (GI) bleeding after cardiac surgery are increasing with increased use of antiplatelets and anticoagulants. We investigated the roles of preoperative screening for fecal occult blood by fecal immunochemical test (FIT) widely used to detect GI bleeding and cancer. METHODS: A retrospective review was done in 1,663 consecutive patients undergoing FIT before cardiac surgery between years 2012 and 2020. One or two rounds of FIT were performed 2 to 3 weeks before surgery, when antiplatelets and anticoagulants were not suspended yet. RESULTS: Positive FIT (> 30 µg of hemoglobin/g of feces) was observed in 227 patients (13.7%). Preoperative risk factors for positive FIT included age > 70 years, anticoagulants, and chronic kidney disease. Of those with positive FIT, 180 patients (79%) received preoperative endoscopy, including gastroscopy (n = 139), colonoscopy (n = 9), and both (n = 32), with no findings of bleeding. The most common finding of gastroscopy was atrophic gastritis (36%) while early gastric cancer was detected in 2 patients. The most common finding of colonoscopy was colon polyps (42%) while colorectal cancer was detected in 5 patients. Of 180 FIT-positive patients receiving endoscopy, 8 (4.4%) underwent preoperative GI treatment, while postoperative GI events were documented in 28 (15.6%). Of 1,436 with negative FIT, 21 (1.5%) presented GI complications after surgery. CONCLUSION: Preoperative FIT, which is influenced by anticoagulant use, has little impacts on identification of GI bleeding sites. However, it may be useful to detect GI malignant lesions, potentially impacting operative risks, surgical strategies, and postoperative management.

Posterior cerebral artery involvement in unilateral moyamoya disease is exclusively ipsilateral and influenced by RNF213 mutation gene dose: The SUPRA Japan study: PCA involvement in unilateral moyamoya.

OBJECTIVES: The characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. POPULATION AND METHODS: We analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. RESULTS: Among the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. CONCLUSIONS: Our findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD.

Flow characteristics of in-situ internal thoracic artery graft with competitive flow.

We report flow characteristics of an in-situ internal thoracic artery (LITA) graft with angiographically competitive flow to the left anterior descending artery (LAD), based upon intraoperative transit-time flow measurement (TTFM) during coronary artery bypass grafting with aortic valve replacement (AVR) and during re-AVR seven years later. Although intraoperative TTFM of the graft showed lower mean flow and higher pulsatility index, suggesting inadequate anastomosis, fast Fourier transform (FFT) analysis of TTFM waveforms presented gradual waning of the amplitude, as shown in patent grafts. FFT analysis of the TTFM waveforms is helpful to judge the patency of LITA to LAD, even with competitive flow. Learning objective: The internal thoracic artery (LITA) graft to left anterior descending artery (LAD) with angiographically competitive flow shows gradual waning of the amplitude on fast Fourier transform (FFT) analysis of the transit-time flow measurement (TTFM) waveforms, although lower mean graft flow, higher pulsatility index, and higher systolic reversal flow may suggest inadequate anastomosis. FFT analysis of the TTFM waveforms is useful to judge the patency of LITA to LAD, even with competitive flow.

Experience of using coronary perfusion balloon catheter for acute middle cerebral artery occlusion.

Background: We present the case of an individual with acute occlusion of the middle cerebral artery caused by atherosclerosis. The patient underwent angioplasty using a coronary perfusion balloon, which resulted in a favorable clinical outcome. Case Description: A 66-year-old male patient presented with an acute onset of right hemiplegia and dysarthria. Magnetic resonance imaging revealed an occlusion of the left middle cerebral artery, and alteplase was administered, followed by a mechanical thrombectomy and intracranial balloon catheter angioplasty. Due to restenosis, a coronary perfusion balloon catheter was used for a 15-minute angioplasty procedure while maintaining the perfusion. This treatment approach led to the recanalization of the artery and favorable clinical outcomes. Conclusion: The coronary perfusion balloon may represent a viable therapeutic alternative for the management of refractory intracranial atherosclerotic large vessel occlusion.

