Long-Term Mortality, Recovery, and Vocational Status After a Maternal Stroke: Register-Based Observational Case-Control Study.

BACKGROUND AND OBJECTIVES: Maternal stroke is a rare event with an increasing incidence. Data on the long-term prognosis after a maternal stroke are limited. We aimed to examine long-term mortality, recovery, vocational status and morbidity after a maternal stroke in a population-based setting including a comparison with matched, stroke-free controls. METHODS: In this register-based study with hospital chart validation, we included all women with a maternal stroke in Finland in 1987-2016 who survived the first year after the event. The recovery of the cases was assessed from the hospital charts by modified Rankin scale (mRS). Three controls matched by delivery year, age, and parity were selected for each case. All deaths until 2022 were identified from the Register for Causes of Death. Data on vocational status were obtained from Statistics Finland and morbidity from the Hospital Discharge Register and patient charts until year 2016. RESULTS: The study included 235 women with a maternal stroke and 694 matched controls. The median follow-up time was 17.5 years (interquartile range [IQR] 9.6-25.4) for mortality and 11.8 years (IQR 3.8-19.8) for vocational status and subsequent morbidity. Mortality among cases was 5.5% and among controls, 2.4% (age-adjusted odds ratio [OR] 2.3, 95% [CI] 1.1-4.9). At the end of the follow-up, 90.3% of the cases were independent in daily activities (mRS ≤2). In 2016, fewer women with a maternal stroke were working compared with controls (65.9% vs 79.1%, OR 0.5, 95% CI 0.4-0.7) and were more often receiving a pension (18.2% vs 4.9%, OR 4.4, 95% CI 2.7-7.3). Cerebrovascular events (age-adjusted OR 8.6 95% CI 4.4-17.1), cardiac diseases (age-adjusted OR 3.3, 95% CI 1.4-7.7), and major cardiovascular events were more common among cases during the follow-up (age-adjusted OR 7.6 95% CI 3.1-18.7). DISCUSSION: Despite having higher overall mortality and higher cardiovascular morbidity, the majority of the maternal stroke survivors recovered well. As expected, the vocational status of cases was inferior to that of controls, but most women were working at the end of the follow-up. Our study provides important information on the prognosis and sequalae after a maternal stroke to help in patient counseling and to improve secondary prevention.

Acute recanalization therapy for ischemic stroke during pregnancy and puerperium.

BACKGROUND: The safety and efficacy of intravenous thrombolysis (IVT) and endovascular thrombectomy for an ischemic stroke (IS) during pregnancy and puerperium are poorly studied. We evaluated the complications and outcome of recanalization therapy in maternal ISs. METHODS: A nationwide cohort of maternal ISs in Finland during 1987-2016 was collected by linking national healthcare registers: Medical Birth Register, Hospital Discharge Register, and Cause-Of-Death Register. The diagnoses were verified retrospectively from patient records. IVT-treated patients were compared to controls, who were young females with non-pregnancy-related IS from the Helsinki Stroke Thrombolysis Registry. RESULTS: Totally, 12 of 97 (12.4%) maternal ISs were treated with recanalization therapy. Compared to controls, IVT-treated maternal IS patients had more frequently early (age-adjusted odds ratio (aOR) = 7.63, 95% CI 1.49-39.04) and major (aOR = 8.59, 95% CI 2.09-35.31) neurological improvements, measured using the National Institute of Health Stroke Scale. Good functional outcomes (modified Rankin Scale 0-2) at three months were equally common in maternal ISs and controls. No other complications were observed in IVT-treated maternal ISs than 1 (9.1%) symptomatic nonfatal intracranial hemorrhage. Among maternal IS patients treated with recanalization or conventional therapy, good functional outcome at the end of the follow-up was less common in recanalization-treated patients (66.7% vs 89.4%, aOR = 0.22, 95% CI 0.052-0.90), but otherwise outcomes were similar. CONCLUSIONS: In this small nationwide cohort of maternal ISs, the complications of recanalization therapy were rare, and the outcomes were similar in IVT-treated maternal IS patients and controls. Maternal ISs should not be excluded from recanalization therapy in otherwise eligible situations.

