Headache characteristics to screen for cervicocerebral artery dissection in patients with acute onset unusual headache.

OBJECTIVES: The aim of this preplanned primary analysis was to investigate the clinical manifestations of headache to screen for CAD patients with acute onset headache only. BACKGROUND: Spontaneous cervicocerebral artery dissection (CAD) with acute onset headache is not rare in clinical practice; however, it is underdiagnosed. On the other hand, subsequent infarction or subarachnoid hemorrhage mainly occurs within 1 week of headache onset. METHODS: Between April 2017 and January 2022, we conducted a single-center, cross-sectional retrospective study on 197 consecutive referred patients from neurosurgical outpatient clinics with acute onset unusual headache (stronger or longer headache than usual). All patients underwent magnetic resonance imaging to screen for secondary headache and were diagnosed based on the diagnostic protocol. We examined patient background data and the following headache characteristics: distribution, condition at the onset of headache, accompanying vomiting or nausea, worsening headache, and analgesic effects against headache. These factors were analyzed to identify independent diagnostic predictors of CAD. In this study, the rate of missing data was 41% for improvement of headache by analgesia and multiple imputation by chained equations was performed. RESULTS: A total of 93 patients (46 men and 47 women; mean age: 48 years, range: 25-73 years) were diagnosed with CAD. Univariate logistic regression analysis showed CAD was associated with current smoking, systolic blood pressure >140 mmHg, unilateral headache, worsening headache, and no headache improvement by analgesia. Unilateral, worsening headache and no headache improvement by analgesia remained independent diagnostic predictors in multivariable logistic regression after multiple imputation. No headache improvement by analgesia had the highest sensitivity (86%), while worsening headache had the highest specificity (84%). CONCLUSIONS: CAD needs to be considered in patients with unilateral, worsening headache and no headache improvement by analgesia.

Association between low levels of anti-inflammatory cytokines during pregnancy and postpartum depression.

AIM: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. METHODS: A nested, case-control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age-matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three-generation cohort. Concentrations of nine plasma cytokines (IFN-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, and TNF-α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. RESULTS: Cross-sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL-4 levels during pregnancy and after delivery than the control group, and that plasma IL-4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL-10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL-10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN-γ, IL-6, IL-12p40, and TNF-α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. CONCLUSIONS: These results suggest a potential protective effect of the anti-inflammatory cytokines IL-4 and IL-10 during pregnancy against the development of PPD.

N-Acetylcysteine Suppresses Microglial Inflammation and Induces Mortality Dose-Dependently via Tumor Necrosis Factor-α Signaling.

N-acetylcysteine (NAC) is an antioxidant that prevents tumor necrosis factor (TNF)-α-induced cell death, but it also acts as a pro-oxidant, promoting reactive oxygen species independent apoptosis. Although there is plausible preclinical evidence for the use of NAC in the treatment of psychiatric disorders, deleterious side effects are still of concern. Microglia, key innate immune cells in the brain, play an important role in inflammation in psychiatric disorders. This study aimed to investigate the beneficial and deleterious effects of NAC on microglia and stress-induced behavior abnormalities in mice, and its association with microglial TNF-α and nitric oxide (NO) production. The microglial cell line MG6 was stimulated by Escherichia coli lipopolysaccharide (LPS) using NAC at varying concentrations for 24 h. NAC inhibited LPS-induced TNF-α and NO synthesis, whereas high concentrations (≥30 mM) caused MG6 mortality. Intraperitoneal injections of NAC did not ameliorate stress-induced behavioral abnormalities in mice, but high-doses induced microglial mortality. Furthermore, NAC-induced mortality was alleviated in microglial TNF-α-deficient mice and human primary M2 microglia. Our findings provide ample evidence for the use of NAC as a modulating agent of inflammation in the brain. The risk of side effects from NAC on TNF-α remains unclear and merits further mechanistic investigations.

Sex-Dependent Effects of the APOE ɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults.

The APOE ɛ4 allele is associated with a risk of Alzheimer's disease in the elderly, with the association being pronounced in females. Conversely, findings of the effects of the APOE ɛ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ɛ4 allele on cognitive functions as well as brain structures among 1258 young adults. After adjusting for multiple comparisons, there were significant effects of the interaction between sex and the number of APOE ɛ4 allele on some speed tasks (e.g., simple processing speed tasks and the reverse Stroop task) as well as on regional white matter volume (rWMV). The observed sex-genotype interaction conferred better cognitive performance and greater rWMV in the anterior frontal and precentral white matter areas in females having more APOE ɛ4 alleles and reduced rWMV in the same areas in male having more APOE ɛ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ɛ4 allele in females.

