Proximal and distant expression of growth differentiation factor 15 (GDF15) correlate with neurological deficit following experimental ischemic stroke.

BACKGROUND AND PURPOSE: Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke. METHODS: Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting. RESULTS: Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score. CONCLUSIONS: Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction.

Prevalence of major embolic findings and incidental findings on early cardiac CT in patients with suspected ischemic stroke.

PURPOSE: The purpose of this study was to assess the type and prevalence of stroke and non-stroke-related findings diagnosed on early cardiac computed tomography (CT) in patients with suspected stroke. The secondary objective was to assess the clinical consequences on the management of patients with non-stroke-related conditions identified by early cardiac CT. MATERIALS AND METHODS: This single-center, retrospective, observational study included 1111 consecutive patients with suspected ischemic stroke between November 2018 and March 2020 who underwent cardiac CT examination in addition to the usual brain CT protocol (i.e., non-enhanced brain CT, perfusion brain CT when needed, aortic arch and supra-aortic CT angiography, and post contrast brain CT). There were 562 women and 549 men with a median age of 74 years (range: 60-85 years). Of these, 415 (415/1111; 37.4%) patients had ischemic stroke and 692 (692/1111; 62.3%) had no stroke. Cardiac CT examinations were retrospectively reviewed for cardiac CT findings at high embolic risk and clinically significant extracardiac incidental findings. RESULTS: Among 1111 included patients, 89 (89/1111; 8.0%) had a stroke-related condition identified on early cardiac CT. This was significantly more frequent in patients with ischemic stroke (66/415; 15.9%) by comparison with those without ischemic stroke (23/696; 3.3%) (P < 0.001), with 41 patients (41/415; 9.9%) diagnosed with left atrial thrombus. Cardiac CT revealed a clinically significant non-stroke-related finding in 173 patients (173/1111; 15.6%), including 17 pulmonary embolisms (1.5%), seven suspicious pulmonary lesions (0.6%), and three breast lesions suspected to be malignant (0.3%). Twenty out of 173 patients (20/173; 11.5%) with incidental findings on early cardiac CT had a change in their management. CONCLUSION: This study shows that adding early cardiac CT to brain CT during the acute phase of an ischemic stroke leads to a higher rate of etiological diagnoses and highlights the major interest of looking at the bigger picture.

IV Thrombolysis With or Without Endovascular Treatment for Suspected Ischemic Stroke in Patients With Intracranial Tumors.

BACKGROUND AND OBJECTIVES: IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce. METHODS: In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS: Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT; among them were 29 patients (28%) with additional endovascular treatment, with suspected, that is, imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in 9 and 4 patients (9% and 4%, respectively). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in 6 and 3 patients (7% and 4%), respectively. In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was 1 symptomatic nonfatal ICH (6%). Of 4 patients with tumors of the pituitary region, 2 patients (50%) had symptomatic ICH including 1 fatal ICH (25%). Tumor size was not associated with the occurrence of symptomatic ICH (odds ratio 2.8, 95% CI 0.3-24.8, p = 0.34). DISCUSSION: In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort seem to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

Sex differences in outcome after carotid revascularization in symptomatic and asymptomatic carotid artery stenosis.

