P2X7 Receptors in Astrocytes: A Switch for Ischemic Tolerance.

A sub-lethal ischemic episode (preconditioning [PC]) protects neurons against a subsequent lethal ischemic injury. This phenomenon is known as ischemic tolerance. PC itself does not cause brain damage, but affects glial responses, especially astrocytes, and transforms them into an ischemia-resistant phenotype. P2X7 receptors (P2X7Rs) in astrocytes play essential roles in PC. Although P2X7Rs trigger inflammatory and toxic responses, PC-induced P2X7Rs in astrocytes function as a switch to protect the brain against ischemia. In this review, we focus on P2X7Rs and summarize recent developments on how astrocytes control P2X7Rs and what molecular mechanisms they use to induce ischemic tolerance.

GH/PRL-secreting pituitary macroadenoma associated with GNAS p.Gln227Leu mutation: pediatric case report and review.

GH-secreting pituitary adenomas (GHomas) are rare in the pediatric population. Guanine nucleotide-binding protein, alpha stimulating (GNAS) somatic mutations are often found in patients with GHoma. Here, we report an 8-year-old girl with GH-secreting pituitary adenoma successfully treated by operative tumor resection and postoperative treatment with octreotide long-acting release (LAR). Tumor DNA sequence analysis revealed a somatic heterozygous c.680A>T (p.Gln227Leu) mutation in GNAS. We reviewed 1,084 cases of GHomas, 409 (37.7%) of which harbored GNAS mutations. In pediatrics cases, aged 15 years or younger, 11 harbored a GNAS mutation, and GNAS p.Arg201Cys was identified in five cases. No other cases of codon 227 mutation were detected. These cases suggest that, in pediatric patients, the clinical features of GHoma may differ from those observed in adults. This is possibly related to octreotide or dopamine agonist resistance. Of six patients with surgical resistance, only one was reactive when treated with octreotide. Our case shows that octreotide LAR is an effective choice for treating GNAS-induced GHoma. This is the first report detailing the effectiveness of octreotide LAR in a GNAS codon 227 mutation-induced GHoma in a pediatric case. Examination of the relationship between genetic variation and clinical features in pediatric patients will enable us to assess the long-term effects of surgical and medical treatment of GHomas.

[Spontaneous Improvement in Visual Symptom after Delivery in a Case of Tuberculum Sellae Meningioma].

A 36-year-old woman presented with temporal visual field defect in the 27th week of her pregnancy. Magnetic resonance(MR)imaging demonstrated a tuberculum sellae meningioma compressing the optic chiasm. Although we planned surgical resection after her delivery, the symptom worsened in the late stage of her pregnancy. After administering a steroid medication, the symptom stabilized. In the 38th week of pregnancy, she delivered a child, and interestingly, her visual field defect improved, and MR imaging demonstrated tumor shrinkage. However, at the request of the patient, we performed the tumor resection by extended endonasal transsphenoidal surgery. The histological diagnosis was angiomatous meningioma, and the tumor cells were strongly positive for progesterone receptors. This is a very rare case of tuberculum meningioma wherein the patient showed a natural improvement in visual function after delivery. Regarding the appropriate surgical timing for meningioma, spontaneous shrinkage of meningioma after delivery would be considered an option.

Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study.

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

A Case of Ruptured Vertebrobasilar Junction Aneurysm Associated with Subclavian Steal Phenomenon.

A 77-year-old woman with arteriovenous shunt for hemodialysis in the left forearm suffered from subarachnoid hemorrhage due to the rupture of a saccular aneurysm located on the left lateral wall of vertebrobasilar junction. Her left subclavian artery was severely stenosed and subclavian steal phenomenon was demonstrated on the digital subtraction angiography. Embolization of the parent artery including the aneurysm using detachable coils resulted in the successful obliteration of the aneurysm through the revascularized left subclavian artery. This is the first case in which the vertebrobasilar junction aneurysm would be caused by the hemodynamic stress due to the subclavian steal phenomenon combined with the shunt for hemodialysis in the left forearm.

Astrocyte-mediated ischemic tolerance.