Long-term cognitive and neurovascular changes after carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) has been associated with both cognitive decline and improvement, but the underlying neurovascular mechanisms are unclear. The aim of this study was to investigate the relationship between neurovascular indices and cognitive changes after CEA. METHODS: We studied 55 patients with severe (≥70%) symptomatic or asymptomatic carotid stenosis before and six months after CEA. A wide array of neuropsychological tests was arranged in eight cognitive domains and cognitive functions specific to hemisphere ipsilateral to operation. Differences in cognitive performance between patients and 38 matching healthy controls were studied with linear mixed models. Neurovascular functioning and microembolic signals were assessed with transcranial Doppler ultrasound of the middle cerebral artery. Associations between neurovascular indices and cognitive change were assessed with linear regression analyses. RESULTS: On group level, the CEA patients improved more than controls in working memory, whereas no cognitive deterioration was detected. Also on individual level, improvement was most frequently observed in working memory. Worse preoperative cerebrovascular reactivity was related with improvement in cognitive functions of the ipsilateral hemisphere. Low preoperative pulsatility index was associated with improvement in executive functioning and ipsilateral cognitive functions. Poorer preoperative blood flow velocity associated with improvement in complex attention. Microembolic signals were rare. CONCLUSION: The present findings suggest that CEA may have beneficial long-term effects on cognition. These effects may specifically involve patients with impaired preoperative circulatory adaptive mechanisms.

Virtual reality tasks with eye tracking for mild spatial neglect assessment: a pilot study with acute stroke patients.

Objective: Increasing evidence shows that traditional neuropsychological tests are insensitive for detecting mild unilateral spatial neglect (USN), lack ecological validity, and are unable to clarify USN in all different spatial domains. Here we present a new, fully immersive virtual reality (VR) task battery with integrated eye tracking for mild visual USN and extinction assessment in the acute state of stroke to overthrow these limitations. Methods: We included 11 right-sided stroke patients and 10 healthy controls aged 18-75 years. Three VR tasks named the Extinction, the Storage and the Shoot the target tasks were developed to assess USN. Furthermore, neuropsychological assessment examining various parts of cognitive functioning was conducted to measure general abilities. We compared VR and neuropsychological task performance in stroke patients - those with (USN+, n = 5) and without USN (USN-, n = 6) - to healthy controls (n = 10) and tentatively reported the usability of VR system in the acute state of stroke. Results: Patients had mostly mild neurological and USN symptoms. Nonetheless, we found several differences between the USN+ and healthy control groups in VR task performance. Compared to controls, USN+ patients showed visual extinction and asymmetry in gaze behavior and detection times in distinct spatial locations. Extinction was most evident in the extrapersonal space and delayed detection times on the extreme left and on the left upper parts. Also, USN+ patients needed more time to complete TMT A compared with USN- patients and TMT B compared with controls. VR system usability and acceptance were rated high; no relevant adverse effects occurred. Conclusion: New VR technology with eye tracking enables ecologically valid and objective assessment methods with various exact measures for mild USN and thus could potentially improve future clinical assessments.

Etiology of intracerebral hemorrhage during pregnancy or puerperium: A nationwide study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage during pregnancy or puerperium (pICH) is one of the leading causes of maternal death worldwide. However, limited epidemiological data exist on the etiology and outcomes of pICH, which is required to guide prevention and treatment. METHODS: A retrospective nationwide cohort study and a nested case-control study was performed in Finland 1987-2016. We identified women with incident pICH by linking the Medical Birth Register (MBR) and the Hospital Discharge Register (HDR). The clinical details were collected from patient records. Three matched controls with a pregnancy without ICH were selected for each case from the MBR. RESULTS: In total, 49 pICH cases were identified. Half of these cases occurred during pregnancy, and the other half during peripartum and puerperium. Based on the SMASH-U (structural vascular lesion, medication, amyloid angiopathy, systemic disease, hypertension, undetermined) classification, 35.4% of the patients had a systemic disease, most commonly preeclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome; 31.3% had a structural vascular lesion; 31.3% had an undetermined etiology; and one patient (2.1%) had hypertension. The most important risk factor was hypertensive disorders of pregnancy (HDP; odds ratio = 3.83, 95% confidence interval = 1.60-9.15), occurring in 31% of the cases. Maternal mortality was 12.5%, and 20.9% of the surviving women had significant disability (modified Rankin Scale = 3-5) 3 months after the pICH. Women with systemic disease had the worst outcomes. CONCLUSIONS: Even in a country with a comprehensive pregnancy surveillance system, the maternal mortality rate for pICH is high, and the sequelae are severe. Early recognition and treatment of the key risk factor, HDP, is crucial to help prevent this serious pregnancy complication.