OBJECTIVE: Sex differences regarding the safety and efficacy of carotid revascularization in carotid artery stenosis have been addressed in several studies with conflicting results. Moreover, women are underrepresented in clinical trials, leading to limited conclusions regarding the safety and efficacy of acute stroke treatments. METHODS: A systematic review and meta-analysis was performed by literature search including four databases from January 1985 to December 2021. Sex differences in the efficacy and safety of revascularization procedures, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), for symptomatic and asymptomatic carotid artery stenoses were analyzed. RESULTS: Regarding CEA in symptomatic carotid artery stenosis, the stroke risk in men (3.6%) and women (3.9%) based on 99,495 patients (30 studies) did not differ (P = .16). There was also no difference in the stroke risk by different time frames up to 10 years. Compared with men, women treated with CEA had a significantly higher stroke or death rate at 4 months (2 studies, 2565 patients; 7.2% vs 5.0%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.04-2.12; I2 = 0%; P = .03), and a significantly higher rate of restenosis (1 study, 615; 17.2% vs 6.7%; OR, 2.81; 95% CI, 1.66-4.75; P = .0001). For CAS in symptomatic artery stenosis, data showed a non-significant tendency toward higher peri-procedural stroke in women, whereas for asymptomatic carotid artery stenosis, data based on 332,344 patients showed that women (compared with men) after CEA had similar rates of stroke, stroke or death, and the composite outcome stroke/death/myocardial infarction. The rate of restenosis at 1 year was significantly higher in women compared with men (1 study, 372 patients; 10.8% vs 3.2%; OR, 3.71; 95% CI, 1.49-9.2; P = .005). Furthermore, CAS in asymptomatic patients was associated with low risk of a postprocedural stroke in both sexes, but a significantly higher risk of in-hospital myocardial infarction in women than men (8445 patients, 1.2% vs 0.6%; OR, 2.01; 95% CI, 1.23-3.28; I2 = 0%; P = .005). CONCLUSIONS: A few sex-differences in short-term outcomes after carotid revascularization for symptomatic and asymptomatic carotid artery stenosis were found, although there were no significant differences in the overall stroke. This indicates a need for larger multicenter prospective studies to evaluate these sex-specific differences. More women, including those aged over 80 years, need to be enrolled in randomized controlled trials, to better understand if sex differences exist and to tailor carotid revascularization accordingly.

Impact of Smoking on Functional Prognosis after Ischemic Stroke according to Deprivation: A Prospective Cohort Study.

BACKGROUND: Smoking influence on poststroke prognosis remains controversial. These conflicting results could be due to some residual confounding factors not fully considered in previous studies, including social deprivation. This study aimed to assess the joint impact of deprivation and smoking on functional outcomes after ischemic stroke. METHODS: Between 2011 and 2014, 1,573 patients with a first-ever stroke were prospectively included in the French multicenter INDIA ("Inegalites sociales et pronostic des accidents vasculaires cerebraux à Dijon et Antilles-Guyane") cohort study. Patients with ischemic stroke and available data on smoking, deprivation, and outcome were considered for the analysis (n = 1,242). Deprivation was assessed using the EPICES "Evaluation de la Précarité et des Inégalites de santé dans les Centres d'Examen de Santé" score. Primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) score at 12 months. Association between smoking and moderate to severe disability (mRS score ≥3) was evaluated with logistic regression model. Interactions between smoking and deprivation were tested. RESULTS: Smokers (n = 189, 15.2%) were younger and more often deprived (EPICES score ≥30.17) than nonsmokers. A significant interaction was found between smoking status and deprivation on disability (p = 0.003). In nondeprived patients, the odds of moderate to severe disability at 12 months were twice as high in smokers as in nonsmokers (adjusted OR = 2.08, 95% CI: 1.04-4.18). This association was not observed in deprived patients (adjusted OR = 0.89, 95% CI: 0.49-1.61). CONCLUSION: The effect of smoking on functional prognosis after ischemic stroke varied according to deprivation status, with poorer outcomes observed in nondeprived patients.

Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Impact of the first COVID-19 pandemic peak and lockdown on the interventional management of carotid artery stenosis in France.

OBJECTIVE: The aim of this study was to evaluate the impact of the COVID-19 pandemic on the trends of carotid revascularization (endarterectomy [CEA], transfemoral carotid artery stenting [TFCAS]) for symptomatic and asymptomatic carotid stenosis before, during, and after the end of the first lockdown in 2020 in France. METHODS: Nationwide data were provided by the French National Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). We retrospectively analyzed patients admitted for CEA or TFCAS in all French public and private hospitals during a 9-month period (January-September) in 2017, 2018, 2019, and 2020. Procedures were identified using the French Common Classification of Medical Procedures. Stenoses were considered symptomatic in the presence of stroke and/or transient ischemic attack codes (according to the International Classification of Diseases-Tenth Revision) during the stay, and asymptomatic in the absence of these codes. Hospitalization rates in 2020 were compared with the rates in the same period in the 3 previous years. RESULTS: Between January and September 2020, 12,546 patients were hospitalized for carotid artery surgery (CEA and TFCAS) in France. Compared with the 3 previous years, there was a decrease in hospitalization rates for asymptomatic (-68.9%) and symptomatic (-12.6%) CEA procedures in April, starting at the pandemic peak concomitant with the first national lockdown. This decrease was significant for asymptomatic CEA (P < .001). After the lockdown, while CEA for asymptomatic stenosis returned to usual activity, CEA for symptomatic stenosis presented a significant rebound, up 18.52% in August compared with previous years. Lockdown also had consequences on TFCAS procedures, with fewer interventions for both asymptomatic (-60.53%) and symptomatic stenosis (-16.67%) in April. CONCLUSIONS: This study demonstrates a severe decrease for all interventions during the first peak of the COVID-19 pandemic in France. However, the trends in the postlockdown period were different for the various procedures. These data can be used to anticipate future decisions and organization for cardiovascular care.

