Association between preoperative cortical magnetic susceptibility and postoperative changes in the cerebral blood flow on cognitive improvement following carotid endarterectomy.

INTRODUCTION: While patients who experience improved cognition following carotid endarterectomy (CEA) typically demonstrate restored brain perfusion after the procedure, it is worth noting that less than 50% of patients in whom postoperative cerebral blood flow (CBF) restoration is achieved actually show improved cognition after postoperatively. This suggests that factors beyond the mere restoration of CBF may play a role in postoperative cognitive improvement. Increased iron deposition in the cerebral cortex may cause neural damage, and quantitative susceptibility mapping (QSM) obtained using magnetic resonance imaging (MRI) quantifies magnetic susceptibility in the cerebral cortex, allowing for the assessment of iron deposition in vivo. The purpose of the present study was to determine whether preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. METHODS: Brain MRI with a three-dimensional gradient echo sequence was preoperatively performed in 53 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), and QSM with brain surface correction and vein removal was obtained. Cortical magnetic susceptibility was measured in the cerebral hemisphere ipsilateral to surgery on QSM. Preoperatively and at two months after the surgery, brain perfusion single-photon emission computed tomography (SPECT) and neuropsychological assessments were conducted. Using these collected data, we evaluated alterations in CBF within the affected hemisphere and assessed cognitive improvements following the operation. RESULTS: A logistic regression analysis showed that a postoperative greater increase in CBF (95% confidence interval [CI], 1.06-1.90; p = 0.0186) and preoperative lower cortical magnetic susceptibility (95% CI, 0.03-0.74; p = 0.0201) were significantly associated with postoperatively improved cognition. Although sensitivity, specificity, and positive- and negative-predictive values with the cutoff value lying closest to the upper left corner of a receiver operating characteristic curve for the prediction of postoperatively improved cognition did not differ between postoperative changes in CBF and preoperative cortical magnetic susceptibility, the specificity and the positive-predictive value were significantly greater for the combination of postoperative changes in CBF and preoperative cortical magnetic susceptibility (specificity, 95% CI, 93-100%; positive-predictive value 95% CI, 68-100%) than for the former parameter alone (specificity, 95% CI, 63-88%; positive-predictive value 95% CI, 20-64%). CONCLUSION: Preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA.

Association between preoperative white matter hyperintensities and postoperative new ischemic lesions on magnetic resonance imaging in patients with cognitive decline after carotid endarterectomy.

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78-28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42-571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA.

Predictors of aneurysmal occlusion following intracranial aneurysms treatment with pipeline embolization device.

PURPOSE: Pipeline embolization device (PED) is thought to induce aneurysmal occlusion through diversion of flow away from the aneurysmal sac with subsequent thrombosis and endothelialization. The impact of different factors especially hypertension (HTN)-a known predisposing factor to hypercoagulability and altered endothelial function-on aneurysmal occlusion after flow diversion has not been studied. We sought to determine predictors of aneurysmal occlusion following PED treatment focusing on impact of blood pressure. METHODS: Database of patients with cerebral aneurysms treated with PED from 2013 to 2019 at our institution was retrospectively reviewed. Patients were defined as hypertensive if (1) they had a documented history of HTN requiring anti-HTN medications or (2) average systolic blood pressure on three measurements was > 130 mmHg. The primary outcome was aneurysm occlusion status at the last imaging follow-up. Multivariable logistic regression model was constructed to assess the effect of HTN on occlusion, controlling for age, smoking, aneurysmal size, fusiform morphology, posterior circulation location, and incorporated branches. RESULTS: A total of 331 aneurysms in 294 patients were identified for this analysis. The mean age was 59 years (79.9% female). Fifty-five percent of the cohort were classified as hypertensive. When controlling for other potential confounders, hypertensive patients trended toward higher odds of achieving complete occlusion compared to non-hypertensive patients (OR = 2.05; 95% CI = 0.99-4.25; p = 0.052). Meanwhile, age (OR = 0.91; 95% CI = 0.88-0.95; p < 0.001) and an incorporated branch into an aneurysm (OR = 0.22; 95% CI = 0.08-0.58; p < 0.002) were associated with decreased odds for complete aneurysmal occlusion. CONCLUSION: Hypertensive patients show a trend toward higher odds of achieving complete occlusion when controlling for potential confounders. The HTN-induced hypercoagulable state, enhanced endothelial activation, and altered extracellular matrix regulation might be the contributing factors. Further research is warranted to explore clinical implications of these findings.

