An exploratory prospective phase II study of preoperative neoadjuvant bevacizumab and temozolomide for newly diagnosed glioblastoma.

PURPOSE: This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB). METHODS: Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy. RESULTS: Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively. CONCLUSION: Preoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively. TRIAL REGISTRATION NUMBER: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233 . Registration Date: Jan. 16, 2017.

Successful spinal cord stimulation using fast-acting sub-perception therapy for postoperative neuropathic pain of syringomyelia with Chiari malformation type 1: a case report and literature review.

BACKGROUND: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). CASE PRESENTATION: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. CONCLUSION: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.

[Simulation for Endovascular Treatment].

With the advent of high-resolution imaging and advancements in computational fluid dynamics(CFD)and computational structural mechanics(CSM)analyses, clinical simulation of endovascular intervention has gradually become feasible. Virtual stents have become indispensable for coil embolization. For braided stents, such as those with low-profile visualized intraluminal support and flow diverters, predicting postplacement elongation and contraction is challenging; however, software development has enabled more precise treatment planning. Additionally, simulations utilizing three-dimensional(3D)printer models can enable realistic simulations of procedures such as intracranial stents and Woven EndoBridge placement. This approach is beneficial for shunt disorders such as arteriovenous malformations and dural arteriovenous fistulas, offering 3D visualization of shunt access routes and intuitive treatment strategy planning, even for beginners. Furthermore, it can be applied to procedures such as open surgical clipping and nidus resection, aiding in the selection of suitable clips and considerations for ideal resection based on nidus curvature. Simulations using CFD, CSM, and 3D printers are crucial for training surgeons and handling new devices. Harnessing medicine-engineering synergy is essential, and regulatory approval(insurance coverage)and appropriate commercialization of simulations are paramount for the future.

Prognostic survival biomarkers of tumor-fused dendritic cell vaccine therapy in patients with newly diagnosed glioblastoma.

Dendritic cell (DC)-based immunotherapy has been applied to glioblastoma (GBM); however, biomarkers informing response remain poorly understood. We conducted a phase I/IIa clinical trial investigating tumor-fused DC (TFDC) immunotherapy following temozolomide-based chemoradiotherapy in patients with newly diagnosed GBM and determined prognostic factors in patients receiving TFDC immunotherapy. Twenty-eight adult patients with GBM isocitrate dehydrogenase (IDH) wild-type (IDH-WT) were enrolled; 127 TFDC vaccine injections (4.5 ± 2.6 times/patient) were administered. Patients with GBM IDH-WT had a respectable 5-year survival rate (24%), verifying the clinical activity of TFDC immunotherapy, particularly against O6-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM (5-year survival rate: 33%). To identify novel factors influencing overall survival (OS) in GBM IDH-WT treated with TFDC immunotherapy, clinical parameters were assessed and comprehensive molecular profiling involving transcriptome and exome analyses was performed. MGMT promoter methylation status, extent of tumor resection, and vaccine parameters (administration frequency, DC and tumor cell numbers, and fusion ratio) were not associated with survival following TFDC immunotherapy. Old age and pre- and post-operative Karnofsky performance status were significantly correlated with OS. Low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were correlated with better prognosis. We validated the activity of TFDC immunotherapy against GBM IDH-WT, including chemoresistant, MGMT promoter unmethylated cases. The identification of molecular biomarkers predictive of TFDC immunotherapy efficacy in GBM IDH-WT will facilitate the design of and patient stratification in a phase-3 trial to maximize treatment benefits.

Thromboelastography 6s for assessment of platelet function during coil embolization of unruptured intracranial aneurysms.

