An autologous duraplasty in situ technique in the treatment of Chiari malformation Type I: a prospective study.

OBJECTIVE: Our study aims to prospectively compare an autologous duraplasty in situ technique (IS group) with the synthetic dural graft duraplasty (SDG group) to clarify the effectiveness and superiority of the former in the treatment of patients with Chiari malformation type 1 (CM-I). METHOD: 29 patients with CM-I were randomly assigned to either IS or SDG group. In both groups, a dissection from the occipital bone was performed. All procedures were performed by the same surgeon. The two duraplasty methods were compared in terms of surgical factors and complications. Data analysis was done for the baseline material, the neurological outcome and MRI-documented syrinx size at the 6 month follow-up. RESULT: 29 patients were enrolled in this study, 14 in the IS group and 15 in the SDG group. The results showed no significant difference in operation time (P = 0.916), amount of bleeding (P = 0.120), operation complications, hospitalization time (P = 0.854) and prognosis between the two groups. The hospitalization cost of IS group was 15,125 yuan less than that of SDG group (P < 0.05). CONCLUSION: The autogenous duraplasty in situ technique is a novel, simple, effective and economical surgical management for patients with CM-I.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer: A case report.

BACKGROUND: Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal (LM) metastasis than other types of lung cancers and have a poor prognosis. Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis. CASE SUMMARY: A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital. She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance. epidermal growth factor receptor (EGFR) mutation was detected by genomic examination, so she was first treated with gefitinib for 10 months before acquiring resistance. Cell-free cerebrospinal fluid (CSF) circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation, while biopsy and cytology from the patient's CSF and the first enhanced cranial magnetic resonance imaging (MRI) showed no positive findings. A month later, the enhanced MRI showed linear leptomeningeal enhancement, and the cytology and biochemical examination in CSF remained negative. Therefore, osimertinib (80 mg/d) was initiated as a second-line treatment, resulting in a good response within a month. CONCLUSION: This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy. Moreover, the routine screening of chest CT with the novel coronavirus may provide unexpected benefits.

Association Between the Severity of Diabetic Retinopathy and Optical Coherence Tomography Angiography Metrics.

Diabetic retinopathy, the most serious ocular complication of diabetes, imposes a serious economic burden on society. Automatic and objective assessment of vessel changes can effectively manage diabetic retinopathy and prevent blindness. Optical coherence tomography angiography (OCTA) metrics have been confirmed to be used to assess vessel changes. The accuracy and reliability of OCTA metrics are restricted by vessel segmentation methods. In this study, a multi-branch retinal vessel segmentation method is proposed, which is comparable to the segmentation results obtained from the manual segmentation, effectively extracting vessels in low contrast areas and improving the integrity of the extracted vessels. OCTA metrics based on the proposed segmentation method were validated to be reliable for further analysis of the relationship between OCTA metrics and diabetes and the severity of diabetic retinopathy. Changes in vessel morphology are influenced by systemic risk factors. However, there is a lack of analysis of the relationship between OCTA metrics and systemic risk factors. We conducted a cross-sectional study that included 362 eyes of 221 diabetic patients and 1,151 eyes of 587 healthy people. Eight systemic risk factors were confirmed to be closely related to diabetes. After controlling these systemic risk factors, significant OCTA metrics (such as vessel complexity index, vessel diameter index, and mean thickness of retinal nerve fiber layer centered in the macular) were found to be related to diabetic retinopathy and severe diabetic retinopathy. This study provides evidence to support the potential value of OCTA metrics as biomarkers of diabetic retinopathy.

Staged Endovascular Treatment for Symptomatic Occlusion Originating From the Intracranial Vertebral Arteries in the Early Non-acute Stage.