Deficient Autophagy in Microglia Aggravates Repeated Social Defeat Stress-Induced Social Avoidance.

Major depressive disorder (MDD) is associated with repeated exposure to environmental stress. Autophagy is activated under various stress conditions that are associated with several diseases in the brain. This study was aimed at elucidating the autophagy signaling changes in the prefrontal cortex (PFC) under repeated social defeat (RSD) to investigate the involvement of microglial autophagy in RSD-induced behavioral changes. We found that RSD stress, an animal model of MDD, significantly induced initial autophagic signals followed by increased transcription of autophagy-related genes (Atg6, Atg7, and Atg12) in the PFC. Similarly, significantly increased transcripts of ATGs (Atg6, Atg7, Atg12, and Atg5) were confirmed in the postmortem PFC of patients with MDD. The protein levels of the prefrontal cortical LC3B were significantly increased, whereas p62 was significantly decreased in the resilient but not in susceptible mice and patients with MDD. This indicates that enhanced autophagic flux may alleviate stress-induced depression. Furthermore, we identified that FKBP5, an early-stage autophagy regulator, was significantly increased in the PFC of resilient mice at the transcript and protein levels. In addition, the resilient mice exhibited enhanced autophagic flux in the prefrontal cortical microglia, and the autophagic deficiency in microglia aggravated RSD-induced social avoidance, indicating that microglial autophagy involves stress-induced behavioral changes.

Diagnostic accuracy of MR vessel wall imaging at 2 weeks to predict morphological healing of vertebral artery dissection.

OBJECTIVES: The spontaneous healing of non-hemorrhagic intracranial vertebral artery dissection (VAD) may be associated with the stabilization of intramural hematoma (IMH). We previously suggested that the signal intensity of IMH increases until approximately 2 weeks in VAD with spontaneous healing. We herein investigated the diagnostic accuracy of the signal intensity of IMH at 2 weeks to predict the spontaneous healing of VAD. METHODS: From April 2017 to April 2021, we prospectively investigated patients with non-hemorrhagic VAD who underwent vessel wall imaging (VWI). Morphological healing of VAD was evaluated by MR angiography three months after its onset. The relative signal intensity (RSI) of IMH against the posterior cervical muscle on VWI was calculated. Univariate and multivariate analyses were performed on factors associated with the spontaneous healing of VAD among patient baseline data, vascular morphology at the diagnosis, and RSI parameters. RESULTS: Forty-eight patients (23 men and 25 women; mean age: 51 years, range: 34-73 years) with 50 non-hemorrhagic VAD were included in the present study. Spontaneous healing was observed in 28 VAD (56%). RSI two weeks after the onset of VAD (RSI2w) and morphological feature such as the string sign were associated with spontaneous healing, respectively. The multivariate logistic regression analysis identified RSI2w as an independent predictive factor of spontaneous healing (OR: 7.3; 95% CI, 1.9-28, p = 0.004). The cut-off value for RSI2w to predict spontaneous healing was 1.22 (AUC = 0.90, sensitivity: 91%, specificity: 82%). CONCLUSION: RSI2w predicted the spontaneous healing of non-hemorrhagic VAD 3 months after its onset.

Effects of additives on reaction of nucleosides with UV light in presence of uric acid and salicylic acid.

Recently, we reported that uric acid and salicylic acid are photosensitizers of the reaction of nucleosides with UV light via radical formation and energy transfer, respectively. In the present study, effects of 45 biologically relevant compounds on nucleoside reactions photosensitized by uric acid and salicylic acid were examined. When a mixed solution of 2'-deoxycytidine, 2'-deoxyguanosine, thymidine, and 2'-deoxyadenosine with uric acid was irradiated with UV light of a wavelength longer than 300 nm, all the nucleosides decreased. The addition of antioxidants suppressed the consumption of nucleosides. When the UV reaction of nucleosides was conducted with salicylic acid, thymidine decreased almost exclusively. Several antioxidants such as ascorbates, thiols, catecholamines, trans-2-hexen-1-ol, penicillin G, and NaHSO3 enhanced the consumption of thymidine, although the other antioxidants suppressed it. The results suggest that antioxidants may be beneficial to protect against DNA damage by photosensitization via radical formation, but that several of them may be detrimental as they facilitate DNA damage by photo-sensitization via energy transfer.

Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex.

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.

The delivery of a placenta/fetus with high gonadal steroid production contributes to postpartum depressive symptoms.

BACKGROUND: A correlation between gonadal steroids and depressive symptoms during the perinatal period has long been suggested; however, the underlying mechanism for this relationship remains unclear. METHODS: This study was designed to examine the correlation between gonadal steroid concentrations of umbilical cord blood and postpartum depressive symptoms as well as longitudinal alterations in maternal plasma gonadal steroid concentrations among 204 perinatal women. The levels of postpartum depressive state at 1 month postpartum were evaluated using the Edinburgh Postnatal Depression Scale. RESULTS: Umbilical progesterone, estradiol, and testosterone levels were significantly higher in infants delivered by depressed mothers (870.7 ± 281.7 ng/ml, 8607.7 ± 4354.6 pg/ml, and 2.5 ± 0.9 ng/ml, respectively) than those delivered by nondepressed mothers (741.3 ± 324.0 ng/ml, 5221.9 ± 3416.3 pg/ml, and 2.1 ± 0.6 ng/ml, p < .01, p < .05, and p < .05, respectively). Postpartum plasma progesterone levels of depressed mothers (3.5 ± 3.1 ng/ml) measured in the early postpartum period were significantly lower than those of nondepressed mothers (9.1 ± 9.7 ng/ml, p < .01). The decrease in progesterone from mid-pregnancy to the early postpartum period was significantly higher in depressed mothers than in nondepressed mothers. Subgroup analyses specific to primiparas or multiparas indicated that a significant drop of progesterone was seen only in primiparas. CONCLUSION: The current study suggests that the delivery of a placenta/fetus with high gonadal steroid production may cause a wider range of fluctuations in maternal plasma gonadal steroid concentrations, which may be concurrent with postpartum depressive symptoms.

Accuracy of thin-slice model-based iterative reconstruction designed for brain CT to diagnose acute ischemic stroke in the middle cerebral artery territory: a multicenter study.

PURPOSE: Model-based iterative reconstruction (MBIR) yields higher spatial resolution and a lower image noise than conventional reconstruction methods. We hypothesized that thin-slice MBIR designed for brain CT could improve the detectability of acute ischemic stroke in the middle cerebral artery (MCA) territory. METHODS: Included were 41 patients with acute ischemic stroke in the MCA territory; they were seen at 4 medical centers. The controls were 39 subjects without acute stroke. Images were reconstructed with hybrid IR and with MBIR designed for brain CT at slice thickness of 2 mm. We measured the image noise in the ventricle and compared the contrast-to-noise ratio (CNR) in the ischemic lesion. We analyzed the ability of reconstructed images to detect ischemic lesions using receiver operating characteristics (ROC) analysis; 8 observers read the routine clinical hybrid IR with 5 mm-thick images, while referring to 2 mm-thick hybrid IR images or MBIR images. RESULTS: The image noise was significantly lower on MBIR- than hybrid IR images (1.2 vs. 3.4, p < 0.001). The CNR was significantly higher with MBIR than hybrid IR (6.3 vs. 1.6, p < 0.001). The mean area under the ROC curve was also significantly higher on hybrid IR plus MBIR than hybrid IR (0.55 vs. 0.48, p < 0.036). Sensitivity, specificity, and accuracy were 41.2%, 88.8%, and 65.7%, respectively, for hybrid IR; they were 58.8%, 86.1%, and 72.9%, respectively, for hybrid IR plus MBIR. CONCLUSION: The additional thin-slice MBIR designed for brain CT may improve the detection of acute MCA stroke.

Monitoring Intramural Hematoma on Vessel Wall Imaging to Evaluate the Healing of Intracranial Vertebral Artery Dissection.

