Renate M. Arntz

Long-term Mortality After Stroke Among Adults Aged 18 to 50 Years

IMPORTANCE Long-term data on mortality after first-ever stroke in adults aged 18 through 50 years are scarce and usually restricted to ischemic stroke. Moreover, expected mortality not related to first-ever stroke is not taken in account. OBJECTIVES To investigate long-term mortality and cause of death after acute stroke in adults aged 18 through 50 years and to compare this with nationwide age- and sex-matched mortality rates. DESIGN, SETTING, AND PARTICIPANTS The Follow -Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study of prognosis after transient ischemic attack (TIA), ischemic stroke, or hemorrhagic stroke in adults aged 18 through 50 years admitted to Radboud University Nijmegen Medical Centre, the Netherlands, between January 1, 1980, and November 1, 2010. The survival status of 959 consecutive patients with a first-ever TIA (n = 262), ischemic stroke (n = 606), or intracerebral hemorrhage (n = 91) was assessed as of November 1, 2012. Mean follow-up duration was 11.1 (SD, 8.7) years (median, 8.3 [interquartile range, 4.0-17.4]). Observed mortality was compared with the expected mortality, derived from mortality rates in the general population with similar age, sex, and calendar-year characteristics. MAIN OUTCOME MEASURES Cumulative 20-year mortality among 30-day survivors of stroke. RESULTS At the end of follow-up, 192 patients (20.0%) had died. Among 30-day survivors, cumulative 20-year risk of death was 24.9% (95% CI, 16.0%-33.7%) for TIA, 26.8% (95% CI, 21.9%-31.8%) for ischemic stroke, and 13.7% (95% CI, 3.6%-23.9%) for intracerebral hemorrhage. Observed mortality was increased compared with expected mortality (standardized mortality ratio [SMR], 2.6 [95% CI, 1.8-3.7] for TIA, 3.9 [95% CI, 3.2-4.7] for ischemic stroke, and 3.9 [95% CI, 1.9-7.2 for intracerebral hemorrhage, respectively). For ischemic stroke, cumulative 20-year mortality among 30-day survivors was higher in men than in women (33.7% [95% CI, 26.1%-41.3%] vs 19.8% [95% CI, 13.8%-25.9%]). The SMR was 4.3 (95% CI, 3.2-5.6) for women and 3.6 (95% CI, 2.8-4.6) for men. For all etiologic subtypes of ischemic stroke, observed mortality exceeded expected mortality. CONCLUSIONS AND RELEVANCE Among adults aged 18 through 50 years, 20-year mortality following acute stroke was relatively high compared with expected mortality. These findings may warrant further research evaluating secondary prevention strategies in these patients.

Long-term risk of recurrent vascular events after young stroke: The FUTURE study

Long‐term data on recurrent vascular events after young stroke are limited. Our objective was to examine the long‐term risk of recurrent vascular events after young stroke.

Long-Term Cognitive Impairment After First-Ever Ischemic Stroke in Young Adults

Background and Purpose— Up to 14% of all ischemic strokes occur in young adults (<50 years). Poststroke cognitive performance is a decisive determinant of their quality of life. However, virtually no studies report on cognition after young stroke, especially not on the long term. This long-term perspective is important because young patients have a long life expectancy during which they start forming a family, have an active social life, and make decisive career moves. We aimed to evaluate the long-term cognitive outcome. Methods— All consecutive patients between January 1, 1980, and November 1, 2010, with a first-ever young ischemic stroke were recruited for cognitive assessment, using a matched stroke-free population as a reference. Composite Z scores for 7 cognitive domains were calculated and the ANCOVA model was used (Bonferroni correction). A below average performance was defined as >1.0 SD below the age-adjusted mean of the controls and cognitive impairment as >1.5 SD. Results— Two hundred seventy-seven patients and 146 matched controls completed cognitive assessment (mean follow-up, 11.0 years, SD, 8.2; age, 50.9 years, SD, 10.3). Long-term cognitive outcome after an ischemic stroke was worse in most cognitive domains compared with a nonstroke population. Up to 50% of the patients had a below average performance or cognitive impairment. Deficits in processing speed, working memory, and attention were most common. Conclusions— Even 11 years after ischemic stroke in young adults, a substantial proportion of patients must cope with permanent cognitive deficits. These results have implications for information given to patients and rehabilitation services.

Post-stroke epilepsy in young adults: a long-term follow-up study.

