A Long-Term Outcome of Symptomatic Middle Cerebral Artery Undergoing Intracranial Angioplasty or Stenting.

OBJECTIVE: For symptomatic stenosis in the middle cerebral artery (MCA), intracranial angioplasty and stenting are frequently employed. However, limited data exist regarding their long-term impact. Our study demonstrates the long-term advantages in preventing ischemic events through a 5-year follow-up period. METHODS: A set of 41 individuals with symptomatic stenosis in the MCA who underwent angioplasty or stenting procedures between October 2004 and April 2018 at various hospitals in Southwest China were prospectively enrolled in the study. The rates of successful revascularization, complications, imaging observations, and clinical outcomes were systematically assessed. RESULTS: A total of 41 individuals successfully underwent stenting, respectively. After stenting, the extent of stenosis was decreased from 71.8% (56-87.8%) to 24.9% (0-45%). The mean follow-up period is 36.9 ± 13.68 months (range, 11-67 months). There was no deterioration of neurological function or a new ischemic event. A DSA or CT angiography was conducted after the procedure and demonstrated no in-stent restenosis. No patient experienced restenosis below 50% during the mean follow-up period. The morbidity and mortality rates of the case series were 7.3% and 2.4%, respectively. CONCLUSIONS: In the treatment of symptomatic MCA atherosclerotic stenoses, intracranial angioplasty and stenting are demonstrated to be technically feasible and safe. Its early and long-term efficacy on ischemic event prevention is acceptable, with a reduced level of restenosis, although the representative sample is tiny.

Vγ4 T cell-derived IL-17A is essential for amplification of inflammatory cascades in ischemic brain tissue after stroke.

BACKGROUND: Through amplifying inflammatory cascades, IL-17A produced by γδ T cells potently attracts neutrophils to the site of injury for exacerbating ischemic tissue damage. Our goal was to identify the precise role of γδ T cell subsets in ischemic brain tissue damage of stroke. METHODS: In a model of experimental stroke, we analyzed the functions of Vγ1 and Vγ4 T cells on γδ T cell-mediated ischemic brain tissue damage of stroke. RESULTS: We identified that, in stroke, Vγ4 T cells are essential for γδ T cell-mediated ischemic brain tissue damage through providing an early source of IL-17A. Both CCL20 and IL-1ß/IL-23 are deeply involved in Vγ4 T cell-mediated amplification of inflammatory responses: CCL20 might promote Vγ4 T cells recruit to infract hemisphere, and IL-1ß/IL-23 powerfully enhance IL-17A production mediated by the infiltrating Vγ4 T cells. Moreover, Vγ4 T cell-derived IL-17A enhances both CCL20 and IL-1ß, and conversely, CCL20 and IL-1ß further enhance both recruitment and IL-17A production of IL-17A-positive cells, in a classic positive feedback loop. CONCLUSION: Our data suggest that in the setting of ischemic stroke, Vγ4 T cell-derived IL-17A, CCL20 and IL-1ß/IL-23 in infract hemisphere coordinately to amplify inflammatory cascades and exacerbate ischemic tissue damage.

Identification of novel FUS and TARDBP gene mutations in Chinese amyotrophic lateral sclerosis patients with HRM analysis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons. More than 30 genes have been linked to ALS to date, including FUS and TARDBP, which exhibit similar roles in RNA metabolism. This study explored the use of high-resolution melting (HRM) analysis to screen for FUS and TARDBP mutation hotspot regions in 146 Chinese ALS patients, which achieved 100% detection. Two FUS mutations were observed in two different familial ALS probands, a missense mutation (p.R521H) and a novel splicing mutation (c.1541+1G>A). Five TARDBP mutations were identified in six ALS patients, including a novel 3'UTR mutation (c.*731A>G) and four missense mutations (p.G294V, p.M337V, p.G348V, and p.I383V). We found that FUS mutations were present in 1.4% of Chinese ALS patients, whereas TARDBP mutations were responsible for 4.1% of Chinese ALS cases. Here, we describe the accuracy of using highly sensitive HRM analysis to identify two novel FUS and TARDBP mutations in Chinese sporadic and familial ALS cases. Our study contributes to the further understanding of the genetic and phenotypic diversity of ALS.

