Densely granulated adenoma pattern is associated with an increased risk of obstructive sleep apnea in patients with acromegaly.

OBJECTIVES: To explore the prevalence of obstructive sleep apnea (OSA) and the association between the adenoma granulation patterns and OSA in patients with acromegaly. METHODS: An overnight polysomnography (PSG) assessment was carried out on participants with acromegaly. Results classified participants into a non-OSA group, mild to moderate OSA group, and severe OSA group. Morphological and biochemical analyses were performed. Demographic, clinical, biochemical, and polysomnographic data were compared among the three groups. Using logistic regression models, the risk of OSA in acromegalic subjects was estimated. RESULTS: OSA was reported in 36 of 49 patients (74%) with acromegaly. Contrasted with the non-OSA group, OSA patients had a larger proportion of the densely granulated (DG) pattern. The OSA groups with DG acromegaly had a smaller maximum tumor diameter and Vol/2 than those with the sparsely granulated (SG) pattern. Furthermore, a higher growth hormone (GH) level (45.0 ± 36.9 vs 18.6 ± 15.8, P = 0.047) and GH index (28.4 ± 13.8 vs 6.6 ± 8.2, P = 0.003) were found in DG acromegaly patients with severe OSA. Additionally, there was a trend toward higher standardized insulin-like growth factor 1 (IGF-1) in patients with DG acromegaly than in those with SG acromegaly in the severe OSA group. After adjusting for potential confounding variables, the DG pattern was correlated with the risk of OSA (OR = 14.84, 95%CI 1.36-162.20, P = 0.027) in patients with acromegaly. CONCLUSIONS: The findings indicate that a high prevalence of OSA exists in patients with acromegaly, and the DG pattern may be a risk factor for OSA in acromegaly.

Association between leg motor restlessness and depression among Chinese males living at high-altitude: the mediating role of insomnia.

OBJECTIVE: Previous research has documented an association between insomnia and depression among patients with restless legs syndrome (RLS)/Willis-Ekbom disease. Given that leg motor restlessness (LMR) is closely related to RLS, the purpose of this study was to investigate the prevalence of insomnia and depression among individuals with LMR. In addition, we examined the associations among LMR, insomnia, and depression in a sample of young Chinese men living in high-altitude areas. METHODS: Chinese military personnel working on the Qinghai Tibet Plateau (Lhasa, an altitude of 3600 m) were recruited in 2019 to complete a series of questionnaires. Participants having the urge to move their legs but not meeting the diagnostic criteria for RLS were classified as having LMR. Hierarchical linear regressions and mediational analyses using the SPSS PROCESS macro in SPSS were conducted to examine the associations among LMR, insomnia, and depression. RESULTS: Of 196 participants, 36 (18%) had LMR. Only 1 participant was diagnosed with RLS. The proportions of participants suffering from insomnia who had LMR and did not have LMR were 44% and 22%, respectively. For depression, the proportions were 47% and 28%, respectively. Results of the hierarchical linear regressions showed that both LMR and depression were associated with increased insomnia symptoms. In addition, results from the mediational analyses indicated that the indirect effect of LMR on depression was significant and accounted for 52% of the total effect. CONCLUSIONS: Participants with LMR had a higher prevalence of insomnia and depression compared with those without LMR. In addition, LMR was correlated with depression, and insomnia played a significant role in this co-occurrence.

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.

ADHD in narcolepsy: A closer look at prevalence and ties.

