Cognitive impairment in asymptomatic cerebral arterial stenosis: a P300 study.

BACKGROUND: Cerebral arterial stenosis (CAS), in the absence of a structural lesion, can result in cognitive impairment that represents an ongoing contention among studies. Accordingly, we investigated cognitive functions in asymptomatic patients with CAS, using P300 which is a neurophysiological tool. We also compared cognition in intracranial stenosis (ICS) and extracranial stenosis (ECS). METHODS: Asymptomatic patients with CAS (≥ 70%) in the absence of structural brain lesions were categorized into ICS and ECS groups of 15 patients each, in addition to 15 normal controls. MRI, MRA, CT angiography, P300 analysis, Mini-Mental State examination (MMSE), Wisconsin Card Sorting Test (WCST), and Wechsler Memory Scale Test-Revised (WMST) were performed to all patients. RESULTS: Impairment on all cognitive scales ranged from 70 up to 100% among CAS group. Prolonged p300 latency and reaction time correlated with worse performance on WMST (p = 0.02), while lower amplitude and decreased accuracy correlated with more errors on WCST (p = 0.01). ICS scores on WCTS were lower than those of ECS group (p = 0.001), while ECS had a longer reaction time (p = 0.02) and lower scores on MMS and WMST than those of ICS group (p = 0.03). CONCLUSION: Patients with asymptomatic CAS had a high prevalence of cognitive dysfunction which places them at risk of higher morbidity. ICS group showed impairment on executive functions, while the ECS group showed predilection to memory and information processing dysfunction.

Improved stenosis outcome in stroke-free sickle cell anemia children after transplantation compared to chronic transfusion.

We report here the 3-year stenosis outcome in 60 stroke-free children with sickle cell anaemia (SCA) and an abnormal transcranial Doppler history, enrolled in the DREPAGREFFE trial, which compared stem cell transplantation (SCT) with standard-care (chronic transfusion for 1-year minimum). Twenty-eight patients with matched sibling donors were transplanted, while 32 remained on standard-care. Stenosis scores were calculated after performing cerebral/cervical 3D time-of-flight magnetic resonance angiography. Fourteen patients had stenosis at enrollment, but only five SCT versus 10 standard-care patients still had stenosis at 3 years. Stenosis scores remained stable on standard-care, but significantly improved after SCT (P = 0·006). No patient developed stenosis after SCT, while two on standard-care did, indicating better stenosis prevention and improved outcome after SCT.

Cerebral venous sinus stenosis should not be neglected when cerebral artery stenosis is confirmed: a case report.

PURPOSE: Cerebral venous sinus stenosis (CVSS) is easily neglected in clinical setting due to its nonspecific symptoms. In patients with cerebral arterial stenosis (CAS), the symptoms caused by CVSS are often mistakenly thought of being attributed to CAS. In this case, we aimed to highlight the clinical manifestations and treatment strategies of CVSS comorbid with CAS. MATERIALS AND METHODS: We present an 83-year-old female who complained a series of nonspecific and non-focal neurological deficits such as tinnitus, head noise, dizziness, etc. She was initially diagnosed as CAS and underwent anti-CAS medication orally for over 2 years, whereas her symptoms were still aggravating. RESULTS: Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) displayed severe stenoses at bilateral sigmoid-transverse sinus conjunctions, and thus, the patient underwent intravenous stenting finally. Her aforementioned symptoms significantly attenuated after venous stenting and even disappeared gradually at 3-month, 6-month and 1-year follow-up. CONCLUSIONS: This paper revealed that cerebral venous outflow disturbance should not be overlooked when the nonspecific and non-focal neurological deficits could not be explained by cerebral artery disease. For this arteriovenous condition, intravenous stenting may be a feasible and effective way for symptoms relieving.

