Power suppression in EEG after the onset of SAH is a significant marker of early brain injury in rat models.

We analyzed the correlation between the duration of electroencephalogram (EEG) recovery and histological outcome in rats in the acute stage of subarachnoid hemorrhage (SAH) to find a new predictor of the subsequent outcome. SAH was induced in eight rats by cisternal blood injection, and the duration of cortical depolarization was measured. EEG power spectrums were given by time frequency analysis, and histology was evaluated. The appropriate frequency band and recovery percentage of EEG (defined as EEG recovery time) to predict the neuronal damage were determined from 25 patterns (5 bands × 5 recovery rates) of receiver operating characteristic (ROC) curves. Probit regression curves were depicted to evaluate the relationships between neuronal injury and duration of depolarization and EEG recovery. The optimal values of the EEG band and the EEG recovery time to predict neuronal damage were 10-15 Hz and 40%, respectively (area under the curve [AUC]: 0.97). There was a close relationship between the percentage of damaged neurons and the duration of depolarization or EEG recovery time. These results suggest that EEG recovery time, under the above frequency band and recovery rate, may be a novel marker to predict the outcome after SAH.

Cardiopulmonary Resuscitation May Not Stop Glutamate Release in the Cerebral Cortex.

BACKGROUND: Cardiopulmonary resuscitation (CPR) may not be sufficient to halt the progression of brain damage. Using extracellular glutamate concentration as a marker for neuronal damage, we quantitatively evaluated the degree of brain damage during resuscitation without return of spontaneous circulation. MATERIALS AND METHODS: Extracellular cerebral glutamate concentration was measured with a microdialysis probe every 2 minutes for 40 minutes after electrical stimulation-induced cardiac arrest without return of spontaneous circulation in Sprague-Dawley rats. The rats were divided into 3 groups (7 per group) according to the treatment received during the 40 minutes observation period: mechanical ventilation without chest compression (group V); mechanical ventilation and chest compression (group VC) and; ventilation, chest compression and brain hypothermia (group VCH). Chest compression (20 min) and hypothermia (40 min) were initiated 6 minutes after the onset of cardiac arrest. RESULTS: Glutamate concentration increased in all groups after cardiac arrest. Although after the onset of chest compression, glutamate concentration showed a significant difference at 2 min and reached the maximum at 6 min (VC group; 284±48 µmol/L vs. V group 398±126 µmol/L, P =0.003), there was no difference toward the end of chest compression (513±61 µmol/L vs. 588±103 µmol/L, P =0.051). In the VCH group, the initial increase in glutamate concentration was suddenly suppressed 2 minutes after the onset of brain hypothermia. CONCLUSIONS: CPR alone reduced the progression of brain damage for a limited period but CPR in combination with brain cooling strongly suppressed increases in glutamate levels.

Incidence and clinical characteristics of spinal arteriovenous shunts: hospital-based surveillance in Okayama, Japan.

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.

Trends in Incidence of Intracranial and Spinal Arteriovenous Shunts: Hospital-Based Surveillance in Okayama, Japan.

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.

4-Hydroxyl-2-Nonenal Localized Expression Pattern in Retrieved Clots is Associated with Large Artery Atherosclerosis in Stroke Patients.

OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).

A Patient with a Cavernous Sinus Dural Arteriovenous Fistula in Whom an Approach through the Jugular Venous Arch Involving Facial Vein Return Was Adopted.

Objective: We report the case of a cavernous sinus dural arteriovenous fistula (CSdAVF) treated by transvenous embolization (TVE) via the jugular venous arch (JVA) connecting bilateral superficial cervical veins. Case Presentation: A male patient in his 50s presenting with diplopia and headache was diagnosed with a CSdAVF. The first session of TVE resulted in incomplete obliteration of the fistula due to poor accessibility through the inferior petrosal sinus (IPS), and postoperative computed tomography angiography (CTA) disclosed a newly developed drainage route into the facial vein (FV) connecting to the anterior jugular vein (AJV) and the JVA. The patient underwent the second session of TVE through the JVA, FV, and the superior ophthalmic vein (SOV), and obliteration was achieved. Conclusion: There is a considerable variation in the anatomy of facio-cervical veins in patients with CSdAVF. Meticulous preoperative evaluation of the venous drainage route using modern diagnostic tools is indispensable to achieve successful results in patients with CSdAVF.

Metal artifact reduction algorithm for image quality improvement of cone-beam CT images of medium or large cerebral aneurysms treated with stent-assisted coil embolization.

