Can we directly visualize what we imagine in our brain together with what we describe? The inherent nature of human perception reveals that, when we think, our body can combine language description and build a vivid picture in our brain. Intuitively, generative models should also hold such versatility. In this paper, we introduce BrainDreamer, a novel end-to-end language-guided generative framework that can mimic human reasoning and generate high-quality images from electroencephalogram (EEG) brain signals. Our method is superior in its capacity to eliminate the noise introduced by non-invasive EEG data acquisition and meanwhile achieve a more precise mapping between the EEG and image modality, thus leading to significantly better-generated images. Specifically, BrainDreamer consists of two key learning stages: 1) modality alignment and 2) image generation. In the alignment stage, we propose a novel mask-based triple contrastive learning strategy to effectively align EEG, text, and image embeddings to learn a unified representation. In the generation stage, we inject the EEG embeddings into the pre-trained Stable Diffusion model by designing a learnable EEG adapter to generate high-quality reasoning-coherent images. Moreover, BrainDreamer can accept textual descriptions (e.g., color, position, etc.) to achieve controllable image generation. Extensive experiments show that our method significantly outperforms prior arts in terms of generating quality and quantitative performance.
BackgroundThe relationship between serum inflammatory biomarkers, carotid atherosclerotic plaque characteristics, and the recurrence of ischemic events remains a subject of ongoing debate.PurposeTo investigate whether the combination of carotid atherosclerotic plaque burden and serum inflammatory biomarkers could help predict ipsilateral ischemic stroke recurrence.Material and MethodsPatients with cerebral infarction were prospectively recruited and received three-dimensional vessel wall imaging (VWI). Baseline serum level of high-sensitivity C-reactive protein (hs-CRP) and the neutrophil-to-lymphocyte ratio (NLR) was recorded. Plaque burden was independently measured by two trained readers. Stroke recurrence was assessed at 1 year after discharge. Factors associated with stroke recurrence were analyzed. Receiver operating characteristic curves were used to calculate areas under the curve (AUCs) of inflammatory biomarkers and plaque burden for predicting stroke recurrence.ResultsA total of 56 patients were included, with recurrence in nine patients. hs-CRP (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.17-2.19; P = 0.017) and carotid normalized wall index (NWI) (OR = 1.08, 95% CI = 1.01-1.16; P = 0.023) were found associated with stroke recurrence. Multivariate logistic regression showed that hs-CRP (OR = 1.67, 95% CI = 1.17-2.38; P = 0.005) and NWI (OR = 1.10, 95% CI = 1.01-1.20, P = 0.023) remained associated with stroke recurrence. Hs-CRP (AUC = 0.806; P = 0.002) and NWI (AUC = 0.738; P <0.001) were predictors of stroke recurrence. The combination of hs-CRP with NWI (AUC = 0.811, P <0.001) demonstrated the best performance in terms of predicting stroke recurrence.ConclusionBoth hs-CRP and NWI were independently associated with stroke recurrence. The combination of hs-CRP and NWI may be a good predictor of 1-year stroke recurrence.
Previous research has commonly regarded overactive bladder syndrome (OAB) and restless legs syndrome (RLS) as distinct disorders in terms of their underlying causes, clinical diagnosis, and treatment approaches. However, there is evidence of an overlap in the occurrence of these two conditions following cerebral infarction(CI). Specifically, restless bladder syndrome (RBS), a subtype of RLS, exhibits symptoms similar to those of OAB. Consequently, further investigation is warranted to better understand the relationship between these two disorders. In this report, we present the cases of two patients who presented with both OAB following CI, along with RLS. Following administration of oral pramipexole, both nocturia and RLS exhibited prompt and efficient alleviation. There may exist a shared pathological foundation between certain RLS cases and OAB. In instances where patients exhibit evident OAB symptoms following CI and concurrently experience RLS, it is advisable to prioritize the administration of dopaminergic agonists over M receptor inhibitors and β3 agonists. Furthermore, it is plausible that the RBS or a subset of RLS cases could potentially be classified as a form of OAB, although this correlation has yet to be definitively established.