Stent retrieval for free-floating thrombus attached to carotid artery stenosis: A report of two cases.

Background: We report two cases who underwent mechanical thrombectomy using a stent retriever in advance of urgent carotid artery stenting (CAS) for carotid artery stenosis with free-floating thrombus (FFT). Case Description: Two patients showing symptomatic carotid artery stenosis with FFT underwent urgent endovascular surgery due to progressive neurological symptoms. The first case showed an FFT with 70% internal carotid artery (ICA) stenosis. After the completion of the common and external carotid artery balloon and distal ICA filter protection, we deployed a 6-mm-diameter stent retriever in the distal part of the stenosis. The white thrombus was retrieved; the angiographic shadow of the FFT disappeared; and CAS was performed. In the second case, due to a 90% severe stenosis lesion with FFT, balloon angioplasty was performed on the lesion using the push wire of the stent retriever. After angioplasty, the stent retriever was smoothly retrieved, and CAS was performed. Postoperative magnetic resonance imaging showed an increase in cerebral embolism in the first case; however, the patient's neurological symptoms improved. The second case showed in-stent plaque protrusion and required two additional stent placements; the patient showed no worsening of his neurological symptoms. Conclusion: In cases of carotid artery stenosis with FFT, it is technically possible to retrieve a thrombus with a stent retriever. Although thrombus removal may help reduce the risk of ischemic complications in a series of urgent CAS procedures, there are concerns such as mechanical irritation to the carotid artery plaque, and its indications and alternative treatments should be carefully considered.

Effects of Fractional Flow Reserve on Coronary Artery Bypass Graft Flow to Left Anterior Descending Artery.

BACKGROUND: The relationships between preoperative fractional flow reserve (FFR) values of the left anterior descending artery (LAD), FFRLAD, and intraoperative transit time flow measurement (TTFM) variables in coronary artery bypass grafting (CABG) remain unclear.Methods and Results: We retrospectively collected data for 74 in situ left internal thoracic artery (LITA) grafts and 27 saphenous vein grafts (SVGs) to the LAD that were shown to be patent on postoperative angiography. Spearman correlation coefficients were determined between FFRLADand TTFM parameters of the LITA graft, as follows: maximum flow (Qmax), -0.22 (P=0.077); minimum flow (Qmin), -0.40 (P=0.014); mean flow (Qm), -0.35 (P=0.039); pulsatility index (PI), 0.33 (P=0.008); diastolic filling (DF): 0.01 (P=0.83); and systolic reverse flow (SRF), 0.37 (P=0.002). Spearman correlation coefficients between FFRLADand TTFM parameters of the SVG to LAD were: Qmax, -0.65 (P=0.004); Qmin, -0.43 (P=0.044); Qm, -0.75 (P=0.001); PI, 0.53 (P=0.033); DF, 0.14 (P=0.48); and SRF, 0.61 (P=0.009). CONCLUSIONS: Both LITA grafts and SVGs to the LAD show negative correlations for FFRLADwith Qminand Qm, but positive correlations for FFRLADwith PI and SFR. These relationships between FFRLADand TTFM variables of CABG grafts to the LAD should be recognized.

Cranial geometry in patients with dystonia and Parkinson's disease.

Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.

Surgical repair of mitral valve regurgitation with anomalous unilateral single pulmonary vein.

We report a case of surgically repaired symptomatic mitral valve regurgitation (MR) in a 61-year-old woman with anomalous unilateral single pulmonary vein. A two-staged surgery was scheduled; first a catheter embolization of anomalous vessel to avoid recirculation of the blood into the left atrium during cardiopulmonary bypass, and second a mitral valve repair via right lateral thoracotomy. Learning objective: Scimitar sign is a horn-like shape on plain chest radiograph. One of the possible diagnoses is partial anomalous pulmonary venous return (APVR), which often requires surgical interventions due to comorbidities of congenital heart disease and recurrent pneumonia [1-3]. Another is anomalous unilateral single pulmonary vein (AUSPV), which is generally asymptomatic, and therefore, requires no medical interventions. This case addresses the advantage of multidetector computed tomography (CT) and the safety of two-staged strategy.