Etiology and risk factors of ischemic stroke during pregnancy and puerperium: A population-based study.

INTRODUCTION: Ischemic stroke (IS) is an uncommon, but potentially life-changing, complication of pregnancy. The aim of this study was to analyze the etiology and risk factors of pregnancy-associated IS. PATIENTS AND METHODS: We collected a population-based retrospective cohort of patients diagnosed with IS during pregnancy or puerperium in Finland from 1987 to 2016. These women were identified by linking the Medical Birth Register (MBR) with the Hospital Discharge Register. Three matched controls were selected from MBR for each case. The diagnosis and temporal relationship of IS to pregnancy, and clinical details were verified from patient records. RESULTS: A total of 97 women (median age 30.7 years) were identified as having pregnancy-associated IS. The most common etiologies based on TOAST classification were cardioembolism in 13 (13.4%), other determined in 27 (27.8%) and undetermined in 55 (56.7%) patients. Fifteen patients (15.5%) had embolic strokes of undetermined sources. The most important risk factors were pre-eclampsia, eclampsia, gestational hypertension, and migraine. IS patients had more frequently traditional and pregnancy-related stroke risk factors than the controls (OR 2.38, 95% CI 1.48-3.84) and the risk of IS multiplied with the number of risk factors (4-5 risk factors: OR 14.21, 95% CI 1.12-180.48). DISCUSSION AND CONCLUSION: Rare causes and cardioembolism were frequent etiologies for pregnancy-associated IS, but in half of the women, the etiology remained undetermined. The risk of IS increased with the number of risk factors. Surveillance and counseling of pregnant women, especially with multiple risk factors, is crucial for the prevention of pregnancy-associated IS.

Pregnancy-associated stroke and the recurrence of stroke and other complications in subsequent pregnancies: Population-based retrospective cohort study.

OBJECTIVE: To examine the outcomes of the subsequent pregnancies from women with a previous pregnancy-associated stroke (PAS) in comparison to matched controls. DESIGN: Population-based retrospective cohort study. SETTING AND POPULATION: All women with a PAS in Finland 1987-2016 (n = 235) and controls (n = 694). METHODS: We identified all subsequent deliveries and induced and spontaneous abortions for women with a previous PAS and their matched controls from the Medical Birth Register and the Hospital Discharge Register until 2016. The number, course and outcomes of the subsequent pregnancies were compared. Patient records were studied for PAS recurrence. MAIN OUTCOME MEASURES: PAS recurrence and pregnancy complications. RESULTS: Women with a previous PAS had fewer subsequent deliveries: 73 (31.1%) women had 122 deliveries in all, whereas 303 (47.3%) of the controls had 442 deliveries (age-adjusted odds ratio [OR] 0.54, 95% CI 0.38-0.76). Hypertensive disorders of pregnancy (HDP) (17.2% versus 5.7%, age-adjusted OR 4.0, 95% CI 1.7-9.3), especially chronic hypertension (age-adjusted OR 5.9, 95% CI 1.5-24.7), and any diabetes during pregnancy (24.6% versus 14.5%, age-adjusted OR 2.0, 95% CI 1.1-3.8) were more common in cases. Regarding HDP, the difference between groups was explained by underlying factors such as index pregnancy HDP (multivariable OR 2.4, 95% CI 0.8-6.7). PAS recurred in four cases (5.5%). CONCLUSIONS: Subsequent pregnancies of women with a history of PAS are more often complicated with hypertensive disorders of pregnancy and any diabetes during pregnancy. PAS recurrence risk is considerable.

