Delayed leukoencephalopathy following non-coil embolization flow diverter stent deployment for an intracranial aneurysm.

This report examines delayed leukoencephalopathy as a postoperative complication after the use of flow diverter (FD) devices for endovascular cerebral aneurysm treatment. A case involving a 78-year-old female treated with a pipeline embolization device for a left internal carotid artery aneurysm is presented. Despite adherence to dual anti-platelet therapy, the patient developed intermittent headaches and memory issues 3 months post-operation. MRI revealed T1-enhancing foci and T2 hyperintense signal abnormalities in the left cerebral hemisphere, without new ischemic lesions, indicating potential embolic events or foreign body reactions. Following aphasia, a change from clopidogrel to prasugrel and the initiation of steroid pulse therapy led to the resolution of symptoms and MRI abnormalities over 6 months. This case underscores the reversibility of delayed leukoencephalopathy with appropriate intervention.

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.

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.

Real-world data of clazosentan in combination therapy for aneurysmal subarachnoid hemorrhage: a multicenter retrospective cohort study.

Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0-6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge.

Concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated with miliary tuberculosis.

Cerebrovascular complications of central nervous system tuberculosis (TB) are predictors of poor prognosis and adverse outcomes. These complications are mainly intracranial arterial involvement, with occasional venous involvement. Here, we present a 67-year-old woman with concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated by miliary tuberculosis. Mycobacterium tuberculosis was observed on the luminal side of the carotid plaques in pathological specimens. Treatment with anti-TB drugs alone would likely not cure the patient, as M. tuberculosis would continue to disseminate. Endarterectomy could directly remove the embolic source, and a complete cure was achieved.

Moyamoya disease-specific extracellular vesicle-derived microRNAs in the cerebrospinal fluid revealed by comprehensive expression analysis through microRNA sequencing.

PURPOSE: To examine the specific changes that occur in the expression levels of extracellular vesicle-derived microRNAs (miRNAs) in intracranial cerebrospinal fluid (CSF) in moyamoya disease. METHODS: Patients with arteriosclerotic cerebral ischemia were used as controls to eliminate the effects of cerebral ischemia. Intracranial CSF was collected from moyamoya disease and control patients during bypass surgery. Extracellular vesicles (EVs) were extracted from the CSF. Comprehensive expression analysis of miRNAs extracted from EVs by next-generation sequencing (NGS) and validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed. RESULTS: Experiments were conducted on eight cases of moyamoya disease and four control cases. In the comprehensive miRNA expression analysis, 153 miRNAs were upregulated, and 98 miRNAs were downregulated in moyamoya disease compared to the control cases (q-value < 0.05 and |log2 fold change|> 1). qRT-PCR performed on the four most variable miRNAs (hsa-miR-421, hsa-miR-361-5p, hsa-miR-320a, and hsa-miR-29b-3p) associated with vascular lesions among the differentially expressed miRNAs gave the same results as miRNA sequencing. On gene ontology (GO) analysis for the target genes, cytoplasmic stress granule was the most significant GO term. CONCLUSIONS: This study is the first comprehensive expression analysis of EV-derived miRNAs in the CSF of moyamoya disease patients using NGS. The miRNAs identified here may be related to the etiology and pathophysiology of moyamoya disease.

Butterfly needle tap and suction (BTS) technique: a treatment for recurrent chronic subdural hematoma after burr hole craniostomy.

