DTI-ALPS: An MR biomarker for motor dysfunction in patients with subacute ischemic stroke.

Purpose: Brain glymphatic dysfunction is involved in the pathologic process of acute ischemic stroke (IS). The relationship between brain glymphatic activity and dysfunction in subacute IS has not been fully elucidated. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was used in this study to explore whether glymphatic activity was related to motor dysfunction in subacute IS patients. Methods: Twenty-six subacute IS patients with a single lesion in the left subcortical region and 32 healthy controls (HCs) were recruited in this study. The DTI-ALPS index and DTI metrics (fractional anisotropy, FA, and mean diffusivity, MD) were compared within and between groups. Spearman's and Pearson's partial correlation analyses were performed to analyze the relationships of the DTI-ALPS index with Fugl-Meyer assessment (FMA) scores and with corticospinal tract (CST) integrity in the IS group, respectively. Results: Six IS patients and two HCs were excluded. The left DTI-ALPS index of the IS group was significantly lower than that of the HC group (t = -3.02, p = 0.004). In the IS group, a positive correlation between the left DTI-ALPS index and the simple Fugl-Meyer motor function score (ρ = 0.52, p = 0.019) and a significant negative correlation between the left DTI-ALPS index and the FA (R = -0.55, p = 0.023) and MD (R = -0.48, p = 0.032) values of the right CST were found. Conclusions: Glymphatic dysfunction is involved in subacute IS. DTI-ALPS could be a potential magnetic resonance (MR) biomarker of motor dysfunction in subacute IS patients. These findings contribute to a better understanding of the pathophysiological mechanisms of IS and provide a new target for alternative treatments for IS.

Clinical and Polysomnographic Characteristics of Nonobese and Obese Chinese Patients With Obstructive Sleep Apnea.

PURPOSE: Obesity is a risk factor associated with the onset and exacerbation of obstructive sleep apnea (OSA). However, the majority of OSA patients in Asian populations are nonobese. To date, there have been insufficient large-scale studies of the differences in the clinical and polysomnographic features of obese and nonobese OSA patients in this population, and few studies have sought to identify predictors of OSA severity in affected obese and nonobese patients. METHODS: We conducted a case-matched retrospective study, including 652 consecutive Chinese OSA patients (326 nonobese and 326 obese) to assess differences in demographic, clinical, and polysomnographic data between these two groups. Independent predictors of OSA severity were identified through multivariate linear regression analysis. RESULTS: The age and gender distributions of our obese and nonobese OSA patient cohorts did not differ significantly ( P > 0.05), and rates of comorbidities were comparable in these two patient groups ( P > 0.05). Nonobese patients were more likely to report atypical symptoms of OSA, including insomnia ( P < 0.001), irritability ( P < 0.05), and depressive symptoms ( P < 0.01), whereas obese patients were more likely to report typical symptoms of OSA, such as habitual snoring ( P < 0.001), witnessed apnea ( P < 0.05), and daytime sleepiness ( P < 0.001). Relative to nonobese patients, those who were obese exhibited significantly higher apnea-hypopnea index during total sleep time ( P < 0.001), apnea-hypopnea index during nonrapid eye movement sleep ( P < 0.001), and apnea-hypopnea index during rapid eye movement sleep ( P < 0.001), in addition to lower average oxygen saturation ( P < 0.001), minimal oxygen saturation ( P < 0.001), and a higher oxygen desaturation index ( P < 0.001) and arousal index ( P < 0.001). Total sleep time was, on average, shorter for nonobese patients ( P < 0.05), who also exhibited decreased sleep efficiency and more frequent awakening relative to obese patients ( P < 0.05). A multivariate linear regression analysis revealed that neck circumference and waist circumference were independent predictors of OSA severity in obese patients ( P < 0.05). CONCLUSIONS: On average, OSA was typically less severe in nonobese patients, who were also more likely to experience atypical OSA symptoms relative to obese patients. These results also suggest that the differential contributions of body fat accumulation and distribution to OSA severity may offer insights into the pathogenesis, clinical manifestations, and optimal management of this condition in nonobese and obese patient populations. It is vital that clinicians consider these differences to properly diagnose and treat this debilitating condition.

Correlation of serum myonectin concentrations with the presence and severity of obstructive sleep apnoea syndrome.

OBJECTIVE: Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating concentrations of free fatty acids in mice. This study is performed to evaluate the association between serum myonectin concentrations with the presence and severity of OSAS. METHODS: This study was performed in a population of 191 patients with OSAS and 105 control subjects. Serum myonectin concentrations were measured using enzyme-linked immunosorbent assay method. RESULTS: Lower serum myonectin concentrations were found in OSAS patients than in the controls. Serum myonectin concentrations were associated with a reduced risk of OSAS (OR: 0.988, 95% CI: 0.984-0.993, P < 0.001). Severe OSAS patients had significantly lower myonectin concentrations compared with mild and moderate OSAS patients (P < 0.001 and P = 0.001, respectively). There are lower serum myonectin concentrations in moderate patients compared with mild patients (P = 0.024). Pearson correlation analysis revealed that serum myonectin concentrations were negatively correlated with the severity of OSAS (r = -0.344, P < 0.001). Simple linear regression analysis showed that serum myonectin concentrations in OSAS patients were negatively correlated with body mass index, fasting plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C) and apnoea hypopnea index. Multiple stepwise regression analysis shows that body mass index (ß = -0.289, P = 0.03), HOMA-IR (ß = -0.19, P = 0.003), total cholesterol (ß = -0.155, P = 0.016), LDL-C (ß = -0.176, P = 0.006) and apnoea hypopnea index (ß = -0.263, P < 0.001) remained to be associated with serum myonectin. CONCLUSION: Serum myonectin concentrations are inversely correlated with the presence and severity of OSAS.

