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.

Long-term risk of recurrent vascular events and mortality in young stroke patients: Insights from a multicenter study.

BACKGROUND: Although the incidence of stroke in the young is rising, data on long-term outcomes in these patients are scarce. We thus aimed to investigate the long-term risk of recurrent vascular events and mortality in a multicenter study. METHODS: We followed 396 consecutive patients aged 18-55 years with ischemic stroke (IS) or transient ischemic attack (TIA) enrolled in three European centers during the period 2007-2010. A detailed outpatient clinical follow-up assessment was performed between 2018 and 2020. When an in-person follow-up visit was not possible, outcome events were assessed using electronic records and registry data. RESULTS: During a median follow-up of 11.8 (IQR 10.4-12.7) years, 89 (22.5%) patients experienced any recurrent vascular event, 62 (15.7%) had any cerebrovascular event, 34 (8.6%) had other vascular events, and 27 (6.8%) patients died. Cumulative 10-year incidence rate per 1000 person-years was 21.6 (95% CI 17.1-26.9) for any recurrent vascular event and 14.9 (95% CI 11.3-19.3) for any cerebrovascular event. The prevalence of cardiovascular risk factors increased over time, and 22 (13.5%) patients lacked any secondary preventive medication at the in-person follow-up. After adjustment for demographics and comorbidities, atrial fibrillation at baseline was found to be significantly associated with recurrent vascular events. CONCLUSIONS: This multicenter study shows a considerable risk of recurrent vascular events in young IS and TIA patients. Further studies should investigate whether detailed individual risk assessment, modern secondary preventive strategies, and better patient adherence may reduce recurrence risk.

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.

Hemicraniectomy for Dominant vs Nondominant Middle Cerebral Artery Infarction: A Systematic Review and Meta-Analysis.

OBJECTIVES: Decompressive hemicraniectomy decreases mortality and severe disability from space-occupying middle cerebral artery infarction in selected patients. However, attitudes towards hemicraniectomy for dominant-hemispheric stroke have been hesitant. This systematic review and meta-analysis examines the association of stroke laterality with outcome after hemicraniectomy. MATERIALS AND METHODS: We performed a systematic literature search up to 6th February 2020 to retrieve original articles about hemicraniectomy for space-occupying middle cerebral artery infarction that reported outcome in relation to laterality. The primary outcome was severe disability (modified Rankin Scale 4‒6 or 5‒6 or Glasgow Outcome Scale 1‒3) or death. A two-stage combined individual patient and aggregate data meta-analysis evaluated the association between dominant-lateralized stroke and (a) short-term (≤ 3 months) and (b) long-term (> 3 months) outcome. We performed sensitivity analyses excluding studies with sheer mortality outcome, second-look strokectomy, low quality, or small sample size, and comparing populations from North America/Europe vs Asia/South America. RESULTS: The analysis included 51 studies (46 observational studies, one nonrandomized trial, and four randomized controlled trials) comprising 2361 patients. We found no association between dominant laterality and unfavorable short-term (OR 1.00, 95% CI 0.69‒1.45) or long-term (OR 1.01, 95% CI 0.76‒1.33) outcome. The results were unchanged in all sensitivity analyses. The grade of evidence was very low for short-term and low for long-term outcome. CONCLUSIONS: This meta-analysis suggests that patients with dominant-hemispheric stroke have equal outcome after hemicraniectomy compared to patients with nondominant stroke. Despite the shortcomings of the available evidence, our results do not support withholding hemicraniectomy based on stroke laterality.

Use of Statins After Ischemic Stroke in Young Adults and Its Association With Long-Term Outcome.