Prediction of cerebral hyperperfusion following carotid endarterectomy using intravoxel incoherent motion magnetic resonance imaging.

OBJECTIVES: One of the risk factors for cerebral hyperperfusion following carotid endarterectomy (CEA) is a chronic reduction in cerebral perfusion pressure due to internal carotid artery (ICA) stenosis, which is clinically detected as increased cerebral blood volume (CBV). The perfusion fraction (f) is one of the intra-voxel incoherent motion (IVIM) parameters obtained using magnetic resonance (MR) imaging that theoretically reflects CBV. The present study aimed to determine whether preoperative IVIM-f on MR imaging predicts development of cerebral hyperperfusion following CEA. MATERIALS AND METHODS: Sixty-eight patients with unilateral ICA stenosis (≥ 70%) underwent preoperative diffusion-weighted 3-T MR imaging, and IVIM-f maps were generated from these data. Quantitative brain perfusion single-photon emission computed tomography (SPECT) was performed before and immediately after CEA. Regions-of-interest (ROIs) were automatically placed in the bilateral middle cerebral artery territories in all images using a three-dimensional stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on IVIM-f maps. RESULTS: Nine patients (13%) exhibited postoperative hyperperfusion (cerebral blood flow increases of ≥ 100% compared with preoperative values in the ROIs on brain perfusion SPECT). Only high IVIM-f ratios were significantly associated with the occurrence of postoperative hyperperfusion (95% confidence interval, 253.8-6774.2; p = 0.0031) on logistic regression analysis. The sensitivity, specificity, and positive and negative predictive values of the IVIM-f ratio to predict the occurrence of postoperative hyperperfusion were 100%, 81%, 45%, and 100%, respectively. CONCLUSIONS: Preoperative IVIM-f on MR imaging can predict development of cerebral hyperperfusion following CEA.

Changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic moyamoya disease.

Periventricular anastomosis in moyamoya disease (MMD) is an unusual angiographic finding that arises from perforating arteries such as the lenticulostriate artery (LSA), thalamic artery (THA), and anterior choroidal artery (AChA). This anastomosis is associated with increased hemorrhagic risk in MMD and can be corrected by direct revascularization surgery. The present supplementary analysis on a prospective cohort aimed to elucidate changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Twenty-two patients with misery perfusion in the symptomatic cerebral hemisphere who underwent indirect revascularization surgery alone also underwent six-vessel cerebral angiography via arterial catheterization before and at 6 months after surgery. Before surgery, two patients (9%) had positive periventricular anastomosis from the LSA and another (5%) from the AChA; all three of these periventricular anastomoses regressed after surgery, but these changes were not statistically significant (p = 0.0833). The degree of formation of collateral vessels from the LSA significantly decreased after surgery (p = 0.0143), but the degree of collateral vessels from the THA or AChA did not differ between pre- and postoperative conditions. Eight patients with postoperative regression of the collateral vessels from any perforating artery exhibited postoperative rich collateral flow from indirect revascularization. Periventricular anastomosis tended to regress after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Collateral vessels formed from the LSA likely regressed after indirect revascularization surgery alone for such patients, but those vessels from the THA or AChA seldom changed.

Long-term outcomes, including the survival rate and period to death, in patients over 80 years old after ruptured cerebral aneurysm clipping.

