Publications by authors named "Nobuhito Saito"

326 Publications

Prognostic Factors for Patients With Brain Metastases Treated With Single-fraction Gamma Knife Radiosurgery.

Anticancer Res 2021 Jun;41(6):3179-3185

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

Background/aim: The aim of this study was to identify prognostic factors for brain metastases treated with Gamma knife radiosurgery.

Patients And Methods: Multivariate Cox proportional hazards regression analyses were conducted for patients who received treatment between June 2013 and March 2018.

Results: A total of 131 consecutive patients were included. The median follow-up period was 16.0 months (range=1.5-61.5 months). Brain metastases [hazard ratio (HR)=0.42, 95%CI=0.27-0.67, p<0.001], history of systemic therapy (HR=2.23, 95%CI=1.28-3.89, p=0.005), and active extracranial disease (HR=2.49, 95%CI=1.30-4.76, p=0.006) were independent predictors of overall survival. Number of brain metastases (HR=0.39, 95%CI=0.26-0.59, p<0.001) and history of systemic therapy (HR=1.90, 95%CI=1.17-3.08, p=0.005) were independent predictors of intracranial progression-free survival.

Conclusion: The number of brain metastases and the history of systemic therapy are associated with patient overall survival and intracranial progression-free survival.
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http://dx.doi.org/10.21873/anticanres.15104DOI Listing
June 2021

Changes in the Risk of Stroke in Dialysis Patients: A Retrospective Analysis over the Last 40 Years.

Toxins (Basel) 2021 05 13;13(5). Epub 2021 May 13.

Department of Neurosurgery, Teraoka Memorial Hospital, Hiroshima 729-3103, Japan.

The stroke incidence in hemodialysis (HD) patients is high, but the associated factors remain largely unknown. This study aimed to analyze stroke incidence in HD patients and changes in risk factors. Data of 291 patients were retrospectively analyzed. The cumulative stroke incidences were 21.6% at 10 years and 31.5% at 20. Diabetic nephropathy (DN) significantly increased overall stroke (hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.21-4.12; = 0.001) and ischemic stroke (HR, 2.16; 95% CI, 1.00-4.64; = 0.049). Patients treated with online HDF were less likely to have overall stroke (HR, 0.13; 95% CI, 0.03-0.56; = 0.006) and ischemic stroke (HR, 0.08; 95% CI, 0.01-0.60; = 0.014). DN (HR, 1.56; 95% CI, 1.08-2.27; = 0.019) and age >80 years at HD initiation (20-49 years old; HR 0.13, 95% CI, 0.05-0.35, < 0.001 and age 50-79 years; HR 0.42, 95% CI, 0.26-0.66, < 0.001 (reference: age >80 years)) were significantly associated with stroke and/or death events. Over time, stroke risk increased in HD patients, due to the increasing number of DN. Although dialysis technology has advanced over time, these advances could not overcome other risk factors for stroke. Further increase in stroke and mortality due to aging remains a concern.
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http://dx.doi.org/10.3390/toxins13050350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170903PMC
May 2021

A Novel Topical Fluorescent Probe for Detection of Glioblastoma.

Clin Cancer Res 2021 May 23. Epub 2021 May 23.

Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Purpose: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma.

Experimental Design: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, and studies using U87 glioblastoma cell line were conducted to validate the findings.

Results: The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 ( to be responsible for cleaving the probe. was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues.

Conclusions: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4518DOI Listing
May 2021

Indocyanine green illuminates the way to cut the tentorium in occipital transtentorial approach: technical note.

Br J Neurosurg 2021 May 19:1-3. Epub 2021 May 19.

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.

Background And Importance: The occipital transtentorial approach is used to address lesions at the posterior incisural space or upper cerebellum. This approach is rarely used, making standardization of the surgical procedure challenging. Here we describe the effectiveness of indocyanine green (ICG) and dye markings before tentorial incision in charting a safe and bloodless surgical trajectory for improved manoeuvrability.

Clinical Presentation: The first case was a 40-year-old man with a residual pineal mass after chemoradiation therapy for pathologically-proven germinoma. Surgical resection was performed via left occipital craniotomy. Incision of the left cerebellar tentorium by a radiofrequency knife was preceded by visualization of the straight sinus and venous lake, which were marked with dye, enabling safe entry into the quadrigeminal cistern. Finally, total-resection of the mature teratoma was achieved. The second case was a 50-year-old man with an enhancing mass at the cerebellar vermis and left hemisphere. Left occipital craniotomy was followed by ICG administration, illuminating the straight sinus and a complex structure of dural venous channels, which were marked with dye. This visualization maximized the tentorial incision by carefully avoiding venous structures and widely exposed the upper cerebellum. Subtotal-resection of the tumor was achieved, with a diagnosis of glioblastoma.

Conclusion: ICG administration and dye marking are feasible and useful methods for precise identification/visualization of venous structures. They enable maximization as well as safe and appropriate tentorial incision to provide a sufficient surgical corridor for the occipital transtentorial approach.
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http://dx.doi.org/10.1080/02688697.2021.1927982DOI Listing
May 2021

Identification of the Facial Colliculus in Two-dimensional and Three-dimensional Images.

Neurol Med Chir (Tokyo) 2021 Jun 11;61(6):376-384. Epub 2021 May 11.

Department of Neurosurgery, The University of Tokyo.

