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.

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.

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.

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.

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.

The Efficacy of Carotid Surgery by Subgroups: The Concept of Stroke Prevention Potential.

OBJECTIVE: Considering carotid endarterectomy (CEA), reporting treatment delay, symptom status, and surgical complication rates separately gives an incomplete picture of efficacy; therefore, the aim was to combine these factors and develop a reporting standard that better describes the number of potentially prevented strokes. With a real life cohort and theoretical inclusion scenarios, the aim was to explore the stroke prevention potential of different carotid practices. METHODS: Landmark studies for symptomatic and asymptomatic patients were revisited. By using published estimates of treatment effect, a simplified calculator was designed to assess the five year stroke prevention rate per 1000 CEAs (stroke prevention potential [SPP], range 0-478), including the presence and recentness of symptoms, sex, increasing stenosis severity, and complication rates. Patients operated on for carotid stenosis at Helsinki University Hospital (HUH) between 2008 and 2016 were collected from a vascular registry (HUSVASC) and categorised according to the model. The local annual complication rate was re-evaluated and added to the model. The HUH patient cohort was incorporated into the SPP model, and changes over time analysed. Finally, theoretical changes in patient selection were compared in order to explore the theoretical impact of patient selection and shortening of the delay. RESULTS: Fifteen hundred and five symptomatic and 356 asymptomatic carotid stenoses were operated on with stroke plus death rates of 3.6% and 0.3%, respectively. The proportion of CEAs performed within two weeks of the index event increased over the follow up period, being 77% in 2016. The SPP increased from 123 in 2008 to 229 in 2016. Theoretically, 350 ischaemic strokes were prevented in the period 2008-16, with 1861 CEAs. CONCLUSIONS: National and international comparison of different CEA series is irrelevant if the inclusion criteria are not considered. A calculator that is easy to apply to large scale high quality registered data was developed and tested. SPP was found to increase over time, which is a probable sign of improved patient selection and an increased number of strokes prevented by the CEAs performed.

Pregnancy-associated stroke -a systematic review of subsequent pregnancies and maternal health.

BACKGROUND: Pregnancy-associated stroke is a rare but life-threatening event, with an estimated incidence of 30/100000 deliveries. Data on the risk of stroke recurrence and the risk of other adverse pregnancy outcomes are essential for adequate counselling and surveillance in subsequent pregnancies. The aim of this systematic review is to describe the implications of a pregnancy-associated stroke for the future health of these women. METHODS: We searched Ovid Medline, PubMed, Cochrane Library and CINAHL for articles published in 1980-2018. Articles including women with pregnancy-associated stroke and information on at least one of the following outcomes were included: 1) recurrence of stroke during subsequent pregnancy, 2) number and course of subsequent pregnancies and their outcomes and 3) subsequent cardiovascular health. RESULTS: Twelve articles were included in the review, with six providing information on subsequent pregnancies, four on subsequent maternal health and two on both. The included articles varied greatly in terms of study design, length of follow up and reported outcomes. We found 252 women with pregnancy-associated stroke for whom the outcomes of interest were reported: 135 women with information on subsequent pregnancies and 123 women with information on future health. In total, 55 pregnancies after stroke were found. In the majority of studies, the incidence of pregnancy complications was comparable to that of the general population. The risk of stroke recurrence during pregnancy was 2%. Data on subsequent health of these women were limited, and the quality of the data varied between the studies. CONCLUSIONS: Data on subsequent pregnancies and health of women with a history of pregnancy-associated stroke are limited. Further research on this topic is essential for adequate counselling and secondary prevention.

Prior Intravenous Stroke Thrombolysis Does Not Increase Complications of Carotid Endarterectomy.