OBJECTIVES: Methods for assessing platelet function in patients with neurovascular disease remain controversial and poorly studied. This study aimed to assess associations between thromboelastography 6s (TEG6s) measurements and postoperative ischemic complications in patients with unruptured intracranial aneurysms (UIAs) treated by coil embolization. METHODS: Eighty-four patients with UIAs taking a combined aspirin and clopidogrel protocol were retrospectively reviewed from January 2021 to May 2022. Blood samples were obtained for TEG6s to assess platelet function on the day of coil embolization. To identify acute ischemic complications, diffusion-weighted imaging (DWI) was performed within 24 h after coil embolization. Multivariate logistic regression analysis was conducted to identify potential risk factors for postoperative positive DWI (DWI (+)) lesions. RESULTS: Forty-three of the 84 patients (51%) with DWI (+) lesions were identified. Compared with patients without DWI (+) lesions, Adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAADP) was significantly higher (53.6 mm [Interquartile range (IQR): 48.3-58.3 mm] vs 46.7 mm [IQR: 36.8-52.2 mm]; p=0.001) and ADP inhibition rate (ADP%) was significantly lower (19% [IQR: 11-31%] vs 31% [IQR: 21-44%]; p=0.001) in DWI (+) patients. Multivariate analysis identified MAADP, ADP%, and procedure time as significant independent predictors of subsequent DWI (+) lesions (odds ratios: 1.07, 0.96, and 1.02, respectively). Based on receiver operating characteristic curve analysis, MAADP >50.9 mm and ADP% <28.8% were associated with postoperative DWI (+) lesions in patients undergoing coil embolization for UIAs. CONCLUSIONS: MAADP and ADP% as assessed by TEG6s can offer reliable parameters to predict postoperative ischemic complications after coil embolization of UIAs. Lower MAADP values and higher ADP% may decrease the risk of postoperative ischemic complications.

Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Multimodal treatment including lumbar facet joint denervation for severe low back pain in patients with neuromuscular disorders.

BACKGROUND: Severe low back pain (LBP) is an occasional complaint in patients with neuromuscular disorders (NMDs). Accurate diagnosis and treatment are required to manage LBP; however, the precise pathophysiology differs for each patient. This study aimed to evaluate the efficacy of lumbar facet joint denervation (FJD) and adjunctive modalities in the treatment of LBP in patients with NMD-associated kyphoscoliosis. METHODS: A total of 16 patients (22 sites) with NMD (bilateral, n = 6; unilateral, n = 10) and LBP treated with lumbar FJD were evaluated. The patients were divided into two groups: those treated with FJD alone (group 1) and those treated with multimodal treatment, including FJD along with radiofrequency ablation for sacroiliac joint pain, piriform muscle block, botulinum toxin injection into the paraspinal muscles, spinal cord stimulation, or any of their combinations (group 2). All patients were followed up for 48 weeks postoperatively. The two groups were compared with respect to the duration required for improvements in LBP by more than 50% (numerical rating scale ≤ 5). RESULTS: There was no significant difference between the groups regarding the age, duration since the onset of Parkinson's syndrome, and radiographic analysis. The effective period of improved pain was greater in group 2 than in group 1 (30.7 vs. 8.4 weeks, P < 0.01). CONCLUSIONS: Multimodal treatment including FJD is safe and relatively effective in patients with NMD-associated kyphoscoliosis. Hence, it is a potential substitute for conventional spinal fixation surgery, which has a higher risk of complications.

Cervical lateral mass screw length analysis in men versus women.

Posterior fixations with lateral mass screws have become popular. The Roy-Camille and the Magerl techniques have been established and screw length was identified as a particularly important element. Sex and ethnicity are significant factors in cervical spine morphology, but few studies have been performed for screw length. We performed measurements using computed tomography (CT) images of adult patients hospitalized for surgery of the cervical spine, with targeted 3D data analysis. The final number of patients was 47 (33 men, 14 women) and 235 vertebrae. With the Roy-Camille technique, the screw length was longest at C3 (men: 13.0 mm ± 1.9 mm, women: 13.0 mm ± 1.9 mm) and smallest at C7 (men: 10.8 mm ± 1.8 mm, women: 9.4 mm ± 1.2 mm). With the Magerl technique, the screw length was smallest at C3 (men: 14.8 mm ± 1.6 mm, women: 14.3 mm ± 1.6 mm) and longest at C7 for men (16.8 mm ± 2.8 mm), and at C6 for women (15.4 mm ± 3.0 mm). To differ from spinal canal or pedicle, cervical lateral mass showed no obvious morphological differences from that of subjects of other ethnicity. The placement of a standard lateral mass screw would not cause complications in Japanese patients, even with the use of devices designed in North America or Europe. However, the anatomical background is essential because it is important to optimize the selection for each patient to avoid complications considering sex and individual differences.

