Bilateral thalamic and brainstem anaplastic astrocytoma: A case report.

RATIONALE: Bilateral thalamic glioma is extremely rare and characterized by strictly limited involvement of bilateral thalami. To investigate its clinical and neuroimaging features, we herein reported a rare case of anaplastic astrocytoma (AA) involving both thalami and the brainstem and reviewed the literature. PATIENT CONCERNS: A-33-year-old Chinese woman was referred to our department owing to persistent headache and nausea and vomiting. Neurological examination showed mild cognitive impairment and positive Kernig sign. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated asymmetrical and swollen lesions involving both thalami, midbrain and pontine tegmentum, without restricted diffusion or enhancement. On day 7 after admission, she was transferred to the department of neurosurgery and underwent a stereotactic brain biopsy of the right thalamic lesion. Histopathological features and immunohistochemistry were consistent with AA, IDH wild-type, World Health Organization grade III. INTERVENTIONS: She was administrated with mannitol and glycerin fructose for decreasing intracranial pressure. OUTCOMES: In spite of receiving chemotherapy, she died on 2-month after her initial diagnosis. LESSONS: AA involving in both thalami and brainstem is a rare entity with poor prognosis. The clinicians and radiologists should deepen their awareness of the specific MRI feature of bilateral thalamic involvement. When MRI alone is insufficient, the utility of stereotactic biopsy is essential for making a definitive diagnosis.

METTL14 Regulates the m6A Modification of TRAF6 to Suppress Mitochondrial Dysfunction and Ferroptosis in Dopaminergic Neurons via the cGAS-STING Pathway.

OBJECTIVES: The degeneration of dopaminergic (DA) neurons has emerged as a crucial pathological characteristic in Parkinson's disease (PD). To enrich the related knowledge, we aimed to explore the impact of the METTL14-TRAF6-cGASSTING axis in mitochondrial dysfunction and ferroptosis underlying DA neuron degeneration. METHODS: 1-methyl-4-phenylpyridinium ion (MPP+) was used to treat DA neuron MN9D to develop the PD cell models. Afterward, a cell counting kit, flow cytometer, DCFH-DA fluorescent probe, and Dipyrromethene Boron Difluoride staining were utilized to measure the cell viability, iron concentration, ROS level, and lipid peroxidation, respectively. Meanwhile, the mitochondrial ultrastructure, the activity of mitochondrial respiratory chain complexes, and levels of malondialdehyde and glutathione were monitored. In addition, reverse transcription-quantitative polymerase chain reaction and western blot assays were adopted to measure the expression of related genes. cGAS ubiquitylation and TRAF6 messenger RNA (mRNA) N6-methyladenosine (m6A) levels, the linkages among METTL14, TRAF6, and the cGAS-STING pathway were also evaluated. RESULTS: METTL14 expression was low, and TRAF6 expression was high after MPP+ treatment. In MPP+-treated MN9D cells, METTL14 overexpression reduced ferroptosis, ROS generation, mitochondrial injury, and oxidative stress (OS) and enhanced mitochondrial membrane potentials. TRAF6 overexpression had promoting impacts on mitochondrial dysfunction and ferroptosis in MPP+-treated MN9D cells, which was reversed by further overexpression of METTL14. Mechanistically, METTL14 facilitated the m6A methylation of TRAF6 mRNA to down-regulate TRAF6 expression, thus inactivating the cGAS-STING pathway. CONCLUSION: METTL14 down-regulated TRAF6 expression through TRAF6 m6A methylation to inactivate the cGAS-STING pathway, thereby relieving mitochondrial dysfunction and ferroptosis in DA neurons.

5-Hydroxytryptamine: a potential therapeutic target in amyotrophic lateral sclerosis.

Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

Case Report: Rheumatoid meningitis with positive NMDAR antibody: A case treated with intravenous immunoglobulin.