Background: The ideal treatment for patients who survive from acute vertebrobasilar artery occlusion but develop aggressive ischemic events despite maximal medical therapy in the early non-acute stage is unknown. This paper reports the technical feasibility and outcome of staged endovascular treatment in a series of such patients with symptomatic intracranial vertebral artery occlusion. Methods: Ten consecutive patients who presented with aggressive ischemic events in the early non-acute stage of intracranial vertebral artery occlusion from Jan 2015 to Nov 2020 were retrospectively reviewed. Among them, eight male and two female patients with a mean age of 66.7 years developed aggressive ischemic events, and the NIHSS score was elevated by a median of 7 points despite medical therapy. All patients received staged endovascular treatment 4-21 days from onset, at an average of 11 days. The strategy of staged treatment was as follows: first, a microwire was passed through the portion of the occlusion, which was then dilated with balloon inflation to maintain the perfusion above TICI grade 2b. Then, with the use of antiplatelet drugs, the residual intravascular thrombus was gradually eliminated by the continuous perfusion and an activated fibrinolytic system, leaving the residual stenosis. A second stage of angioplasty with stent implantation was subsequently performed if residual stenosis was ≥50%. The NIHSS scores and mRS scores were compared between pre- and post-endovascular treatment groups and in the follow-up period. Results: Technical success was achieved in 9 patients who received staged endovascular treatment (perforation occurred in one patient during the first stage). The NIHSS scores were significantly improved, with a median score 7 points lower on discharge compared with the scores for the most severe status. Favorable outcomes with mRS score ≤ 2 were achieved in 7 and 9 patients at the 3-month follow-up and the latest follow-up, respectively, which was better than the preoperative status. Conclusion: Staged endovascular treatment might be a safe, efficient, and viable option in carefully selected patients with symptomatic intracranial vertebral artery occlusion in the early non-acute stage. However, this needs to be confirmed by further investigation, preferably in a large, controlled setting.

Thirty-Day and One-Year Outcomes of Endovascular Treatments for Severe Atherosclerotic Stenosis of Intracranial ICA: Results From a Single Center.

Background: Endovascular treatment for intracranial atherosclerotic stenosis (ICAS) has been developed. However, the intracranial internal carotid artery (ICA) presents a particular challenge due to the location and tortuous route, and the outcomes of endovascular treatment in patients with stenosis of the intracranial ICA still have not been reported. This article retrospectively investigated the 30-day and 1-year outcomes of tailored endovascular treatment for patients with severe intracranial ICA stenosis from a single center. Methods: Between June 2014 and December 2017, 96 consecutive patients with severe atherosclerotic stenosis (70-99%) of the intracranial ICA were managed with endovascular treatment in Beijing Tiantan Hospital. Three different kinds of treatments [angioplasty with balloon dilatation alone (BD group), balloon-mounted stent (BMS group), and self-expanding stent (SES group)] were performed according to the characteristics of the lesions. The primary endpoints included any stroke or death within 30 days and ipsilateral ischemic stroke afterwards within 1 year. Secondary endpoints included the revascularization success rate (residual stenosis <30%) and the restenosis rate (stenosis ≥ 50%) within 1 year. Results: The 30-day death rate was 0, and the stroke rate of all patients was 7.3% (7/96). The stroke rate was higher in the BD group (15.8%) and SES group (9.8%) than in the BMS group (0%) (p = 0.047). Thirteen (13.5%) patients suffered at least one onset of ischemic stroke in the ipsilateral ICA territory within 1 year, and there was no significant difference among the three groups (p = 0.165). The overall revascularization success rate was 93.8%, and the revascularization success rate was significantly higher in the SES group (100%) than in the BD group (78.9%) (p = 0.006). The restenosis rate of all patients within 12 months was 20.8%, and there was no significant difference among the three groups. Patients with Mori type C target lesions were more likely to suffer stroke within 30 days (25%) and restenosis within 1 year (31.3%). Conclusions: Both the 30-day and 1-year outcomes of tailored endovascular treatments seemed to be acceptable in the treatment of symptomatic atherosclerotic stenosis of the intracranial ICA. However, this needs to be confirmed by further investigation, preferably in large multicenter randomized controlled clinical trials.

Case Report: Multi-Orifices Vertebral Arteriovenous Fistula With Severe Scoliosis in Neurofibromatosis Type 1: Might Be a Congenital Disease With Mesodermal Dysplasia.

Background: Vertebral arteriovenous fistula (AVF) associated with neurofibromatosis type 1 (NF-1) is a rare condition in the previous reports. However, whether vertebral AVF in NF-1 is congenital or NF-1 disease progression hasn't been clarified. Case Description: We reported a 48-year-old male case of vertebral AVF simultaneously combined with thoracic scoliosis and NF-1. Preoperative CT angiography showed the AVF with multiple orifices located on the vessel wall of the vertebral artery, which was proved during the procedure of endovascular treatment. By occluding the parent vertebral artery, the AVF was finally cured. Further whole-exome sequencing identified a novel germline heterozygous point nonsense mutation, c.G397T(p.E133X), in the NF1(NM_000267) gene exon4. Conclusions: From this patient, we speculate that vertebral AVF associated with NF-1 might be a congenital disease as a manifestation of mesodermal dysplasia.