Evaluation of Serial Intra-Arterial Indocyanine Green Videoangiography in the Surgical Treatment of Cranial and Craniocervical Junction Arteriovenous Fistulae: A Case Series.

BACKGROUND AND OBJECTIVES: Intravenous indocyanine green (IV-ICG) videoangiography is commonly performed to detect blood flow in the microscopic view. However, intra-arterial ICG (IA-ICG) videoangiography provides high-contrast imaging, repeatability within a short period of time, and clear-cut separation of the arterial and venous phases compared with IV-ICG. These features are useful for detecting retrograde venous drainage (RVD) and shunt occlusion in arteriovenous fistulae (AVF) surgery. This study aimed to investigate whether IA-ICG videoangiography can be repeatable within a short period of time and be useful for detecting RVD and shunt occlusion in cranial- and craniocervical junction (CCJ)-AVF surgery. METHODS: Between January 2012 and December 2022, 50 patients were treated with endovascular or surgical intervention for cranial- and CCJ-AVF at Tokushima University Hospital. Of these, 5 patients (6 lesions) underwent open surgery with IA-ICG videoangiography in a hybrid operating room. We analyzed the data of these 5 patients (6 lesions). RESULTS: There were 4/patient (median, range 2-12) and 3.5/lesion (median, range 2-10) intraoperative IA-ICG runs. IA-ICG videoangiography detected RVD in all patients. Clearance of IA-ICG-induced fluorescence was achieved within 30 seconds in all patients at each region of interest. After the disconnection of the fistulae, IA-ICG videoangiography and intraoperative digital subtraction angiography (DSA) confirmed the disappearance of RVD in all patients. There were no complications associated with IA-ICG videoangiography. CONCLUSION: This study showed that IA-ICG videoangiography is repeatable within a short period of time before and after obliteration and can be useful for detecting RVD and shunt occlusion in cranial- and CCJ-AVF surgery. IA-ICG videoangiography also allows intraoperative DSA studies in a hybrid operating room. Considering the recent advancements in hybrid operating rooms, combining IA-ICG videoangiography with intraoperative DSA is a useful strategy for cranial- and CCJ-AVF surgery.

Neuronal Loss in the Bilateral Medial Frontal Lobe Revealed by 123I-iomazenil Single-photon Emission Computed Tomography in Patients with Moyamoya Disease: The First Report from Cognitive Dysfunction Survey of Japanese Patients with Moyamoya Disease (COSMO-Japan Study).

Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had <85 in each index were 27.8%-33.3% in the WAIS-III and 16.7%-47.2% in the Wechsler Memory Scale-Revised. The group analysis of iomazenil SPECT demonstrated a decreased accumulation in the bilateral medial frontal areas in comparison with the normal control, whereas there were no specific characteristics on conventional imaging in the cohort. Iomazenil SPECT is a possible universal diagnostic method for the extraction of patients with cognitive impairment in MMD.

Prognostic factors for acute large vessel occlusion with NIHSS 5 or lower.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular treatment have been performed for severe large vessel occlusion (LVO) and the results have been reported at high levels of evidence. However, acute treatment for LVO with mild symptom remains controversial. We retrospectively examined prognostic factors for LVO with mild symptoms. METHOD: We studied retrospectively the patients within 24 h of onset with large vessel occlusion with NIHSS score ??5. Outcomes were evaluated by modified Rankin Scale (mRS) at 90 days, with 0?2 defined as a good outcome and 3?6 as a poor outcome. Clinical characteristics of each case were examined. RESULT: Participants comprised 76 patients. Of the 76 patients. ICA occlusion showed good outcome in 17?/?19 cases (90%), whereas MCA occlusion showed good outcome in 36?/?54 cases (67%). Among the 14 cases showing positive results for distal intraarterial signal (d-IAS), outcomes were good in 6 cases (43%). On the other hand, the 32 d-IAS-negative cases showed good outcome in 28 cases (88%). Outcomes were thus significantly poorer for d-IAS-positive cases. CONCLUSION: MCA occlusion is associated with poor prognosis, even with NIHSS score ??5, and d-IAS may provide a predictor. J. Med. Invest. 70 : 22-27, February, 2023.

