Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

Assessment of language lateralization in epilepsy patients using the super-selective Wada test.

BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.

[Academia-Industry Alliance: Recent Trend].

Industry-academia Collaboration is an academic activity within academia(educational institutions such as universities, research institutes, etc.)formed to research and develop new technologies, create new businesses and knowledge, and recruit outsourcing human resources. There is a collaboration between an industry(a private company, a group that engages in broad commercial activities and links research and development directly to economic activity)and academia. Amidst the dramatic changes in the environment surrounding the goals of research and development of new technologies and the creation of new businesses, there are changes in what academia can do complementarily. We will outline the changes and current situation, including the efforts of the Tohoku University Hospital.

Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

A first-in-human study of the anti-inflammatory profibrinolytic TMS-007, an SMTP family triprenyl phenol.

AIMS: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation. We aim to evaluate the safety, pharmacokinetics and pharmacodynamics of TMS-007 in healthy volunteers. METHODS: This was a randomized, placebo-controlled, double blind, dose-escalation study, administered as a single intravenous infusion of TMS-007 in cohorts of healthy male Japanese subjects. Six cohorts were planned, but only five were completed. In each cohort (n = 8), individuals were randomized to receive one of five doses of TMS-007 (3, 15, 60, 180 or 360 mg; n = 6) or placebo (n = 2). RESULTS: TMS-007 was generally well tolerated, and no serious adverse events were attributed to the drug. A linear dose-dependency was observed for plasma TMS-007 levels. No symptoms of bleeding were observed on brain MRI analysis, and no bleeding-related responses were found on laboratory testing. The plasma levels of the coagulation factor fibrinogen and the anti-fibrinolysis factor α2 -antiplasmin levels were unchanged after TMS-007 dosing. A slight increase in the plasma level of plasmin-α2 -antiplasmin complex, an index of plasmin formation, was observed in the TMS-007 group in cohort 2. CONCLUSIONS: TMS-007 is generally well tolerated and exhibits favourable pharmacokinetic profiles that warrant further clinical development.

Principal component analysis of texture features for grading of meningioma: not effective from the peritumoral area but effective from the tumor area.

PURPOSE: To investigate whether texture features from tumor and peritumoral areas based on sequence combinations can differentiate between low- and non-low-grade meningiomas. METHODS: Consecutive patients diagnosed with meningioma by surgery (77 low-grade and 28 non-low-grade meningiomas) underwent preoperative magnetic resonance imaging including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1WI (CE-T1WI). Manual segmentation of the tumor area was performed to extract texture features. Segmentation of the peritumoral area was performed for peritumoral high-signal intensity (PHSI) on T2WI. Principal component analysis was performed to fuse the texture features to principal components (PCs), and PCs of each sequence of the tumor and peritumoral areas were compared between low- and non-low-grade meningiomas. Only PCs with statistical significance were used for the model construction using a support vector machine algorithm. k-fold cross-validation with receiver operating characteristic curve analysis was used to evaluate diagnostic performance. RESULTS: Two, one, and three PCs of T1WI, apparent diffusion coefficient (ADC), and CE-T1WI, respectively, for the tumor area, were significantly different between low- and non-low-grade meningiomas, while PCs of T2WI for the tumor area and PCs for the peritumoral area were not. No significant differences were observed in PHSI. Among models of sequence combination, the model with PCs of ADC and CE-T1WI for the tumor area showed the highest area under the curve (0.84). CONCLUSION: The model with PCs of ADC and CE-T1WI for the tumor area showed the highest diagnostic performance for differentiating between low- and non-low-grade meningiomas. Neither PHSI nor PCs in the peritumoral area showed added value.

Simulation of the occipital transtentorial approach incorporating visualization of the cerebellar tentorium using three-dimensional computed tomography angiography and gadolinium-enhanced T1-weighted magnetic resonance imaging: technical note.