Preconditioning (PC) using a preceding sublethal ischemic insult is an attractive strategy for protecting neurons by inducing ischemic tolerance in the brain. Although the underlying molecular mechanisms have been extensively studied, almost all studies have focused on neurons. Here, using a middle cerebral artery occlusion model in mice, we show that astrocytes play an essential role in the induction of brain ischemic tolerance. PC caused activation of glial cells without producing any noticeable brain damage. The spatiotemporal pattern of astrocytic, but not microglial, activation correlated well with that of ischemic tolerance. Interestingly, such activation in astrocytes lasted at least 8 weeks. Importantly, inhibiting astrocytes with fluorocitrate abolished the induction of ischemic tolerance. To investigate the underlying mechanisms, we focused on the P2X7 receptor as a key molecule in astrocyte-mediated ischemic tolerance. P2X7 receptors were dramatically upregulated in activated astrocytes. PC-induced ischemic tolerance was abolished in P2X7 receptor knock-out mice. Moreover, our results suggest that hypoxia-inducible factor-1α, a well known mediator of ischemic tolerance, is involved in P2X7 receptor-mediated ischemic tolerance. Unlike previous reports focusing on neuron-based mechanisms, our results show that astrocytes play indispensable roles in inducing ischemic tolerance, and that upregulation of P2X7 receptors in astrocytes is essential.

A case of complete clearance of chronic subdural hematoma accompanied by recurrent glioblastoma multiforme after administration of bevacizumab.

The efficacy of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), as an adjuvant therapy against various malignant tumors was recently established. Its pharmacological effects in malignant tumors, including gliomas, were speculated to involve neovascularization inhibition and vascular permeability. Recently, it has been reported that the outer membrane of chronic subdural hematoma (CSDH) contains high levels of VEGF, which were implicated in neovascularization of the outer membrane. Furthermore, studies suggested that VEGF has the etiology in CSDH development, although its involvement is not fully understood. Here, we report the first case of chronic subdural hematoma that was improved by bevacizumab administration for recurrent glioblastoma. The present case could contribute to the hypothesis that VEGF may be associated with CSDH. We also discuss the pathogenesis and mechanism of CSDH recurrence from the viewpoint of VEGF function.

Long-Term Follow-Up for a Giant Basilar Trunk Aneurysm Surgically Treated by Proximal Occlusion and External Carotid Artery to Posterior Cerebral Artery Bypass Using a Saphenous Vein Graft.

The authors describe a case of a basilar trunk aneurysm with long-term follow-up after successful bypass and proximal occlusion. A 64-year-old woman had a giant aneurysm of the basilar trunk and underwent external carotid artery-to-posterior cerebral artery vein graft bypass surgery and proximal clipping of the basilar artery, which was followed by low-dose aspirin (100 mg/d) treatment. No ischemic symptoms and lesions developed and the thrombosed aneurysm was stable during 11 years of follow-up. An extracranial-intracranial high flow bypass combined with immediate proximal occlusion and aspirin administration may be an acceptable treatment option for patients with giant posterior circulation aneurysms.

Phase II Trial of Intravenous Low-Dose Granulocyte Colony-Stimulating Factor in Acute Ischemic Stroke.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has shown neuroprotective and neurogenerative activities in experimental studies, and our previous phase I clinical study suggested the safety and potential efficacy of low-dose G-CSF in acute ischemic stroke patients. The present phase II trial is aimed to evaluate the effect of G-CSF administration on neurological function and infarct volume, compared with a placebo group. METHODS: Forty-nine acute ischemic stroke patients (29 males, 20 females; 71 ± 10 years) within 24 hours after onset were recruited. Eligible patients were randomized 2:2:1 to receive G-CSF 150 µg/body/day, G-CSF 300 µg/body/day, and placebo, respectively. We evaluated clinical outcome in terms of the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index at 90 days after onset, together with changes in infarct volume on magnetic resonance imaging. RESULTS: We found no serious adverse event, including change in leukocyte levels, which remained below 31,000/µL, at 150 and 300 µg G-CSF/body/day. Clinical outcome scores did not show any significant difference among the 3 groups. Chronological changes in infarct volume also showed no significant difference. CONCLUSIONS: G-CSF was well-tolerated at 150 and 300 µg/body/day in patients with acute ischemic stroke. However, administration of G-CSF at both 150 and 300 µg/body/day neither contributed to functional recovery nor reduced infarct volume at 3 months after onset, compared with the control group. The apparent lack of effectiveness may have been due to the small sample size. A trial of combination therapy with recombinant tissue plasminogen activator and G-CSF is planned.

Maximal Resection of Gliomas Adjacent to the Corticospinal Tract Using 3-T Intraoperative Magnetic Resonance Imaging.