The facial colliculus (FC), an important landmark for planning a surgical approach to brainstem cavernous malformation (BCM), is a microstructure; therefore, it may be difficult to identify on magnetic resonance imaging (MRI). Three-dimensional (3D) images may improve the FC-identification certainty; hence, this study attempted to validate the FC-identification certainty between two-dimensional (2D) and 3D images of patients with a normal brainstem and those with BCM. In this retrospective study, we included 10 patients with a normal brainstem and 10 patients who underwent surgery for BCM. The region of the FC in 2D and 3D images was independently identified by three neurosurgeons, three times in each case, using the method for continuously distributed test results (0-100). The intra- and inter-rater reliability of the identification certainty were confirmed using the intraclass correlation coefficient (ICC). The FC-identification certainty for 2D and 3D images was compared using the Wilcoxon signed-rank test. The ICC (1,3) and ICC (3,3) in both groups ranged from 0.88 to 0.99; therefore, the intra- and inter-rater reliability were good. In both groups, the FC-identification certainty was significantly higher for 3D images than for 2D images (normal brainstem group; 82.4 vs. 61.5, P = .0020, BCM group; 40.2 vs. 24.6, P = .0059 for the unaffected side, 29.3 vs. 17.3, P = .0020 for the affected side). In the normal brainstem and BCM groups, 3D images had better FC-identification certainty. 3D images are effective for the identification of the FC.
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http://dx.doi.org/10.2176/nmc.oa.2020-0417DOI Listing
June 2021

Comparison of postoperative temporalis muscle atrophy between the muscle-preserving pterional approach and the mini-pterional approach in the treatment of unruptured intracranial aneurysms.

Neurosurg Rev 2021 May 6. Epub 2021 May 6.

Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, HongoTokyo, Japan.

This study aimed to compare the muscle-preserving pterional approach (modified classic pterional approach, mCP) and the mini-pterional approach (mPA) with respect to postoperative temporalis muscle atrophy.From November 2013 to April 2020, 78 patients with unruptured intracranial aneurysm of the anterior circulation underwent surgery using mCP or mPA in our institution. Patients' background characteristics, postoperative complications, and temporalis muscle volume (MV) rates (operative side/healthy side) were retrospectively investigated. In 64 patients (n = 31, mCP group; n = 33, mPA group), excluding 14 patients with missing imaging data from 6 to 24 months after surgery, associations between the MV rate and clinical variables were assessed. A multiple regression model was used to examine the association between the MV rate and the surgical method, which is a predictor of postoperative atrophy.The mCP group had a significantly higher mean MV rate than the mPA group (0.955 ± 0.040 and 0.915 ± 0.070, respectively; p = 0.008). Based on the results of the univariate analysis, a multiple regression model was established using sex, age, follow-up period, and the presence of diabetes in addition to the surgical method. Patients who underwent mCP had a higher MV rate than those who underwent mPA (t value = 2.33, p = 0.023).The present result suggested that mCP has a preventive effect on postoperative temporalis muscle atrophy. However, further studies are needed in order to prove that mCP is also effective in terms of postoperative aesthetic and functional outcomes.
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http://dx.doi.org/10.1007/s10143-021-01558-6DOI Listing
May 2021

Musical Auditory Alpha Wave Neurofeedback: Validation and Cognitive Perspectives.

Appl Psychophysiol Biofeedback 2021 Apr 30. Epub 2021 Apr 30.

Department of Neurosurgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Neurofeedback through visual, auditory, or tactile sensations improves cognitive functions and alters the activities of daily living. However, some people, such as children and the elderly, have difficulty concentrating on neurofeedback for a long time. Constant stressless neurofeedback for a long time may be achieved with auditory neurofeedback using music. The primary purpose of this study was to clarify whether music-based auditory neurofeedback increases the power of the alpha wave in healthy subjects. During neurofeedback, white noise was superimposed on classical music, with the noise level inversely correlating with normalized alpha wave power. This was a single-blind, randomized control crossover trial in which 10 healthy subjects underwent, in an assigned order, normal and random feedback (NF and RF), either of which was at least 4 weeks long. Cognitive functions were evaluated before, between, and after each neurofeedback period. The secondary purpose was to assess neurofeedback-induced changes in cognitive functions. A crossover analysis showed that normalized alpha-power was significantly higher in NF than in RF; therefore, music-based auditory neurofeedback facilitated alpha wave induction. A composite category-based analysis of cognitive functions revealed greater improvements in short-term memory in subjects whose alpha-power increased in response to NF. The present study employed a long period of auditory alpha neurofeedback and achieved successful alpha wave induction and subsequent improvements in cognitive functions. Although this was a pilot study that validated a music-based alpha neurofeedback system for healthy subjects, the results obtained are encouraging for those with difficulty in concentrating on conventional alpha neurofeedback.Trial registration: 2018077NI, date of registration: 2018/11/27.
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http://dx.doi.org/10.1007/s10484-021-09507-1DOI Listing
April 2021

Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans.

Cereb Cortex 2021 Apr 28. Epub 2021 Apr 28.

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.
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http://dx.doi.org/10.1093/cercor/bhab103DOI Listing
April 2021

Development of Innovative Neurosurgical Operation Support Method Using Mixed-Reality Computer Graphics.

World Neurosurg X 2021 Jul 13;11:100102. Epub 2021 Mar 13.

Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured.

Methods: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks.

Results: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6.

Conclusions: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.
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http://dx.doi.org/10.1016/j.wnsx.2021.100102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059082PMC
July 2021

Long-Term Outcomes of Stereotactic Radiosurgery for Trigeminal, Facial, and Jugular Foramen Schwannoma in Comparison with Vestibular Schwannoma.

Cancers (Basel) 2021 Mar 7;13(5). Epub 2021 Mar 7.

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo 113-8655, Japan.

