Climate Change and Stroke: A Topical Narrative Review.

The impacts of accumulating atmospheric greenhouse gases on the earth's climate are now well established. As a result, there have been increases in ambient temperatures and resultant higher frequency and duration of temperature extremes and other extreme weather events, which have been linked to a wide range of adverse health outcomes. This topical narrative review provides a summary of published evidence on the links between climate change and stroke. There is consistent evidence of associations between stroke incidence and mortality and increasing ambient temperature and air pollution. Associations have also been shown for changes in barometric pressure, wildfires, and desert dust and sandstorms, but current evidence is limited. Flooding and other extreme weather events appear to primarily cause service disruption, but more direct links to stroke may emerge. Synergies between dietary changes that reduce stroke risk and may also reduce carbon footprint are being explored. We also discuss the impact on vulnerable populations, proposed pathophysiologic mechanisms, mitigation strategies, and current research priorities. In conclusion, climate change increasingly impacts the stroke community, warranting elevated attention.

More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL <70 mg/dL After a Stroke.

BACKGROUND: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated. METHODS: The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P<0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; P=0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; P=0.75). CONCLUSIONS: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Time to onset of cardiovascular and cerebrovascular outcomes after hypertensive disorders of pregnancy: a nationwide, population-based retrospective cohort study.

BACKGROUND: The increased maternal cardiocerebrovascular risk after a pregnancy complicated by hypertensive disorders of pregnancy, is well documented in the literature. Recent evidence has suggested a shorter timeframe for the development of these postnatal outcomes, which could have major clinical implications. OBJECTIVE: This study aimed to determine the risk of and time to onset of maternal cardiovascular and cerebrovascular outcomes after a pregnancy complicated by hypertensive disorders of pregnancy. STUDY DESIGN: This study included 2,227,711 women, without preexisting chronic hypertension, who delivered during the period 2008 to 2010: 37,043 (1.66%) were diagnosed with preeclampsia, 34,220 (1.54%) were diagnosed with gestational hypertension, and 2,156,448 had normotensive pregnancies. Hospitalizations for chronic hypertension, heart failure, coronary heart disease, cerebrovascular disease, and peripheral arterial disease were studied. A classical Cox regression was performed to estimate the average effect of hypertensive disorders of pregnancy over 10 years compared with normotensive pregnancy; moreover, an extended Cox regression was performed with a step function model to estimate the effect of the exposure variable in different time intervals: <1, 1 to 3, 3 to 5, and 5 to 10 years of follow-up. RESULTS: The risk of chronic hypertension after a pregnancy complicated by preeclampsia was 18 times higher in the first year (adjusted hazard ratio, 18.531; 95% confidence interval, 16.520-20.787) to only 5 times higher at 5 to 10 years after birth (adjusted hazard ratio, 4.921; 95% confidence interval, 4.640-5.218). The corresponding risks of women with gestational hypertension were 12 times higher (adjusted hazard ratio, 11.727; 95% confidence interval, 10.257-13.409]) and 6 times higher (adjusted hazard ratio, 5.854; 95% confidence interval, 5.550-6.176), respectively. For other cardiovascular and cerebrovascular outcomes, there was also a significant effect with preeclampsia (heart failure: adjusted hazard ratio, 6.662 [95% confidence interval, 4.547-9.762]; coronary heart disease: adjusted hazard ratio, 3.083 [95% confidence interval, 1.626-5.844]; cerebrovascular disease: adjusted hazard ratio, 3.567 [95% confidence interval, 2.600-4.893]; peripheral arterial disease: adjusted hazard ratio, 4.802 [95% confidence interval, 2.072-11.132]) compared with gestational hypertension in the first year of follow-up. A dose-response effect was evident for the severity of preeclampsia with the averaged 10-year adjusted hazard ratios for developing chronic hypertension after early, preterm, and late preeclampsia being 10, 7, and 6 times higher, respectively. CONCLUSION: The risks of cardiovascular and cerebrovascular outcomes were the highest in the first year after a birth complicated by hypertensive disorders of pregnancy. We found a significant relationship with both the severity of hypertensive disorders of pregnancy and the gestational age of onset suggesting a possible dose-response relationship for the development of cardiovascular and cerebrovascular outcomes. These findings call for an urgent focus on research into effective postnatal screening and cardiocerebrovascular risk prevention for women with hypertensive disorders of pregnancy.

