Cerebral small vessel disease markers and long-term prognosis in spontaneous intracerebral hemorrhage: the HAGAKURE-ICH study.

We investigated the effects of individual and cumulative cerebral small vessel disease (SVD) markers on long-term clinical outcomes in spontaneous intracerebral hemorrhage (sICH) patients. This prospective, single-center cohort study was conducted from 2012 to 2019. SVD markers, including lacunae, cerebral microbleeds, white matter hyperintensity (WMH), and perivascular spaces in the basal ganglia, were assessed to calculate a summary SVD score. Patients were categorized into severe (score ≥3) and non-severe (score 0-2) SVD burden groups. Functional prognosis was defined as recovery, no change, or decline based on modified Rankin Scale changes at 2 years after discharge, excluding death. Associations of SVD burden and individual SVD markers with outcomes were evaluated using Cox proportional hazards modeling for recurrent stroke and all-cause mortality, and using ordinal logistic regression for functional prognosis. Among 155 sICH patients who underwent MRI, 98 showed severe SVD burden. Recurrent stroke and all-cause mortality rates were 2.2 and 8.3 per 100 patient-years, respectively, over a median 2.1-year follow-up. In terms of functional prognosis, 57 patients (51.8%) recovered, 32 (29.1%) showed no change, and 21 (19.1%) declined. A significant association was apparent between severe SVD burden and poorer functional prognosis (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.04-6.04; p = 0.042), particularly with moderate-to-severe WMH (OR 2.54, 95%CI 1.02-6.54; p = 0.048). The cumulative effects of SVD markers inhibited long-term functional recovery in sICH patients. Severe SVD burden, as well as moderate-to-severe WMH, can be indicators of long-term prognosis after sICH.

Traumatic Vertebral Artery Dissection Without Cervical Spine Injury Treated by Mechanical Thrombectomy.

A 59-year-old female injured in a motor vehicle accident presented with progressively impaired consciousness, and emergent magnetic resonance imaging (MRI) revealed basilar artery occlusion (BAO). Mechanical thrombectomy (MT) was performed immediately and achieved complete recanalization. Contrast-enhanced MRI also indicated right vertebral artery dissection (VAD), and the patient was subsequently diagnosed with artery-to-artery embolism caused by traumatic VAD. Anticoagulation therapy was initiated postoperatively, and there was no VAD or BAO recurrence during the three-month follow-up. This is the first reported case of BAO caused by traumatic VAD in an adult without accompanying cervical vertebral fracture treated using MT.

Subarachnoid iodine leakage on dual-energy computed tomography after mechanical thrombectomy is associated with malignant brain edema.

BACKGROUND: Dual-energy computed tomography (DE-CT) can differentiate between hemorrhage and iodine contrast medium leakage following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We determined whether subarachnoid hemorrhage (SAH) and subarachnoid iodine leakage (SAIL) on DE-CT following MT were associated with malignant brain edema (MBE). METHODS: We analyzed the medical records of 81 consecutive anterior circulation AIS patients who underwent MT. SAH or SAIL was diagnosed via DE-CT performed immediately after MT. We compared the procedural data, infarct volumes, MBE, and modified Rankin scale 0-2 at 90 days between patients with and without SAH and between patients with and without SAIL. Furthermore, we evaluated the association between patient characteristics and MBE. RESULTS: A total of 20 (25%) patients had SAH and 51 (63%) had SAIL. No difference in diffusion-weighted imaging (DWI)-infarct volume before MT was observed between patients with and without SAH or patients with and without SAIL. However, patients with SAIL had larger DWI-infarct volumes 1 day following MT than patients without SAIL (95 mL vs 29 mL; p=0.003). MBE occurred in 12 of 81 patients (15%); more patients with SAIL had MBE than patients without SAIL (22% vs 3%; p=0.027). Severe SAIL was significantly associated with MBE (OR, 12.5; 95% CI, 1.20-131; p=0.006), whereas SAH was not associated with MBE. CONCLUSION: This study demonstrated that SAIL on DE-CT immediately after MT was associated with infarct volume expansion and MBE.

Associations for progression of cerebral small vessel disease burden in healthy adults: the Kashima scan study.