Background Little is known about the incidence and risk of seizures after stroke in young adults. Especially in the young seizures might dramatically influence prognosis and quality of life. We therefore investigated the long-term incidence and risk of post-stroke epilepsy in young adults with a transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH). Methods and Findings We performed a prospective cohort study among 697 consecutive patients with a first-ever TIA, IS or ICH, aged 18–50 years, admitted to our hospital between 1-1-1980 till 1-11-2010. The occurrence of epilepsy was assessed by standardized questionnaires and verified by a neurologist. Cumulative risks were estimated with Kaplan-Meier analysis. Cox proportional hazard models were used to calculate relative risks. After mean follow-up of 9.1 years (SD 8.2), 79 (11.3%) patients developed post-stroke epilepsy and 39 patients (5.6%) developed epilepsy with recurrent seizures. Patients with an initial late seizure more often developed recurrent seizures than patients with an initial early seizure. Cumulative risk of epilepsy was 31%, 16% and 5% for patients with an ICH, IS and TIA respectively (Logrank test ICH and IS versus TIA p<0.001). Cumulative risk of epilepsy with recurrent seizures was 23%, 8% and 4% respectively (Logrank ICH versus IS p = 0.05, ICH versus TIA p<0.001, IS versus TIA p = 0.01). In addition a high NIHSS was a significant predictor of both epilepsy and epilepsy with recurrent seizures (HR 1.07, 95% CI 1.03–1.11 and 1.08, 95% CI 1.02–1.14). Conclusions Post-stroke epilepsy is much more common than previously thought. Especially patients with an ICH and a high NIHSS are at high risk. This calls upon the question whether a subgroup could be identified which benefits from the use of prophylactic antiepileptic medication. Future studies should be executed to investigate risk factors and the effect of post-stroke epilepsy on quality of life.

Epilepsy after TIA or stroke in young patients impairs long-term functional outcome The FUTURE Study

Objective: To determine the influence of poststroke epilepsy on long-term functional outcome in young stroke survivors. Methods: This study is a prospective cohort study among 537 stroke survivors with a first-ever TIA, ischemic stroke, or intracerebral hemorrhagic (ICH) stroke, aged 18 to 50 years. After a mean follow-up of 9.8 years (SD 8.4), we performed a follow-up assessment that included an evaluation for poststroke epilepsy and functional outcome. Odds ratios for poor outcome on the modified Rankin Scale (mRS) (score >2) and Instrumental Activities of Daily Living (IADL) (score <8) were calculated using logistic regression analysis. Results: Forty patients (12.7%) with ischemic stroke, 4 patients (2.2%) with TIA, and 10 patients (25.6%) with ICH developed poststroke epilepsy. Ischemic stroke patients with epilepsy more often had a poor functional outcome than those without, both on the mRS and IADL (mRS score >2: 27.5% vs 9.8%, p = 0.001; IADL <8: 27.8% vs 12.6%, p = 0.02). Epilepsy was not related to functional outcome in patients with TIA and ICH. Multiple regression analysis revealed that epilepsy was an independent predictor of poor functional outcome after ischemic stroke assessed by mRS (mRS score >2: odds ratio 3.38, 95% confidence interval 1.33–8.60). In contrast, there was no such relation for IADL. Conclusions: Epilepsy after stroke in young patients is a common problem that negatively affects functional outcome, even more than 10 years after ischemic stroke.

Poor Long-Term Functional Outcome After Stroke Among Adults Aged 18 to 50 Years: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) Study

Background and Purpose— Stroke in young adults has a dramatic effect on life; therefore, we investigated the long-term functional outcome after transient ischemic attack, ischemic stroke, or intracerebral hemorrhage in adults aged 18 to 50 years. Methods— We studied 722 young patients with first-ever stroke admitted between January 1, 1980, and November 1, 2010. Functional outcome was assessed by stroke subtype with the modified Rankin Scale and Instrumental Activities of Daily Living scale. Results— After a mean follow-up of 9.1 (SD, 8.2) years, 32.0% of all patients had a poor functional outcome (modified Rankin Scale, >2); for ischemic stroke, this was 36.5%, for intracerebral hemorrhage 49.3%, and for transient ischemic attack 16.8%. At follow-up, 10.8% of transient ischemic attack, 14.6% of ischemic stroke, and 18.2% of intracerebral hemorrhage patients had a poor outcome as assessed by Instrumental Activities of Daily Living (<8). Conclusions— Ten years after ischemic stroke or intracerebral hemorrhage in young adults, 1 of 8 survivors is still dependent in daily life.

Poststroke Epilepsy Is Associated With a High Mortality After a Stroke at Young Age Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation Study

Background and Purpose— Poststroke epilepsy is a common complication after a young stroke. We investigated the association between poststroke epilepsy and mortality. Methods— We performed a prospective cohort study among 631 patients with a first-ever transient ischemic attack or ischemic stroke, aged 18 to 50 years. Survival analysis and Cox proportional hazard analysis were used to estimate cumulative mortality and hazard ratios for patients with and without epilepsy. Results— After mean follow-up of 12.5 years (SD 8.6), 76 (12.0%) developed poststroke epilepsy. Case fatality was 27.4% for patients with poststroke epilepsy and 2.1% for those without. Poststroke epilepsy was associated with 30-day mortality (hazard ratio, 4.8; 95% confidence interval, 1.7–14.0) and long-term mortality (hazard ratio, 1.8; 95% confidence interval, 1.2–2.9). Conclusions— Epilepsy is a common problem after a young stroke and is associated with an increased short-term and long-term mortality.