Asymmetric crying facies in an elderly, when a facial asymmetry is not a facial paralysis but a marker of possible congenital malformations: case report and review of the literature.

BACKGROUND: Facial asymmetry when crying at birth (then called asymmetric crying facies or ACF) or when smiling or speaking loudly in adulthood is the consequence of the agenesis or hypoplasia of the muscle of one of the labial commissures. This developmental disorder of complex mechanism is well known by pediatricians to be a warning sign for underlying developmental disorders of variable severity. CASE REPORT: An 80-year-old man with medical history of renal agenesis was hospitalized for a transient motor deficit of the right face and arm revealing a lacunar stroke. Clinical examination showed an isolated left facial asymmetry upon smiling or talking out loud which had been known since childhood and was not related to the stroke, leading to the diagnosis of ACF. Cardiac ultrasound revealed a patent foramen. Chromosomal investigations could not be performed. DISCUSSION AND CONCLUSION: ACF is a rare disorder that may conceal associated congenital disorders such as heart, skeletal, or renal malformations. Its causing mechanisms are to this day still poorly understood but may include a genetic component as shown by familial cases and the identification of 22q11.2 deletions or trisomy 18 in some patients. Knowledge of this disorder seems highly relevant for adult neurologists, first because of the differential diagnosis with facial palsy, but mostly because it will allow them to screen patients for other congenital disorders such as heart malformations. Conversely, cardiologists and cardiac surgeon may search for an ACF when faced with a patient with a congruent heart defect.

High efficiency and clinical relevance of exome sequencing in the daily practice of neurogenetics.

OBJECTIVE: To assess the efficiency and relevance of clinical exome sequencing (cES) as a first-tier or second-tier test for the diagnosis of progressive neurological disorders in the daily practice of Neurology and Genetic Departments. METHODS: Sixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labelled 'other') were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analysed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection. RESULTS: In 29/67 individuals, cES identified clearly pathogenic variants leading to a 43% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin. CONCLUSION: This study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients.

BACKGROUND: We evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS). METHODS: IS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity. RESULTS: Among the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages. CONCLUSION: Impaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.

Intracranial Hemorrhage in the TST Trial.

BACKGROUND AND PURPOSE: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. METHODS: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. RESULTS: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38-4.04] and 2.32/1000 patient-years [95% CI, 1.61-3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01-6.31], P=0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00-5.62], P=0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. CONCLUSIONS: Targeting an LDL cholesterol of <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

Yield of Dual Therapy With Statin and Ezetimibe in the Treat Stroke to Target Trial.

BACKGROUND: In atherosclerotic stroke, lipid-lowering treatment with a target LDL (low-density lipoprotein) cholesterol of <70 compared with 100±10 mg/dL reduced the risk of subsequent cardiovascular events. This post hoc analysis explored the relative effects of the combination of statin and ezetimibe (dual therapy) and statin monotherapy in achieving the lower LDL cholesterol target and in reducing the risk of major vascular events, as compared with the higher target group. METHODS: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 or 100±10 mg/dL, using statin and/or ezetimibe as needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients who were on dual therapy during the trial in the lower target group had a higher baseline LDL cholesterol as compared to patients on statin monotherapy (141±38 versus 131±36, respectively, P<0.001). In patients on dual therapy and on statin monotherapy, the achieved LDL cholesterol was 66.2 and 64.1 mg/dL respectively, and the primary outcome was reduced during dual therapy as compared with the higher target group (HR, 0.60 [95% CI, 0.39-0.91]; P=0.016) but not during statin monotherapy (HR, 0.92 [95% CI, 0.70-1.20]; P=0.52), with no significant increase in intracranial bleeding. CONCLUSIONS: In the TST trial (Treat Stroke to Target), targeting an LDL cholesterol of < 70 mg/dL with a combination of statin and ezetimibe compared with 100±10 mg/dL consistently reduced the risk of subsequent stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01252875. URL: clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

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.

Carotid Atherosclerosis Evolution When Targeting a Low-Density Lipoprotein Cholesterol Concentration <70 mg/dL After an Ischemic Stroke of Atherosclerotic Origin.