OBJECTIVE:To investigate the potential value of serum inflammatory markers combined with carotid plaque characteristics for predicting subsequent recurrent ischemic events. METHODS:Patients with cerebral infarction localized to the internal carotid artery territory were recruited. Carotid MRI examinations were performed, and the plaque characteristics were evaluated at baseline. Serum samples were obtained, and clinical characteristics were documented at baseline. All participants received clinical follow-up 1 year after discharge. Recurrent ipsilateral ischemic stroke was considered the clinical endpoint. Logistic regression analyses were employed to assess the correlations between serum inflammatory biomarkers, plaque characteristics, and the endpoint. The diagnostic performances were evaluated using receiver operating characteristic curves. DeLong's test was used to compare the areas under the curve (AUCs) of the models. RESULTS:In total, 89 patients (84.3% men; mean age, 56.57 ± 9.05 years) with recent anterior circulation (carotid territory) cerebral hemisphere ischemia were included. Sixteen patients presented with an endpoint within the 1-year follow-up. Multivariate logistic regression demonstrated that the normalized wall index, intraplaque hemorrhage, lipid-rich necrotic core, and high-sensitivity C-reactive protein (Hs-CRP) were associated with the endpoint. The model combining plaque characteristics and Hs-CRP had the highest diagnostic performance with an AUC of 0.855. CONCLUSIONS:Serum Hs-CRP level and plaque characteristics may provide complementary information for predicting recurrent stroke. The combination of these two indicators may be a better potential predictor of the population at high risk of stroke recurrence.
Background and ObjectivesAbnormal glymphatic system-related proteins have been identified in a small-scale pathologic study of patients with Creutzfeldt-Jakob disease (CJD). However, it remains unclear whether glymphatic dysfunction occurs in vivo in patients with CJD and whether this decline begins during the preclinical stage. This study aimed to investigate the relationship between glymphatic dysfunction and clinical characteristics in patients with CJD, as well as potential glymphatic impairment in preclinical CJD. MethodsThis prospective cohort study recruited patients with CJD and healthy controls (HCs) from the Department of Neurology at Xuanwu Hospital, Capital Medical University, Beijing, China, from 2018 to 2022. In addition, a family with preclinical genetic CJD carrying the G114V pathogenic variant was followed over 6 years with 3 evaluations. All participants underwent diffusion tensor imaging along the perivascular space (DTI-ALPS) to measure glymphatic function in vivo and 18F-fludeoxyglucose-PET to identify CJD-related metabolic patterns. Associations between the DTI-ALPS index and Medical Research Council Prion Disease Rating Scale (MRC-PDRS) score were evaluated using multiple linear regression. ResultsWe enrolled 35 patients with CJD (mean age 59.6 +/- 10.7 years, 40% female, with the time from onset to glymphatic dysfunction assessment averaging 39% of the total disease course), 28 age-matched and sex-matched HCs, and a family with preclinical genetic CJD consisting of 7 carriers and 7 noncarriers. Patients with CJD exhibited lower DTI-ALPS values compared with HCs (p < 0.001). Partial correlation analyses revealed significant correlations between the DTI-ALPS index and MRC-PDRS score (r = 0.346, p = 0.049) and disease progression (r = -0.468, p = 0.006), but not with disease duration or cognitive severity after adjusting for age and sex. Multivariate linear analysis demonstrated that poorer MRC-PDRS scores (beta = 0.702, p = 0.014) were associated with a lower DTI-ALPS index. The DTI-ALPS index of asymptomatic G114V carriers showed no significant difference compared with noncarriers. However, a preclinical CJD case exhibited an 8.2% decrease in the DTI-ALPS index 3.3 years before onset. No significant correlation was found between regional metabolic standardized uptake value ratios and DTI-ALPS index. DiscussionOur study indicates that glymphatic dysfunction is associated with CJD severity and disease progression. Glymphatic dysfunction may occur in the preclinical stage, but these findings should be interpreted with caution because they are based on individual findings.
