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Accelerated bone loss is closely associated with Alzheimer's disease (AD), but the relationship between bone mineral density (BMD) and imaging markers of neurodegeneration remains uncertain. We examined the effect of low bone mass (osteopenia) on regional cerebral blood flow (rCBF) in patients with AD (n = 19) and non-demented aging (n = 12). We enrolled 31 female outpatients diagnosed with osteopenia (age ≥ 65 years) who had both a single-photon emission computed tomography brain scan and dual-energy X-ray absorptiometry bone scan taken at their initial investigation. We analyzed the relationship between osteopenia (-2.5 < T-score < -1) and rCBF in 62 cortical areas measured using the stereotactic extraction estimation analysis on single-photon emission computed tomography (SPECT) (mean Z-scores). We found that the mean Z-scores of 14 cerebral subregions, most of which are often affected early in AD, were significantly lower in the AD group than the non-demented group (P < .001). The age-stratified multivariate regression analysis showed that the decreased rCBF in the left posterior cingulate cortex (PCC) was an independent predictor of osteopenia (r = -0.395; P = .005). BMD and rCBF in the left PCC were significantly correlated in the overall population (r = -0.54; P = .001), as well as the AD group (r = -0.514; P = .02). These imaging data suggest that osteopenia may contribute to neurodegeneration of a brain network hub associated with AD.

Case series Patients: Female, 69-year-old • Male, 70-year-old Final Diagnosis: Nonconvulsive status epilepticus Symptoms: Altered mental status • cognitive impairment Medication: — Clinical Procedure: ASL perfusion MRI Specialty: Neurology Objective: Challenging differential diagnosis Background: The diagnosis of early non-convulsant status epilepticus (NCSE) can be challenging and can overlap with other critical conditions. Two patients with Alzheimer’s disease are reported with clinically suspected NCSE presenting in the emergency setting who were diagnosed using arterial spin-labeling magnetic resonance imaging (ASL-MRI) sequences. Case Reports: In Case 1, a 69-year-old woman with mild Alzheimer’s disease and diabetes presented with acute worsening of cognitive status and fluctuating level of consciousness. In Case 2, a 70-year-old man with mild cognitive impairment due to Alzheimer’s disease and hypertension presented with acute loss of consciousness and left hemiparesis, without evidence of hypoglycemia or a hypertensive crisis. In both cases, ASL-MRI perfusion images showed focal cerebral hyperperfusion in the posterior cingulate and parietal associative cortex, which involved neurodegenerative areas associated with epilepsy in early Alzheimer’s disease. In both cases, the patients developed generalized tonic-clonic epileptic seizures that lasted for 5 minutes or more, which indicated the emergence of status epilepticus that developed from the initial presentation of NCSE. In both cases, electroencephalogram (EEG) findings confirmed that the seizures were controlled by intravenous administration of antiepileptic drugs. Both patients discharged home from the hospital without recurrence of seizures, between 10–12 days after the onset of symptoms. Conclusions: These two cases have demonstrated that ASL-MRI is feasible as an emergency diagnostic tool in clinically suspected NCSE in patients with Alzheimer’s disease.

Recently, type 2 diabetes mellitus (T2DM) has been reported to be strongly associated with Alzheimer’s disease (AD). This is partly due to insulin resistance in the brain. Insulin signaling and the number of insulin receptors may decline in the brain of T2DM patients, resulting in impaired synaptic formation, neuronal plasticity, and mitochondrial metabolism. In AD patients, hypometabolism of glucose in the brain is observed before the onset of symptoms. Amyloid-β accumulation, a main pathology of AD, also relates to impaired insulin action and glucose metabolism, although ketone metabolism is not affected. Therefore, the shift from glucose metabolism to ketone metabolism may be a reasonable pathway for neuronal protection. To promote ketone metabolism, medium-chain triglyceride (MCT) oil and a ketogenic diet could be introduced as an alternative source of energy in the brain of AD patients.

Early brain injury (EBI) is closely linked to the development of delayed cerebral ischemia and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to evaluate the neuroprotective effect of neurotropin on EBI in a murine model of SAH. Twenty-four C57BL/6N mice were treated with intraperitoneal injections of either saline or 2.4 units of neurotropin at 1 h after SAH induction and for 3 days consecutively. SAH was created by an endovascular perforation method. In addition to the assessment of cerebral infarction and survival rate, motor and neurocognitive functions were also measured after SAH. Compared to the saline control group, the neurotropin group showed better recovery from locomotive and neurological declines after SAH. The neurotropin group also showed lower rates of post-SAH acute cerebral infarction and better memory and route-learning scores (p &lt, 0.05). Meanwhile, there was no significant between-group differences in the overall mortality, hemodynamic parameters, or body weights. In conclusion, post-event treatment with neurotropin could be protective against EBI, lowering the incidence of ischemia and improving some motor and neurocognitive functions after SAH.

Elongated axial length of the eye increases the morbidity of glaucoma. Myopia also associates with elongated axial length, and such ellipsoid shape of the eyeball strongly contributes its pathogenesis. Morphological features of the eyeballs, which could be important factors for developing glaucoma, have not been well described. The aim of this study was to investigate the three-dimensional (3D) topographic features of glaucomatous eyeballs with/without myopia to evaluate the potential of those features for predicting glaucoma. Using a 3.0-tesla MRI, volume-isotropic turbo-spin-echo acquisition T2-weighted images were obtained from 55 patients with glaucoma and 22 controls to delineate the eyeballs. Eyeball volumes, axial lengths and transverse lengths were semi-automatically calculated and compared between four groups: normal, myopia, glaucoma, and glaucoma with myopia. Both glaucoma and myopia increased the eyeball volume compared to the normal eyes. An increased anisotropy ratio (axial/transversus length) was observed in myopic eyes compared to normal, whereas in the glaucomatous eyes, with or without myopia, no increase in anisotropy ratio was observed. Increasing volume of eyes can be caused by myopia and glaucoma. Myopic eyes were ellipsoid in shape, but there was less anisotropy and a near-spherical shape in glaucomatous eyes, even in glaucomatous myopic eyes.