Stereotactic radiosurgery (SRS) is known to provide excellent tumor control with functional preservation for vestibular schwannomas (VS), but its efficacy in the other major intracranial schwannomas including trigeminal (TS), facial (FS), and jugular foramen schwannomas (JFS) has not been established yet due to their rarity. We retrospectively analyzed data of 514 consecutive patients who had intracranial schwannomas (460 VS, 22 TS, 7 FS, and 25 JFS) and underwent SRS. The 5- and 10-year tumor control rates were 97% and 94% for VS, 100% and 100% for TS, 80% and 80% for FS, and 100% and 80% for JFS. Radiation-induced complications included one hydrocephalus for TS (4.5%), no cases for FS (0%), and one hydrocephalus and one lower palsy for JFS (8.0%). Through matched cohort analysis between patients with VS and each of the non-VS, we found no statistical difference in tumor control and radiation-induced adverse events. SRS seems to provide long-term tumor control with functional preservation for TS, FS and JFS and the efficacies are similar to VS.
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http://dx.doi.org/10.3390/cancers13051140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961475PMC
March 2021

Associations of pathological diagnosis and genetic abnormalities in meningiomas with the embryological origins of the meninges.

Sci Rep 2021 Mar 26;11(1):6987. Epub 2021 Mar 26.

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.

Certain driver mutations and pathological diagnoses are associated with the anatomical site of meningioma, based on which the meninges have different embryological origins. We hypothesized that mutations and pathological diagnoses of meningiomas are associated with different embryological origins. We comprehensively evaluated associations among tumor location, pathological diagnosis (histological type), and genetic alterations including AKT1, KLF4, SMO, POLR2A, and NF2 mutations and 22q deletion in 269 meningioma cases. Based on the embryological origin of meninges, the tumor locations were as follows: neural crest, paraxial mesodermal, and dorsal mesodermal origins. Tumors originating from the dura of certain embryologic origin displayed a significantly different pathological diagnoses and genetic abnormality ratio. For instance, driver genetic mutations with AKT1, KLF4, SMO, and POLR2A, were significantly associated with the paraxial mesodermal origin (p = 1.7 × 10). However, meningiomas with NF2-associated mutations were significantly associated with neural crest origin (p = 3.9 × 10). On analysis of recurrence, no difference was observed in embryological origin. However, POLR2A mutation was a risk factor for the tumor recurrence (p = 1.7 × 10, Hazard Ratio 4.08, 95% Confidence Interval 1.28-13.0). Assessment of the embryological origin of the meninges may provide novel insights into the pathomechanism of meningiomas.
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http://dx.doi.org/10.1038/s41598-021-86298-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998008PMC
March 2021

Rotational Angiography-Based Gamma Knife Radiosurgery for Brain Arteriovenous Malformations: Preliminary Therapeutic Outcomes of the Novel Method.

Neurosurgery 2021 Jun;89(1):60-69

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.

Background: High-definition vascular imaging is desirable for treatment planning in Gamma Knife radiosurgery (GKRS; Elekta AB) for brain arteriovenous malformations (BAVMs). Currently, rotational angiography (RA) provides the clearest 3-dimensional visualization of niduses with high spatial resolution; however, its efficacy for GKRS has not been clarified. At our institution, RA has been integrated into GKRS (RA-GKRS) for better treatment planning and outcomes since 2015.

Objective: To evaluate RA-GKRS outcomes of BAVMs and compare them with conventional GKRS (c-GKRS) outcomes.

Methods: We retrospectively analyzed the radiosurgical outcomes of 50 BAVMs treated with RA-GKRS compared with the 306 BAVMs treated with c-GKRS. Considering possible differences in the baseline characteristics, we also created propensity score-matched cohorts and compared the radiosurgical outcomes between them to ensure comparability.

Results: The obliteration time was shorter in the RA-GKRS group (cumulative rate, 88% vs 65% at 4 yr [P = .001]). Multivariate Cox proportional hazards analysis demonstrated that the RA-GKRS group (hazard ratio 2.38, 95% CI 1.58-3.60; P = .001) had a better obliteration rate. The cumulative 4-yr post-GKRS hemorrhage rates were 4.0% and 2.6% in the RA-GKRS and c-GKRS groups, respectively (P = .558). There was a trend toward early post-GKRS signal change in the RA-GKRS group compared with the c-GKRS group (cumulative rate, 38% vs 29% at 2 yr; P = .118). Those results were also confirmed in the matched cohort analyses.

Conclusion: The integration of RA into GKRS is promising and may provide earlier nidus obliteration.
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http://dx.doi.org/10.1093/neuros/nyab066DOI Listing
June 2021

Possible Association Between Rupture and Intranidal Microhemodynamics in Arteriovenous Malformations: Phase-Contrast Magnetic Resonance Angiography-Based Flow Quantification.

World Neurosurg 2021 Jun 16;150:e427-e435. Epub 2021 Mar 16.

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.

Objective: To examine a potential association between intranidal microhemodynamics and rupture using a phase-contrast magnetic resonance angiography (PCMRA)-based flow quantification technique in arteriovenous malformations (AVMs).

Methods: We retrospectively collected data on 30 consecutive patients with AVMs (23 unruptured and 7 ruptured). Based on PCMRA data, maximal (V) and mean (V) intranidal velocities were calculated. Logistic regression analysis was performed to assess factors associated with previous AVM rupture.

Results: All ruptures occurred within 6 months before PCMRA. The mean nidus volume was 4.7 mL. Eleven patients (37%) had deep draining vein(s), and 6 patients (20%) had a deep-seated nidus. The mean ± standard deviation V and V were 9.6 ± 2.8 cm/second and 66.7 ± 26.2 cm/second, respectively. The logistic regression analyses revealed that higher V (P = 0.075, unit odds ratio [OR] = 1.05, 95% confidence interval [95% CI] = 1.00-1.10) was significantly associated with prior hemorrhage. The receiver-operating curve analyses demonstrated that a V of 10.8 cm/second (area under the curve = 0.671) and V of 90.2 cm/second (area under the curve = 0.764) maximized the Youden Index. A V > 90 cm/second was significantly associated with AVM rupture both in the univariate (P = 0.025, OR = 9.0, 95% CI = 1.3-61.1) and multivariate (P = 0.008, OR = 51.7, 95% CI = 2.8-968.3) analyses.