OBJECTIVE: This study aimed to identify the long-term outcomes, including the survival rate, period to death, causes of death, and predictors of poor outcomes, in patients aged over 80 years who underwent surgical clipping for a ruptured anterior circulation aneurysm. MATERIALS AND METHODS: In this retrospective observational study, the medical records of patients from April 1, 1994, to June 30, 2019, were evaluated. All patients underwent surgical clipping within 72 h of subarachnoid hemorrhage (SAH) onset. Information on the patient, SAH, and outcomes were collected. RESULTS: The mean hospitalization and long-term follow-up periods for all patients were 54.5 days and 53.3 months, respectively. The period to death was significantly shorter in patients with modified Rankin scale (mRS) of 4-5 than for those with an mRS of 0-3 at discharge (p=0.001). The Kaplan-Meier method using the log-rank test demonstrated that patients with an mRS of 4-5 at discharge had a significantly lower survival rate compared to those with an mRS of 0-3 at discharge (p<0.05). Univariate analysis revealed that the proportion of patients with Hunt and Hess grade and presence of surgical complications were significantly larger in the group with an mRS of 4-5 than in that with an mRS of 0-3 at discharge (p=0.0013 and 0.011, respectively). Multivariate analysis demonstrated that presence of surgical complications was the only independent predictor of poor outcomes (p=0.043, odds ratio [OR] 7.937, 95% confidence interval [CI] 1.061-59.38). The Kaplan-Meier method using the log-rank test demonstrated that patients with surgical complications had a significantly lower survival rate compared to those with no surgical complications (p<0.05). CONCLUSIONS: Especially in patients aged over 80 years, those with H-H grade 2 and a good clinical condition can be candidates for surgical clipping, whereas avoiding surgical complications is essential for achieving good outcomes.

Outcomes of Medical Management Alone for Adult Patients with Cerebral Misery Perfusion Due to Ischemic Moyamoya Disease.

OBJECTIVES: Although revascularization surgery is recommended for adult patients with moyamoya disease (MMD) who present with ischemic symptoms due to hemodynamic compromise, the clinical course of such patients who are treated with medical management alone remains unclear. Here, we report outcomes of adult patients with cerebral misery perfusion due to ischemic MMD who received medical management alone. MATERIALS AND METHODS: We prospectively followed up patients who showed misery perfusion in the symptomatic cerebral hemisphere on 15O gas positron emission tomography (PET) and received strict medical management alone after refusing revascularization surgery. RESULTS: Of 57 patients who showed symptomatic misery perfusion on 15O gas PET, three (5%) were included into the present study. Two of these patients suffered further ischemic events at 7 and 8 months after inclusion, after which, their modified Rankin disability scale scores deteriorated. In the remaining patient, fatal intracerebral hemorrhage developed at 10 months after inclusion. CONCLUSIONS: These findings suggest that receiving medical management alone is associated with considerably poor outcomes for adult patients with cerebral misery perfusion due to ischemic MMD.

Sodium Variability and Probability of Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Vasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4-14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm. MATERIALS AND METHODS: A single-center retrospective analysis from 2007-2016 was conducted of aSAH patients. Daily serum sodium levels were recorded up to day 14 post-admission. Hyponatremia was defined as a serum sodium value of < 135 mEq/L. We evaluated the relationship to radiologic vasospasm, neurologic deterioration, functional status at discharge, and mortality. A repeated measures analysis using a mixed-effect regression model was performed to assess the interindividual relationship between serum sodium trends and outcomes. RESULTS: A total of 271 aSAH patients were included. There were no significant differences in interindividual serum sodium values over time and occurrence of radiographic vasospasm, neurologic deterioration, functional, or mortality outcomes (p = .59, p = .42, p = .94, p = .99, respectively) using the mixed-effect regression model. However, overall mean serum sodium levels were significantly higher in patients who had neurologic deterioration, poor functional outcome (mRS 3-6), and mortality. CONCLUSIONS: Serum sodium level variations are not associated with subsequent development of cerebral vasospasm in aSAH patients. These findings indicate that serum sodium may not have an impact on vasospasm, and avoiding hypernatremia may provide a neurologic, functional and survival benefit.