As a rare complication of rheumatoid arthritis (RA) in the central nervous system (CNS), rheumatoid meningitis (RM) mainly affects the meninges and has various clinical symptoms. The diagnostic and treatment approaches currently used are not practical. RM cases with positive NMDAR antibodies (Abs) have never been reported. In the present study, a 66-year-old man with a 1-year history of RA presented recurrent left lower limb weakness during activities for 1 month. The results showed that rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were positive in the serum, and NMDAR Abs were present in cerebrospinal fluid (CSF). Hyperintensity was observed in the leptomeninges of the right frontal and parietal lobes, and subtle hyperintensity was observed in the left frontal and parietal lobes, as indicated by brain MRI. A meningeal biopsy revealed non-specific inflammation with the absence of rheumatoid nodules. The patient was given IVIg on day 7 after admission. The clinical symptoms were relieved, the lesions were alleviated, and abnormal biochemical indicators were gradually recovered 1 week after initiation of the treatment, while NMDAR Abs were present in CSF even after treatment. After 5 months of follow-up, the patient's serum and CSF ACPA and IL-6 levels were still high. The findings showed that brain MRI was adequate for the diagnosis of RM. ACPA and IL-6 might be the specific biomarkers for disease activity in RM. IVIg was effective as induction therapy for RM. Further studies should explore whether the presence of NMDAR Abs is associated with RM.

The stroke mechanism, clinical presentation, and radiological feature of bilateral medial medullary infarction.

BACKGROUND: Bilateral medial medullary infarction (BMMI) is a rare type of posterior circulation stroke. The aim of this study is to characterize its stroke mechanisms, clinical manifestations, neuroradiological features, and prognosis. METHODS: From January 2015 to June 2021, a retrospective review of 15 patients diagnosed with BMMI was conducted. The clinical and neuroradiological features were summarized by our experienced neurologists. RESULTS: Fifteen patients (12 male, 3 female), ranging in age from 48 to 72 years, satisfied the inclusion criteria. The common clinical presentations included motor weakness (100%), deep sensory disturbance (93.3%), vertigo/dizziness (80%), dysarthria (93.3%), and dysphagia (66.7%). Vertically, infarct lesions in the rostral medulla were observed in all included patients. Horizontally, "heart appearance," "Y appearance," and "fan appearance" infarcts occurred in 9 cases (60%), 5 cases (33.3%), and 1 (6.7%) case, respectively. Patients (53.3%) had severe stenosis or occlusion in unilateral vertebral artery (VA), and 33.3% had normal findings in the vertebrobasilar artery. Patients (93.3%) achieved poor prognosis. CONCLUSION: BMMI is more frequently located in the rostral medulla and comprises three forms of infarction. The two main stroke etiologies of BMMI are large-artery atherosclerosis (LAA) and small vessel disease (SVD). BMMI is always associated with bad clinical outcome.

Vinpocetine and coenzyme Q10 combination alleviates cognitive impairment caused by ionizing radiation by improving mitophagy.

OBJECTIVE: This research was designed to ascertain the effect and mechanism of vinpocetine (VIN) and coenzyme Q10 (CoQ10) combination on cognitive impairment induced by ionizing radiation (IR). METHODS: Cognitive impairment in mice was induced by 9-Gy IR, and they were intraperitoneally injected with VIN, CoQ10, or VIN + CoQ10. Then novel object recognition and Morris water maze tests were used to detect cognitive function. The number of hippocampal neurons and BrdU+Dcx+ cells was observed by Nissl and immunofluorescence staining. Mitochondrial respiratory complex I, adenosine triphosphate (ATP), and mitochondrial membrane potential (MMP) were evaluated, as well as oxidative stress injury. Mitophagy in hippocampal neurons was evaluated by observing the ultrastructure of hippocampal neurons and assessing the expression of mitophagy-related proteins. RESULTS: IR reduced novel object discrimination index, the time for platform crossing, and the time spent in platform quadrant, in addition to neuron loss, downregulated levels of mitochondrial respiratory complex I, ATP, and MMP, aggravated oxidative stress injury, increased expression of LC3 II/I, Beclin1, PINK1, and parkin, and decreased P62 expression. VIN or CoQ10 treatment mitigated cognitive dysfunction, neurons loss, mitochondrial damage, and oxidative stress injury, and enhanced mitophagy in hippocampal neurons. VIN and CoQ10 combination further protected against IR-induced cognitive dysfunction than VIN or CoQ10 alone. CONCLUSION: VIN combined with CoQ10 improved neuron damage, promoted mitophagy, and ameliorated cognitive impairment in IR mice.

Research progress and clinical application prospects of miRNAs in oral cancer.

