Faculty Profiles - HASEGAWA Hitoshi

Papers - HASEGAWA Hitoshi

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CRISPR/CasRx suppresses KRAS-induced brain arteriovenous malformation developed in postnatal brain endothelial cells in mice. International journal

Shoji Saito, Yuka Nakamura, Satoshi Miyashita, Tokiharu Sato, Kana Hoshina, Masayasu Okada, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii, Jakob Körbelin, Yoshiaki Kubota, Kazuki Tainaka, Manabu Natsumeda, Masaki Ueno

JCI insight 9 ( 22 ) 2024.11

Language：English Publishing type：Research paper (scientific journal)

Brain arteriovenous malformations (bAVMs) are anomalies forming vascular tangles connecting the arteries and veins, which cause hemorrhagic stroke in young adults. Current surgical approaches are highly invasive, and alternative therapeutic methods are warranted. Recent genetic studies identified KRAS mutations in endothelial cells of bAVMs; however, the underlying process leading to malformation in the postnatal stage remains unknown. Here we established a mouse model of bAVM developing during the early postnatal stage. Among 4 methods tested, mutant KRAS specifically introduced in brain endothelial cells by brain endothelial cell-directed adeno-associated virus (AAV) and endothelial cell-specific Cdh5-CreERT2 mice successfully induced bAVMs in the postnatal period. Mutant KRAS led to the development of multiple vascular tangles and hemorrhage in the brain with increased MAPK/ERK signaling and growth in endothelial cells. Three-dimensional analyses in cleared tissue revealed dilated vascular networks connecting arteries and veins, similar to human bAVMs. Single-cell RNA-Seq revealed dysregulated gene expressions in endothelial cells and multiple cell types involved in the pathological process. Finally, we employed CRISPR/CasRx to knock down mutant KRAS expression, which efficiently suppressed bAVM development. The present model reveals pathological processes that lead to postnatal bAVMs and demonstrates the efficacy of therapeutic strategies with CRISPR/CasRx.

DOI： 10.1172/jci.insight.179729

Clinical and Hemodynamic Features of Aneurysm Rupture in Coil Embolization of Intracranial Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kohei Shibuya, Hidemoto Fujiwara, Makoto Oishi

Diagnostics (Basel, Switzerland) 14 ( 11 ) 2024.6

Language：English Publishing type：Research paper (scientific journal)

Intraprocedural rupture (IPR) during coil embolization (CE) of an intracranial aneurysm is a significant clinical concern that necessitates a comprehensive understanding of its clinical and hemodynamic predictors. Between January 2012 and December 2023, 435 saccular cerebral aneurysms were treated with CE at our institution. The inclusion criterion was extravasation or coil protrusion during CE. Postoperative data were used to confirm rupture points, and computational fluid dynamics (CFD) analysis was performed to assess hemodynamic characteristics, focusing on maximum pressure (Pmax) and wall shear stress (WSS). IPR occurred in six aneurysms (1.3%; three ruptured and three unruptured), with a dome size of 4.7 ± 1.8 mm and a D/N ratio of 1.5 ± 0.5. There were four aneurysms in the internal carotid artery (ICA), one in the anterior cerebral artery, and one in the middle cerebral artery. ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with Pmax in five aneurysms (83.3%). Time-averaged WSS was locally reduced around this area (1.3 ± 0.7 [Pa]), significantly lower than the aneurysmal dome (p < 0.01). Hemodynamically unstable areas have fragile, thin walls with rupture risk. A microcatheter was inserted along the inflow zone, directed towards the caution area. These findings underscore the importance of identifying hemodynamically unstable areas during CE. Adjunctive techniques should be applied with caution, especially in small aneurysms with axial misalignment, to minimize the rupture risk.