The occipital transtentorial approach (OTA) is one of the useful approaches to the lesions of the pineal region, dorsal brainstem, and supracerebellar region. However, a wide operative field is sometimes difficult to obtain due to the tentorial sinus and bridging veins. This study evaluated the usefulness of preoperative simulation of OTA, specifically including the cerebellar tentorium in 9 patients. All patients underwent computed tomography angiography and venography and gadolinium-enhanced three-dimensional T1-weighted magnetic resonance images (Gd-3D-T1WI). The images were fused, and the cerebellar tentorium, vessels, and tumor were manually extracted from Gd-3D-T1WI to obtain the simulation images. Visualization of the cerebellar tentorium could discriminate between bridging veins from the occipital lobe and cerebellum, and recognize the site of bridging to the tentorial sinus and variants which may interfere with the tentorial incision. Simulation of the tentorial incision was also possible based on the relationships between the tumor, tentorial sinus, bridging vein, and cerebellar tentorium. The simulation suggested that safe tentorial incision was difficult in two sides because of the crossed tentorial sinus draining the left basal vein and draining veins from the glioblastoma. The OTA was performed in eight cases, and no difficulty was experienced in the tentorial incision in all cases. The simulation findings of the bridging vein and tentorial sinus were consistent with the intraoperative findings. Preoperative simulation including the cerebellar tentorium is useful for determining the optimum and safe side and required extent of the tentorial incision necessary for tumor resection with the OTA.

Formation of internal carotid artery aneurysms following gamma knife radiosurgery for pituitary adenomas: a case series and literature review.

Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far. Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic. The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought.

Visualization of the lenticulostriate arteries, long insular arteries, and long medullary arteries on intra-arterial computed tomography angiography with ultrahigh resolution in patients with glioma.

PURPOSE: The anatomical association between the lesion and the perforating arteries supplying the pyramidal tract in insulo-opercular glioma resection should be evaluated. This study reported a novel method combining the intra-arterial administration of contrast medium and ultrahigh-resolution computed tomography angiography (UHR-IA-CTA) for visualizing the lenticulostriate arteries (LSAs), long insular arteries (LIAs), and long medullary arteries (LMAs) that supply the pyramidal tract in two patients with insulo-opercular glioma. METHODS: This method was performed by introducing a catheter to the cervical segment of the internal carotid artery. The infusion rate was set at 3 mL/s for 3 s, and the delay time from injection to scanning was determined based on the time-to-peak on angiography. On 2- and 20-mm-thick UHR-IA-CTA slab images and fusion with magnetic resonance images, the anatomical associations between the perforating arteries and the tumor and pyramidal tract were evaluated. RESULTS: This novel method clearly showed the relationship between the perforators that supply the pyramidal tract and tumor. It showed that LIAs and LMAs were far from the lesion but that the proximal LSAs were involved in both cases. Based on these results, subtotal resection was achieved without complications caused by injury of perforators. CONCLUSION: UHR-IA-CTA can be used to visualize the LSAs, LIAs, and LMAs clearly and provide useful preoperative information for insulo-opercular glioma resection.

Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.

Convection-enhanced delivery (CED) delivers agents directly into tumors and the surrounding parenchyma. Although a promising concept, clinical applications are often hampered by insufficient treatment efficacy. Toward developing an effective CED-based strategy for delivering drugs with proven clinical efficacy, we performed a basic characterization study to explore the locally delivered characteristics of the water soluble nitrosourea nimustine hydrochloride (ACNU). First, ACNU distribution after CED in rodent brain was studied using mass spectrometry imaging. Clearance of 14C-labeled ACNU after CED in striatum was also studied. ACNU was robustly distributed in rodent brain similar to the distribution of the hydrophilic dye Evans blue after CED, and locally delivered ACNU was observed for over 24 h at the delivery site. Subsequently, to investigate the potential of ACNU to induce an immunostimulative microenvironment, Fas and transforming growth factor-ß1 (TGF-ß1) was assessed in vitro. We found that ACNU significantly inhibited TGF-ß1 secretion and reduced Fas expression. Further, after CED of ACNU in 9L-derived intracranial tumors, the infiltration of CD4/CD8 lymphocytes in tumors was evaluated by immunofluorescence.CED of ACNU in xenografted intracranial tumors induced tumor infiltration of CD4/CD8 lymphocytes. ACNU has a robust distribution in rodent brain by CED, and delayed clearance of the drug was observed at the local infusion site. Further, local delivery of ACNU affects the tumor microenvironment and induces immune cell migration in tumor. These characteristics make ACNU a promising agent for CED.

Spontaneous Shrinkage of isocitrate dehydrogenase (IDH)-mutant astrocytoma caused by intra-tumoural cyst rupture: a case report.

