Effects of female bone marrow transplantation on male reproductive organs.

Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function.

Effect of the addition of 123I-iomazenil single-photon emission computed tomography to brain perfusion single-photon emission computed tomography on the detection accuracy of misery perfusion in adult patients with ischemic moyamoya disease.

OBJECTIVE: The present prospective study aimed to determine whether the addition of 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) to brain perfusion SPECT could improve the detection accuracy of misery perfusion on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). METHODS: Oxygen extraction fraction (OEF) and brain perfusion were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine (IMP) SPECT, respectively, in 137 patients. IMZ SPECT was also performed. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories ipsilateral to the symptomatic cerebral hemisphere and in the contralateral posterior cerebral artery territory using a three-dimensional stereotaxic ROI template. The radioactive count of the MCA ROI to the contralateral posterior cerebral artery ROI was calculated on IMP SPECT (relative SPECT-IMP uptake) and IMZ SPECT (relative SPECT-IMZ uptake). The relative SPECT-IMZ uptake to the relative SPECT-IMP uptake was also calculated (relative SPECT-IMZ/IMP uptake). Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest PET-OEF value (one ROI per patient) was selected for analysis. RESULTS: Significant correlations were observed between the PET-OEF and relative SPECT-IMP uptake (correlation coefficient, - 0.683) and relative SPECT-IMZ/IMP uptake (correlation coefficient, 0.875). The area under the receiver operating characteristic curve for detecting misery perfusion (PET-OEF > 51.3%) was significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake (difference between areas, 0.080; p = 0.0004). The sensitivity, specificity, and positive- and negative-predictive values for the relative SPECT-IMZ/IMP uptake for detecting misery perfusion were 100%, 92%, 81%, and 100%, respectively. The specificity and positive-predictive value were significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake. CONCLUSIONS: The addition of IMZ SPECT to brain perfusion SPECT improves the detection accuracy of misery perfusion on PET in adult patients with ischemic MMD.

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.

Rupture of Vertebral Artery Dissecting Aneurysm after mRNA Anti-COVID-19 Vaccination: A Report of Two Cases.

The coronavirus disease 2019 (COVID-19) pandemic continues to spread around the world, and widespread vaccination is considered the most effective way to end it. Although the efficacy of COVID-19 vaccines has been confirmed, their safety remains a concern. In this paper, we report two cases of ruptured vertebral artery dissecting aneurysm (VADA) immediately after messenger RNA (mRNA) anti-COVID-19 vaccination. In Case 1, a 60-year-old woman experienced sudden headache 3 weeks before her first dose of the Moderna mRNA-1273 COVID-19 vaccine. Magnetic resonance imaging showed dilatation of the right vertebral artery (VA) without intracranial hemorrhage. A day after the vaccination, she developed subarachnoid hemorrhage with pulmonary effusion due to a ruptured right VADA. She underwent endovascular internal trapping and parent artery occlusion under general anesthesia. In Case 2, a 72-year-old woman with a previous history of the left VA occlusion due to arterial dissection developed subarachnoid hemorrhage 7 days after the first dose of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine due to a ruptured right VADA and underwent stent-assisted coil embolization under general anesthesia. The postoperative courses of these two cases were uneventful. The accumulation of more cases and further study are warranted to clarify the relationship between COVID-19 mRNA vaccination and ruptured intracranial dissecting aneurysms.

Five-Year Outcomes of Medical Management Alone for Adult Patients with Ischemic Moyamoya Disease without Cerebral Misery Perfusion.

INTRODUCTION: No clear guidelines for treating adult patients with ischemic moyamoya disease (MMD) without cerebral hemodynamic compromise such as misery perfusion have been established. Our previous prospective cohort study of adult patients with MMD without misery perfusion who were treated with medical management alone, including an antiplatelet drug, showed a recurrent ischemic event rate of 3% per 2 years. The present prospective study aimed to elucidate the 5-year clinical, cerebral perfusion, and cognitive outcomes of medical management alone for Japanese adult patients with ischemic MMD without cerebral misery perfusion by following the same patients for another 3 years. METHODS: In total, 68 patients without recurrent events at a 2-year follow-up were prospectively followed up for another 3 years. Cerebral blood flow (CBF) in the symptomatic cerebral hemisphere was measured using brain perfusion single-photon emission computed tomography at inclusion and at the end of the subsequent 3-year follow-up. Neuropsychological testing was performed at inclusion and at the end of the initial 2- and subsequent 3-year follow-ups. RESULTS: During the subsequent 3-year follow-up, 2 patients (3%) developed further ischemic events. In patients without further ischemic events, CBF was significantly greater at the end of the subsequent 3-year follow-up than at inclusion (p = 0.0037), and all neuropsychological test scores improved or remained unchanged at the end of initial 2- and subsequent 3-year follow-ups compared with that at inclusion. CONCLUSION: In adult patients receiving medical management alone for ischemic MMD without cerebral misery perfusion, the incidence of further ischemic events was 6% per 5 years and did not change between the initial 2 years after the last is-chemic event and the subsequent 3 years. In patients without further ischemic events, CBF and cognitive function had not deteriorated at 5 years after the last ischemic event.

Development of cerebral microbleeds in patients with cerebral hyperperfusion following carotid endarterectomy and its relation to postoperative cognitive decline.

