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.

Determination of the Target Temperature Required to Block Increases in Extracellular Glutamate Levels During Intraischemic Hypothermia.

This study aimed to determine a target temperature for intraischemic hypothermia that can block increases in extracellular glutamate levels. Two groups of 10 rats each formed the normothermia and intraischemic hypothermia groups. Extracellular glutamate levels, the extracellular potential, and the cerebral blood flow were measured at the adjacent site in the right parietal cerebral cortex. Cerebral ischemia was induced by occlusion of the bilateral common carotid arteries and hypotension. In the intraischemic hypothermia group, brain hypothermia was initiated immediately after the onset of membrane potential loss. In the normothermia group, extracellular glutamate levels began to increase simultaneously with the onset of membrane potential loss and reached a maximum level of 341.8 ± 153.1 µmol·L-1. A decrease in extracellular glutamate levels was observed simultaneously with the onset of membrane potential recovery. In the intraischemic hypothermia group, extracellular glutamate levels initially began to increase, similarly to those in the normothermia group, but subsequently plateaued at 140.5 ± 105.4 µmol·L-1, when the brain temperature had decreased to <32.6°C ± 0.9°C. A decrease in extracellular glutamate levels was observed simultaneously with the onset of membrane potential recovery, similarly to the findings in the normothermia group. The rate of decrease in extracellular glutamate levels was the same in both groups (-36.6 and -36.0 µmol·L-1 in the normothermia and intraischemic hypothermia groups, respectively). In conclusion, the target temperature for blocking glutamate release during intraischemic hypothermia was found to be 32.6°C ± 0.9°C. Our results suggest that the induction of intraischemic hypothermia can maintain low glutamate levels without disrupting glutamate reuptake. Institutional protocol number: OKU-2016146.

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.

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.

Role of endoscopic third ventriculostomy at infected cerebrospinal fluid shunt removal.

OBJECT: Cerebrospinal fluid shunt infection is distressing, especially in the pediatric population. Usually, infected CSF shunts are removed, and after temporary external CSF drainage, reinsertion of the CSF shunt is necessary. Unfortunately, it is not rare to encounter CSF reinfection after shunt renewal, and furthermore, the reinserted CSF shunt is at a considerable risk of malfunction. Endoscopic third ventriculostomy (ETV) is a potent option in managing CSF shunt infection, although ETV failure may occur more frequently when it is used to remove an infected shunt. The authors retrospectively evaluated CSF reinfection after using ETV during removal of infected CSF shunts; then the longevity of ETV and of successive reinserted ventriculoperitoneal shunts (VPSs) after ETV failure were also examined. METHODS: Children with shunted hydrocephalus were retrospectively reviewed, and data on their initial CSF shunt infections were extracted. Thirty-six children underwent VPS reinsertion (the VPS group), and 9 underwent ETV after removal of the infected CSF shunt (the ETV group). As the primary outcome, ETV efficacy against CSF reinfection within 6 months was analyzed by comparing the reinfection rates, and the risk factors for CSF reinfection were analyzed by logistic regression. The longevity of the reinserted shunt in the VPS group was calculated using the Kaplan-Meier method, which was compared with ETV longevity as the secondary outcome, and also with the longevity of reinserted VPSs in the ETV group after ETV failure as the tertiary outcome. RESULTS: Reinfection of CSF was seen in 27.8% of children in the VPS group. Among 9 children in the ETV group, only 1 (11.1%) had CSF reinfection. However, logistic regression analysis failed to show that performing ETV was a significant factor protecting against CSF reinfection: the significant risk factors were younger age at reinsertion of VPS or ETV (p = 0.037) and a history of shunt revisions (p = 0.011). The longevity of reinserted VPSs in the VPS group was calculated to be 658 ± 166.3 days (mean ± SE). Longevity of ETV was compared in the analysis of the secondary outcome, which was 929.2 ± 511.1 days, and there were no significant differences between these durations. Only 2 ETVs stayed patent, and a VPS was eventually implanted in the other 7 children. The longevity of this reinserted VPS in the ETV group, calculated based on these 7 children, was 2011.1 ± 540.7 days, which was confirmed to be longer than that in the VPS group (p = 0.031). CONCLUSIONS: Although the protective effect of using ETV during removal of an infected CSF shunt on reinfection is marginal, the ETV longevity can be considered equivalent to that of reinserted VPSs. Even if ETV failure occurs, the reinserted VPS has significantly better longevity than a VPS reinserted without using ETV, and use of ETV during infected CSF shunt removal can be considered a potent alternative or at least an adjunct to VPS reinsertion.

