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Background: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. Methods: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0–1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. Results: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24–20.6]; P =0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P =0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62–30.7]; P =0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. Conclusions: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: UMIN000006640.

The lateral spinal artery (LSA) perfuses the dorsolateral part of the spinal cord at the craniocervical junction (CCJ). We analyzed the angioarchitecture of the normal LSA and CCJ arteriovenous fistula (AVF).The first study included 26 patients with a cerebral aneurysm of the posterior circulation. Using slab maximum intensity projection (MIP) images from three-dimensional rotational angiography (3D-RA) and contrast-enhanced cone-beam CT (CE-CBCT), we analyzed the origin of the LSA, its anastomosis with the posterior inferior cerebellar artery (PICA), the point where it reaches the spinal cord, and the visualized range. In the second study, we analyzed the angioarchitecture and treatment results of 7 CCJAVF lesions treated in our department between 2016 and 2021.We visualized the normal LSA for all patients. In 23 patients with an intradural origin PICA, all LSAs originated from the C1 or C2 radicular artery, and 8 patients had an anastomosis with the PICA. In three patients with a C1 level origin PICA, all LSAs originated from the PICA. All LSAs reached the dorsolateral part of the spinal cord. The mean visualized range of the LSA was 27.4 mm. The LSA was involved in five of seven CCJAVF lesions (71%). There was one lesion with a spinal infarction after LSA embolization. Other lesions were treated by direct interruption of the AVF, and the ASA and LSA were preserved.This is the first report that visualized the LSA's normal anatomy using slab MIP images from 3D-RA and CE-CBCT. Knowledge of LSA anatomy is critical to avoid complications during the treatment of CCJAVF.

The morphological changes of the pipeline embolization device (PED; Medtronic, Minneapolis, MN, USA), such as delayed migration or foreshortening, can relate to the incomplete occlusion of aneurysms.A 30-year-old man with a giant cavernous carotid artery aneurysm was treated with two PEDs using the overlapping technique. Six months after treatment, follow-up angiography showed morphological changes of the PEDs and residual flow into the aneurysm. Chronological cone-beam computed tomography fusion imaging clearly revealed the dynamic foreshortening of the first PED and the disconnection of both PEDs, so we decided to implant an additional PED.This case illustrates that a three-dimensional understanding can be useful for assessing the cause of treatment failure or recurrence.

OBJECTIVE There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

OBJECTIVE: To assess the ability of the "wall-carving (WC) image technique", which uses vascular images from 3-dimensional digital subtraction angiograms (3DDSAs). Also, to verify the accuracy of the resulting 3D-printed hollow models of intracranial aneurysms. METHODS: The 3DDSA data from 9 aneurysms were processed to obtain volumetric models suitable for the stereolithography apparatus. The resulting models were filled with iodinated contrast media. 3D rotational angiography of the models was carried out, and the aneurysm geometry was compared with the original patient data. The accuracy of the 3D-printed hollow models' sizes and shapes was evaluated using the nonparametric Wilcoxon signed-rank test and the Dice coefficient index. RESULTS: The aneurysm volumes ranged from 34.1 to 4609.8 mm 3 (maximum diameters 5.1-30.1 mm), and no statistically significant differences were noted between the patient data and the 3D-printed models (P = 0.4). Shape analysis of the aneurysms and related arteries indicated a high level of accuracy (Dice coefficient index value: 88.1%-97.3%; mean + SD: 93.6% +/- 2.5%). The vessel wall thickness of the 3D-printed hollow models was 0.4 mm for the parent and 0.2 mm for small branches and aneurysms, almost the same as the patient data. CONCLUSIONS: The WC technique, which involves volume rendering of 3DDSAs, can provide a detailed description of the contrast enhancement of intracranial vessels and aneurysms at arbitrary depths. These models can provide precise anatomic information and be used for simulations of endovascular treatment.

In this paper, we will discuss the relationship between neuroendovascular therapy and infection in two parts: the risk of infectious complications in neuroendovascular therapy and neuroendovascular therapy for infectious diseases. The risk of infectious complications associated with neuroendovascular therapy is rare but should not be ignored. We must comply with clean procedures and consider prophylactic antibiotic administration in selected cases. Neuroendovascular therapy for infectious diseases is a high-risk treatment, and a safer treatment strategy should be considered for each case.