The reported prevalence of attention deficit hyperactivity disorder (ADHD) in narcolepsy varies considerably, while the associated factors remain inadequately established. A systematic search of studies published in PubMed, EMBASE, and the Cochrane Library was performed from inception to March 2023. Ten studies with 839 patients with narcolepsy were included in the study. Utilizing a random effects model, the pooled prevalence of ADHD in narcolepsy was 25% (95% CI, 14-38%). Notably, patients with narcolepsy type 2 showed a significantly higher prevalence of ADHD than that of narcolepsy type 1 (46% vs. 20%, p = 0.045). Furthermore, the rate of ADHD was notably elevated in narcolepsy compared with the healthy controls (odds ratio 9.59, 95% CI, 4.06-22.63, p < 0.001). Several factors such as excessive daytime sleepiness (EDS), fatigue, insomnia severity, and the quality of life were significantly associated with ADHD in narcolepsy (all ps < 0.05). These findings highlight the importance of monitoring and managing ADHD in narcolepsy, and provide a clue to help reducing ADHD by intervening in these associated factors.

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.

Case report: Overlapping anti-AMPAR encephalitis with anti-IgLON5 disease post herpes simplex virus encephalitis.

Autoimmune encephalitis (AE) is the result of an autoimmune process that occurs as a rapidly advancing encephalopathy. Autoimmune encephalitis was commonly linked to herpes simplex virus 1 (HSV-1) as the most frequently identified virus. The main areas affected by this invasion are the temporal lobe, frontal lobe, and limbic system. Limbic encephalitis is a highly uncommon occurrence involving anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and anti-IgLON family member 5 (IgLON5) disease, both belonging to the rare category. As far as we know, this is the first report showing that a patient diagnosed with AMPAR encephalitis overlapped with anti-IgLON5 disease post herpes simplex virus encephalitis (HSE), which helps to broaden the range of this uncommon autoimmune disease. We recommend autoantibody testing in all patients with HSE, particularly those involving neurological relapses or progression.

Effectiveness of one-week internet-delivered cognitive behavioral therapy for insomnia to prevent progression from acute to chronic insomnia: A two-arm, multi-center, randomized controlled trial.

Acute insomnia is common and a substantial proportion of people with acute insomnia (i.e. 3 days to 3 months) transit into chronic insomnia (i.e. 3 months or longer). Therefore, early intervention for acute insomnia is vital to prevent chronicity. Previous trials with small sample sizes have shown that brief versions of both individual and group-based face-to-face cognitive behavioral therapy for insomnia (CBT-I) can improve insomnia symptoms among those with acute insomnia. However, it is unknown whether one-week internet-delivered cognitive behavioral therapy for insomnia (CBT-I) is effective in treating acute insomnia. This was a randomized controlled trial and 192 participants were randomly assigned to the CBT-I group (n = 95) or control group (n = 97). The primary outcome was the incidence of chronic insomnia, determined via a structured diagnostic questionnaire for insomnia disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Secondary outcomes were Insomnia Severity Index (ISI), Dysfunctional Beliefs and Attitudes about Sleep (DBAS), Epworth Sleepiness Scale (ESS), Pre-sleep Arousal Scale (PSAS), Ford Insomnia Response to Stress Test (FIRST), Sleep Hygiene and Practices Scale (SHPS), Hospital Anxiety and Depression Scale (HADS), and Short-Form 12-Item Health Survey version 2 (SF-12v2). At week 12, the incidence of chronic insomnia was significantly lower in the CBT-I group compared with control group (33.3% [27/81] vs. 65.8% [52/79]). Participants in the CBT-I group achieved significantly more improvements in ISI, ESS, PSAS, FIRST, SHPS, HADS-Depression, and the mental component summary and physical component summary of SF-12v2 than control group, but not DBAS and HADS-Anxiety. This one-week internet-delivered CBT-I program is an effective tool to prevent the chronicity of acute insomnia.

Changed epidemiology of narcolepsy before, during, and after the 2009 H1N1 pandemic: a nationwide narcolepsy surveillance network study in mainland China, 1990-2017.

