Infection and Pediatric Arterial Ischemic Stroke Presumably Related to Focal Cerebral Arteriopathy: Data From the COVID-19 Pandemic.

BACKGROUND: Infection may trigger pediatric arterial ischemic stroke (PAIS), notably when related to focal cerebral arteriopathy. Community- and individual-level nonpharmaceutical interventions during the COVID-19 pandemic resulted in a major decrease in pediatric viral infections. We explored the consequences on the incidence of PAIS. METHODS: Using national public health databases, we identified children hospitalized between 2015 and 2022 with PAIS. Using an age proxy (29 days to 7 years) and excluding patients with cardiac and hematologic conditions, we focused on children with PAIS presumably related to focal cerebral arteriopathy or with no definite cause. Considering the delay between infection and PAIS occurrence, we compared a prepandemic reference period, a period with nonpharmaceutical interventions, and a post-nonpharmaceutical intervention period. RESULTS: Interrupted time-series analyses of the monthly incidence of PAIS in this group showed a significant decrease in the nonpharmaceutical intervention period compared with the prepandemic period: -33.5% (95% CI, -55.2%, -1.3%); P=0.043. CONCLUSIONS: These data support the association between infection and PAIS presumably related to focal cerebral arteriopathy.

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.

BACKGROUND: Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases. METHODS: In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging score in the PC. RESULTS: Thirty-five children with a median age of 6.3 (interquartile range, 2.7-8.2 [95% CI, 0.9-15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11-0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75-21.0) compared with 4.5 (interquartile range, 2.0-8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54). CONCLUSIONS: FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.

Current treatment for childhood arterial ischaemic stroke.

Paediatric arterial ischaemic stroke is an important cause of neurological morbidity in children, with consequences including motor disorders, intellectual impairment, and epilepsy. The causes of paediatric arterial ischaemic stroke are unique compared with those associated with stroke in adulthood. The past decade has seen substantial advances in paediatric stroke research and clinical care, but many unanswered questions and controversies remain. Shortage of prospective evidence for the use of recanalisation therapies in patients with paediatric stroke has resulted in little standardisation of disease management. Substantial time delays in diagnosis and treatment continue to challenge best possible care. In this Review, we highlight on some of the most pressing and productive aspects of research in the treatment of arterial ischaemic stroke in children, including epidemiology and cause, rehabilitation, secondary stroke prevention, and treatment updates focusing on advances in hyperacute therapies such as intravenous thrombolysis, mechanical thrombectomy, and critical care. Finally, we provide a future perspective for improving outcomes and quality of life for affected children and their families.

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study.

OBJECTIVE: To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations. DESIGN: Population based cohort study. SETTING: Nationwide healthcare registers in Denmark and Norway. PARTICIPANTS: All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts. MAIN OUTCOME MEASURES: Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries. RESULTS: The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected. CONCLUSIONS: Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Focal Cerebral Arteriopathy of Childhood: Clinical and Imaging Correlates.

Background and Purpose: Focal cerebral arteriopathy (FCA) of childhood with unilateral stenosis of the anterior circulation is reported to account for up to one-quarter of childhood arterial ischemic stroke, with stroke recurrence in 25% of cases. Limited knowledge regarding pathophysiology and outcome results in inconsistent treatment of FCA. Methods: Children with arterial ischemic stroke due to FCA between January 1, 2009, and January 1, 2019, were retrospectively identified at our institution which serves the US Pacific Northwest region. Electronic health record data, including neuroimaging studies, were reviewed, and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point. Results: Fifteen children were diagnosed with FCA, accounting for 19% of children with cerebral arteriopathies (n=77). Among children with FCA, the median age at the time of stroke was 6.8 years (Q1­Q3, 1.9­14.0 years). Four (20%) patients had worsening stroke, 3 of whom had concurrent infection. Three (20%) FCA cases were treated with steroids, one of whom had worsening stroke. Median Pediatric Stroke Outcome Measure at 1 year was 1.0 (Q1­Q3, 0.6­2.0). Variability in arteriopathy severity was observed within many patients. Patients with more severe arteriopathy using the Focal Cerebral Arteriopathy Severity Score had larger strokes and were more likely to have worsening stroke. The most common long-term neurological deficit was hemiparesis, which was present in 11 (73%) patients and associated with middle cerebral artery arteriopathy and infarcts. Conclusions: FCA may be less common than previously reported. Neuroimaging in FCA can help identify patients at greater risk for worsening stroke.

To what degree is late life cognitive decline driven by age-related neuropathologies?