Gender differences in clinical manifestations and polysomnographic findings in Chinese patients with obstructive sleep apnea.

PURPOSE: The gender differences in patients with obstructive sleep apnea (OSA) are not fully understood so far, as previous studies had conflicting results. No reports have addressed the differences in OSA between Chinese men and women. Therefore, the purpose of this study was to investigate the clinical and polysomnographic differences between Chinese men and women with OSA. METHODS: This case-paired control retrospective study included 580 consecutive Chinese patients (290 males and 290 females) newly diagnosed as OSA by overnight polysomnography from the Sleep Disorders Center of Tangdu Hospital affiliated to the Fourth Military Medical University of China. Demographic, clinical, and polysomnographic data of men and women with OSA were compared. Order logistic regression analysis was used to determine the risk factors for OSA severity. RESULTS: Male and female patients had similar age (57.3 ± 9.2 vs. 58.2 ± 8.9, p > 0.05) and body mass index (BMI) (25.4 ± 3.4 vs. 25.5 ± 3.9, p > 0.05). Women more commonly presented with insomnia (70.3% vs. 40.3%, p < 0.001), poor sleep quality (58.3% vs. 40.7%, p < 0.001), and headache on awakening (23.1% vs. 13.8%, p < 0.01) than men, while men more frequently reported habitual snoring (69.0% vs. 52.1%, p < 0.001) compared with women. The apnea-hypopnea index (AHI) during total sleep time and non-rapid eye movement sleep was higher in men compared with women (25.8 ± 20.4 vs. 19.3 ± 16.8; 22.0 ± 18.2 vs. 15.1 ± 15.4; p < 0.001, respectively), whereas AHI during rapid eye movement sleep was higher in women than in men (4.2 ± 3.6 vs. 3.7 ± 4.3, p < 0.01). Compared with men, women had lower sleep efficiency (75.4 ± 15.7 vs. 78.1 ± 15.5, p < 0.05), longer REM latency (128.9 ± 88.6 vs. 107.7 ± 72.4, p < 0.01), and greater wakefulness after sleep onset (WASO) (98.3 ± 70.2 vs. 88.0 ± 70.3, p < 0.05). No significant differences in the lowest oxygen desaturation and oxygen desaturation index (ODI) were observed between men and women (80.4 ± 10.8 vs. 80.8 ± 9.0; 17.0 ± 20.9 vs. 13.1 ± 16.5; p > 0.05, respectively). In addition, ordinal logistic regression analysis identified neck circumference as an independent risk factor for OSA severity in male patients (OR, 1.161; 95% CI, 1.020-1.325; p < 0.05) and in female patients (OR, 1.163; 95% CI, 1.013-1.338; p < 0.05). CONCLUSIONS: Overall, female patients had less severe OSA when compared with male patients. The female patients more commonly reported "atypical" OSA symptoms, while male patients more frequently reported "typical" OSA symptoms. In clinical practices, physicians dealing with OSA need to take the gender disparity into consideration for more precise diagnosis and treatment, as women may be atypically symptomatic at a less severe OSA.

Expression of the LIM-homeodomain gene Lmx1a in the postnatal mouse central nervous system.

The LIM-homeodomain transcription factor Lmx1a plays critical roles in roof plate formation as well as in the cell fate determination of midbrain dopaminergic neurons during embryonic development, but its function in the adult brain remains unknown. In the present study, as the first step in exploring its function in adult brain, we examined the expression of Lmx1a in the mouse central nervous system (CNS) from birth to adulthood by in situ hybridization. Lmx1a was expressed at high levels in the posterior hypothalamic area, supremammillary nucleus, ventral premammillary nucleus, subthalamic nucleus, ventral tegmental area, compact part of the substantia nigra and parabrachial nucleus from birth to adulthood, and co-localized with its paralogue Lmx1b in these regions. On the other hand, Lmx1a expression in the cochlear nuclei, medial cerebellar nucleus and superior vestibular nucleus was only observed until postnatal day (P) 30 and showed no colocalization with Lmx1b. Lmx1a-expressing neurons in the ventral midbrain were dopaminergic as evidenced by co-expression with tyrosine hydroxylase in these regions. Furthermore, Lmx1a expression was also found in the choroid plexuses and ependymal cells, although its expression was only detected during the first two postnatal weeks. These results suggest that Lmx1a may be involved in postnatal development as well as in maintenance of some aspects of normal brain function.

Expression of the transcription factor GATA3 in the postnatal mouse central nervous system.

GATA binding protein 3 (GATA3) is an important regulator of central nervous system (CNS) development, but its expression pattern in the postnatal CNS has not been studied. In the present study, we examined the distribution of GATA3 mRNA in the mouse CNS at different postnatal stages by in situ hybridization. During the first 2 weeks of postnatal development, numerous GATA3-expressing cells were found in the intergeniculate leaf, ventral lateral geniculate nucleus, pretectal nucleus, nucleus of the posterior commissure, superior colliculus, inferior colliculus, periaqueductal grey, substantia nigra and raphe nuclei. Few notable changes in the profile of GATA3 expression occurred over this time period. As postnatal development progressed, however, GATA3 expression weakened, and was maintained in only a few regions of the adult CNS. Throughout the brain, we found that GATA3-expressing cells were NeuN-positive, and no colocalization with glial fibrillary acidic protein (GFAP) was observed. In the substantia nigra, GATA3 was exclusively expressed in cells of the reticulate part and some of which were found to be GABAergic. This study presents a comprehensive overview of GATA3 expression in the CNS throughout postnatal life, and the dynamics that we observed provide insights for further investigations of the roles of GATA3 in postnatal development and the maintenance of the mature CNS.