Effects of cilostazol on the progression and regression of symptomatic intracranial artery stenosis:it reduces the risk of ischemic stroke

OBJeCTIve：To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL： We searched the main databases for eligible trials including Medline （from 1966 to June 2014）, Embase （from 1980 to June 2014）, Cochrane Library （Issue 6, 2014）, Chinese National Knowledge Infrastructure （from 1995 to June 2014）, Current Controlled Trials （http：//controlled-trials.com）, Clinical Trials.gov （http：//clinicaltrials.gov）, and Chinese Clinical Trial Registry （http：//www.chictr.org）. All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the En-glish words： “cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke.” No restrictions were put on publications or publication language. SeLeCTION CRITeRIA：Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspi-rin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria de-scribed in Cochrane Reviewer’s Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOMe MeASUReS： Clinical efifcacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnet-ic resonance angiography and transcranial Doppler. ReSULTS：Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis （OR = 0.21, 95%CI： 0.09–0.47,P 〈 0.01）, it had no beneifcial effect on symptom regression （OR = 1.42, 95%CI： 0.80–2.51,P = 0.24）. During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION：Cilostazol may prevent the progression of symptomatic intracranial artery ste-nosis, which could reduce the incidence of ischemic stroke.

Stenting of Intracranial Artery Stenosis:Complications and Management

Background and Purpose Symptomatic intracranial artery stenosis is a high-risk factor of ipsilateral ischemic stroke. Angioplasty with stent has been introduced to treat patients with transient ischemic attack (TIA) and minor stroke attributed to intracranial stenosis since 1996. However, procedure-related neurological complications, either ischemic or hemorrhagic, could result in stroke and death, and benefits of stenting might be offset by higher disable stroke and death. So, the neurovascular angioplasty team should make great efforts to control procedural complications below an acceptable level, such as 10%, because it is impossible to avoid complication absolutely. The team should also be able to recognize, analyze and manage various procedure-related complications, to reduce the risk of disable stroke and death. The purposes of this article were to report our experiences of 20 complications, which occurred during the period of periprocedure.Methods Between September 5, 2001 and August 12, 2004, a total of 155 patients with 170 symptomatic intracranial stenoses of ≥ 50% received intracranial stenting. The management strategies for complication were as follow: ① intra-thrombus urokinase thrombolysis through micro-catheter for acute or subacute occlusion. ② another stenting for dissection. ③ antiplatelet and anticoagulation therapy for penetrator events. ④ continuing nimodipine intravenously for vasospasm. ⑤ to control blood pressure below 110 / 70 mm Hg, to neutralize heparin with protamine sulfate and to discontinue antithrombotic agents, etc, for intracranial hemorrhage. Disable stroke was defined as one that led to a modified Rankin scale (mRS) score of ≥2, 30 days after stroke. Results Procedure -related neurological complications occurred in 20 patients (12.9%, 20/ 155) and 20 lesions (11.7%, 20/ 170), including 6 intracranial hemorrhage (symptomatic, n=4; asymptomatic, n=2), 13 ischemic cerebral events (stroke, n=12; transient ischemic attacks, n=1) and 1 asymptomatic dissection. The probable causes, managements and outcomes of 20 complications are shown in table. Finally, by the means of aggressive endovascular and medical therapies, disable stroke and death within 30 days was 3.2% (5/155) and 1.3% (2/155), respectively. Conclusions Higher risk of procedure-related neurological complications may occur in stenting of intracranial stenosis. To reduce the possibility of disable stroke and death within 30 days, it is mandatory to develop strict procedural and periprocedural management strategies.

Association of bone turnover biomarkers with severe intracranial and extracranial artery stenosis in type 2 diabetes mellitus patients