The role of TLR4 and HO-1 in neuroinflammation after subarachnoid hemorrhage.

This review on the mechanisms of neuroinflammation following subarachnoid hemorrhage will focus mainly on toll-like receptor 4 (TLR4), Heme Oxygenase-1 (HO-1), and the role of microglia and macrophages in this process. Vasospasm has long been the focus of research in SAH; however, clinical trials have shown that amelioration of vasospasm does not lead to an improved clinical outcome. This necessitates the need for novel avenues of research. Our work has demonstrated that microglial TLR4 and microglial HO-1, not only affects cognitive dysfunction, but also circadian dysrhythmia in a mouse model of SAH. To attempt to translate these findings, we have also begun investigating macrophages in the cerebrospinal fluid of SAH patients. The goal of this review is to provide an update on the role of TLR4, HO-1, and other signal transduction pathways in SAH-induced neuroinflammation.

Cigarette smoking and risk of intracranial aneurysms in middle-aged women.

BACKGROUND AND PURPOSE: We previously reported a single-centre study demonstrating that smoking confers a six-fold increased risk for having an unruptured intracranial aneurysm (UIA) in women aged between 30 and 60 years and this risk was higher if the patient had chronic hypertension. There are no data with greater generalisability evaluating this association. We aimed to validate our previous findings in women from a multicentre study. METHODS: A multicentre case-control study on women aged between 30 and 60 years, that had magnetic resonance angiography (MRA) during the period 2016-2018. Cases were those with an incidental UIA, and these were matched to controls based on age and ethnicity. A multivariable conditional logistic regression was conducted to evaluate smoking status and hypertension differences between cases and controls. RESULTS: From 545 eligible patients, 113 aneurysm patients were matched to 113 controls. The most common reason for imaging was due to chronic headaches in 62.5% of cases and 44.3% of controls. A positive smoking history was encountered in 57.5% of cases and in 37.2% of controls. A multivariable analysis demonstrated a significant association between positive smoking history (OR 3.7, 95%CI 1.61 to 8.50), hypertension (OR 3.16, 95% CI 1.17 to 8.52) and both factors combined with a diagnosis of an incidental UIA (OR 6.9, 95% CI 2.49 to 19.24). CONCLUSIONS: Women aged between 30 and 60 years with a positive smoking history have a four-fold increased risk for having an UIA, and a seven-fold increased risk if they have underlying chronic hypertension. These findings indicate that women aged between 30 and 60 years with a positive smoking history might benefit from a screening recommendation.

[Factors Contributing to Surgical Intervention for Subacute Subdural Hematoma Enlargement in Patients with Mild Head Injuries].

Delayed neurological deterioration following mild head injury(MHI)usually occurs within 24 hours. However, some cases require delayed surgical evacuation of an acute subdural hematoma(ASDH), owing to subacute progressive hematoma enlargement. This study aimed to determine radiological or clinical parameters associated with surgical intervention in ASDH cases in which surgery was not initially considered necessary. From 2010 to 2015, 64 patients were non-surgically treated for ASDH following MHI. We evaluated the various outcomes of eventual surgical ASDH evacuation after the first 48 hours following injury, due to hematoma enlargement and clinical deterioration. Univariate and multivariate analyses were applied to both the demographic and initial radiographic features to identify risk factors for ASDH progression and surgery. Overall, at the time of their last follow-up computed tomography, 57 patients(89%)demonstrated minimal ASDH or spontaneous hematoma resolution with conservative non-surgical management. The remaining 7 patients(11%)received delayed surgical ASDH evacuation a median of 5.1 days after the head trauma. There were no significant differences between the two groups for baseline characteristics, including age, prior history of anticoagulants, the presence of cerebral contusions, or subarachnoid hemorrhages. On multivariate analysis, use of antiplatelet drugs(p=0.013, OR=28, 95%CI=1.82-24)was independently associated with delayed hematoma evacuation. These data indicate that as much as 11% of patients with minimal ASDHs after MHI can deteriorate over the course of a week and then require surgical intervention, and that patients on concurrent antiplatelet medication require especially careful monitoring of hematoma progression.

