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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.

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.

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.

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 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

Aims Neurocardiac dysfunction is a life-threatening systemic consequence of subarachnoid hemorrhage (SAH) that contributes to triggering delayed cerebral ischemia (DCI). This study aimed to determine the impact of dobutamine cardiac support during isoflurane postconditioning on post-SAH DCI. Main methods Male C57BL/6 mice were subjected to SAH, SAH plus isoflurane postconditioning, or SAH plus isoflurane postconditioning with dobutamine. Severity of SAH was graded from 1 to 4 (mild, 1–2; severe, 3–4) based on T2*-weighted magnetic resonance imaging (MRI). Cardiac output (CO) measured by transthoracic pulsed wave Doppler-echocardiography was titrated at a supra-normal level with intravenous dobutamine infusion. Neurological function was examined daily by neurological score and Rotarod tests. DCI was analyzed 3 days later by determining new infarction on diffusion-weighted MRI. In a separate experiment, mice were pretreated with hypoxia-inducible factor (HIF) inhibitor 2-methoxyestradiol (2ME2). Key findings Clinically relevant CO depression was notable in severe SAH grade mice, in which dobutamine CO management combined with isoflurane postconditioning showed earlier and improved functional recovery than postconditioning with single isoflurane inhalation. Incidence of infarction and volumes on day 3 reduced significantly in this subgroup. All of the effects during preconditioning were attenuated by 2ME2 pretreatment. Significance Isoflurane postconditioning under dobutamine cardiac support improves recovery from SAH-induced early brain injury, leading to reduced DCI resultant from severe experimental SAH. These results indicate the importance of neuro-cardiac protection, in which HIF may be acting as a critical mediator, as a promising therapeutic approach to SAH.

A small part of the patients with subarachnoid hemorrhage (SAH) are not properly diagnosed until they suffer ischemic neurological deficits and/or rebleeding during vasospasm. We therefore investigated the clinical profile of such patients. We retrospectively analyzed 581 patients with aneurysmal SAH experienced in our institute between 2001 and 2009. Patient’s characteristics, presence and severity of headache before final diagnosis, imaging investigations they received, their World Federation of Neurological Surgeons (WFNS) grades at admission, the location of aneurysm, treatment, and outcome at discharge were investigated. Five patients were not correctly diagnosed until they presented neurological deficits due to vasospasm or experienced simultaneous rebleeding. Their mean age was 69.4, and all were female. Although all patients had a bad headache, they did not undergo any imaging examinations. Immediate coil embolization was performed for 2 patients, 1 died due to rupturing during embolization procedure. The other 3 were treated by open clipping surgery (2 delayed and 1 immediate). Four patients had some disability as a sequel, and their outcomes were significantly worse compared with 53 patients with SAH in WFNS Grade II. The patients with SAH who had not been properly diagnosed in the acute stage had a poor outcome. We should be very careful when we see patients complaining of severe headache.

Hemodynamic augmentation by increasing cardiac output with dobutamine (DOB) is believed to be a useful method of elevating decreased cerebral blood flow in the territory affected by vasospasm following aneurysmal subarachnoid hemorrhage (SAH). We described the clinical utility of uncalibrated radial artery-based pulse contour cardiac output (APCO) and near-infrared spectroscopy regional cerebral oxygen saturation (rSO(2)) monitoring for reversing vasospasm symptoms with DOB-induced hyperdynamic therapy.Seven consecutive patients who underwent surgical clipping within 24 h of SAH onset and subsequently developed delayed ischemic neurological deficits attributable to vasospasm were investigated. They were treated with DOB administered at a dose of 3 μg/kg/min and then increased in 3 μg/kg/min increments until resolution of the symptoms. Continuous APCO and rSO(2) measurements in conjunction with the assessment of clinical courses and outcomes were performed.In spasm-affected territories, decreased and/or fluctuating rSO(2) was detected at baseline compared with recordings in other brain regions. Patients who exhibited rapid elevation of APCO in response to an incremental dose of DOB had subsequent uptake and stabilization of rSO(2) followed by improvement of vasospasm-related clinical symptoms with a maximal dose of DOB, resulted in favorable functional outcomes thereafter. A fairly strong relationship was found between peak APCO slope and rSO(2) elevation, with a significantly high area under the receiver operating characteristic curve predicting neurological improvement with DOB treatment.Our clinical experience indicates that integrative monitoring with APCO and rSO(2) may provide continuous, real-time, and clinically relevant information on the effectiveness of medical treatment of distal vessel vasospasm.