The ageing brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease, infarcts, and Lewy bodies, account for ∼40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline [e.g. limbic predominant age-related TDP-43 encephalopathy (LATE-NC), hippocampal sclerosis, other cerebrovascular conditions]. We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. Deceased participants (n = 1164) from two longitudinal clinical-pathological studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathological examinations provided 11 pathological indices, including markers of Alzheimer's disease, non- Alzheimer's disease neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathological indices with global cognitive decline, and random change point models examined the relation of the pathological indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, P < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, P < 0.001). When considered separately, 10 of 11 pathological indices were associated with faster decline and accounted for between 2% and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathological indices together accounted for 43% of the variation in decline; Alzheimer's disease-related indices accounted for 30-36% of the variation, non-Alzheimer's disease neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathological indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive ageing and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

OBJECTIVE: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features. METHODS: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes. RESULTS: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions. CONCLUSION: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

Evaluation of intracranial and extracranial atherosclerotic lesions in patients with symptomatic coronary artery disease.

OBJECTIVES: Patients with coronary artery disease (CAD) concomitant with extracranial and intracranial atherosclerotic disease (EICAD) may have an increased risk of stroke and myocardial ischemic events. This study aimed to evaluate the concomitant atherosclerotic lesions in extra- and intracranial arterial beds in patients with CAD. METHODS: A total of 1274 patients who underwent coronary angiography due to ischemic heart disease were included. All patients underwent ultrasound screening of the extra- and intracranial arteries before coronary angiography, and the degrees of extracranial carotid artery disease (ECAD) and intracranial cerebral artery disease (ICAD) were recorded. RESULTS: A total of 1062 cases of CAD were confirmed. The prevalence of ECAD, ICAD, and EICAD (ECAD combined with ICAD) in patients with CAD was 15.6%, 11.2% and 11.9%, respectively. For patients with 3-vessel disease, the prevalence was 20.5%, 13.8% and 18.1%, and for patients with severe coronary artery stenosis, the prevalence was 15.8%, 12.1% and 13.2%, respectively. The presence and extent of ECAD and ICAD were positively correlated with the number of lesion vessels and degree of CAD. The posterior circulation arteries were more prone to lesions in patients with ECAD, while the anterior circulation arteries were more vulnerable to lesions in patients with ICAD. CONCLUSIONS: The prevalence of ECAD, ICAD and EICAD is high in patients with CAD, and the presence of these conditions is positively correlated with the extent and degree of CAD. Evaluations of ECAD and ICAD should be highly recommended for CAD patients to reduce the future risk of cardiovascular diseases.

Symptomatic and asymptomatic intracranial atherosclerotic stenosis: 3 years' prospective study.

BACKGROUND: Intracranial stenoses can cause TIA/ischaemic stroke. The purpose of this study was to assess vascular risk factors, clinical and imaging findings and outcome in Caucasians with intracranial stenosis under best prevention management. METHODS: In this prospective observational study (from 05/2012, to last follow-up 06/2017) we compared vascular risk factors, imaging findings and long-term outcome in Swiss patients with symptomatic versus asymptomatic intracranial atherosclerotic stenoses on best prevention management. RESULTS: 62 patients were included [35.5% women, median age 68.3 years], 33 (53.2%) with symptomatic intracranial stenoses. Vascular risk factors (p = 0.635) and frequency of anterior circulation stenoses (66.7% vs. 55.2%; p = 0.354) did not differ between symptomatic and asymptomatic patients, but CT/MR-perfusion deficits in the territory of the stenosis (81.8% vs. 51.7%; p = 0.011) were more common in symptomatic patients. Outcome in symptomatic and asymptomatic patients at last follow-up was similar (mRS 0-1:66.7% vs. 75%;adjp = 0.937, mRS adjp-shift = 0.354, survival:100% vs. 96.4%;adjp = 0.979). However, during 59,417 patient follow-up days, symptomatic patients experienced more cerebrovascular events (ischaemic stroke or TIA) [37.5% vs. 7.1%;adjHR 7.58;adjp = 0.012], mainly in the territory of the stenosis [31.3% vs. 3.6%;adjHR 12.69;adjp = 0.019], more vascular events (i.e. ischaemic stroke/TIA/TNA and acute coronary/peripheral vascular events) [62.5% vs. 14.3%;adjHR 6.37;adjp = 0.001]) and more multiple vascular events (p-trend = 0.006; ≥ 2:37.5% vs. 10.7%;adj OR 5.37;adjp = 0.022) than asymptomatic patients. CONCLUSIONS: Despite best prevention management, one in three patients with a symptomatic intracranial stenosis suffered a cerebrovascular event, three in five a vascular event and two in five ≥ 2 vascular events. There is an unmet need for more rigorous and effective preventive strategies in patients with symptomatic intracranial stenoses.

