Frank G. van Rooij

Background and ObjectivesPoststroke fatigue (PSF) in young adults is a common symptom with devastating consequences. Data on the prevalence, trajectory, and prognostic factors of PSF in young adult...

Background: Atrial fibrillation (AF) is an important risk factor for stroke with increasing prevalence and incidence, especially in older people. However, prevalence and risk factors of AF in young patients with stroke remain unclear. The aim of this study was to determine the prevalence and factors associated with AF in young patients with stroke. Methods: We included patients with first‐ever ischemic stroke (18–49 years) with imaging‐confirmed ischemia from the ODYSSEY (Observational Dutch Young Symptomatic Stroke) study. All patients underwent cardiac evaluation, including ECG, cardiac rhythm monitoring, and echocardiography. Results: Of 1259 patients (mean age 41.8 years, SD 7.5, 47.3% female), 13 patients (1%) had a known history of AF. Additionally, AF was found in 19 patients (1.5%), predominantly detected during telemetric observation within first 24 hours. Patients with AF had higher National Institutes of Health Stroke Scale scores at admission (adjusted odds ratio [aOR], 1.1 [95% CI, 1.0–1.2]) and more frequent history of cardiac pathology (aOR, 5.0 [95% CI, 2.2–10.9]). The most important factors associated with AF were history of heart valve abnormalities (OR, 6.5 [95% CI, 2.1–16.7]) and hypertension (aOR, 2.5 [95% CI, 1.1–6.1]). Recurrence of ischemic stroke occurred more frequently in patients with AF (aOR, 2.5 [95% CI, 1.0–5.9], adjusted hazard ratio, 2.2 [95% CI, 1.0–4.7]) compared with those without AF. Conclusions: Approximately 2.5% of young patients with stroke have AF, with about half previously known and half detected through rhythm observation, all within 24 hours. Furthermore, most patients with AF had structural cardiac pathology, especially heart valve abnormalities, suggesting an increased risk of developing AF. Patients with AF had more severe strokes and higher recurrence of vascular events.

Introduction: Limited data exist on cognitive performance and return to work after ischemic stroke, especially in patients under 50 years. We investigated whether cognitive performance in the subacute phase after ischemic stroke in young adults was associated with unemployment and the inability to retain their jobs among those who returned to work. Patients and methods: We conducted a multicenter prospective cohort study between 2013 and 2021, enrolling patients aged 18–49 years with first-ever ischemic stroke. Cognitive assessments were performed within 6 months following the index event, covering seven cognitive domains. We categorized patients with cognitive impairment (Z-score < −1.5 on a domain) and as no/mild or major vascular cognitive disorder (VCD; Z-score < −2.0 in one or more domains). Cognitive performance and other predefined characteristics were chosen to identify factors associated with unemployment and, among patients who returned to work, the inability to maintain employment. Results: Of 525 patients (median age 44.3 [IQR 38.0–47.4] years; 243 women [46.3%]); median follow-up of 6.6 [IQR 4.5–8.2] years), 426 patients (81.1%) returned to work. Sixty-five patients (15.3%) were unable to maintain employment. In multivariable logistic regression analysis, major VCD (OR = 2.0; 95% CI 1.3–3.0; p = 0.002) and cognitive impairment in processing speed (OR = 2.0; 95% CI 1.3–3.3; p = 0.004) were associated with unemployment, but not with the inability to maintain employment. Discussion and conclusion: In young patients after a first-ever ischemic stroke, major VCD and impaired processing speed in the subacute phase after stroke were independently associated with unemployment, but not with the inability to maintain employment.