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

BACKGROUND: Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension. METHODS: The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition in patients with IS (n = 78) and cerebral arterial stenosis (CAS) (n = 75) and controls (n = 77) were analyzed by ultra-performance liquid chromatography. RESULTS: Eleven initial glycans and 10 derived glycans in IgG glycome representing galactosylation, sialylation, and bisecting GlcNAc significantly differed between IS patients and CAS and healthy controls after controlling for gender, age, obesity, diabetes, hypertension, and dyslipidemia. Logistic regression models incorporating IgG glycan traits were able to distinguish IS from CAS (area under receiver-operator characteristic curves (AUC), 0.802; 95% confidence interval (CI), 0.732-0.872) and controls (AUC, 0.740; 95% CI, 0.661-0.819). The canonical correlation analysis indicated that initial N-glycan structures are significantly correlated with inflammation markers (r = 0.566, p < 0.001). CONCLUSION: Our findings indicated that loss of galactose and sialic acid, as well as addition of bisecting GlcNAc, might involve in pro- or anti-inflammatory IgG functionality and further contribute to the pathogenesis of IS. IgG glycan profiles may be developed as clinical useful biomarkers for chronic disease in the future.

Early arteriopathy in Aicardi-Goutières syndrome 5. Case report and review of literature.

Aicardi-Goutières syndrome (AGS) is an autosomal recessive disease that mimics congenital viral infection and mainly affects the brain, immune system, and skin. The dominant clinical symptom is the subacute onset of severe encephalopathy, which manifests as irritability, loss of ability, slowing of head growth, and poor nutrition. Arteriopathy in AGS is an uncommon manifestation usually associated with mutations in the SAMHD1 gene. We present a rare case of a 3-year-old male due to failure to thrive, global developmental delay, microcephaly, poor vision, upper and lower limbs spasticity, and gastroesophageal reflux disease (GERD), who harbored early stenotic lesions of the large and medium intracranial arteries with ischemic sequelae in the early postnatal life. Performed genetic testing confirmed homozygous gene mutation, SAMHD1 associated with AGS type 5. By reviewing the available literature, we were able to find only one patient whose arterial lesions were diagnosed after 6 months.

Functional Assessment of Cerebral Artery Stenosis by Angiography-Based Quantitative Flow Ratio: A Pilot Study.

BACKGROUND: Increasing attention has been paid to the hemodynamic evaluation of cerebral arterial stenosis. We aimed to demonstrate the performance of angiography-based quantitative flow ratio (QFR) to assess hemodynamic alterations caused by luminal stenoses, using invasive fractional pressure ratios (FPRs) as a reference standard. METHODS: Between March 2013 and December 2019, 29 patients undergoing the pressure gradient measurement of cerebral atherosclerosis were retrospectively enrolled. Wire-based FPR was defined by the arterial pressure distal to the stenotic lesion (Pd) to proximal (Pa) pressure ratios (Pd/Pa). FPR < 0.70 or FPR < 0.75 was assumed as hemodynamically significant stenosis. The new method of computing QFR from a single angiographic view, i.e., the Murray law-based QFR, was applied to the interrogated vessel. An artificial intelligence algorithm was developed to realize the automatic delineation of vascular contour. RESULTS: Fractional pressure ratio and QFR were assessed in 38 vessels from 29 patients. Excellent correlation and agreement were observed between QFR and FPR [r = 0.879, P < 0.001; mean difference (bias): -0.006, 95% limits of agreement: -0.198 to 0.209, respectively). Intra-observer and inter-observer reliability in QFR were excellent (intra-class correlation coefficients, 0.996 and 0.973, respectively). For predicting FPR < 0.70, the area under the receiver-operating characteristic curves (AUC) of QFR was 0.946 (95% CI, 0.820 to 0.993%). The sensitivity and specificity of QFR < 0.70 for identifying FPR < 0.70 was 88.9% (95% CI, 65.3 to 98.6%) and 85.0% (95% CI, 62.1 to 96.8%). For predicting FPR < 0.75, QFR showed similar performance with an AUC equal to 0.926. CONCLUSION: Computational QFR from a single angiographic view achieved comparable results to the wire-based FPR. The excellent diagnostic performance and repeatability empower QFR with high feasibility in the functional assessment of cerebral arterial stenosis.

Incidence, kinetics, and risk factors for intra- and extracranial cerebral arteriopathies in a newborn sickle cell disease cohort early assessed by transcranial and cervical color Doppler ultrasound.