Conclusions: Presence of faster velocities in intranidal vessels may suggest aberrant microhemodynamics and thus be associated with AVM rupture. PCMRA-based velocimetry seems to be a promising tool to predict future AVM rupture.
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http://dx.doi.org/10.1016/j.wneu.2021.03.036DOI Listing
June 2021

Correlation of Inflow Velocity Ratio Detected by Phase Contrast Magnetic Resonance Angiography with the Bleb Color of Unruptured Intracranial Aneurysms.

World Neurosurg X 2021 Apr 13;10:100098. Epub 2021 Jan 13.

Department of Neurosurgery, University of Tokyo, Tokyo, Japan.

Background: Intraoperative rupture is the most fatal and catastrophic complication of surgery for unruptured intracranial aneurysms (UIAs); thus, it is extremely useful to predict reddish and thin-walled regions of the UIA before surgery. Although several studies have reported a relationship between the hemodynamic characteristics and intracranial aneurysm wall thickness, a consistent opinion is lacking. We aimed to investigate the relationship between objectively and quantitatively evaluated bleb wall color and hemodynamic characteristics using phase-contrast magnetic resonance angiography (PC-MRA).

Methods: Ten patients diagnosed with UIA who underwent surgical clipping and preoperative magnetic resonance imaging along with PC-MRA were included in this study. Bleb wall color was evaluated from an intraoperative video. Based on the Red (R), Green, and Blue values, bleb wall redness (modified R value; mR) was calculated and compared with the hemodynamic characteristics obtained from PC-MRA.

Results: The wall redness distribution of 18 blebs in 11 UIAs in 10 patients was analyzed. Bleb/neck inflow velocity ratio (Vb/Va: r = 0.66,  = 0.003) strongly correlated with mR, whereas bleb/neck inflow rate ratio (r = 0.58,  = 0.012) correlated moderately. Multivariate regression analysis revealed that only Vb/Va ( = 0.017) significantly correlated with mR. There was no correlation between wall shear stress and mR.

Conclusions: The bleb redness of UIAs and Vb/Va, calculated using PC-MRA, showed a significantly greater correlation. Thus, it is possible to predict bleb thickness noninvasively before surgery. This will facilitate more detailed pre- and intraoperative strategies for clipping and coiling for safe surgery.
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http://dx.doi.org/10.1016/j.wnsx.2021.100098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941010PMC
April 2021

Development of Integrated 3-Dimensional Computer Graphics Human Head Model.

Oper Neurosurg (Hagerstown) 2021 05;20(6):565-574

Department of Neurosurgery, The University of Tokyo, Tokyo, Japan.

Background: Understanding the complex anatomy of neurostructures is very important in various stages of medical education, from medical students to experienced neurosurgeons, and, ultimately, for the knowledge of human beings.

Objective: To develop an interactive computer graphics (CG) anatomic head model and present the current progress.

Methods: Based on the prior head 3-dimensional CG (3DCG) polygon model, 23 additional published papers and textbooks were consulted, and 2 neurosurgeons and 1 CG technician performed revision and additional polygon modeling. Three independent neurosurgeons scored the clear visibility of anatomic structures relevant to neurosurgical procedures (anterior petrosal and supracerebellar infratentorial approaches) in the integrated 3DCG model (i model) and patients' radiological images (PRIs) such as those obtained from computed tomography, magnetic resonance imaging, and angiography.

Results: The i model consisted of 1155 parts (.stl format), with a total of 313 763 375 polygons, including 10 times more information than the foundation model. The i model was able to illustrate complex and minute neuroanatomic structures that PRIs could not as well as extracranial structures such as paranasal sinuses. Our subjective analysis showed that the i model had better clear visibility scores than PRIs, particularly in minute nerves, vasculatures, and dural structures.

Conclusion: The i model more clearly illustrates minute anatomic structures than PRIs and uniquely illustrates nuclei and fibers that radiological images do not. The i model complements cadaveric dissection by increasing accessibility according to spatial, financial, ethical, and social aspects and can contribute to future medical education.
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http://dx.doi.org/10.1093/ons/opab012DOI Listing
May 2021

Label cleaning and propagation for improved segmentation performance using fully convolutional networks.

Int J Comput Assist Radiol Surg 2021 Mar 3;16(3):349-361. Epub 2021 Mar 3.

Department of Biomedical Information, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.

Purpose: In recent years, fully convolutional networks (FCNs) have been applied to various medical image segmentation tasks. However, it is difficult to generate a large amount of high-quality annotation data to train FCNs for medical image segmentation. Thus, it is desired to achieve high segmentation performances even from incomplete training data. We aim to evaluate performance of FCNs to clean noises and interpolate labels from noisy and sparsely given label images.

Methods: To evaluate the label cleaning and propagation performance of FCNs, we used 2D and 3D FCNs to perform volumetric brain segmentation from magnetic resonance image volumes, based on network training on incomplete training datasets from noisy and sparse annotation.

Results: The experimental results using pseudo-incomplete training data showed that both 2D and 3D FCNs could provide improved segmentation results from the incomplete training data, especially by using three orthogonal annotation images for network training.