Importance Recent studies have revealed that autopsy skin samples from cadavers with prion diseases (PRDs) exhibited a positive prion seeding activity similar to cerebrospinal fluid (CSF). It is worthwhile to validate the findings with a large number of biopsy skin samples and compare the clinical value of prion seeding activity between skin biopsies and concurrent CSF specimens. Objective To compare the prion seeding activity of skin biopsies and CSF samples and to determine the effectiveness of combination of the skin biopsies from multiple sites and numerous dilutions on the diagnosis for various types of PRDs. Design, Setting, and Participants In the exploratory cohort, patients were enrolled from September 15, 2021, to December 15, 2023, and were followed up every 3 months until April 2024. The confirmatory cohort enrolled patients from December 16, 2023, to June 31, 2024. The exploratory cohort was conducted at a single center, the neurology department at Xuanwu Hospital. The confirmatory cohort was a multicenter study involving 4 hospitals in China. Participants included those diagnosed with probable sporadic Creutzfeldt-Jakob disease or genetically confirmed PRDs. Patients with uncertain diagnoses or those lost to follow-up were excluded. All patients with PRDs underwent skin sampling at 3 sites (the near-ear area, upper arm, lower back, and inner thigh), and a portion of them had CSF samples taken simultaneously. In the confirmatory cohort, a single skin biopsy site and CSF samples were simultaneously collected from a portion of patients with PRDs. Exposures The skin and CSF prion seeding activity was assessed using the real-time quaking-induced conversion (RT-QUIC) assay, with rHaPrP90-231, a Syrian hamster recombinant prion protein, as the substrate. In the exploratory cohort, skin samples were tested at dilutions of 10(-2) through 10(-4). In the confirmatory cohort, skin samples were tested at a dilution of 10(-2). A total of four 15-mu L wells of CSF were used in the RT-QUIC assay. Main Outcomes and Measures Correlations between RT-QUIC results from the skin and CSF and the final diagnosis of enrolled patients. Results In the exploratory cohort, the study included 101 patients (mean [SD] age, 60.9 [10.2] years; 63 female [62.4%]) with PRD and 23 patients (mean [SD] age, 63.4 [9.1] years; 13 female [56.5%]) without PRD. A total of 94 patients had CSF samples taken simultaneously with the skin biopsy samples. In the confirmatory cohort, a single skin biopsy site and CSF sample were taken simultaneously in 43 patients with PRDs. Using an experimental condition of 10(-2) dilution, the RT-QUIC positive rates of skin samples from different sites were comparable with those of the CSF (skin: 18 of 26 [69.2%] to 74 of 93 [79.6%] vs CSF: 71 of 94 [75.5%]). When tested at 3 different dilutions, all skin sample positivity rates increased to over 80.0% (79 of 93 for the near-ear area, 21 of 26 for the upper arm, 77 of 92 for the lower back, and 78 of 92 for the inner thigh). Combining samples from skin sites near the ear, inner thigh, and lower back in pairs yielded positivity rates exceeding 92.1% (93 of 101), significantly higher than CSF alone (71 of 94 [75.5%]; P =.002). When all skin sample sites were combined and tested at 3 dilution concentrations for RT-QUIC, the sensitivity reached 95.0% (96 of 101). In the confirmatory cohort, the RT-QUIC positive rate of a single skin biopsy sample was slightly higher than that of the CSF (34 of 43 [79.1%] vs 31 of 43 [72.1%]; P = .45). Conclusions and Relevance Results of this diagnostic study suggest that the sensitivity of an RT-QUIC analysis of a combination of 2 or more skin sites was superior to that of CSF in diagnosing PRDs.
Introduction Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types.Methods Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8).Results The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis.Discussion COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.