Background: Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population can convert into a PFO that causes stroke in a few. Recent studies reported a significant association between certain trigger factors and ischemic stroke in young adults. This study aims to investigate these triggers in PFO-associated stroke. Methods: The ODYSSEY study, a multicenter prospective cohort study between 2013 and 2021, included patients aged 18–49 years experiencing their first-ever ischemic event. Participants completed a questionnaire about exposure to potential trigger factors. A case-crossover design was used to assess the relative risks (RR) with 95% confidence intervals (95% CI). The primary outcome was the RR of potential trigger factors for PFO-associated stroke. Results: Overall, 1043 patients completed the questionnaire and had an ischemic stroke, of which 124 patients had a PFO-associated stroke (median age 42.1 years, 45.2% men). For patients with PFO-associated stroke, the RR was 26.0 (95% CI 8.0–128.2) for fever, 24.2 (95% CI 8.5–68.7) for flu-like disease, and 3.31 (95% CI 2.2–5.1) for vigorous exercise. Conclusion: In conclusion, flu-like disease, fever, and vigorous exercise may convert an asymptomatic PFO into a stroke-causing PFO in young adults. Data access statement: The raw and anonymized data used in this study can be made available to other researchers on request. Written proposals can be addressed to the corresponding author and will be assessed by the ODYSSEY investigators for appropriateness of use, and a data sharing agreement in accordance with Dutch regulations will be put in place before data are shared.

Background Limited data exists on cognitive recovery in young stroke patients. We aimed to investigate the longitudinal course of cognitive performance during the first year after stroke at young age and identify predictors for cognitive recovery. Methods We conducted a multicentre prospective cohort study between 2013 and 2021, enrolling patients aged 18–49 years with first-ever ischaemic stroke. Cognitive assessments were performed within 6 months and after 1 year following the index event, covering seven cognitive domains. Composite Z-scores using normative data determined cognitive impairment (Z-score<−1.5). A Reliable Change Index (RCI) assessed cognitive recovery (RCI>1.96) or decline (RCI<−1.96). Results 393 patients (median age 44.3 years, IQR 38.4–47.2) completed cognitive assessments with a median time interval of 403 days (IQR 364–474) between assessments. Based on RCI, a similar proportion of patients showed improvement and decline in each cognitive domain, while the majority exhibited no cognitive change. Among cognitively impaired patients at baseline, improvements were observed in processing speed (23.1%), visuoconstruction (40.1%) and executive functioning (20.0%). Younger age was associated with better cognitive recovery in visuoconstruction, and larger lesion volume was related to cognitive recovery in processing speed. No other predictors for cognitive recovery were identified. Conclusions Cognitive impairment remains prevalent in young stroke even 1 year after the event. Most patients showed no cognitive change, however, recovery may have occurred in the early weeks after stroke, which was not assessed in our study. Among initially cognitively impaired patients, cognitive recovery is observed in processing speed, visuoconstruction and executive functioning. It is still not possible to predict cognitive recovery in individual patients.

Background: Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current classification systems (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] and atherosclerosis, small vessel disease, cardiac pathology, other causes, dissection [ASCOD]). The aim was to identify risk factors and leads for (new) causes of cryptogenic ischemic stroke in young adults, using the pediatric classification system from the IPSS study (International Pediatric Stroke Study). Methods: This is a multicenter prospective cohort study conducted in 17 hospitals in the Netherlands, consisting of 1322 patients aged 18 to 49 years with first-ever, imaging confirmed, ischemic stroke between 2013 and 2021. The main outcome was distribution of risk factors according to IPSS classification in patients with cryptogenic and noncryptogenic stroke according to the TOAST and ASCOD classification. Results: The median age was 44.2 years, and 697 (52.7%) were men. Of these 1322 patients, 333 (25.2%) had a cryptogenic stroke according to the TOAST classification. Additional classification using the ASCOD criteria reduced the number patients with cryptogenic stroke from 333 to 260 (19.7%). When risk factors according to the IPSS were taken into account, the number of patients with no potential cause or risk factor for stroke reduced to 10 (0.8%). Conclusions: Among young adults aged 18 to 49 years with a cryptogenic ischemic stroke according to the TOAST classification, risk factors for stroke are highly prevalent. Using a pediatric classification system provides new leads for the possible causes in cryptogenic stroke, and could potentially lead to more tailored treatment for young individuals with stroke.