Cardiovascular Surgical Emergencies in France, before, during and after the First Lockdown for COVID-19 in 2020: A Comparative Nationwide Retrospective Cohort Study.

BACKGROUND: There are still gaps regarding the impact of the nationwide lockdown on non-COVID-19 emergency hospitalizations. This study aims to describe the trends in hospitalizations for cardiovascular surgical emergencies in France, before, during and after the first lockdown. MATERIALS AND METHODS: All adults admitted for mechanical complications of myocardial infarction (MI), aortic dissection, aortic aneurysm rupture, acute and critical limb ischemia, circulatory assistance, heart transplantation and major amputation were included. This retrospective cohort study used the French National Hospital Discharge database. The numbers of hospitalizations per month in 2020 were compared to the previous three years. RESULTS: From January to September 2020, 94,408 cases of the studied conditions were reported versus 103,126 in the same period in 2019 (-8.5%). There was a deep drop in most conditions during the lockdown, except for circulatory assistance, which increased. After the lockdown, mechanical complications of MI and aortic aneurysm rupture increased, and cardiac transplantations declined compared with previous years. CONCLUSION: We confirmed a deep drop in most cardiovascular surgical emergencies during the lockdown. The post-lockdown period was characterized by a small over-recovery for mechanical complications of MI and aortic aneurysm rupture, suggesting that many patients were able to access surgery after the lockdown.

Investigating the association between cancer and the risk of dementia: Results from the Memento cohort.

INTRODUCTION: Studies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding. METHODS: This study uses data from the Memento cohort, a French multicenter cohort following persons with either mild or isolated cognitive complaints for a median of 5 years. Illness-death models (IDMs) were used to estimate transition-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer in relation to dementia from time since study entry. RESULTS: The analytical sample (N = 2258) excluded 65 individuals without follow-up information. At the end of follow-up, 286 individuals were diagnosed with dementia, 166 with incident cancer, and 95 died. Incident cancer was associated with a reduced risk of dementia (HR = 0.58, 95% CI = 0.35-0.97), with a corresponding E-value of 2.84 (lower CI = 1.21). DISCUSSION: This study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms.

The epidemiology and management of stroke in French Guiana.

BACKGROUND: French Guiana has the highest incidence of ischemic and hemorrhagic stroke of all French territories. However, there is no further information on the epidemiology and management of stroke in French Guiana. Our goal was to describe the characteristics of patients in French Guiana in order to generate hypotheses regarding the determinants explaining the magnitude of this public health problem. METHODS: We used the data of the French multicentre INDIA prospective cohort study which included consecutive patients aged > 18 years with a first-ever stroke from June 2011 to October 2014. For the present study, only patients with ischemic or hemorrhagic stroke admitted in one of the 3 participating hospitals were analyzed. RESULTS: Among the 298 patients (mean age 62.2 ± 14.5 years, 63.7% man) included in French Guiana, 52% were born abroad. Most strokes were ischemic strokes (79%), 14% of which were thrombolyzed. Hypertension (70.2%), history of smoking (22%) and diabetes (25%) were the most common risk factors and 28.4% of patients had known but untreated hypertension. Overall 89 (38%) patients with ischemic stroke were admitted less than 4.5 h after the first symptoms. In-hospital mortality was greater for intracerebral hemorrhage (18.7%) than for ischemic stroke (4.2%). Overall, 84.5% had health insurance coverage and among these, 41.9% had CMU, the universal health insurance for the poor. CONCLUSIONS: The present study is the first epidemiologic description of stroke in French Guiana. The comparisons of these results show that stroke patients in French Guiana are epidemiologically atypical because they are younger, and more likely to be males than patients in mainland France. Stroke risk factors and delay between stroke and hospital admission were comparable with what is observed in France, suggesting that efforts should focus on primary care and social inequalities of health to alleviate the main determinants of stroke in French Guiana.