BACKGROUND Intracranial and extracranial artery stenosis is associated with cerebral infarction.Vascular calcification and atherosclerosis are the main causes of stenosis and major risk factors for cardiovascular and cerebrovascular events in patients with type 2 diabetes mellitus(T2DM).Bone turnover biomarkers(BTMs)are associated with vascular calcification,atherosclerosis,glucose,and lipid metabolism.AIM To investigate the association of circulating BTM levels with severe intracranial and extracranial artery stenosis in patients with T2DM.METHODS For this cross-sectional study including 257 T2DM patients,levels of the BTMs serum osteocalcin(OC),C-terminal cross-linked telopeptide of type I collagen(CTX),and procollagen type I N-peptide were measured by electrical chemiluminescent immunoassay,and artery stenosis was assessed by color Doppler and transcranial Doppler.Patients were grouped according to the existence and location(intracranial vs.extracranial)of artery stenosis.Correlations between BTM levels,previous stroke,stenosis location,and glucose and lipid metabolism were analyzed.RESULTS T2DM patients with severe artery stenosis had a higher frequency of previous stroke and levels of all three tested BTMs(all P<0.05)than patients without.Some differences in OC and CTX levels were observed according to the location of artery stenosis.Significant associations were also observed between BTM levels and some glucose and lipid homeostasis parameters.On multivariate logistic regression analysis,all BTMs were significant predictors of artery stenosis in T2DM patients with and without adjustment for confounding factors(all P<0.001),and receiver operating characteristic curve analysis demonstrated the ability of BTM levels to predict artery stenosis in T2DM patients.CONCLUSION BTM levels were found to be independent risk factors for severe intracranial and extracranial artery stenosis and were differentially associated with glucose and lipid metabolism in patients with T2DM.Therefore,BTMs may be promising biomarkers and potential therapeutic targets for artery stenosis.

Intracranial large artery embolism due to carotid thrombosis caused by a neck massager:A case report

BACKGROUND There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager.Herein we report such a case.CASE SUMMARY A 49-year-old woman presented with left limb weakness and dysarthria after a history of neck massage for 1 mo.Neurological examination showed left central facial paralysis and left hemiparesis with a National Institutes of Health Stroke Scale score of 12.Brain magnetic resonance imaging revealed restricted diffusion on diffusion-weighted imaging in the right parietal and temporal lobes.Computed tomography angiography(CTA)indicated M3 segment embolism of the right middle cerebral artery.Neck CTA revealed thrombosis of the bilateral common carotid arteries.Carotid ultrasound showed thrombosis in the bilateral common carotid arteries(approximately 2 cm below the proximal end of the carotid sinus),and contrast-enhanced ultrasound did not suggest enhancement.No hypertension,diabetes,heart disease,vasculitis,or thrombophilia was found after admission.After 1 wk of treatment with aspirin 200 mg and atorvastatin 40 mg,a carotid ultrasound reexamination showed that the thrombosis had significantly reduced.CONCLUSION Neck massager may cause carotid artery thrombosis.

Subintimal recanalization for non-acute occlusion of intracranial vertebral artery in an emergency endovascular procedure:A case report

BACKGROUND Endovascular recanalization of non-acute intracranial artery occlusion is technically difficult,particularly when the microwire enters the subintima.Although the subintimal tracking and re-entry technique has been well established in the endovascular treatment of coronary artery occlusion,there is limited experience with its use in intracranial occlusion due to anatomical variations and a lack of dedicated devices.CASE SUMMARY A 74-year-old man was admitted to the hospital two days after experiencing acute weakness in both lower extremities,poor speech,and dizziness.After admission,imaging revealed acute ischemic stroke and non-acute occlusion of bilateral intracranial vertebral arteries(ICVAs).On the fourth day of admission,the patient's condition deteriorated and an emergency endovascular recanalization of the left ICVA was performed.During this procedure,a microwire was advanced in the subintima of the vessel wall and successfully reentered the distal true lumen.Two stents were implanted in the subintima.The patient's Modified Rankin Scale was 1 at three months postoperatively.CONCLUSION We present a technical case of subintimal recanalization for non-acute ICVA occlusion in an emergency endovascular procedure.However,we emphasize the necessity for caution when applying the subintimal tracking approach in intracranial occlusion due to the significant dangers involved.

Drug-coated balloon angioplasty for the treatment of intracranial arterial stenosis in a young stroke patient:A case report

BACKGROUND Intracranial arterial narrowing is a significant factor leading to brief episodes of reduced blood flow to the brain,known as transient ischemic attacks,or fullblown strokes.While atherosclerosis is commonly associated with intracranial arterial narrowing,it is frequently of a non-atherosclerotic nature in younger patients.CASE SUMMARY Here,we present the case of a young stroke patient with narrowing of the middle cerebral artery(MCA),characterized as non-atherosclerotic lesions,who experienced an ischemic stroke despite receiving standard drug therapy.The patient underwent digital subtraction angiography(DSA)to assess the entire network of blood vessels in the brain,revealing significant narrowing(approximately 80%)in the M1 segment of the right MCA.Subsequently,the patient underwent Drug-Coated Balloon Angioplasty to treat the stenosis in the right MCA's M1 segment.Follow-up DSA confirmed the resolution of stenosis in this segment.Although the remaining branches showed satisfactory blood flow,the vessel wall exhibited irregularities.A review of DSA conducted six months later showed no evident stenosis in the right MCA,with a smooth vessel wall.CONCLUSION The use of drug-coated balloon angioplasty demonstrated favorable outcomes in repairing and reshaping the blood vessel wall in young patients.Therefore,it may be considered a promising treatment option for similar cases.