Background and Objectives: Causes of stroke in young adults differ from those in the elderly, and in a larger percentage no cause can be determined. To gain more insight in the etiology of (cryptogenic) stroke in the young, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role. Methods: Patients aged 18-49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17 participating centers in the Netherlands completed a questionnaire about exposure to nine potential trigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used to assess relative risks (RR) with 95% confidence intervals (95% CI) by the Mantel-Haenszel case-crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologic subgroups of ischemic stroke. Results: 1146 patients completed the questionnaire (1043 patients with an ischemic stroke, 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke an increased risk emerged within one hour of cola consumption (RR 2.0, 95% CI 1.5-2.8) and vigorous physical exercise (RR 2.6, 95% CI 2.2-3.0), within two hours after sexual activity (RR 2.4, 95% CI 1.6-3.5), within 4 hours after illicit drug use (RR 2.8, 95% CI 1.7-4.9) and within 24 hours after fever or flu-like disease (RR 14.1, 95% CI 10.5-31.2; RR 13.9, 95% CI 8.9-21.9). Four trigger factors increased the risk of other determined and cryptogenic ischemic stroke, three that of cardio-embolic stroke, two that of large vessel atherosclerosis and likely atherothrombotic stroke combined and stroke with multiple causes, none that of stroke due to small vessel disease. Discussion: We identified cola consumption, vigorous physical exercise, sexual activity, illicit drug use, fever- and flu-like disease as potential trigger factors for stroke in the young, and found differences in type and number of trigger factors associated with different etiologic subgroups of ischemic stroke. These findings might help in better understanding the pathophysiological mechanisms of (cryptogenic) stroke in the young.

Introduction: Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of plexus anesthesia or general anesthesia in traditional carotid endarterectomy is, to date, not unequivocally proven to be superior to one other. A systematic review was needed for evaluation of benefits and harms to determine which technique, plexus anesthesia or general anesthesia is more effective for traditional carotid endarterectomy in patients with symptomatic carotid stenosis. Methods: The review was conducted according to our protocol following the recommendations of Cochrane and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Searches were updated on the October 1, 2020. We did not find any randomized clinical trial comparing plexus anesthesia and general anesthesia in carotid endarterectomy with patch angioplasty matching our protocol criteria in patients with a symptomatic and significant (≥50%) carotid stenosis. Conclusions: Based on the current, high risk of bias evidence, we concluded there is a need for new randomized clinical trials with overall low risk of bias comparing plexus anesthesia with general anesthesia in carotid endarterectomy with patch closure of the arterial wall in patients with a symptomatic and significant (≥50%) stenosis of the internal carotid artery. Protocol unique identification number (UIN): CRD42019139913, (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139913);

Background and Purpose—: Although by definition transient, both transient ischemic attack (TIA) and transient neurological attack (TNA) are associated with cognitive impairment. Determinants and course of cognitive function afterward are, however, unclear. We prospectively determined cognitive performance after TIA and TNA in relation to clinical diagnosis and diffusion-weighted imaging (DWI) results. Methods—: TIA and TNA patients aged ≥45 years without prior stroke or dementia underwent comprehensive cognitive assessment and magnetic resonance imaging within 7 days after the qualifying event. Cognitive tests were repeated after 6 months. Domain-specific compound z scores based on the baseline mean and SD were calculated. Repeated-measures analysis was used to test for differences in domain-specific cognitive performance over time between DWI-positive and DWI-negative patients, as well as between TIA and TNA patients. Results—: One hundred twenty-one patients were included (mean age (SD), 64.6 years (9.2 years), 60% TIA and 40% TNA) of whom 32 (26%) had a DWI lesion. Executive function performance decreased over time (mean change in compound score −0.23; P =0.01 adjusted for age, sex, education), whereas attention improved (0.11; P =0.02), and information processing speed and episodic memory remained unchanged. Patients with a DWI lesion had worse executive function at baseline than those without a DWI lesion (compound scores −0.26 versus 0.08; P =0.048), which persisted throughout the study period ( P =0.04). Clinical diagnosis (TIA or TNA) was not related to cognitive function over time. Conclusions—: Executive function declines during the first 6 months after TIA or TNA. Patients with an initial DWI lesion have persisting worse executive function than those without.