OBJECTIVE: Unruptured intracranial vertebral artery dissection (VAD) generally heals spontaneously. A chronological evaluation of intramural hematoma (IMH) using T1-weighted vessel wall imaging (VWI) may provide a more detailed understanding of the pathophysiology of VAD. We herein investigated the relationship between chronological signal changes in IMH on VWI and the spontaneous healing of VAD. MATERIALS AND METHODS: We retrospectively investigated 26 patients with 27 unruptured VADs who underwent magnetic resonance (MR) imaging more than three times during the follow-up period. Morphological changes were evaluated using MR angiography (MRA). The relative signal intensity (RSI) of IMH against the posterior cervical muscle on T1-weighted VWI was calculated. The ratio of chronological RSI changes was defined as follows: maximum RSI/minimum RSI (RSI max/min). Based on the median value of RSI max/min, 27 VADs were divided into VADs with and without chronological RSI changes. Statistical analyses were performed to compare clinical and radiological findings between the two groups. RESULTS: Spontaneous healing occurred in 17 out of 27 VADs (63%). The median value of RSI max/min was 1.48. The RSI of VADs with chronological RSI changes (RSI max/min ≥ 1.48) increased until three weeks after their onset and decreased over time, while that of VADs without chronological RSI changes (RSI max/min < 1.48) showed no change. The frequency of healing was significantly higher in VADs with than without chronological RSI changes (100% vs 23%, p < 0.0001). CONCLUSIONS: Chronological signal changes in IMH on T1-weighted VWI have potential as a diagnostic imaging marker of the spontaneous healing of VAD.

Peptidylarginine Deiminase 4 as a Possible Biomarker of Plaque Instability in Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: Neutrophil extracellular traps (NETs) exhibit pro-inflammatory and pro-thrombotic properties. However, they have only been reported as important regulators in atherosclerosis, especially in atherothrombosis. We investigated the presence of NETs and plaque instability in patients with carotid artery stenosis. MATERIAL AND METHODS: A total of 39 consecutive patients with carotid artery stenosis were evaluated. All patients underwent carotid artery stenting (CAS) with dual protection (simultaneous flow reversal + distal filter) and blood aspiration as a method of distal embolism prevention. Local arterial blood was aspirated at the stent site and peptidylarginine deiminase 4 (PAD4), which is essential for the formation of NETs, was measured. The relationships between PAD4 and the patient profile, blood examination and plaque data were investigated. RESULTS: The mean value of PAD4 in local arterial blood in CAS was 0.5 ng/ml. Bivariate analysis demonstrated that PAD4 was associated with the neutrophil to lymphocyte ratio (p = 0.007), high-density lipoprotein (p = 0.02), triglycerides to high-density lipoprotein ratio (p = 0.007), ulceration (p = 0.02) and plaque contrast enhancement on T1 black blood imaging (p = 0.03). In multiple linear regression analyses, PAD4 was correlated with the neutrophil to lymphocyte ratio (p = 0.01) and ulceration (p = 0.01, cut-off value: 0.49 odds ratio: 19.3). CONCLUSIONS: PAD4, representative of the presence of NETs, was high in carotid plaques with unstable features. The neutrophil to lymphocyte ratio in peripheral blood was suggested to be a biomarker of vulnerable plaques. Elucidating the role of NETs may aid in clarifying factors that promote the instability of carotid plaques.

A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity.

Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women. Here we investigated the sex-specific effects of the CACNA1C variant rs1024582 on psychiatry-related traits, brain activity during tasks and rest, and brain volume in 1207 normal male and female subjects. After correcting for multiple comparisons, there were significant interaction effects between sex and the minor allele of this polymorphism on the hostile behavior subscale scores of the Coronary-Prone Type Scale mediated by higher scores in female carriers of the minor allele. Imaging analyses revealed significant interaction effects between sex and the minor allele on fractional amplitude of low-frequency fluctuations in the right dorsolateral prefrontal cortex and on brain activity during the 2-back task in areas of the right posterior cingulate cortex, right thalamus, and right hippocampus, which were all mediated by reduced activity in female carriers of the minor allele. Our results demonstrated that the rs1024582 risk variant of CACNA1C is associated with reduced activity in the frontolimbic regions at rest and during a working memory task as well as with greater hostility in females in the healthy population.

