Increased Risk of Pregnancy Complications After Stroke: The FUTURE Study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation).

BACKGROUND AND PURPOSE: The study goal was to investigate the prevalence of pregnancy complications and pregnancy loss in women before, during, and after young ischemic stroke/transient ischemic attack. METHODS: In the FUTURE study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation), a prospective young stroke study, we assessed the occurrence of pregnancy, miscarriages, and pregnancy complications in 223 women aged 18 to 50 years with a first-ever ischemic stroke/transient ischemic attack. Pregnancy complications (gestational hypertension, diabetes mellitus, preeclampsia, and hemolysis, elevated liver enzymes, low platelet count syndrome) were assessed before, during, and after stroke using standardized questionnaires. Primary outcome was occurrence of pregnancy complications and the rate of pregnancy loss compared with the Dutch population. Secondary outcome was the risk of recurrent vascular events after stroke, stratified by a history of hypertensive disorder in pregnancy. RESULTS: Data were available for 213 patients. Mean age at event was 39.6 years (SD=7.8) and mean follow-up 9.5 years (SD=8.5). Miscarriages occurred in 35.2% and fetal death in 6.2% versus 13.5% and 0.9% in the Dutch population, respectively (P<0.05). In nulliparous women after stroke (n=22), in comparison with Dutch population, there was a high prevalence of hypertensive disorders in pregnancy (33.3 versus 12.2%; P<0.05), hemolysis, elevated liver enzymes, low platelet count syndrome (9.5 versus 0.5%; P<0.05), and early preterm delivery <32 weeks (9.0 versus 1.4%; P<0.05). In primi/multiparous women (n=141) after stroke, 29 events occurred (20-year cumulative risk 35.2%; 95% confidence interval, 21.3-49.0), none during subsequent pregnancies, and a history of a hypertensive disorder in pregnancy did not modify this risk (log-rank P=0.62). CONCLUSIONS: When compared with the general population, women with young stroke show higher rates of pregnancy loss throughout their lives. Also, after stroke, nulliparous women more frequently experienced serious pregnancy complications.

Prothrombotic factors do not increase the risk of recurrent ischemic events after cryptogenic stroke at young age: the FUTURE study.

BACKGROUND: The role of hypercoagulable states and preceding infections in the etiology of young stroke and their role in developing recurrent ischemic events remains unclear. Our aim is to determine the prevalence of these conditions in patients with cryptogenic stroke at young age and to assess the long-term risk of recurrent ischemic events in patients with and without a hypercoagulable state or a recent pre-stroke infection with Borrelia or Syphilis. PATIENTS AND METHODS: We prospectively included patients with a first-ever transient ischemic attack or ischemic stroke, aged 18-50, admitted to our hospital between 1995 and 2010. A retrospective analysis was conducted of prothrombotic factors and preceding infections. Outcome was recurrent ischemic events. RESULTS: Prevalence of prothrombotic factors did not significantly differ between patients with a cryptogenic stroke and with an identified cause (24/120 (20.0%) and 32/174 (18.4%) respectively). In patients with a cryptogenic stroke the long-term risk [mean follow-up of 8.9 years (SD 4.6)] of any recurrent ischemic event or recurrent cerebral ischemia did not significantly differ between patients with and without a hypercoagulable state or a recent infection. In patients with a cryptogenic stroke 15-years cumulative risk of any recurrent ischemic event was 24 and 23% in patients with and without any prothrombotic factor respectively. CONCLUSIONS: The prevalence of prothrombotic factors and preceding infections did not significantly differ between stroke patients with a cryptogenic versus an identified cause of stroke and neither is significantly associated with an increased risk of recurrent ischemic events after cryptogenic stroke.

Spatial Neglect Predicts Upper Limb Use in the Activities of Daily Living.

BACKGROUND AND PURPOSE: Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL. METHODS: Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment. RESULTS: Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later. CONCLUSIONS: This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients.

Effect of Formal Education on Vascular Cognitive Impairment after Stroke: A Meta-analysis and Study in Young-Stroke Patients.