BACKGROUND: In this study, we propose a butterfly needle tap and suction (BTS) technique for recurrent chronic subdural hematoma (CSDH) as an alternative to reoperation with burr hole craniostomy (BHC) and investigate its efficacy and safety. The procedure involves percutaneous puncture through the burr hole created during the previous surgery and subsequent hematoma evacuation using a butterfly needle. METHODS: This retrospective study included patients who underwent BTS for CSDH at Ogaki Municipal Hospital between January 2017 and December 2020. The follow-up CT scans were reviewed after several weeks. We evaluated the number of percutaneous punctures required to resolve CSDH during the BTS technique, the volume of the evacuated hematoma, and procedure-related complications. RESULTS: Twenty-six patients were enrolled in the study, 21 of whom achieved resolution of the hematoma using punctures with the BTS technique alone (mean, 2.2 ± 1.5). Five patients had a recurrence of hematoma after one or more punctures during the BTS technique, and they underwent reoperation with BHC according to the surgeon's decision or patient requests. Among the 55 punctures, 43.0 ± 16.0 ml of hematoma was evacuated per puncture. The evacuated hematoma volume was 41.9 ± 16.4 ml in the BTS-alone group and 49.4 ± 12.9 ml in the reoperation group, with no significant difference (p = 0.25). Three patients complained of a headache during the puncture procedure, and no other complications, including intracranial hemorrhage or infection, were reported therein. CONCLUSIONS: The BTS technique is an effective alternative to reoperation with BHC.

The prognosis and treatment effectiveness of de novo aneurysm formation after radiation therapy for brain tumor.

Radiation therapy is a well-established, minimally invasive method of treating brain tumors. In recent years, the number of post-radiotherapy patients has increased, and delayed side effects are evident. De novo aneurysm formation after radiation often manifests as fatal subarachnoid hemorrhage (SAH), resulting in severe clinical outcomes. Nevertheless, the prognosis and therapeutic efficacy of radiation-induced aneurysms (RIAs) remain unclear. Using the PubMed database from 1980 to 2021, we screened 45 articles (53 individual cases) on RIAs; approximately 70% of RIAs were diagnosed after rupture. Of 38 ruptured RIAs, 12 (31.6%) had modified Rankin scale (mRS) 5-6. On the other hand, all unruptured RIAs (15 cases) recovered without neurological deficits (p = 0.012). Ten of the 39 ruptured RIAs were treated surgically, and 22 were treated endovascularly. There was no significant difference in mRS between treatment modalities (p = 0.393), but conservative therapy was significantly related to unfavorable outcomes (p = 0.025). To improve clinical outcomes, RIAs need to be diagnosed before rupture. Surgeons should be aware of de novo aneurysm formation in patients long after radiation therapy.

Advantages of petrosectomy for superficial temporal artery to superior cerebellar artery bypass based on three-dimensional distance measurements using cadaver heads.

Superficial temporal artery (STA) to superior cerebellar artery (SCA) bypass is usually performed via the subtemporal approach (StA), anterior transpetrosal approach (ApA), or combined petrosal approach (CpA), but no study has yet reported a quantitative comparison of the operative field size provided by each approach, and the optimal approach is unclear. The objective of this study is to establish evidence for selecting the approach by using cadaver heads to measure the three-dimensional distances that represent the operative field size for STA-SCA bypass. Ten sides of 10 cadaver heads were used to perform the four approaches: StA, ApA with and without zygomatic arch osteotomy (ApA-ZO- and ApA-ZO+), and CpA. For each approach, the major-axis length and the minor-axis length at the anastomosis site (La-A and Li-A), the major-axis length and the minor-axis length at the brain surface (La-B and Li-B), the depth from the brain surface to the anastomosis site (Dp), and the operating angles of the major axis and the minor axis (OAa and OAi) were measured. Shallower Dp and wider operating angle were obtained in the order CpA, ApA-ZO+, ApA-ZO-, and StA. In all parameters, ApA-ZO- extended the operative field more than StA. ApA-ZO+ extended La-B and OAa more than ApA-ZO-, whereas it did not contribute to Dp and OAi. CpA significantly decreased Dp, and widened OAa and OAi more than ApA-ZO+. ApA and CpA greatly expanded the operative field compared with StA. These results provide criteria for selecting the optimal approach for STA-SCA bypass in light of an individual surgeon's anastomosis skill level.

Challenging direct bypass surgery for very young children with moyamoya disease: technical notes.