Assessment of Somatosensory Reorganization by Functional Magnetic Resonance Imaging After Hand Replantation.

INTRODUCTION: Amputation of the hand is a rare and extremely intense trauma. Replanting and allografting after this type of injury require a major reorganization of the brain. Brain plasticity, though better known in the context of disorders of the central nervous system, is just as indispensable when the extremities are damaged. MATERIALS AND METHODS: A 17-year-old patient underwent replantation of the nondominant hand after transmetaphyseal amputation after traumatic injury. After 18 days in hospital and subsequent treatment in a physical rehabilitation center, the patient attended clinical and radiology follow-up sessions over the next 2 years. RESULTS: The management of this patient led to an excellent functional outcome in conjunction with successful social and professional reintegration. Electromyography at 18 months confirmed nerve regrowth. Functional magnetic resonance imaging was done at 2 years to evaluate cerebral plasticity. Motor function, largely dependent on the primary motor area, is aided by the addition of secondary and accessory motor areas for both simple and complex movements. A change in sensory information is stimulation in its own right hemisphere and increases solicitation of the contralateral precentral and postcentral gyrus. CONCLUSIONS: There seems to be a real reversible dynamic plasticity under the balance of inhibitory and excitatory influences exerted on the cortical neurons. Any disruption of this balance requires the brain to adapt to the new circumstances to reestablish the hand as a functioning part of the body.

Ischemic Stroke Increases Heart Vulnerability to Ischemia-Reperfusion and Alters Myocardial Cardioprotective Pathways.

Background and Purpose- For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo and how they influence cardiac vulnerability to ischemia-reperfusion injury. Methods- Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery. Stroke lesions were evaluated by microsphere counting, tissue staining, and assessment of neurological deficit 2 hours, 24 hours, and 7 days after surgery. Cardiac function was evaluated in vivo by echocardiography and ex vivo in isolated perfused hearts. Heart vulnerability to ischemia-reperfusion injury was investigated ex vivo at different times post-embolization and with varying degrees of myocardial ischemia. Left ventricles (LVs) were analyzed with Western blotting and quantitatve real-time polymerase chain reaction. Results- Our stroke model produced large cerebral infarcts with severe neurological deficit. Cardiac contractile dysfunction was observed with an early but persistent reduction of LV fractional shortening in vivo and of LV developed pressure ex vivo. Moreover, after 20 or 30 minutes of global cardiac ischemia, recovery of contractile function was poorer with impaired LV developed pressure and relaxation during reperfusion in both stroke groups. Following stroke, circulating levels of catecholamines and GDF15 (growth differentiation factor 15) increased. Cerebral embolization altered nitro-oxidative stress signaling and impaired the myocardial expression of ADRB1 (adrenoceptor ß1) and cardioprotective Survivor Activating Factor Enhancement signaling pathways. Conclusions- Our findings indicate that stroke not only impairs cardiac contractility but also worsens myocardial vulnerability to ischemia. The underlying molecular mechanisms of stroke-induced myocardial alterations after cerebral embolization remain to be established, insofar as they may involve the sympathetic nervous system and nitro-oxidative stress.

Determinants and outcome of multiple and early recurrent cervical artery dissections.