Early venous filling after reperfusion therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Early venous filling after endovascular mechanical thrombectomy in acute ischemic stroke (AIS) is a specific finding that may serve as a biomarker for intracranial hemorrhage. However, the pathophysiology of early venous filling and postoperative hemorrhage remains unclear. The aim of this study was to investigate correlation between early venous filling and various factors involving patient demographics and perioperative imaging. METHODS: We prospectively analyzed 35 patients with AIS due to cardioembolism (CE) who underwent successful acute revascularization (TICI ≥2). Ischemic lesions were scored by magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI). Outcomes were assessed using the modified Rankin Scale (mRS) 90 days after stroke onset. Blood flow analysis was evaluated by MRI with arterial spin labeling (ASL). Early venous filling was assessed by digital subtraction angiography (DSA). Univariate analysis was performed to investigate correlations between early venous filling and patient demographics and imaging findings. RESULTS: Early venous filling was observed in 22 of 35 (66%) patients after reperfusion therapy. There was a significant correlation between early venous filling and DWI-ASPECTS (6.2 vs 8.8, p=0.0003), outcome (5 vs 9, p=0.006), hyperperfusion (17 vs 1, p< 0.0001), and hemorrhagic transformation (17 vs 1, p=0.005). CONCLUSIONS: This comprehensive study revealed that early venous filling after reperfusion therapy is associated with postoperative hyperperfusion. Early venous filling may be a marker of the process of hyperperfusion, leading to hemorrhage and an unfavorable outcome. Detection of early venous filling may be an important finding on DSA for subsequent intensive perioperative management.

Blood Flow Pattern Analysis for Carotid Plaque Evaluation.

BACKGROUND AND PURPOSE: Previous studies suggested that turbulent flow is closely related to plaque vulnerability. Two-dimensional (2D) flow analysis is a novel modality that enables real-time blood flow analysis by picturing particle movement in the contrast medium. We evaluated flow patterns in the carotid plaque to investigate the correlation between blood flow and plaque vulnerability. MATERIAL AND METHODS: A total of 36 consecutive patients with cervical carotid artery stenosis were evaluated. The flow pattern of carotid artery stenosis was evaluated using 2D real-time flow analysis in the digital subtraction angiography (DSA). The flow pattern was classified into either turbulent or laminar flow as vectors. Plaque vulnerability was evaluated on MR plaque imaging. Univariate analysis was performed to assess the correlation between the flow pattern and plaque features. RESULTS: The turbulent pattern was identified in 28 of 36 plaques (77.8%). Turbulence around plaques was significantly associated with Gadolinium enhancement (P = .0004). The maximum degree of stenosis (P = .0005) and concomitant ulceration (P = .02) were significantly associated with the turbulent pattern. There was no relationship between the turbulent pattern and clinical neurological symptoms. CONCLUSIONS: In the present study, the majority of carotid plaques exhibited a turbulent flow pattern, which was significantly associated with Gadolinium enhancement on MR plaque imaging and morphologic factors. Thus, real-time flow analysis may clarify the pathophysiology of plaque instability and the formation of ulceration.

Magnetic resonance vessel wall imaging predicts morphological deterioration in unruptured intracranial artery dissection.

OBJECTIVE: The mechanism involved in progression of unruptured intracranial artery dissection (IAD) is poorly understood. We investigated the relationship between contrast enhancement of dissecting lesions on magnetic resonance vessel wall imaging (MR-VWI) and unruptured IAD progression on the hypothesis that this finding might predict its instability. METHODS: A total of 49 unruptured IADs were investigated retrospectively. Three-dimensional T1-weighted fast spin-echo sequences were obtained before and after injection of contrast medium, and the dissecting lesion/pituitary stalk contrast enhancement ratio (CRstalk) was calculated. Unruptured IAD progression was defined as morphological deterioration; progressive dilatation or stenosis. The relations between unruptured IAD progression and potential risk factors were statistically investigated. RESULTS: Morphological deterioration was demonstrated in eleven of 49 unruptured IADs (22 %). The CRstalk value and male predominance was significantly higher in progressed IADs than stable ones (1.0 vs. 0.65; p = 0.0035, 82% vs 37%; p= 0.015, respectively). On stepwise multivariable logistic regression analysis, the CRstalk value was independently associated with unruptured IAD progression with odds ratio of 102.5 (95% CI, 2.59-4059, P=0.0013). The optimal cutoff value of CRstalk to estimate IADs with progression was 0.87 (sensitivity, 0.82; specificity, 0.74). Multimodalic images showed contrast enhancement on VWI corresponded to residual stagnant flow in dissecting lesions. CONCLUSIONS: Quantitative analysis of contrast enhancement on VWI could predict instability of unruptured IADs. Contrast enhancement in dissecting lesions would be a clue to understand the mechanism of unruptured IAD progression.

Vessel Wall Imaging of Evolving Unruptured Intracranial Aneurysms.