Arterial ischemic stroke in non-neonate children: Diagnostic and therapeutic specificities.

Pediatric arterial ischemic stroke (AIS) is a severe condition, with long-lasting devastating consequences on motor and cognitive abilities, academic and social inclusion, and global life projects. Awareness about initial symptoms, implementation of pediatric stroke code protocols using MRI first and only and adapted management in the acute phase, individually tailored recanalization treatment strategies, and multidisciplinary rehabilitation programs with specific goal-centered actions are the key elements to improve pediatric AIS management and outcomes. The main cause of pediatric AIS is focal cerebral arteriopathy, a condition with unilateral focal stenosis and time-limited course requiring specific management. Sickle cell disease and moyamoya angiopathy patients need adapted screening and therapeutics.

Intracranial Artery Stenosis and Its Association With Conventional Risk Factors in a General Population of Japanese Men.

Background and Purpose- Few community-based studies have reported the prevalence of intracranial artery stenosis (ICAS) assessed with magnetic resonance angiography. The aim was to determine the prevalence of ICAS using magnetic resonance angiography in a general population of Japanese men and to investigate the associations between ICAS and conventional cardiovascular risk factors. Methods- The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited and examined participants from Kusatsu City, Shiga, Japan, in 2006 to 2008 (baseline); 740 men returned for follow-up and underwent 1.5 T brain magnetic resonance angiography in 2012 to 2015. Participants were categorized as having no-ICAS, mild-ICAS (1 to <50%), or severe-ICAS (≥50%) in any of the arteries examined. After excluding the men with a history of stroke, 709 men were analyzed using multivariable logistic regression to assess independent associations of conventional cardiovascular risk factors with reference to the no-ICAS group. Results- The participants' mean age was 68.0 years. The age-standardized prevalences of mild and severe-ICAS were 20.7% and 4.5%, respectively (with the population of the 2010 Japanese vital statistics as the reference). Age, hypertension, diabetes mellitus, and dyslipidemia were associated with a higher prevalence of severe-ICAS after simultaneous adjustment for conventional cardiovascular risk factors. Conclusions- In a community-based sample of Japanese men, ICAS was estimated to be present in 25.2%, and related to metabolic risk factors, in addition to hypertension and age. These results support the importance of comprehensive management of conventional cardiovascular risk factors for stroke prevention.

The Management of Acute Ischemic Strokes and the Prevalence of Large Vessel Occlusion in Left Ventricular Assist Device.

BACKGROUND: Ischemic and hemorrhagic strokes are frequent complications among those with left ventricular assist device (LVAD). Scarce data exist regarding the prevalence of acute large vessel occlusion (LVO) and treatment of acute ischemic stroke (AIS) in this setting. METHODS: We reviewed prospectively collected data of LVAD patient registry from a single, tertiary center from October 2004 to November 2016. Among those with AIS complications, patients were divided into early stroke (during implantation hospitalization) and late stroke (post-discharge) groups, and neuroimaging was reviewed and data on acute stroke therapy were collected. RESULTS: Of 477 persons with LVAD, 49 (10.3%) AIS occurred. The majority (29/49, 59%) of AIS occurred in-hospital. Thirty-two (65%) persons had international normalized ratios less than 1.7 at the time of AIS, but none qualified to receive acute intravenous thrombolysis. Of 25 (51%) persons who underwent CT angiography (CTA), 33% (16/49) had acute LVOs. Thirty-one percent (5/16) of persons with acute LVOs underwent intra-arterial endovascular therapy. All of 5 cases presented with middle cerebral artery syndrome with a median pre-procedural National Institutes of Health Stroke Scale of 13 (interquartile range 10-18). Successful recanalization was achieved in all 5 cases. CONCLUSIONS: In-hospital strokes and acute LVOs are common in LVAD-associated AIS. Prompt evaluation with CTA and endovascular therapy should be pursued for these critically ill patients.

Rates and Risk Factors for Arterial Ischemic Stroke Recurrence in Children.