Cerebral revascularization for moyamoya disease (MMD) is an effective treatment for improving cerebral ischaemia and preventing rebleeding. Although direct bypass surgery is commonly performed on older children and adults, it is challenging in very young children due to the high difficulty level of the procedure. The subjects were MMD patients under 3 years of age on whom surgery was performed by a single surgeon (Y.A.). Preoperative clinical findings, information related to direct bypass surgery, bypass patency, and the incidence of postoperative stroke were investigated. Combined revascularization, including direct bypass surgery, was performed on 3 MMD patients (3 sides) under 3 years of age. The average diameter of the grafts used in direct bypass was 0.8 mm. The average recipient diameter was 0.8 ± 0.17 (range 0.6-1) mm. In all cases, the anastomotic procedure was completed using 11-0 monofilament nylon thread, and patency was confirmed. Direct bypass for MMD patients under 3 years old is technically challenging. However, despite the anatomical differences between very young children and elderly individuals, direct bypass surgery could certainly be completed. In addition, a rapid recovery from cerebral blood flow insufficiency could yield a promising neurological outcome.

Changes in cerebral blood flow in the postoperative chronic phase after combined cerebral revascularization for moyamoya disease with ischaemic onset.

The purpose of this study was to examine the effects of combined revascularization for ischaemic-onset moyamoya disease (MMD) on cerebral haemodynamics by comparing cerebral blood flow (CBF) during the postoperative chronic phase with preoperative CBF. A retrospective cohort of 24 MMD patients (representing 31 surgeries) who received single photon emission computed tomography (SPECT) before and more than 6 months after surgery was investigated. The CBF value of each vascular territory was extracted from SPECT data, and the value relative to the ipsilateral cerebellar value (relative CBF, or RCBF) was calculated. The correlation between the revascularization effect and the proportional change in RCBF before and after surgery (calculated as post-RCBF/pre-RCBF ("post/pre-RCBF")) was analysed. Furthermore, the relationships between changes in neurological symptoms and post/pre-RCBF were investigated. Preoperative and postoperative mean RCBF values were 0.92 ± 0.15 and 0.96 ± 0.13 (p = 0.619) in the anterior cerebral artery territory, 0.99 ± 0.17 and 1.01 ± 0.17 (p = 0.598) in the middle cerebral artery territory and 1.15 ± 0.22 and 1.14 ± 0.19 (p = 0.062) in the posterior cerebral artery territory, respectively. No significant correlation was found between the revascularization score and post/pre-RCBF. The revascularization score and post/pre-RCBF were not significant predictors of worsening neurological symptoms postoperatively. No significant change in RCBF was observed in any vascular territory in the chronic phase after revascularization. Combined revascularization may assist in the redirection of blood flow from the internal to the external carotid system and contribute to CBF maintenance.

Efficacy and safety of the endoscopic "wet-field" technique for removal of supratentorial cavernous malformations.

OBJECTIVE: Cerebral cavernous malformations (CMs) presenting with focal neurological symptoms or mass effects require surgical removal. In recent years, cylindrical retractors have been widely utilized for the removal of deep-seated lesions during both microscopic and endoscopic surgery. In the present study, we evaluated the efficacy and safety of endoscopic transcylinder removal of CMs using a novel wet-field technique. METHODS: We included 13 patients with supratentorial CMs who had undergone endoscopic transcylinder surgery between April 2013 and March 2022. One patient experienced recurrence of the CM and underwent a second endoscopic transcylinder surgery. Therefore, we retrospectively evaluated 14 procedures. The surgical field was continuously irrigated with artificial cerebrospinal fluid to maintain expansion and visualization of the tumor bed. We termed this method as the "wet-field technique." Patient characteristics, symptoms, and pre- and postoperative magnetic resonance imaging results were obtained from medical records. RESULTS: The average maximum CM diameter was 35.3 mm (range: 10-65 mm). Cylinder diameters were 6 mm in eight procedures, 10 mm in four procedures, and 17 mm in one procedure. Wet-field technique was applied in all cases. The endoscope provided a bright field of view even under water. Continuous water irrigation made it easier to observe the entire tumor bed which naturally expanded by water pressure. Gross total resection was achieved in 13 procedures, while subtotal resection was achieved in one procedure. No surgical complications were observed. CONCLUSIONS: The endoscopic transcylinder removal using wet-field technique is safe and effective for the removal of symptomatic intracranial supratentorial CMs.