The Japanese EC-IC Bypass Trial(JET)Study demonstrated that a superficial temporal artery-middle cerebral artery(STA-MCA)bypass is effective in preventing the recurrence of ischemic stroke in cases of atherosclerotic internal carotid artery or MCA steno-occlusive lesions with symptoms. The JET-2 Study revealed that the hemodynamic criteria for STA-MCA bypass in the JET Study(rest cerebral blood flow80% and cerebrovascular reactivity10%)were adequate. An STA-MCA bypass was ranked as recommendation B; the level of evidence was moderate under the conditions of quantitative evaluation of cerebral hemodynamics and low frequency of perioperative complications, as described in the Japanese Guidelines for the Management of Stroke 2021. An education system for the accurate assessment of cerebral hemodynamics, meticulous surgical procedures, and perioperative management for STA-MCA bypass is necessary to hand over evidence of STA-MCA bypass efficacy in Japan to future generations. Simultaneously, new evidence of STA-MCA bypass efficacy should be explored with the advancement of medicine and should be disseminated worldwide.

The effectiveness of adenosine-induced flow arrest in surgical clipping for the cerebral aneurysms with difficulties in temporary clip placement to the proximal main trunk has been reported. This is the first clinical trial to evaluate the safety and feasibility of adenosine-assisted clipping surgery for unruptured cerebral aneurysms (UCAs) in Japan. The inclusion criteria are as follows: patients over 20 years old, patients who agree to be enrolled in this study after providing informed consent, patients who undergo clipping surgery for UCA in our institute, and patients in whom the surgeons (T.H. or I.D.) judge that decompression of the aneurysm is effective. The primary endpoint is a modified Rankin Scale (mRS) score 30 days after surgery. We plan to enroll 10 patients in this study. The original protocol of adenosine administration was established in this trial. Herein, we present the study protocol.

In recent years, endovascular treatment has become the treatment of choice for distal anterior cerebral artery (DACA) aneurysms. In this study, we report the outcomes of coil embolization for DACA aneurysms.Eighteen DACA aneurysms in 16 patients treated with endovascular treatment between January 2010 and December 2020 were included in this study. We retrospectively analyzed patient characteristics, data on aneurysms, the reason for the selection of endovascular treatment, treatment technique, and treatment outcomes.There were 18 procedures in 16 patients. The average age was 65.7 years and 56% of patients were male. The average diameter of the dome was 5.5 mm, and the location of aneurysm was A3 in 83% and A4 in 17%. We mainly selected endovascular treatment for patients with a past history of craniotomy and head trauma, or with systemic comorbidities. The technical success rate was 94%, and adequate obliteration immediately after treatment was achieved in 72%. There were no symptomatic periprocedural complications. The retreatment rate was 11.1%.Coil embolization for DACA aneurysms yielded good treatment outcomes. Endovascular treatment for DACA aneurysms will become more common with advances in endovascular devices and the establishment of stable perioperative antiplatelet therapy.

Arteriovenous fistulas (AVFs) located in the cavernous sinus (CS), clivus, and condyle can be osseous shunts in nature. Here, we reviewed the angioarchitecture, clinical characteristics, and treatment results of AVFs in these lesions. Twenty-five patients with 27 lesions who underwent rotational angiography in our department between May 2013 and December 2019 were reviewed. We examined 20 CS AVFs, 2 clival AVFs, and 5 condylar AVFs. We divided the anatomical shunted pouches into five locations: the dorsum sellae (posteromedial of the CS), posterolateral wall of the CS, lateral wall of the CS, clivus, and condyle. We divided the AVFs into three categories: intraosseous, transitional, and nonosseous shunts. We analyzed the characteristics and treatment results. A total of 33 shunted pouches or points were identified in 27 lesions. The dorsum sellae (n = 16) was the most frequent location. Fourteen AVFs (88%) in the dorsum sellae were osseous (intraosseous or transitional) shunts. All AVFs in the clivus or condyle were also osseous shunts. Eleven lesions (92%) of intraosseous and all lesions of transitional shunts exhibited bilateral external carotid artery involvement as feeders. Ten lesions (83%) of intraosseous shunts were treated with selective transvenous embolization of the shunted pouch with or without additional partial embolization of the sinus. Eleven (92%) intraosseous shunts were completely occluded, and symptom resolution was achieved in all intraosseous shunts. Most of the CS AVFs with shunted pouches in the dorsum sellae and all of the AVFs in the clivus and condyle share similar characteristics.