BACKGROUND AND PURPOSE: Recurrent ischemic events are common in children with arterial ischemic stroke (AIS) and put patients at risk for further neurological impairment. This study sought to identify rates and risk factors for recurrent AIS or transient ischemic attack in a cohort of children seen after index AIS and uniformly investigated and managed using contemporary clinical guidelines. METHODS: Case note and radiology review of children >28 days and <18 years of age who presented to Great Ormond Street Hospital from 2005 to 2015 with index AIS. Demographic characteristics, medical history, index AIS features, radiological findings, and neurological outcome were examined. Recurrence was identified from clinical records and coded as AIS (if there was associated new cerebral infarction) or transient ischemic attack. RESULTS: Eighty-four children (43 girls; median age at index AIS, 4.1 years) were identified. Cumulative AIS recurrence was 5% at 1 month, 10% at 3 months, 12% at 6 months, 12% at 12 months, and 15% at 60 months after index event. Factors that independently predicted AIS recurrence were referral to Great Ormond Street Hospital from outside the catchment area, a prior relevant diagnosis, bilateral arteriopathy, and AIS CASCADE category 3A or 3B (Childhood AIS Standardized Classification and Diagnostic Evaluation). Multiple infarcts and evidence of mature, as well as acute, infarcts on first brain imaging, although independently associated with AIS recurrence, were also associated with bilateral arteriopathy. Only CASCADE categories 3A and 3B (bilateral cerebral arteriopathy with or without collaterals) remained significant in multivariate analysis. AIS recurrence was not associated with poor neurological outcome. CONCLUSIONS: AIS recurrence remains a significant problem, despite the wide use of antithrombotic medications. AIS subtypes should direct clinicians and future trials to use stratified management strategies and durations of treatment. Bilateral cerebral arteriopathies are especially sinister, and consensus criteria should be developed to improve consistency of management.

Large Vessel Arteriopathy After Cranial Radiation Therapy in Pediatric Brain Tumor Survivors.

Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA. We identified 10 patients with cerebral arteriopathy. The cumulative incidence of arteriopathy 5 years post-cranial radiation therapy was 5.4% (CI 0.6%-10%) and 10 years was 16% (CI 4.6%-26%). One patient had an arterial ischemic stroke 2.4 years post-cranial radiation therapy in the distribution of a radiation-induced stenotic artery. We conclude that large vessel arteriopathies can occur within a few years of cranial radiation therapy and can become apparent on MRA in under a year.

Prevalence of Carotid Web in Patients with Acute Intracranial Stroke Due to Intracranial Large Vessel Occlusion.

Purpose To investigate the prevalence of symptomatic carotid web in patients with acute ischemic stroke due to intracranial large vessel occlusion, to determine the clinical and imaging profile of patients with carotid web as well as their association with ischemic stroke, and to determine the interobserver agreement in the assessment of carotid webs. Materials and Methods All patients (n = 500) of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) in whom the carotid bifurcation could be assessed (n = 443) were included. The presence of a carotid web at the carotid bifurcations was evaluated at computed tomographic (CT) angiography. Demographics, clinical characteristics, and imaging baseline characteristics were presented by descriptive statistics for patients with an identified carotid web. Interobserver agreement in the detection of carotid webs was examined by using kappa statistics. Results Eleven (2.5%) carotid webs were found at the symptomatic side and two (0.5%) carotid webs were found at the asymptomatic side. Ten (91%) patients with a symptomatic carotid web were female. Nine patients with a symptomatic carotid web did not have major risk factors or other causes for ischemic stroke (82%). Fair to good interobserver agreement (κ, 0.72) was observed for diagnosing carotid webs at CT angiography. Conclusion Carotid webs at the symptomatic carotid bifurcation were observed in 2.5% of the patients with acute ischemic stroke due to large vessel occlusion and were mostly diagnosed in female patients with a fair to good interobserver agreement. © RSNA, 2017 Clinical trial registration nos. NTR1804 and ISRCTN10888758 Online supplemental material is available for this article.

Influence of cerebrovascular reactivity on outcome of the patients with ≥50% symptomatic unilateral middle cerebral artery stenosis.