BACKGROUND: Gliomas adjacent to the corticospinal tract (CST) should be carefully resected to preserve motor function while achieving maximal surgical resection. Modern high-field intraoperative magnetic resonance imaging (iMRI) enables precise visualization of the residual tumor and intraoperative tractography. We prospectively evaluated the extent of resection and distance between the tumor resection cavity and CST using 3-T iMRI combined with motor evoked potentials (MEP) in glioma surgery. METHODS: Participants comprised patients who underwent surgery for solitary supratentorial glioma located within 10 mm of the CST. All cases underwent surgery using neuronavigation with overlaid CST under MEP monitoring. The correlation between distance from CST and transcortical MEP amplitude was calculated using Spearman rank correlation. RESULTS: Among the 63 patients who underwent surgery, 27 patients were enrolled in the study. Gross total resections were achieved in 26 of the 27 cases. Volumetric analysis showed the extent of resection was 98.6%. Motor function was stable or improved in 24 patients (Stable/Improved group) and deteriorated in 3 patients (Deteriorated group). All patients in the Deteriorated group showed motor deficit before surgery. Mean intraoperative minimal distance was significantly longer in the Stable/Improved group (7.3 mm) than in the Deteriorated group (1.1 mm; P < 0.05). MEP amplitude correlated with minimal distance between the resection cavity and CST (R = 0.64). CONCLUSIONS: Resection of gliomas adjacent to CST with a navigation system using 3-T iMRI could result in an ultimate EOR >98%. The combination of intraoperative tractography and MEP contributes to maximal removal of motor-eloquent gliomas.

Iodine-123-Iomazenil Single-Photon Emission Computed Tomography Revealed Recovery of Neuronal Viability in Association With Improvement of Cognitive Dysfunction After Revascularization in Moyamoya Disease.

BACKGROUND AND OBJECTIVES: Recent studies indicate that 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) can demonstrate neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult patients with moyamoya disease (MMD), no standard neuroradiological methods to define such conditions have been established. We examined the relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in patients with MMD. METHODS: The study participants were 16 adult patients with MMD whose cerebrovascular reactivities were decreased only on the surgical sides of combined revascularization. Cognitive function was examined using the Mini-Mental State Examination (MMSE; cutoff: 27) and the Frontal Assessment Battery (FAB; cutoff: 16) before and at 3 to 6 months after surgery. 123I-iodoamphetamine (123I-IMP) SPECT with acetazolamide challenge and 123I-IMZ SPECT were performed concurrently while evaluating cognitive function. The radioreactivities of 123I-IMZ SPECT in regions with decreased cerebrovascular reactivities on 123I-IMP SPECT were investigated using affected-to-contralateral side asymmetry ratio (IMZ-ACR). RESULTS: Twelve patients showed normal cognitive function (MMSE: 29.8 ± 0.4, FAB: 18 ± 0) before surgery. No evident laterality of 123I-IMZ uptake was seen (IMZ-ACR: 0.98 ± 0.04). Neither cognitive function nor 123I-IMZ SPECT worsened after surgery (MMSE: 29.8 ± 0.3, FAB: 18 ± 0, IMZ-ACR: 1.00 ± 0.04). By contrast, 4 patients presented cognitive dysfunction (MMSE: 24.3 ± 3.9, FAB: 14.8 ± 2.7) before revascularization. Preoperative imaging of these patients showed decreased 123I-IMZ uptake, and their IMZ-ACRs (0.83 ± 0.08) were significantly lower than those of the normal group. After revascularization, cognitive functions and 123I-IMZ uptake tended to ameliorate (MMSE: 27.5 ± 1.7, FAB: 16.3 ± 2.2, IMZ-ACR: 0.94 ± 0.09). CONCLUSION: Preoperative cognitive function was associated with 123I-IMZ uptake in adult patients with MMD. After revascularization, cognitive function could be recovered in the viable areas of the brain, which is consistent with 123I-IMZ SPECT findings.

Simultaneous onset of anterior and middle cerebral artery dissections with an old vertebral artery dissection.

Multiple arterial dissections in the anterior circulation with simultaneous onset are extremely rare. We report a patient with infarctions caused by simultaneous arterial dissections in the right anterior cerebral artery and the left middle cerebral artery and discuss the characteristic feature of this vascular disorder. A 53-year-old woman presented with a severe headache and a mild aphasia. Magnetic resonance imaging revealed multiple acute cerebral infarctions in the left temporal and right frontal lobes. The initial angiographic findings revealed arterial dissections of the anterior cerebral, left middle cerebral, and right vertebral arteries. The follow-up angiographic examination found improvement of the stenosis in both the anterior cerebral and middle cerebral arteries. We have concluded that the lesion of the vertebral artery was not in an acute stage, because no interval change was seen during the radiologic evaluation. She underwent conservative therapy, and her symptoms disappeared. Multiple arterial dissections are rare, especially those developing simultaneously in different arteries. This is the first case of multiple arterial dissections of the different arteries in the anterior circulation manifesting cerebral infarction simultaneously.