Conclusion: This paper presented a validation for label cleaning and propagation based on FCNs. FCNs might have the potential to achieve improved segmentation performances even from sparse annotation data including possible noises by manual annotation, which can be an important clue to more efficient annotation.
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http://dx.doi.org/10.1007/s11548-021-02312-5DOI Listing
March 2021

Treatment of ischemic neuronal death by introducing brain-derived neurotrophic factor mRNA using polyplex nanomicelle.

Biomaterials 2021 03 21;270:120681. Epub 2021 Jan 21.

Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 1010062, Tokyo, Japan; Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 2100821, Kawasaki, Kanagawa, Japan. Electronic address:

Ischemic neuronal death causes serious lifelong neurological deficits; however, there is no proven effective treatment that can prevent neuronal death after the ischemia. We investigated the feasibility of mRNA therapeutics for preventing the neuronal death in a rat model of transient global ischemia (TGI). By intraventricular administration of mRNA encoding brain-derived neurotrophic factor (BDNF) using a polymer-based carrier, polyplex nanomicelle, the mRNA significantly increased the survival rate of hippocampal neurons after TGI, with a rapid rise of BDNF in the hippocampus. Interestingly, mRNA administration on Day 2 after TGI provided significantly better survival rate than the administration immediately after TGI. Eventually, dosing twice on Day 2 and 5 exerted long-term therapeutic effects, which were confirmed by a Y-maze behavioral test demonstrating improved spatial memory compared with untreated rats on Day 20. Immunohistochemical analysis showed that astrocytes were chief targets of the BDNF mRNA-loaded nanomicelles, suggesting that the augmented BDNF secretion from astrocytes creates a supportive microenvironment for the neurons to tolerate changes caused by ischemic stresses, and terminate the process of progressive neuronal death after the ischemic attack. Overall, the unique mechanism of action of mRNA therapeutics provide a promising approach for preventing ischemic neuronal death.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120681DOI Listing
March 2021

Embolization of dural arteriovenous fistula during twin pregnancy - A case report and literature review.

Interv Neuroradiol 2021 Jan 28:1591019921991396. Epub 2021 Jan 28.

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Several literature reviews have suggested that pregnancy may trigger the formation of dural arteriovenous fistulae (DAVF). However, few case reports have described DAVF discovered during pregnancy, and treatment strategies remain largely unknown. A 28-year-old primigravid woman without any medical history of note presented to our hospital for natural twin conception. She started to feel left-sided pulsatile tinnitus in 23 weeks of gestation. Magnetic resonance imaging of the head raised suspicion of left cavernous sinus DAVF with leptomeningeal venous drainage. Considering the risk of intracerebral hemorrhage due to the increased cardiac output in the third trimester of a twin pregnancy, we performed transarterial embolization for the DAVF, which was successfully achieved without complications in 28 weeks of gestation. Tinnitus resolved immediately after the procedure, and the postoperative course proved uneventful. Both fetuses were safely delivered by cesarean section on 37 1/7 weeks of gestation.

Conclusions: We encountered a case of cavernous sinus DAVF during a twin pregnancy. This case suggests that hemodynamic shift due to pregnancy has potential to cause higher shunt flow in an arteriovenous fistula. The timing of treatment should be determined in consideration of the hemodynamic change in the course of pregnancy. If X-ray exposures and iodine contrast media are appropriately managed, endovascular intervention is one treatment option, even during pregnancy.
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http://dx.doi.org/10.1177/1591019921991396DOI Listing
January 2021

Long-term Outcomes of Gamma Knife Radiosurgery for Treating Vestibular Schwannoma With a Lower Prescription Dose of 12 Gy Compared With Higher Dose Treatment.

Otol Neurotol 2020 12;41(10):e1314-e1320

Department of Neurosurgery, the University of Tokyo Hospital, Tokyo, Japan.

Objective: Gamma knife radiosurgery (GKRS) is commonly used to treat vestibular schwannomas (VSs). The risk of complications from GKRS decreases at lower doses, but it is unknown if long-term tumor control is negatively affected by dose reduction.

Study Design: This was a retrospective case review and analysis of patient data.

Setting: Tertiary referral center.

Patients: Patients with VSs who underwent GKRS between 1990 and 2007 at the authors' institution.

Intervention(s): The subjects were divided into two cohorts based on the prescribed doses of radiation received: a 12 Gy cohort (96 patients) with a follow-up period of 124 months and a >12 Gy cohort (118 patients) with a follow-up period of 143 months.

Main Outcome Measures: Tumor control rates at 10 to 15 years, frequency of facial and trigeminal nerve complications, and hearing function.

Results: The 10 to 15-year tumor control rates were 95% in the 12 Gy cohort and 88% in the > 12 Gy cohort, but the differences were not significant. Compared with the >12 Gy cohort, facial and trigeminal nerve deficits occurred significantly less frequently in the 12 Gy cohort, with the 10-year cumulative, permanent deficit-free rates being 2% and 0%, respectively. Multivariate analyses revealed that treatment doses exceeding 12 Gy were associated with a significantly higher risk for cranial nerve deficits. The percentage of subjects retaining pure-tone average ≤ 50 dB at the final follow-up did not significantly differ between the cohorts (12 Gy cohort, 30% and >12 Gy cohort, 33%; p = 0.823).

Conclusions: Dose reduction to 12 Gy for GKRS to treat VSs decreased facial and trigeminal nerve complications without worsening tumor control rates.
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http://dx.doi.org/10.1097/MAO.0000000000002885DOI Listing
December 2020

Delayed Postoperative Hyponatremia Following Endoscopic Transsphenoidal Surgery for Non-Adenomatous Parasellar Tumors.

Cancers (Basel) 2020 Dec 20;12(12). Epub 2020 Dec 20.

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo 113-8655, Japan.