OBJECTIVES: The extent of vascular cognitive impairment (VCI) after stroke varies greatly across individuals, even when the same amount of brain damage is present. Education level is a potentially protective factor explaining these differences, but results on its effects on VCI are inconclusive. METHODS: First, we performed a meta-analysis on formal education and VCI, identifying 21 studies (N=7770). Second, we examined the effect of formal education on VCI in young-stroke patients who were cognitively assessed on average 11.0 (SD=8.2) years post-stroke (the FUTURE study cohort). The total sample consisted of 277 young-stroke patients with a mean age at follow-up 50.9 (SD=10.3). Age and education-adjusted expected scores were computed using 146 matched stroke-free controls. RESULTS: The meta-analysis showed an overall effect size (z') of 0.25 (95% confidence interval [0.18-0.31]), indicating that formal education level had a small to medium effect on VCI. Analyses of the FUTURE data showed that the effect of education on post-stroke executive dysfunction was mediated by age (ß age -0.015; p<.05). Below-average performance in the attention domain was more frequent for low-education patients (χ2(2)=9.8; p<.05). CONCLUSIONS: While education level was found to be related to post-stroke VCI in previous research, the effects were small. Further analysis in a large stroke cohort showed that these education effects were fully mediated by age, even in relatively young stroke patients. Education level in and of itself does not appear to be a valid indicator of cognitive reserve. Multi-indicator methods may be more valid, but have not been studied in relation to VCI. (JINS, 2017, 23, 223-238).

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.

Kidney Dysfunction Increases Mortality and Incident Events after Young Stroke: The FUTURE Study.

BACKGROUND: In about 30% of young stroke patients, no cause can be identified. In elderly patients, kidney dysfunction has been suggested as a contributing risk factor for mortality as well as stroke. There are hypotheses that novel non-traditional risk factors, like chronic inflammation and oxidative stress, are involved in chronic kidney disease, affecting the cerebral microvasculature that would in turn lead to stroke. Our objective is to investigate the influence of kidney dysfunction on long-term mortality and incident vascular events after stroke in young adults aged 18 through 50 and if this relationship would be independent of other cardiovascular risk factors. METHODS: We prospectively included 460 young stroke patients with an ischemic stroke or transient ischemic attack admitted to our department between January 1, 1980 and November 1, 2010. Follow-up was done between 2014 and 2015. Estimated glomerular filtration rate (eGFR) was calculated from baseline creatinine levels and was divided in 3 subgroups: eGFR <60, 60-120 and >120 ml/min/1.73 m2. Cox proportional hazard models were used to determine the effect of kidney dysfunction on mortality and incident vascular events, adjusting for cardiovascular risk factors. RESULTS: An eGFR <60 (HR 4.6; 95% CI 2.6-8.2) was associated with an increased risk of death and an increased risk of incident stroke (HR 4.1; 95% CI 1.9-9.0) independent of cardiovascular risk factors, but it was not associated with other vascular events. The point estimate for the 15-year cumulative mortality was 70% (95% CI 46-94) for patients with a low eGFR, 24% (95% CI 18-30) for patients with a normal eGFR and 30% (95% CI 12-48) for patients with a high eGFR. The point estimate for the 15-year cumulative risk of incident stroke was 45% (95% CI 16-74) for patients with a low eGFR, 13% (95% CI 9-17) for patients with a normal eGFR and 8% (95% CI 0-18) for patients with a high eGFR. CONCLUSIONS: Kidney dysfunction is related to long-term mortality and stroke recurrence, but not to incident cardiovascular disease, on average 11 years after young stroke. This warrants a more intensive follow-up of young stroke patients with signs of kidney dysfunction in the early phase. In addition, the clear association between kidney dysfunction and incident stroke seen in our young stroke population might be a first step in the recognition of kidney dysfunction as a new risk factor for the development of stroke at young age. Also, it can lead to new insights in the etiological differences between cardiovascular and cerebrovascular disease.

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.

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.

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. OR's 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.

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.

Persistent cognitive impairment after transient ischemic attack.