Retinal vessel diameters and microvascular abnormalities in patients with carotid stenosis before and 6 months after carotid endarterectomy: A prospective study.

PURPOSE: To assess retinal findings in patients with severe carotid stenosis (CS) before and after carotid endarterectomy (CEA) compared to those in controls. METHODS: This study is based on 70 patients (male 81%, mean age 69) scheduled for CEA in Helsinki University Hospital and 41 healthy nonmedicated controls (male 76%, mean age 68). Our examinations included fundus photographs. Semi-automated software (Vesselmap, Imedos) served for evaluation of central retinal arterial equivalent (CRAE) and venular equivalent (CRVE), and arterio-venous ratio (AVR) in both eyes. We assessed fundus photographs to subjectively grade microvascular abnormalities in the ipsilateral eyes including focal arteriolar narrowing and irregularities, arteriolar wall reflex, arterio-venous crossing signs and arteriolar and venular tortuosity in the macula. RESULTS: CRAE was similar in the ipsi-and contralateral eyes of our patients, and similar to that of the controls both pre- and postoperatively. Preoperatively, we observed higher CRVE in the patients' ipsilateral than in their contralateral eyes (222 vs. 217 µm, p = 0.009), and likewise higher than in controls' eyes (222 vs. 214 µm, p = 0.024). CRVE decreased postoperatively in the patients' ipsilateral eyes (222 vs. 217 µm, p = 0.037). Among the microvascular abnormalities, arteriolar and venular tortuosity in the macula showed higher grades in the patients than in the controls preoperatively (p = 0.035 and p = 0.043), but not postoperatively (p = 0.15 and p = 0.10). CONCLUSIONS: CRVE decreased after CEA, showing that venules constrict after the mechanical hindrance of blood flow is removed. Higher grades in arteriolar and venular tortuosity in the macula, a potential ocular biomarker of CS, subsided after CEA.

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS: SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS: Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION: Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT03192332.

Subarachnoid Hemorrhage During Pregnancy and Puerperium: A Population-Based Study.

BACKGROUND: Pregnancy-related subarachnoid hemorrhage (pSAH) is rare, but it causes high mortality and morbidity. Nevertheless, data on pSAH are limited. The objectives here were to examine the incidence trends, causes, risk factors, and outcomes of pSAH in a nationwide population-based cohort study in Finland covering 30 years. METHODS: We performed a retrospective population-based cohort study and nested case-control study in Finland for the period 1987-2016 (Stroke in Pregnancy and Puerperium in Finland). The Medical Birth Register was linked to the Hospital Discharge Register to identify women with incident stroke during pregnancy or puerperium. A subcohort of women with SAH is included in this analysis. The temporal connection of SAH to pregnancy and clinical details were verified from patient records. RESULTS: The unadjusted incidence of pSAH was 3.21 (95% CI, 2.46-4.13) per 100 000 deliveries. No significant increase occurred in the incidence throughout the study period. However, the age of the mother had a significant increasing effect on the incidence. In total, 77% of patients suffered an aneurysmal pSAH, resulting in death in 16.3% of women and with only 68.2% achieving good recovery (modified Rankin Scale score 0-2) at 3 months. Patients with nonaneurysmal pSAH recovered well. The significant risk factors for pSAH were smoking (odds ratio, 3.27 [1.56-6.86]), prepregnancy hypertension (odds ratio, 12.72 [1.39-116.46]), and pre-eclampsia/eclampsia (odds ratio, 3.88 [1.00-15.05]). CONCLUSIONS: The incidence of pSAH has not changed substantially over time in Finland. The majority of pSAH cases were aneurysmal and women with aneurysm had considerable mortality and morbidity. Counseling of pregnant women about smoking cessation and monitoring of blood pressure and symptoms of pre-eclampsia are important interventions to prevent pSAH.

Glutamine synthetase in human carotid plaque macrophages associates with features of plaque vulnerability: An immunohistological study.