Little is known about delayed postoperative hyponatremia (DPH) accompanied with transsphenoidal surgery for non-adenomatous skull base tumors (NASBTs). Consecutive data on 30 patients with parasellar NASBT was retrospectively reviewed with detailed analyses on perioperative serial sodium levels. Serological DPH (sodium ≤ 135 mmol/L) was observed in eight (27%), with four (13%) of them being symptomatic. DPH developed on postoperative day 7-12 where the mean sodium levels were 134 mmol/L (a mean of 7 mmol/L drop from the baseline) in asymptomatic and 125 mmol/L (a mean of 17.5 mmol/L drop from the baseline) in symptomatic DPH. Serological DPH was accompanied with "weight loss and hemoconcentration (cerebral salt wasting type)" in four (50%), "weight gain and hemodilution (syndrome of inappropriate antidiuretic hormone secretion type)" in three (38%), and no significant weight change in one. Intraoperative extradural retraction of the pituitary gland was the only significant factor for serological DPH ( = 0.035; odds ratio, 12.25 (95% confidence interval, 1.27-118.36)). DPH should be recognized as one of the significant postsurgical complications associated with TSS for NASBTs. Although the underlying mechanism is still controversial, intraoperative extradural compression of the pituitary gland and subsequent dysregulation of the hypothalamo-hypophyseal axis may be responsible.
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http://dx.doi.org/10.3390/cancers12123849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766216PMC
December 2020

Outcomes of stereotactic radiosurgery for hemorrhagic arteriovenous malformations with or without prior resection or embolization.

J Neurosurg 2020 Dec 4:1-9. Epub 2020 Dec 4.

Departments of1Neurosurgery and.

Objective: The major concern about ruptured arteriovenous malformations (rAVMs) is recurrent hemorrhage, which tends to preclude stereotactic radiosurgery (SRS) as a therapeutic modality for these brain malformations. In this study, the authors aimed to clarify the role of SRS for rAVM as a stand-alone modality and an adjunct for a remnant nidus after surgery or embolization.

Methods: Data on 410 consecutive patients with rAVMs treated with SRS were analyzed. The patients were classified into groups, according to prior interventions: SRS-alone, surgery and SRS (Surg-SRS), and embolization and SRS (Embol-SRS) groups. The outcomes of the SRS-alone group were analyzed in comparison with those of the other two groups.

Results: The obliteration rate was higher in the Surg-SRS group than in the SRS-alone group (5-year cumulative rate 97% vs 79%, p < 0.001), whereas no significant difference was observed between the Embol-SRS and SRS-alone groups. Prior resection (HR 1.78, 95% CI 1.30-2.43, p < 0.001), a maximum AVM diameter ≤ 20 mm (HR 1.81, 95% CI 1.43-2.30, p < 0.001), and a prescription dose ≥ 20 Gy (HR 2.04, 95% CI 1.28-3.27, p = 0.003) were associated with a better obliteration rate, as demonstrated by multivariate Cox proportional hazards analyses. In the SRS-alone group, the annual post-SRS hemorrhage rates were 1.5% within 5 years and 0.2% thereafter and the 10-year significant neurological event-free rate was 95%; no intergroup difference was observed in either outcome. The exclusive performance of SRS (SRS alone) was not a risk for post-SRS hemorrhage or for significant neurological events based on multivariate analyses. These results were also confirmed with propensity score-matched analyses.

Conclusions: The treatment strategy for rAVMs should be tailored with due consideration of multiple factors associated with the patients. Stand-alone SRS is effective for hemorrhagic AVMs, and the risk of post-SRS hemorrhage was low. SRS can also be favorably used for residual AVMs after initial interventions, especially after failed resection.
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http://dx.doi.org/10.3171/2020.7.JNS201502DOI Listing
December 2020

Medical Care-Related Decisions among Patients Diagnosed with Early Stage Malignant Brain Tumor: A Qualitative Study.

Glob Qual Nurs Res 2020 Jan-Dec;7:2333393620960059. Epub 2020 Sep 29.

The University of Tokyo, Tokyo, Japan.

Medical care-related decision-making among patients with malignant brain tumors has not been sufficiently discussed. This study aimed to develop a framework for understanding patients' experiences in the decision-making process. Semi-structured interviews with 14 patients were analyzed using a grounded theory approach, focusing on their 48 decision-making points. Additionally, interviews with two family members and seven healthcare providers, and participant observations were used to gain contextual insight into patients' experiences. Patients faced decisions while they under shock, fear, and anxiety while hoping. Under this context, they showed four decision-making patterns: (1) , (2) , (3) , and (4) . Across these patterns, the patients were generally satisfied with their decisions even when they did not actively participate in the process. Healthcare providers need to understand patients' contexts and their attitudes toward yielding decision-making to others.
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http://dx.doi.org/10.1177/2333393620960059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560538PMC
September 2020

Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination.

Brain Tumor Pathol 2021 Jan 18;38(1):71-77. Epub 2020 Oct 18.

Department of Neurosurgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.

Dissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2 years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In addition, the methylation class determined by the methylation profiling classifier developed by the German Cancer Research Center (DKFZ)/University Hospital Heidelberg/German Consortium for Translational Cancer Research was consistent with that of common hemangioblastomas. However, genetic analyses showed significant gains and losses throughout the whole genome, indicating that highly aberrant copy number profiles may be the key to elucidating this rare but life-threatening clinical entity. Accumulation of more detailed case reports based on the comparison of specimens obtained before and after surgery or radiation is necessary to better understand the pathophysiology of the dissemination phenotype of hemangioblastoma.
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http://dx.doi.org/10.1007/s10014-020-00387-7DOI Listing
January 2021

Targeted deep sequencing of DNA from multiple tissue types improves the diagnostic rate and reveals a highly diverse phenotype of mosaic neurofibromatosis type 2.