OBJECTIVEEmbolization is the most common treatment for dural arteriovenous fistulas (dAVFs). A retrospective, multicenter observational study was conducted in Japan to clarify the nature, frequency, and risk factors for complications of dAVF embolization.METHODSPatient data were derived from the Japanese Registry of Neuroendovascular Therapy 3 (JR-NET3). A total of 40,169 procedures were registered in JR-NET3, including 2121 procedures (5.28%) in which dAVFs were treated with embolization. After data extraction, the authors analyzed complication details and risk factors in 1940 procedures performed in 1458 patients with cranial dAVFs treated with successful or attempted embolization.RESULTSTransarterial embolization (TAE) alone was performed in 858 cases (44%), and transvenous embolization (TVE) alone was performed in 910 cases (47%). Both TAE and TVE were performed in one session in 172 cases (9%). Complications occurred in 149 cases (7.7%). Thirty-day morbidity and mortality occurred in 55 cases (2.8%) and 16 cases (0.8%), respectively. Non–sinus-type locations, radical embolization as the strategy, procedure done at a hospital that performed dAVF embolization in fewer than 10 cases during the study period, and emergency procedures were independent risk factors for overall complications.CONCLUSIONSComplication rates of dAVF embolization in Japan were acceptable. For better results, the risk factors identified in this study should be considered in treatment decisions.

Endovascular therapy to the spinal dural arteriovenous fistula (SDAVF) with a common origin of the radiculomedullary artery and the feeder of the shunt has the risk of spinal cord infarction. This study aimed to retrospectively assess the detection rate of normal spinal arteries from the feeder of SDAVF. We retrospectively collected the angiographic and clinical data of SDAVFs. This study included 19 patients with 20 SDAVF lesions admitted to our department between January 2007 and December 2018. We assessed the detection rate of normal radiculomedullary artery branched from the feeder of SDAVF between the period using the image intensifier (II) and flat panel detector (FPD) and evaluated the treatment results. The detection rates of the radiculomedullary artery branched from the feeder of SDAVF were 10% (1/10 lesions) during the II period and 30% (3/10 lesions) during the FPD period. During the FPD period, all normal radiculomedullary arteries branched from the feeder were only detected on slab maximum intensity projection (MIP) images of rotational angiography, and we could not detect them in 2D or 3D digital subtraction angiography. All lesions that had a common origin of a normal radiculomedullary artery and the feeder were completely obliterated without complications. There was no recurrence during the follow-up period. The flat panel detector and slab MIP images seem to show the common origin of the normal radiculomedullary arteries from the feeder more accurately. With detailed analyses, SDAVF can be safety treated.

Although temporary clipping of the parent artery is an indispensable technique in clipping surgery for intracranial aneurysms, the permissive duration of temporary clipping is still not well known. The aim of this study is to confirm the safety of precise motor evoked potential (MEP) monitoring and to estimate the permissive duration of temporary clipping for middle cerebral artery (MCA) aneurysm based on precise MEP monitoring results. Under precise MEP monitoring via direct cortical stimulation every 30 seconds to 1 minute, surgeons released a temporary clip and waited for MEP amplitude to recover following severe (>50%) reduction of MEP amplitude during temporary clipping. Precise MEP monitoring was safely performed. Twenty-eight instances of temporary clipping were performed in 42 MCA aneurysm clipping surgeries. Because precise MEP monitoring could be used to determine when to release a temporary clip even with a severe reduction in MEP amplitude due to lengthy temporary clipping, no patients experienced permanent postoperative hemiparesis. Based on logistic regression analysis, if a temporary clip is applied for 312 seconds or more, there is a higher probability of a severe reduction in MEP amplitude. We should therefore release temporary clips after 5 minutes in order to avoid permanent postoperative hemiparesis.