STUDY OBJECTIVES: Increased incidence of narcolepsy was reported in children during the 2009 H1N1 pandemic following Pandemrix, a H1N1 flu vaccine. A link with A(H1N1) pdm09 infections remains controversial. Using nationwide surveillance data from China (1990 to 2017), the epidemiology of narcolepsy was analyzed. METHODS: Individual records of narcolepsy patients were collected from 15 of 42 hospitals across China known to diagnose cases. Incidence was estimated assuming the representativeness of these hospitals. Age-specific incidence, epidemiological and clinical characteristics of patients were evaluated before, during, and after the 2009 H1N1 pandemic. Sensitivity analyses were conducted by including NT1 cases only and excluding the effect of the 2009 H1N1 vaccination. RESULTS: Average annual incidence was 0.79 per 100 000 person-years (PY) from 1990 to 2017 and 1.08 per 100 000 PY from 2003 to 2017. Incidence increased 4.17 (95% CI 4.12, 4.22) and 1.42 (95% CI 1.41, 1.44) fold during and after the 2009 H1N1 pandemic when compared to baseline. These results were robust in sensitivity analyses. Patients with the onset of narcolepsy during the pandemic period were younger (notably in 5-9-year-old strata), and the age shift toward younger children reversed to baseline following the pandemic. CONCLUSIONS: Increased incidence of narcolepsy was observed during the 2009 H1N1 pandemic period. This is likely to be associated with the circulation of the wild type A(H1N1)pdm09 virus. This observation should be considered for future influenza pandemic preparedness plans.

NREM-AHI greater than REM-AHI versus REM-AHI greater than NREM-AHI in patients with obstructive sleep apnea: clinical and polysomnographic features.

PURPOSE: Previous studies show a high prevalence of obstructive sleep apnea (OSA) patients with a higher non-rapid eye movement (NREM) apnea-hypopnea index (AHI) (NREM-AHI) than rapid eye movement (REM) AHI (REM-AHI). However, the clinical significance of this phenomenon in patients with OSA is unknown. This study aimed to investigate whether there were significant differences in clinical and polysomnographic features between the NREM-AHI > REM-AHI group and the REM-AHI > NREM-AHI group and to determine whether NREM-AHI > REM-AHI or REM-AHI > NREM-AHI is a specific clinical entity. METHODS: One hundred forty-two patients with OSA, including 114 males and 28 females, were assessed for specific sleep-related complaints using a semistructured clinical questionnaire, for daytime sleepiness using the Epworth Sleepiness Scale (ESS), for depression using the Beck Depression Inventory (BDI), and for health-related quality of life using the Medical Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36). Anthropometric, clinical, and polysomnographic characteristics were examined between patients with NREM-AHI > REM-AHI and those with REM-AHI > NREM-AHI. RESULTS: A higher NREM-AHI than REM-AHI was found in 54.9% of the 142 patients with OSA. Overall, males predominated in each group, and there were no significant differences in age, body mass index, medical history, and drug intake between the NREM-AHI > REM-AHI group and the REM-AHI > NREM-AHI group. A high occurrence of NREM-AHI > REM-AHI (94.9%) or REM-AHI > NREM-AHI (90.6%) was found in moderate-to-severe cases each group. Although several indexes of OSA were worse in the NREM-AHI > REM-AHI group than in the REM-AHI > NREM-AHI group, no significant differences in specific sleep-related complaints, ESS score, BDI score, the incidence of daytime sleepiness or depression, and scores of sub-dimensions and the total score on SF-36 were present between the two groups. As compared separately, no significant differences in clinical features were observed in the clinical data for males and females between the two groups. CONCLUSIONS: Our results show that either NREM-AHI > REM-AHI or REM-AHI > NREM-AHI is more common in moderate-to-severe OSA cases, and there are no significant differences in clinical features between the NREM-AHI > REM-AHI group and the REM-AHI > NREM-AHI group. These findings may suggest that either NREM-AHI > REM-AHI or REM-AHI > NREM-AHI should be considered as a part of the spectrum of OSA, rather than a specific clinical entity.

Rapid eye movement sleep and slow wave sleep rebounded and related factors during positive airway pressure therapy.