[Purpose] We aimed to translate and validate a Japanese language version of the cerebral palsy quality of life for children questionnaire for primary caregivers and assess the relationship between quality of life of Japanese parents and their children’s motor skills. [Participants and Methods] Fifty children (aged 4 to 12 years) and their parents (mothers) were enrolled. The parent-proxy version of the cerebral palsy quality of life for children questionnaire translated to Japanese was administered, and a validation study was performed using Cronbach’s α as the key metric. The relationships between the parents’ quality of life and children’s Gross Motor Function Classification Scale levels were analyzed. [Results] We found that the age of the children and their parents and gender of the children were not significant factors affecting the quality of life domains. Significantly high values of internal consistency were detected among items within each quality of life domain, wherein Cronbach’s α was between 0.72 and 0.89. Two quality of life domains (Emotional well-being and Feeling about functioning) were significantly associated with Gross Motor Function Classification Scale levels. [Conclusion] Our data suggest that the original English version of the cerebral palsy quality of life for children questionnaire for primary caregivers was successfully translated to Japanese for use by Japanese-speaking parents caring for their children.

Background Convincing evidence regarding gait and balance function in elderly women with low bone mineral density (BMD) and/or osteoporosis is limited. In the present study, we aimed to compare the gait characteristics in elderly women with and without low BMD and to analyze plausible parameter(s) for predicting low BMD. Material/Methods We retrospectively analyzed prospectively collected data of 26 consecutive postmenopausal women aged >65 years who were admitted to our geriatric outpatient service. They were assigned to 2 groups, with (n=14) and without (n=12) low BMD based on T-score (0.05). Receiver operating characteristic curve analysis demonstrated that LI can predict low BMD in the femur neck with moderate accuracy (area under the curve=0.75, 95% confidence interval 0.55–0.95; P=0.031). The optimal cut-off value was 17%, with 67% specificity and 86% sensitivity. Conclusions These results suggest that elderly women with low BMD may walk with asymmetrical trunk movement, but they are able to generate gait patterns similar to healthy peers. The LI may provide valuable quantitative information for preventing fractures in subjects with osteoporosis.

Early brain injury and related cardiac consequences play a key role in the devastating outcomes after subarachnoid hemorrhage (SAH). We reported that rapamycin exerts neuroprotection against cortical hypoxia early after SAH, but its mechanism is poorly understood. This in vivo study aimed to determine the potential role of the transcription factor STAT3 in the rapamycin-mediated neuroprotection in a mouse model of SAH. Forty C57BL/6 N mice were treated with an intracerebroventricular injection of rapamycin or vehicle (control) given after SAH induction by a filament perforation method, with or without STAT3 (Stattic) or ERK (PD98059) inhibitor pretreatment. Cerebral blood flow signals (%vascularity), brain tissue oxygen saturation (SbtO2), and cardiac output (CO) were analyzed using an ultrasound/photoacoustic imaging system. Clinically relevant neurocardiac depression was notable in severe SAH mice. Rapamycin improved %vascularity, SbtO2, and CO on day 1 after SAH onset. The beneficial effects of rapamycin on cerebral blood flow and oxygenation persisted until day 3, resulting in a significant reduction in post-SAH new cerebral infarctions and survival, as well as improved neurological functions, compared to the control group. All of the effects were attenuated by pretreatment with Stattic or PD98059. These data suggest that ERK and JAK/STAT3 pathways play an important role in the neurocardiac protection by rapamycin after SAH. We propose that rapamycin is a novel pharmacological strategy to target STAT3 activation, with a possible crosstalk through the ERK pathway, for the treatment of post-SAH early brain injury.

We aimed to evaluate the feasibility of a non-invasive method of cerebral blood flow (CBF) measurement using high-frequency power Doppler ultrasound imaging in a mouse model of subarachnoid haemorrhage (SAH). The 3-dimensionally (3D) reconstructed blood flow signals (%vascularity) within the brain volume of the middle cerebral artery territory correlated well with reference parameters, baseline carotid artery blood flow (r2 = 0.52, P

ObjectivesMetabolic tumor volume (MTV) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a promising prognostic predictor in pancreatic ductal adenocarcinoma (PDAC). However, the optimal segmentation method and threshold value to determine MTV for PDAC are still unclear. We explored the optimal method and threshold value for the prognostic value of MTV measured on pre-treatment 18F-FDG-PET/CT.MethodsSeventy-three patients with resected PDAC who underwent 18F FDG-PET/CT before surgical resection were enrolled. MTV values of the tumor were measured on FDG-PET/CT by the two fixed-threshold methods using threshold values as 2.0, 2.5, 3.0, and 3.5 for the absolute method and 35%, 40%, 42%, 45%, and 50% for the relative method. Receiver operating characteristic curve analysis for prediction of 1-year survival rates was conducted for determining the optimal threshold values, and we selected the optimal method and threshold value considering area under the curve. The prognostic values of each FDG-PET/CT parameter for disease-specific survival and recurrence-free survival were assessed with Kaplan–Meier method and Cox proportional hazard models.ResultsIn receiver operating characteristic curve analysis, MTV by the fixed-absolute threshold method based on a threshold value of 3.5 (MTV3.5) performed best in our study with area under the curve 0.724, sensitivity of 65%, and specificity of 75%. In univariate and multivariate analyses, MTV3.5 was significantly associated with disease-specific and recurrence-free survival.ConclusionsMTV3.5 by absolute threshold on pre-treatment FDG-PET/CT was the best independent prognostic predictor in resectable PDAC compared with other absolute threshold values and relative threshold values.