J Med Genet 2020 Oct 16. Epub 2020 Oct 16.

Department of Neurosurgery, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Background: Although 60% of patients with de novo neurofibromatosis type 2 (NF2) are presumed to have mosaic NF2, the actual diagnostic rate of this condition remains low at around 20% because of the existing difficulties in detecting variants with low variant allele frequency (VAF). Here, we examined the correlation between the genotype and phenotype of mosaic NF2 after improving the diagnostic rate of mosaic NF2.

Methods: We performed targeted deep sequencing of 36 genes including using DNA samples from multiple tissues (blood, buccal mucosa, hair follicle and tumour) of 53 patients with de novo NF2 and elucidated their genotype-phenotype correlation.

Results: Twenty-four patients (45.2%) had the germline variant, and 20 patients with NF2 (37.7%) had mosaic NF2. The mosaic NF2 phenotype was significantly different from that in patients with germline variant in terms of distribution of NF2-related disease, tumour growth rate and hearing outcome. The behaviour of schwannoma correlated to the extent of VAF with variant in normal tissues unlike meningioma.

Conclusion: We have improved the diagnostic rate of mosaic NF2 compared with that of previous studies by targeted deep sequencing of DNA from multiple tissues. Many atypical patients with NF2 diagnosed with 'unilateral vestibular schwannoma' or 'multiple meningiomas' presumably have mosaic NF2. Finally, we suggest that the highly diverse phenotype of NF2 could result not only from the type and location of variant but also the extent of VAF in the variant within normal tissue DNA.
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http://dx.doi.org/10.1136/jmedgenet-2020-106973DOI Listing
October 2020

Single-Cell Information Analysis Reveals That Skeletal Muscles Incorporate Cell-to-Cell Variability as Information Not Noise.

Cell Rep 2020 09;32(9):108051

Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. Electronic address:

Cell-to-cell variability in signal transduction in biological systems is often considered noise. However, intercellular variation (i.e., cell-to-cell variability) has the potential to enable individual cells to encode different information. Here, we show that intercellular variation increases information transmission of skeletal muscle. We analyze the responses of multiple cultured myotubes or isolated skeletal muscle fibers as a multiple-cell channel composed of single-cell channels. We find that the multiple-cell channel, which incorporates intercellular variation as information, not noise, transmitted more information in the presence of intercellular variation than in the absence according to the "response diversity effect," increasing in the gradualness of dose response by summing the cell-to-cell variable dose responses. We quantify the information transmission of human facial muscle contraction during intraoperative neurophysiological monitoring and find that information transmission of muscle contraction is comparable to that of a multiple-cell channel. Thus, our data indicate that intercellular variation can increase the information capacity of tissues.
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http://dx.doi.org/10.1016/j.celrep.2020.108051DOI Listing
September 2020

Association Between the Onset Pattern of Adult Moyamoya Disease and Risk Factors for Stroke.

Stroke 2020 10 1;51(10):3124-3128. Epub 2020 Sep 1.

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Japan (Y.H., S.M., H.H., K.O., S.D., Y.T., H.N., N.S.).

Background And Purpose: Few previous studies have comprehensively explored the relationship between the onset pattern of adult moyamoya disease and risk factors for stroke. We performed a retrospective analysis focusing on risk factors for stroke and related findings on magnetic resonance imaging/angiography with respect to the pattern of disease onset. We also examined whether risk factors for stroke were associated with an increased risk for symptomization in asymptomatic patients.

Methods: A total of 178 adult patients with moyamoya disease (asymptomatic, n=84; ischemic, n=71; hemorrhagic, n=23) at the University of Tokyo Hospital from 2000 to 2018 were included in this study. Data pertaining to patient background and magnetic resonance imaging findings were analyzed retrospectively. In the asymptomatic group, the effects of stroke-associated risk factors on symptom onset were analyzed.

Results: Comparisons among the 3 groups revealed no significant difference in the frequency of risk factors for stroke. The proportion of patients with magnetic resonance imaging/angiography findings indicating anterior choroidal artery anastomosis or microbleeds was significantly higher in the hemorrhagic group than in the asymptomatic or ischemic group. Among asymptomatic patients, the hazard ratios for symptomization with hypertension and dyslipidemia were 6.69 ([95% CI, 1.23-36.4] =0.028) and 8.14 ([95% CI, 1.46-45.2] =0.017), respectively.

Conclusions: The development of anterior choroidal artery anastomosis and microbleeds on magnetic resonance imaging/angiography was significantly associated with hemorrhagic onset. Hypertension and dyslipidemia may increase the risk of cerebrovascular events in asymptomatic patients, and thus, early intervention to these factors may be important.
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http://dx.doi.org/10.1161/STROKEAHA.120.030653DOI Listing
October 2020

Retro-odontoid Pseudotumor: Two Cases of Intradural Ganglion Cysts Arising From the Odontoid Process with Syringobulbia.

World Neurosurg 2020 12 20;144:148-153. Epub 2020 Aug 20.

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Ganglion cysts mostly occur in the knuckles and wrists, but they rarely present in the odontoid process and can cause neurological symptoms by compressing the spinal cord. They are mostly localized in the epidural space, but may very rarely appear in the intradural space. There are no reports of cases of intradural ganglion cyst involving syringobulbia.

Case Description: We report the presentation and management of 2 cases of an intradural ganglion cyst of the odontoid process. Several treatment options for ganglion cysts of the odontoid process have been reported, such as rest and use of a neck collar, posterior decompression and fusion, and transoral anterior decompression. Because our 2 cases progressed rapidly and had severe neurological symptoms, surgical treatment was performed for rapid decompression and definitive pathological diagnosis. The mass was resected as much as possible using the lateral occipital fossa approach, and the operation was completed without dissection of the brain stem or manipulation of the syringobulbia. Postoperatively, neurological symptoms promptly improved, and the syringobulbia reduced.