Ruptured anterior communicating artery aneurysm associated with anterior cranial fossa dural arteriovenous fistula--case report.

A 77-year-old man presented with an extremely rare association of anterior cranial fossa dural arteriovenous fistula (AVF) with anterior communicating artery (ACoA) aneurysm manifesting as consciousness deterioration due to intracerebral hemorrhage in the left frontal lobe and diffuse subarachnoid hemorrhage. Angiography confirmed the association of a dural AVF fed by both ethmoidal arteries and an ACoA aneurysm. Surgery for these two lesions was performed concurrently, and the ACoA aneurysm was found to be responsible for the hemorrhage. This association seems incidental, but is clinically significant since the preoperative determination of the bleeding point is difficult. We conclude that these two lesions should be treated simultaneously, to avoid leaving the ruptured point untreated.

Limited efficacy of endoscopic third ventriculostomy for hydrocephalus following aneurysmal subarachnoid hemorrhage.

Endoscopic third ventriculostomy (ETV) has not been recognized as a surgical option for hydrocephalus following aneurysmal subarachnoid hemorrhage (SAH), since hydrocephalus following aneurysmal SAH is considered to result from the communicating component. However, obstructions in the ventricular system may exist, so ETV could help resolve the condition. The present study evaluated the efficacy of ETV for hydrocephalus appearing within one month after aneurysmal SAH. This prospective study evaluated a total of 118 patients admitted to our hospital with aneurysmal SAH. Nine of 66 surgically treated patients suffered hydrocephalus within one month after aneurysmal SAH and 8 underwent ETV. Seven of these 8 patients showed no further ventricular enlargement or deterioration in consciousness, and required no external cerebrospinal fluid (CSF) drainage at least temporarily, and could commence early physical rehabilitation. Four patients also experienced cognitive improvements after ETV, but none made a full cognitive recovery. Ventriculoperitoneal (VP) shunt was implanted for one patient who did not respond to ETV, and the necessity of VP shunt was evaluated including the CSF removal test for the other patients, due to residual cognitive impairment even after initiating the rehabilitation. Five of the 8 patients eventually had VP shunts implanted, and 3 patients, including two patients who improved cognitively after ETV, had further cognitive improvements. ETV for hydrocephalus following aneurysmal SAH is likely to help manage intracranial pressure. ETV may improve cognitive impairment in some patients, but whether the maximum resolution is obtained only with ETV remains uncertain. VP shunt implantation should be the main treatment for hydrocephalus after aneurysmal SAH, but ETV can be employed as a temporary intervention in certain conditions, such as during the waiting period for the clearance of aneurysmal SAH.

The relationship between leukoaraiosis volume and parameters of carotid artery duplex ultrasonographic scanning in asymptomatic diabetic patients.

The significance of asymptomatic leukoaraiosis is unknown although cerebral microangiopathy is regarded as its pathology. To confirm the relationship between leukoaraiosis and cerebral microangiopathy, the pulsatility index (PI) at the cervical internal carotid artery (CA) which has been proposed as an indicator of microangiopathy, was evaluated in relation to leukoaraiosis. With 122 asymptomatic diabetic patients, leukoaraiosis volume was calculated with magnetic resonance imaging and its correlation with age, microalbuminuria and parameters of extracranial CA duplex ultrasonographic scanning were analyzed. The leukoaraiosis volume correlated with PI on the right side (p=0.027), and intima-media thickness on the left (p=0.017). However multivariate analysis indicated that age alone was a significant independent factor, positively correlating with leukoaraiosis volume on both sides (p<0.0001 on both sides). The underlying pathology of leukoaraiosis should be multifactorial. Further exploration is necessary to distinguish "ischemic" and "non-ischemic" leukoaraiosis.