Intracranial artery stenosis: Current status of evaluation and treatment in China

Intracranial artery stenosis (ICAS), a common cause of ischemic stroke, is a growing cause of concern in China. Recently, many epidemiological, etiological, pathophysiological, therapy, and diagnostic imaging studies have focused on ICAS, and guidelines and consensus on the diagnosis and treatment of ICAS have been published and updated by domestic experts. Such work is pivotal to our enhanced comprehension, diagnosis, and treatment of ICAS. In this review, we summarize the latest progress in the eval-uation and treatment of ICAS in China.

A novel cerebrovascular drug-coated balloon catheter for treating symptomatic intracranial atherosclerotic stenosis lesions:Study protocol for a prospective,multicenter,single-arm,target-value clinical trial

Background:Previous single-center studies have demonstrated that drug-coated balloons(DCBs)may reduce restenosis rates,which is an important factor affecting the prognosis for intracranial interventional therapy.However,currently available cardiac DCBs are not always suitable for the treatment of intracranial atherosclerotic stenosis(ICAS).This study aimed to evaluate the safety and efficacy of a novel DCB catheter designed for patients with severely symptomatic ICAS.Methods:This prospective,multicenter,single-arm,target-value clinical trial was conducted in 9 Chinese stroke centers to evaluate the safety and efficacy of a novel DCB catheter for treating symptomatic severe ICAS.Primary metrics and other indicators were collected and analyzed using SAS version 9.4(SAS Institute,Cary,NC,USA).Results:A total of 155 patients were enrolled in this study.The preliminary collection of follow-up data has been completed,while data quality control is ongoing.Conclusion:Results of this study demonstrated the patency rate,safety,and effectiveness of a novel on-label paclitaxel DCB designed for the treatment of ICAS.Ethics and dissemination:This study,involving human participants,was reviewed and approved by the Ethics Committee of Drugs(Devices)Clinical Experiment at Henan Provincial People’s Hospital(reference number:2020-145-03)and other research centers participating in the clinical trial.The results of this study will be presented at international conferences and sent to peer-reviewed journals for publication.Standard protocol items:The Recommendations for Interventional Trials checklist was used when drafting the study protocol.Trial registration number:Registered with the Chinese Clinical Trial Registry on June 11,2021(Chi CTR2100047223).

Endovascular coil embolization of parent artery for giant intracranial basilar dissection:a case report and literature review

Objective The purpose of the current study was to evaluate the method and result of endovascular treatment for a giant unruptured dissection of the basilar artery (BA) . Methods A 14-year-old boy underwent computed tomography (CT) scan following a minor head trauma was incidentally found a lesion located

Matrix metalloproteinase 9 level as an indicator for restenosis following cervical and intracranial angioplasty and stenting

Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study in-vestigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that resteno-sis occurred in 30% （3/10） of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% （2/17） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% （1/23） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically signiifcant （P 〉 0.05）. Experimental ifndings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervi-cal and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis.

INTRACRANIAL ARTERIAL OCCLUSIVE LESION IN PATIENTS WITH GRAVES DISEASE

Objective To investigate the distribution and clinical manifestations of intracranial arterial occlusive lesions （IA- OLs）, and their correlation with thyroid function. Methods We enrolled 7 patients who had Graves＇ disease （GD） with IAOLs screened and evidenced by transcranial Doppler, then further confirmed with digital substract angiography in 2 patients and magnetic resonance angiography in 5 patients. Brain magnetic resonance imaging （MRI） was performed in all 7 patients. Three patients were followed up. Results Among 7 patients, 1 was male and 6 were females. The mean age was 32.0 ± 5.5 （ range from 11 to 49） years old. Six of them had symptoms of GD but one was asymptomatic with abnormality of I3, T4, and thyroid stimulating hormone. The lesions of intracranial arteries were symmetrical bilaterally in the intemal carotid artery system in 6 patients, as well as asymmetrical in 1 patient. Terminal internal carotid artery （TICA） were involved in all 7 patients. Middle cerebral artery （MCA） were involved in 3, anterior cerebral artery in 2, and basilar artery in 1 patient. Net-like collateral vessels and mimic moyamoya disease were observed in the vicinity of the occlusive arteries in 2 patients. All patients presented symptoms of ischemic stroke including transient ischemic attack and/or infarction while IA- OLs were found. Three patients had obvious involuntary movements. Brain MRI revealed infarctions located in the cortex, basal ganglion, or hemiovular center in 5 patients. The remaining 2 patients had normal brain MRI. The neurological symptoms were improved concomitant with relief of the thyroid function in 2 patients, while IAOLs were aggravated with deterioration of the thyroid function in 1 patient. Conclusion IAOLs in patients with GD mainly involve intracranial arteries, especially the TICA and MCA, which is similar to moyamoya disease. The neurological symptoms and severity of involved arteries may relieve while the hyperthyroidism is gradually under control.