Introduction: Recent epidemiological studies suggest that atrial fibrillation (AF) is a risk factor for cognitive decline and dementia in elderly population, which may be attributable to reduced stroke volume and related brain hypoperfusion as a potential cause. Catheter ablation therapy is an option for radical cure of AF. Although several researchers mentioned the possibility to improve cognition after the intervention, specific topographic features of the brain perfusion have not been well investigated. Hypothesis: To visualize hemodynamic alteration in regional cerebra blood flow (rCBF) associated with catheter ablation therapy using noninvasive MRI voxel-based analysis method and to clarify the relationship between AF and cognitive decline. Methods: Eight patients with persistent AF (2 male, average age 63.4±7.3) underwent noninvasive brain MRI perfusion imaging with a novel dynamic model-free arterial spin-labeling (ASL) technique (quantitative STAR labeling of arterial regions [QUASAR]) and cognitive tests including Mini-Mental State Exam (MMSE) and Ray Auditory Verbal Learning Test (RAVLT) before and after 6-months of intervention. QUASAR-ASL images were spatially normalized with SPM 12 applied by partial volume correction, followed by comparison of rCBF of each brain areas with voxel-based paired-t test. Results: After the ablation therapy, QUASAR-ASL showed significantly increased rCBF in the left posterior cingulate gyrus (PCC) (FWE, P < 0.05, MNI coordinates = -9 -45 5, Figure), which was accompanied by improved scores of the RAVLT ( P < 0.001). Conclusions: The PCC is a critical part of the limbic system initially affected focal energy metabolism by Alzheimer’s disease. Improved rCBF in left PCC in patients with AF after catheter ablation therapy, as demonstrated by QUASAR-ASL method, may prevent episodic memory decline related to the auditory-verbal cognitive function.

Alzheimer’s disease (AD) is a common neurodegenerative disease and a major contributor to progressive cognitive impairment in an aging society. As the pathophysiology of AD involves chronic neuroinflammation, the resolution of inflammation and the group of lipid mediators that actively regulate it—i.e., specialized pro-resolving lipid mediators (SPMs)—attracted attention in recent years as therapeutic targets. This review focuses on the following three specific SPMs and summarizes their relationships to AD, as they were shown to effectively address and reduce the risk of AD-related neuroinflammation: maresin 1 (MaR1), resolvin D1 (RvD1), and neuroprotectin D1 (NPD1). These three SPMs are metabolites of docosahexaenoic acid (DHA), which is contained in fish oils and is thus easily available to the public. They are expected to become incorporated into promising avenues for preventing and treating AD in the future.

Background: Decreased bone mineral density (BMD) was associated with poorer cognitive function and increased risk of Alzheimer's disease (AD). However, objective evidence for the relationship between osteoporosis and AD in humans has not been extensively described. Objectives: We aimed to evaluate the relationships between BMD and the cortical volumes of brain regions vulnerable to AD; hippocampus, parahippocampal gyrus, precuneus, posterior cingulate, and angular gyrus, using voxel-based morphometry (VBM), to investigate the association between bone loss and AD. Methods: A cohort of 149 consecutive elderly participants who complained of memory disturbance underwent high-resolution structural brain magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA). We used SPM12 software to conduct a voxel-based multiple regression analysis to examine the association between femoral neck BMD values and regional gray matter volume (rGMV) on structural T1-weighted MRI. Results: After adjusting for subject age, gender, total brain volume (TBV), and mini-mental state examination (MMSE) scores, the multiple regression analysis showed significant correlations between BMD loss and rGMV decline in the left precuneus, which is an important neural network hub vulnerable to AD. Conclusion: These data suggest that the bone and brain communicate with each other, as in "bone-brain crosstalk," and that control of BMD factors could contribute to cognitive function and help prevent AD.

ObjectiveOptimizing cardiac stroke volume during high-risk surgical anesthesia is of particular interest with regard to a therapeutic target to reduce the incidence of postoperative complications. However, intensive fluid management in critically ill small animals with pulmonary hypertension (PH) has been empirically performed, and thus it can be challenging. Stroke volume variation (SVV) has been used as a dynamic preload predictor of fluid responsiveness. We hypothesized that if SVV exhibited robust reliability in the setting of hemodynamically unstable condition, it would provide more precise information on fluid resuscitation to translate it into veterinary anesthesia. Thus the aim of this study was to investigate the utility of SVV measured by the electrical velocimetry (EV) method for predicting fluid responsiveness in dogs with PH.MethodsSixteen dogs undergoing emergency abdominal surgery and diagnosed with PH secondary to myxomatous mitral valve disease (MMVD) on preoperative transthoracic echocardiogram were included. Dogs were randomly assigned to 2 groups with and without inotropic cardiac support with dobutamine. Hemodynamic measurements including stroke volume and SVV derived from the EV device were performed under general anesthesia before (baseline) and after surgery (fluid challenge with a colloid solution defined by a SV increase of ≥ 10%).ResultsIn both groups, SVV elevated significantly after abdominal surgery compared with baseline. In dobutamine infused group, the SVV values decreased significantly after fluid challenge (P < 0.05) with a greater number of responders than saline infused control group (P < 0.01). Receiver operating curve analysis of SVV confirmed high positive predictive value for dogs during dobutamine infusion (P < 0.05; cut-off value of 15%; specificity 90%, sensitivity 82%).ConclusionsNoninvasive EV monitoring may be useful for the prediction of fluid responsiveness in critically ill dogs with left-sided heart failure-related PH. This normalization of dynamic preload indices, which could be achieved more precisely under inotropic support, may prevent further detrimental consequence of fluid loading.