The risk of stroke in children with sickle cell disease (SCD) is detected by abnormal intracranial arterial time-averaged mean of maximum velocities (TAMVs ≥200 cm/s). Recently, extracranial internal carotid artery (eICA) arteriopathy has been reported, and a cross-sectional study showed that eICA-TAMVs ≥160 cm/s are significantly associated with eICA kinkings and stenosis. The cumulative incidence of and predictive risk factors for intracranial arteriopathy are well described in sickle cell anemia (SCA=SS/Sß0) but are lacking for SC/Sß+ children, as is the cumulative incidence of eICA arteriopathy. We report a prospective longitudinal cohort study including 493 children with SCD (398 SCA, 95 SC/Sß+), all assessed by transcranial and cervical color Doppler ultrasound. Cerebral MRI/MRA data were available in 375 children with SCD and neck MRA in 365 children. eICA kinkings were defined as eICA tortuosities on neck MRA, with an internal acute angle between the two adjacent segments <90°. The median follow-up was 10.6 years. The cumulative incidence of kinkings was significantly lower in SC/Sß+ children than in children with SCA, and no SC/Sß+ child developed intra- or extracranial stenotic arteriopathy. The 10-year KM estimate of cumulative incidence (95% CI) for eICA-TAMVs ≥160 cm/s revealed its development in the 2nd year of life in children with SCA, reaching a plateau of 17.4% (13.2-21.6%) by about 10 years of age, while the plateau for eICA stenosis was 12.3% (8.3-16.3%). eICA assessment identified 13.5% (9.3-17.7%) patients at risk of stroke who were not detected by transcranial color Doppler ultrasound. We also show, for the first time, that in addition to a congenital origin, eICA kinkings sin patients with SCD can develop progressively with aging as a function of eICA-TAMVs, themselves related to anemia severity. Ongoing hydroxyurea treatment was significantly associated with a lower risk of abnormal intracranial arteriopathy and eICA kinkings. After adjustment with hydroxyurea, baseline low hemoglobin, high reticulocyte, and WBC counts remained independent risk factors for intracranial arteriopathy, while low hemoglobin and SEN ß-haplotype number were independent risk factors for extracranial arteriopathy. The association between extracranial arteriopathy and SEN ß-haplotype number suggested a genetic link between the ethnic origin and incidence of eICA kinkings. This prospective cohort study shows the importance of systematically assessing the eICA and of recording biological parameters during the 2nd year of life before any intensive therapy to predict the risk of cerebral arteriopathy and treat patients with severe baseline anemia.

Association Between Metabolic Syndrome and Asymptomatic Cerebral Arterial Stenosis: A Cross-Sectional Study in Shandong, China.

Metabolic syndrome (MetS) can worsen cerebral arterial atherosclerosis stenosis in patients with stroke; however, its effect on patients without stroke remains ambiguous. This study explored the association of MetS and its individual components with asymptomatic intracranial arterial stenosis (aICAS) and asymptomatic extracranial arterial stenosis (aECAS) among older Chinese adults. A total of 1988 participants from the Kongcun Town study aged ≥40 years and without a history of stroke were enrolled. The baseline data were obtained via face-to-face interviews. MetS was defined according to International Diabetes Federation criteria. Detection of aICAS was conducted using transcranial Doppler ultrasound, followed by diagnosis via magnetic resonance angiography. The evaluation of aECAS was performed using bilateral carotid ultrasonography. The aICAS and aECAS groups were 1:1 matched separately to the non-stenosis group by age and sex. The association between MetS and aICAS or aECAS was analyzed using multivariate logistic regression. Among the 1988 participants, 909 were diagnosed with MetS. The prevalence of MetS was higher in the aICAS group than in the non-stenosis group (P <0.001), but did not differ significantly between the aECAS and non-stenosis groups. The prevalence of aICAS increased with the number of MetS components from 3.4% in the ≤ 1 component group to 12.7% in the ≥4 components group (P for trend <0.001). After adjusting for confounding factors, MetS components associated with aICAS included central obesity, elevated triglyceride levels, and elevated blood pressure. None of the MetS components was associated with aECAS. MetS was positively associated with aICAS, but not with aECAS. Further, different components play different roles in the pathological process leading to aICAS.

