Severe underweight and cerebral microbleeds

Severely low and/or high body mass index (BMI) has been associated with intracerebral hemorrhage (ICH) risk in several large cohorts. The aim of this study is to assess the relationship between BMI and the presence of cerebral microbleeds. The presence and number of microbleeds were assessed on three-dimensional T2*-weighted gradient-recalled-echo sequence on magnetic resonance imaging (MRI). The inclusion criteria were participants aged >40?years old without aneurysmal subarachnoid hemorrhage and any type of cerebral vascular malformations. BMI was categorized into severe underweight (<17.0?kg/m²), mild underweight (17.0?C18.4?kg/m²), normal range (18.5?C24.9?kg/m²), overweight (25.0?C29.9?kg/m²), and obese (??30.0?kg/m²). Multivariate analyses were adjusted for age, sex, hypertension, smoking, alcohol, stroke subtype, severity of periventricular hyperintensities and deep white matter hyperintensities, and dementia. Additionally, we conducted stratification analyses by age, ICH, smoking habit, or history of any kind of cancer, respectively. A total of 384 participants (232 males, 152 females; mean age 67.5?years) met our inclusion criteria. Overall mean BMI was 22.8?±?3.6?kg/m². On multivariate analyses, severe underweight carried a significantly higher risk for cerebral microbleeds (3.48, 1.06?C11.4) compared with normal range BMI, even after stratification in the subgroup aged ??60?years (7.23, 1.57?C33.2), nonsmokers (4.75, 1.10?C20.5), noncancer subgroup (5.66, 1.31?C24.5), and non-ICH subgroup (3.81, 1.14?C12.7). We found that severe underweight was an independent significant risk factor for presence of cerebral microbleeds, even after effect of aging, smoking, or preexisting illness was eliminated.     

Dual-task repetition alters event-related brain potentials and task performance

ObjectiveWe examined the modulation of event-related brain potentials (ERPs) and the accuracy of sensori-motor coordination on short-term repetition of the concurrent performance of a somatosensory discrimination (oddball) task and a visuo-motor tracking task.MethodsThe subjects concurrently performed visuomotor tracking and somatosensory oddball tasks. In the dual-task condition, the subjects performed the visuomotor tracking and somatosensory oddball tasks concurrently for about an hour. In the oddball-only condition, they performed just the oddball task for the same period.ResultsTracking performance improved with task repetition. The amplitude of the P300 elicited by somatosensory stimulation in the oddball-only condition decreased significantly with task repetition, whereas in the dual-task condition, it showed a complex pattern of change. The earlier responses were decreased in amplitude in the dual-task condition compared to the oddball-only condition, and gradually decreased with task repetition in both conditions.ConclusionsDynamic changes in ERPs and task performance with dual-task repetition support the idea that dual-task repetition produces changes in resource allocation following the automation of stimulus processing in addition to so-called habituation.SignificanceThis study also provides evidence for use of ERP amplitudes as physiological indices of functionally different types of resources.     

Ectopic Overexpression of Orexin Alters Sleep/Wakefulness States and Muscle Tone Regulation during REM Sleep in Mice

Orexins (also called hypocretins), which are neuropeptides exclusively expressed by a population of neurons specifically localized in the lateral hypothalamic area, are critically implicated in the regulation of sleep/wake states. Orexin deficiency results in narcoleptic phenotype in rodents, dogs, and humans, suggesting that orexins are important for maintaining consolidated wakefulness states. However, the physiological effect of constitutive increased orexinergic transmission tone, which might be important for understanding the effects of orexin agonists that are promising candidates for therapeutic agents of narcolepsy, has not been fully characterized. We report here the sleep/wakefulness abnormalities in transgenic mice that exhibit widespread overexpression of a rat prepro-orexin transgene driven by a β-actin/cytomegalovirus hybrid promoter (CAG/orexin transgenic mice). CAG/orexin mice exhibit sleep abnormalities with fragmentation of non-rapid eye movement (REM) sleep episode and a reduction in REM sleep. Non-REM sleep was frequently disturbed by short episodes of wakefulness. EEG/EMG studies also reveal incomplete REM sleep atonia with abnormal myoclonic activity during this sleep stage. These results suggest that endogenous orexinergic activity should be appropriately regulated for normal maintenance of sleep states. Orexinergic transmission should be activated during wakefulness, while it should be inactivated or decreased during sleep state to maintain appropriate vigilance states.     