BACKGROUND Fluid resuscitation is a cornerstone of minimizing morbidity and mortality in critically ill patients, but the techniques for predicting fluid responsiveness is still a matter of debate. In this study, we aimed to evaluate the utility of noninvasive stroke volume variation (SVV), pulse pressure variation (PPV), and systolic pressure variation (SPV) as a dynamic predictor for assessing fluid responsiveness during different ventilation modes in anaesthetized, intubated dogs recovering from cardiac surgery. MATERIAL AND METHODS Thirty-six adult Beagle dogs undergoing experimental surgery for isolated right ventricular failure were monitored for SVV, PPV, and SPV simultaneously using electrical velocimetry device. The relationships between each indicator and SVI before and after volume loading were compared in 3 ventilatory modes: assist control (A/C), synchronized intermittent mandatory ventilation (SIMV), and continuous positive airway pressure (CPAP). Responders were defined as those whose stroke volume index increased by ≥10%. RESULTS In all of the indices, the baseline values were greater in responders than in nonresponders (P0.01) under A/C and SIMV. Receiver operating curve analysis confirmed the best predictive value during A/C [area under the curve (AUC): SVV, 0.90; PPV, 0.88; SPV, 0.85; P0.05] followed by SIMV (AUC: SVV, 0.86; PPV, 0.83; CPAP, 0.80; P0.05), with their sensitivities and specificities of ≥7 5%. By contrast, no statistically significance detected in any parameter during CPAP (AUC: SVV, 0.71; PPV, 0.66; CPAP, 0.65; P0.05). CONCLUSIONS SVV, PPV, and SVV are all useful to predict cardiac response to fluid loading in dogs during A/C and SIMV, while their reliabilities during CPAP are poor.

Case Non-convulsive status epilepticus (NCSE) is among the differential diagnoses of decreased consciousness, but often presents a diagnostic challenge. A 65-year-old woman was admitted to our emergency department with bradylalia. No abnormal finding was detected by computed tomography or magnetic resonance imaging. Subsequently, acquired arterial spin-labeling images showed hyperperfusion in the right hemisphere. Outcome After the examination, the patient began experiencing left hemifacial seizures, which were relieved by diazepam; however, she was still agitated. Ictal confusion due to NCSE was suspected. Electroencephalography revealed periodic, generalized epileptiform activities with brief seizures of facial muscles by intermittent photic stimulation. Another supportive case of NCSE detected by arterial spin-labeling from a 56-year-old right-handed man has also been presented. Conclusion Arterial spin-labeling magnetic resonance perfusion imaging provides valuable information regarding cerebral perfusion status in NCSE patients in emergency/acute settings.

The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17–84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin’s lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.

We evaluated the utility of noninvasive stroke volume variation (SVV) as a functional haemodynamic predictor for fluid responsiveness under different ventilation modes [assist control (A/C), synchronized intermittent mandatory ventilation (SIMV), and continuous positive airway pressure (CPAP)] in 45 anaesthetized dogs, using an electrical velocimetry device. Receiver operating curve analysis confirmed the best predictive value during SVVA/C (12.5% of cut-off value; 75% sensitivity and 86% specificity) followed by SVVSIMV (13.5% of cut-off value; 75% sensitivity and 75% specificity), while no statistically significance detected during SVVCPAP (P > .05). These data suggest that SVV is useful for the prediction of fluid responsiveness in laboratory dogs during A/C and SIMV, while its reliability during CPAP is poor. This article is protected by copyright. All rights reserved.

We evaluated the neuroprotective role of rapamycin, a mammalian target of rapamycin (mTOR) kinase inhibitor, in cerebral ischaemia and locomotor function in a mouse model of subarachnoid haemorrhage (SAH). Pretreatment with rapamycin, an mTOR kinase inhibitor, resulted in better recovery from cerebral hypoxia early after SAH than control (P .05), while the values of peak flow velocity in the middle cerebral artery did not change significantly (P .05). Average distance travelled and the ratio of central-area distance/total travelled distance determined by open-field test after day 14 was significantly higher in mice pretreated with rapamycin than in control mice (P .05). Inhibition of the mTOR pathway could be protective against post-SAH early brain injury, ameliorating brain tissue hypoxia and locomotor hypoactivity.

Patient: Female, 72 Final Diagnosis: Primary cardiac lymphoma Symptoms: Cardiac tamponade • dyspnea Medication: — Clinical Procedure: FDG-PET/CT scan Specialty: Nuclear Medicine Objective: Rare disease Background: Primary cardiac lymphoma is rare and can be an aggressive disease, depending on the grade. A case is reported of low-grade primary cardiac lymphoma associated with a pericardial effusion. 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) imaging was useful in the diagnosis and in evaluating the disease activity in this case. Case Report: A 72-year-old Japanese woman visited a general practitioner, complaining of dyspnea associated with cardiac tamponade. Pericardiocentesis was performed, and Group V malignant cells were identified by cytology, suspicious for malignant lymphoma. Whole-body FDG-PET/CT scans showed no pleural effusion or lymph node metastasis supporting the diagnosis of primary cardiac lymphoma diagnosed on pericardial effusion. The laboratory investigations showed that levels of serum soluble interleukin-2 (IL-2) receptor (sIL-2R), a diagnostic and prognostic marker for malignant lymphoma, were not elevated (258 U/ml). A six-month follow-up FDG-PET/CT scan showed an increased volume of the pericardial effusion and mild but abnormal uptake diffusely in the pericardial space, and the sIL-2R was slightly elevated (860 U/ml). No abnormal FDG accumulation outside the retained pericardial effusion was noted, which was compatible with a clinical picture of low-grade primary cardiac lymphoma, and in a period of watchful waiting during the first two years later, the sIL-2R had reduced to 195 U/ml. Conclusions: This is a rare case of low-grade primary cardiac lymphoma detected in a pericardial effusion, and highlights the utility of the FDG-PET/CT scan as a valuable diagnostic and follow-up modality.