DOI： 10.3390/diagnostics14111203

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

Yohei Mineharu, Yasushi Takagi, Akio Koizumi, Takaaki Morimoto, Takeshi Funaki, Tomohito Hishikawa, Yoshio Araki, Hitoshi Hasegawa, Jun C Takahashi, Satoshi Kuroda, Kiyohiro Houkin, Susumu Miyamoto

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 33 ( 2 ) 107513 - 107513 2024.2

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1016/j.jstrokecerebrovasdis.2023.107513

Non-sinus type of transverse sinus dural arteriovenous fistulas on the arachnoid granulation of the dural sinus wall. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kohei Shibuya, Hidemoto Fujiwara, Makoto Oishi

Surgical neurology international 15 43 - 43 2024

Language：English

BACKGROUND: The etiology of a non-sinus-type dural arteriovenous fistulas (DAVFs) with shunt points located on the sinus wall, previously described as on-the-wall-type DAVFs, is unknown. CASE DESCRIPTION: Two cases of non-sinus-type transverse sinus DAVF with a shunt point limited to the dural sinus wall, causing cortical venous reflux, were successfully treated with endovascular transarterial Onyx embolization. The Onyx cast showed multiple feeders from the occipital and middle meningeal arteries aggregated in the arachnoid granulation (AG), which dilated the draining vein. CONCLUSION: Non-sinus-type DAVFs with shunt points located on the AG may be one of the presentations of an on-the-wall-type DAVF.

DOI： 10.25259/SNI_930_2023

血栓回収治療成績の県内悉皆調査

渋谷航平, 長谷川仁, 鈴木倫明, 藤原秀元, 西山慶, 大石誠

脳血管内治療 8 ( Suppl. ) S267 - S267 2023.11

Investigation of Mechanical Thrombectomy in Elderly Patients over 85 Years Old: A Multicenter Study.

Kohei Shibuya, Hitoshi Hasegawa, Tomoaki Suzuki, Haruhiko Takahashi, Kei Nishiyama, Makoto Oishi, Yukihiko Fujii

Neurologia medico-chirurgica 63 ( 9 ) 393 - 399 2023.9

Language：English Publishing type：Research paper (scientific journal)

In Japan, which has a super-aging society, there are increasing opportunities to perform mechanical thrombectomy for the elderly; however, there is no recorded evidence of thrombectomy for the elderly. This study examined the usefulness of thrombectomy in the elderly. We retrospectively analyzed patient data using a multicenter acute ischemic stroke registry (NGT-FAST). We examined outcomes in patients 75 years and older who underwent thrombectomies between January 1, 2021, and December 31, 2021. The patients were divided into two groups: the 75-84-year-old group and the 85+-year-old group. There was no difference in the pretreatment National Institutes of Health Stroke Scale score or Alberta Stroke Program Early Computed Tomography Score between the two groups, but the 85+-year-old group had a significantly lower rate of pre-stroke modified Rankin Scale (mRS) score of 0-2. There were no differences in time from onset to treatment or effective recanalization rate, but complications tended to be more common in the 85+-year-old group. The number of patients with a good outcome at discharge (an mRS score of 0-3) was significantly lower in the 85+-year-old group than in the 75-84-year-old group. In addition, 90.9% of patients in the 85+-year-old group with a pre-stroke mRS score of 3 deteriorated after treatment. The pre-stroke mRS score is very important in determining the indication for thrombectomy in the elderly because their preoperative condition is more likely to influence the outcome than that of younger patients.

DOI： 10.2176/jns-nmc.2023-0039

Usefulness of silent magnetic resonance angiography for intracranial aneurysms treated with a flow re-direction endoluminal device. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kazuhiro Ando, Kouhei Shibuya, Haruhiko Takahashi, Shoji Saito, Hidemoto Fujiwara, Makoto Oishi, Yukihiko Fujii

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences 15910199231174546 - 15910199231174546 2023.5