Medical Management of a Mural Thrombus Inducing Repeated Ischemic Strokes in a Patient with Congenital Afibrinogenemia.

OBJECTIVES: Congenital afibrinogenemia is an autosomal recessive inherited disorder that can cause thrombotic as well as hemorrhagic events. We describe a case of repeated mild ischemic strokes due to a mural thrombus in the carotid artery and our medical treatment. CASE DESCRIPTION: A 49-year-old woman with congenital afibrinogenemia developed two minor ischemic strokes in two months. Clinical images revealed scattered fresh infarcts in the right middle cerebral artery region and mild cervical carotid artery stenosis. The risk for surgical treatment was considered to be extraordinarily high. The patient was treated with 100 mg/day of aspirin and 3 g fibrinogen infusion every two weeks. After the one-year course of medication, the mural thrombus gradually decreased, and there were no bleeding or ischemic stroke events. CONCLUSION: This case report highlights the successful treatment of an ischemic stroke in a patient with a congenital afibrinogenemia with an antiplatelet agent and fibrinogen replacement. There are no guidelines for managing ischemic stroke in patients with congenital afibrinogenemia, and further studies are needed.

Postoperative stroke and neurological outcomes in the early phase after revascularization surgeries for moyamoya disease: an age-stratified comparative analysis.

Stroke and neurological outcomes in the early phase following revascularization for moyamoya disease (MMD) may depend on the patient's age. In this study, an age-stratified comparative analysis was performed to clarify this issue. We reviewed 105 MMD patients who underwent 179 revascularization surgeries. The demographic characteristics were collected in four age groups (≤ 5 and 6-17 years for pediatric patients and 18-49 and ≥ 50 years for adults). Additionally, we assessed the incidence of subsequent stroke and deterioration of modified Rankin Scale (mRS) score. Then, we evaluated predictors of postoperative stroke and mRS deterioration using logistic regression. The mean patient age was 26.2 ± 18.5 years. No significant difference in the incidence of postoperative stroke was observed between age groups; however, the incidence tended to be increased among patients aged ≤ 5 years (17.9%) and patients aged ≥ 50 years (16.7%). Deterioration of mRS scores was significantly associated with ages ≤ 5 years (17.9%) and ≥ 50 years (11.1%). Logistic regression showed that posterior cerebral artery involvement (odds ratio [OR], 4.6) and postoperative transient neurological events (TNEs) (OR, 5.93) were risk factors for postoperative stroke. Age ≤ 5 years (OR, 9.73), postoperative TNEs (OR, 7.38), and postoperative stroke (OR, 49) were identified as predictors of unfavorable neurological outcomes. The novel feature of this comparative analysis by age group is that membership in the early-childhood MMD patient group (under 5 years old) was an independent risk factor for unfavorable short-term neurological outcomes and was mainly associated with the incidence of postoperative severe cerebral infarction.

Transcriptome-wide analysis of intracranial artery in patients with moyamoya disease showing upregulation of immune response, and downregulation of oxidative phosphorylation and DNA repair.