OBJECTIVE: A primary cause of cognitive decline after carotid endarterectomy (CEA) is cerebral injury due to cerebral hyperperfusion. However, the mechanisms of how cerebral hyperperfusion induces cerebral cortex and white matter injury are not known. The presence of cerebral microbleeds (CMBs) on susceptibility-weighted imaging (SWI) is independently associated with a decline in global cognitive function. The purpose of this prospective observational study was to determine whether cerebral hyperperfusion following CEA leads to the development of CMBs and if postoperative cognitive decline is related to these developed CMBs. METHODS: During the 27-month study period, patients who underwent CEA for ipsilateral internal carotid artery stenosis (≥ 70%) also underwent SWI and neuropsychological testing before and 2 months after surgery, as well as quantitative brain perfusion SPECT prior to and immediately after surgery. RESULTS: According to quantitative brain perfusion SPECT and SWI before and after surgery, 12 (16%) and 7 (9%) of 75 patients exhibited postoperative cerebral hyperperfusion and increased CMBs in the cerebral hemisphere ipsilateral to surgery, respectively. Cerebral hyperperfusion was associated with an increase in CMBs after surgery (logistic regression analysis, 95% CI 5.08-31.25, p < 0.0001). According to neuropsychological assessments before and after surgery, 10 patients (13%) showed postoperative cognitive decline. Increased CMBs were associated with cognitive decline after surgery (logistic regression analysis, 95% CI 6.80-66.67, p < 0.0001). Among the patients with cerebral hyperperfusion after surgery, the incidence of postoperative cognitive decline was higher in those with increased CMBs (100%) than in those without (20%; p = 0.0101). CONCLUSIONS: Cerebral hyperperfusion following CEA leads to the development of CMBs, and postoperative cognitive decline is related to these developed CMBs.

Optimal timing for measuring cerebral blood flow after acetazolamide administration to detect preexisting cerebral hemodynamics and metabolism in patients with bilateral major cerebral artery steno-occlusive diseases: 15O positron emission tomography studies.

The present study determined the optimal timing of scanning for measurement of cerebral blood flow (CBF) after acetazolamide (ACZ) administration for detection of preexisting cerebral hemodynamics and metabolism in bilateral major cerebral artery steno-occlusive diseases. Thirty three patients underwent 15O gas positron emission tomography (PET) and each parameter was obtained in the bilateral middle cerebral artery (MCA) territories. CBF was also obtained using H2 15O PET scanning performed at baseline and at 5, 15, and 30 min after ACZ administration. Relative CBF at each time point after ACZ administration to baseline CBF was calculated. For MCA territories with normal cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), CBF continued increasing until 15 min after ACZ administration. For MCA territories with abnormally increased CBV, CBF decreased 5 min after ACZ administration. After that, CBF continued increasing until 30 min after ACZ administration. For MCA territories with abnormally decreased CMRO2, CBF did not change 5 min after ACZ administration. Ten min later, CBF increased. The accuracy to detect abnormally increased CBV was significantly greater for relative CBF5 than for relative CBF15. The accuracy to detect abnormally decreased CMRO2 was significantly greater for relative CBF5 or CBF15 than for relative CBF30. For detecting abnormally increased oxygen extraction fraction, the accuracy did not differ among each relative CBF. These findings suggested that CBF measurement at 5 min after ACZ administration is the optimal timing for detection of preexisting cerebral hemodynamics and metabolism in bilateral major cerebral artery steno-occlusive diseases.

Comparison of Subjective and Objective Assessments on Improvement in Gait Function after Carotid Endarterectomy.

The purpose of the present study was to determine whether objective gait test scores obtained using a tri-axial accelerometer can detect subjective improvement in gait as determined by the patient after carotid endarterectomy (CEA). Each patient undergoing CEA for ipsilateral internal carotid artery stenosis determined whether their gait was subjectively improved at six months after CEA when compared with preoperatively. Gait testing using a tri-axial accelerometer was also performed preoperatively and six months postoperatively. Twelve (15%) of 79 patients reported subjectively improved gait. Areas under the receiver operating characteristic curve for differences between pre- and postoperative test values in stride time, cadence, and ground floor reaction for detecting subjectively improved gait were 0.995 (95% confidence interval (CI), 0.945-1.000), 0.958 (95%CI, 0.887-0.990), and 0.851 (95%CI, 0.753-0.921), respectively. Cut-off points for value differences in detecting subjectively improved gait were identical to mean -1.7 standard deviation (SD) for stride time, mean +1.6 SD for cadence, and mean +0.4 SD for ground floor reaction of control values from normal subjects. Objective gait test scores obtained using the tri-axial accelerometer can detect subjective gait improvements after CEA. When determining significant postoperative improvements in gait using a tri-axial accelerometer, optimal cut-off points for each test value can be defined.

Decrease in 18F-Florbetapir Accumulation in the Cerebral Hemisphere With Hypoperfusion and Misery Perfusion Due to Chronic Atherosclerotic Occlusion of the Internal Carotid Artery.

A 67-year-old man had a slowly progressing impairment of recent memory. Cerebral angiography showed atherosclerotic occlusion of the right internal carotid artery with insufficient collateral circulation. Positron emission tomography (PET) using O2 gas showed reduced cerebral blood flow, reduced cerebral metabolic rate of oxygen, and elevated oxygen extraction fraction in the precentral region of the right cerebral hemisphere. Use of F-florbetapir PET depicted amyloid ß deposition as decreased tracer uptake in the precentral region in the right cerebral hemisphere when compared with the contralateral hemisphere.