Background and Purpose- Carotid endarterectomy (CEA) is recommended within 14 days after carotid artery stroke to prevent recurrence. However, the optimal timing of CEA after intravenous thrombolysis (IVT) remains unclear. We studied the safety of CEA after IVT while taking into account both stroke recurrence and CEA-related complications. Methods- Patients who underwent IVT followed by CEA in Helsinki University Hospital 2005 to 2016 were withdrawn from prospectively collected registers. The incidence of stroke recurrence during the time between IVT and CEA, peri/postoperative stroke, hyperperfusion syndrome or drug-resistant high blood pressure, and 3-month outcome measured by modified Rankin Scale was recorded. Stroke patients treated with CEA without preceding IVT were used as controls. Results- Altogether 128 CEAs with preceding IVT and 777 CEAs for stroke without IVT were identified. The median time from IVT to CEA was 9 days (range, 0-349 days; interquartile range, 16). Seven patients (5.5%) underwent CEA within 24 hours, 20 (15.6%) within 48 hours and 87 (68.0%) within 2 weeks from IVT. Stroke recurrence in IVT-CEA patients was 5.5% at median 4 days after IVT (range, 0-8 days). Outcome from CEAs performed within 48 hours from IVT did not differ from CEAs performed later with respect to peri/postoperative ischemic strokes (5.0% and 3.7%), hemorrhagic strokes (5.0% and 1.9%), neck hematomas (5.0% and 8.3%), myocardial infarctions (0.0% and 0.9%), or 3-month modified Rankin Scale. There was a tendency toward higher incidence of hyperperfusion syndrome in the patients operated within 48 hours from IVT (20.0% versus 6.5%; P=0.070). The CEA-related stroke rate was similar to that of the operation without thrombolysis. Only smoking was significantly associated with peri/postoperative stroke (odds ratio, 21.82; 95% confidence interval, 1.08-439.58). Conclusions- Time between IVT and CEA was not associated with CEA-related complications. The high rate of stroke recurrence during the waiting time for CEA underscores the importance of shortening surgery delays.

Haptoglobin Hp2 Variant Promotes Premature Cardiovascular Death in Stroke Survivors.

BACKGROUND AND PURPOSE: Haptoglobin (Hp) is an acute phase plasma protein protecting tissues from oxidative damage. It exists in 2 variant alleles (hp1/hp2) giving rise to 3 protein isoforms with different biochemical properties and efficiency to limit oxidative stress. We previously found that hp2 variant is associated with stroke risk in the patients with carotid stenosis and the risk of ischemic cardiovascular events in a general population cohort. This study examined the hypothesis that Hp genotype is associated with general cardiovascular risk in patients with stroke. METHODS: Hp was genotyped in SAM study (Helsinki Stroke Aging Memory, n=378). A total of 1426 individuals ascertained from a nationally representative cross-sectional health survey served as population controls. RESULTS: Hp genotype frequencies were 15.6% (hp1-1), 44.2% (hp1-2), and 40.2% (hp2-2) in patients with stroke. During a mean of 7.5-year follow-up after first-ever stroke, hp2 carriers had a substantially higher rate of cardiac deaths (24.5% versus 8.5%; P=0.006) and a trend toward more fatal strokes (23.5% versus 13.6%; P=0.122). The combined risk of ischemic cardiovascular deaths was 2.4-fold higher among hp2 carriers (95% confidence interval, 1.28-4.43) after adjustment for major cardiovascular risk factors. CONCLUSIONS: Hp2 allele is associated with premature ischemic cardiovascular deaths after first-ever ischemic stroke.

Recognizing subtle near-occlusion in carotid stenosis patients: a computed tomography angiographic study.