Sleep disordered breathing in childhood-onset acid maltase deficiency

Objectives: To clarify the feature of sleep disordered breathing (SDB) associated with childhood-onset acid maltase deficiency (AMD): the progressive nature of SDB and the stage of AMD. Study design: We retrospectively studied 4 patients with childhood-onset AMD by analyzing the results of neurological examinations for muscle wasting and muscle strength and the data on venous gas and from a pulmonary function test and nocturnal polysomnography (PSG). Results: Three out of the 4 patients showed muscular symptoms including myalgia, lordoscoliosis, muscle wasting and muscle weakness. They also complained of sleep-related symptoms such as tiredness in the morning and daytime sleepiness. All of them showed SDB by PSG, even in a patient in the earliest stage who exhibited no signs or symptoms of muscle weakness. In 3 patients, noninvasive intermittent positive pressure ventilation during sleep was introduced; and thereafter sleep-related symptoms were resolved and no lower respiratory infection reoccurred. Although their quality of life was improved, no improvement of respiratory function was shown by spirometry over a 2-year follow-up period. Conclusions: SDB seems to be common in childhood-onset AMD, which is not always accompanied by daytime muscular symptoms, especially in mild patients. PSG should be utilized for detecting SDB, which could be one of the earliest signs of respiratory muscle involvement in childhood-onset AMD.     

Novel partial deletions,frameshift and missense mutations of CSF1R in patents with CSF1R-related leukoencephalopathy

Background and purpose

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features.

Methods

Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study.

Results

CSF1R mutations were identified in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C-terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features.

Conclusions

Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.     

Human decidual macrophages suppress IFN-γ production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy

In human pregnancy, CD14⁺ decidual macrophages (DMs) are the dominant professional antigen-presenting cells in the decidua, comprising 20–30% of the local leukocyte population. Although the relevance of DMs to feto-maternal immune tolerance has been described, the molecular mechanisms underlying these functions have not been fully elucidated. B7-H1, a costimulatory ligand in the B7 family, negatively modulates T cell activity by binding to its corresponding receptor, PD-1. The present study aimed to investigate the functional significance of costimulatory interactions between DMs and T cells, with a particular focus on B7-H1:PD-1 signaling. An analysis of the expression profile of B7 ligands on human DMs revealed that B7-H1 was present on DMs isolated from early but not term pregnancies. B7-H1 was not expressed on the peripheral monocytes (PMs) of pregnant women. In response to IFN-γ, B7-H1 expression was induced on PMs and was enhanced on DMs, suggesting that this cytokine might be a key factor in the control of B7-H1 expression in the decidua. The majority of decidual T cells were noted to exhibit robust expression of PD-1, whereas the expression was limited to a small subpopulation of circulating T cells. Functional assays demonstrated that DMs are able to suppress T cell IFN-γ production via B7-H1:PD-1 interactions. This suppressive property was not observed for PMs, which lack B7-H1. B7-H1 on DMs may function as a key regulator of local IFN-γ production and thereby contribute to the development of appropriate maternal immune responses to the fetus in early pregnancy.     