To investigate the association between vascular risk factors and progression of cerebral small vessel disease (SVD), we conducted a longitudinal study with neurologically healthy cohort composed mostly of middle-aged adults (n = 665, mean age, 57.7 years). Subjects, who had both baseline data of brain health examinations including MRI and follow-up MRI at least 1 year after the baseline MRI, were included this study. The presence of features of SVD, including lacunes, cerebral microbleeds, white matter hyperintensity, and basal ganglia perivascular spaces were summed to obtain "total SVD score" (range, 0-4). Progression of SVD was evaluated among subjects with a total SVD score of ≤ 3 and was defined as a ≥ 1 point increase in that score at follow-up relative to baseline. As the primary analysis, multivariate logistic regression analyses were performed to determine the associations of progression of SVD at baseline. The median follow-up period was 7.3 years and progression of SVD was observed in 154 subjects (23.2%). Even after adjustment with confounders multivariate logistic regression analyses showed that progression of SVD was associated with age (per 10-year increase, odds ratio [OR]: 2.08, 95% confidence interval [CI] 1.62-2.67), hypertension (OR 1.55, 95%CI 1.05-2.29), systolic blood pressure (BP) (per standard deviation [SD] increase, OR 1.27, 95%CI 1.04-1.54), diastolic BP (per SD increase, OR 1.23, 95%CI 1.01-1.50), and mean arterial pressure (per SD increase, OR 1.27, 95%CI 1.04-1.55). Age and high blood pressure appear to play key roles in the progression of cerebral small vessel burden after mid-life.

Three-Dimensional (3D) Microcatheter Shaping Using Touch Screen Devices for Cerebral Aneurysm Coil Embolization.

OBJECTIVE: In cerebral aneurysm coil embolization, proper microcatheter shaping is crucial to reduce complications and achieve sufficient embolization. Shaping a microcatheter in 3 dimensions (3D) is often required but can be challenging. We assessed the usefulness of a novel shaping on screen (SOS) method that displays real-size 3D rotational angiography (RA) images on a touch screen device during cerebral aneurysm embolization to facilitate 3D microcatheter shaping. METHODS: In this study, 18 patients with cerebral aneurysm treated with this technique were included. Real-size 3D-RA images obtained during the embolization procedure were displayed on the touch screen device, which allowed for real-time manipulation. The shape of the microcatheter was adjusted to conform to the curvature of the vessel by swiping the touch screen device and bending the mandrel accordingly. We assessed the clinical and angiographic results, along with the accuracy and stability of the microcatheter. RESULTS: No procedure-related complications were observed. The mean packing density was 41% ± 12%. In all but 1 case, microcatheters were inserted into the aneurysms without guidewire assistance. After coiling, all microcatheter forms were stable. CONCLUSIONS: Three-dimensional (3D) microcatheter shaping using touch screen devices during cerebral aneurysm coil embolization may be simple and safe and can achieve high packing density of aneurysms.

Pituitary adenoma presenting as isolated oculomotor nerve palsy.

Background: Isolated oculomotor nerve palsy is a relatively uncommon symptom of pituitary adenoma that usually occurs in association with pituitary apoplexy or cavernous sinus (CS) invasion. Case Description: We report two cases of relatively small pituitary adenomas with neither apoplexy nor CS invasion presenting as isolated oculomotor nerve palsy. Both patients presented with gradually worsening diplopia, without headache or visual field defects. Magnetic resonance imaging (MRI) showed a pituitary tumor with no evidence of intratumoral hemorrhage. Computed tomography revealed a lateroposterior extension of the tumor with the erosion of the posterior clinoid process. Constructive interference in steady-state MRI revealed compression of the oculomotor nerve by the tumor at the oculomotor triangle. The patients underwent endoscopic transsphenoidal surgery, and the intraoperative findings showed that the tumors did not invade the CS. The tumors were completely resected, and the oculomotor palsies resolved fully. Conclusion: These cases illustrate the need to consider isolated oculomotor nerve palsy as an initial manifestation of a relatively small pituitary adenoma with neither apoplexy nor CS invasion. Based on the characteristic radiological findings, early surgical treatment is recommended to preserve oculomotor function.

Microaerophilic Activated Sludge System for Ammonia Retention toward Recovery from High-Strength Nitrogenous Wastewater: Performance and Microbial Communities.