Diagnostic performance of intraoperative cone beam computed tomography compared with postoperative magnetic resonance imaging for detecting hemorrhagic transformation after endovascular treatment following large vessel occlusion.

OBJECTIVES: Early detection of hemorrhagic transformation (HT) in patients with large vessel occlusion (LVO) after endovascular treatment is important for postoperative patient management. We investigated the diagnostic performance of intraoperative cone beam computed tomography (CBCT) with reference standard magnetic resonance imaging (MRI) for detecting HT. MATERIALS AND METHODS: Consecutive patients with LVO treated by endovascular treatment who underwent intraoperative CBCT and postoperative MRI were included. Two observers evaluated all images for the presence of HT. Sensitivity and specificity for detecting HT were calculated with MRI as reference standard. The observers classified HT according to the European Cooperative Acute Stroke Study (ECASS). Inter-method and inter-rater agreement for the detection of HT and for the ECASS classification were assessed using kappa or weighted Brennan-Prediger (wBP) statistics. RESULTS: Images of 106 procedures (94 for anterior circulation) were analyzed. The sensitivity and specificity for detecting HT on CBCT were 0.77 and 0.83, respectively, for all procedures and 0.83 and 0.8, respectively, for anterior circulation. The inter-method agreement for HT detection (κ = 0.63 overall, κ = 0.69 anterior circulation) and ECASS classification (wBP = 0.67 overall, wBP = 0.77 anterior circulation) were substantial. The inter-rater agreement for HT detection (κ = 0.87 overall, κ = 0.85 anterior circulation) and for ECASS classification (wBP = 0.95 overall, wBP = 0.92 anterior circulation) were almost perfect. CONCLUSIONS: The diagnostic performance of CBCT for the detection of HT in stroke patients treated for LVO was acceptable with excellent inter-rater agreement. Intraoperative CBCT may be useful to trigger early interventions if HT is detected, although detailed classifications of HT may be difficult.

[Surgical Strategy of Benign Skull Base Tumors Based on Membrane Structure].

Meningiomas, schwannomas, and pituitary adenomas are typically benign tumors of intracranial origin, but all of these tumors have a border with the surrounding tissue. The basic structure is a clear "boundary" between the tumor and its surroundings, with a thin membrane layer to create that separation. This layer of membrane is the boundary between the tumor and its surroundings and provides a space for the tumor to grow its cells, and can be viewed as the so-called "tumor capsule. Based on the relationship between the membrane structure of the tumor capsule and the surrounding normal tissues, we perform surgery to reduce surgical complications. We histologically evaluated three types of tumor capsules(meningioma, schwannoma, and pituitary adenoma)and compared the membrane structure of each tumor with that seen in clinical surgery.

Communication-type smartphone application can contribute to reducing elapsed time to reperfusion therapy.