Squamous cell carcinoma invading peripheral cerebral blood vessels and causing repeated cerebral hemorrhage : A case report.

Squamous cell carcinoma (SCC) is known to have less brain metastasis, but the reasons are not well established. Herein, we report the case of an 82-year-old man with recurrent cerebral hemorrhage of unknown cause ; upon brain biopsy, SCC was diagnosed infiltrating peripheral blood vessels of the brain and that it was state of micro-metastasis. It is possible that the blood-brain barrier blocked the infiltration of SCC into the brain parenchyma, and it did not form a mass in the brain parenchyma. In addition, because it did not form a mass, it could not be diagnosed as a metastatic brain tumor by contrast-enhanced magnetic resonance imaging or contrast-enhanced computed tomography. Among cases of recurrent cerebral hemorrhage of unknown cause in a short period, there may be cases of vascular infiltration without crossing the blood-brain barrier. Thus, if similar cases of recurrent cerebral hemorrhage of unknown cause is observed, it is necessary to distinguish metastatic brain tumors even if there is no evidence of suspected tumor on contrast-enhanced magnetic resonance imaging scan. J. Med. Invest. 70 : 276-280, February, 2023.

Circulating miR-20b-5p and miR-330-3p are novel biomarkers for progression of atrial fibrillation: Intracardiac/extracardiac plasma sample analysis by small RNA sequencing.

BACKGROUND: Circulating microRNAs (miRNAs, miR) have been considered as biomarkers reflecting the underlying pathophysiology in atrial fibrillation (AF). Nevertheless, miRNA expression in the peripheral blood samples might not reflect a cardiac phenomenon since most miRNAs are expressed in numerous organs. This study aimed to identify the cardiac-specific circulating miRNAs as biomarkers for AF. METHODS: Plasma samples were obtained from a luminal coronary sinus catheter (CS, cardiac-specific samples) and femoral venous sheath (FV, peripheral samples) in patients with AF and paroxysmal supraventricular tachycardia (control, CTL) undergoing catheter ablation. The circulating miRNA profiles were analyzed by small RNA sequencing. Differently expressed miRNAs between AF and CTL were identified in each sample of the CS and FV; miRNAs exhibiting similar expression patterns in the CS and FV samples were selected as candidates for cardiac-specific biomarkers. The selected miRNAs were related to the outcome of catheter ablation of AF. RESULTS: Small RNA sequencing detected 849 miRNAs. Among the top 30 most differently expressed miRNAs between AF and CTL, circulating hsa-miR-20b-5p, hsa-miR-330-3p, and hsa-miR-204-5p had a similar pattern in the CS and FV samples. Another set of peripheral blood samples was obtained from AF patients undergoing catheter ablation (n = 141). The expression of the miR-20b-5p and miR-330-3p, but not the miR-204-5p, negatively correlated with the echocardiographic left-atrial dimension and was decreased in patients with AF recurrence as compared to those without AF recurrence during a 1-year follow-up. CONCLUSION: Circulating miR-20b-5p and miR-330-3p can be cardiac-specific biomarkers for atrial remodeling progression and arrhythmia recurrence after catheter ablation in AF patients.

Differences in amyloid-ß and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic traumatic brain microhemorrhages.

BACKGROUND: Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-ß (Aß), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear. OBJECTIVES: To test our hypothesis that Aß, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied. METHODS: Seven-week-old C57BL/6 male mice were injected with 15 µL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aß, tau, and p-tau were assessed immunohistochemically over time. RESULTS: On day 7 after blood injection, Iba-1+ and S100B+ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aß deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aß. Deposits of Aß, but not tau/p-tau, were phagocytosed by CD163+ macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aß and tau/p-tau. CONCLUSION: Deposition and regulation differ between Aß and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.