BACKGROUND: The TST trial (Treat Stroke to Target) showed the benefit of targeting a low-density lipoprotein cholesterol (LDL-C) concentration of <70 mg/dL in terms of reducing the risk of major cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature. The impact on carotid atherosclerosis evolution is not known. METHODS: TST-PLUS (Treat Stroke to Target-Plaque Ultrasound Study) included 201 patients assigned to an LDL-C concentration of <70 mg/dL and 212 patients assigned to a target of 100±10 mg/dL. To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe as needed. Ultrasonographers were certified and carotid ultrasound examinations were performed using M'Ath software at baseline and at 2, 3, and 5 years. All images were uploaded to the Intelligence in Medical Technologies database directly from the carotid ultrasound device. The central core laboratory performed all offline measurements of the intima-media thickness of both common carotid arteries blinded from the randomization arm. The main outcomes were newly diagnosed atherosclerotic plaque on carotid bifurcation or internal carotid artery using the Mannheim consensus definition and between-group comparison of common carotid arteries intima-media thickness change. RESULTS: After a median follow-up of 3.1 years, the achieved LDL-C concentrations were 64 mg/dL (1.64 mmol/L) in the lower-target group and 106 mg/dL (2.72 mmol/L) in the higher-target group. Compared with the higher-target group, patients in the lower-target group had a similar incidence of newly diagnosed carotid plaque: 46/201 (5-year rate, 26.1%) versus 45/212 (5-year rate, 29.7%). The change in common carotid arteries intima-media thickness was -2.69 µm (95% CI, -6.55 to 1.18) in the higher-target group and -10.53 µm (95% CI, -14.21 to -6.85) in the lower-target group, resulting in an absolute between-group difference of -7.84 µm (95% CI, -13.18 to -2.51; P=0.004). CONCLUSIONS: In patients with ischemic stroke and atherosclerosis, an LDL-C target of <70 mg/dL (1.8 mmol/L) did not reduce the incidence of new carotid plaques but produced significantly greater regression of carotid atherosclerosis than an LDL-C target of 90 to 110 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.

Hospitalizations for Stroke in France During the COVID-19 Pandemic Before, During, and After the National Lockdown.

BACKGROUND AND PURPOSE: In France, the entire population was put under a total lockdown from March 17 to May 11, 2020 during the peak of the coronavirus disease 2019 (COVID-19) pandemic. Whether the lockdown had consequences on the management of medical emergencies such as stroke and transient ischemic attack (TIA) has yet to be fully evaluated. This article describes hospitalization rates for acute stroke in 2 French regions that experienced contrasting rates of COVID-19 infection, before, during, and after the nationwide lockdown (January to June 2020). METHODS: All patients admitted for acute stroke/TIA into all public and private hospitals of the 2 study regions were included. Data were retrieved from the National Hospitalization Database (PMSI). In the most affected region (Grand-Est), the hospitalization rates observed in April 2020 were compared with the rates in the same period in the least affected region (Occitanie) and in the 3 prior years (2017-2019). RESULTS: There was a significant decline in hospitalization rates for stroke/TIA within the region most affected by COVID-19 during the month of April 2020 compared with previous years, while no significant change was seen in the least affected region. After lockdown, we observed a fast rebound in the rate of hospitalization for stroke/TIA in the most affected region, contrasting with a slower rebound in the least affected region. In both regions, patients with COVID-19 stroke more frequently had ischemic stroke, a nonsignificant greater prevalence of diabetes, they were less frequently admitted to stroke units, and mortality was higher than in patients without COVID-19. CONCLUSIONS: Our results demonstrates a significant drop in stroke/TIA hospitalizations and a fast recovery after the end of the French lockdown in the most affected region, while the least affected region saw a nonsignificant drop in stroke/TIA hospitalizations and a slow recovery. These results and recommendations could be used by the health authorities to prepare for future challenges.

Temporal Trends in the Incidence of Ischemic Stroke in Young Adults: Dijon Stroke Registry.

