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Intracranial aneurysms (IAs) are a high-risk factor for life-threatening subarachnoid hemorrhage. Their etiology, however, remains mostly unknown at present. We conducted screening for sporadic somatic mutations in 65 IA tissues (54 saccular and 11 fusiform aneurysms) and paired blood samples by whole-exome and targeted deep sequencing. We identified sporadic mutations in multiple signaling genes and examined their impact on downstream signaling pathways and gene expression in vitro and an arterial dilatation model in mice in vivo. We identified 16 genes that were mutated in at least one IA case and found that these mutations were highly prevalent (92%: 60 of 65 IAs) among all IA cases examined. In particular, mutations in six genes (PDGFRB, AHNAK, OBSCN, RBM10, CACNA1E, and OR5P3), many of which are linked to NF-κB signaling, were found in both fusiform and saccular IAs at a high prevalence (43% of all IA cases examined). We found that mutant PDGFRBs constitutively activated ERK and NF-κB signaling, enhanced cell motility, and induced inflammation-related gene expression in vitro. Spatial transcriptomics also detected similar changes in vessels from patients with IA. Furthermore, virus-mediated overexpression of a mutant PDGFRBinduced a fusiform-like dilatation of the basilar artery in mice, which was blocked by systemic administration of the tyrosine kinase inhibitor sunitinib. Collectively, this study reveals a high prevalence of somatic mutations in NF-κB signaling pathway–related genes in both fusiform and saccular IAs and opens a new avenue of research for developing pharmacological interventions.

A craniotomy that passes through the frontal air sinus (FAS) often results in postoperative complications such as infection, cerebrospinal fluid leakage or mucocele formation. A good understanding of FAS reconstruction can decrease the morbidity rate of complications. This study describes the outcomes of treatment and establishes the most effective technique for FAS reconstruction in our institution. We enrolled 107 patients who had a bifrontal craniotomy which exposed the FAS during the operation for an anterior communicating artery (ACoA) aneurysm. Demographic data including the follow-up information were collected and analyzed. The complications after surgery were observed and described in the treatment procedure. The patency of the nasofrontal outflow tract (NFOT) was proved by removal of blood clots and bone dust by irrigation and by direct inspection under a microscope before closure of the frontal sinus mucosa with a monofilament non-absorbable 7/0 material suture. The dura was closed in a watertight fashion and an abdominal fat graft was packed into the FAS cavity. There were 33 male and 74 female patients and the mean age (range) was 64years (32–90years). The mean follow-up time was 13months (1–35months) and complications were found in only 2 patients. One patient suffered from dislocation of the fat graft and the other patient developed a surgical wound infection. At post-operation the first patient sneezed several times and the second patient suffered from trauma in the nasal area after discharge to home. Both patients were surgically treated and cured. In conclusion, FAS reconstruction from our technique is very effective for the prevention of complications after bifrontal craniotomy. Direct suturing of the frontal sinus mucosa and proving the patency of the NFOT are keys to successful treatment.

Despite technological advances in endovascular therapy, surgical clipping of paraclinoid aneurysms remains an indispensable treatment option and has an acceptable profile risk. Intraoperative monitoring of motor and somatosensory evoked potentials has proven to be an effective tool in predicting and preventing postoperative motor deficits during aneurysm clipping.1,2 We describe the case of a 61-yr-old Japanese woman with a history of hypertension and smoking. During follow-up for bilateral aneurysms of ophthalmic segment of the internal carotid artery (ICA), left-sided aneurysm growth was detected. A standard pterional approach with extradural clinoidectomy was used to approach the aneurysm. After clipping, a significant intraprocedural change in motor evoked potential (MEP) amplitude was observed despite native vessel patency was confirmed through micro-Doppler and indocyanine green video angiography.3-5 After extensive dissection of the sylvian fissure and exposure of the communicating segment of ICA, the anterior choroidal artery was found to be compressed and occluded by the posterior clinoid because of an inadvertent shift of the ICA after clip application and removal of brain retractors. Posterior clinoidectomy was performed intradurally with microrongeur and MEP amplitude returned readily to baseline values. Computed tomography (CT) angiogram demonstrated complete exclusion of the aneurysm, and magnetic resonance imaging (MRI) was negative for postoperative ischemic lesions on diffusion weighted images. The patient tolerated the procedure well and was discharged home on postoperative day 3 with modified Rankin Scale (mRS) 0. The patient signed the Institutional Consent Form to undergo the surgical procedure and to allow the use of her images and videos for any type of medical publications.