OBJECTIVE: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive occlusion of the internal carotid artery and the secondary formation of collateral vessels. Patients with MMD have ischemic attacks or intracranial bleeding, but the disease pathophysiology remains unknown. In this study, the authors aimed to identify a gene expression profile specific to the intracranial artery in MMD. METHODS: This was a single-center, prospectively sampled, retrospective cohort study. Microsamples of the middle cerebral artery (MCA) were collected from patients with MMD (n = 11) and from control patients (n = 9). Using microarray techniques, transcriptome-wide analysis was performed. RESULTS: Comparison of MCA gene expression between patients with MMD and control patients detected 62 and 26 genes whose expression was significantly (p < 0.001 and fold change > 2) up- or downregulated, respectively, in the MCA of MMD. Gene set enrichment analysis of genes expressed in the MCA of patients with MMD revealed positive correlations with genes involved in antigen processing and presentation, the dendritic cell pathway, cytokine pathway, and interleukin-12 pathway, and negative correlations with genes involved in oxidative phosphorylation and DNA repair. Microarray analysis was validated by quantitative polymerase chain reaction. CONCLUSIONS: Transcriptome-wide analysis showed upregulation of genes for immune responses and downregulation of genes for DNA repair and oxidative phosphorylation within the intracranial artery of patients with MMD. These findings may represent clues to the pathophysiology of MMD.

Effects of aspirin and heparin treatment on perioperative outcomes in patients with Moyamoya disease.

BACKGROUND: When superficial temporal artery-middle cerebral artery bypass is combined with indirect methods (e.g., revascularization surgery) to treat Moyamoya disease (MMD), antiplatelet treatment can impact bypass patency, infarction, or hemorrhage complications. Recently, heparin has been proposed as an anticoagulant treatment against white thrombus at the anastomosis site. The study aims to evaluate the effect of aspirin on the perioperative outcomes and investigate the results of heparin treatment for white thrombus. METHODS: This retrospective study included 74 procedures of combined revascularization surgery for MMD patients who either received or did not receive aspirin. Perioperative outcomes were compared between the two groups. In addition, the effects of heparin treatment for white thrombus were evaluated. RESULTS: The rate of white thrombus at the anastomosis site was significantly higher in the non-aspirin medication group (univariate: p = 0.032, multivariate: p = 0.044) and, accordingly, initial bypass patency was lower in the non-aspirin medication group (p = 0.049). Of the 17 patients with white thrombus development, five received heparin injections, and all white thrombi disappeared; however, there was one case of epidural hematoma and another of subdural hematoma. The risk of hemorrhagic complications was significantly higher in the surgical procedures that received heparin injections (p = 0.021). CONCLUSIONS: In MMD patients who received combined revascularization surgery, aspirin medication lowered the occurrence of white thrombus. Heparin injections help to treat white thrombus but can enhance the risk of hemorrhagic complications.

Ipsilateral late stroke after revascularization surgery for patients with Moyamoya disease.

BACKGROUND: Ipsilateral late stroke events occurring after cerebral revascularization for Moyamoya disease (MMD) and their risk factors have not been fully investigated. METHODS: We retrospectively analyzed 123 patients with MMD who underwent 212 revascularizations. We investigated preoperative demographic data, surgical procedures, and ipsilateral stroke events occurring more than 1 month after surgery. The effect of revascularization and the residual Moyamoya vessel (MMV) score were examined using magnetic resonance angiography (MRA). Then, predictive factors for postoperative late stroke occurrence were evaluated by logistic regression. RESULTS: The mean age was 26 ± 18.4 years (range 1 to 66 years). Ipsilateral late stroke events were present in 11 of 123 (9%) patients. Stroke occurred in 11 out of 212 surgeries (5.2%) on a hemispheric basis. During the 1300.1 hemisphere-years of follow-up more than 1 month after surgery, the annual stroke rate was 0.84%. The postoperative MRA time-of-flight image showed a mean revascularization score of 1.82 ± 0.6 and a mean residual MMV score of 1.91 ± 0.83. Postoperative strokes occurring within 1 month after cerebral revascularization (36.4%, p = 0.0026) and lower revascularization scores (1.82 ± 0.6 vs 2.51 ± 0.59, p = 0.0006) were significant factors related to the presence of ipsilateral late stroke. Logistic regression showed that stroke events within 1 month after revascularization (odds ratio [OR], 9.79; 95% confidence interval [CI], 0.02-0.57; p = 0.0103), low revascularization score (OR, 0.15; 95% CI, 0.001-0.37; p = 0.0069), and high residual MMV score (OR, 16.2; 95% CI, 1.88-187.4; p = 0.0107) were risk factors for ipsilateral stroke more than 1 month after revascularization. CONCLUSIONS: MMD patients who have a stroke within 1 month after cerebral revascularization are at high risk for late strokes. Less effective revascularization or remarkable residual MMV are risk factors for late stroke events. Additional revascularization may be considered for patients in such situations. CLINICAL TRIAL REGISTRATION: This study was approved by the Bioethics Review Committee of Nagoya University Hospital for the treatment and prognosis of Moyamoya disease (2016-0327).