Plasma adiponectin concentrations and placental adiponectin expression in pre-eclamptic women

This study was conducted to compare maternal plasma adiponectin concentrations and adiponectin expression in term placentas between normotensive pregnant women and pre-eclamptic women. Plasma adiponectin concentrations were assessed by a sandwich enzyme-linked immunosorbent assay in 81 normotensive pregnant women, 27 pre-eclamptic women and 15 non-pregnant healthy women. The expression of adiponectin in the placentas was assessed by immunohistochemistry. Plasma adiponectin concentrations in normotensive pregnant women did not show a significant change during pregnancy and postpartum compared with non-pregnant women. However, plasma adiponectin concentrations in pre-eclamptic women were significantly (p < 0.05) lower than in non-pregnant and normotensive pregnant women. No immunoreactive adiponectin was detected in the term placentas of normotensive pregnant women, whereas a positive immunostaining for adiponectin was observed in endothelial cells of chorionic vessels in pre-eclamptic women. Our data suggest that decreased plasma adiponectin concentrations may contribute to the pathophysiology of pre-eclampsia and that adiponectin localized in chorionic vessels may play a role in the restoring of endothelial damage in the feto-maternal units of pre-eclampsia.     

Ectopic pregnancy following emergency contraception with ethinyloestradiol-levonorgestrel: A case report

Background?Emergency contraception with ethinyloestradiol-levonorgestrel is effective, and ectopic pregnancy following its failure is rare.

Case?A 21-year-old nulligravid Japanese woman with regular menstrual periods took ethinyloestradiol-levonorgestrel pills for emergency contraception (EC) 36 and 48 hours after a coitus complicated by retention of the condom in the vagina. She started bleeding vaginally 24 days after that intercourse. As the bleeding continued for three weeks she consulted a gynaecologist. The pregnancy test was positive. Two weeks later she complained of lower abdominal pain, and transvaginal ultrasonography suggested a pelvic blood collection. At emergency surgery, she was found to have a left tubal pregnancy.

Conclusion?Although ectopic pregnancy after failure of EC is rare, one should be alert to its possible occurrence.     

Effective treatment of pelvic lymphocele by lymphaticovenular anastomosis

ObjectivePelvic lymphocele can be a severe complication associated with surgical procedures such as pelvic lymphadenectomy. Lymphaticovenular anastomosis (LVA) is increasing in popularity as a surgical treatment for lymphedema. The aim of this study was to evaluate whether LVA is an effective treatment for lymphocele, which is caused by an obstruction of the lymphatic flow in a manner similar to the development of lymphedema.MethodsEleven female patients, who presented with lymphocele, were treated with LVA. Before the operation, 3 of them were treated with a percutaneous catheter. Lymphocele size and the volume of daily drainage were measured before and after LVA.ResultsThe lymphocele was completely resolved in 6 patients and partially resolved in the remaining 5 patients. The mean size of the pelvic lymphocele changed from 400 ml (range 50–1050 ml) to 43 ml (range 0–120 ml) (P < 0.01). In the 3 patients who had percutaneous drainage catheters, the volume of fluid drained decreased from 340 ml/day to 20 ml/day after LVA.ConclusionsOur technique is minimally invasive and is performed under local anesthesia. LVA is effective regardless of the size of the lymphocele. Therefore, LVA should be considered as a therapy for lymphocele because of its low invasiveness and its effectiveness in re-establishing circulation of lymphatic flow. Further studies should be performed to compare LVA with other minimally invasive techniques, such as percutaneous catheter and sclerotherapy.     

Ostial common carotid artery occlusion and balloon-mounted stenting: Implication of embolic protection device in tandem lesion

Ostial common carotid artery (CCA) stenosis is rare, compared to extracranial internal carotid artery bifurcation lesions. In cases of a tandem lesion, the proximal lesion usually involves the extracranial internal carotid artery, and the ostial CCA is rarely implicated. A 69-year-old woman who underwent 3 months of antiplatelet therapy for asymptomatic, right ostial, severely calcified CCA stenosis presented with sudden onset left hemiparesis. Radiographic examination revealed an ostial CCA-intracranial artery tandem lesion. After intracranial revascularization using a clot retrieval stent, we performed the endovascular treatment with a balloon-mounted stent using an embolic protection device. This procedure may be superior to others because it is possible to achieve early intracranial revascularization and prevent distal embolism during the complete treatment of proximal lesions.