Background and Purpose- Knowledge of the use of secondary preventive medication in young adults is limited. We studied the use of statins and its association with subsequent vascular events in young adults with ischemic stroke-a patient group with a known low burden of atherosclerosis. Methods- The study population included 935 first-ever 30-day ischemic stroke survivors aged 15 to 49 years from the Helsinki Young Stroke Registry, 1994 to 2007. Follow-up data until 2012 were obtained from the Social Insurance Institution of Finland (Drug Prescription Register), the Finnish Care Register, and Statistics Finland. The association of the use of statins (defined as at least 2 purchases) with all-cause mortality, recurrent stroke, and other recurrent vascular events was assessed through adjusted Cox regression analyses. We further compared propensity score-matched statin users with nonusers. Results- Of our 935 patients, 46.8% used statins at some point during follow-up. Higher age, dyslipidemia, heavy alcohol use, and hypertension were significantly associated with purchasing statins. Statin users exhibited lower risk of all-cause mortality (hazard ratio, 0.38 [95% CI, 0.25-0.58]) and recurrent stroke (hazard ratio, 0.29 [95% CI, 0.19-0.44]) than nonusers, after adjustment for dyslipidemia, stroke subtype, and other confounders. These results remained unchanged after propensity score-matched comparison. Conclusions- Less than half of young ischemic stroke patients used statins; use was affected by age and risk factor profile. Statin use was independently associated with lower risk of all-cause mortality and recurrent stroke.

Sex Differences and Functional Outcome After Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)-treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care. METHODS: Data were obtained from IVT registries of 12 European tertiary hospitals. The primary outcome was poor functional outcome, defined as a modified Rankin scale score of 3 to 6 at 3 months. We stratified outcome by age in decades. Safety measures were symptomatic intracranial hemorrhage and mortality at 3 months. RESULTS: In this cohort, 9495 patients were treated with IVT, and 4170 (43.9%) were women with a mean age of 71.9 years. After adjustments for baseline differences, female sex remained associated with poor functional outcome (odds ratio, 1.15; 95% confidence interval, 1.02-1.31). There was no association between sex and functional outcome when data were stratified by age. Symptomatic intracranial hemorrhage rate was similar in both sexes (adjusted odds ratio, 0.93; 95% confidence interval, 0.73-1.19), whereas mortality was lower among women (adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99). CONCLUSIONS: In this large cohort of IVT-treated patients, women more often had poor functional outcome compared with men. This difference was not dependent on age.

Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke.

BACKGROUND AND PURPOSE: High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. METHODS: The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. RESULTS: Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P<0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP ≥160 mm Hg compared with those with SBP <160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; P<0.001) occurring earlier (13.9 years [13.0-14.6] versus 16.2 [15.8-16.6]; P<0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. CONCLUSIONS: In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes.

Cancer in young adults with ischemic stroke.

BACKGROUND AND PURPOSE: Cancer is a risk factor for ischemic stroke. Little is known about cancer among young adults with ischemic stroke. We studied the frequency of cancer and its association with long-term risk of death among young patients with first-ever ischemic stroke. METHODS: 1002 patients aged 15 to 49 years, registered in the Helsinki Young Stroke Registry, and with a median follow-up of 10.0 years (interquartile range 6.5-13.8) after stroke were included. Historical and follow-up data were derived from the Finnish Care Register and Statistics Finland. Survival between groups was compared with the Kaplan-Meier life-table method, and Cox proportional hazard models were used to identify factors associated with mortality. RESULTS: One or more cancer diagnosis was made in 77 (7.7%) patients, of whom 39 (3.9%) had cancer diagnosed prestroke. During the poststroke follow-up, 41 (53.2%) of the cancer patients died. Median time from prestroke cancer to stroke was 4.9 (1.0-9.5) years and from stroke to poststroke cancer was 6.7 (2.7-10.9) years. Poststroke cancer was associated with age>40 years, heavy drinking, and cigarette smoking. The cumulative mortality was significantly higher among the cancer patients (68.6%, 95% confidence interval 52.0%-85.3%) compared with patients without cancer (19.7%, 95% confidence interval 16.3%-23.2%). Active cancer at index stroke, melanoma, and lung/respiratory tract cancer had the strongest independent association with death during the follow-up when adjusted for known poststroke mortality prognosticators. CONCLUSIONS: Cancer, and especially active cancer and no other apparent cause for stroke, is associated with unfavorable survival among young stroke patients.

Long-term mortality after first-ever and recurrent stroke in young adults.