Progressive stenosis and radiological findings of vasculitis over the entire internal carotid artery in moyamoya vasculopathy associated with graves' disease: a case report and review of the literature.

BACKGROUND: Moyamoya vasculopathy (MMV) associated with Graves' disease (GD) is a rare condition resulting in ischemic stroke accompanied by thyrotoxicity. Radiological findings of vasculitis have been reported in the walls of distal internal carotid arteries (ICAs) in these patients; however, no reports have described in detail the processes of progression of the lesions in the proximal ICA. Moreover, treatments to prevent recurrence of ischemic stroke and progression of MMV have not yet been sufficiently elucidated. CASE PRESENTATION: We report a progressive case of MMV associated with GD and review the literature to clarify relationships among recurrence, progression, thyrotoxicity and treatment. Our patient developed cerebral infarction during thyrotoxicity with no obvious stenosis of ICAs. Five months later, transient ischemic attacks recurred with thyrotoxicity. Antiplatelet therapy and intravenous methylprednisolone stopped the attacks. Stenosis of the left ICA from the proximal to distal portion and champagne bottle neck sign (CBN) were found. She declined any surgery. Afterward, gradual progression with mild thyrotoxicity was observed. Eventually, we found smooth, circumferential, concentric wall thickening with diffuse gadolinium enhancement of the left ICA from the proximal to the distal portion on T1-weighted imaging, suggesting vasculitis radiologically. The clinical and radiological similarities to Takayasu arteritis encouraged us to provide treatment as for vasculitis of medium-to-large vessels. In a euthyroid state and after administration of prednisolone and methotrexate, improved flow in the cerebrovascular arteries on magnetic resonance angiography was observed. Based on our review of the literature, all cases with recurrence or progression were treated with anti-thyroid medication (ATM) alone and accompanied by thyrotoxicity. CBN was observed in all previous cases for which images of the proximal ICA were available. CONCLUSIONS: We report the details of progressive stenosis from a very early stage and radiological findings of vasculitis over the entire ICA in MMV associated with GD. Cerebral infarction can occur with no obvious stenosis of the ICA. We treated the patient as per vasculitis of a medium-to-large vessel. Management of GD by ATM alone seems risky in terms of recurrence. Adequate management of GD and possible vasculitis may be important for preventing recurrence and progression.

Subarachnoid hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser1412 in the dentate gyrus of the rat brain.