Patient: Male, 61 Final Diagnosis: Semantic dementia Symptoms: Primary progressive aphasia Medication: — Clinical Procedure: Neuroimaging Specialty: Nuclear Medicine Objective: Rare co-existance of disease or pathology Background: Semantic dementia (SD) is a type of primary progressive aphasia with prominent language dysfunction, mostly within the spectrum of frontotemporal lobar degeneration (FTLD). Although there is an overlap in clinical manifestations of SD attributable to FTLD and neuropathologically proven Alzheimer disease (AD), clinical diagnostic clues are not readily available. We present a characteristic finding based on a single-photon emission computed tomography (SPECT)-based regional cerebral blood flow study and its statistical imaging analysis for a rare case of SD with AD-like pathology. Case Report: A 61-year-old male was referred to our hospital due to difficulties in self-management and impaired comprehension of word meaning suggestive of SD. Although his brain MRI revealed mild frontal lobe atrophy, his SPECT with three-dimensional stereotactic surface projections (3D-SSP) analysis showed left-sided hypo-perfusion that was more prominent in the inferior temporal gyrus and the inferior parietal lobule, with bilateral frontal lobe hypo-perfusion. The SPECT scan also showed involvement of the right inferior parietal area and, in medial aspects, the posterior cingulate cortex and adjacent precuneus; these finding were compatible with early hypo-perfused areas seen in AD. The lumbar cerebrospinal fluid biomarker findings seemed to fit SD in association with probable AD pathology. Conclusions: This is the first reported case to use SPECT with 3D-SSP statistical analysis as a potential, useful imaging modality for the diagnosis of SD with probable AD pathology.

Summary Tooth loss and related changes in the functionality may lead to worse outcome of stroke patients, but the link involved in this pathway remains unclear. This study aimed to determine the effect of comorbid masticatory impairment on acute cerebral ischemia and neurobehavioral outcome after experimental subarachnoid hemorrhage (SAH). Thirty C57BL/6 mice with (molar-less) or without (control) prior treatment of cutting off the upper molars (separated by at least one week), were subjected to SAH by endovascular perforation. Grading of SAH and acute cerebral infarction were assessed by T2*- and diffusion-weighted MR images, respectively. Cerebral blood flow (CBF) by continuous arterial spin labeling and parameters related to locomotor activity and exploration ability by open-field test were analyzed serially until 2 weeks after SAH. In all mice, global CBF depression was notable immediately after SAH induction (P 0.05). These data suggest a possible link between comorbid masticatory impairment and early brain injury/ischemia to deteriorate neurobehavioral functional outcome in patients after SAH. This article is protected by copyright. All rights reserved.

Summary The aim of this study was to evaluate the impact of cerebral blood flow (CBF) recovery obtained from brain single-photon emission computed tomography (SPECT) images on postoperative outcome after aneurysmal subarachnoid hemorrhage (SAH). Twenty-nine patients who had undergone surgical clipping for ruptured anterior communicating artery aneurysms were analyzed prospectively. Routine measurements of CBF were performed using technetium-99m hexamethyl propyleneamine oxine SPECT on days 4 and 14 after SAH. Regional voxel data analyzed by three dimensional stereotactic surface projection (3D-SSP) were compared between patients and age-matched normal database (NDB). In 3D-SSP analysis of all patients, cortical hypoperfusion around the surgical site in bilateral frontal lobes was evident on day 4 (P

BACKGROUND The optic radiation (OR) is a white-matter bundle connecting the lateral geniculate body and the visual cortex. Phase difference-enhanced imaging (PADRE) is a new MRI technique that is able to achieve precise delineation of the OR. The aim of this study was to investigate the effect of age on the volume and signal intensity of the OR using PADRE, and to establish a volumetric reference of the OR from a healthy population, compared with diffusion tensor imaging (DTI). MATERIAL AND METHODS Thirty-nine healthy volunteers underwent MR imaging with PADRE and DTI sequences on a 3.0-T scanner. For the volumetric analysis with PADRE, the OR corresponding to the external sagittal stratum was manually traced, while an automated thresholding method was used for the DTI-based volumetric analysis of the OR. RESULTS The mean right and left OR volumes measured from the PADRE images were 1469.0±242.4 mm³ and 1372.6±310.2 mm³, respectively. Although OR volume showed no significant correlation with age, the normalized OR signal intensity showed a linear correlation with increasing age (r²=0.50-0.53; P

Background and purpose Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. Methods Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1 h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. Results Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n = 12; caudate putamen, n = 3; hippocampus, n = 1) or multiple lesions (cortex and caudate putamen, n = 6; cortex and hippocampus, n = 2; cortex, hippocampus and thalamus/hypothalamus, n = 3; bilateral cortex, n = 2). The mortality rate within 24 h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P = 0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r2 = 0.31, P = 0.0002). Conclusion Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction.