This study aimed to investigate the clinical characteristics and predictors of increased rapid eye movement (REM) sleep or slow wave sleep (SWS) in patients with obstructive sleep apnea (OSA) following positive airway pressure (PAP) therapy. The study retrospectively analyzed data from patients with OSA who underwent both diagnostic polysomnography (PSG) and pressure titration PSG at the Tangdu Hospital Sleep Medicine Center from 2011-2016. Paired diagnostic PSG and pressure titration studies from 501 patients were included. REM rebound was predicted by a higher oxygen desaturation index, lower REM proportion, higher arousal index, lower mean pulse oxygen saturation (SpO2), higher Epworth sleepiness score and younger age (adjusted R2 = 0.482). The SWS rebound was predicted by a longer total duration of apneas and hypopneas, lower N3 duration, lower SpO2 nadir, lower REM proportion in diagnostic PSG and younger age (adjusted R2 = 0.286). Patients without REM rebound or SWS rebound had a high probability of comorbidities with insomnia and mood complaints. Some parameters (subjective and objective insomnia, excessive daytime sleepiness, age and OSA severity) indicate changes in REM sleep and SWS between diagnostic and titration PSG tests. Treatment of insomnia and mood disorders in patients with OSA may helpful to improve the use PAP.

Characteristics of Objective Sleep and Its Related Risk Factors Among Parkinson's Disease Patients With and Without Restless Legs Syndrome.

Objective: This study aimed to investigate the objective sleep characteristics and their related risk factors among Parkinson's disease (PD) patients with and without restless legs syndrome (RLS). Methods: A total of 125 patients with PD who underwent overnight polysomnography (PSG) were recruited consecutively. Eighty-one patients, including 27 PD with RLS (PD-RLS) and 54 PD without RLS (PD-NRLS), were included in the final analysis after 1:2 propensity score matching. Demographic, clinical, and polysomnographic data were compared between PD patients with and without RLS. The risk factors for sleep quality were examined using a multiple linear regression model. Results: The prevalence of RLS among PD patients was 28.0% (35/125). The PD-RLS group exhibited a higher score for the Unified Parkinson Disease Rating Scale (UPDRS) III than the PD-NRLS group. Also, the PD-RLS patients displayed significantly shorter total sleep times, worse sleep quality, decreased stage 3 duration, a longer wake time after sleep onset, and a higher arousal index than those without RLS (all p < 0.05). In the multiple linear regression model, PD duration (ß = -0.363, 95% CI: -0.652 to -0.074; p = 0.016), UPDRS-III (ß = -0.356, 95% CI: -0.641 to -0.071; p = 0.016), and periodic limb movement index (PLMI) (ß = -0.472, 95% CI: -0.757 to -0.187; p = 0.002) were determined to be the risk factors influencing sleep quality in PD-RLS patients. The UPDRS-III (ß = -0.347, 95% CI: -0.590 to -0.104; p = 0.006) and HAMD scores (ß = -0.343, 95% CI: -0.586 to -0.100; p = 0.007) were significantly associated with sleep quality after adjusting for confounding factors in PD-NRLS patients, respectively. Conclusions: PD-RLS patients exhibited more disturbed and fragmented sleep in objective sleep architecture than PD-NRLS patients. The severity of motor symptoms in PD was significantly associated with poor sleep quality in both PD-RLS and PD-NRLS patients. Notably, our findings indicated that periodic limb movements during sleep (PLMS) was the risk factor that influenced the objective sleep quality in PD patients with RLS.

Ginsenoside Rd attenuates mouse experimental autoimmune neuritis by modulating monocyte subsets conversion.