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Flow re-direction endoluminal device (FRED) is a novel dual-layer flow-diverting stent to treat cerebral aneurysms with high obliteration rates, however, it induces inevitable metal-related artifacts. We compared silent magnetic resonance angiography (MRA), a new MRA method using ultra-short time of echo and arterial spin-labeling, with conventional time-of-flight (TOF)-MRA for imaging aneurysms treated using FRED. METHODS: Between May 2020 and September 2022, 16 patients with unruptured internal carotid aneurysms treated using FRED simultaneously underwent silent MRA and TOF-MRA after treatment, with 36 follow-up sessions in total. Two observers independently graded the quality of intra-aneurysmal flow and stented parent arteries under both types of MRA from 1 (not visible) to 4 (nearly equal to digital subtraction angiography [DSA]), with reference to DSA images as a standard criterion. RESULTS: The mean scores for intra-aneurysmal flow and stented parent arteries were significantly better for silent MRA (3.93 ± 0.21 and 3.82 ± 0.32, respectively) than for TOF-MRA (2.08 ± 0.99 and 1.92 ± 0.79, respectively) (P < 0.01). Intermodality agreements for intra-aneurysmal flow and stented parent arteries were 0.87 and 0.90, respectively. CONCLUSION: Silent MRA is superior to TOF-MRA for assessing patients treated with FRED, with potential as an alternative imaging modality to DSA.

DOI： 10.1177/15910199231174546

Superior Visualization of Neovascularization with Silent Magnetic Resonance Angiography Compared to Time-of-flight Magnetic Resonance Angiography after Bypass Surgery in Moyamoya Disease. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kohei Shibuya, Haruhiko Takahashi, Hidemoto Fujiwara, Makoto Oishi, Yukihiko Fujii

World neurosurgery 2023.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The evaluation of postsurgical neoangiogenesis in patients with moyamoya disease (MMD) is crucial for appropriate patient management. This study aimed to assess the visualization of neovascularization after bypass surgery using non-contrast-enhanced silent magnetic resonance angiography (MRA) with ultra-short echo time (UTE) and arterial spin labeling (ASL). METHODS: After bypass surgery, 13 patients with MMD were followed up for >6 months between September 2019 and November 2022. They underwent silent MRA in the same session as time-of-flight MRA (TOF-MRA) and digital subtraction angiography (DSA). Two observers independently rated the visualization of neovascularization in both types of MRA from 1 (not visible) to 4 (nearly equal to DSA), with reference to DSA images as the standard. RESULTS: The mean scores were significantly higher for silent MRA compared with TOF-MRA (3.81 ± 0.48 and 1.92 ± 0.70, respectively) (p <0.01). The inter-modality agreements were 0.83 and 0.71 for silent MRA and TOF-MRA, respectively. TOF-MRA depicted the donor artery and recipient cortical artery after direct bypass surgery, although fine neovascularization developed after indirect bypass surgery was poorly visualized. Silent MRA could reveal the developed bypass flow signal and perfused MCA territory, which was almost equal to the DSA images. CONCLUSIONS: Silent MRA achieves better visualization of postsurgical revascularization in patients with MMD than TOF-MRA. Moreover, it may have the potential to provide visualization of the developed bypass flow equivalent to DSA.

DOI： 10.1016/j.wneu.2023.04.119

[Arteriovenous Malformations:Endovascular Techniques and Devices].

Hitoshi Hasegawa

No shinkei geka. Neurological surgery 51 ( 2 ) 265 - 277 2023.3

Language：Japanese Publishing type：Research paper (scientific journal)

Endovascular embolization using liquid materials is a safe and effective treatment option for cerebral arteriovenous malformations(AVM). Onyx and n-butyl cyanoacrylate, currently available in Japan, have specific features. Appropriate embolic agents should be selected based on their characteristics. Transarterial embolization(TAE)is the standard endovascular treatment approach. However, there have been some recent reports regarding the efficacy of transvenous embolization(TVE). TVE is potentially curative for small AVM with hemorrhagic onset, inaccessible arterial feeders, deep location, and/or a single draining vein. In specific cases, TVE may provide a higher chance of complete obliteration of the AVM than TAE. Some unsolved problems need further clarification, such as the relative positions of liquid embolization against direct surgery, dealing with unruptured AVM, and effective treatment for high-grade AVM.