OBJECTIVE: To assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD). METHODS: We combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed. RESULTS: Of 1,958 patients with CeAD (mean ± SD age 44.3 ± 10 years, 43.9% women), 1,588 (81.1%) had single nonrecurrent CeAD, 340 (17.4%) had multiple CeAD, and 30 (1.5%) presented with single CeAD at admission and had early recurrent CeAD. Patients with multiple or early recurrent CeAD did not significantly differ with respect to putative risk factors, clinical presentation, and outcome. In multivariable analyses, patients with multiple or early recurrent CeAD more often had recent infection (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.29-2.53), vertebral artery dissection (OR 1.82, 95% CI 1.34-2.46), family history of stroke (OR 1.55, 95% CI 1.06-2.25), cervical pain (OR 1.36, 95% CI 1.01-1.84), and subarachnoid hemorrhage (OR 2.85, 95% CI 1.01-8.04) at initial presentation compared to patients with single nonrecurrent CeAD. Patients with multiple or early recurrent CeAD also had a higher incidence of cerebral ischemia (hazard ratio 2.77, 95% CI 1.49-5.14) at 3 to 6 months but no difference in functional outcome compared to patients with single nonrecurrent CeAD. CONCLUSION: Patients with multiple and early recurrent CeAD share similar risk factors, clinical characteristics, and functional outcome. Compared to patients with single nonrecurrent CeAD, they are more likely to have recurrent cerebral ischemia at 3 to 6 months, possibly reflecting an underlying transient vasculopathy.

Cerebral Infarct Topography and Early Outcome after Surgery for Symptomatic Carotid Stenosis: A Multicentre Study.

INTRODUCTION: Although carotid stenosis can cause both territorial and border-zone (BZ) cerebral infarcts (CI), the influence of CI topography on postoperative complications after surgery remains unclear. We compared early outcomes after endarterectomy on the basis of CI location: territorial (T group) or BZ group. MATERIAL AND METHODS: During the period between 2009 and 2013, ischaemic stroke patients who had undergone surgery for symptomatic carotid stenosis were identified from prospective databases from 3 French centres. The outcome was the identification of a combined stroke/death rate 30 days after endarterectomy. RESULTS: Two hundred and eighty-nine patients were included, 216 (74.7%) in the T group and 73 (25.3%) in the BZ group. The mean degree of stenosis was comparable in the 2 groups (78 ± 12% in the T group vs. 80 ± 12% in the BZ group, p = 0.105), with, however, more sub-occlusions (stenosis >90%) in the BZ group (38.4 vs. 23.1%, p = 0.012). The mean time between the time CI developed and the time surgery was performed was 19.6 ± 24.8 days, with a majority of patients being operated upon within 2 weeks following the formation of CI (66.7% in the T group vs. 60.3% in the BZ group, p = 0.322). The combined endpoint was significantly more frequent in the BZ group (9.6 vs. 1.9%, p = 0.003), with 4 ischaemic strokes and 3 deaths. In multivariate analysis, BZ CI was an independent predictor of postoperative stroke or death at 30 days (HR 4.91-95% CI [1.3-18.9], p = 0.020). CONCLUSION: BZ infarcts carry a greater risk of postoperative complications after carotid surgery, thus suggesting that topography of the CI should be considered in the decision-making process regarding surgery.

Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the role of radiation dose received to the circle of Willis (WC) during radiation therapy (RT) and of potential dose-response modifiers on the risk of stroke after treatment of childhood cancer. METHODS: We evaluated the risk factors for stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median time of 26 years. Radiation doses to the WC and brain structures were estimated for each of the 2202 children who received RT. RESULTS: Fifty-four patients experienced a confirmed stroke; 39 were ischemic. Patients not receiving RT had a stroke risk similar to that of the general population, whereas those who received RT had an 8.5-fold increased risk (95% confidence interval [CI]: 6.3-11.0). The excess of incidence of stroke increased yearly. The dose of radiation to the WC, rather than to other brain structures, was found to be the best predictor of stroke. The relative risk was 15.7 (95% CI: 4.9-50.2) for doses of 40 Gy or more. At 45 years of age, the cumulative stroke incidence was 11.3% (95% CI: 7.1%-17.7%) in patients who received 10 Gy or more to the WC, compared with 1% expected from general population data. Radiation doses received to the heart and neck also increased the risk. Surgery for childhood brain cancer was linked to hemorrhagic strokes in these patients. CONCLUSION: The WC should be considered as a major organ at risk during RT for childhood brain cancers. The incidence of radiation-induced ischemic stroke strongly increases with long-term follow-up.