ABSTRACT Objective To assess the proportion of clinically diagnosed MM2‐type sporadic Creutzfeldt–Jakob disease (sCJD) in a Chinese cohort, describe the clinical features of MM2‐cortical (MM2C) and MM2‐thalamic (MM2T) type sCJD to improve the early detection of MM2‐type sCJD. Methods A total of 209 patients with sCJD admitted to the Xuanwu Hospital between February 2012 and August 2022 were reviewed. The patients were classified into probable MM2C, MM2T‐type sCJD, and other types of sCJD according to current clinical diagnostic criteria. Clinical and ancillary data were compared between the groups. Results Fifty‐one (24.4%) patients were clinically diagnosed with MM2‐type sCJD, of which 44 were diagnosed with MM2C‐type sCJD and 7 with MM2T‐type sCJD. In the absence of RT‐QuIC, 27 (61.3%) patients of MM2C‐type sCJD did not meet the US CDC sCJD criteria for possible sCJD on admission, even though the mean period from onset to admission was 6.0 months. However, all of these patients had cortical hyperintensity on DWI. Compared to the other types of sCJD, MM2C‐type sCJD was associated with slower disease progression and the absence of the typical clinical features of sCJD; the MM2T‐type sCJD group had a higher proportion of males, earlier age of onset, longer duration of disease, and a higher incidence of bilateral thalamic hypometabolism/hypoperfusion. Interpretation In the absence of multiple typical sCJD symptoms within 6 months, the presence of cortical hyperintensity on DWI should raise concerns for MM2C‐type sCJD after excluding other etiologies. Bilateral thalamic hypometabolism/hypoperfusion may be more helpful in the clinical diagnosis of MM2T‐type sCJD.
1. Methyltransferase-like 21C (METTL21C) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) play important roles in the proliferation of chicken myoblasts. However, it remains unclear whether there is protein-protein interaction between METTL21C and IGF2BP1 to regulate proliferation of chicken myoblasts.2. In this study, the Igf2bp1 gene was amplified from cDNA of liver tissue of Lueyang black-bone chicken to construct the overexpression vector HA-Igf2bp1. The HA-Igf2bp1 and Flag-Mettl21c vectors were individually transfected and co-transfected into HEK293T, respectively. Co-immunoprecipitation (Co-IP) assay indicated a protein-protein interaction between METTL21C and IGF2BP1.3. Using the Western blotting and LC-MS/MS, it was found that METTL21C could mediate the lysine methylation modification of IGF2BP1. Furthermore, the His-tagged overexpression vector HA-Igf2bp1-His was constructed, transfected and co-transfected with Flag-Mettl21c into HEK293T. His-tagged IGF2BP1 was purified by nickel ion affinity chromatography. Western blotting revealed that IGF2BP1 was successfully purified, and the trimethylation modification level of co-transfection group was significantly elevated compared with the single-transfection Igf2bp1 group.4. Mettl21c and Igf2bp1 overexpression vectors were transfected and co-transfected into primary chicken myoblasts, respectively. The results of 5-ethynyl-2'-deoxyuridine assay and the expression level of Pax7 and MyoD indicated that overexpression of Igf2bp1 alone inhibited the chicken myoblast proliferation, whereas co-expression of Mettl21c and Igf2bp1 eliminated the inhibitory effects of Igf2bp1, thereby favouring cell proliferation and differentiation.5. The results, for the first time, revealed that METTL21C mediated the lysine trimethylation modification of IGF2BP1 to regulate the proliferation of chicken myoblasts, which provided a new insight into in-depth analysis of the molecular mechanism of METTL21C methylation involved in regulating the growth and development of skeletal muscle in Lueyang black-bone chicken.
Background Despite the continuing effort in investigating the preventive therapies for stroke-associated pneumonia (SAP), which is closely associated with unfavorable outcomes, conclusively effective therapy for the prevention of SAP is still lacking. Remote ischemic conditioning (RIC) has been proven to improve the survival in the sepsis model and inflammatory responses have been indicated as important mechanisms involved in the multi-organ protection effect of RIC. This study aimed to assess the safety and the preliminary efficacy of RIC in the prevention of SAP in patients with acute ischemic stroke. Methods We performed a proof-of-concept, pilot open-label randomized controlled trial. Eligible patients (age > 18 years) within 48 h after stroke onset between March 2019 and October 2019 with acute ischemic stroke were randomly allocated (1:1) to the RIC group and the control group. All participants received standard medical therapy. Patients in the RIC group underwent RIC twice daily for 6 consecutive days. The safety outcome included any adverse events associated with RIC procedures. The efficacy outcome included the incidence of SAP, changes of immunological profiles including mHLA-DR, TLR-2, and TLR-4 as well as other plasma parameters from routine blood tests. Results In total, 46 patients aged 63.1 ± 12.5 years, were recruited (23 in each group). Overall, 19 patients in the RIC group and 22 patients in the control group completed this study. No severe adverse event was attributed to RIC procedures. The incidence of SAP was lower in the remote ischemic conditioning group (2 patients [10.5%]) than that in the control group (6 patients [27.3%]), but no significant difference was detected in both univariate and multivariate analysis ( p = 0.249 and adjusted p = 0.666). No significance has been found in this pilot trial in the level of immunological profiles HLA-DR, TLR4 and TLR2 expressed on monocytes as well as blood parameters tested through routine blood tests between the two groups ( p > 0.05). The IL-6 and IL-1β levels at day 5 after admission in the RIC group were lower than those in the control group ( p < 0.05). Interpretation This proof-of-concept pilot randomized controlled trial was to investigate RIC as a prevention method for SAP. Remote ischemic conditioning is safe in the prevention of SAP in patients with acute ischemic stroke. The preventive effect of RIC on SAP should be further validated in future studies.