DOI： 10.11477/mf.1436204742

A Case of Paradoxical Cerebral Embolism Due to Pulmonary Arteriovenous Fistula Mimicking Vertebral Artery Dissection With Wallenberg Syndrome. International journal

Masaru Isogai, Tomoaki Suzuki, Shyunichi Kato, Yoshinori Taniguchi, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii

Cureus 15 ( 2 ) e34564 2023.2

Language：English

Pulmonary arteriovenous fistula (PAVF) leads to paradoxical cerebral embolism, which can be fatal if left untreated. We report a rare case of brainstem infarction with acute severe headache and Wallenberg syndrome caused by a PAVF mimicking vertebral artery (VA) dissection. A 40-year-old man presented with a sudden occipital headache accompanied by right hemisensory disturbance. Magnetic resonance imaging revealed left lateral medullary infarction and poor depiction of the left VA. However, it was clearly recanalized on day six, and there were no findings of VA dissection. Whole-body contrast-enhanced computed tomography (CT) revealed a PAVF in the right lung and a thrombus in the feeding artery. The patient was diagnosed with hereditary hemorrhagic telangiectasia due to recurrent epistaxis and peripheral vasodilation of the tongue. An anticoagulant was administered for preventing further ischemic stroke, and a follow-up CT confirmed the disappearance of the thrombus in three months. Thoracoscopic partial lung resection was performed five months after the onset, and no recurrence of ischemic stroke was observed.

DOI： 10.7759/cureus.34564

Usefulness of Y-shaped PulseRider-assisted coil embolization for basilar artery tip aneurysm with a misaligned axis: A case report. International journal

Kohei Shibuya, Hitoshi Hasegawa, Tomoaki Suzuki, Hidemoto Fujiwara, Satoshi Shibuma, Kazuki Shida, Makoto Oishi

Surgical neurology international 14 300 - 300 2023

Language：English

BACKGROUND: Endovascular treatment of wide-necked bifurcation aneurysms remains challenging. Although the advent of PulseRider and Web has expanded treatment options, aneurysms with a large deviation from the parent artery axis remains difficult to treat. We present the case of a wide-necked bifurcation aneurysm that was misaligned with the angle between the long axis of the parent artery and the aneurysm and was successfully treated with Y-shaped PulseRider-assisted coil embolization. CASE DESCRIPTION: A 64-year-old woman presented with an unruptured basilar tip aneurysm. Cerebral angiography showed a wide-necked aneurysm measuring 8.1 mm × 6.1 mm, neck 5.7 mm. The aneurysm was strongly tilted to the right and posterior relative to the basilar artery, and the bilateral posterior cerebral artery (PCA) and superior cerebellar artery (SCA) diverged from the aneurysm body. PulseRider-assisted coil embolization was performed. A Y-shaped PulseRider was selected to be placed in a hybrid fashion with the right arch in the aneurysm and the left arch in the branch. Adequate coil embolization with preservation of the bilateral PCA and SCA was possible, and cerebral angiography immediately after the treatment showed slight dome filling. Cerebral angiography 6 months after the procedure showed that the embolic status had improved to complete occlusion. CONCLUSION: For wide-neck bifurcation aneurysms with a misaligned axis, a Y-shaped PulseRider used in a hybrid fashion, in which the leaflet on the side with the tilted axis is placed in the aneurysm, allows the PulseRider to be deployed more closely to the aneurysm, thereby enabling good coil embolization.