Influence of the type of cerebral infarct and timing of intervention in the early outcomes after carotid endarterectomy for symptomatic stenosis.

OBJECTIVE: Our objectives were to compare early postoperative outcomes after carotid endarterectomy for symptomatic carotid stenosis and to analyze the impact of time to treatment between patients with a territorial or a border-zone infarct. METHODS: This is a single-center, retrospective study carried out on data from a single-center, prospective database. Patients undergoing carotid endarterectomy for symptomatic carotid stenosis after an ipsilateral acute ischemic stroke were included between January 1, 2009 and December 31, 2013. The only exclusion criterion was a mixed-topography stroke. We included 114 patients who were retrospectively divided into groups according to the location of the infarct: group TI for territorial infarction and group BZ for border-zone infarction. The primary end point was the 30-day death or stroke rate. RESULTS: Ninety patients were included in the TI group (79%) and 24 in the BZ group (21%) with a mean age of 73 ± 11 years. All demographic data were similar between the two groups except for dyslipidemia, which was greater in the BZ group (72% vs 47%, P = .03) and the subocclusive feature of carotid stenosis (14% in the TI group vs 33% in the BZ group, P .04). There was one death and one stroke in each group, with a 30-day death and stroke rate of 2% in the TI group and 8% in the BZ group (P = .18). Multivariate analysis showed that the National Institute of Health Stroke Score (NIHSS) score was the only independent predictive factor of complications with an increase of 36% per additional point in this score. Sixty-eight patients (76%) in the TI group and 14 (58%) in the BZ group were operated on during the first 2 weeks after the neurological event. In this subgroup, the 30-day death or stroke rate was 2% in the TI group (one stroke) vs 14% in the BZ group (one stroke and one death; P = .06). The preoperative NIHSS score was again the only factor significantly associated with the postoperative complication rate (P = .03). CONCLUSIONS: In our series, surgery for patients with symptomatic carotid stenosis after border-zone infarction resulted in more complications than after territorial infarction, although no significant differences were found. This study nonetheless raised questions concerning the optimal timing of carotid surgery depending on the type of the original stroke. Other larger-scale studies are necessary to determine whether the type of cerebral infarction needs to be taken into account in decisions whether to operate on the diseased carotid as early as possible.

The use of national administrative data to describe the spatial distribution of in-hospital mortality following stroke in France, 2008-2011.

BACKGROUND: In the context of implementing the National Stroke Plan in France, a spatial approach was used to measure inequalities in this disease. Using the national PMSI-MCO databases, we analyzed the in-hospital prevalence of stroke and established a map of in-hospital mortality rates with regard to the socio-demographic structure of the country. METHODS: The principal characteristics of patients identified according to ICD10 codes relative to stroke (in accordance with earlier validation work) were studied. A map of standardized mortality rates at the level of PMSI geographic codes was established. An exploratory analysis (principal component analysis followed by ascending hierarchical classification) using INSEE socio-economic data and mortality rates was also carried out to identify different area profiles. RESULTS: Between 2008 and 2011, the number of stroke patients increased by 3.85%, notably for ischemic stroke in the 36-55 years age group (60% of men). Over the same period, in-hospital mortality fell, and the map of standardized rates illustrated the diagonal of high mortality extending from the north-east to the south-west of the country. The most severely affected areas were also those with the least favorable socio-professional indicators. CONCLUSIONS: The PMSI-MCO database is a major source of data on the health status of the population. It can be used for the area-by-area observation of the performance of certain healthcare indicators, such as in-hospital mortality, or to follow the implementation of the National Stroke Plan. Our study showed the interplay between social and demographic factors and stroke-related in-hospital mortality. The map derived from the results of the exploratory analysis illustrated a variety of areas where social difficulties, aging and high mortality seemed to meet. The study raises questions about access to neuro-vascular care in isolated areas and in those in demographic decline. Telemedicine appears to be the solution favored by decision makers. The aging of the population managed for stroke must not mask the growing incidence in younger people, which raises questions about the development of classical (smoking, hypertension) or new (drug abuse) risk factors.

Delay between symptoms and surgery for carotid artery stenosis: modification of our practice.