Post-stroke fatigue and its association with poor functional outcome after stroke in young adults

Introduction Post-stroke fatigue negatively influences short-term functional outcome in older stroke survivors. In young adults, in the midst of their active working and family life, this influence may even be more pronounced. However, there are only few studies on this topic in young patients with stroke. Therefore, we investigated the long-term prevalence of post-stroke fatigue in patients with a young transient ischaemic attack (TIA) or ischaemic stroke and its association with functional outcome. Methods This study is part of a large cohort study among 511 stroke survivors with a first-ever TIA or ischaemic stroke, aged 18–50 years. After a mean follow-up of 9.8 (SD 8.4) years, we assessed the presence of fatigue with the fatigue subscale of the Checklist Individual Strength questionnaire and functional outcome. Prevalence of fatigue between young patients with stroke and 147 stroke-free sex-matched and age-matched controls was compared. ORs for poor functional outcome on modified Rankin Score (mRS>2) and Instrumental Activities of Daily Living (IADL<8) and cognitive performance were calculated using logistic regression analysis. Results Of the young patients with stroke, 41% experienced symptoms of fatigue, versus 18.4% in controls (p 0.0005). Fatigue was associated with a poor functional outcome, as assessed by the mRS (OR 4.0 (95% CI 1.6 to 9.6), IADL (OR 2.2 (95% CI 1.1 to 4.6), and impairment in speed of information processing (OR 2.2 (95% CI 1.3 to 3.9). Conclusions Fatigue was very common in young stroke survivors and was associated with a poor functional outcome, even after almost a decade of follow-up.

Ipsilateral hippocampal atrophy is associated with long‐term memory dysfunction after ischemic stroke in young adults

Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However, neurodegenerative disease, such as amyloid pathology, is generally absent at young age. Accumulating evidence suggests that infarction itself may cause secondary neurodegeneration in remote areas. Therefore, we investigated the relation between long‐term memory performance and hippocampal volume in young patients with first‐ever ischemic stroke. We studied all consecutive first‐ever ischemic stroke patients, aged 18–50 years, admitted to our academic hospital center between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87 stroke‐free controls. Hippocampal volume was determined using FSL‐FIRST, with manual correction. On average 10 years after stroke, patients had smaller ipsilateral hippocampal volumes compared with controls after left‐hemispheric stroke (5.4%) and right‐hemispheric stroke (7.7%), with most apparent memory dysfunctioning after left‐hemispheric stroke. A larger hemispheric stroke was associated with a smaller ipsilateral hippocampal volume (b=−0.003, P<0.0001). Longer follow‐up duration was associated with smaller ipsilateral hippocampal volume after left‐hemispheric stroke (b=−0.028 ml, P=0.002) and right‐hemispheric stroke (b=−0.015 ml, P=0.03). Our results suggest that infarction is associated with remote injury to the hippocampus, which may lower or expedite the threshold for cognitive impairment or even dementia later in life. Hum Brain Mapp 36:2432–2442, 2015.

Remote lower white matter integrity increases the risk of long-term cognitive impairment after ischemic stroke in young adults

Background and Purpose— Poststroke cognitive impairment occurs frequently in young patients with ischemic stroke (18 through 50 years of age). Accumulating data suggest that stroke is associated with lower white matter integrity remote from the stroke impact area, which might explain why some patients have good long-term cognitive outcome and others do not. Given the life expectancy of decades in young patients, we therefore investigated remote white matter in relation to long-term cognitive function. Methods— We included all consecutive first-ever ischemic stroke patients, left/right hemisphere, without recurrent stroke or transient ischemic attack during follow-up, aged 18 through 50 years, admitted to our university medical center between 1980 and 2010. One hundred seventeen patients underwent magnetic resonance imaging scanning including a T1-weighted scan, a diffusion tensor imaging scan, and completed a neuropsychological assessment. Patients were compared with a matched stroke-free control group (age, sex, and education matched). Cognitive impairment was defined as >1.5 SD below the mean cognitive index score of controls and no cognitive impairment as ⩽1 SD. Tract-Based Spatial Statistics was used to assess the white matter integrity (fractional anisotropy and mean diffusivity). Results— About 11 years after ischemic stroke, lower remote white matter integrity was associated with a worse long-term cognitive performance. A lower remote white matter integrity, even in the contralesional hemisphere, was observed in cognitively impaired patients (n=25) compared with cognitively unimpaired patients (n=71). Conclusions— These findings indicate that although stroke has an acute onset, it might have long lasting effects on remote white matter integrity and thereby increases the risk of long-term cognitive impairment.