DOI： 10.25259/SNI_449_2023

Opposite L-configuration double stenting for rupture of an extremely wide-necked anterior communicating artery aneurysm at the acute stage: illustrative case. International journal

Nobuyuki Genkai, Kouichirou Okamoto, Hitoshi Hasegawa

Journal of neurosurgery. Case lessons 4 ( 18 ) 2022.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Wide-necked aneurysms can be treated by double stenting in an X- or Y-configuration or by a double waffle-cone technique. However, some aneurysms remain untreatable. OBSERVATIONS: The rupture of a complex wide-necked anterior communicating artery (AcomA) aneurysm that caused acute subarachnoid hemorrhage (SAH) was treated successfully using double stents with an opposite L-configuration as an alternative to the X-stent technique. The aneurysm involved both A1-A2 junctions in the aneurysm neck with acutely oriented A2 segments of the anterior cerebral artery bilaterally. It was densely packed and completely obliterated angiographically with preserved blood flow by implanting each stent in the ipsilateral A1-A2 bilaterally. Blood flow from the left A1 to the right A2 was confirmed through the AcomA on injection of the left internal carotid artery immediately after the procedure without critical infarction in the subthalamic area. Although the AcomA was not demonstrated by injection of the left internal carotid artery on angiography at 3 months or 1 year later, no cerebral infarction was seen on magnetic resonance images at the final hospital visit. LESSONS: Opposite L-configuration double stenting was used successfully as rescue stent-assisted coiling for a rupture of a complex wide-necked AcomA aneurysm in a patient with acute SAH.

DOI： 10.3171/CASE22165

Long-Term Characteristics of De Novo Bleb Formation at the Aneurysm Neck After Coil Embolization in Unruptured Cerebral Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

World neurosurgery 161 e767-e775 2022.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: De novo bleb formation at the aneurysm neck after coil embolization of unruptured intracranial aneurysms is a rarely observed type of recurrence. The aim of this study was to elucidate the clinical characteristics of recurrent aneurysms in the long-term period. METHODS: Between January 2002 and December 2015, 290 unruptured intracranial aneurysms were treated with coil embolization at our institution. Patients who underwent retreatment due to aneurysm recurrence were divided into 2 patterns of recanalization: de novo bleb formation at the neck of a coiled sac (type DNV) and an enlarged residual cavity without de novo bleb formation (type non-DNV). RESULTS: Twenty-seven patients with aneurysms (9.3%) underwent retreatment (type DNV, 7; type non-DNV, 20). The initial aneurysm size of type DNV aneurysms was significantly smaller than that of type non-DNV (6.1 ± 2.2 mm vs. 10.1 ± 3.6 mm; P < 0.01), and time to retreatment in type DNV was significantly longer than that in type non-DNV (9.4 ± 5.3 years vs. 2.0 ± 2.0 years; P < 0.01). Two type DNV basilar artery (BA) aneurysms ruptured after a few years; however, the other type DNV aneurysms, including 4 anterior circulation aneurysms (including the internal carotid artery), were observed to grow gradually without rupture for >10 years until retreatment. CONCLUSIONS: De novo bleb formation at the neck of a coiled sac emerges with insidious growth during long-term follow-up. Constant caution should be exercised, even in cases of small- and medium-sized anterior circulation aneurysms. A risk of rupture risk may be anticipated, especially in BA lesions.

DOI： 10.1016/j.wneu.2022.02.092

Non-contrast-enhanced silent magnetic resonance angiography for assessing cerebral aneurysms after PulseRider treatment.

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Japanese journal of radiology 40 ( 9 ) 979 - 985 2022.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Conventional time-of-flight (TOF) magnetic resonance angiography (MRA) failed to depict clear visualization of coiled cerebral aneurysms with PulseRider due to metal-induced susceptibility artifacts. Our aim was to overcome the metal artifact using a novel imaging technique of non-contrast-enhanced ultrashort echo-time magnetic resonance angiography (UTE-MRA). MATERIALS AND METHODS: Five unruptured intracranial aneurysms were treated using PulseRider and the patients underwent silent MRA (UTE-MRA). The images were compared with TOF-MRA and digital subtraction angiography (DSA). RESULTS: Silent MRA can visualize the residual cavity of the coiled aneurysms, which was not well visualized and rather defective when using TOF-MRA. While a segment of the proximal marker composed of stainless steel was poorly visualized, the other parts of the parent artery and the arteries of bifurcation, including the aneurysmal neck, were clearly visualized, equivalent to that of DSA. CONCLUSIONS: UTE-MRA achieves better visualization of cerebral aneurysms after PulseRider treatment than TOF-MRA.