BACKGROUND Peripheral or cranial nerve root dysfunction secondary to invasion of the CNS in multiple myeloma is a rare clinical event that is frequently mistaken for other diagnoses. We describe the clinical utility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scanning for diagnosing neuro-myelomatosis. CASE REPORT A 63-year-old woman whose chief complaints were right shoulder and upper extremity pain underwent MRI and 18F-FDG PET/CT scan. MRI revealed a non-specific brachial plexus tumor. 18F-FDG PET/CT demonstrated intense FDG uptake in multiple intramedullary lesions and in the adjacent right brachial plexus, indicating extramedullary neural involvement associated with multiple myeloma, which was confirmed later by a bone marrow biopsy. CONCLUSIONS This is the first reported case of neuro-myelomatosis of the brachial plexus. It highlights the utility of the 18F-FDG PET/CT scan as a valuable diagnostic modality.

BACKGROUND Delayed cerebral ischemia (DCI) is one of the main causes of poor outcomes after subarachnoid hemorrhage (SAH). The early identification of DCI by noninvasive imaging modalities would provide valuable information of therapeutic intervention for improving the patient outcomes. We aimed to describe the clinical features of cerebral blood flow (CBF) data obtained from the single-photon emission computed tomography (SPECT) during the risk period for DCI after SAH. MATERIAL AND METHODS Clinical data from 94 SAH patients who underwent surgical clipping of anterior circulation aneurysms were reviewed retrospectively. 99mTc-HMPAO SPECT images were visually and semiquantitatively analyzed on days 7 and 14 after SAH. RESULTS In all cases, the areas of hypoperfusion were found in the middle cerebral artery territories. By contrast, the areas of mild hyperperfusion were always detected on the surgical side, the prevalence which increased from days 7 (n=28; 30%) to 14 (n=48; 51%) without neurological defects. Univariate analysis revealed that the hyperperfusion on day 14 had a significant relationship with functional outcome at 3 months (P=0.04). Multivariate analysis including age, clinical SAH grade, DCI, and hyperperfusion on day 14 showed that DCI (P=0.004; odds ratio [OR], 0.10; 95% confidence interval [CI], 0.02-0.48) and hyperperfusion on day 14 (P=0.002; OR, 2.44; 95% CI, 1.40-4.29) were independently associated with functional outcome at 3 months. CONCLUSIONS Delayed mild hyperperfusion around the surgical site can predict good prognosis after SAH, although it may hinder the CBF diagnosis of focal ischemia attributable to DCI.

BACKGROUND Osteoporosis is a major global public health problem in the current aging era. Osteoporosis is often diagnosed only after patients have a fracture that causes a severe decline in ability to perform activities of daily life. Although the current criterion standard for diagnosing osteoporosis is dual-energy X-ray absorptiometry (DXA), this modality remains less prevalent among general practitioners in geriatric medicine. The aim of this study was to determine the diagnostic utility of visual inspection of lumbar radiography in detecting bone mineral density (BMD) decline. MATERIAL AND METHODS We retrospectively reviewed medical data of 78 patients who underwent both lateral lumbar radiography and DXA. Board-certified radiologists determined the clinical grade of each patient's condition according to the semiquantitative (SQ) method of lumbar fracture assessment. We compared the grades and young adult means of BMD in the lumbar spine and hips as measured using DXA. RESULTS BMD of the femoral neck was significantly lower in patients with severe osteoporosis (grades 2 and 3 as classified using the SQ method) than in those with mild osteoporosis (grades 0 and 1; P

Background: Cerebral palsy (CP) is a permanent motor disorder that occurs at birth or during early infancy. Despite advances in fetal and maternal medicine, the incidence of CP remains high. Hippotherapy has gradually been recognized as an excellent rehabilitation tool for children with CP. However, a scientific basis for how it achieves long-term functional improvements or provides additional benefits to patients' caregivers remains unknown. Objectives: We performed a prospective trial to determine how hippotherapy affects the gross motor and gait functions in children with CP and how it may also impact the quality of life (QOL) of patients' caregivers. Methods: In total, 24 children with CP (11 boys, 13 girls; age: 4-14 years; Gross Motor Function Classification System [GMFCS] II-III) underwent a program (30 min/day, once a week) of hippotherapy or day-care recreation (control) over a 1-year intervention and a 3-month follow-up period. Assessment measures used for the children were gait parameters for a 5-m walk test, Gross Motor Function Measure (GMFM)-66, and GMFM dimension-E (GMFM-E). The QOL of the caregivers was estimated using a brief version of the World Health Organization Quality Of Life (WHOQOL-BREF) self-assessment questionnaire. Results: In addition to better GMFM-66 and GMFM-E scores, hippotherapy was associated with increased cadence, step length, and mean acceleration; stabilized horizontal/vertical displacement of patients; and better relationship between the psychological status and QOL of the caregivers than those seen in the control group (p < 0.05). Additionally, the initially improved children's step length and their caregivers' psychological QOL domain (particularly in the "positive feeling" facet) tended to be preserved up to the 3-month follow-up. Conclusion: These data suggest that compared with common day-care recreational activities, a 1-year program of once-weekly hippotherapy can improve not only the walking ability of children with CP but also the psychological health and QOL of their caregivers. Clinical Trial Registration:: www.umin.ac.jp/ctr/, identifier: UMIN000022986.

We aimed to investigate the effect of hippotherapy on gait symmetry in children with cerebral palsy (CP). Twelve children with Gross Motor Function Classification System (GMFCS) levels II-IV received weekly hippotherapy lesson for 1 year. Gait analyses were performed during a 5-m walking test, using a portable, tri-axial accelerometer-based motion recorder. The baseline symmetry index derived from the Lissajous index (LI) figure before hippotherapy was greater than the LI in age-matched normal subjects (P < 0.01). Hippotherapy was associated with a decreased LI (-10.4 ± 4.9%, P = 0.018) and an improved GMFCS score (-0.6 ± 0.7, P = 0.02). These data suggest that hippotherapy has a beneficial effect on symmetry of the trunk movement in children with CP.