Cerebral Arterial Stenosis in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) and ischemic stroke share common vascular risk factors such as aging and hypertension. Previous studies suggested that the rate of recurrent ICH and ischemic stroke might be similar after ICH. Presence of cerebral arterial stenosis is a potential risk factor for future ischemic stroke. This study investigated the prevalence and factors associated with cerebral arterial stenosis in Korean patients with spontaneous ICH. METHODS: A total of 167 patients with spontaneous ICH were enrolled. Intracranial arterial stenosis (ICAS) and extracranial arterial stenosis (ECAS) were assessed by computed tomography angiography. Presence of ICAS was defined if patients had arterial stenosis in at least one intracranial artery. ECAS was assessed in the extracranial carotid artery. More than 50% luminal stenosis was defined as presence of stenosis. Prevalence and factors associated with presence of ICAS and cerebral arterial stenosis (presence of ICAS and/or ECAS) were investigated by multivariable logistic regression analysis. RESULTS: Thirty-two (19.2%) patients had ICAS, 7.2% had ECAS, and 39 (23.4%) patients had any cerebral arterial stenosis. Frequency of ICAS and ECAS did not differ among ganglionic ICH, lobar ICH, and brainstem ICH. Age was higher in patients with ICAS (67.6±11.8 vs. 58.9±13.6 years p=0.004) and cerebral arterial stenosis (67.9±11.6 vs. 59.3±13.5 years, p<0.001) compared to those without stenosis. Patients with ICAS were older, more frequently had diabetes, had a higher serum glucose level, and had a lower hemoglobin level than those without ICAS. Patients with cerebral arterial stenosis were older, had diabetes and lower hemoglobin level, which was consistent with findings in patients with ICAS. However, patients with cerebral arterial stenosis showed higher prevalence of hypertension and decreased kidney function compared to those without cerebral arterial stenosis. Multivariable logistic regression analyses showed that aging and presence of diabetes independently predicted the presence of ICAS, and aging, diabetes, and hypertension were independently associated with presence of cerebral arterial stenosis. CONCLUSION: 19.2% of patients with spontaneous ICH had ICAS, but the prevalence of ECAS was relatively lower (7.2%) compared with ICAS. Aging and diabetes were independent factors for the presence of ICAS, whereas aging, hypertension, and diabetes were factors for the cerebral arterial stenosis.

Indirect Revascularization for Non-Moyamoya Disease Anterior Circulation Arterial Steno-occlusion: Clinical Features, Surgical Treatment, and Medium-Term Outcomes in Adults.

BACKGROUND: Symptomatic anterior arterial steno-occlusion is often associated with neurofunctional deficits or a high risk of recurrent stroke or both. Although both medical and endovascular treatments are useful and suitable, few studies have investigated the continued use of indirect encephaloduroarteriosynangiosis (EDAS) bypass in patients with non-moyamoya disease ischemia. We retrospectively investigated clinical features, surgical treatments, and medium-term outcomes of indirect revascularization for patients with non-moyamoya disease anterior circulation arterial steno-occlusion in China. METHODS: EDAS without burr holes was performed in 51 adult patients with cerebral ischemic events and diagnosed nonmoyamoya anterior circulation arterial steno-occlusion. Preoperative, postoperative, and follow-up neurologic status was evaluated using the National Institutes of Health Stroke Scale; changes on angiography and perfusion-weighted magnetic resonance imaging were evaluated. RESULTS: Unilateral EDAS was performed in 48 patients, and bilateral EDAS was performed in 3 patients. Four patients experienced complications before hospital discharge; only 23 patients underwent follow-up angiograms. Of the 51 patients, 44 (86.3%) exhibited improved muscle strength; 21 of 23 patients (91.3%) with follow-up angiography data exhibited evidence of new visible branches from the superficial temporal artery or middle meningeal artery or both. Preoperative and postoperative perfusion-weighted magnetic resonance imaging was performed for 5 patients. Despite clinical improvement in all patients, only 2 exhibited hemodynamic improvement. CONCLUSIONS: Indirect revascularization may be safe and effective for improving blood flow to the ischemic region following nonmoyamoya anterior circulation arterial steno-occlusion, especially in patients with residual postinfarction neurologic deficits. Our study demonstrates that improvements in ischemic symptoms after EDAS correspond to neovascularization from the superficial temporal artery or middle meningeal artery in ischemic brain areas.