DOI： 10.1007/s11604-022-01276-z

Endovascular treatment of an infectious aneurysm using the selective provocative test and transcranial motor evoked potential monitoring under general anesthesia: a case report. International journal

Kazuhiro Ando, Tetsuya Hiraishi, Makoto Oishi, Hitoshi Hasegawa, Bumpei Kikuchi, Manabu Natsumeda, Tomoaki Suzuki, Shoji Saito, Tomoyoshi Ota, Yuichi Yoshida, Yukihiko Fujii

Acta neurochirurgica 164 ( 5 ) 1265 - 1269 2021.9

Language：English Publishing type：Research paper (scientific journal)

The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.

DOI： 10.1007/s00701-021-05001-z

Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group. International journal

Yohei Mineharu, Yasushi Takagi, Akio Koizumi, Takaaki Morimoto, Takeshi Funaki, Tomohito Hishikawa, Yoshio Araki, Hitoshi Hasegawa, Jun C Takahashi, Satoshi Kuroda, Kiyohiro Houkin, Susumu Miyamoto

Journal of neurosurgery 136 ( 4 ) 1 - 10 2021.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS: The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS: Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 63 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS: These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.

DOI： 10.3171/2021.3.JNS203913

Delayed Bleeding of Unruptured Intracranial Aneurysms After Coil Embolization: A Retrospective Case Series. International journal

Kazuhiro Ando, Hitoshi Hasegawa, Tomoaki Suzuki, Shoji Saito, Kohei Shibuya, Haruhiko Takahashi, Makoto Oishi, Yukihiko Fujii

World neurosurgery 149 e135-e145 2021.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Delayed bleeding of unruptured intracranial aneurysms (UIAs) after coil embolization is rare; this study aimed to analyze the occurrence of delayed bleeding of UIAs after coil embolization. METHODS: We retrospectively analyzed patients with UIAs after coil embolization between January 2002 and December 2018 and assessed the features of UIAs with delayed bleeding after coil embolization. RESULTS: Analysis included 307 patients with 335 UIAs. Mean follow-up was 7.1 ± 4.9 years, and total follow-up was 2365 aneurysm-years. There were 271 (80.9%) aneurysms located in the anterior circulation and 64 (19.1%) aneurysms located in the posterior circulation. Significant differences were observed between the 2 groups in terms of maximum size of the aneurysm (P < 0.01), width of the aneurysm neck (P < 0.01), and number of retreatment cases (P < 0.01). During the follow-up period, delayed bleeding occurred in 4 aneurysms (annual bleeding rate of 0.17%); all were located in the posterior circulation. The original size was not relatively large (mean 8.6 ± 2.4 mm). All aneurysms bled within 5 years (mean 35 ± 9.6 months) after the initial treatment. Two were de novo aneurysms that developed adjacent to the coiled aneurysms and were not detected on follow-up magnetic resonance angiography. CONCLUSIONS: Cautious follow-up of UIAs with digital subtraction angiography is important, articularly within the first 5 years after the procedure. If there are changes in the anatomic outcomes, short-term reassessment or additional treatment should be actively considered, particularly for aneurysms in the posterior circulation.

DOI： 10.1016/j.wneu.2021.02.061

Development and natural course of lateral posterior choroidal artery aneurysms arising from fragile choroidal collaterals in moyamoya disease: illustrative cases. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kouichirou Okamoto, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Journal of neurosurgery. Case lessons 1 ( 15 ) CASE2110 2021.4