The aims of this study were to introduce our newly developed device equipped with a contact surface force sensor (FlexiForce) for monitoring extraocular compression continuously, and to illustrate its potential clinical application using this device in patients undergoing uncomplicated frontotemporal or bifrontal craniotomy for surgical clipping of unruptured anterior circulation aneurysms. In a pilot study with volunteers, we determined the critical force of 100 gf to cause painful ocular sensation. Then we performed the bilateral extraocular force measurements in 15 patients undergoing uncomplicated frontotemporal or bifrontal craniotomy for surgical clipping of unruptured anterior circulation aneurysms. Extraocular force increased immediately after retraction of the flap, increased to 144+/-26 gf (mean+/-SD) during lower craniotomy close to the orbit, was maintained at 91+/-18 gf during microsurgery, and returned close to baseline at 24+/-14 gf after restoration of skin flap retraction. Such changes were observed only on the surgical side in frontotemporal craniotomy. Abnormal increase in extraocular force was effectively reduced by placing a real-time digital panel meter to warn surgeons to avoid excessive skin flap retraction during the surgical procedure. In conclusion, this new tool may allow us to monitor the external forces that can be applied intraoperatively to the ocular globe in the supine position.

Blood blister-like aneurysms are dangerous aneurysms with fragile walls arising from the supraclinoid internal carotid artery (ICA). Primary treatment of these aneurysms in the acute stage is challenging, due to the substantial risk of periprocedural bleeding. We describe a series of 4 patients who presented with ruptured blister-like aneurysm of the ICA and were treated with completion of extracranial-intracranial high-flow bypass followed by inspection and trapping of the aneurysm. All patients were treated in the acute stage, within 48 hours of bleeding. External carotid artery to proximal middle cerebral artery bypass with interposed radial artery (RA) graft was established followed by approach to the lesion and trapping of the parent vessels. The aneurysms in 3 patients ruptured during dissection of the lesion from the surrounding structures, but bleeding was easily controlled. RA grafts were patent in all patients and no postoperative symptomatic ischemic or hemorrhagic complications were encountered, resulting in excellent outcomes with modified Rankin scale scores of 0 at follow up after 3 months. Our present strategy for surgical treatment of blister-like aneurysms completely avoided the risk of devastating intraoperative hemorrhage, offering a most cautious strategy associated with minimal risk of intraoperative massive bleeding.

We report intraoperative difficulties we have encountered during clipping surgery for unruptured cerebral aneurysms. There is a low risk of intraoperative rupture, but when it occurs, it can be managed either by tentative clipping or proximal flow control. The risk of aneurysm rupture can be decreased by gentle manipulation of the aneurysm, as well as full mobilization of the aneurysm and its neighboring vessels. Adhesions of vascular structures, arteries, and/or veins can be separated from the aneurysm in almost all cases with careful and sharp dissection. Injuries to perforating vessels are the most common problems. The risk of permanent injury can be reduced by combining multiple monitoring methods, especially MEP (motor evoked potential) and micro-Doppler. It is vitally important that we be aware of the difficulties that may occur during surgery and develop methods to avoid or manage them.

Neurogenic pulmonary edema (NPE) is a potentially catastrophic but treatable systemic event after subarachnoid hemorrhage (SAH). The development of NPE most frequently occurs immediately after SAH, and the severity is usually self-limiting. Despite extensive research efforts and a breadth of collective clinical experience, accurate diagnosis of NPE can be difficult, and effective hemodynamic treatment options are limited. Recently, a bedside transpulmonary thermodilution device has been introduced that traces physiological patterns consistent with current theories regarding the mechanism (hydrostatic or permeability PE) of NPE. This article provides an overview of the clinical usefulness of the advanced technique for use in the neurointensive care unit for the diagnosis and management of post-SAH NPE.