In-stent thrombosis after carotid artery stenting despite sufficient antiplatelet therapy in a bladder cancer patient.

In-stent thrombosis (IST) after carotid artery stenting (CAS) is a rare but potentially devastating complication. We present a case of early IST after CAS despite sufficient antiplatelet therapy in a patient with bladder cancer. A 77-year-old man under preventive triple antiplatelet therapy underwent CAS without any intra- or periprocedural complications. However, the patient developed a large asymptomatic IST 6 days after CAS. Anticoagulant therapy with argatroban was reintroduced to treat IST concomitant with antiplatelet agents. Subsequently, the IST shrank and disappeared without any thrombotic symptoms. Malignancy is regarded as an acquired thrombophilic condition associated with a significant risk of thrombosis. In the field of coronary stents, cancer is associated with a significant increasing risk of IST. The cause of IST in our case was possibly related in hypercoagulable state because of the patient's cancer. Attention for IST should be paid in CAS cases with these risk factors, and repeated examination is recommended.

A Novel Staged Revascularization Strategy for Bilateral Severe Internal Carotid Artery Stenosis at High Risk for Hyperperfusion Syndrome.

OBJECTIVE: Since bilateral severe internal carotid artery stenosis often is associated with severely decreased cerebrovascular reactivity (CVR) due to poor collateral blood flow, revascularization carries a high risk for development of hyperperfusion syndrome. In this study, we report a new staged strategy to prevent postoperative hyperperfusion syndrome in such patients. METHODS: Bilateral severe cervical internal carotid artery stenosis patients with decreased CVR to 10% or less on one side were prospectively enrolled in this study. We first performed carotid artery stenting on the side with the milder CVR decrease (lower-risk side), aiming to improve hemodynamics associated with the severe CVR decrease on the greater-risk side. Then, carotid endarterectomy or carotid artery stenting was performed on the contralateral side after an interval of 4-8 weeks. RESULTS: In all 3 cases enrolled in this study, CVR on the greater-risk side improved to 10% or more 1 month after the first treatment. The ratio of regional cerebral blood flow on the contralateral greater-risk side was 114% 1 day after the second treatment, and HPS did not develop in any of the cases. CONCLUSIONS: Our treatment strategy, in which revascularization on the lower-risk side precedes that on the greater-risk side, is effective for the prevention of HPS in bilateral ICA stenosis patients.

Hemorrhagic cervical juxta-facet cyst presenting with Brown-Séquard syndrome: illustrative case.

BACKGROUND: Intraspinal juxta-facet cysts of the spine are known to predominate at the lumbar level and is relatively rare at the cervical level. Most cervical spinal lesions are found incidentally, but they sometimes cause myelopathy or radiculopathy in a chronic course. OBSERVATIONS: The authors present a rare case of hemorrhagic cervical juxta-facet cyst presenting with Brown-Séquard syndrome. An 86-year-old woman presented with acute-onset right hemiparesis following neck pain and was admitted to the local hospital. She was started on antithrombotic therapy with a suspected diagnosis of cerebral infarction, but quadriplegia progressed 2 days later. Cervical magnetic resonance imaging revealed an intraspinal mass at the C4-5 level and she was referred to the authors' hospital. Her neurological findings on admission revealed right Brown-Séquard syndrome. In emergency surgery, the mass was resected with a posterior approach. Pathological findings showed hemosiderin deposition and fibroblast proliferation, consistent with a juxta-facet cyst with intracystic hemorrhage. The patient recovered well and returned to an independent daily life. LESSONS: Rarely, juxta-facet cyst of the cervical spine can cause acute Brown-Séquard syndrome due to intraspinal hemorrhage. In a case of hemiparesis that develops following neck pain, hemorrhagic cervical juxta-facet cyst should be taken into consideration as a differentiation.

Analysis of vascular perfusion territory using selective intraarterial injection CT angiography before and after revascularization surgery in patients with moyamoya disease.