BACKGROUND AND OBJECTIVES: Communication-type medical smartphone applications enable text, neuroimaging, photos, and videos to be shared securely among the stroke team. Our aim was to investigate whether use of a smartphone application would shorten the duration from admission to reperfusion therapy in patients with hyper-acute ischemic stroke. METHODS: Enrolled were acute ischemic stroke patients who underwent reperfusion therapy (intravenous tissue plasminogen activator (IV t-PA) and mechanical thrombectomy (MT)) at our hospital between October 2012 and September 2018. We divided the patients into two groups based on the date of availability on smartphones of communication-type medical application: (1) Control group, conventional communication prior to September 2015, and (2) App group, communication via the smartphone app from October 2015 onwards. We compared door-to-image time (DIT), image-to-needle time (INT), door-to-needle time (DNT) for thrombolysis, and DIT, image-to-puncture time (IPT), and door-to-puncture time (DTP) for thrombectomy between the groups. RESULTS: We retrospectively enrolled 139 patients (68% male; median age, 69 years; median NIHSS score, 7) who were assigned into the App group (n = 86) and Control group (n = 53). Of the overall patients, 109 underwent IV t-PA (IV t-PA alone, 79 patients), and 63 underwent MT (MT alone, 30 patients), and 33 patients underwent combined IV t-PA and MT. There was no significant difference in DIT between the App and Control groups (23 min vs. 22 min, p = 0.493). DNT, DPT, INT, and IPT were significantly shorter in the App group than in the Control group (DNT, 62 min for the App group vs. 72 min for Control group, p = 0.038; INT, 42 vs. 48 min, p = 0.009; DPT, 106 vs. 129 min, p = 0.046; IPT, 89 vs. 117 min, p = 0.004). CONCLUSION: The present findings indicate that communication-type medical smartphone apps have potential for shortening the time elapsed between admission and reperfusion therapy, especially INT and IPT.

MRI characteristics of syringomyelia associated with foramen magnum arachnoiditis: differentiation from Chiari malformation.

BACKGROUND: It is important to distinguish foramen magnum arachnoiditis (FMA) from Chiari malformation (CM) before surgery because the operative strategies for these diseases differ. In the current study, we compared pretreatment magnetic resonance imaging (MRI) of FMA with CM and investigated the MRI findings useful to differentiate between these diseases. METHODS: We retrospectively reviewed patients with FMA or CM aged ≥ 18 years who underwent surgeries at our institution between 2007 and 2019. The morphologies of the syrinx, neural elements, and posterior cranial fossa were preoperatively evaluated with MRI. We used the receiver operating characteristic (ROC) curve for the fourth ventricle-to-syrinx distance (FVSD). RESULTS: Ten patients with FMAs and 179 with CMs were included. FVSD in the FMA group was significantly shorter than that in the CM group (7.5 mm [IQR, 2.8-10 mm] in FMA vs. 29.9 mm [IQR, 16.3-52.9 mm] in CM, p < 0.0001). The other MRI findings that showed the height, size, and length of the syrinx; size of the foramen magnum; degree of cerebellar tonsillar descent; shape of the cerebellar tonsil; and dorsal subarachnoid space at the foramen magnum differed significantly between the two groups. The ROC curve analysis showed that patients whose FVSD was less than 11 mm could be diagnosed with FMA with a specificity of 90% and sensitivity of 96%. CONCLUSIONS: A more cranial syrinx development (FVSD < 11 mm) appears to be the characteristic MRI finding in FMA.

Using a Smartphone Application for the Accurate and Rapid Diagnosis of Acute Anterior Intracranial Arterial Occlusion: Usability Study.

BACKGROUND: Telestroke has developed rapidly as an assessment tool for patients eligible for reperfusion therapy. OBJECTIVE: To investigate whether vascular neurologists can diagnose intracranial large vessel occlusion (LVO) as quickly and accurately using a smartphone application compared to a hospital-based desktop PC monitor. METHODS: We retrospectively enrolled 108 consecutive patients with acute ischemic stroke in the middle cerebral artery territory who underwent magnetic resonance imaging (MRI) within 24 hours of their stroke onset. Two vascular neurologists, blinded to all clinical information, independently evaluated magnetic resonance angiography and fluid-attenuated inversion recovery images for the presence or absence of LVO in the internal carotid artery and middle cerebral artery (M1, M2, or M3) on both a smartphone application (Smartphone-LVO) and a hospital-based desktop PC monitor (PC-LVO). To evaluate the accuracy of an arterial occlusion diagnosis, interdevice variability between Smartphone-LVO and PC-LVO was analyzed using κ statistics, and image interpretation time was compared between Smartphone-LVO and PC-LVO. RESULTS: There was broad agreement between Smartphone-LVO and PC-LVO evaluations regarding the presence or absence of arterial occlusion (Reader 1: κ=0.94; P<.001 vs Reader 2: κ=0.89; P<.001), and interpretation times were similar between Smartphone-LVO and PC-LVO. CONCLUSIONS: The results indicate the evaluation of neuroimages using a smartphone application can provide an accurate and timely diagnosis of anterior intracranial arterial occlusion that can be shared immediately with members of the stroke team to support the management of patients with hyperacute ischemic stroke.