Intracranial hemorrhage following hyperperfusion syndrome (HPS) is a rare but potentially fatal complication after carotid artery stenting (CAS). Staged angioplasty (SAP) is a two-stage form of CAS that can prevent the abrupt increase of cerebral blood flow. In this study, we investigated the safety and efficacy of SAP. One hundred thirty-four patients who underwent CAS for high-grade carotid artery stenosis between January 2010 and December 2018 were enrolled. Patients who showed severe impairment of hemodynamic reserve in 123I-IMP SPECT with acetazolamide received SAP (SAP group), while the others received regular CAS (RS group). Twenty-six (19.4%) patients at risk for HPS received SAP. HPS was not observed in either group. Diffusion-weighted image (DWI)-positive lesions on postoperative MRI were observed in 56 (52.3%) cases in the RS group and 16 (64.0%) cases in the SAP group. Symptomatic procedure-related complications occurred in 5 (4.6%) cases in the RS group and 1 (3.8%) case in the SAP group. These differences were not statistically significant. Modified Rankin Scale score had declined 30 days after discharge in 4 (3.0%) cases. Distal filter protection was significantly correlated to the occurrence of new DWI-positive lesions. For patients at high risk of HPS, SAP was a reasonable treatment strategy to prevent HPS. SAP did not increase the rate of DWI-positive lesions or procedure-related complications compared with regular CAS.

Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) worsens the neurological outcome. We hypothesize that a longer duration of depolarization and excessive release of glutamate aggravate neurological outcomes after SAH, and that brain hypothermia can accelerate repolarization and inhibit the excessive release of extracellular glutamate and subsequent neuronal damage. So, we investigated the influence of depolarization time and extracellular glutamate levels on the neurological outcome in the ultra-early phase of SAH using a rat injection model as Experiment 1 and then evaluated the efficacy of brain hypothermia targeting ultra-early brain injury as Experiment 2. Dynamic changes in membrane potentials, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and extracellular glutamate levels were observed within 30 min after SAH. A prolonged duration of depolarization correlated with peak extracellular glutamate levels, and these two factors worsened the neuronal injury. Under brain hypothermia using pharyngeal cooling after SAH, cerebral perfusion pressure in the hypothermia group recovered earlier than that in the normothermia group. Extracellular glutamate levels in the hypothermia group were significantly lower than those in the normothermia group. The early induction of brain hypothermia could facilitate faster recovery of cerebral perfusion pressure, repolarization, and the inhibition of excessive glutamate release, which would prevent ultra-early brain injury following SAH.

BACKGROUND: The Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and 3 (JR-NET3) were nationwide surveys that evaluated clinical outcomes after neuroendovascular therapy in Japan. The aim of this study was to compare the prevalence and risk factors of complications of intracranial tumor embolization between JR-NET2 and JR-NET3. METHODS: A total of 1018 and 1545 consecutive patients with intracranial tumors treated with embolization were enrolled in JR-NET2 and JR-NET3, respectively. The prevalence of complications in intracranial tumor embolization and related risk factors were compared between JR-NET2 and JR-NET3. RESULTS: The prevalence of complications in JR-NET3 (3.69%) was significantly higher than that in JR-NET2 (1.48%) (p = 0.002). The multivariate analysis in JR-NET2 showed that embolization for tumors other than meningioma was the only significant risk factor for complication (odds ratio [OR], 3.88; 95% confidence interval [CI], 1.13-12.10; p = 0.032), and that in JR-NET3 revealed that embolization for feeders other than external carotid artery (ECA) (OR, 3.56; 95% CI, 2.03-6.25; p CONCLUSIONS: Embolization for feeders other than ECA and use of liquid materials could increase the complication rate in intracranial tumor embolization.

Background High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.

Angiogenesis involves new blood vessels sprouting from preexisting blood vessels. This process may serve to improve brain circulation. Moyamoya disease (MMD) is a cerebrovascular disorder causing intracranial stenosis which significantly reduces the blood supply to the brain. Mainly stroke is the first symptom of the disorder, so treatments that reduce the risk of stroke are used for patients with MMD. To prevent stroke for those with chronic cerebral hypoperfusion, more blood needs to flow to the brain, which was thought to be achieved by enhancing angiogenesis. Indirect bypass surgery, such as encephalo-myo-synangiosis (EMS), is used for revascularization. However, EMS alone sometimes cannot provide enough circulation to avoid ischemic strokes. The current study examined if EMS combined with high-mobility group box-1 (HMGB1) and vascular endothelial growth factor (VEGF) enhanced angiogenesis and increased cerebral circulation. The results indicated that HMGB1 administered with EMS increased angiogenesis through a VEGF-dependent mechanism. In addition, exercising and stem cell transplantation possess possible means to increase angiogenesis. Overall, EMS with gene therapy, maintaining fitness, and stem cell utilization may prevent or help one recover from stroke by enhancing brain angiogenesis. Thus, these treatments may be applicable for patients with MMD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed.