OBJECTIVE: In moyamoya disease (MMD), blood flow to the internal carotid artery (ICA) system is supplied via the basal fine vascular network, leptomeningeal anastomoses, and transdural collateral vessels from the external carotid artery (ECA). After revascularization, there is a dramatic change in cerebral perfusion to the ECA system. Understanding this shift in blood supply is important for evaluating treatment efficacy and elucidating the postoperative pathophysiology. However, anatomical and quantitative methods for doing so have not yet been established. In the present study, selective intraarterial injection CT angiography (iaCTA) was performed in patients with MMD, and blood supply changes in each arterial system before and after revascularization surgery were evaluated. METHODS: This study included 10 hemispheres in 10 patients who underwent combined revascularization surgery for adult MMD. Digital subtraction angiography was performed before and 3 months after surgery, and selective iaCTA was performed from the ICA, ECA, and vertebral artery (VA) at the same times in a hybrid CT/digital subtraction angiography suite. The anatomical distribution of each vessel was determined and perfusion volume was measured quantitatively on contrast-enhanced axial CT images. RESULTS: Selective iaCTA clearly depicted the anatomical distribution of perfusion for each vessel. Conversion of blood supply from the ICA and VA to the ECA system was observed in the cerebral cortices and insulae but not in the basal ganglia. The mean volume of perfusion territories of the ECA (preoperative 0.9 cm3, postoperative 98.8 cm3); ICA (preoperative 225.7 cm3, postoperative 159.3 cm3); and VA (preoperative 244.0 cm3, postoperative 163.6 cm3) in the cerebral hemispheres changed significantly after revascularization. There was a correlation between increase in the ECA territory volume and decrease in the VA territory volume due to revascularization (R = -0.84, p < 0.005). CONCLUSIONS: Selective iaCTA enabled clear visualization of anatomical changes in each vascular perfusion territory and quantitative measurement of each perfusion volume. Perfusion conversion to the ECA system after bypass surgery was observed in the cortical regions and in the insulae on the bypass operation sides, but not in the basal ganglia. Combined revascularization promoted the development of ECA-perfused territory, which correlated with a decrease in hemodynamic burden of the posterior cerebral artery.

Blood Blister-Like Aneurysms at the Junction of the Internal Carotid and Posterior Communicating Artery: Characteristics and Treatment Strategies.

BACKGROUND: Blood blister-like aneurysms (BBAs) usually arise from the anterior walls of the internal carotid artery, and such lesions at the junction of the internal carotid artery and posterior communicating artery (PCoA) have not been reported to date. Here, we report our experiences of BBAs at PCoA. We studied their clinical and angiographical characteristics including the internal carotid-PCoA angle, an indicator of hemodynamic stress at the bifurcation. METHODS: Three patients with BBAs located at the origin of PCoA were studied. Wrap-clipping was adopted as the first-line therapy, but direct clipping was conducted when difficult. RESULTS: All patients were elderly females (mean age 81.3 years), and BBAs were small in size (mean maximum diameter 1.5 mm), which arose at the origins of wide-angled fetal-type PCoAs (mean internal carotid-PCoA angle 37.8 degrees). All the lesions were treated by surgery (direct clipping 2, wrap-clipping 1), and severe atherosclerotic changes were observed at adjacent arterial walls in all cases. Ordinary wrap-clipping using a polytetrafluoroethylene membrane via the transsylvian approach was difficult because of the limited working space, requiring some special techniques such as usage of fenestrated clips, polyglycolic acid sheets, and combined approach with subtemporal craniotomy. Good clinical outcomes were achieved in 2 patients. CONCLUSION: BBAs at PCoA were predominantly occurred as the small bulges at the origins of wide-angled fetal-type PCoAs in elderly females. Hemodynamic stress and atherosclerosis would contribute to the aneurysmal formation. Wrap-clipping or direct clipping with additional techniques would be useful for this rare condition.

Chronological Change of the Clinical Features and Treatment Outcomes for Subarachnoid Hemorrhage in Japan: A Multicenter Retrospective Study.