BACKGROUND AND PURPOSE: By definition, the symptoms of a transient ischemic attack (TIA) subside completely within 24 hours. Imaging studies show signs of persistent ischemic tissue damage in a substantial amount of patients with TIA. Cerebral infarction can cause permanent cognitive impairment. Whether permanent cognitive impairment occurs after TIA is unclear, as is its profile. METHODS: Patients with TIA aged 45 to 65 years without prior stroke or dementia underwent comprehensive neuropsychological testing within 3 months. Z scores per cognitive domain were obtained, based on the mean of a control group within the same age range. Cognitive impairment was defined as a domain z score <-1.65. Patients underwent either computed tomography or MRI brain imaging. RESULTS: One hundred seven patients with TIA (63% women, mean age, 56.6 years) were included and compared with 81 controls (56% women, mean age, 52.9 years). Patients performed worse on all cognitive domains except episodic memory. Working memory (25%), attention (22%), and information processing speed (16%) were most frequently impaired and more often than in the control group (age- and sex-adjusted odds ratios, respectively, 22.5 [95% confidence interval, 2.9-174.3], 6.8 [1.9-24.3], 7.1 [1.5-32.5]). More than 35% of patients with TIA had impairment of ≥1 cognitive domain. Presence of silent brain infarcts was related to worse executive functioning but did not explain the whole relationship between TIA and cognitive impairment. CONCLUSIONS: More than a third of patients with TIA have impairment of ≥1 cognitive domain within 3 months after their TIA. The affected domains fit in the vascular cognitive impairment profile.

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

OBJECTIVE: 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. METHODS: We prospectively included 724 consecutive patients with a first-ever transient ischemic attack (TIA), ischemic stroke, or intracerebral hemorrhage (ICH), aged 18 to 50 years, admitted to our hospital between January 1, 1980 and November 1, 2010. Outcomes were (1) stroke; (2) myocardial infarction or cardiac or peripheral arterial revascularization procedures; or (3) composite event of these, whichever occurred first. RESULTS: After a mean follow-up of 9.1 years (standard deviation = 8.2, range = 0-31.0), 142 patients (19.6%) had at least 1 recurrent vascular event. Cumulative 20-year risk of stroke was 17.3% (95% confidence interval [CI] = 9.5-25.1) after TIA, 19.4% (95% [CI] = 14.6-24.3) after ischemic stroke, and 9.8% (95% CI = 1.0-18.7) after ICH. Cumulative 20-year risk of any vascular event was 27.7% (95% CI = 18.5-37.0) after TIA and 32.8% (95% CI = 26.7-38.9) after ischemic stroke. Age and male sex were associated with other arterial events, but not with stroke. Among TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes, adjusted for age, sex, and decennium of inclusion, atherothrombotic stroke, cardioembolic stroke, and lacunar stroke were associated with recurrent stroke (hazard ratio [HR] = 2.72, 95% CI = 1.34-5.52; HR = 2.49, 95% CI = 1.23-5.07; and HR = 2.92, 95% CI = 1.45-5.88, respectively). INTERPRETATION: Patients with young stroke remain at substantial risk of recurrent vascular events for decades, suggesting that the underlying disease that caused stroke at a young age continues to put these patients at a high risk for vascular disease throughout their lives.

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.

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.

Profiling Daily Life Performance Recovery in the Early Subacute Phase After Stroke Using a Graphical Modeling Approach.

Background Laboratory-based assessments have shown that stroke recovery is heterogeneous between patients and affected domains such as motor and language function. However, laboratory-based assessments are not ecologically valid and do not necessarily reflect patients' daily life performance. Therefore, we aimed to give an innovative view on stroke recovery by profiling daily life performance recovery across domains in patients with early subacute stroke and determine their interrelatedness, taking stroke localization into account. Methods and Results Daily life performance was observed at neurorehabilitation admission and weekly thereafter until discharge, using a scale containing 7 daily life domains. Graphical modeling was applied to investigate the conditional independence between recovery of these domains depending on stroke localization. There were 592 patients analyzed. Four clusters of interrelated domains were identified within the first 6 weeks poststroke. The first cluster included recovery in learning and applying knowledge, general tasks and demands, and domestic life. The second cluster comprised recovery in self-care and general tasks and demands. The third cluster included recovery in mobility and self-care; it incorporated interpersonal interactions and relationships in left supratentorial stroke, and learning and applying knowledge in right supratentorial stroke. The final cluster included only communication recovery. Conclusions Daily life recovery dynamics early poststroke show that although impairments in body functions are anatomically determined, their impact on performance is comparable. Second, some, but by no means all, domains show an interrelated recovery. Domains requiring cognitive abilities are especially interrelated and seem to be essential for concomitant recovery in mobility and domestic life.