Oral cancer is one of the most common malignant tumors worldwide, and it is also one of the most important and difficult clinical problems to be solved. Due to the regional differences in diet culture, some areas have taken the 'hardest hit' of oral cancer cases. However, the existing clinical treatment methods (surgery as the main treatment method, radiotherapy and chemotherapy as the auxiliary ones) do not have satisfactory treatment effects; therefore, new diagnosis and treatment methods need to be developed and utilized. Micro RNAs (miRNAs), as a class of substances that play an important regulatory role in the development of tumors, have an important value in the diagnosis and treatment of various tumors. At the same time, many miRNAs have obvious expression differences in oral cancer tissues compared to normal tissues. Therefore, they may have diagnostic and therapeutic effects on oral cancer. In this review, we evaluate the miRNAs that play a regulatory role in the development of oral cancer and those that are expected to be applied in the diagnosis and treatment of oral cancer. At the same time, we summarize the important challenges that need to be addressed, aiming to provide evidence and suggestions for the application of miRNAs in the diagnosis and treatment of oral cancer.

Potential of nobiletin against Alzheimer's disease through inhibiting neuroinflammation.

OBJECTIVE: This study aimed to explore the mechanism of Nobiletin attenuating Alzheimer's disease (AD) by inhibiting neuroinflammation. METHODS: The expression of inflammatory cytokines and HMGB-1 in serum of AD patients were examined. Microglia (MGs) were treated with different doses of Nobiletin before LPS and Nigericin induction. Cell viability and apoptosis were determined by CCK-8 and TUNEL assays, respectively. APP/PS1 mice were gavaged with Nobiletin, and Morris water maze (MWM) was established to record swimming speed, escape latency, the number of platform crossings, and time spent in the platform quadrant. MGs activation in brain tissues was evaluated by immunofluorescence. The expression of pyroptosis-related proteins, inflammatory cytokines, and HMGB-1 was determined in the hippocampus and MGs. RESULTS: The levels of inflammatory cytokines and HMGB-1 were high in serum of AD patients. Treatment with different concentrations of Nobiletin prominently enhanced cell viability and reduced apoptosis and the expression of inflammatory cytokine and pyroptosis-related proteins in LPS + Nigericin-induced MGs. Gavage of different doses of Nobiletin into APP/PS1 mice shortened the escape latency in mice, diminished MGs activation in brain tissues, and remarkably elevated the number of platform crossings and the time spent in the platform quadrant without obvious change in swimming speed, suggesting that Nobiletin improved the spatial learning and memory abilities in APP/PS1 mice. The expression of pyroptosis-related proteins, HMGB-1, and inflammatory cytokines was decreased dramatically by Nobiletin in the hippocampus of APP/PS1 mice. CONCLUSIONS: Nobiletin can inhibit neuroinflammation by inhibiting HMGB-1, pyroptosis-related proteins, and inflammatory cytokines, thus mitigating AD.

Bipolar disorder and the risk for stroke incidence and mortality: a meta-analysis.

OBJECTIVE: Bipolar disorder (BD) may be associated with an increased risk of stroke, but to date, the results of the studies are still controversial. This study aimed to assess the association of BD with stroke incidence and mortality by a meta-analysis. METHOD: PubMed, EMBASE, the Cochrane library databases, and Web of Science databases were searched from inception to July 2020. We regarded stroke as a composite endpoint. The pooled hazard ratio (HRs) of 95% confidence interval (Cls) was calculated. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: A total of 7 studies involving a total of 13,305,007 participants were included in this meta-analysis. Pooled analysis showed participants with BD experienced a significantly increased risk of both stroke incidence (combined HR, 1.43; 95% CI, 1.24-1.66; p = 0.000) and stroke mortality (combined HR, 1.54; 95% CI, 1.09-2.18; p = 0.013) compared to participants without BD. In addition, the pooled estimate of multivariate HRs of stroke incidence and mortality were 1.35 (95% CI: 1.26-1.45); 2.30 ( 95% CI: 1.37-3.85) among men and 1.43 (95% CI:1.27-1.60); 2.08 (95% CI:1.60-2.71) among women respectively. CONCLUSIONS: This meta-analysis suggests that BD may modestly increase the risk of both stroke incidence and mortality. Extensive clinical observational studies should be conducted in the future to explore whether BD is a potentially modifiable risk factor for stroke.

The rs2619566, rs10260404, and rs79609816 Polymorphisms Are Associated With Sporadic Amyotrophic Lateral Sclerosis in Individuals of Han Ancestry From Mainland China.