Language：English

BACKGROUND: Choroidal collaterals are a risk factor for hemorrhagic stroke, even in the nonhemorrhagic hemisphere, among patients with moyamoya disease (MMD). Peripheral choroidal aneurysms rupture in fragile collaterals; however, the development and natural course of these aneurysms remain elusive. OBSERVATIONS: A 51-year-old woman, who had experienced a right cerebral hemorrhage 3 years earlier, presented with asymptomatic minor bleeding from a left lateral choroidal artery aneurysm in a predeveloped choroidal anastomosis. Although the aneurysm spontaneously thrombosed within 2 months, the choroidal collaterals persisted. After bypass surgery, the choroidal anastomosis regressed, and neither a de novo aneurysm nor a hemorrhagic stroke occurred. A 75-year-old woman with MMD, who had experienced a left frontal infarction 6 years earlier, experienced recurrent right intraventricular hemorrhage from a ruptured lateral choroidal artery aneurysm that developed in the choroidal anastomosis. The aneurysm spontaneously regressed 3 days after the rebleeding with no recurrence over the following 7 years. LESSONS: Choroidal artery aneurysms may develop in the choroidal anastomosis and rupture in the nonsurgical or contralateral hemispheres. Patients with MMD who have a history of hemorrhagic or ischemic stroke and impaired cerebral blood flow require careful observation. Although aneurysms may rapidly regress spontaneously, bypass surgery can stabilize hemodynamic stress and prevent further hemorrhage.

DOI： 10.3171/CASE2110

Unilateral oculomotor nerve palsy caused by arterial compression accompanying subarachnoid hemorrhage: a case report. International journal

Shoji Saito, Hitoshi Hasegawa, Toru Takino, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Jotaro On, Tomoaki Suzuki, Makoto Oishi, Yukihiko Fujii

Acta neurochirurgica 163 ( 3 ) 813 - 816 2021.3

Language：English Publishing type：Research paper (scientific journal)

Unilateral oculomotor nerve palsy, often caused by aneurysmal compression, is one of the decisive findings for confirming the site of a ruptured aneurysm. However, arterial compression can also cause unilateral oculomotor nerve palsy. Here, we present the case of a 59-year-old woman with a ruptured right internal carotid-posterior communicating artery aneurysm accompanied by contralateral oculomotor nerve palsy. The nerve was found to be compressed by the posterior cerebral artery and was isolated from the ruptured aneurysm. When confirming a ruptured aneurysm based on the evidence of unilateral oculomotor palsy, the arteries surrounding the nerve must be thoroughly assessed.

DOI： 10.1007/s00701-020-04633-x

Repeated cerebellar infarction in the affected nondominant vertebral artery distribution with reversible vertebral artery occlusion elicited by head tilt: illustrative case. International journal

Takanori Nozawa, Kouichirou Okamoto, Shinji Nakazato, Kunio Motohashi, Tomoaki Suzuki, Kotaro Morita, Hideki Tashi, Kei Watanabe, Hitoshi Hasegawa, Masato Watanabe, Hiroyuki Kawashima, Yukihiko Fujii

Journal of neurosurgery. Case lessons 1 ( 8 ) CASE2061 2021.2

Language：English

BACKGROUND: Bow hunter's syndrome or stroke (BHS) is characterized by rotational vertebrobasilar insufficiency elicited by rotation of the neck. It is caused by dynamic and reversible occlusion of the vertebral artery (VA). Reversible symptoms of rotational vertebrobasilar insufficiency are described as bow hunter's syndrome, although brain infarction is rarely reported as bow hunter's stroke. OBSERVATIONS: A 70-year-old man experienced repeated cerebellar infarctions three times in the posterior inferior cerebellar artery (PICA) distribution of the nondominant right VA connecting the basilar artery. The onset of symptoms indicating cerebellar infarcts and the patient's head position changes were unrelated. Dynamic digital angiography (DA) revealed that the nondominant right VA was occluded by an osteophyte from the C4 vertebral body, and the right PICA branches were shown to be passing through the distal right VA from the left VA. These findings were observed when the patient's head was tilted to the right. An arterio-arterial embolic mechanism was suggested as the cause of repeated cerebellar infarctions. LESSONS: Transient nondominant VA occlusion has been rarely reported as a cause of BHS when the head is tilted. To confirm the diagnosis of BHS, additional head tilt is recommended when performing dynamic DA in patients with a cervical osteophyte.

DOI： 10.3171/CASE2061

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