Cerebral stroke is the leading cause of death and permanent disability in elderly persons. The impaired glucose and oxygen transport to the brain during ischemia causes bioenergetic failure, leading to oxidative stress, inflammation, blood-brain barrier dysfunction, and eventually cell death. However, the development of effective therapies against stroke has been hampered by insufficient oral absorption of pharmaceuticals and subsequent delivery to the brain. Nanotechnology has emerged as a new method of treating cerebral diseases, with the potential to fundamentally change currently available therapeutic approaches using compounds with low bioavailability. This perspective review provides an overview of the therapeutic potential of oral nanomedicines for stroke, focusing on novel natural product-loaded delivery system with potent antioxidant and anti-inflammatory effects.

[Purpose] This case series aims to evaluate the effects of hippotherapy on gait and balance ability of children and adolescents with cerebral palsy using quantitative parameters for physical activity. [Subjects and Methods] Three patients with gait disability as a sequela of cerebral palsy (one female and two males; age 5, 12, and 25 years old) were recruited. Participants received hippotherapy for 30 min once a week for 2 years. Gait parameters (step rate, step length, gait speed, mean acceleration, and horizontal/vertical displacement ratio) were measured using a portable motion recorder equipped with a tri-axial accelerometer attached to the waist before and after a 10-m walking test. [Results] There was a significant increase in step length between before and after a single hippotherapy session. Over the course of 2 year intervention, there was a significant increase in step rate, gait speed, step length, and mean acceleration and a significant improvement in horizontal/vertical displacement ratio. [Conclusion] The data suggest that quantitative parameters derived from a portable motion recorder can track both immediate and long-term changes in the walking ability of children and adolescents with cerebral palsy undergoing hippotherapy.

Patient: Male, 54 Final Diagnosis: Cerebral infarction Symptoms: Amnesia Medication: — Clinical Procedure: MRI (magnetic resonance imaging) Specialty: Neurology Objective: Rare disease Background: The fornix is a white matter tract bundle that acts as the major output of the hippocampus and is an important component of the Papez circuit. We present an instructive imaging case of sudden onset of persistent amnesia due to selective ischemic damage of the anterior fornix. Case Report: A 54-year-old Japanese male came to our attention for a sudden onset of retrograde amnesia, associated with severe anterograde amnesia. The brain magnetic resonance imaging demonstrated a bright diffusion restriction, which was associated with swollen fornices bilaterally. His symptoms gradually improved, but episodic memory impairment still persisted after 1 month. The coronal T1-weighted MPRAGE (magnetization-prepared rapid acquisition with gradient echo) sequence clearly showed disruption of the left anterior fornix. Diffusion tensor tracking showed decrease in the density of entire fiber tracts on the Papez circuit as well as location of the left fornix. Conclusions: When dealing with sudden, persistent amnesia associated with small fornix infarction, it is prudent to consider the possibility of tract damage along with limbic system damage using MPRAGE sequence.

BACKGROUND Fluid therapy guided by cardiac output measurements is of particular importance for adequate cerebral perfusion and oxygenation in neurosurgical patients. We examined the usefulness of a noninvasive electrical velocimetry (EV) device based on the thoracic bioimpedance method for perioperative hemodynamic monitoring in patients after aneurysmal subarachnoid hemorrhage. PATIENTS AND METHODS In total, 18 patients who underwent surgical clipping or endovascular coiling for ruptured aneurysms were examined prospectively. Simultaneous cardiac index (CI) measurements obtained with EV (CIEV) and reference transpulmonary thermodilution (CITPTD) were compared. A total of 223 pairs of data were collected. RESULTS A significant correlation was found between CIEV and CITPTD (r=0.86; P

Carotid artery stenting (CAS) has become a common treatment for carotid artery stenosis. However, complications, such as an ischemic event, can occur with CAS during intra- and post-operative periods. Among these ischemic complications, plaque protrusion into the stent and thrombus on the stent have occurred after CAS. We retrospectively evaluated the temporal profile and treatment options for these complications in 32 consecutive cases who underwent CAS at our hospital between April 2009 and December 2011. The cases were evaluated pre-operatively for risk factors, as well as the plaque morphology and characteristics using computed tomographic angiography (CTA), ultrasound (US), and magnetic resonance imaging (MRI). Post-operatively, lesions were examined by CTA and/or US within 1 week of CAS. As a result, among the 32 cases, 8 experienced plaque protrusions or thrombus, which were treated with medication (anti-platelet and/or anti-coagulation reinforcement). In 7 of these 8 cases, the plaque protrusion or thrombus was stabilized with medication alone. However, the remaining case showed growth and migration of the plaque protrusion or thrombus when treated with medication alone, and therefore, required further endovascular treatment. We identified that a history of symptomatic cerebral infarction and plaques with ulceration were risk factors for plaque protrusion or thrombus formation after CAS, and pre dilatation can decrease the risk of these complications. Medication was effective in most cases of plaque protrusion or thrombus; however, further endovascular treatment was required when medication alone was unsuccessful.