A phase II randomized trial of sodium oligomannate in Alzheimer's dementia.

BACKGROUND: Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients. METHODS: The 24-week multicenter, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized in a 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer's Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL, and NPI at 24 weeks after treatment compared with baseline. A subgroup study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements. RESULTS: Comparing with the placebo group (n = 83, change - 1.45), the ADAS-cog12 score change in the GV-971 600-mg group (n = 76) was - 1.39 (p = 0.89) and the GV-971 900-mg group (n = 83) was - 2.58 (p = 0.30). The treatment responders according to CIBIC-Plus assessment were significantly higher in the GV-971 900-mg group than the placebo group (92.77% vs. 79.52%, p < 0.05). The GV-971 900-mg subgroup showed a lower decline of cerebral metabolic rate for glucose than the placebo subgroup at the left precuneus, right posterior cingulate, bilateral hippocampus, and bilateral inferior orbital frontal at uncorrected p = 0.05. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%. CONCLUSIONS: GV-971 was safe and well tolerated. GV-971 900 mg was chosen for phase III clinical study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01453569 . Registered on October 18, 2011.

The efficacy and safety of endovascular recanalization of occluded large cerebral arteries during the subacute phase of cerebral infarction: a case series report.

BACKGROUND: Intravenous tissue plasminogen activator with or without mechanical thrombectomy during the acute phase are approved therapies for ischaemic stroke. Due to the short treatment time window (<6 hours) and often treatment failure, these patients would still have an intracranial arterial occlusion (IAO). It is unclear whether these patients can benefit from subsequent interventional recanalizationof their occluded artery in the subacute phase. In this retrospective study, we have examined the efficacy and safety in patients who have received either percutaneous transluminal angioplasty (PTA) or percutaneous transluminal angioplasty and stenting (PTAS) for IAO in the subacute phase of their stroke. METHODS: Patients with subacute symptomatic ischaemic stroke caused by IAO were assessed to identify the responsible artery and low perfusion areas by CT angiography, MR angiography or digital subtraction angiography. In eligible patients, a PTA or PTAS was performed to reopen the occluded artery. Regular antithrombotic therapy, use of statins, control of risk factors and rehabilitation therapy were prescribed after the procedure. All patients had regular follow-up up to 12 months. RESULTS: PTA or PTAS was performed in 16 patients with cerebral infarction caused by IAO in the subacute phase. After the procedure, 12 cases were recanalized, two were partially recanalized and two failed to open. One patient with left C6 segment occlusion of the carotid artery had a central retinal artery embolism after PTAS. The perioperative adverse events were 6.25%. At 3 months, the distribution of modified Rankin scale scores was 0 (seven cases), 1 (three cases), 2 (five cases) and 3 (one case). CONCLUSION: Selective PTA or PTAS could be performed in ischaemic stroke patients with a small infarct size and large area of hypoperfusion from an occluded large cerebral artery after the acute phase. It may improve neurological dysfunction and reduce the incidence of disability.

Intra-arterial DynaCT angiography: an alternative tool to assess the patency of intracranial stent lumen.

OBJECTIVE: The aim of this retrospective study was to assess the clinical utility of intra-arterial DynaCT angiographic imaging for the evaluation of intracranial stent patency. METHODS: Between July 2011 and May 2014, 35 patients with symptomatic intracranial atherosclerotic stenosis (ICAS) were treated with percutaneous transluminal angioplasty and stents. All were evaluated with intra-arterial DynaCT angiographic imaging during the operations and follow-up. All images were further processed with three different kernels (sharp, normal, or smooth). RESULTS: Thirty-six stents were implanted into the parent arteries. DynaCT provided "good" quality images (median score of 2 or 3 on a 5-point scale) with minimal artifact interference as rated by observers blind to treatment history and other imaging results. The median subjective visibility score was highest (3) using the sharp kernel. CONCLUSIONS: DynaCT with sharp kernel image processing achieved good visualization of luminal patency following intracranial stents.

Imbalance between IL-17A-producing cells and regulatory T cells during ischemic stroke.