INTRODUCTION: Stroke is associated with major consequences in terms of socioeconomic impact and lost disability-adjusted life in young victims, thus justifying a careful surveillance of epidemiological trends. This study aimed to assess changes in the incidence of ischemic stroke in young adults over a long period. METHODS: All cases of first-ever ischemic stroke that occurred among adults aged 18-55 years were prospectively recorded using the population-based Dijon Stroke Registry, from 1985 to 2017. Sex-specific annual incidence rates were calculated and were presented according to 6 time periods. Incidence rate ratios (IRRs) were determined to assess sex differences in stroke incidence. RESULTS: Over the whole study period, 4,451 patients suffered a first-ever ischemic stroke. Among these patients, 469 (10.5%) were young adults (median age: 46 years, IQR: 39-50; 53.9% men). Incidence rates rose from the study period 2003 to 2007 compared with previous periods and remained stable thereafter, both in men and women. Hence, incidence per 100,000 per year was globally 11.0 (95% CI: 9.4-12.7) before 2003 and 22.9 (20.3-25.6) thereafter. In individuals aged 18-45 years, incidence rates were 5.4 (4.3-6.9) overall, 4.1 (2.7-6.0) in men, and 6.7 (4.9-9.0) in women, before 2003. After 2003, incidence rates rose to 12.8 (10.7-15.1) overall, 12.0 (9.2-15.4) in men, and 13.6 (10.6-17.0) in women. In this age group, the men/women IRR was 0.78 (95% CI: 0.62-1.26, p = 0.08), although sex differences decreased over time (IRR = 0.62; 95% CI: 0.36-1.02, p = 0.046 before 2003, vs. IRR = 0.88; 95% CI: 0.62-1.26, p = 0.48 after 2003). In individuals aged 45-55 years, incidence rates before 2003 were 47 (37-61) in men and 25 (17-35) in women (IRR = 1.90; 95% CI: 1.24-2.97, p < 0.001), and they increased to 82 (67-100) in men and 46 (35-59) in women (IRR = 1.79; 95% CI: 1.29-2.49, p < 0.001) after 2003. CONCLUSIONS: The incidence of ischemic stroke in young adults increased during the early 2000s and remained stable thereafter. These results highlight the priority need for dedicated prevention strategies for the young to reduce the burden of stroke.

Current characteristics and early functional outcome of older stroke patients: a population-based study (Dijon Stroke Registry).

BACKGROUND: the ongoing growing and ageing population is associated with an increase in older patients suffering a stroke. We aimed to assess the current profile of these patients in a population-based setting. METHODS: all patients with acute stroke were prospectively identified among residents of Dijon, France, between 2013 and 2017, using a population-based registry. Characteristics and early outcome of patients were compared according to age groups. RESULTS: 1,288 stroke cases were recorded (median age: 81.1 years, interquartile range: 66.1-86.7, 54% women). Patients aged 75-85 years and those >85 years accounted for 27.6 and 33.9% of overall cases. Increasing age was associated with a greater prevalence of vascular risk factors, pre-existing cognitive impairment and handicap, higher initial severity, more frequent cardioembolic ischemic stroke, post-stroke pulmonary infection and delirium. Only 41% of patients aged 75-85 years and 18% of those aged >85 years had a good early recovery. Compared with patients aged <75 years, patients aged 75-85 years [adjusted odds ratio (OR) = 2.61; 95% confidence interval (CI): 1.74-3.93, P < 0.001] and those aged >85 years (adjusted OR = 7.18; 95% CI: 4.58-11.3, P < 0.001) had an increased risk of poor post-stroke functional outcome. Among survivors, the proportion of patients discharged to home was 60% in age group <75 years, compared with 49% in patients aged 75-85 years and 29% in those aged >85 years. Thirty per cent of patients >85 years old required a long-term care institution. CONCLUSION: the increasing burden of stroke in older people has major implications for future treatment strategies and need for dedicated care facilities.

Self-management of immunomodulatory drug treatment in multiple myeloma patients.