Recent clinical data suggest that postoperative hemodynamic profile and fluid management may differ in aneurysmal subarachnoid hemorrhage patients depending on the treatment option: surgical clipping or endovascular coiling. Our aim was to determine the differences in hemodynamic parameters between the 2 modalities using an advanced transpulmonary thermodilution technique.We studied 73 consecutive aneurysmal subarachnoid hemorrhage patients treated with either clipping or coiling. Transpulmonary thermodilution was established for monitoring cardiac index, global end-diastolic volume index (GEDI), and extravascular lung water index (ELWI). Blood biochemical markers were sampled in parallel.Hypovolemia (GEDI: 656±72 vs. 713±40 mL/m; P=0.0001) and elevated plasma brain natriuretic peptide (114.0±56.7 vs. 68.6±47.4 pg/mL; P=0.0004) were evident on initial measurements in the clipping group. The number of fluid challenges until normalization of GEDI and ROC-based prediction of the responders (GEDI≥10%) during vasospasm risk period (day 4 to 14 of ictus) were less with coiling than with clipping (P0.05). Therapy-related pulmonary edema was detected only in the clipping group (8%, n=3). Although length of intensive care unit stay was shorter in the coiling group (P=0.016), incidences of delayed ischemia (13% vs. 11%; P=0.50) and poor functional outcome on modified Rankin Scale score 4 to 6 at 1 month (37% vs. 46%; P=0.30) were not statistically different.Surgical clipping is associated with higher cardiac output and hypovolemia in the early postoperative stage and poorer preload responsiveness to volume therapy during the vasospasm risk period compared with endovascular coiling.

The aim of this study was to obtain data of gait parameters on predicting long-term outcome of hippotherapy. In 20 participants (4-19 years; GMFCS levels I to III) with cerebral palsy (CP), gait and balance abilities were examined after 10-m walking test using a portable motion recorder. Hippotherapy was associated with increased Gross Motor Function Measure (GMFM)-66 at 1 year from the baseline (P

An 11-month-old ASA 1 male miniature dachshund was anaesthetised for neutering. Butorphanol and midazolam were administered as preanaesthetic medication along with cefazolin. Anaesthesia was induced with propofol and maintained with isoflurane. Latex products (surgical gloves and a breathing bag) were used intraoperatively. Intraoperative vital signs were within normal ranges. Approximately 5 min after extubation, the dog developed intense urticarial erythema, hypotension and pulmonary oedema. First-line treatment with repeated intramuscular epinephrine, oxygenation, fluid loading, corticosteroids and antihistamines to address severe hypotension was unsuccessful. Additional vasopressin, continuous epinephrine infusion, mechanical ventilation and cardiopulmonary resuscitation proved unsuccessful and the owners opted for euthanasia. The causative agent remains unclear; serological or skin tests were not performed. This is the first report of severe perioperative anaphylactic shock in a dog unresponsive to current therapeutic recommendations based on epinephrine administration. Further research is warranted to advance clinical guidelines for managing anaphylaxis in dogs.

Introduction: Hyperdynamic therapy with dobutamine (DOB) administration on patients with subarachnoid hemorrhage (SAH) is a useful strategy for treating cerebral vasospasm and neurological deterioration. Even some reports have suggested that DOB administration caused the cerebral blood flow (CBF) augmentation by increasing cardiac output, microcirculatory behavior in brain remains unclear. Hypothesis: Red blood cell (RBC) velocity should be increased under DOB administration. To investigate the cortical microcirculation, two-photon laser scanning microscopy with successive line-scans was used for red blood cell (RBC) velocity estimation. Methods: SAH was induced in ten male wild-type C57BL/6 mice (23 - 25g) using endovascular perforation technique. Five days after SAH, a cranial window was prepared for optical access to the cortical vasculature. Then we observed two-photon microscopy with intravenously injected rhodamine-dextran. The RBC velocity was visualized as dark objects against the fluorescent plasma background. The velocity was estimated from dark objects angle in successive line-scans analyzed by Radon function based algorithm. DOB was administrated intravenously at the dose of 6 and 12 μg/kg/min. Results: RBC velocity was increased in 8 mice after the DOB administration and 2 mice were reduced. The RBC velocity in increased mice of baseline , 6 , and 12 μg/kg/min was 1.29±0.40, 1.70±0.74 and 1.37±0.53 mm/sec, respectively. In the reduced mice, the RBC velocity was dropped almost half value of baseline at the DOB administration. Conclusions: DOB administration was increased RBC velocity in cortical microcirculation. It indicates DOB hyperdynamic therapy on patients with SAH is effective in the viewpoint of cortical microcirculatory control.

Acute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH.Twenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively.Initial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (P0.05). MIL raised CBF in a dose-dependent manner (P0.001), resulted in lower incidence of DCI (P=0.008) and better recovery from neurobehavioral decline than control (P0.001). The CBF values on day 1 predicted DCI with a cut-off of 42.5ml/100g/min (82% specificity and 83% sensitivity), which was greater in mice treated with MIL than those of control (51.7 versus 37.6ml/100g/min; P0.001).MIL improves post-SAH acute hypoperfusion that can lead to the prevention of DCI and functional worsening, acting as a neurocardiac protective agent against EBI.

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P

Early brain injury/ischemia is a recent therapeutic target that contributes to triggering delayed cerebral ischemia (DCI) in the setting of subarachnoid hemorrhage (SAH). This study aimed to determine the role of dobutamine for inotropic cardiac support in improving cerebral blood flow (CBF) and outcomes after experimental SAH, mediated by hypoxia-inducible factor (HIF). Thirty-one mice were subjected to SAH by endovascular perforation, and assigned to either 2% isoflurane postconditioning performed between 1 and 2.5h after SAH induction or concomitant intravenous dobutamine infusion (15μg/kg/min) with or without HIF inhibitor 2-methoxyestradiol (2ME2) (10mg/kg) administered intraperitoneally. Neurobehavioral function was assessed daily by neurological scores and open field testing. DCI was defined 3days later by detecting a new infarction on MRI. Global CBF depression was notable early after SAH, but dobutamine showed significant improvement in CBF, lower incidence of DCI, and better recovery of neuroscores and open field test variables compared with isoflurane postconditioning (P