The pathogenesis of sporadic amyotrophic lateral sclerosis (sALS) remains unknown; however, recent research suggests that genetic factors may play an important role. This study aimed at investigating possible genetic risk factors for the pathogenesis of sALS. In our previous study, we conducted a genome-wide association study (GWAS) in 250 sALS patients and 250 control participants of Han ancestry from mainland China (HACM) and retrospectively analyzed the previously reported candidate loci related with sALS including our GWAS investigated results. In this study, twenty-seven candidate loci that were most likely associated with sALS were selected for further analysis in an independent case/control population of 239 sALS patients and 261 control subjects of HACM ethnicity using sequenom massARRAY methodology and DNA sequencing. We discovered that the polymorphism rs2619566 located within the contactin-4 (CNTN4) gene, rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene, and rs79609816 in the inositol polyphosphate-5-phosphatase B (INPP5B) gene were strongly associated with sALS in subjects of HACM ethnicity. Subjects harboring the minor C allele of rs2619566 and the minor T allele of rs79609816 exhibited an increased risk for sALS development, while carriers of the minor C allele of rs10260404 showed a decreased risk of sALS development compared to the subjects of other genotypes. The polymorphisms of rs2619566, rs10260404, and rs79609816 may change or affect the splicing, transcription, and translation of CNTN4, DPP6, and INPP5B genes and may play roles in the pathogenesis of sALS roles in the pathogenesis of sALS.

Unilateral cerebral cortical encephalitis (CCE) with positive anti-MOG antibodies: A case report.

RATIONALE: Nowadays, myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) is regarded as an independent inflammatory demyelinating disease. Here, we report a rare case of unilateral cerebral cortical encephalitis (CCE) with positive anti-MOG antibodies. PATIENT CONCERNS: A 19-year-old woman was admitted to our hospital owing to acute onset fever and headache. Four days later, she experienced a focal seizure that progressed to generalized tonic-clonic seizures. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated cortical lesions in the left cerebral hemisphere on T2-weighted fluid-attenuated inversion recovery imaging. The patient was positive for anti-MOG antibodies in serum and diagnosed with anti-MOG antibody-associated unilateral CCE. INTERVENTIONS: She was administrated with intravenous methylprednisolone followed by oral corticosteroids. OUTCOMES: On day 14 after admission, a repeat MRI revealed partial resolution of the initial abnormalities. The patient received a quick recovery without residual symptoms. CONCLUSIONS: Unilateral CCE with positive anti-MOG antibodies has emerged as a special clinical phenotype of MOGAD. It should be emphasized that the characteristic neuroradiological features of CCE would be an important clue to the correct diagnosis of MOGAD.

Association between kidney stones and risk of developing stroke: a meta-analysis.

BACKGROUND: Many studies have described the relationship between kidney stones and stroke, but the results are controversial, so we conducted this meta-analysis to estimate the relationship between kidney stones and the risk of developing stroke. METHODS: Studies were marked with a comprehensive search of PubMed, EMBASE, Google, and ISI Web of Science databases through 25 March 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and a random-effects model or fix-effects model was used to compute the pooled combined risk estimate. Heterogeneity was reported as I2. We performed subgroup and sensitivity analysis to assess potential sources of heterogeneity. RESULTS: Eight studies of seven articles involving 3,526,808 participants were included in the meta-analysis. Overall, kidney stones were associated with a moderate risk of stroke incidence (HR, 1.24; 95% CI, 1.11-1.40; I2=79.6%; p=0.000). We conducted a sensitivity analysis by removing the studies that had a high risk of bias. Heterogeneity subsequently decreased significantly, while an increased risk of stroke in patient with kidney stones was again demonstrated (HR, 1.16; 95% CI, 1.11-1.23; I2=28.7%; p=0.000). Stratifying analysis showed that the results were more pronounced for ischemic stroke (HR, 1.14; 95% CI, 1.08-1.22; I2=15.6%; p=0.00) and the follow-up duration ≥10 years (HR, 1.18; 95% CI, 1.10-1.27; I2=31.6%; p=0.003). CONCLUSIONS: Our meta-analysis suggests that patients with kidney stones may have a modestly increased risk of developing stroke, especially in ischemic stroke. More large-scaled and clinical trials should be done to identify the relative impact of kidney stones on stroke outcomes in the future.

The clinical and neuroradiological features of patients of coexisting atraumatic convexity subarachnoid hemorrhage and large artery atherosclerosis stroke: A retrospective observational study.