Whether Intracranial Aneurysm Could Be Well Treated by Flow Diversion: A Comprehensive Meta-Analysis of Large-Sample Studies including Anterior and Posterior Circulation.

BACKGROUND: Flow diversion (FD) has become a widely adopted treatment method for intracranial aneurysms in the clinic, but a comprehensive meta-analysis of large-sample studies including anterior and posterior circulation is still lacking. METHODS: The PubMed, Embase, Web of Science, and Cochrane databases were searched between January 1, 2008, and December 1, 2019. A random-effect model was used to calculate the efficacy and safety data as well as 95% confidence intervals (CIs). RESULTS: The pooled sample size of all included studies was 6695 patients; the mean age was 55.5 years old, with a total of 7406 aneurysms. For efficacy, the complete occlusion rate in angiographic follow-up (AFU) at 6 months was 78% (95% CI, 0.77, 0.80), and the AFU rate at 6-12 months was 90% (95% CI, 0.88, 0.92). For safety, the hemorrhagic event rate was 2%, the ischemic event rate was 5%, and the mortality rate was 3%. CONCLUSION: FD is an effective and safe treatment for intracranial aneurysm with high complete occlusion rate and acceptable complication rate.

Superficial siderosis of the central nervous system with epilepsy originating from traumatic cervical injury: illustrative case.

BACKGROUND: Superficial siderosis of the central nervous system (SSCNS) is a rare condition that results from hemosiderin deposition in the brain, brainstem, cerebellum, and spinal cord as a result of chronic, repeated, and recurrent subarachnoid hemorrhage. SSCNS that originates in the spinal cord is rarely reported, and epilepsy as a manifestation of such a case has not been reported before. OBSERVATIONS: The authors reported a rare case of SSCNS with epilepsy originating from traumatic cervical injury and presented a literature review of all reported SSCNS cases that originated in the spine. The patient was a 29-year-old man with a 16-year history of progressive headache accompanied by seizures, ataxia, and sensorineural hearing loss. He had experienced a traumatic cervical injury at age 7. Magnetic resonance imaging revealed a characteristic hypointense rim around the pons and cervical spinal cord on susceptibility-weighted imaging scans. Cerebrospinal fluid examination during a headache episode confirmed subarachnoid hemorrhage and increased intracranial pressure. Surgical exploration revealed a C6 dural defect with bone spurs inserted into the dura mater. After the patient underwent dura mater repair and shunt implantation, his symptoms disappeared completely except for hearing loss. LESSONS: This rare case indicated that symptomatic epilepsy followed by SSCNS can be eliminated by complete repair of the cervical dura mater.

Neuroprotective Effects of Early Brain Injury after Subarachnoid Hemorrhage in Rats by Calcium Channel Mediating Hydrogen Sulfide.

The present study explored the modulating apoptosis effect of hydrogen sulfide (H2S) in subarachnoid hemorrhage (SAH) rats and its exact mechanism. A rat SAH model established by intravascular puncturing was used for the present study. After giving NaHS (donor of H2S), an L-type calcium channel opener (Bay K8644), or a calcium channel agonist (nifedipine), the neurological function of the rats, associated pathological changes, and expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and microtubule-associated protein (MAP-2) were examined. The concentration of H2S and expression of cystathionine beta synthase in the hippocampus changed upon early brain injury (EBI) after SAH. Compared with the SAH group, the neurological function of the rats and microstructure observed by electron microscopy were better in the SAH + NaHS group and SAH + Bay K8644 group. It was observed that apoptosis was more obvious in the SAH group than in the control group and was alleviated in the SAH + NaHS group. Furthermore, the alleviating effect of NaHS was partially weakened by nifedipine, indicating that the effect of anti-apoptosis in H2S might be correlated with the calcium channel. The expression of Bax and caspase-3 was elevated, while the expression of Bcl-2 decreased in the SAH group but improved in the SAH + NaHS and SAH + Bay K8644 group. Compared with the SAH + NaHS group, the expression of pro-apoptotic proteins was higher in the SAH + NaHS + nifedipine group. Therefore, upon EBI following SAH, the H2S system plays an important neurological protective effect by modulating the function of the L-type calcium channel and inhibiting apoptosis.