Impaired leptomeningeal collateral flow contributes to the poor outcome following experimental stroke in the Type 2 diabetic mice.

Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects.

Impaired Collateral Flow Compensation During Chronic Cerebral Hypoperfusion in the Type 2 Diabetic Mice.

BACKGROUND AND PURPOSE: The presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion. METHODS: We examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in db/+ and db/db mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters. RESULTS: After unilateral CCAO, db/db mice exhibited diminished leptomeningeal collateral flow compensation compared with db/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO. db/db mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with db/+ mice. CONCLUSIONS: Type 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.

RF frequency sextupling via an optical two-tone signal generated from two modulation lightwaves from one Mach-Zehnder optical modulator.

An optical two-tone (OTT) signal is generated with a wide frequency separation, based on the suppression of ± 1st-order optical sidebands without using optical band-rejection filtering. By combining two orthogonally polarized lightwaves modulated with different modulation indices, each optical sideband constituting the combined lightwave has a different polarization. Some of these optical sidebands can be suppressed using a polarizer. By using a single Mach-Zehnder optical modulator to achieve two optical modulations, an OTT signal with a 60-GHz frequency-separation was successfully generated with 32-dB suppression of undesired ± 1st-order optical sidebands. An rf signal was also obtained from the OTT signal.

Optical two-tone signal generation without use of optical filter for photonics-assisted radio-frequency quadrupling.

Optical two-tone (OTT) signal generation is demonstrated without optical wavelength filtering for wavelength-free operation in radio-frequency (RF) upconversion assisted by photonics. This principle is based on selective polarization manipulation for the optical carrier; the optical carrier's polarization is first tilted, and the carrier is then suppressed using a polarizer. Owing to optimized conditions obtained from theoretical calculation and the high polarization extinction ratio achieving a 25.7-dB carrier suppression, a 40-GHz separated OTT signal is successfully generated by an optical intensity modulator driven by a 10-GHz sinusoidal RF signal. Conversion into a frequency-quadrupled RF signal is also demonstrated experimentally.

Conformational change in transfer RNA is an early indicator of acute cellular damage.

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.

[A case of akin moyamoya disease associated with type-I diabetes mellitus managed by extracranial-intracranial bypass].

Moyamoya disease is characterized by idiopathic steno-occlusion at the terminal portion of the internal carotid artery with concomitant abnormal vascular networks that can lead to transient ischemic attacks and hemorrhagic stroke with symptoms of headache, confusion, dizziness, ataxia, seizure, and cognitive and personality changes. Because these symptoms also occur in patients with type 1 diabetes mellitus(T1DM), patients with both diseases might go unnoticed and without the less common diagnosis of akin moyamoya disease, accurate diagnosis and treatment could be delayed. Here, we report the case of a 32-year-old woman with past history of T1DM for 26 years presenting with right amaurosis, which was diagnosed as akin moyamoya disease even though she had suffered right incomplete hemiparesis 2 years ago. She underwent superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in the left hemisphere without complication. She had no cerebrovascular events postoperatively. Although akin moyamoya disease associated with T1DM is rare in Japan, we recommend that clinicians consider the coexistence of both diseases when evaluating patients with T1DM who have neurologic signs or symptoms and not overlook the possibility of cerebrovascular diseases, such as akin moyamoya disease.

[A case of atherothrombotic embolization developing with slowly progressive symptoms and requiring differential diagnosis from metastatic tumor recurrence].