Guillain-Barré Syndrome (GBS), characterized by peripheral nerve demyelination and axonal damage, is initiated and aggravated through various of immunopathogenesis. Ginsenoside Rd, main active components extracted from ginseng saponins, is known to exhibit immune-regulate functions in many immune-mediated diseases. However, the evidence of preventive effect of Ginsenoside Rd on GBS is lacking. Experimental autoimmune neuritis (EAN) mice, classic model of GBS, were established and treated with GSRd or vehicle. Clinical score and nerve tissue histomorphology were evaluated. Monocytes in peripheral blood and tissue were detected by flow cytometry analysis and immunofluorescence staining. For the in vitro study, GSRd and vehicle were added in the culture medium to assess their regulatory function on monocytes phenotype. In vivo data showed a protective role of GSRd on alleviating symptoms and tissue damage on Day 20 and 25. Administration of GSRd increased non-classical Ly6Clo monocytes in both peripheral blood and injured nerve tissue, and also switched tissue macrophages phenotype into resolution-phase. In vitro study indicated similar role of GSRd on monocytes differentiation status. Transcription factors like Nr4a1 were elevated after GSRd treatment. These findings revealed the protective role of GSRd against EAN, and potential preventive function on GBS patients.

Effects of transcranial direct current stimulation on performance and recovery sleep during acute sleep deprivation: a pilot study.

BACKGROUND: Previous studies claimed that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) improves cognition in neuropsychiatric patients with cognitive impairment, schizophrenia, organic hypersomnia, etc, but few studies evaluated the effects of tDCS on cognitive improvement following sleep deprivation. The objective of this study was to determine whether tDCS (anode on the left DLPFC and cathode on the right DLPFC with a 2-mA current for 30 min) improves cognition following sleep deprivation. METHODS: Seven participants received active tDCS and eight participants received sham tDCS when their cognition declined during at least 30 h of sleep deprivation. All participants completed the psychomotor vigilance task, Trail Making Tests A and B, digit cancellation test, Stroop color word test, the Brief Visuospatial Memory Test-Revised and a procedural game every 2 h during the sleep deprivation and after recovery sleep. RESULTS: Compared to the sham stimulation, active tDCS (anode on the left DLPFC and cathode on the right DLPFC at a 2-mA current for 30 min) had beneficial effects on attention, memory, executive function, processing speed, and the ability to inhibit cognitive interference, and improved in subjective drowsiness and fatigue following sleep deprivation. The lasting effect of a single tDCS on cognition during sleep deprivation was greater than 2 h. In all participants, tDCS did not disturb recovery sleep, and cognitive performance recovered to the baseline levels after recovery sleep. CONCLUSIONS: The study results indicate that tDCS can improve cognition following sleep deprivation and does not disturb recovery sleep or cognitive performance after recovery sleep. The possible pathophysiological mechanisms might be related to the modulation of the corticothalamic pathway. We believe that tDCS can be applied in the treatment of sleep disorders involving sleepiness. TRIAL REGISTRATION NUMBER: ChiCTR2000029420. DATE OF REGISTRATION: 2020-1-31.

Mediator Med23 Regulates Adult Hippocampal Neurogenesis.

Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-CreER:Med23flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP+/Sox2+ NSCs and Tbr2+ progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions.

Severe bilateral pyramidal tract involvement in a patient with Parry-Romberg syndrome.

Parry-Romberg syndrome (PRS) is a rare clinical entity of unknown etiology, generally characterized by a slow and progressive atrophy that affects 1 side of the face. A variety of neurologic abnormalities have been shown to coexist with PRS. However, few studies regarding pyramidal tract involvement in this disorder have been reported. We report a unique case, in which the patient presented with bilateral pyramidal tract insult and an unusual sequence of disease onset and progression. This case suggests a rarer variant of PRS, and the neurologic findings indicate that the underlying essential neural degeneration may contribute to the processing of pyramidal tract insult or this syndrome.

Delayed parkinsonism with a selective symmetric basal ganglia lesion after manual strangulation.