Thoracic and lumbar spine pedicle morphology in Japanese patients.

PURPOSE: Pedicle morphology is important for intraoperative surgical anatomy and to define pedicle screw design and parameters. However, differences of pedicle size according to ethnicity and gender are not well studied. The purpose of this study is to investigate morphological characteristics of the pedicle in Japanese patients for determining adequate screw size and optimal surgical planning. METHODS: We investigated thoracic and lumbar pedicle morphology in Japanese patients using computed tomography (CT) measurements and analyzed the standard size of pedicles on upper thoracic to lumbar spine CT images in 227 Japanese patients. RESULTS: Gender had a larger impact on the shape and size of pedicles than racial differences. In the distribution of pedicle width, we calculated the ratio of values less than 4.5 mm, that in females resulted to be over 30% for the Th3-Th9 segment, and particularly high, above 60% at Th4 and Th5. CONCLUSION: Our measurement analysis showed that pedicle morphological parameters in Japanese patients showed tendency to be smaller to those found in other studies, and particularly in female patients, they were statistically significantly smaller. Adequate transpedicular instrumentation for Japanese patients will require smaller size pedicle-related devices that will match our anatomical findings to achieve safe device placement. In addition, serving ethnically non-homogenous patient population can require further to spinal morphometric for precise device selection.

[History and Recent Development of Basic Research Using an Experimental Intracranial Aneurysm Model].

Since intracranial aneurysm(IA)is a disease that follows an extremely unpredictable course, from initiation to rupture, experimental models have greatly contributed to a better understanding of IA pathophysiology. This article aims to review the history of IA models through the pivotal theme of the ideal IA model. In addition, this article introduces updated findings from the application of these experimental models. Though the first IA model, known as a venous pouch model, was reported in 1954, it mimicked only the shape of the IA, without reproducing its pathological structure or blood-flow characteristics. Currently, two models are generally applied: the "Hashimoto model," produced by unilateral common carotid artery(CCA)ligation followed by systemic hypertension and weakening of the vascular wall, and the "elastase injection model," induced by intraventricular elastase injection and also followed by systemic hypertension. In addition, other models, including a rabbit basilar top IA, developed after bilateral CCA ligation, and an artificial bifurcation model, generated by an anastomosis between the CCAs, have been found to be valuable for computational fluid dynamics analysis. Through this advancement, the IA model has gradually elucidated the pathophysiology of IA as a flow-induced inflammatory disease. Nowadays, vascular inflammation is suggested to be regulated by bacterial flora. Further development of IA models and a better understanding of IA pathophysiology are expected in the future.