Objective Anti-γ-aminobutyric acid-B receptor (GABABR) encephalitis is a rare type of autoimmune encephalitis. There are only a few, small, published studies regarding prognosis, so prediction of prognosis is of limited accuracy. We identified 37 cases of anti-GABABR encephalitis in China. Here, we present these patients' clinical characteristics and long-term outcomes. Methods We collected and retrospectively analyzed the clinical data of 37 patients with anti-GABABR encephalitis from Beijing Fengtai You'anmen Hospital. Results The study cohort comprised 37 patients of anti-GABABR encephalitis of median age 61 years (range: 11–77), 28 of whom were male. The main clinical manifestations were epilepsy (91.9%, 34/37), psychiatric disorders (94.6%, 35/37) and cognitive impairment (97.3%, 36/37). Tumors were identified in 18 (48.6%) patients. First-line immunotherapy was administered to 34 patients, 31 of whom (90.6%) responded favorably. During a median follow-up of 18 months (range: 1–72 months), 21 patients had good outcomes [Modified Ranking Scale (mRS ≤2)], 16 (43.2%) died (mRS 6), and 7 (18.9%) relapsed. Age (P = 0.005), disturbance of consciousness (P = 0.018), admission to the Neurology Intensive Care Unit (P = 0.003), mechanical ventilation (P = 0.009), more numerous clinical manifestations (P = 0.008), comorbid malignancy (P = 0.008), multiple anti-neuronal antibodies (P = 0.029), and hyponatremia (P = 0.023) differed significantly between patients with good outcomes (mRS 0–2) and those with poor outcomes (mRS 3–6). Conclusion Men aged 50–70 years accounted for most of the patients with anti-GABABR encephalitis in our case series. The main clinical manifestations were epilepsy and neuropsychiatric dysfunction. The participants often had concomitant lung cancer, particularly small-cell lung cancer. Patients with lung tumors and/or serious manifestations usually had a poor prognosis with high mortality. Early identification and treatment of tumors improved the poor prognosis to some extent.
ABSTRACT Background This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. Methods In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. Results A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8‐2.3; χ 2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 ‐ 5.2; χ 2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups ( F = 6.51, p < 0.001). The scores of gastrointestinal symptoms ( F = 7.42, p < 0.001) and dizziness ( F = 9.82, p < 0.001) but not headache ( F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO 2 ) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude ( F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO 2 (R = 0.38, p < 0.001), and SpO 2 was moderately inversely correlated with the LLS (R = –0.48, p < 0.001). Conclusion This study demonstrated that a four‐week RIPC intervention but not a one‐week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.
As an opportunistic phytopathogen, Sarocladium strictum has only been shown to cause neurological disease in immunocompromised patients, where antifungal therapy was not effective. We report a case of Sarocladium strictum meningoencephalitis in an apparently immunocompetent young woman who presented with severe headache and slight fever after undergoing transnasal endoscopic repair of cerebrospinal fluid rhinorrhea. Chronic sinusitis and suspicious intracranial fungal lesions were observed on enhanced magnetic resonance imaging (MRI). Both culture and metagenomic next-generation sequencing of her cerebrospinal fluid were positive for Sarocladium strictum. After local debridement, treatment with amphotericin B plus voriconazole and Ommaya reservoir implantation, the patient improved significantly. Unfortunately, her symptoms worsened again despite plenty of antifungal therapy for a month.