BACKGROUND AND AIMS: Glutamine synthetase (GLUL), the sole generator of glutamine, is a metabolic nexus molecule also involved in atherosclerosis. We recently demonstrated a 2.2-fold upregulation of GLUL mRNA in stroke-causing carotid plaques when compared with plaques from asymptomatic patients. Here we compared in the same cohort GLUL mRNA expression with plaque gross morphology, and the colocalization of immunodetectable GLUL protein with histopathological changes and molecular and mechanical mediators linked to plaque development. METHODS: Endarterectomy specimens from 19 asymptomatic and 24 stroke patients were sectioned longitudinally and immunostained for GLUL, CD68, α-smooth muscle actin, iron, heme oxygenase-1 and CD163, and graded semiquantitatively in every 1 mm2. The amounts of cholesterol clefts and erythrocytes were graded. The fibrous cap thickness within each 1 mm2 area was measured. The association between the local pathological findings was analyzed by a hierarchical mixed modelling approach. RESULTS: The previously found correlation between GLUL mRNA and clinical symptomatology was supported by the increased GLUL mRNA in diseased tissue and increased local GLUL immunoreactivity in areas with multiple different atherosclerotic changes. A longer symptom-to-operation time correlated with lower GLUL mRNA (Rs = -0.423, p=0.050) but few outliers had a significantly higher GLUL mRNA levels, which persisted throughout the post-symptomatic period. Plaque ulceration associated with 1.8-fold higher GLUL mRNA (p=0.006). Macrophages were the main GLUL immunoreactive cells. GLUL immunostaining colocalized with erythrocytes, iron, CD163, and heme oxygenase-1. The correlations between local variables were consistent in both asymptomatic and stroke-causing plaques. An inverse correlation was found between the fibrous cap thickness and local GLUL immunoreactivity (p=0.012). Considerable variability in interplaque expression pattern of GLUL was present. CONCLUSIONS: Our results link connect macrophage GLUL expression with carotid plaque features characterizing plaque vulnerability.

Trends in the Incidence and Risk Factors of Pregnancy-Associated Stroke.

Pregnancy is a female-specific risk factor for stroke. Although pregnancy-associated stroke (PAS) is a rare event, PAS leads to considerable maternal mortality and morbidity. It is estimated that 7.7-15% of all maternal deaths worldwide are caused by stroke and 30-50% of surviving women are left with persistent neurological deficits. During last decade, several studies have reported an increasing incidence of PAS. The objective of this review is to summarize studies on time trends of PAS in relation to trends in the prevalence of stroke risk factors in pregnant women. Seven retrospective national healthcare register-based cohort studies from the US, Canada, UK, Sweden, and Finland were identified. Five studies from the US, Canada, and Finland reported an increasing trend of PAS. Potential biases include more sensitive diagnostics and improved stroke awareness among pregnant women and professionals toward the end of the study period. However, the concurrent increase in the prevalence of several stroke risk factors among pregnant women, particularly advanced age, hypertensive disorders of pregnancy, diabetes, and obesity, indicate that the findings are likely robust and should be considered seriously. To reduce stroke in pregnancy, increased awareness among all medical specialties and pregnant women on the importance of risk-factor management during pregnancy and stroke symptoms is necessary. Important preventive measures include counseling for smoking cessation and substance abuse, treatment of hypertensive disorders of pregnancy, use of aspirin in women at high risk for developing preeclampsia, and antithrombotic medication and pregnancy surveillance for women with high-risk conditions. Epidemiological data from countries with a high risk-factor burden are largely missing. National and international registries and prospective studies are needed to increase knowledge on the mechanisms, risk factors, management, and future implications for the health of women who experience this rare but devastating complication of pregnancy.

Flicker-induced retinal vascular dilation in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study.