Sex and Genetic Background Effects on the Outcome of Experimental Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Intracranial aneurysm formation and rupture risk are, in part, determined by genetic factors and sex. To examine their role, we compared 3 mouse strains commonly used in cerebrovascular studies in a model of intracranial aneurysm formation and rupture. METHODS: Intracranial aneurysms were induced in male CD1 (Crl:CD1[ICR]), male and female C57 (C57BL/6NCrl), and male 129Sv (129S2/SvPasCrl or 129S1/SvImJ) mice by stereotaxic injection of elastase at the skull base, combined with systemic deoxycorticosterone acetate-salt hypertension. Neurological deficits and mortality were recorded. Aneurysms and subarachnoid hemorrhage grades were quantified postmortem, either after spontaneous mortality or at 7 to 21 days if the animals survived. In separate cohorts, we examined proinflammatory mediators by quantitative reverse transcriptase-polymerase chain reaction, arterial blood pressure via the femoral artery, and the circle of Willis by intravascular latex casting. RESULTS: We found striking differences in aneurysm formation, rupture, and postrupture survival rates among the groups. 129Sv mice showed the highest rates of aneurysm rupture (80%), followed by C57 female (36%), C57 male (27%), and CD1 (21%). The risk of aneurysm rupture and the presence of unruptured aneurysms significantly differed among all 3 strains, as well as between male and female C57. The same hierarchy was observed upon Kaplan-Meier analysis of both overall survival and deficit-free survival. Subarachnoid hemorrhage grades were also more severe in 129Sv. CD1 mice showed the highest resistance to aneurysm rupture and the mildest outcomes. Higher mean blood pressures and the major phenotypic difference in the circle of Willis anatomy in 129Sv provided an explanation for the higher incidence of and more severe aneurysm ruptures. TNFα (tumor necrosis factor-alpha), IL-1ß (interleukin-1-beta), and CCL2 (chemokine C-C motif ligand 2) expressions did not differ among the groups. CONCLUSIONS: The outcome of elastase-induced intracranial aneurysm formation and rupture in mice depends on genetic background and shows sexual dimorphism.

Rupture Risk of Small Unruptured Intracranial Aneurysms in Japanese Adults.

Background and Purpose- Therapeutic decision making for small unruptured intracranial aneurysms (<10 mm) is difficult. We aimed to develop a rupture risk model for small intracranial aneurysms in Japanese adults, including clinical, morphological, and hemodynamic parameters. Methods- We analyzed 338 small unruptured aneurysms; 35 ruptured during the observation period, and 303 remained stable. Clinical, morphological, and hemodynamic parameters were considered. Computational fluid dynamics was used to calculate hemodynamic parameters based on computed tomography images of all aneurysms in their unruptured state. Differences between the ruptured and unruptured groups were tested by the Mann-Whitney U or Fisher exact tests. Multivariate logistic regression was applied to obtain a rupture risk model. Its predictive ability was investigated by receiver operating characteristic analysis. Results- The risk model revealed that rupture may be more likely to in younger patients (odds ratio [OR], 0.92 for each age increase of 1 year [95% CI, 0.88-0.96] P<0.001) with multiple aneurysms (OR, 2.58 [95% CI, 1.07-6.19] P=0.03), located at a bifurcation (OR, 5.45 [95% CI, 1.87-15.85] P=0.002), with a bleb (OR, 4.09 [95% CI, 1.42-11.79] P=0.009), larger length (OR, 1.91 for each increase of 1 mm [95% CI, 1.42-2.57] P<0.001), and lower pressure loss coefficient (OR, 0.33 for each decrease of 1 unit [95% CI, 0.14-0.77] P=0.01). The sensitivity, specificity, and area under the curve were 0.800, 0.752, and 0.826 (95% CI, 0.739-0.914) respectively. Conclusions- Younger age, presence of multiple aneurysms, location at a bifurcation, presence of a bleb, larger length, and lower pressure loss coefficient were identified as risk factors for rupture of small intracranial aneurysms. The risk model should be validated in further studies.

Eliminating transmissibility of bovine spongiform encephalopathy by dry-heat treatment.

Bovine spongiform encephalopathy (BSE) prion is more resistant to heat inactivation compared to other prions, but the effect of heat inactivation has been reported to differ depending on the BSE-contaminated tissue state or heating type. We aimed to evaluate the secure level of inactivation of original BSE transmissibility by dry-heating. Cattle tissues affected with BSE were subjected to dry-heat treatment for 20 min at various temperatures ranging from 150 to 1000 °C. To assess the inactivation effect, we conducted protein misfolding cyclic amplification (PMCA) and follicular dendritic cell (FDC) assays in transgenic mice expressing bovine prion protein genes. Under dry-heating at 600 °C or higher, BSE cattle tissues lost their transmissibility in transgenic mice. In contrast, transmissibility was detected in the cattle tissues treated at temperatures of 400 °C or lower through the FDC assay combined with PMCA. In this study, we confirmed that transmissibility was eliminated in BSE-affected cattle tissues by dry-heating at 600 °C or higher.