ABSTRACT: Atraumatic convexity subarachnoid hemorrhage (c-SAH) concomitant with large artery atherosclerosis (LAA) stroke has been rarely discussed in the literature. Our aim in this study is to characterize the clinical and neuroradiological features of patients with LAA stroke and c-SAH.A retrospective study from a single institution was performed between January 2016 and June 2020. Only patients diagnosed with c-SAH and LAA stoke were included in this study. The clinical presentation and neuroimaging finding were summarized by our experienced neurologists.In total, 12 patients (8 men, 4 women), ranging in age from 45 to 75 years, were identified. All of them had cardiovascular risk factors and hypertension was the commonest (50%). Almost all patients presented hemiparesis (91.7%). Other clinical presentations included, dysarthria (41.7%), hemianesthesia (33.3%), facial palsy (33.3%), aphasia (16.7%), and cognitive impairment (8.3%). Internal border-zone (IBZ) infarction and cortical border-zone (CBZ) infarction occurred in 12 and 3 patients, respectively. c-SAH might occurred in different cortical sulcis. Percentages of frontal lobe, parietal lobe and fronto-parietal lobe were 41.7% (n = 5), 25% (n = 3) and 25% (n = 3), respectively. All ischemic lesions were ipsilateral to the sites of c-SAH. High-grade atherosclerotic stenosis of large artery was detected in all patients. The M1 segment of middle cerebral artery (MCA) is the second most common atherosclerotic artery after internal carotid artery (ICA).Our data suggest that LAA stroke is always ipsilateral to the site of c-SAH. Severe atherosclerotic changes can also been seen in the M1 segment of MCA apart from extracranial ICA. Moreover, border zone infarction may be a specific form of infarct when c-SAH is confronted with LAA stroke.

Simvastatin improves cerebrovascular injury caused by ischemia­reperfusion through NF­κB­mediated apoptosis via MyD88/TRIF signaling.

Cerebrovascular injury is the most prevalent human cerebrovascular disease and frequently results in ischemic stroke. Simvastatin may be a potential therapeutic agent for the treatment of patients with cerebrovascular injury. The present study aimed to investigate the efficacy of and the potential mechanisms regulated by simvastatin in a rat model of ischemia­reperfusion (I/R)­induced cerebrovascular injury. Cerebrovascular injury model rats were established and were subsequently treated with simvastatin or a vehicle control following I/R injury. Cell damage, neurological functions and neuronal apoptosis were examined, as well as the nuclear factor (NF)­κB­mediated myeloid differentiation primary response protein 88 (MyD88)/toll­interleukin­1 receptor domain­containing adapter molecule 1 (TRIF) signaling pathway following simvastatin treatment. The results of the present study demonstrated that simvastatin treatment led to a reduction in cell damage, improvement of neurological functions and decreased neuronal apoptosis compared with vehicle­treated I/R model rats, 14 days post­treatment. In addition, simvastatin treatment reduced cerebral water content and blood­brain barrier disruption in cerebrovascular injury induced by I/R. The results also revealed that simvastatin treatment inhibited neuronal apoptosis via the NF­κB­mediated MyD88/TRIF signaling pathway. In conclusion, simvastatin treatment may reduce I/R­induced neuronal apoptosis via inhibition of the NF­κB­mediated MyD88/TRIF signaling pathway.

Bilateral wallerian degeneration of the middle cerebellar peduncles secondary to pontine infarction: A case series.

OBJECTIVE: Wallerian degeneration (WD) of middle cerebellar peduncles (MCPs) secondary to pontine infarction is rarely reported in the literature. Our aim in this study is to characterize its clinical and neuroradiological features. METHODS: A retrospective review of 7 patients from a single institution was conducted. Only patients with pontine infarction and subsequent degeneration of the MCPs were included in the analysis. The features of clinical presentation and neuroimaging finding were summarized by our experienced neurologists. RESULTS: Seven patients (5 male, 2 female), ranging in age from 50 to 77 years, satisfied the inclusion criteria. All patients had cardiovascular risk factors and hypertension was the most common one. Almost all of the patients had hemiparesis and dysarthria, and could achieved good clinical outcome. On the initial scan, hyperintense on T2- and diffusion-weighted images suggested the acute pontine infarction. On the follow-up scan, however, hyperintensities of bilateral MCPs on T2-weight and FLAIR images were apparently demonstrated in all patients. The specific lesions in the MCPs were attributed to bilateral WD of the pontocerebellar fibres secondary to pontine infarction. CONCLUSION: WD should be taken into account when patients are initially diagnosed with paramedian pontine infarction and follow-up MRI manifest as symmetrical hyperintense in the MCPs.