INTRODUCTION: Near-occlusion of the internal carotid artery (ICA) is a significant luminal diameter (LD) reduction beyond a tight atherosclerotic carotid stenosis (CS). Recognition of even subtle near-occlusions is essential to prevent underestimation of the stenosis degree. Our goal was to investigate the prevalence of near-occlusion among CS patients using a single standard criterion to facilitate its recognition, even when distal ICA LD reduction is not visually evident in computed tomography angiography (CTA). METHODS: We analysed carotid artery CTAs of 467 patients with moderate-to-severe CS scheduled for endarterectomy. We performed measurements of the bilateral distal ICA LDs from thin axial source images and utilized a 1.0 mm intra-individual side-to-side distal ICA LD difference to distinguish near-occlusions, based on a previous study, aware of the vagaries of measurement. For analysis stratification, we excluded cases with significant carotid pathology affecting LD measurements. RESULTS: We discovered 126 near-occlusions fulfilling our criterion of ipsilateral near-occlusion: the mean LD side-to-side difference (mm) with 95% confidence interval being 1.8 (1.6, 1.9) and a standard deviation of 0.8 mm. Among the 233 cases not meeting our near-occlusion criterion, we found 140 moderate (50-69%) and 93 severe (70-99%) ipsilateral stenoses. CONCLUSION: The utilization of 1.0 mm cut-off value for the intra-individual distal ICA LD side-to-side difference to distinguish atherosclerotic ICA near-occlusion leads to a relatively high incidence of near-occlusion. In CTA, recently suggested to be used for near-occlusion diagnosis, a discriminatory 1.0 mm cut-off value could function as a pragmatic tool to enhance the detection of even subtle near-occlusions.

[Carotid artery stenosis as predictor of the risk of cerebral and cardiac infarction]. / Kaulavaltimoahtauma aivo- ja sydäninfarktin riskin ennustajana.

Carotid artery stenoses are the cause of approx. 15% of cerebral infarctions which are often difficult and prone to recur. Endarterectomy of a carotid artery stenosis that has caused disturbances of the cerebral circulation is an effective remedy: operating six tight stenoses will prevent one cerebral infarction. One of the most promising methods to identify the patients having the highest risk of cerebral infarction is noninvasive imaging of the stenosis. Since the detection of a significant carotid artery stenosis is predictive of an increased risk of cerebral and cardiac infarction, the vascular risk factors should be identified on an individual basis and treated effectively. Screening of asymptomatic carotid artery stenoses is, however, not yet recommended.

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.

Intracranial Arteriovenous Malformations During Pregnancy and Puerperium-A Retrospective Nationwide Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: The knowledge about the management of patients with brain arteriovenous malformations (AVM) during pregnancy is limited, owing partly to insufficient evidence about the outcomes of newborns. This study aims to explore symptomatic AVMs and their outcomes during pregnancy, delivery, and the postpartum period. METHODS: We conducted a retrospective analysis by combining patients with symptomatic AVM from a nationwide population-based cohort of all women with a pregnancy resulting in delivery during 1987 to 2016 (n = 1 773 728 deliveries) and our AVM database (n = 805, 1942-2014). Cerebrovascular events during pregnancy were identified through International Classification of Diseases-9, International Classification of Diseases-10, or surgical procedure codes from the Hospital Discharge and Medical Birth Registers. Our analysis focused on treatment characteristics and outcomes of patients with AVM hemorrhage or symptomatic AVM during pregnancy, delivery, or puerperium. RESULTS: A total of 28 women with symptomatic AVMs during pregnancy, delivery, or postpartum period were followed for an average of 12.8 years (SD = 15.5) after admission. Among them, 21 (75%) experienced AVM hemorrhages during pregnancy, puerperium, or delivery. The mean age of patients was 28.9 years (SD = 5.5). Hemorrhages occurred predominantly during the second (n = 9, 43% of all ruptures) or the third trimester (n = 5, 24%). Two AVM ruptures occurred during labor. Treatment for AVM took place during pregnancy (n = 7, 25%) or puerperium (n = 3, 14%) in 10 patients (35.7%). Only 5 mothers (17.8%) had not been previously pregnant. There was no significant difference in mean Apgar scores between those with AVM hemorrhage (8.3) and those without (8.4). CONCLUSION: Most mothers in the study had prior pregnancies, suggesting a potentially weaker association between AVM rupture and pregnancy compared to previous reports. Notably, 2 AVM ruptures occurred during spontaneous vaginal deliveries. Outcomes were generally favorable in both mothers and infants. More research is needed to refine our understanding of the optimal timing for invasive treatment during pregnancy.

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 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.

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.

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.

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.

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.

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.