OBJECTIVE: Immunomodulatory drugs (IMIDs: thalidomide, lenalidomide and pomalidomide) are widely used in patients with multiple myeloma (MM). The aim of our study was to validate a questionnaire to evaluate the self-capacity of MM patients to manage IMID treatment including side effects. METHODS: We used a method adapted from the recommendations of the European Organisation for Research and Treatment of Cancer (EORTC) to validate a French questionnaire for patients with MM treated with IMIDs. RESULTS: The face validity was evaluated in 15 patients and the construct validity in 56 patients. For discriminant validity, two groups were constituted by gender and depending on whether they had a previous IMID treatment. The median questionnaire score was 11.33/16 (IQR 9.75-12.08) with a minimum of 5.2 and a maximum of 14.75. For discriminant validity, a statistically significant difference was observed for patient capacity to contact healthcare professionals in specific situations and drug intake in case of swallowing disorder. Convergent validity showed an acceptable reliability for the scores of the different questions. CONCLUSION: The questionnaire has shown to be a valid tool for the assessment of the adherence and side-effect management skills for MM patients with IMID treatment.

Influence of Preexisting Cognitive Impairment on Clinical Severity of Ischemic Stroke: The Dijon Stroke Registry.

Background and Purpose- The ongoing ageing population is associated with an increasing number of patients with stroke who have preexisting cognitive impairment. This study aimed to evaluate clinical severity in patients with ischemic stroke according to prestroke cognitive status. Methods- Patients with ischemic stroke were prospectively identified among residents of Dijon, France using a population-based registry (2013-2017). Prestroke cognitive status (no impairment, mild cognitive impairment [MCI], or dementia) was recorded, and severity at stroke onset was measured using the National Institutes of Health Stroke Scale (NIHSS) score. Association between prestroke cognitive status and severity was evaluated using ordinal regression analysis models in which the NIHSS score was considered as a categorical variable. Results- Among the 1048 patients (mean age, 76.3±15.2 years; 54.0% women), a greater severity was observed in those with MCI (n=132; median NIHSS: 6; interquartile range, 2-15), and those with dementia (n=164; median NIHSS: 7; interquartile range, 3-16), than in patients without cognitive impairment (n=752; median NIHSS: 3; interquartile range, 1-9). MCI (odds ratio [OR], 1.70 [95% CI, 1.21-2.38]; P=0.002) and dementia (OR, 2.24 [95% CI, 1.65-3.04]; P<0.001) were both associated with a greater severity at onset. The association was still observed after adjustment for clinical variables and proximal arterial occlusion (OR, 1.52 [95% CI, 1.02-2.28]; P=0.04 for MCI; OR, 2.16 [95% CI, 1.45-3.22]; P<0.001 dementia). Further adjustment for prestroke handicap slightly reduced the magnitude of the association (OR, 1.49 [95% CI, 0.98-2.25]; P=0.06 for MCI, and OR, 1.98 [95% CI, 1.26-3.12]; P=0.02 for dementia). The greater severity in patients with prestroke cognitive impairment was not specifically driven by a more severe impairment of either motor or language function. Conclusions- Patients with preexisting cognitive impairment suffered more severe ischemic stroke. This result could reflect a lower brain tolerance of acute ischemia. Further studies are needed to explore the underlying mechanisms that could be targeted from therapeutic perspectives focusing on neuroprotection.

Incidence of Acute Ischemic Stroke With Visible Arterial Occlusion: A Population-Based Study (Dijon Stroke Registry).

BACKGROUND AND PURPOSE: Because of several methodological limitations, previous studies focusing on the prevalence of large vessel occlusion in ischemic stroke (IS) patients provided conflicting results. We evaluated the incidence of IS with a visible arterial occlusion using a comprehensive population-based registry. METHODS: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Annual incidence rates of IS (first-ever and recurrent events) and IS with a visible occlusion were calculated. RESULTS: One thousand sixty cases of IS were recorded (mean age: 76.0±15.8 years, 53.9% women). Information about arterial imaging was available in 971 (91.6%) of them, and only preexisting dementia was independently associated with having missing information (odds ratio=0.34 [95% CI, 0.18-0.65], P=0.001). Among these patients, 284 (29.2%) had a visible arterial occlusion. Occlusion site was the anterior circulation in 226 patients (23.3% of overall patients with available data) and the posterior circulation in 58 patients (6.0%). A proximal occlusion of the anterior circulation was observed in 167 patients (17.2%). The crude annual incidence rate of total IS per 100 000 was 138 (95% CI, 129-146). Corresponding standardized rates were 66 (95% CI, 50-82) to the World Health Organization and 141 (95% CI, 118-164) to the 2013 European populations. The crude annual incidence rate of IS with a visible arterial occlusion per 100 000 was 37 (95% CI, 33-41) and that of IS with a proximal occlusion of the anterior circulation was 22 (95% CI, 18-25). Corresponding standardized rates were 18 (95% CI, 10-26) and 10 (95% CI, 8-13) to the World Health Organization population, and 38 (95% CI, 26-50) and 23 (95% CI, 19-26) to the 2013 European population, respectively. CONCLUSIONS: These results will be helpful to plan the need for thrombectomy-capable stroke center resources.

Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke.

Background and Purpose- The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of <70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque >4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods- One thousand seventy-three French patients were assigned to <70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90-110 mg/dL, 2.3-2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results- After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57-0.94]; P=0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% (P=0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% (P=0.023). The primary outcome or intracranial hemorrhage was reduced by 25% (P=0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53-2.62]; P=0.70). Conclusions- After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of <70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.

Long-Term Relative Survival after Stroke: The Dijon Stroke Registry.

OBJECTIVE: The aim of this study was to assess long-term survival after stroke and to compare survival profiles of patients according to stroke subtypes, age, and sex, using relative survival (RS) method. METHODS: All patients with a first-ever stroke were prospectively recorded in the population-based Dijon Stroke Registry from 1987 to 2016. RS is the survival that would be observed if stroke was the only cause of death. Ten-year RS was estimated using a flexible parametric model of the cumulative excess mortality rate, which was obtained by matching the observed all-cause mortality in the stroke cohort to the expected mortality in the general population. A separate model was fitted for each stroke subtypes, first fitted for each age and sex separately, and then adjusted for age and sex. RESULTS: In total, 5,259 patients (mean age 74.9 ± 14.3 years, 53% women) were recorded including 4,469 ischemic strokes (IS), 655 intracerebral hemorrhages (ICH), and 135 undetermined strokes. In IS patients, unadjusted RS was 82% at 1 year and decreased to 62% at 10 years. Adjusted RS showed a lower survival in older age groups (p < 0.001), but no difference between men and women (p = 0.119). In ICH patients, unadjusted RS was 56 and 42% at 1 and 10 years, respectively, with a lower adjusted survival in older age groups (p < 0.001), but no sex differences (p = 0.184). CONCLUSION: This study showed that RS after stroke is lower in older than in younger patients but without significant sex differences, and survival profiles differ according to stroke subtypes. Since RS allows a better estimation of stroke-related death than observed survival does, especially in old patients, such a method is adapted to provide reliable information when considering long-term outcome.

Influence of Pre-Existing Mild Cognitive Impairment and Dementia on Post-Stroke Mortality. The Dijon Stroke Registry.

OBJECTIVE: We assessed the association between pre-stroke cognitive status and 90-day case-fatality. METHODS: Patients with ischemic stroke (IS) or spontaneous intracerebral hemorrhage (ICH) were prospectively identified among residents of Dijon, France, between 2013 and 2015, using a population-based registry. Association between pre-stroke cognitive status and case-fatality at 90 days was evaluated using Cox regression. RESULTS: Seven hundred sixty-two patients were identified, and information about pre-stroke cognitive status was obtained for 716 (92.6%) of them, including 603 IS (84.2%) and 113 ICH (15.8%). Before stroke, 99 (13.8%) patients had mild cognitive impairment (MCI) and 98 (13.7%) had dementia. Patients with cognitive impairment were older, had a higher prevalence of several risk factors, more severe stroke, more frequent ICH, and less admission to stroke unit. Case-fatality rate at 90 days was 11.7% in patients without cognitive impairment, 32.3% in MCI patients, and 55.1% in patients with dementia. In multivariable analyses, pre-existing MCI (hazard ratio [HR] 2.22, 95% CI 1.21-4.05, p = 0.009) and dementia (HR 4.35, 95% CI 2.49-7.61, p < 0.001) were both associated with 90-day case-fatality. CONCLUSION: Pre-stroke MCI and dementia were both associated with increased mortality. These associations were not fully explained by baseline characteristics, pre-stroke dependency, stroke severity or patient management, and underlying reasons need to be investigated.