PURPOSE: Retinal vascular function was assessed in patients with carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) and in controls at a six-month interval. METHODS: We studied 68 patients (81% male, mean age 69) and 41 healthy non-medicated controls (77%, 68) from March 2015 to December 2018. Our ophthalmological examination included flicker-induced arteriolar and venular measurements with a Dynamic Vessel Analyser in both eyes. RESULTS: At baseline, flicker-induced arteriolar and venular dilation was reduced in the ipsilateral eyes of the patients compared with dilation in the controls (arteriolar 1.0% versus 2.6%, p = 0.001 and venular 2.2% versus 2.8%, p = 0.049). These differences subsided after CEA. In patients' ipsilateral eyes, flicker-induced arteriolar dilation was borderline postoperatively (preoperative 1.0% versus postoperative 1.6%, p = 0.06), whereas venular dilation increased (2.2% versus 2.8%, p = 0.025). We found various tentative associations with the change in flicker-induced dilations after CEA, but not with the preoperative dilations. CONCLUSIONS: Postoperative recovery of the reduced flicker-induced arteriolar and venular dilatation in the ipsilateral eye shows that, after CEA, the activity-dependent vascular reactivity of haemodynamically compromised retinal tissue can improve.

Ocular signs of carotid stenosis in ipsi- and contralateral eyes before and after carotid endarterectomy: a prospective study.

PURPOSE: We describe hypoperfusion-related and embolic ocular signs of carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) in a CS population. METHODS: We enrolled prospectively 70 CEA patients (81% male, mean age 69) and 41 non-medicated control subjects (76%, 68), from March 2015 to December 2018, assessing intraocular pressure (IOP), best-corrected visual acuity (BCVA) in logMAR units and performing a bio-microscopy examination. RESULTS: Main index symptoms included amaurosis fugax (Afx) (29, 41%) and hemispheric TIA (17, 24%), and 17 (24%) were asymptomatic. Of the 70, 17 patients (24%, 95% CI 16-36) showed ocular signs of CS. Of four embolic (Hollenhorst plaques) findings, one small macular plaque disappeared postoperatively. Four had hypoperfusion, that is ocular ischaemic syndrome (OIS), requiring panretinal photocoagulation: one for multiple mid-peripheral haemorrhages, two for iris neovascularization and one for neovascular glaucoma (NVG); only the NVG proved irreversible. Nine (de novo in three) showed mild OIS, that is only few mid-peripheral haemorrhages, ranging pre- /postoperatively in ipsilateral eyes from one to eleven (median two)/ one to two (median one), and in contralateral eyes from three to nine (median five)/ one to six (median three). Pre- and postoperative median BCVA was 0 or better, and mean IOP was normal, except in the NVG patient. Temporary visual impairment from 0 to 0.3 occurred in one eye soon after CEA due to ocular hyperperfusion causing macular oedema. CONCLUSIONS: Ocular signs of CS are common in CEA patients, ranging from few mid-peripheral haemorrhages to irreversible NVG. Clinicians should be aware of these signs in detecting CS.

Carotid Endarterectomy After Intracranial Endovascular Thrombectomy for Acute Ischaemic Stroke in Patients with Carotid Artery Stenosis.

OBJECTIVE: Recent randomised controlled trials demonstrated the benefit of intracranial endovascular thrombectomy (EVT) in acute ischaemic stroke. There is no consensus, however, on how to treat concomitant extracranial carotid artery stenosis after EVT. The aim of this study was to evaluate the outcome in patients treated with carotid endarterectomy (CEA) after EVT, comparing complication rates among patients undergoing CEA for stroke without previous EVT. METHODS: This was a registry study of all patients (n = 3 780) treated with CEA after stroke in Sweden and the capital Helsinki region, Finland, from January 2011 to September 2020. Sixty three patients (1.7%; 0.5% 2011, 4.3% 2019) underwent EVT prior to CEA. The primary outcome was 30 day stroke and death rate. RESULTS: The EVT+CEA group had major stroke as the qualifying neurological event (QNE) in 79%, but just 5.9% had this in the CEA only group (p < .001). Intravenous thrombolysis was administered before EVT in 54% of patients in the EVT+CEA group, but in just 12% in those receiving CEA only (p < .001). The combined stroke and death rate at 30 days for EVT+CEA was 0.0% (95% confidence interval [CI] 0.0 - 5.7). One patient had a post-operative TIA, none had post-operative intracerebral or surgical site haemorrhage. CEA was performed within a median of seven days (interquartile range 4, 15) after QNE, and 75% had CEA ≤14 days from QNE. The main reason to postpone CEA was an infarct larger than one third of the middle cerebral artery territory. The stroke and death rate in patients treated with CEA only was 3.7% (95% CI 3.2 - 4.4), CEA was performed a median of eight days after QNE, and in 79.7% in ≤14 days. The three year survival after EVT+CEA was 93% (95% CI 85 - 100), compared with 87% (95% CI 86 - 88) after CEA only. Cox regression analysis adjusting for age showed no increased all cause mortality after EVT+CEA (HR 1.3, 95% CI 0.6 - 2.7, p = .52). CONCLUSION: These results indicate that CEA is safe to perform after previous successful EVT for acute ischaemic stroke. Results were comparable with those undergoing CEA only, despite the EVT+CEA patients having more severe stroke symptoms prior to surgery, and timing was similar.

Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification.

Background: Long-term treatment with the vitamin K antagonist warfarin is widely used for the prevention of venous thrombosis and thromboembolism. However, vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries. Methods: Overall, 500 consecutive patients underwent carotid endarterectomy, 82 of whom had received long-term warfarin therapy. The extent of calcification was assessed with preoperative computed tomography angiography, and both macroscopic morphological grading and microscopic histological examination of each excised carotid plaque were performed after carotid endarterectomy. Results: Compared with non-users, warfarin users had significantly more computed tomography angiography-detectable vascular calcification in the common carotid arteries (odds ratio 2.64, 95% confidence interval 1.51-4.63, P < 0.001) and even more calcification in the internal carotid arteries near the bifurcation (odds ratio 18.27, 95% confidence interval 2.53-2323, P < 0.001). Histological analysis revealed that the intramural calcified area in plaques from warfarin users was significantly larger than in plaques from non-users (95% confidence interval 3.36-13.56, P = 0.0018). Conclusions: Long-lasting warfarin anticoagulation associated with increased calcification of carotid atherosclerotic plaques, particularly in locations known to be the predilection sites of stroke-causing plaques. The clinical significance of this novel finding warrants further investigations.

Stroke in Pregnancy and Puerperium: Validated Incidence Trends With Risk Factor Analysis in Finland 1987-2016.

OBJECTIVE: To investigate whether previously reported increasing incidence of pregnancy-associated stroke (PAS) is observed in chart-validated register data in Finland. In an exploratory analysis, we studied risk factors for PAS. METHODS: We performed a retrospective population-based cohort study and nested case-control study in Finland from 1987 to 2016. The Medical Birth Register (MBR) was linked to the Hospital Discharge Register to identify women with incident stroke (ischemic stroke, cerebral venous thrombosis, intracerebral or subarachnoid hemorrhage) during pregnancy or puerperium. Cases were verified from patient records. Incidence of PAS over the study period in 5-year age groups and pregnancy/postpartum period was calculated per number of deliveries. Three matched controls were selected for each case from MBR to compare risk factors. RESULTS: After chart review, 29.6% (257 of 868) of cases were PAS. The incidence of PAS was 14.5 (95% confidence interval [CI] 12.8-16.3) per 100,000 deliveries. Incidence increased from 11.1 to 25.2 per 100,000 deliveries from 1987 to 1991 to 2012 to 2016 (p < 0.0001). Incidence increased by age from 9.8 to 29.9 per 100,000 deliveries from 20 to 24 years to >40 years of age (p < 0.0001). During the early postpartum period, incidence was 5-fold greater compared to the first trimester. Maternal mortality was 6.6%. In the multivariable-adjusted model, smoking beyond 12 gestational weeks (odds ratio [OR] 1.8, 95% CI 1.2-2.7), migraine (OR 16.3, 95% CI 5.3-49.8), and hypertensive disorders of pregnancy (OR 4.0, 95% CI 2.5-6.3) were the most important risk factors for PAS. CONCLUSION: PAS incidence is increasing, stressing the importance of careful pregnancy surveillance and risk factor management, particularly in older expectant mothers and extending to puerperium. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that smoking beyond 12 gestational weeks, migraine, and hypertensive disorders of pregnancy are associated with an increased risk of PAS.

Subfoveal choroidal thickness in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study.