A transition to ammonia recovery from wastewater has started; however, a technology for sustainable nitrogen retention in the form of ammonia and organic carbon removal is still in development. This study validated a microaerophilic activated sludge (MAS) system to efficiently retain ammonia from high-strength nitrogenous wastewater. The MAS is based on conventional activated sludge (CAS) with aerobic and settling compartments. Low dissolved oxygen (DO) concentrations (<0.2 mg/L) and short solids retention times (SRTs) (<5 days) eliminated nitrifying bacteria. The two parallel MASs were successfully operated for 300 days and had ammonia retention of 101.7 ± 24.9% and organic carbon removal of 85.5 ± 8.9%. The MASs mitigated N2O emissions with an emission factor of <0.23%, much lower than the default value of CAS (1.6%). A short-term step-change test demonstrated that N2O indicated the initiation of nitrification and the completion of denitrification in the MAS. The parallel MASs had comparable microbial diversity, promoting organic carbon oxidation while inhibiting ammonia-oxidizing microorganisms (AOMs), as revealed by 16S rRNA gene amplicon sequencing, the quantitative polymerase chain reaction of functional genes, and fluorescence in situ hybridization of ß-proteobacteria AOB. The microbial analyses also uncovered that filamentous bacteria were positively correlated with effluent turbidity. Together, controlling DO and SRT achieved organic carbon removal and successful ammonia retention, mainly by suppressing AOM activity. This process represents a new nitrogen management paradigm.

Hypertension, cerebral Amyloid, aGe Associated Known neuroimaging markers of cerebral small vessel disease Undertaken with stroke REgistry (HAGAKURE) prospective cohort study: Baseline characteristics and association of cerebral small vessel disease with prognosis in an ischemic stroke cohort.

Introduction: Cerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, "total SVD score" - which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia- and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke. Methods and design: This prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0-4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan-Meier method. Results: Consecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0-83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33-64.23; HR 2.81, 95% CI 1.08-7.30; HR 2.90, 95% CI 1.22-6.88, respectively). Conclusion: The accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

Cervical Cord Compression by Aberrant Vertebral Artery Presenting with Neuralgic Pain: A Case Report.

The vertebral artery (VA) is often affected by anatomical variations; however, it is usually asymptomatic and is found incidentally. Herein, we report a case of cervical cord compression caused by bilateral aberrant VAs. A 65-year-old woman presented with paroxysmal lancinating pain in the neck that later extended to the shoulders and upper arms bilaterally. Magnetic resonance imaging and computed tomographic angiography revealed an aberrant course of both VAs entering the spinal canal between the atlas and axis and compressing the cervical cord at the atlas level. Microvascular decompression was performed with transposition of the VAs, and the pain resolved immediately after the surgery. A certain number of anatomical variants of the distal VA can be explained by size variations and connection of the lateral spinal artery (LSA). Considering that an aberrant VA may correspond to an enlarged LSA, optimal transposition should be performed to prevent neurological complications.

Microsurgical Approach for True Posterior Communicating Artery Aneurysms: Literature Review and Illustrative Case.

True posterior communicating artery (PCoA) aneurysms are rare. Although true PCoA aneurysms have been reported to be located close to the internal carotid artery, at the middle part of PCoA, or close to the posterior cerebral artery; the best surgical approach to treat true PCoA aneurysms in each location remains unclear. We conducted a literature review using data from PubMed. Data on demographics, location, and projecting direction of the aneurysm, surgical approach, and surgical complications were collected. A total of 47 true PCoA aneurysms were included. Twenty-nine aneurysms originated from the proximal portion, 10 from the middle portion, and 6 from the distal portion; there were two giant aneurysms. The ipsilateral pterional approach was used for 37 true PCoA aneurysms (27 in proximal portion, 8 in middle portion, and 2 in distal portion of PCoA). The anterior temporal approach was used for two distal-portion aneurysms and one giant aneurysm. The anterior subtemporal approach was used for one distal-portion aneurysm. The subtemporal approach was used for two middle-portion aneurysms and one giant aneurysm. The contralateral pterional approach was used for two proximal-portion and one distal-portion aneurysms. Although most true PCoA aneurysms can be treated by the pterional approach, other means such as anterior temporal and subtemporal approaches can be applicable for aneurysms in the middle and distal portions of the PCoA or giant aneurysms. Surgeons should select an appropriate approach for each aneurysm while considering the advantages and disadvantages of each technique.