Background: The anterior cingulate cortex (ACC) seems to play an important role in behavioral deficits and executive dysfunctions in patients with behavioral variant frontotemporal dementia (bvFTD), while its specific and independent contribution requires clarification. Objective: To identify whether ACC abnormalities in gray matter (GM) volume and standardized uptake value ratio (SUVR) images are associated with disease severity of bvFTD, by analyzing hybrid T1 and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Methods: We enrolled 21 bvFTD patients and 21 healthy controls in the study. Each subject underwent a hybrid PET/MRI study and a standardized neuropsychologic assessment battery. GM volume and SUVR are voxel-wise calculated and compared. Then we estimate the mean value inside ACC for further partial Pearson’s correlation to explore the association between GM volume/SUVR of the ACC and severity of behavioral deficit as well as executive dysfunction. Results: ACC was shown to be involved in both atrophy and hypometabolism patterns. The partial Pearson’s correlation analysis showed that the SUVR of the ACC was strongly correlated with frontal behavior inventory total score (left r = –0.85, right r = –0.85, p < 0.0001), disinhibition subscale score (left r = –0.72, p = 0.002; right = –0.75, p < 0.0001), and apathy subscale score (left = –0.87, right = –0.85, p < 0.0001). Conclusion: These findings demonstrated decreased ACC activity contributes to behavioral disturbances of both apathetic and disinhibition syndromes of bvFTD, which can be sensitively detected using 18F-FDG PET.
Ischemic stroke is one of the most lethal and severely disabling diseases that seriously affects human health and quality of life. The maintenance of self-renewal and differentiation of neural stem cells are closely related to metabolism. This study aimed to investigate whether hypoxic postconditioning (HPC) could promote neurogenesis after ischemic stroke, and to investigate the role of neuronal stem cell metabolism in HPC-induced neuroprotection. Male C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO), and HPC was performed for 3 h per day. Immunofluorescence staining was used to assess neurogenesis. The cell line NE-4C was used to elucidate the proliferation of neuronal stem cells in 21% O2 or 8% O2. HPC promoted the recovery of neurological function in mice on day 14. HPC promoted neuronal precursor proliferation in the subventricular zone (SVZ) on day 7 and enhanced neuronal precursor migration in the basal ganglia and cortex on day 14. Fatty acid oxidation (FAO) and glycolysis of neural stem cells in the SVZ changed after MCAO with or without HPC. HPC promoted the proliferation of NE-4C stem cells, decreased FAO and increased glycolysis. All these beneficial effects of HPC were ablated by the application of an FAO activator or a glycolysis inhibitor. In conclusion, cerebral ischemia modulated the FAO and glycolysis of neural stem cells. HPC promoted the proliferation and migration of neural stem cells after MCAO, and these effects may be related to the regulation of metabolism, including FAO and glycolysis.
Background: Aphasia is one of the common complications of stroke, and it considerably influences the quality of life of patients. Acupuncture, a therapy used in traditional Chinese medicine for aphasia after stroke, has potential therapeutic effects. We aimed to investigate the therapeutic effect of acupuncture on individuals with poststroke aphasia. Methods: Randomized controlled trials (RCTs) on acupuncture for poststroke aphasia (either alone or combined with other therapies) were included and compared. We conducted a systematic review and meta-analysis by searching databases, such as MEDLINE, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP, and Wanfang, from inception to July 15, 2019. No language restrictions were applied in this study. Results: Fourteen trials involving 936 participants had poor reporting and methodological quality. Our meta-analysis showed that compared to the speech and language therapy (SLT) group, acupuncture combined with SLT could improve the rate of Boston Diagnostic Aphasia Examination (BDAE) (OR: 0.15, 95% confidence interval [CI]: 0.04–0.25, p = 0.005), scores of Aphasia Battery of Chinese (ABC) which includes repeating ability (SMD: 1.46, 95% CI: 1.24–1.69, p < 0.00001), reading ability (SMD: 1.57, 95% CI: 1.25–1.90, p < 0.00001), writing ability (SMD: 1.52, 95% CI: 1.19–1.86, p < 0.00001), naming ability (SMD: 1.40, 95% CI: 1.04–1.76, p < 0.00001), and listening comprehension ability (SMD: 0.57, 95% CI: 0.22–0.92, p = 0.001). All RCTs were considered at high risk of biased assessment. Conclusions: Acupuncture (either alone or combined with SLT) may be effective for poststroke aphasia. In the future, rigorous clinical trials with an accurate method design and high reporting quality are required to validate our results.