Immune responses and inflammation are key elements in the pathogenesis of ischemic stroke (IS). Although the involvement of IL-17A in IS has been demonstrated using animal models, the involvement of IL-17A and IL-17-secreting T cell subsets in IS patients has not been verified, and whether the balance of Treg/IL-17-secreting T cells is altered in IS patients remains unknown. In the present study, we demonstrated that the proportion of peripheral Tregs and the levels of IL-10 and TGF- ß were reduced in patients with IS compared with controls using flow cytometry (FCM), real-time PCR, and ELISA assays. However, the proportions of Th17 and γ δ T cells, the primary IL-17A-secreting cells, increased dramatically, and these effects were accompanied by increases in the levels of IL-17A, IL-23, IL-6, and IL-1 ß in IS patients. These studies suggest that the increase in IL-17A-producing cells and decrease in Treg cells might contribute to the pathogenesis of IS. Manipulating the balance between Tregs and IL-17A-producing cells might be helpful for the treatment of IS.

Stent placement for treatment of long-segment (≥40 mm) carotid atherosclerotic stenosis: results and long-term follow-up in a single-center experience.

BACKGROUND: Treatment of long segment carotid stenosis (≥40 mm) with carotid artery stenting (CAS) has rarely been reported. In randomized trials, use of longer stents (>40 mm) has been associated with adverse clinical events. Here, we report our preliminary experience on the stent length and outcome in treating long segment carotid arterial stenosis. METHODS AND RESULTS: Between August 2003 and February 2013, 22 patients with long segment stenosis of the carotid artery were treated by CAS. The mean stent length was 58.5 mm (50-60 mm). The procedures were successful in all patients, and all reported remarkable relief of symptoms immediately after stent placement. Complications included 1 case of cerebral hemorrhage and one death from myocardial infarction at 10 months. The mean follow up was 27.3 months (10-60 months). One follow-up was lost. 2 patients had late stent thrombosis at 22 and 36 months by CTA follow-up. 18 patients had persistent relief, and angiography/CTA showed normal carotid flow. CONCLUSIONS: Our study showed that stenting for long carotid stenosis (≥40 mm) can be beneficial. Large scale clinical trial is needed to further evaluate its efficacy and safety.

Influences of cerebral stent implantation on CD4+ CD25+ FOXP3+ Treg, Th1 and Th17 cells.

Stent implantation is primarily used for the treatment of artery stenosis. However, the application and use of stent struts induces local and systemic inflammation, leading to intractable neointimal hyperplasia. CD4(+) T cells are involved in artery stenosis diseases, but little is known about the influence of the CD4(+) T cells on the inflammation reaction after stent implantation. In this study, we analyzed the frequency of signature transcription factors and proinflammatory cytokine expression from each subtype of CD4(+) T cells in 50 patients receiving intracranial or cervical stent implantations from December 2011 to June 2012. The results showed that the frequency of signature transcription factor/cytokine production in Treg cells was reduced in the first week and returned to control levels at 3 months after stent implantation. However, we observed opposite trends for Th17 cells, showing increased signature transcription factor/cytokine production during the acute phase, which returned to control levels after 3 months. No significant difference in the frequency of signature transcription factor/cytokine expression was observed in Th1 cells from patients before and after stent implantation. We speculate that the maintenance of the frequency and function of Tregs controls the inflammatory response, which otherwise induces acute inflammation after stent implantation.

Stent placement for treatment of long segment (≥80 mm) carotid artery stenosis in patients with Takayasu disease.

PURPOSE: To evaluate the effectiveness and safety of carotid artery stent (CAS) placement for treatment of long segment stenosis in patients with Takayasu arteritis. MATERIALS AND METHODS: Between January 2002 and February 2012, all patients with Takayasu arteritis found to have long segment (≥80 mm) carotid artery stenoses at a single institution were retrospectively analyzed. Five patients treated by CAS placement with either long or multiple self-expandable stents were included. All patients had focal neurologic symptoms, including three strokes and two transient ischemic attacks (TIAs). Six self-expanding stents were used in five patients. The mean follow-up period was 19.2 months (range, 6-30 mo); all patients had clinical evaluation, laboratory examination, and vascular imaging follow-up. RESULTS: Improvement in clinical symptoms was shown after successful angioplasty. There were no perioperative or in-hospital deaths. Four patients exhibited persistent relief, and repeated angiography or computed tomography (CT) angiography showed normal flow. One patient stopped taking her medications after CAS placement and became symptomatic 8 months later as a result of a severe in-stent stenosis. CONCLUSIONS: CAS placement was shown to be a feasible option for treating long segment (≥80 mm) stenosis of carotid arteries in patients with Takayasu arteritis with encouraging results.