Functional brain connectivity in young adults with post-stroke epilepsy.

Approximately 1 in 10 young stroke patients (18-50 years) will develop post-stroke epilepsy, which is associated with cognitive impairment. While previous studies have shown altered brain connectivity in patients with epilepsy, little is however known about the changes in functional brain connectivity in young stroke patients with post-stroke epilepsy and their relationship with cognitive impairment. Therefore, we aimed to investigate whether young ischaemic stroke patients have altered functional networks and whether this alteration is related to cognitive impairment. We included 164 participants with a first-ever cerebral infarction at young age (18-50 years), along with 77 age- and sex-matched controls, from the Follow-Up of Transient Ischemic Attack and Stroke patients and Unelucidated Risk Factor Evaluation study. All participants underwent neuropsychological testing and resting-state functional MRI to generate functional connectivity networks. At follow-up (10.5 years after the index event), 23 participants developed post-stroke epilepsy. Graph theoretical analysis revealed functional network reorganization in participants with post-stroke epilepsy, in whom a weaker (i.e. network strength), less-integrated (i.e. global efficiency) and less-segregated (i.e. clustering coefficient and local efficiency) functional network was observed compared with the participants without post-stroke epilepsy group and the controls (P < 0.05). Regional analysis showed a trend towards decreased clustering coefficient, local efficiency and nodal efficiency in contralesional brain regions, including the caudal anterior cingulate cortex, posterior cingulate cortex, precuneus, superior frontal gyrus and insula in participants with post-stroke epilepsy compared with those without post-stroke epilepsy. Furthermore, participants with post-stroke epilepsy more often had impairment in the processing speed domain than the group without post-stroke epilepsy, in whom the network properties of the precuneus were positively associated with processing speed performance. Our findings suggest that post-stroke epilepsy is associated with functional reorganization of the brain network after stroke that is characterized by a weaker, less-integrated and less-segregated brain network in young ischaemic stroke patients compared with patients without post-stroke epilepsy. The contralesional brain regions, which are mostly considered as hub regions, might be particularly involved in the altered functional network and may contribute to cognitive impairment in post-stroke epilepsy patients. Overall, our findings provide additional evidence for a potential role of disrupted functional network as underlying pathophysiological mechanism for cognitive impairment in patients with post-stroke epilepsy.

Demographic and geographic vascular risk factor differences in European young adults with ischemic stroke: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. METHODS: We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. RESULTS: In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. CONCLUSIONS: Primary preventive strategies for ischemic stroke in young adults-having high rate of modifiable risk factors-should be targeted according to sex and age at continental level.

Visual Neglect after PICA Stroke-A Case Study.

After cerebellar stroke, cognition can be impaired, as described within the framework of the so-called Cerebellar Cognitive Affective Syndrome (CCAS). However, it remains unclear whether visual neglect can also be part of CCAS. We describe the case of a patient with a subacute cerebellar stroke after thrombosis of the left posterior inferior cerebellar artery (PICA), who showed a left-sided visual neglect, indicating that the cerebellum also has a modulatory function on visual attention. The neglect, however, was mild and only detectable when using the sensitive neuro-psychological Five-Point Test as well as video-oculography assessment, yet remained unnoticed when evaluated with common neglect-specific paper-pencil tests. Three weeks later, follow-up assessments revealed an amelioration of neglect symptoms. Therefore, these findings suggest that visual neglect may be a part of CCAS, but that the choice of neglect assessments and the time delay since stroke onset may be crucial. Although the exact underlying pathophysiological mechanisms remain unclear, we propose cerebellar-cerebral diaschisis as a possible explanation of why neglect can occur on the ipsilateral side. Further research applying sensitive assessment tools at different post-stroke stages is needed to investigate the incidence, lesion correlates, and pathophysiology of neglect after cerebellar lesions.