INTRODUCTION: We previously demonstrated that cyclic AMP-dependent protein kinase (PKA) phosphorylates neuronal nitric oxide synthase (nNOS) at Ser1412 in the hippocampal dentate gyrus after forebrain ischemia; this phosphorylation event activates NOS activity and might contribute to depression after cerebral ischemia. In this study, we revealed chronological and topographical changes in the phosphorylation of nNOS at Ser1412 immediately after subarachnoid hemorrhage (SAH). METHODS: In a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24 h after SAH. Samples from rats that were not injected with autologous blood were used as controls. NOS was partially purified from crude samples via an ADP-agarose gel. Levels of nNOS, nNOS phosphorylated at Ser1412 (p-nNOS), PKA, and p-PKA at Thr197 were studied in the rat hippocampus and cortex using Western blot analyses and immunohistochemistry. RESULTS: According to the Western blot analysis, levels of p-nNOS at Ser1412 were significantly increased in the hippocampus, but not in the cortex, between 1 and 3 h after SAH. Immunohistochemistry revealed the phosphorylation of nNOS at Ser1412 and PKA at Thr197 in the dentate gyrus, but not in the CA1 area, 1 h after SAH. An injection of saline instead of blood also significantly increased levels of p-nNOS at Ser1412 in the hippocampus 1 h after the injection. CONCLUSIONS: An immediate increase in intracranial pressure (ICP) might induce transient cerebral ischemia and promote the PKA-mediated phosphorylation of nNOS at Ser1412 in the dentate gyrus. This signal transduction pathway induces the excessive production of nitric oxide (NO) and might be involved in cognitive dysfunction after SAH.

Association between CYP2C19 genotype and the additional effect of cilostazol to clopidogrel resistance in neuroendovascular therapy.

We investigated the association between CYP2C19 genotype and additional effect of cilostazol on clopidogrel resistance (CR) in neuroendovascular therapy. Between January 2012 and January 2016, 447 consecutive patients were administered with 75-mg cilostazol/day. The VerifyNow System was used for evaluating P2Y12 reaction units (PRU) > 230 and/or percentage inhibition of platelet function (% Inhibition) ≤ 20 as CR. Among 158 patients with CR, 31 were administered with additional 100- or 200-mg cilostazol/day and their platelet function was evaluated. According to CYP2C19 genotypes revealed using the Spartan RX and DNeasy Blood & Tissue Kit, patients were classified into three phenotypic groups: extensive metabolizer (EM, three patients), intermediate metabolizer (IM, 12 patients), and poor metabolizer (PM, 16 patients). Administration of additional cilostazol decreased PRU (EM group: 160.7 ± 85.2 after vs 278.3 ± 40.1 before, P = 0.15; IM group: 205.6 ± 74.0 vs 254.3 ± 35.0, P = 0.02; and PM group: 227.8 ± 52.2 vs 282.1 ± 30.4, P = 0.003), and increased % Inhibition (EM group: 40.0 ± 27.9 vs 9.3 ± 3.8, P = 0.25; IM group: 31.4 ± 18.0 vs 11.8 ± 8.2, P = 0.001; and PM group: 24.6 ± 15.0 vs 10.4 ± 9.3, P = 0.001). However, the rate of normalized-clopidogrel response, thromboembolic lesions, and bleeding complications were not significantly different among the three groups. Thus, the addition of cilostazol was effective on CR in terms of PRU, % Inhibition, rate of change of normalized-clopidogrel response, thromboembolic events, and bleeding complications irrespective of phenotype.

Rapid contralateral progression of focal cerebral arteriopathy distinguished from RNF213-related moyamoya disease and fibromuscular dysplasia.

BACKGROUND: Focal cerebral arteriopathy includes unifocal or multifocal lesions that are unilateral or bilateral. Large- and/or medium-sized vessels are involved and can be visualized on angiography. CASE REPORT: We report a case of cerebral infarction in a 9-year-old Japanese female who presented with a transient ischemic attack. Steno-occlusion involving the distal part of the internal carotid artery, proximal middle cerebral artery, and anterior cerebral artery was observed. Digital subtraction angiography demonstrated a beaded appearance in the cervical portion of the diseased internal carotid artery. Revascularization surgery was performed 45 days after the onset. A new infarction appeared on the other side of the anterior cerebral artery territory 7 months after the first onset. Antiplatelets and vasodilators were administered, and no progression was observed during 18 months of follow-up. Genetic analysis did not show ring finger protein 213 (RNF213)-related moyamoya disease, and pathological examination revealed no characteristics of fibromuscular dysplasia. CONCLUSION: The radiological and genetic features coincided with focal cerebral arteriopathy, which is a distinct entity from fibromuscular dysplasia and RNF213-related moyamoya disease.