Clinical usefulness of ankle brachial index and brachial-ankle pulse wave velocity in patients with ischemic stroke

Ankle brachial index （ABI） and brachial-ankle pulse wave velocity （baPWV） are widely used noninvasive modalities to evaluate atherosclerosis. Recently, evidence has increased supporting the use of ABI and baPWV as markers of cerebrovascular disease. This study sought to examine the relationship between ABI and baPWV with ischemic stroke. This study also aimed to determine which pathogenic mechanism, large artery disease （LAD） or small vessel disease （SVD）, is related to ABI or baPWV. Retrospectively, 121 patients with ischemic stroke and 38 subjects with no obvious ischemic stroke history were recruited. First, ABI and baPWV were compared between the groups. Then, within the stroke group, the relevance of ABI and baPWV with regard to SVD and LAD, which were classified by brain magnetic resonance image （MRI） and magnetic resonance angiography （MRA） or computed tomography angiography （CTA） findings, was assessed. The baPWV was higher in the stroke group than non-stroke group （1,944.18±416.6 cm/s vs. 1,749.76±669.6 crn/s, P 〈 0.01）. Regarding LAD, we found that mean ABI value was lower in the group with extracranial large artery stenosis （P 〈 0.01）, and there was an inverse linear correlation between ABI and the grade of extracranial large artery stenosis （P〈 0.01）. For SVD, there was a significant correlation between SVD and baPWV （2,057.6±456.57 cm/s in the SVD （＋） group vs. 1,491±271.62 cm/s in the SVD （-） group; P 〈 0.01）. However, the grade of abnormalities detected in SVD did not correlate linearly with baPWV. These findings show that baPWV is a reliable surrogate marker ofischemic stroke. Furthermore, baPWVand ABI can be used to indicate the presence of small vessel disease and large arterial disease, respectively.

CEREBRAL ARTERY RECONSTRUCTION IN THE TREATMENT OF LARGE AND GIANT INTRACRANIAL ANEURYSMS

From 1978 to 1988, 14 giant intracranial aneurysms(more than 2.4 cm in diameter) and one large aneurysm (1.5cm in diameter) were treated by extracranial/intracranial(EC/IC) bypass or cerebral artery reconstruction. Of theaneurysms, 10 were located at the intracavernous carotid ar-tery (CCA). One of the 10 anourysms was posttraumatic andlocated at both the carotid-ophthalmic artery segment and thebifurcation of the internal carotid artery (ICA). Three wereseen at the middle cerebral artery (MCA) trunk.Theaneurysms were demonstrated by angiography and CTscanning. They were treated with trapping of the aneurysm andsuperficial temporal artery (STA)/middle cerebral artery(STA-MCA) bypass with/without a graft (6 cases), cervicalICA ligation and STA-MCA bypass with / without a graft (6)aneurysm excision with an end-to-end anastomosis of theMCA and a STA-MCA bypass with a graft (1), proximal

Effect of arteriosclerotic intracranial arterial vessel wall enhancement on downstream collateral flow

Background:The effect of arteriosclerotic intracranial arterial vessel wall enhancement(IAVWE)on downstream collateral flow found in vessel wall imaging(VWI)is not clear.Regardless of the mechanism underlying IAVWE on VWI,damage to the patient’s nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow.The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow.Methods:The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery(MCA)M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset.The patients were divided into 4 groups according to IAVWE and the stenosis ratio(Group 1,n=17;Group 2,n=19;Group 3,n=13;Group 4,n=14),and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling(3D-pCASL)and RAPID software.The National Institutes of Health Stroke Scale(NIHSS)scores of the patients were also recorded.Two-factor multivariate analysis of variance using Pillai’s trace was used as the main statistical method.Results:No statistically significant difference was found in baseline demographic characteristics among the groups.IAVWE,but not the stenosis ratio,had a statistically significant significance on the late-arriving retrograde flow proportion(LARFP),hypoperfusion intensity ratio(HIR),and NIHSS scores(F=20.941,P<0.001,Pillai’s trace statistic=0.567).The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables:LARFP(R^(2)=0.088,F=10.899,P=0.002),HIR(R^(2)=0.234,F=29.354,P<0.001),and NIHSS(R^(2)=114.339,F=33.338,P<0.001).Conclusions:Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits.It was an independent factor affecting downstream collateral flow and NIHSS scores,which should be a focus of future studies.Trial Registration:ChiCTR.org.cn,ChiCTR2100053661.