Neuroimaging Parameters Are Not Associated With Chronic Post-stroke Fatigue in Young Stroke Patients.

Introduction: Post-stroke fatigue is frequently present in young adults, but its underlying mechanism is still unclear. The aim of the study was to investigate the association between lesion location, network efficiency and chronic post-stroke fatigue based on voxel-based lesion-symptom mapping and structural network connectivity analysis. Patients and Methods: One hundred and thirty five young patients, aged 18-50 years, with a first-ever transient ischemic attack or cerebral infarction from the Follow-Up of Transient ischemic attack and stroke patients and Unelucidated Risk factor Evaluation (FUTURE) study, underwent 1.5T MRI and were assessed for fatigue using the self-report Checklist Individual Strength. Stroke lesions were manually segmented, and structural network efficiency was calculated using the diffusion MRI-based brain networks and graph theory for each patient. Univariate and multivariate analyses was performed to study the associations between MRI parameters and chronic post-stroke fatigue. In addition, we used voxel-based lesion-symptom mapping to analyze the relationship between the lesion location and chronic post-stroke fatigue. Results: Mean age at index event was 39.0 years (SD ± 8.2), and mean follow-up duration was 11.0 years (SD ± 8.0). 50 patients (37%) had post-stroke fatigue. Voxel-based lesion-symptom mapping showed no significant relation between stroke lesions and the presence of chronic post-stroke fatigue. Furthermore, there were no significant associations between the lesion size or network efficiency, and the presence of chronic post-stroke fatigue. Discussion: We did not find any association between stroke characteristics (lesion location and size) and chronic post-stroke fatigue (CIS20-R), nor associations between structural brain network connectivity and post-stroke fatigue on the long term in young stroke patients.

Long-term Risk of Bleeding and Ischemic Events After Ischemic Stroke or Transient Ischemic Attack in Young Adults.

BACKGROUND AND OBJECTIVES: Guidelines recommend antithrombotic medication as secondary prevention for patients with ischemic stroke or transient ischemic attack (TIA) at young age based on results from trials in older patients. We investigated the long-term risk of bleeding and ischemic events in young patients after ischemic stroke or TIA. METHODS: We included 30-day survivors of first-ever ischemic stroke or TIA aged 18-50 years from the Follow-Up of TIA and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study of stroke at young age. We obtained information on recurrent ischemia based on structured data collection from 1995 until 2014 as part of the FUTURE study follow-up, complemented with information on any bleeding and ischemic events by retrospective chart review from baseline until last medical consultation or June 2020. Primary outcome was any bleeding; secondary outcome any ischemic event during follow-up. Both were stratified for sex, age, etiology, and use of antithrombotic medication at discharge. Bleeding and ischemic events were classified according to location and bleeding events also by severity. RESULTS: We included 544 patients (56.1% women, median age of 42.2; interquartile range [IQR] 36.5-46.7 years) with a median follow-up of 9.6 (IQR 2.5-14.3) years. Ten-year cumulative risk of any bleeding event was 21.8% (95% CI 17.4-26.0) and 33.9% (95% CI 28.3-37.5) of any ischemic event. Risk of bleeding was higher in women with a cumulative risk of 28.2% (95% CI 21.6-34.3) vs 13.7% (95% CI 8.2-18.9) in men (p < 0.01), mainly because of gynecologic bleeds. Female sex (p < 0.001) and age between 40 and 49 years (p = 0.04) were independent predictors of bleeding. DISCUSSION: Young patients after ischemic stroke or TIA have a substantial long-term risk of both bleeding (especially women) and ischemic events. Future studies should investigate the effects of long-term antithrombotics in young patients, taking into account the risk of bleeding complications.