CT angiography(CTA)plays a crucial role in the diagnosis of intracerebral hemorrhage(ICH). An 85-year-old woman presented with a disturbance of consciousness and right hemiparesis. Non-contrast CT of the brain revealed intracerebral hemorrhage in the left thalamus spreading to the internal capsule, corona radiata, and midbrain and a "swirl sign." CTA revealed no vascular anomaly. The early and delayed CTA phases revealed the"spot sign" and "leakage sign," respectively. Non-contrast CT three hours after the initial CT showed the enlargement of the hematoma. After the detection of ICH by initial non-contrast CT, CTA should be performed to differentiate between the causes of secondary ICH and detect the imaging markers of hematoma expansion or rebleeding. Previous studies have demonstrated that the "spot sign" detected by CTA is a valid imaging marker for hematoma expansion. In this article, the differential diagnosis of ICH and the detection of the imaging markers of hematoma expansion using non-contrast CT and CTA have been discussed.

Background and Purpose: To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan. Methods: We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated. Results: Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018. Conclusions: In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.

Background: Hemifacial spasm (HFS) due to vertebral artery (VA) dissecting aneurysm (VADA) is rare and endovascular treatment has been performed in selected cases. Case Description: We encountered a case of HFS caused by VADA that was managed with endovascular stent placement and additional stent-in-stent placement. Therapeutic strategies and benefits based on pre- and post-treatment evaluation by 3D multifusion imaging using silent MRA were discussed. Conclusion: This is the first case report of stent-in-stent placement in successful treatment of HFS caused by VADA, in which relief of neurovascular contact was demonstrated by multifusion imaging.

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 67 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.

Background The patients with ruptured vertebral artery dissecting aneurysm (rVADA) should be treated as early as possible because VADA carries extremely high risk of rebleeding in the acute phase. We have established a mobile endovascular strategy for the patients with rVADA between our flagship center and its affiliated local hospitals. We introduced and reviewed our mobile endovascular therapy in this study. Methods We retrospectively evaluated 98 consecutive patients who underwent endovascular surgery for rVADA from 2000 to 2018 at our institution or five affiliated hospitals. When each patient was initially transported to the local affiliated hospitals, neuroendovascular surgeons traveled directly to the affiliated hospital from the flagship center in order to treat the patient there. Clinical outcomes using modified Rankin Scale at 6 months after treatment, radiological results, and procedure-related complications were reviewed to justify our mobile endovascular strategy. Results All aneurysms were cured successfully by internal trapping. Favorable outcome was achieved in 61 patients (62.2%) even though 53 patients (54.1%) had presented with severe subarachnoid hemorrhage. Overall mortality rate, treatment-related mortality rate, and treatment related complication rate were 18.4% (18/98), 0%, and 16% (16/98), respectively. There were no differences in clinical and radiological outcomes between the patients treated in the flagship center and those who treated in the affiliated hospitals. Treatment in the affiliated hospital was not a predictive factor of unfavorable outcome in our multivariate analysis, and elderly age (>= 60) was negatively associated with favorable outcome. Conclusions Our results prove the efficacy and safety of mobile endovascular therapy for the treatment of rVADA in the ultra-acute stage. Mobile endovascular therapy may work well in the acute treatment of rVADAs in the certain circumstance.

Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for &ldquo, oxidative phosphorylation&rdquo, was significantly upregulated while fourteen other gene sets including &ldquo, apoptosis&rdquo, &ldquo, hypoxia&rdquo, and &ldquo, reactive oxygen species&rdquo, showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.

BACKGROUND AND PURPOSE: Detailed arterial anatomy of the sphenoid ridge and olfactory groove meningiomas is complicated due to the fine angioarchitecture and anastomoses between each feeder. Herein, we present details of the arterial anatomy and the relationships of feeders in these lesions. MATERIALS AND METHODS: This study included 20 patients admitted to our department between April 2015 and March 2020. Conditions of subjects consisted of 16 sphenoid ridge meningiomas and 4 olfactory groove meningiomas. We mainly analyzed arterial anatomy using 3D rotational angiography and slab MIP images of these lesions. We also analyzed the anastomoses of each feeder. RESULTS: We found that 19 (95%), 15 (75%), and 15 (75%) lesions had feeders from the ophthalmic, internal carotid, and external carotid arteries, respectively. As feeders from the ophthalmic artery, recurrent meningeal arteries were involved in 18 lesions (90%). Fifteen lesions (75%) had anastomoses between each feeder. CONCLUSIONS: Most of the meningiomas in the sphenoid ridge and olfactory groove had feeders from the ophthalmic and internal carotid arteries. There were various anastomoses between each feeder. This is the first report to demonstrate the detailed arterial anatomy and frequency of recurrent branches from the ophthalmic artery and their anastomoses using detailed imaging techniques.