Background:Myelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) has highly heterogenous clinical and imaging presentations, in which encephalitis is an important phenotype. In recent years, some atypical presentations in MOG-ab-associated encephalitis (MOG-E) have been increasingly reported but have not yet been described well. The aim of the study was to describe the clinical and imaging features of patients with MOG-E in our center. Atypical phenotypes would be reported, which is expected to expand the spectrum of MOGAD.Methods:We reviewed medical records of 59 patients with MOGAD diagnosed in our center and identified cases who had ever experienced encephalitic symptoms. Three hundred ten patients with autoimmune encephalitis (AE) were also reviewed, and cases with positive MOG-ab were identified. Besides, patients with chronically progressive encephalitis were identified from 13 MOG-E and 310 AE patients. We collected demographic, clinical, laboratory, radiological, and outcome data to explore clinical and imaging characteristics in MOG-E, especially in the atypical phenotype of chronically progressive encephalitis.Results:We identified 13 patients (7 males, 6 females) with MOG-E. The median age at onset was 33 years (range 13~62 years). Most (9/13, 69.2%) of patients showed acute or subacute onset of encephalitic symptoms. Brain MRI abnormalities were observed in all patients. The most common lesion locations on MRI were cortical/subcortical (11/13, 84.6%), deep/periventricular white matter (10/13, 76.9%) and corpus callosum (4/13, 30.8%). Brain MRI patterns were categorized into four phenotypes. The most common pattern was cortical encephalitis with leptomeningeal enhancement/brain atrophy (10/13, 76.9%). Eight (8/13, 61.5%) patients had a good response to immunotherapy. Four (4/13, 30.8%) patients with chronically progressive course were identified from MOG-E cohort. They showed leukodystrophy-like pattern, multifocal hazy lesions, or cortical encephalitis on MRI. With immunotherapy, they only showed mild or no improvement. We also identified four (4/310, 1.3%) patients with chronically progressive course from AE cohort. They had better outcomes than counterparts in MOG-E.Conclusions:This study demonstrates that encephalitic presentations in MOGAD had complex clinical patterns. Chronically progressive encephalitis may be a new phenotype of MOGAD. We recommend to test MOG-ab in subacute and chronic progressive dementia with leukodystrophy-like MRI lesions.
Oxygen supply for ischemic brain tissue during stroke is critical to neuroprotection. Remote ischemic conditioning (RIC) treatment is effective for stroke. However, it is not known whether RIC can improve brain tissue oxygen supply. In current study, we employed a mouse model of stroke created by middle cerebral artery occlusion (MCAO) to investigate the effect of RIC on oxygen supply to the ischemic brain tissue using a hypoxyprobe system. Erythrocyte oxygen-carrying capacity and tissue oxygen exchange were assessed by measuring oxygenated hemoglobin and oxygen dissociation curve. We found that RIC significantly mitigated hypoxic signals and decreased neural cell death, thereby preserving neurological functions. The tissue oxygen exchange was markedly enhanced, along with the elevated hemoglobin P50 and right-shifted oxygen dissociation curve. Intriguingly, RIC markedly elevated 2,3-biphosphoglycerate (2,3-BPG) levels in erythrocyte, and the erythrocyte 2,3-BPG levels were highly negatively correlated with the hypoxia in the ischemic brain tissue. Further, adoptive transfusion of 2,3-BPG-rich erythrocytes prepared from RIC-treated mice significantly enhanced the oxygen supply to the ischemic tissue in MCAO mouse model. Collectively, RIC protects against ischemic stroke through improving oxygen supply to the ischemic brain tissue where the enhanced tissue oxygen delivery and exchange by RIC-induced 2,3-BPG-rich erythrocytes may play a role.