BACKGROUND AND PURPOSE: Mortality after first-ever stroke, and particularly after recurrent stroke, and predictors of long-term mortality among young and middle-aged stroke patients are not well-known. We assessed 17-year risk of mortality with focus on the effect of recurrence on the risk of death of young and middle-aged patients with stroke. METHODS: Mortality and recurrent stroke rate of 970 consecutive 30-day survivors of first-ever ischemic stroke aged 15 to 49 years (1994-2007) were studied. Prospective follow-up data came from the Finnish Care Register for Health Care and Statistics Finland. Mean follow-up was 10.2±4.3 years. We compared survival between clinical subgroups and identified factors associated with mortality. Standardized mortality ratio was calculated for demographic and pathogenetic subgroups using mortality data of the general population matched with age, sex, calendar year, and geographical area. RESULTS: At the end of follow-up, 152 (15.7%) patients had died (cumulative risk, 23.0%; 95% confidence interval, 19.1%-26.9%) and 132 (13.6%) had experienced a recurrent stroke. After adjusting for baseline characteristics, recurrent stroke was statistically the most important risk factor for mortality after first-ever ischemic stroke (hazard ratio, 16.68; 95% confidence interval, 2.33-119.56; P=0.005). Observed mortality was 7-fold higher than the expected mortality (standardized mortality ratio, 6.94; 95% confidence interval, 5.84-8.04) and particularly high among patients who experienced a recurrent stroke (standardized mortality ratio, 14.43; 95% confidence interval, 10.11-18.74). CONCLUSIONS: The high mortality rates and the striking impact of recurrent stroke on the risk of death should lead to development of more robust primary and secondary prevention strategies for young patients with stroke.

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.

Etiologic subtypes of first and recurrent ischemic stroke in young patients using A-S-C-O and TOAST classification criteria: A retrospective follow-up study.

INTRODUCTION: Scarce data exist on the etiology of recurrent ischemic strokes (ISs) among young adults. We analyzed the etiology of first-ever and recurrent events and the differences between them. PATIENTS AND METHODS: Patients aged 15-49 years with a first-ever IS in 1994-2007 were included in the Helsinki Young Stroke Registry. In this retrospective cohort study, data on recurrent ISs were identified from Care Register for Health Care until the end of 2017 and Causes of Death Register and from patient records until the end of 2020. All first-ever and recurrent ISs were classified using Atherosclerosis-Small vessel disease-Cardioembolism-Other Cause (A-S-C-O) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications. RESULTS: A total of 970 patients were included (median age at index IS 46 years, interquartile range 43-48, 33% women), of which 155 (16.0%) patients had recurrent IS, with 8 (5.2%) fatal cases and 5 (3.2%) unverifiable cases. The median follow-up was 17.4 (IQR 13.9-21.7) years. Median time from the index event to the first recurrent event was 4.5 (interquartile range [IQR] 1.6-10.2) years. Recurrence was more often due to definite cardioembolism (10.7% vs 18.0%, p = 0.013), while the proportion of other definite A-S-C-O subgroups remained the same. With TOAST classification, the proportion of true cryptogenic ISs decreased (16.7% vs 6.7%, p = 0.003), while those with incomplete evaluation increased (9.3% vs 19.3%, p = 0.015). Other TOAST phenotypes remained the same. CONCLUSION: The proportion of definite cardioembolism increased at recurrence using the A-S-C-O classification and the number of cryptogenic ISs decreased using the TOAST classification, while cases with incomplete evaluation increased. Most etiologies remained the same.

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.

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 post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke.

OBJECTIVE: We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. PATIENTS AND METHODS: The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. RESULTS: Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. CONCLUSIONS: In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding.KEY MESSAGESInitiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term.Patients starting antidepressants after IS should be followed up more closely in case of recurrent events.Future studies are needed to verify the results and to further study the nature of this finding.

Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study.

OBJECTIVE: Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. METHODS: Helsinki Young Stroke Registry includes patients aged 15-49 years with first-ever IS, 1994-2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1 year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. RESULTS: We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100 days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48-4.31) and during later follow-up among those with silent infarcts (2.04; 1.27-3.28), prior use of antidepressants (2.09; 1.26-3.46) and moderate versus mild stroke (2.06; 1.18-3.58). The relative difference in the hazard rate for moderate-severe limb paresis persisted both within the first 100 days (3.84, 2.12-6.97) and during later follow-up (4.54; 2.51-8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11-1.97) as well as lower (1.78; 1.25-2.54) and upper white-collar workers (2.00; 1.24-3.23) compared to blue-collar workers. CONCLUSION: One-fourth of young adults started PSADs within 1 year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up.

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative.

BACKGROUND AND OBJECTIVES: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression. RESULTS: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

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.