BACKGROUND: T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign is a specific imaging finding of isocitrate dehydrogenase (IDH)-mutant astrocytomas. Histologically, a hypointense area on FLAIR images indicates the presence of microcysts. Here we report a case of IDH-mutant astrocytoma that shrunk spontaneously. CASE DESCRIPTION: A 26-year-old woman presented with a complaint of headache. Her magnetic resonance (MR) images revealed a lesion mass with a T2-FLAIR mismatch sign in the left frontal lobe. Subsequently, after 1 month, she was referred to our department, and we found that the lesion had unexpectedly shrunk; however, no further shrinkage was observed in the next 3 months. Furthermore, a biopsy was performed, and the results indicated a diagnosis of astrocytoma, IDH-mutant CNS WHO grade 3. Thus, she underwent subtotal resection. We found no neurological deficits in the patient, and she received 60 Gy of radiotherapy at the local site and chemotherapy with nimustine hydrochloride (ACNU), followed by the administration of ACNU every 8 weeks for 2 years. Overall, after 36 months of tumour resection, she was in good health and exhibited no recurrence. Notably, her histological and MR image findings suggested that the macroscopic cyst was formed by the fusion of microcysts, which is a characteristic feature of IDH-mutant astrocytoma with a T2-FLAIR mismatch sign, and that the tumour shrunk because of the rupture of the cyst in the Sylvian cistern. CONCLUSION: The present case report suggests that IDH-mutant astrocytoma cannot be ruled out even when the lesion shrinks spontaneously.

Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury.

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

Optogenetic stimulus-triggered acquisition of seizure resistance.

Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such "kindling" process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed using in vivo microdialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.

Transient Global Cerebral Hypoperfusion as a Characteristic Cerebral Hemodynamic Pattern in the Acute Stage after Combined Revascularization Surgery for Pediatric Moyamoya Disease: N-Isopropyl-P-[123I] Iodoamphetamine Single-Photon Emission Computed Tomography Study.

INTRODUCTION: Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow (CBF) in both adult and pediatric patients with moyamoya disease (MMD). Uneven hemodynamic changes, including local cerebral hyperperfusion and remote ischemia, can cause delayed intracerebral hemorrhage and perioperative infarctions in adult MMD patients, but the characteristic hemodynamic pattern among pediatric MMD patients after revascularization surgery is poorly understood. METHODS: This study included 16 consecutive pediatric MMD patients (age, 6-16 years; mean age, 11.3) undergoing superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-myo-synangiosis on 21 affected hemispheres. Perioperative management was conducted by aspirin administration and strict blood pressure control (110-130 mm Hg). We prospectively performed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography on postoperative days (POD) 1 and 7 and analyzed the temporal changes in perioperative hemodynamics. RESULTS: Four patients (19.0%, 4/21) exhibited immediate CBF improvement from POD 1, which was classified as "immediate redistribution pattern." In contrast, 9 (42.9%, 9/21) demonstrated transient hemispheric global hypoperfusion at POD 1 and subsequent CBF improvement at POD 7, which was defined as "transient hypoperfusion pattern." Although 8 patients, including 4 with "transient hypoperfusion pattern" (44.4, 4/9), developed mild transient neurological deterioration in the acute stage, it resolved in all 21 patients, and there were no permanent neurological deficits. DISCUSSION/CONCLUSIONS: This study revealed that the "transient hypoperfusion pattern" after revascularization surgery is relatively common among pediatric MMD patients, and its outcome is favorable under strict perioperative management.

Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c.14576G>A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c.14576G>A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS. METHODS: This retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020. RESULTS: PPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c.14576G>A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0% (0/101), 0.5% (1/200), and 40% (2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c.14576G>A was statistically significant in MMD/quasi-MMD patients (p = 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction. CONCLUSIONS: The homozygote variant of RNF213 polymorphism c.14576G>A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.

Intraoperative motor-evoked potential monitoring during coil embolization for anterior choroidal artery aneurysms.