A Tumor Suppressor Gene, N-myc Downstream-Regulated Gene 1 (NDRG1), in Gliomas and Glioblastomas.

The development of potent and selective therapeutic approaches to glioblastoma (GBM) requires the identification of molecular pathways that critically regulate the survival and proliferation of GBM. Glioblastoma stem-like cells (GSCs) possess stem-cell-like properties, self-renewal, and differentiation into multiple neural cell lineages. From a clinical point of view, GSCs have been reported to resist radiation and chemotherapy. GSCs are influenced by the microenvironment, especially the hypoxic condition. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress the proliferation, invasion, and migration of cancer cells. Previous studies have reported that deregulated expression of NDRG1 affects tumor growth and clinical outcomes of patients with GBM. This literature review aimed to clarify the critical role of NDRG1 in tumorigenesis and acquirement of resistance for anti-GBM therapies, further to discussing the possibility and efficacy of NDRG1 as a novel target of treatment for GBM. The present review was conducted by searching the PubMed and Scopus databases. The search was conducted in February 2022. We review current knowledge on the regulation and signaling of NDRG1 in neuro-oncology. Finally, the role of NDRG1 in GBM and potential clinical applications are discussed.

Case of de novo cerebral microbleeds in ischemic-type pediatric moyamoya disease.

BACKGROUND: Studies on pediatric patients with moyamoya disease who presented with de novo cerebral microbleeds (CMBs) are extremely rare. CASE DESCRIPTION: Herein, we report a 7-year-old boy with moyamoya disease who had de novo CMBs during treatment. He presented with transient left-side motor weakness and was diagnosed with moyamoya disease. He underwent revascularization surgery on the right cerebral hemisphere. Six months after the surgery, he presented with transient right-side motor weakness and MRA revealed progression of stenosis in the left middle cerebral artery. After another 3 months, three de novo CMBs were identified. He underwent revascularization surgery on the left side. The symptom disappeared completely after surgery and no additional de novo CMBs were identified 1 year after surgery. CONCLUSION: This is the first report on de novo CMBs in pediatric patients. Although the significance of de novo CMBs in pediatric patients is completely unknown, attention should be paid to not only ischemic stroke but also hemorrhagic stroke. Although the short-term course is good in the current case, follow-up period is too short to assess for rebleeding and long-term follow-up is still important. Further, more cases should be collected.

Elimination of the check-valve mechanism of the sacral Tarlov cyst using a rotation flap technique in a pediatric patient: technical note.

OBJECTIVE: Symptomatic Tarlov cysts in children are not sufficiently reported and treatment methods for Tarlov cysts are still controversial. The goal of this manuscript is to introduce a new variation of the surgical technique. METHODS: We performed surgery to eliminate the one-way check valve mechanism of the Tarlov cyst in a 7-year-old female who presented with urinary and fecal incontinence. A relatively large S3 nerve root cyst showed a one-way check valve on computed tomography myelography. The inlet of the check valve was enlarged with rotation flap reconstruction. RESULTS: Two months after surgery, the patient had established normal sphincter control. MRI performed two years later showed that the treated cyst was collapsing, and no recurrence occurred. CONCLUSIONS: Rotation flap enlargement of the check valve inlet is a safe and efficacious option for the treatment of pediatric patients with sacral Tarlov cysts.

Increased levels of plasma nucleotides in patients with rheumatoid arthritis.

Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive non-targeted metabolomics approach combining capillary electrophoresis time-of-flight mass spectrometry (TOFMS) and liquid chromatography TOFMS. We constructed metabolomics profiling of 286 plasma samples of a Japanese population [92 RA patients, 13 systemic lupus erythematosus (SLE) patients and 181 healthy controls). RA case-control association tests showed that seven metabolites exhibited significantly increased levels in RA samples compared with controls (P < 1.0 × 10-4; UTP, ethanolamine phosphate, ATP, GDP, ADP, 6-aminohexanoic acid and taurine), whereas one exhibited a decreased level (xanthine). The plasma levels of these eight metabolites were not significantly different between seropositive and seronegative RA patients (P > 0.05; n = 68 and 24, respectively). The four nucleotide levels (UTP, ATP, GDP and ADP) were significantly higher in the non-treatment patients in comparison between patients with and without treatment (P < 0.014; n = 57 and 35, respectively). Furthermore, we found that none of the four nucleotide levels showed significant differences in SLE case-control association tests (P > 0.2; 13 patients with SLE and the 181 shared controls) and psoriatic arthritis (PsA) case-control association tests (P > 0.11; 42 patients with PsA and 38 healthy controls), indicating disease specificity in RA. In conclusion, our large-scale metabolome analysis demonstrated the increased plasma nucleotide levels in RA patients, which could be used as potential clinical biomarkers of RA, especially for seronegative RA.