PURPOSE: To compare subfoveal choroidal thickness (SFCT) and associated clinical variables in patients with carotid stenosis (CS) before and 6 months after carotid endarterectomy (CEA). METHODS: The prospective non-randomized Helsinki Carotid Endarterectomy Study - Brain and Eye Sub-sTudy included seventy patients (81% male, mean age 69 years) and 40 control subjects (77% male, 68 years), from March 2015 to December 2018. Ophthalmological examination included SFCT measured with enhanced-depth imaging-optical coherence tomography. Carotid stenosis (CS) was more severe (≥70% stenosis in 92%) ipsilateral to the CEA than contralaterally (<50% stenosis in 74%; p < 0.001). RESULTS: At baseline, patients had thinner mean SFCT than control subjects in both eyes (ipsilateral, 222 versus 257 µm and contralateral, 217 versus 258 µm, p ≤ 0.005). At follow-up, SFCT did not change in ipsi- and contralateral eyes compared to baseline in patients (p = 0.68 and p = 0.77), or in control subjects (p = 0.59 and p = 0.79). Patients with coronary artery disease had thinner mean SFCT versus those without it in ipsilateral eyes before CEA (200 versus 233 µm, p = 0.027). In ipsilateral eyes of patients before CEA, thinner SFCT and ocular signs of CS, plaque and hypoperfusion related findings combined, were associated (p = 0.036), and the best-corrected visual acuity, measured in logMAR, increased with increasing SFCT (r = -0.25; p = 0.046). CONCLUSIONS: Subfoveal choroidal thickness (SFCT) is thinner in patients with CS without association between SFCT and the grade of CS. Unchanged SFCT after CEA suggests, that choroidal vessels in severe CS are unable to react to increased blood flow. Bilaterally thin SFCT could be considered as yet another sign of CS.

Predictive Factors for Pre-operative Recurrence of Cerebrovascular Symptoms in Symptomatic Carotid Stenosis.

OBJECTIVE: Across stroke subtypes, carotid artery stroke carries the highest risk of recurrence. Despite initiation of best medical therapy (BMT), some patients suffer recurrent neurological events before undergoing carotid endarterectomy (CEA). The aim was to identify clinical predictors of early recurrent events in patients with symptomatic carotid stenosis (sCS) awaiting CEA on modern BMT. METHODS: The Helsinki Carotid Endarterectomy Study 2 (HeCES2) is a cross sectional, longitudinal, prospective, and consecutive cohort study, which enrolled 500 symptomatic or asymptomatic patients with carotid stenosis scheduled for CEA in a tertiary stroke centre. Symptomatic patients were included for this analysis (n = 324). RESULTS: Of all 324 patients with sCS, 39 (12%) had a recurrent cerebrovascular event at a median of six days after the index symptom: four had an ischaemic stroke (1.2%), 16 a hemispheric transient ischaemic attack (TIA; 4.9%), and 19 amaurosis fugax (AFX; 5.9%). The recurrence rate was 4.0 % (n = 13) within 48 h and 9.9% (n = 32) within two weeks. None of the patients (n = 108) presenting with ocular symptoms (AFX or retinal artery occlusion) suffered recurrent hemispheric TIA or stroke. In Cox regression analysis, comorbid hypertension (hazard ratio [HR] 6.58, 95% confidence interval [CI] 1.33-32.47), hemispheric TIA as the index symptom (HR 3.42, 95% CI 1.70-6.90), the number of prior attacks (HR 1.12, 95% CI 1.08-1.15), and high low density lipoprotein/high density lipoprotein ratio (HR 1.51, 95% CI 1.09-2.11) were independently associated with an increased risk of recurrent event, while a history of major cardiovascular event (HR 0.33, 95% CI 0.11-0.96) and high serum fibrinogen level (HR 0.59, 95% CI 0.41-0.86) were associated with a decreased risk. CONCLUSION: More than every tenth patient with sCS experienced an early recurrent cerebrovascular event prior to scheduled CEA, despite optimal medication. However, stroke recurrence was lower than in earlier observational studies, which could be explained by improved care pathways, more aggressive medication, and expedited CEA. All recurrent strokes occurred in patients initially presenting with minor stroke.