A 21-year-old woman, who experienced manual strangulation, developed delayed parkinsonism associated with a selective symmetric basal ganglia lesion. The patient had recovered completely one year after early combination therapy. This case emphasizes the need for greater attention in detecting early brain injuries in those afflicted with strangulation so as to provide optimal management.

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.

S14G-Humanin ameliorates Abeta25-35-induced behavioral deficits by reducing neuroinflammatory responses and apoptosis in mice.

Cerebral amyloid-beta protein (Abeta) deposition and associated neuroinflammation and apoptosis are increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease (AD). Humanin (HN) and its derivative, S14G-HN (HNG), are best known for their ability to suppress neuronal death induced by AD-related insults in vitro. Furthermore, limited in vivo studies show that HNG can ameliorate memory impairment induced by intracerebroventricular injection of anti-cholinergic drugs or Abeta25-35. However, the mechanism underlying the in vivo effect remains unclear. In this study, we sought to determine the effects of HNG on neuroinflammatory responses and apoptosis associated with behavioral deficits induced by Abeta25-35 in vivo. Our results indicate that intracerebroventricular injection of aggregated Abeta25-35 induced impairment of learning and memory, markedly elevated numbers of reactive astrocytes, activated microglia, and apoptotic cells, as well as remarkable increased levels of IL-6 and TNFalpha. Moreover, intraperitoneal HNG treatment ameliorated behavioral deficits, and reduced neuroinflammatory responses and apoptotic cells in the brain. Cumulatively, these finding demonstrate for the first time that HNG may have the potential for attenuating Abeta-induced cognitive deficits by reducing inflammatory responses and apoptosis in vivo, which may add to the novel evidence for anti-inflammatory and antiapoptosis properties of HNG in AD treatment.

Expression of DCX and Transcription Factor Profiling in Photothrombosis-Induced Focal Ischemia in Mice.

Adult neurogenesis is present in the dentate gyrus and the subventricular zone in mammalian brain under physiological conditions. Recently, adult neurogenesis has also been reported in other brain regions after brain injury. In this study, we established a focal striatal ischemic model in adult mice via photothrombosis (PT) and investigated how focal ischemia elicits neurogenesis in the striatum. We found that astrocytes and microglia increased in early post-ischemic stage, followed by a 1-week late-onset of doublecortin (DCX) expression in the striatum. The number of DCX-positive neurons reached the peak level at day 7, but they were still observed at day 28 post-ischemia. Moreover, Rbp-J (a key effector of Notch signaling) deletion in astrocytes has been reported to promote the neuron regeneration after brain ischemia, and we provided the change of gene expression profile in the striatum of astrocyte-specific Rbp-J knockout (KO) mice glial fibrillary acidic protein (GFAP-CreER:Rbp-Jfl/fl), which may help to clarify detailed potential mechanisms for the post-ischemic neurogenesis in the striatum.

Severe sleep-disordered breathing in a patient with Brown-Vialetto-Van Laere syndrome: polysomnographic findings.

Brown-Vialetto-Van Laere (BVVL) syndrome is a rare disorder with clinical features that include progressive bilateral sensorineural deafness and a variety of cranial nerve impairments. Respiratory compromise has been observed in most familial and sporadic cases; however, few studies have been published regarding sleep-disordered breathing in this syndrome. We report the unique case of a 16-year-old girl with the clinical features of BVVL syndrome who presented with bilateral sensorineural hearing loss and then progressively developed paralysis of the 7th and 9th-12th cranial nerves. More importantly, she presented with the unusual feature of severe sleep-disordered breathing. A polysomnographic study showed evidence of dominant central sleep apnea, and the majority of apneic episodes more likely occurred in stage 2 during NREM sleep. The central sleep apnea was associated with rapid respiratory deterioration and death. This report raises the fact that a patient with BVVL syndrome may present with severe sleep-disordered breathing as a life-threatening condition, which emphasizes the need for greater attention to the early detection of potential sleep-disordered breathing in these afflicted with the BVVL syndrome for optimal clinical management.