Purpose/aim of the study: Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels, which is an important marker for assessing cerebrovascular disease. The present study is to investigate whether CVR impairment increases adverse long-term outcome risk of patients with ≥ 50% symptomatic unilateral middle cerebral artery (MCA) stenosis (ischemic stroke (IS) or transient ischemic attack (TIA)). MATERIAL AND METHODS: Digital subtraction angiography (DSA) was used to assess the degree of stenosis, and perfusion CT and 5% CO2 inhalation were adopted to evaluate CVR. Patients with ≥ 50% symptomatic unilateral MCA stenosis were assigned to non-CVR impairment group and CVR impairment group according to CVR status. The long-term follow-up endpoint was composite of any IS ( in the territory of the studied MCA) or death within 12 months. RESULTS: Seventy-three patients with ≥ 50% symptomatic unilateral MCA stenosis, involving 31 non-CVR impairment cases and 42 CVR impairment cases, were included in the present study. Finally, IS occurred in six CVR impairment patients, and no endpoint happened in the non-CVR impairment group. Therefore, the annual rate of IS was 14.29% in the CVR impairment group and 0% in the non-CVR impairment group (P = 0.035). Besides, further Kaplan-Meier analysis found CVR impairment was closely associated with the IS risk (Kaplan-Meier Log-rank 4.719, P = 0.030). CONCLUSIONS: Our results showed that for patients with ≥ 50% symptomatic unilateral MCA stenosis, there was significant difference between non-CVR impairment cases and CVR impairment cases in the annual rate of IS. It suggests that CVR impairment increases the risk of adverse long-term outcomes.

Nocturnal oxyhemoglobin desaturation and arteriopathy in a pediatric sickle cell disease cohort.

OBJECTIVE: The purpose of this study of sickle cell disease (SCD) was to determine whether arteriopathy, measurable as intracranial vessel signal loss on magnetic resonance angiography (MRA), was associated with low nocturnal hemoglobin oxygen saturation (SpO2) or hemolytic rate, measurable as reticulocytosis or unconjugated hyperbilirubinemia. METHODS: Ninety-five East London children with SCD without prior stroke had overnight pulse oximetry, of whom 47 (26 boys, 39 hemoglobin SS; mean age 9.1 ± 3.1 years) also had MRA, transcranial Doppler (TCD), steady-state hemoglobin, and reticulocytes within 34 months. Two radiologists blinded to the other data graded arteriopathy on MRA as 0 (none) or as increasing severity grades 1, 2, or 3. RESULTS: Grades 2 or 3 arteriopathy (n = 24; 2 with abnormal TCD) predicted stroke/TIA compared with grades 0 and 1 (log-rank χ2 [1, n = 47] = 8.1, p = 0.004). Mean overnight SpO2 correlated negatively with reticulocyte percentage (r = -0.387; p = 0.007). Despite no significant differences across the degrees of arteriopathy in genotype, mean overnight SpO2 was higher (p < 0.01) in those with grade 0 (97.0% ± 1.6%) than those with grades 2 (93.9 ± 3.7%) or 3 (93.5% ± 3.0%) arteriopathy. Unconjugated bilirubin was not associated but reticulocyte percentage was lower (p < 0.001) in those with grade 0 than those with grades 2 and 3 arteriopathy. In multivariable logistic regression, lower mean overnight SpO2 (odds ratio 0.50, 95% confidence interval 0.26-0.96; p < 0.01) predicted arteriopathy independent of reticulocyte percentage (odds ratio 1.47, 95% confidence interval 1.15-1.87; p = 0.003). CONCLUSION: Low nocturnal SpO2 and reticulocytosis are associated with intracranial arteriopathy in children with SCD. Preventative strategies might reduce stroke risk.

Cerebral misery perfusion due to carotid occlusive disease.

PURPOSE: Cerebral misery perfusion (CMP) is a condition where cerebral autoregulatory capacity is exhausted, and cerebral blood supply in insufficient to meet metabolic demand. We present an educational review of this important condition, which has a range of clinical manifestations. METHOD: A non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease, using Pubmed and Sciencedirect. FINDINGS: Patients with CMP may present with strokes in watershed territories, collapses and transient ischaemic attacks or episodic movements associated with an orthostatic component. While positron emission tomography is the gold standard investigation for misery perfusion, advanced MRI is being increasingly used as an alternative investigation modality. The presence of CMP increases the risk of strokes. In addition to the devastating effect of stroke, there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease (COD) and misery perfusion. The evidence for revascularisation in the setting of complete carotid occlusion is weak. Medical management constitutes careful blood pressure management while addressing other vascular risk factors. DISCUSSION: The evidence for the management of patients with COD and CMP is discussed, together with recommendations based on our local experience. In this review, we focus on misery perfusion due to COD. CONCLUSION: Patients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many specialties. Early identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow, while avoiding potentially harmful treatment.

The Prevalence of and Factors Related to Vascular Hyperintensity on T1-Weighted Imaging in Acute Ischemic Stroke.

BACKGROUND: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. METHODS: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. RESULTS: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). CONCLUSION: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.