Graphical Abstract

Objects The aim of this study was to clarify predictors for poor intellectual outcome in pediatric moyamoya disease. Methods Fifty-two pediatric patients were included. Clinical diagnosis was transient ischemic attacks (TIA) in 35 and completed stroke in 17. Ten patients underwent indirect synangiosis through “small craniotomy,” whereas the other 42 underwent superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis and indirect synangiosis through “large craniotomy.” Full-scale IQ (FSIQ) was measured using the Wechsler intelligence scale for children (WISC) after surgery. Multivariate logistic regression models were applied to test the effect of clinical factors on intellectual outcome. Results and conclusion Eight patients revealed mentally impaired status (FSIQ<70). Multivariate analysis revealed that completed stroke and “small craniotomy” surgery were significantly associated with poor intellectual outcome. Odds ratios of each factor were 33.4 (95% CI, 2.4–474) and 19.6 (95% CI, 1.8–215) respectively. Early diagnosis and the revascularization procedure over as wide an area as possible may be essential to improve their intellectual outcome.

Regional cerebral blood flow (rCBF) and its reactivity to acetazolamide were analyzed in a series of 15 cases of childhood moyamoya disease, using the xenon-133 inhalation method and single photon emission CT (SPECT). Most of the patients had normal mean hemispheric cerebral blood flow (mCBF), comparable to that of age-matched healthy children. However, they had abnormal rCBF distribution and disturbed reactivity to acetazolamide in the territory of the internal carotid artery, especially in the frontal lobe. Surgical revascularization for the anterior circulation, which consisted of STA-MCA anastomosis and indirect synangiosis, dramatically improved theses cerebral hemodynamics in the anterior circulation, including the frontal lobe, and reactivity to acetazolamide in the whole brain. These results suggest that surgical revascularization for the anterior circulation should be carried out in order to improve cerebral hemodynamics as widely as possible, especially in the frontal lobe, and may improve cerebral perfusion reserve in the posterior circulation.

The authors report four cases of familial occurrence of moyamoya disease. Although the pathogenesis of moyamoya disease is not clear, there is extensive evidence that this disease has a tendency to show multifactorial inheritance. Therefore, a screening test for those at high risk, i.e., who have a moyamoya patient among their blood relatives, is clinically important. Magnetic resonance angiography (MRA) successfully revealed abnormal findings specific to moyamoya disease in members of the four probands families. MRA is a powerful and noninvasive way of detecting individuals at high risk of developing moymoya disease.

“Re-build-up” phenomenon, induced by hyperventilation, is a characteristic finding on electroencephalogram (EEG) in children with moyamoya disease, and suggests close correlation with cerebral ischemic attack. Its mechanism, however, remains obscure. In this study, we examined the relationship between the cerebral hemodynamics and this phenomenon before and after vascular reconstructive surgery. Regional cerebral blood flow and its reactivity to acetazolamide were analyzed using the xenon-133 inhalation method and single photon emission computed tomography in six children with moyamoya disease. These results were compared with the EEG. Regional vasoreactivity to acetazolamide was significantly lower in “re-build-up”-positive regions than in “re-build-up”-negative regions. Postoperative studies revealed a significant improvement of reactivity in the regions where the “re-build-up” phenomenon disappeared after surgery. These results suggest that the “re-build-up” phenomenon represents a focal reduction of the cerebral perfusion reserve in moyamoya disease.

BACKGROUND When we encounter an inaccessible internal carotid artery lesion, we sacrifice the inaccessible internal carotid artery and, at the same time, establish a high-flow extracranial-to-intracranial arterial bypass (EC-IC bypass). Questions and concerns remain, however, about the dynamics of the patient's cerebral blood flow postoperatively. METHOD Ten hemispheres from 9 patients had received radial artery grafting as an EC-IC bypass with the simultaneous obstruction of the internal carotid artery. Their mean hemispheric cerebral blood flow (mCBF) was measured longitudinally during 1 year after surgery by single photon emission computed tomography (SPECT) and a 133 Xenon-inhalation method. RESULTS The serial mCBF values of the five hemispheres with giant aneurysm or paracavernous meningioma were attenuated during the postoperative 3-month period and then returned to the normal range. In only one case did the postoperative reduction of mCBF fail to return to normal; in addition there was a memory disturbance that had developed and progressed. Five hemispheres with the ICA stenosis did not present reduction in mCBF. In three out of five hemispheres, transient elevation of mCBF at 1 month after surgery was observed. CONCLUSIONS We conclude from our study that the internal carotid artery can be safely substituted by the radial artery graft from the view point of cerebral blood flow.

We present surgical techniques for optimal revascularization in childhood moyamoya disease. During the past 10 years we performed revascularization surgery for childhood moyamoya disease using direct revascularization with superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect revascularization of encephalo-duro-arterio-myo-synangiosis (EDAMS) 43 times. Points of this surgery are as follows: (1) craniotomy and durai opening for the most extensive possible exposure of the brain surface, (2) protective manipulation of the STA, temporal muscle and middle meningeal artery, (3) STA-MCA anastomosis to the frontal branch of the MCA to improve cerebral circulation of the frontal lobe using a small branch of the STA, and (4) a small opening in the arachnoid membrane and watertight closure.

•A pair of micro-scissors as a combined stimulation-dissection instrument.•Attaching the monopolar stimulating lead wire to a pair of micro-scissors.•Sharp dissection around cranial nerves and simultaneous monitoring of them.