PURPOSE: The aim of the present study was to assess image quality improvement using a metal artifact reduction (MAR) algorithm in cases of medium or large cerebral aneurysms treated with stent-assisted coil embolization (SAC), and to analyze factors associated with the usefulness of the MAR algorithm. METHODS: We retrospectively evaluated the cone-beam computed tomography (CBCT) data sets of 18 patients with cerebral aneurysms treated with SAC. For subjective analysis, images of all cases with and without MAR processing were evaluated by five neurosurgeons based on four criteria using a five-point scale. For objective analysis, the CT values of all cases with and without MAR processing were calculated. In addition, we assessed factors associated with the usefulness of the MAR by analyzing the nine cases in which the median score for criterion 1 improved by more than two points. RESULTS: MAR processing improved the median scores for all four criteria in 17/18 cases (94.4%). Mean CT values of the region of interest at the site influenced by metal artifacts were significantly reduced after MAR processing. The maximum diameter of the coil mass (< 17 mm; odds ratio [OR], 4.0; 95% confidence interval [CI], 1.2-13.9; p = 0.02) and vessel length covered by metal artifacts (< 24 mm; OR, 2.3; 95% CI, 1.1-4.7; p = 0.03) was significantly associated with the usefulness of the MAR. CONCLUSIONS: This study suggests the feasibility of a MAR algorithm to improve the image quality of CBCT images in patients who have undergone SAC for medium or large aneurysms.

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

OBJECTIVE Although 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. METHODS Twenty-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. RESULTS Changes 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. CONCLUSIONS CSD 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.

Combined gene therapy with vascular endothelial growth factor plus apelin in a chronic cerebral hypoperfusion model in rats.

OBJECTIVE The 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. METHODS A 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. RESULTS The 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. CONCLUSIONS Combined 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.

[A Case of Traumatic Vertebral Arteriovenous Fistula Treated by Internal Trapping of the Vertebral Artery].

BACKGROUND: Traumatic vertebral arteriovenous fistula (TVAVF) is an uncommon disease that occurs after traumatic injury. Here we report a case of TVAVF presenting with cervical bruit successfully treated by internal trapping using coils. CASE PRESENTATION: A 66-year-old man was transferred to our hospital after falling into a ditch. Initial CT revealed a C2 fracture into the right transverse foramen, and the patient had been treated with conservative management. A vascular abnormality was suspected because the patient exhibited cervical bruit on admission. CT angiography revealed right TVAVF at the V2 segment of the right vertebral artery (VA) near the C2 fracture. Digital subtraction angiography also revealed right TVAVF between the V2 segment of the right VA and the vertebral venous plexus, draining into the right internal jugular vein and the deep cervical vein as well as the intracranial venous system. The fistula was also opacified by retrograde flow from the contralateral VA through the union, while the flow in the basilar artery was antegrade. The patient was diagnosed with TVAVF with large transection of the right VA, and underwent endovascular treatment with internal trapping of the right VA using coils starting distal to the transection and proceeding in a proximal direction. After treatment, the right VAVF and right VA were completely occluded. The patient achieved clinical symptom resolution with no neurological deficits. CONCLUSION: Endovascular treatment with internal trapping of the VA using coils is safe and effective against TVAVF.

Cerebral vasospasm in patients over 80 years treated by coil embolization for ruptured cerebral aneurysms.

OBJECT: The effect on clinical outcomes of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH) in patients over 80 years who underwent coil embolization was evaluated. METHODS: Forty-four cases were reviewed and divided into two groups according to patient age: Group A, 79 years or younger, and Group B, 80 or older. Patient characteristics, prevalence of symptomatic vasospasm, modified Rankin Scale (mRS) scores at discharge and frequency of symptomatic vasospasm in patients with mRS scores of 3-6 were analyzed. RESULTS: Thirty-two (73%) of the 44 cases were categorized as Group A and 12 (27%) as Group B. Group B had a significantly higher prevalence of symptomatic vasospasm compared to Group A (P=0.0040). mRS scores at discharge were significantly higher in Group B than in Group A (P=0.0494). Among cases with mRS scores of 3-6, there was a significantly higher frequency of symptomatic vasospasm in Group B than in Group A (P=0.0223). CONCLUSIONS: In our cohort of aneurysmal SAH patients treated by coil embolization, patients over 80 years of age were more likely to suffer symptomatic vasospasm, which significantly correlated with worse clinical outcomes, than those 79 years and under.