Activated sludge microbiome in a membrane bioreactor for treating Ramen noodle-soup wastewater.

Population shifts in the activated sludge microbiome of a membrane bioreactor (MBR) during the treatment of Ramen noodle-soup wastewater were analyzed by high-throughput sequencing. An MBR underwent stable treatment of wastewater containing increasing oil concentrations (from 135 to 1,350 mg/L) for 26 days; however, after feeding with wastewater containing 2,700 mg/L of oil, the mixed liquor suspended solids and transmembrane pressure exhibited gradual and rapid increases, respectively, leading to clogging of the membrane. Phylogenetic analysis revealed an oil supply-dependent increase in the abundance of Cupriavidus gilardii (relative abundance of 26.2% at Day 30) in the sludge together with Parasegetibacter terrae (9.9%) and Ferruginibacter yonginensis (9.4%). These dominant species may play important roles in noodle-soup wastewater treatment.

Influence of Microcatheter Position on First-pass Success of Thrombectomy for Acute Ischemic Stroke.

OBJECTIVE: In acute ischemic stroke, patient outcomes can be improved by first-pass successful recanalization of the occluded vessel. This study investigated whether microcatheter position could influence the success of first-pass recanalization. METHODS: We retrospectively analyzed 59 consecutive acute ischemic stroke patients who underwent intra-arterial thrombectomy with stent retrievers for middle cerebral artery (M1) occlusion. Angiography findings obtained via the first pass of the microcatheter were analyzed. The microcatheter was considered to be inserted into M2 segments that gave rise to parietal arteries (M2P) if the anterior or posterior parietal artery was observed. Recanalization results were compared between patients with and without microcatheter insertion into M2P. The angle and diameter of vessels were measured using post-procedural magnetic resonance angiography. RESULTS: The rate of first-pass successful recanalization (modified thrombolysis in cerebral infarction score of ≥2b) was significantly higher in patients with microcatheter insertion into M2P than in those without (56% vs. 22%, P = 0.016). The number of passes was lower in patients with first-pass microcatheter insertion into M2P than in those without (1.8 ± 1.0 vs. 2.5 ± 1.5, P = 0.05). The mean diameter of M2P was significantly larger than that of the other M2 (1.9 ± 0.6 mm vs. 1.7 ± 0.5 mm, P = 0.035). The M1/M2P angle was significantly smaller than that between M1 and the other M2. (49° ± 32° vs. 67° ± 31°, P = 0.006). CONCLUSIONS: First-pass microcatheter insertion into M2P may contribute to fast successful recanalization in patients with M1 occlusion who undergo intra-arterial thrombectomy using stent retrievers.

Ultrafast Synthesis of Silica-Based Molecular Sieve Membranes in Dielectric Barrier Discharge at Low Temperature and Atmospheric Pressure.

Microporous silica membranes have shown promise as potential candidates for energy-efficient chemical separation. Herein, we report the ultrafast synthesis of silica membranes, on the order of minutes, in atmospheric-pressure, low-temperature plasma. Direct deposition in the discharge region of atmospheric-pressure plasma enables the immediate formation of a thin silica layer on a porous substrate. The plasma-deposited layer had a thickness of ∼13 nm and was confined to the immediate surface of the substrate. With an increase in deposition temperature, we observed an increase in the inorganic nature of the plasma-deposited layer and simultaneous improvement in the membrane performance. Consequently, the resulting membranes exhibited outstanding permeance for small-sized gas molecules, such as H2 (>10-6 mol m-2 s-1 Pa-1), with a high H2/SF6 permeance ratio of ∼6300, providing a nonthermal alternative for the fabrication of silica-based membranes.