A novel SOD1 mutation in amyotrophic lateral sclerosis with a distinct clinical phenotype.

Familial amyotrophic lateral sclerosis (FALS) accounts for about 5% of cases of the neurodegenerative disorder ALS. At least 100 Cu/Zn superoxide dismutase (SOD1) genetic mutations have been associated with FALS. We identified a FALS family in China with an atypical clinical phenotype. To investigate the SOD1 gene mutations in this family, five exons of the SOD1 gene from each living patient were amplified by PCR and screened by SSCP and direct DNA sequencing. SSCP analysis demonstrated a mutation in exon 2 of SOD1, and DNA sequencing demonstrated the presence of an insertion mutation in exon 2 that has not been reported previously. The mutant SOD1 gene encodes a truncated protein of 35 amino acid residues compared to the normal SOD1 protein of 153 amino acids. In conclusion, The SOD1 exon 2 mutation is likely to be the etiological factor of ALS in this family.

Five-year follow-up of stenting for a symptomatic posterior cerebral artery stenosis.

Angioplasty and stenting in symptomatic intracranial stenosis is technically possible and may reduce the risk of stroke in patients with symptomatic arterial stenosis. We report a patient with P1 segment stenosis of posterior cerebral artery treated successfully with angioplasty and stenting with a favorable outcome. He had 5 years of clinical and imaging follow-up and no in-stent stenosis or new ischemic event was observed.

Development of transgenic endothelial progenitor cell-seeded stents.

Endothelial progenitor cell (EPC)-seeded intravascular stents may reduce or prevent in-stent restenosis. A20 can play an important role for preventing vascular restenosis. Therefore, it is very important how to enhance the seeding efficiency of A20-modified EPCs on the stent for preventing in-stent restenosis. To approach this problem, we developed a novel transgenic EPC-seeded stent and evaluated its feasibility and efficiency. EPCs were isolated and purified from umbilical blood using immunomagnetic beads and then transfected with the A20 gene. One stent type (type 1) was coated with EDC cross-linked collagen, and another stent type (type 2) was coated with EDC cross-linked collagen and bound to the CD34 antibody using the bifunctional coupling agent N-succinmidyl3-(2-pyridyldithio) propionate (SPDP). Then, the stents were seeded with EPCs transfected with the A20 gene. The stents were implanted in biological artificial vessels, and cell adhesion was determined in a flow chamber. Cell growth was also measured. EPCs were transfected successfully with the A20 gene. The cells covered both types of stents with favorable biological function. After placement in a flow chamber, the number of cells attached to type 1 stents significantly dropped and their distribution was scattered. Type 2 stents were basically covered with cells and there were more cells on type 2 stents than on type 1 stents (p < 0.01). Collagen-coupled antibody effectively improves the seeding of transgenic EPCs, offering a new choice of stents to prevent restenosis caused by vascular disease after interventional treatment.

[Identification of the mutation of SOD1 gene in a familial amyotrophic lateral sclerosis].

OBJECTIVE: To identify the mutation of Cu/Zn superoxide dismutase(SOD1) gene in an amyotrophic lateral sclerosis (ALS) family with unique phenotype. METHODS: Five exons of SOD1 gene were amplified by PCR. The differences of these products were analyzed by PCR-single strand conformation polymorphism and visualized by silver staining. RESULTS: Abnormal bands were found in exons 2 and 5 of SOD1 gene in several familial members. DNA sequence analysis verified that a base pair insertion occurred in the codon area of exon 2 and in the intron area of exon 5. And the insertion mutation of exon 2 led to a frameshift mutation and premature stop. It is a new type of SOD1 mutation which may be associated with familial amyotrophic lateral sclerosis. CONCLUSION: Insertion mutation of exon 2 may be responsible for the disease of an ALS family in Chongqing.