Introduction Takotsubo cardiomyopathy (TCM) is a life-threatening systemic consequence early after subarachnoid hemorrhage (SAH), but precise hemodynamics and related outcomes have not been studied. The purpose of this study was to investigate TCM-induced cardiac function by transpulmonary thermodilution and its impact on clinical outcome of SAH. Methods We retrospectively analyzed 46 consecutive postoperative SAH patients who developed TCM. Patients were divided into two groups of echocardiographic left ventricular ejection fraction (LVEF) 14 ml/kg after day 4 increased the risk of poor functional outcome at 3-month follow-up (OR = 2.10, 95% CI = 1.11 to 3.97; P = 0.04). Conclusions Prolonged cardiac dysfunction and pulmonary edema increased the risk of DCI and poor 3-month functional outcome in postoperative SAH patients with TCM. Serial measurements of CFI and ELWI by transpulmonary thermodilution may provide an easy bedside method of detecting early changes in cardiopulmonary function to direct proper post-SAH treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0482-4) contains supplementary material, which is available to authorized users.

Intensive hemodynamic augmentation by increasing cardiac output (CO) is a valuable method of elevating cerebral blood flow and oxygenation in the dysautoregulated vascular territories after subarachnoid hemorrhage (SAH). We prospectively assessed the effect of hyperdynamic therapy with dobutamine (DOB) or milrinone (MIL) on regional cerebral oxygenation (rSO 2 ) for reversing clinical deterioration induced by delayed cerebral ischemia, using an integrative monitoring with uncalibrated pulse contour CO analysis and multi-channel near-infrared spectroscopy. One-hundred ten SAH patients diagnosed to have clinical deterioration due to delayed cerebral ischemia were assigned to receive hemodynamic augmentation with DOB or MIL (n=56 per each group). For hyperdynamic therapy, each inotrope was initiated at low dose (DOB: 3μg/kg/min; MIL 0.15μg/kg/min) and then increased in each dose increment until resolution of the symptoms unless any adverse effects occur during the therapy, based on our predefined hemodynamic regimen to induce similar dose-related increase in CO. Real-time CO and rSO 2 changes in conjunction with the assessment of neurological improvements were compared. A total of 425 dose increment challenges (DOB, n=197; MIL, n=228) were performed. In spasm-affected territories, decreased and/or fluctuating rSO 2 was detected compared with recordings in other brain region. Patients who exhibited rapid elevation of CO by each challenge had subsequent uptake and stabilization of rSO 2 . The responses (total number and degree of neurological improvements) were more significant in patients treated with DOB than those treated with MIL ( P < 0.05), although tachycardia that may affect stroke volume depression during the DOB therapy was more evident (DOB 28% vs. MIL 9%). Area under the ROC curve to predict rSO 2 elevation or neurological improvement for both drug groups were significant ( P < 0.0001) and the values were significantly greater in DOB than in MIL ( P < 0.05). In conclusion, DOB can provide more effective hemodynamic augmentation in relieving focal cerebral ischemia in patients after SAH. MIL is also effective in the hyperdynamic therapy but may be used as a second line in a patient subgroup when DOB was contraindicated.

Children chronically exposed to environmental tobacco smoke (ETS) have more coughs, wheezes, and airway obstruction, which may result in part from stimulation of lung C fibers. We examined the effect of chronic exposure to sidestream tobacco smoke (SS, a surrogate for ETS) on lung C-fiber responsiveness in guinea pigs, in which dynamic compliance (Cdyn), lung resistance, tracheal pressure, arterial blood pressure, and heart rate were also monitored. Guinea pigs were exposed to SS (1 mg/mm3total suspended particulates) or filtered air 5 days/wk from 1 to 6 wk of age. They were then anesthetized, and lung C fibers ( n = 55), identified by a conduction velocity of