Clinical predictors of surgical outcomes of severe carpal tunnel syndrome patients: utility of palmar stimulation in a nerve conduction study.

BACKGROUND: Carpal tunnel syndrome is a common peripheral nerve compression disorder. However, there is no established opinion regarding the predictors of symptom improvement after surgery. This study aimed to identify the predictors of surgical outcomes of severe carpal tunnel syndrome patients. METHODS: In the patients who underwent a carpal tunnel syndrome surgery, we selected the patients who had a preoperative Bland's classification of grade 5 or 6, and assessed for the changes in Bland's classification grade before and after surgery. Those who showed improvement from preoperative grades 5-6 to postoperative grades 1-4 comprised the improvement group. In contrast, those who did not show improvement and had postoperative grades 5 or 6 comprised the non-improvement group. In a nerve conduction study, amplitudes of the compound muscle action potential and sensory nerve action potential of the palms were assessed between the improvement and non-improvement groups. RESULTS: Among the 60 hands of 46 patients who had a preoperative Bland's classification of grade 5 or 6, 49 hands of 37 patients comprised the improvement group, and 11 hands of 9 patients comprised the non-improvement group. The amplitudes of the compound muscle action potential and sensory nerve action potential of the palms before surgery were significantly higher in the improvement group. The degree of improvement in Bland's classification grade was correlated with the degree of clinical symptom improvement. CONCLUSIONS: Amplitudes of compound muscle action potential and sensory nerve action potential before surgery induced by palmar stimulation can predict improvements in nerve conduction study scores and clinical findings after surgical treatment.

Reliability of Smartphone for Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores in Acute Ischemic Stroke Patients: Diagnostic Test Accuracy Study.

BACKGROUND: High-quality neuroimages can be viewed using a medical app installed on a smartphone. Although interdevice agreement between smartphone and desktop PC monitor was found to be favorable for evaluating computed tomography images, there are no interdevice agreement data for diffusion-weighted imaging (DWI). OBJECTIVE: The aim of our study was to compare DWI interpretation using the Join smartphone app with that using a desktop PC monitor, in terms of interdevice and interrater agreement and elapsed interpretation time. METHODS: The ischemic change in the DWI of consecutive patients with acute stroke in the middle cerebral artery territory was graded by 2 vascular neurologists using the Join smartphone app and a desktop PC monitor. The vascular neurologists were blinded to all patient information. Each image was categorized as either Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores (DWI-ASPECTS) ≥7 or DWI-ASPECTS <7 according to the Japanese Society for Neuroendovascular Therapy. We analyzed interdevice agreement and interrater agreement with respect to DWI-ASPECTS. Elapsed interpretation time was compared between DWI-ASPECTS evaluated by the Join smartphone app and a desktop PC monitor. RESULTS: We analyzed the images of 111 patients (66% male; median age=69 years; median National Institutes of Health Stroke Scale score on admission=4). Interdevice agreement regarding DWI-ASPECTS between the smartphone and the desktop PC monitor was favorable (vascular neurologist 1: κ=0.777, P<.001, vascular neurologist 2: κ=0.787, P<.001). Interrater agreement was also satisfactory for the smartphone (κ=0.710, P<.001) and the desktop PC monitor (κ=0.663, P<.001). Median elapsed interpretation time was similar between the smartphone and the desktop PC monitor (vascular neurologist 1: 1.7 min vs 1.6 min; P=.64); vascular neurologist 2: 2.4 min vs 2.0 min; P=.14). CONCLUSIONS: The use of a smartphone app enables vascular neurologists to estimate DWI-ASPECTS accurately and rapidly. The Join medical smartphone app shows great promise in the management of acute stroke.