Conclusions: For intradural ganglion cysts with syringobulbia, we suggest relief of the compression by resection of the mass and treatment of the syringobulbia in 2 stages, if necessary, to avoid the risk of damage to the brainstem.
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http://dx.doi.org/10.1016/j.wneu.2020.08.120DOI Listing
December 2020

Stent-Assisted Coil Embolization of a Basilar Artery Dissecting Aneurysm Involved in Skull Base Chordoma Before Endoscopic Transsphenoidal Transclival Resection.

World Neurosurg 2020 11 11;143:466-470. Epub 2020 Aug 11.

Department of Neurosurgery, The University of Tokyo, Tokyo, Japan.

Background: Skull base chordomas will occasionally penetrate the clival dura mater and extend into the prepontine cistern, involving the basilar artery. Few reports have described cases of skull base chordoma accompanying a dissecting aneurysm of the basilar artery, and the treatment strategies have remained largely unknown.

Case Description: A 28-year-old man was referred to our hospital with a complaint of severe headache. A skull base chordoma involving a basilar artery dissecting aneurysm was diagnosed. We initially performed endovascular surgery for the dissecting aneurysm after dual antiplatelet therapy before surgical resection of the tumor, which was successfully achieved without complications. Follow-up angiography 3 months after endovascular surgery disclosed obliteration of the dissecting aneurysm. We then stopped the dual antiplatelet therapy, and performed judicious resection using an endoscopic transclival approach. The residual tumor was treated with radiosurgery. At the last follow-up examination, the patient was stable, and the tumor remained sufficiently controlled.

Conclusions: We have reported a case of a dissecting aneurysm of the basilar artery with clival chordoma. Our findings suggest that chordoma with intradural vascular encasement has the potential to invade the vessel wall. To avoid rupture of those critical vascular structures, treatment strategies that minimize stress on the involved arteries and offer safe and sufficient surgical resection should be considered.
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http://dx.doi.org/10.1016/j.wneu.2020.08.054DOI Listing
November 2020

Giant Fusiform and Dolichoectatic Aneurysms of the Basilar Trunk and Vertebrobasilar Junction-Clinicopathological and Surgical Outcome.

Neurosurgery 2020 12;88(1):82-95

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Giant fusiform and dolichoectatic aneurysms of the basilar trunk and vertebrobasilar junction (BTVBJ-GFDA) are extremely difficult to treat.

Objective: To evaluate factors influencing survival and outcome of BTVBJ-GFDA by performing a retrospective multicenter cohort study.

Methods: A total of 32 patients with BTVBJ-GFDA were included in this study. Clinicopathological characteristics, treatment measures, and outcomes were collected from medical records and imaging studies. Autopsy and histological findings of the aneurysm and adjacent brain tissue were also obtained in 9 cases.

Results: A total of 11 patients did not undergo surgery, of whom 10 died; 3 from progressive brainstem compression, 4 from subarachnoid hemorrhage, 2 from brainstem infarction, and 1 from associated atherosclerotic disease. The remaining 21 patients underwent a surgical treatment, consisting of immediately proximal parent artery occlusion, remotely proximal parent artery occlusion, clip reconstruction, and distal bypass and achieved significantly longer overall survival compared with those who received conservative therapy (adjusted hazard ratio 1.508, 95% CI 1.058-2.148, P = .02). Histological examination of the aneurysms demonstrated staged clots, open lumen, and intrathrombotic channels with endothelial lining. The patients younger than 45 yr of age showed statistically longer survival than those equal and older than 45 yr (P = .03).

Conclusion: Surgical intervention achieved greater survival than conservative management in BTVBJ-GFDA. Narrow ideal treatment window of the blood flow within the aneurysm to maintain sufficient but not excess supply should be targeted based on the hemodynamics of both the posterior communicating arteries and perforating vessel collaterals.
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http://dx.doi.org/10.1093/neuros/nyaa317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891276PMC
December 2020

Comprehensive investigation of RNF213 nonsynonymous variants associated with intracranial artery stenosis.

Sci Rep 2020 07 20;10(1):11942. Epub 2020 Jul 20.

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Intracranial artery stenosis (ICAS) is the most common cause of ischemic stroke worldwide. RNF213 single nucleotide variant c.14429G > A (p.Arg4810Lys, rs112735431) was recently reported to be associated with ICAS in East Asians. However, the disease susceptibility of other RNF213 variants has not been clarified. This study comprehensively investigated ICAS-associated RNF213 variants in a pool of 168 Japanese ICAS patients and 1,194 control subjects. We found 138 nonsynonymous germline variants by target resequencing of all coding exons in RNF213. Association study between ICAS patients and control subjects revealed that only p.Arg4810Lys had significant association with ICAS (P = 1.5 × 10, odds ratio = 29.3, 95% confidence interval 15.31-56.2 [dominant model]). Fourteen of 138 variants were rare variants detected in ICAS patients not harboring p.Arg4810Lys variant. Two of these rare variants (p.Cys118Arg and p.Leu2356Phe) consistent with variants previously reported in moyamoya disease patients characterized by stenosis of intracranial artery and association with RNF213, and three rare variants (p.Ser193Gly, p.Val1817Leu, and p.Asp3329Tyr) were found neither in control subjects and Single Nucleotide Polymorphism Database. The present findings may improve our understanding of the genetic background of intracranial artery stenosis.
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http://dx.doi.org/10.1038/s41598-020-68888-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371676PMC
July 2020