We report a case of atherothrombotic embolization that developed with slowly progressive symptoms and required differential diagnosis from metastatic tumor recurrence. A 64-year-old man with a history of lung cancer and metastatic brain tumor was carefully followed at our outpatient department for tumor recurrence. Five years after surgery for brain metastasis and whole brain radiation therapy, he had no recurrence and systemic disease was well controlled. At a routine follow up in October 2013, he complained of slight right arm dysesthesia. Follow up brain magnetic resonance (MR) imaging revealed no lesion. Two months later, he developed right hemiparesthesia and gait disturbance. Spinal MR imaging was unremarkable. However, at a routine follow up in January 2014, multiple enhancements were detected near the resection cavity and regions delineating the sulci. At first, this was diagnosed as tumor recurrence. However, 3 days later, additional MR imaging detected new multiple small infarctions after worsening right hemiparesis and dysarthria. With the diagnosis of embolic stroke, we searched for an embolic source. Cardiogenic embolization and carotid bifurcation stenosis studies were negative, but severe stenosis and thrombosis were detected near the left common carotid artery origin. This site was in the field of radiation the patient received as treatment for primary lung cancer.

Conditional ablation of neuroprogenitor cells in adult mice impedes recovery of poststroke cognitive function and reduces synaptic connectivity in the perforant pathway.

The causal relationship between neurogenesis and the recovery of poststroke cognitive function has not been properly explored. The current study aimed to determine whether depleting neuroprogenitor cells (NPCs) affects poststroke functional outcome in nestin-δ-HSV-TK-EGFP transgenic mice, in which the expression of a truncated viral thymidine kinase gene and EGFP was restricted to nestin-expressing NPCs. Ganciclovir (GCV; 200 mg/kg/d) or saline was continuously administered via osmotic pumps in mice for 4 weeks before the induction of experimental stroke. Both baseline and stroke-induced type 1 and type 2 NPCs were conditionally ablated. GCV eliminated NPCs in a duration-dependent fashion, but it did not attenuate the genesis of astroglia or oligodendrocytes in the peri-infarct cortex, nor did it affect infarct size or cerebral blood reperfusion after stroke. Transgenic stroke mice given GCV displayed impaired spatial learning and memory in the Barnes maze test compared with saline control or wild-type stroke mice given GCV, suggesting a contributing role of stroke-induced neurogenesis in the recovery of cognitive function. However, there was no significant difference in poststroke motor function between transgenic mice treated with GCV and those treated with vehicle, despite a significant ablation of NPCs in the subventricular zone of the former. Furthermore, nestin-δ-HSV-TK-EGFP mice treated with GCV had fewer retrogradely labeled neurons in the entorhinal cortex (EC) when injected with the polysynaptic viral marker PRV614 in the dentate gyrus (DG), suggesting that there might be reduced synaptic connectivity between the DG and EC following ablation of NPCs, which may contribute to impaired poststroke memory function.

A Case of Rheumatoid Meningitis Diagnosed with FLAIR Images and Anti-cyclic Citrullinated Peptide Antibodies Levels.

Rheumatoid meningitis (RM) is a rare but serious extra-articular manifestation of rheumatoid arthritis. Due to the absence of specific biomarkers, imaging findings, or guidelines for its detection, the diagnosis of RM is difficult. This report describes a patient of RM diagnosed with an open biopsy and discusses the utility of anticyclic citrullinated peptide antibodies (ACPA) levels in the serum and cerebrospinal fluid (CSF), and contrast-enhanced (CE) fluid-attenuated inversion recovery (FLAIR) images for screening and monitoring RM. A 65-year-old woman presented with a 2-month history of headaches. Imaging studies showed asymmetric meningeal and leptomeningeal involvement seen on brain magnetic resonance imaging (MRI). An open biopsy of the meninges and leptomeninges depicted palisaded and necrotizing granulomatous inflammation, which suggests rheumatoid nodules. Treatment with prednisolone and tocilizumab led to symptom improvement and reduced lesion intensity on follow-up MRI. Throughout the treatment, the ACPA index in her serum and CSF, and the findings of CE-FLAIR images, rather than the CE T1WI, reflected disease activity. For 6 months, the patient has been stable without symptom recurrence. The ACPA index and the CE-FLAIR images were useful for the diagnosis and monitoring of RM. To validate these findings, further studies are necessary.