Background and Purpose- Unruptured intracranial aneurysms (UIAs) have various scenarios of growth and rupture. Magnetic resonance vessel wall imaging can detect aneurysmal wall thickening with inflammation and neovascularization. This study was performed to explore the vessel wall imaging findings of UIAs with consecutive follow-up. Methods- A total of 60 aneurysms with serial angiography over 2 years (mean period, 49 months, range, 24-192 months) were evaluated by vessel wall imaging. UIAs were morphologically categorized into 3 patterns: stable, whole sac expansion, or daughter sac formation. Aneurysm wall enhancement (AWE) was evaluated after administration of gadolinium. Results- Thirty-three of the 60 UIAs (55%) demonstrated no morphological changes, whereas 16 UIAS (27%) showed whole sac expansion and 11 UIAs (18%) demonstrated daughter sac formation. AWE was significantly less frequent in stable UIAs compared with UIAs showing morphological changes ( P<0.01). Aneurysms with daughter sac formation showed a significantly higher frequency of AWE than those demonstrating whole sac expansion. In the majority of UIAs with daughter sac formation, AWE was detected in the main aneurysm and not in the developing component. Conclusions- UIAs demonstrate various modes of growth. The pattern of AWE might be useful for identifying unfavorable morphological changes of UIAs.

Minimal amount of tissue-based pH measurement to improve quality control in neuropsychiatric post-mortem brain studies.

AIM: Tissue pH and RNA integrity are crucial quality-control indicators of human post-mortem brain tissues in the identification of the pathogeneses of neuropsychiatric disorders, but pH has not been measured as often due to limitations in the amount of tissue available. This study was designed to develop and validate a protocol for tissue pH evaluation using a minimal amount of human post-mortem tissues. METHODS: A procedure that included a proper ratio of brain tissue weight to water for homogenization and the duration of homogenization was designed based on preliminary experiments using mouse brain tissues. The minimal (10 mg) and typical (100 mg) amounts of post-mortem brain tissue from 52 subjects were homogenized in 5 volumes (50 µL/10 mg tissue) and 10 volumes (1000 µL/100 mg tissue) of nuclease-free water and subjected to pH measurements using an InLab Ultra micro pH electrode. RESULTS: The pH values based on the new protocol using a minimal amount of tissue significantly correlated with measurements of the standard protocol (r2 = 0.86). The correlation coefficients of the pH values between gray and white matter of the same brain region, and the values between different brain regions were 0.73 and 0.54, respectively. CONCLUSION: The proposed protocol used one-tenth of the tissue amount of current standard protocol and enabled us to evaluate the exact quality of post-mortem brain tissue subjected to subsequent analyses. The application of this protocol may improve the detection of biological phenomena of interest in post-mortem brain studies by diminishing confounding factors.

Hyperperfusion after Endovascular Reperfusion Therapy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke (AIS) may display prolonged neurological deficits and conscious disturbance even after successful endovascular thrombectomy. We hypothesized that hemodynamic change after reperfusion might influence outcomes. This study investigated the factors causing hyperperfusion and outcomes. METHODS: We retrospectively analyzed 27 patients with AIS who underwent successful acute revascularization (TICI: Thrombolysis in Cerebral Infarction 2b + 3). Changes of the neurological status were precisely assessed by using the National Institutes of Health Stroke Scale (NIHSS). Ischemic lesions were scored by MRI with diffusion-weighted imaging (DWI), and blood flow in the middle cerebral artery territory was assessed by MRI with arterial spin labeling. Univariate analysis was performed to investigate correlations between hyperperfusion and demographic factors or the functional prognosis. RESULTS: Thirteen of the 27 (48%) patients developed hyperperfusion after reperfusion. A significant correlation was seen between hyperperfusion and the improvement of NIHSS at 24 hours (P < .0001), the duration of disturbance of consciousness (days) (P < .0001), DWI-ASPECTS (P = .001), hemorrhagic transformation (P = .007), and mRS less than or equal to 2 at 90 days (P = .007). CONCLUSIONS: The present findings suggested that some patients with AIS will develop hyperperfusion after successful acute revascularization. The status of hyperperfusion could prolong conscious disturbance and affect outcomes. Since the mechanism of hyperperfusion after revascularization depends on stroke etiology, diagnosing the type of ischemic stroke in the acute stage is important for managing postoperative treatment.