Dysregulated Expression and Methylation Analysis Identified TLX1NB as a Novel Recurrence Marker in Low-Grade Gliomas.

Low-grade gliomas (LGGs) are the most common CNS tumors, and the main therapy for LGGs is complete surgical resection, due to its curative effect. However, LGG recurrence occurs frequently. Biomarkers play a crucial role in evaluating the recurrence and prognosis of LGGs. Numerous studies have focused on LGG prognosis. However, the multiomics research investigating the roles played by gene methylation and expression in LGG recurrence remains limited. In this study, we integrated the TCGA and GEO datasets, analyzing RNA and methylation data for recurrence (R) and nonrecurrence (NR) groups. We found a low expression of TLX1NB and high methylation in recurrence patients. Low expression of TLX1NB is associated with poor survival (OS: p = 0.04). The expression of TLX1NB is likely to play a role in the prognosis of LGG. Therefore, TLX1NB may represent an alternative early biomarker for the recurrence of low-grade gliomas.

Hydrogen Sulfide Reduces Cognitive Impairment in Rats After Subarachnoid Hemorrhage by Ameliorating Neuroinflammation Mediated by the TLR4/NF-κB Pathway in Microglia.

Background and Aims: Cognitive impairment is one of the major complications of subarachnoid hemorrhage (SAH) and is closely associated with neuroinflammation. Hydrogen sulfide (H2S) has been shown to have an anti-inflammatory effect and reduce cognitive impairment in neurodegenerative diseases, but its effects in SAH have been little studied. This study aimed to investigate the effects of H2S on cognitive impairment after SAH and the possible underlying mechanisms. Methods: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into three groups: a sham group, a SAH group, and a SAH + NaHS (an H2S donor) group. The endovascular perforation technique was used to establish the experimental SAH model. NaHS was administered intraperitoneally. An active avoidance test (AAT) was performed to investigate cognitive function. The expression of TNF-α, toll-like receptor 4 (TLR4), and NF-κB p65 in the hippocampus was measured by Western blot and immunohistochemistry. The types of cells expressing TNF-α were detected by double immunofluorescence staining. Results: Compared to that in the sham group, the learning and memory ability of rats in the SAH group was damaged. Furthermore, the expression of TNF-α, TLR4, and NF-κB p65 in the hippocampus was elevated in the SAH group (p < 0.05). TNF-α was mainly expressed in activated microglia, which was consistent with the expression of TLR4. Treatment with NaHS significantly decreased the cognitive impairment of rats after SAH and simultaneously reduced the expression of TNF-α, TLR4, and NF-κB p65 and alleviated the nuclear translocation of NF-κB p65 (p < 0.05). Conclusions: The neuroinflammation reaction in microglia contributes to cognitive impairment after SAH. H2S reduced the cognitive impairment of rats after SAH by ameliorating neuroinflammation in microglia, potentially via the TLR4/NF-κB pathway.

Characterization of the gp120 of circulating HIV type 1 in a group of infected Chinese blood/plasma donors with asymptomatic and symptomatic stages of the disease.

The C2-V5 regions of the HIV envelope gene were cloned and sequenced from DNA samples of four asymptomatic and five AIDS patients from a cohort of HIV-1-infected Chinese plasma and blood donors. Sequence analysis revealed that regardless of the stage of disease, all the patient's HIV-1 belonged to either clade B' or circulating recombinant form 15 (CRF15) subtype. However, since these blood donors were infected at a time when circulating CRF15 was not known in that region, it is likely these HIV-1 types belong to clade B'. However, the C2-V5 sequences from AIDS patients clustered differently in the phylogenetic tree than those present in asymptomatic patients and showed a significantly higher divergence and lower diversity compared to those from asymptomatic patients. In addition, more syncytia-inducing viral genotypes were present in AIDS patients than in asymptomatic patients. These results contribute to a better understanding of the pathogenesis of circulating HIV-1 in infected Chinese plasma and blood donors, warrant additional investigation of the possible presence of CRF15 in Chinese blood donors, and may have important implications in the future design of therapeutic strategies for treating these infected patients.