Chinese specialist consensus on imaging diagnosis of intracranial arterial dissection

Intracranial arterial dissection is an important cause of stroke in young and middle-aged adults, but there are no domestic or globally-accepted criteria for the diagnosis and classification of intracranial arterial dissections. The evidence base for the benefits of diagnostic and interventional angiography techniques is lacking, and the imaging features of intracranial arterial dissections are not yet universally recognized or understood by clinicians. These issues influence the diagnosis and treatment of intracranial arterial dissection. Therefore, a consensus conference was convened by Neurointerventional Expert Committee of Chinese Congress of Neurological Surgeons, Chinese Interventional Neuroradiology Society of Chinese Stroke Association and Young Physicians Committee of Chinese Congress of Neurological Surgeons. The aim of this document is to report an expert consensus on the imaging diagnosis of intracranial arterial dissection. The participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. The expert consensus was intended to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

Multiple factor analysis of symptomatic intracranial arterial stenosis

Objective: To discuss the correlation among intracranial arterial stenosis and its risk factors. Methods: A total of 486 patients with transient ischemic attack(TIA) or ischemic cerebral infarction were examined using color doppler flow imaging(CDFI) and transcranial doppler ultrosonography(TCD). According to the degrees of extracranial arterial stenosis, patients with mild-to-moderate extracranial stenosis were classified into group A(435 cases) while those with constant severe stenosis or occlusion were classified into group B(51 cases). The differences between the two groups of risk factors were compared, and the multi-factor logistic regression analysis of risk factors associated with moderately severe intracranial arterial stenosis was performed. Results:(1) The risk factors that were significantly associated with intracranial arterial stenosis included age(P = 0.034) and gender(P = 0.044).(2) Intracranial artery stenosis was observed in both anterior and posterior cerebral arteries in patients with hypertension, diabetes, and coronary heart disease respectively(P < 0.05).(3) Compared with group A, patients in group B were older(P = 0.000), with a higher proportion of men(P = 0.037), and the intracranial arterial stenosis degrees were significantly higher(P = 0.013).(4) Multi-factor logistic regression analysis showed that diabetes is a risk factor for moderately severe intracranial arterial stenosis(P < 0.05), and hyperlipidemia is a protective factor(P = 0.012). Conclusions: Age, gender, hypertension, diabetes, coronary heart disease, and smoking are risk factors for the distribution of intracranial arterial stenosis. The degrees of intracranial arterial stenosis are related with extracranial arterial stenosis. Diabetes is a risk factor for moderately severe intracranial arterial stenosis while hyperlipidemia is a protective factor.

High-resolution Magnetic Resonance Imaging of Moyamoya Disease

Objective： To introduce the imaging characteristics of moyamoya disease （MMD） using high-resolution magnetic resonance imaging （HR-MRI） and to discuss the role of HR-MRI in differentiating MMD from other intracranial artery diseases, especially intracranial atherosclerotic disease （ICAD）. Data Sources： This review was based on the data in articles published between 2005 and 2015, which were obtained from PubMed. The keywords included HR-MRI, MMD, ICAD, and intracranial artery diseases. Study Selection： Articles related to HR-MRI for MMD or other intracranial artery diseases were selected for review. Results： There are differences between the characteristic patterns of HR-MRI in MMD and ICAD. MMD is associated with inward remodeling, smaller outer diameters, concentric occlusive lesions and homogeneous signal intensity, while ICAD is more likely to be associated with outward remodeling, normal outer diameters, eccentric occlusive lesions, and heterogeneous signal intensity. Other intracranial artery diseases, such as dissection and vasculitis, also have distinctive characteristics in HR-MRI. HR-MRI may become a useful tool for the differential diagnosis of MMD in the future. Conclusions： HR-MRI of MMD provides a more in-depth understanding of MMD, and it is helpful in evaluating pathological changes in the vessel wall and in differentiating MMD from other intracranial artery steno-occlusive diseases, particularly ICAD.以