PURPOSE: Intraoperative motor-evoked potential (MEP) monitoring is widely used in the neck clipping of cerebral aneurysms. Little is known regarding the usefulness of intraoperative MEP monitoring in endovascular aneurysm surgery. The purpose of this study was to validate the feasibility of intraoperative MEP monitoring during the coil embolization of anterior choroidal artery (AChA) aneurysms. METHODS: Clinical and angiographic data of consecutive patients who underwent coil embolization for unruptured AChA aneurysms with or without intraoperative MEP monitoring between January 2014 and December 2018 at our institute were abstracted and analyzed retrospectively. RESULTS: Twenty-three unruptured AChA aneurysms were treated. Eleven patients received MEP monitoring, and three of them experienced intraoperative reduction or disappearance of the MEP wave. Even during MEP changes, AChA filling showed no change in any of the three cases. Although one case with MEP monitoring encountered the disappearance of AChA filling, there was no change in MEP. This might be due to retrograde filling of the AChA from the anastomosis with the lateral posterior choroidal artery. AChA blood flow detected by angiography did not always reflect MEP status. When comparing the presence or absence of MEP monitoring, the volume embolization ratio of coiled aneurysms was significantly better in the MEP group. CONCLUSION: Intraoperative MEP monitoring during endovascular coiling for AChA aneurysms may be feasible. AChA blood flow detected by angiography does not always reflect MEP status.

Prediction of atherosclerotic changes in cavernous carotid aneurysms based on computational fluid dynamics analysis: a proof-of-concept study.

PURPOSE: Recent computational fluid dynamics (CFD) studies have demonstrated the concurrence of atherosclerotic changes in regions exposed to prolonged blood residence. In this proof-of-concept study, we investigated a small but homogeneous cohort of large, cavernous carotid aneurysms (CCAs) to establish the clinical feasibility of CFD analysis in treatment planning, based on the association between pathophysiology and hemodynamics. METHODS: This study included 15 patients with individual large CCAs. We identified calcifications, which indicated atherosclerotic changes, using the masking data of digital subtraction angiography. We conducted a CFD simulation under patient-specific inlet flow rates measured using magnetic resonance (MR) velocimetry. In the post-CFD analysis, we calculated the blood residence time ([Formula: see text]) and segmented the surface exposed to blood residence time over 1 s ([Formula: see text]). We measured the decrease in volume after flow diversion using the original time-of-flight MR angiography data. RESULTS: Calcifications were observed in the region with [Formula: see text]. In addition, the ratio of [Formula: see text] to the surface of the aneurysmal domain exhibited a negative relationship with the rate of volume reduction at the 6- and 12-month follow-ups. Post-CFD visualization demonstrated that intra-aneurysmal swirling flow prolonged blood residence time under the condition of a small inlet flow rate, when compared to the aneurysmal volume. CONCLUSION: The results of this study suggest the usefulness of CFD analysis for the diagnosis of atherosclerotic changes in large CCAs that may affect the therapeutic response after flow diversion.

Quantitative assessment of microstructural evolution of intracranial aneurysm wall by vessel wall imaging.

PURPOSE: This study aimed to evaluate new quantitative parameters of aneurysm wall enhancement (AWE) on magnetic resonance vessel wall imaging (VWI) in differentiating between the stable and evolving unruptured intracranial aneurysms (UIAs). METHODS: Thirty-eight consecutive patients with UIAs (27 stable and 11 evolving) underwent VWI with contrast-enhanced 3D T1 volume isotropic turbo spin echo acquisition. The voxel-based enhancement maps were created using pre- and post-contrast images. The aneurysmal lumen with signal suppression by black-blood method was segmented. Then, one voxel outer and inner layers of the lumen contour were automatically segmented. The shape features of the aneurysms and AWE of the two layers were compared between stable and evolving groups. RESULTS: The shape features, including aneurysm volume, surface, and compacity were significantly different between the stable and evolving groups (P = 0.024, 0.028, and 0.033, respectively). Stable and evolving groups also differed significantly in the AWE at the union of outer and inner layers of the aneurysm wall (P = 0.0082) but not in that of the outer or inner layer alone. Multivariate logistic regression analysis revealed significant differences in aneurysm volume, surface, and AWE at the union of outer and inner layers between the two groups (P = 0.0029, 0.0092, and 0.0033, respectively). Receiver operating characteristics curve analysis revealed that the area under the curve of the logistic regression model was 0.89. CONCLUSION: Quantitative combined analysis of aneurysm shape features and AWE of the union of outer and inner layers were effective for differentiating between stable and evolving UIAs.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.