BACKGROUND: Recent data from the literature concerning symptomatic carotid stenosis show that the long-term benefits of surgery are greater when the surgery is performed soon after the neurologic event, ideally within 2 weeks. Since 2009, following recommendations, we decided to perform surgery as quick as possible. The aim of the study was to determine whether this approach increased postoperative morbimortality and the way it could change our practice. METHODS: Using a prospective database containing a consecutive and continuous series of 1,500 carotid endarterectomies performed between 2003 and 2012, we extracted the records concerning the 417 symptomatic carotid stenoses (27.8%). We compared the 30-day and long-term outcome in 3 groups of patients: those operated within 2 weeks of the neurologic event (early surgery group [ESG], n = 158, 37.9%), those operated between 16 days and 6 weeks after the event (deferred surgery group [DSG], n = 79, 18.9%), and those operated more than 6 weeks after the event (late surgery group [LSG], n = 180, 43.2%). In the second part, to assess the new management beginning 2009, patients were divided in 2 periods 2003-2008 (period A) and 2009-2012 (period B) and we compared the 2 period's descriptive data and outcome. The primary outcome was the 30-day combined stroke and death rate. Secondary end points were follow-up freedoms from mortality and stroke. RESULTS: The mean time between symptom onset and surgery was 7.7 ± 3.8 days for the ESG, 28.3 ± 8.6 days for the DSG, and 89.4 ± 36.7 days for the LSG. In the 3 groups, the types of symptoms leading to the indication for carotid surgery were comparable, with a stroke in 221 cases (53.0%), a transient ischemic attack in 146 cases (35.40%), and amaurosis fugax in 50 cases (12.0%). The groups were comparable in terms of comorbidities. The overall 30-day stroke rate was 1.4% (6 cases), the 30-day death rate was 1.7% (7 cases), and the combined stroke and death rate was 3.4% (3.2% in the ESG, 5.1% in the DSG, and 2.8% in the LSG [P = 0.808]). Survival rates at 24, 48, and 60 months were, respectively, 95%, 78%, and 78% in ESG, 86%, 81%, and 81% in DSG, and 91%, 83%, and 74% in LSG (P = 0.78). Freedom from stroke at 60 months showed to be, respectively, 97% in ESG, 96% in DSG, and 91% in LSG (P = 0.32). During the period A (2003-2008), we had taken care of 217 symptomatic carotid artery stenosis patients (22.3% of stenosis) and during the period B (2009-2012), 200 symptomatic stenosis (37.9% of stenosis). During the period A, an early surgery (<15 days) had place in 31 cases (14.3%), and during the period B, in 127 cases (63.5%). The 30-day stroke and death rate was of 3.7% during the period A and of 3.0% during the period B (P = 0.455). The 24-month survival and stroke-free survival rates were comparable between the 2 periods. CONCLUSIONS: In our experience, surgery for symptomatic carotid stenosis can be performed early without increasing the rate of postoperative and long-term outcome. We have modified our practice, performing more and more early surgery for symptomatic stenosis without any impact on the outcome.

Stroke associated with giant cell arteritis: a population-based study.

BACKGROUND: Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. METHODS: All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptoms and 4 weeks after the start of treatment. RESULTS: Among the 57 biopsy-proven patients with GCA (incidence rate 10.9/100 000/year in individuals ≥50 years), 4 (7.0%) experienced a GCA-related stroke. Three were men and all had ≥2 vascular risk factors and were ≥80 years. The stroke was vertebrobasilar for 3/4 patients and undetermined for the remaining one. The incidence rate of GCA-related stroke in patients ≥50 years was 0.76/100 000/year (95% CI 0 to 2.47), 1.36/100 000/year in men (95% CI 0 to 3.63) and 0.33/100 000/year (95% CI 0 to 1.45) in women. CONCLUSIONS: This population-based study demonstrated that GCA-related stroke essentially affects the vertebrobasilar territory and mainly occurs in old men with associated vascular risk factors. Although rare, GCA symptoms must be searched for in elderly patients with stroke, and optimal vascular prevention must be conducted carefully in patients with GCA with a high vascular risk before initiating GCA treatment.