Aneurysmal subarachnoid hemorrhage (SAH) treatment has progressed, and patients are rapidly aging in Japan. Consequently, dynamic changes must have emerged in the clinical practice of SAH. This study aimed to elucidate chronological changes of aneurysmal SAH and the prognostic factors in the previous quarter century in Japan. We conducted a retrospective survey regarding aneurysmal SAH in eight institutions in Japan. The study included 848, 863, and 781 patients in the first (1989-1993), second (1999-2003), and third (2009-2013) periods, respectively. The chronological changes of factors that influenced the poor outcomes and differences between the nonelderly (<75 years) and elderly patients were investigated. Mean age was significantly higher in patients in the third period (61.4 years) than in those in the other two periods (first, 57.8 years; second, 59.5 years). During these periods, the proportion of good outcomes did not change; however, the mortality rate significantly decreased from 19% in the first period to 11% and 9.2% in the second and third periods, respectively. The poor outcome was mainly caused by the significantly higher incidence of systemic complication and procedural complication in the first period and the significantly lower incidence of delayed ischemic neurological deficit in the third period. The elderly patients had significantly poorer clinical outcomes than the nonelderly ones. During the last 25 years, the age of patients with aneurysmal SAH has rapidly increased. The study results may contribute to the improvement of the treatment strategy of SAH in advanced countries with a rapidly aging population.

Neuronal dysfunction and hemodynamic disturbance due to venous congestion in dural arteriovenous fistula revealed by 123I-iomazenil SPECT.

OBJECTIVE: Retrograde leptomeningeal venous drainage (RLVD) of a dural arteriovenous fistula (dAVF) is associated with neurological morbidity and unfavorable outcomes. However, the direct damage to cortical neurons by dAVF with RLVD has not been elucidated. 123I-iomazenil (123I-IMZ) SPECT can reveal cerebral blood flow and cortical neuronal damage in early and late images, respectively. This study aimed to assess the cerebral venous congestive encephalopathy caused by dAVF using 123I-IMZ SPECT. METHODS: Based on the pre- and posttreatment MRI findings, patients were divided into three groups: a normal group, an edema group, and an infarction group. Radioactive counts in the early and late images of 123I-IMZ SPECT were investigated using the affected-to-contralateral side asymmetry ratio (ACR). RESULTS: None of the patients in the normal group showed any symptoms related to venous congestion. In contrast, all the patients in the edema and infarction groups developed neurological symptoms. The ACR in early images in the edema group was significantly lower than that in the normal group and significantly higher than that in the infarction group. The ACR in the late images of the infarction group was significantly lower than those of the normal and edema groups. After treatment, the neurological signs disappeared in the edema group, but only partial improvement was observed in the infarction group. The ACR in early images significantly improved after treatment in the edema group, but the ACR in late images did not change in any groups. CONCLUSIONS: 123I-IMZ SPECT is useful for evaluating hemodynamic disturbances and neuronal damage in dAVFs. The reduction in early images was correlated with the severity of venous congestive encephalopathy, and the significant reduction in late images is a reliable indicator of irreversible venous infarction caused by RLVD.

Soluble C-type lectin-like receptor 2 in stroke (CLECSTRO) study: protocol of a multicentre, prospective cohort of a novel platelet activation marker in acute ischaemic stroke and transient ischaemic attack.

INTRODUCTION: Soluble C-type lectin-like receptor 2 (sCLEC-2) is a new biomarker for platelet activation, which can be easily measured by usual blood collection. We conducted the CLECSTRO, a prospective, observational cohort study, to evaluate the clinical implications of sCLEC-2 in patients with acute ischaemic stroke (AIS) and transient ischaemic attack (TIA). METHODS AND ANALYSIS: The participants are patients with AIS/TIA and control patients required for differentiation from AIS/TIA. The target population is 600, including the patients and controls, who would be recruited from eight stroke centres across Japan. The inclusion criteria are AIS within 24 hours of onset and a modified Rankin Scale (mRS) score of 0-2, TIA within 7 days of onset, and contemporary patients required for differentiation from AIS/TIA. Plasma sCLEC-2 will be measured by high-sensitive chemiluminescent enzyme immunoassay using residual blood samples from routine laboratory examinations at the first visit in all patients and 7 days later or at discharge in patients with AIS/TIA. The outcomes include plasma levels of sCLEC-2 in patients with AIS/TIA and controls, sCLEC-2/D-dimer ratio in non-cardioembolic and cardioembolic AIS/TIA, correlation of sCLEC-2 with recurrence or worsening of stroke, severity of stroke, infarct size, ABCD2 score in TIA and outcome (mRS) at 7 days and 3 months. ETHICS AND DISSEMINATION: This study was approved by the Ethical Committee of the University of Yamanashi as the central ethical committee in agreement with the ethical committees of all collaborative stroke centres. Informed consent will be obtained by an opt-out form from the patients at each stroke centre according to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects by the Japanese Ministry of Health, Labour and Welfare. TRIAL REGISTRATION NUMBERS: NCT05579405, UMIN000048954.