Malignant glioma is one of the most common brain cancers in humans, which is very devastating. The expression of reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is decreased in various human cancers. Lately, we have developed a novel second-generation adenoviral vector that expresses REIC/Dkk-3 (Ad-SGE-REIC) and revealed its antiglioma efficacy. The present investigator-initiated clinical trial is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed at Okayama University Hospital, Okayama, Japan. The primary end points are dose-limiting toxicities and the incidence of adverse events. The secondary end points are the objective response rate and immunological assessment. Use of Ad-SGE-REIC will help to improve the prognosis of patients with malignant brain tumors.

OBJECTIVEAlthough cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH.METHODSTwenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites.RESULTSChanges in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P50) was estimated to be 22.4 minutes (95% confidence intervals 17.0–30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after initiation of SAH. On NADH fluorescence images CSD was initially observed in the anterior cortex; it propagated through the entire hemisphere in the direction of the occipital cortex at a rate of 3 mm/minute, with repolarization in 2.3 ± 1.2 minutes. DC potential recording sites that had undergone CSD were found to have intact tissue 24 hours later. Compared with depolarization that caused 50% neuronal damage, the duration of CSD was too short to cause histological damage.CONCLUSIONSCSD was successfully visualized using NADH fluorescence. It propagated from the anterior to the posterior cortex along with an increase in CBF. The duration of depolarization in CSD (2.3 ± 1.2 minutes) was far shorter than that causing 50% neuronal damage (22.4 minutes) and was not associated with histological damage in the current experimental setting.

OBJECTIVEThe aim of this study was to evaluate whether combined gene therapy with vascular endothelial growth factor (VEGF) plus apelin during indirect vasoreconstructive surgery enhances brain angiogenesis in a chronic cerebral hypoperfusion model in rats.METHODSA chronic cerebral hypoperfusion model induced by the permanent ligation of bilateral common carotid arteries (CCAs; a procedure herein referred to as “CCA occlusion” [CCAO]) in rats was employed in this study. Seven days after the CCAO procedure, the authors performed encephalo-myo-synangiosis (EMS) and injected plasmid(s) into each rat's temporal muscle. Rats were divided into 4 groups based on which plasmid was received (i.e., LacZ group, VEGF group, apelin group, and VEGF+apelin group). Protein levels in the cortex and attached muscle were assessed with enzyme-linked immunosorbent assay (ELISA) on Day 7 after EMS, while immunofluorescent analysis of cortical vessels was performed on Day 14 after EMS.RESULTSThe total number of blood vessels in the cortex on Day 14 after EMS was significantly larger in the VEGF group and the VEGF+apelin group than in the LacZ group (p < 0.05, respectively). Larger vessels appeared in the VEGF+apelin group than in the other groups (p < 0.05, respectively). Apelin protein on Day 7 after EMS was not detected in the cortex for any of the groups. In the attached muscle, apelin protein was detected only in the apelin group and the VEGF+apelin group. Immunofluorescent analysis revealed that apelin and its receptor, APJ, were expressed on endothelial cells (ECs) 7 days after the CCAO.CONCLUSIONSCombined gene therapy (VEGF plus apelin) during EMS in a chronic cerebral hypoperfusion model can enhance angiogenesis in rats. This treatment has the potential to be a feasible option in a clinical setting for patients with moyamoya disease.

The prevalence of unruptured cerebral aneurysms (UCAs) in elderly patients is increasing in our aging population. UCA management in elderly patients has some difficulties, such as reduced life expectancy, increased comorbidities and treatment risks, and poor prognosis in case of rupture. In this review article, we summarize the most recent findings on the natural history, therapeutic options and treatment results for UCAs exclusively in elderly patients, and describe possible medical treatments for patients with UCAs.