Search

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 ObjectivesCauses of stroke in young adults differ from those in the elderly individuals, and in a larger percentage, no cause can be determined. To gain more insight into the etiology of (cryptogenic) stroke in the young population, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role.MethodsPatients 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 9 potential trigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used to assess relative risks (RRs) with 95% confidence intervals (95% CIs) by the Mantel-Haenszel case-crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologic subgroups of ischemic stroke.ResultsOne thousand one hundred forty-six patients completed the questionnaire (1,043 patients with an ischemic stroke and 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke, an increased risk emerged within 1 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 2 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, 3 that of cardioembolic stroke, 2 that of large vessel atherosclerosis and likely atherothrombotic stroke combined and stroke with multiple causes, and none that of stroke due to small vessel disease.DiscussionWe 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 population and found differences in the type and number of trigger factors associated with different etiologic subgroups of ischemic stroke. These findings might help in better understanding the pathophysiologic mechanisms of (cryptogenic) stroke in the young population.

Brody disease is a rare myopathy characterized by exercise-induced muscle stiffness caused by mutations in the ATP2A1 gene. In the largest cohort of Brody patients to date, Molenaar et al. clarify the phenotype and diagnostic possibilities to help improve understanding and recognition of this distinct myopathy., Brody disease is an autosomal recessive myopathy characterized by exercise-induced muscle stiffness due to mutations in the ATP2A1 gene. Almost 50 years after the initial case presentation, only 18 patients have been reported and many questions regarding the clinical phenotype and results of ancillary investigations remain unanswered, likely leading to incomplete recognition and consequently under-diagnosis. Additionally, little is known about the natural history of the disorder, genotype-phenotype correlations, and the effects of symptomatic treatment. We studied the largest cohort of Brody disease patients to date (n = 40), consisting of 22 new patients (19 novel mutations) and all 18 previously published patients. This observational study shows that the main feature of Brody disease is an exercise-induced muscle stiffness of the limbs, and often of the eyelids. Onset begins in childhood and there was no or only mild progression of symptoms over time. Four patients had episodes resembling malignant hyperthermia. The key finding at physical examination was delayed relaxation after repetitive contractions. Additionally, no atrophy was seen, muscle strength was generally preserved, and some patients had a remarkable athletic build. Symptomatic treatment was mostly ineffective or produced unacceptable side effects. EMG showed silent contractures in approximately half of the patients and no myotonia. Creatine kinase was normal or mildly elevated, and muscle biopsy showed mild myopathic changes with selective type II atrophy. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity was reduced and western blot analysis showed decreased or absent SERCA1 protein. Based on this cohort, we conclude that Brody disease should be considered in cases of exercise-induced muscle stiffness. When physical examination shows delayed relaxation, and there are no myotonic discharges at electromyography, we recommend direct sequencing of the ATP2A1 gene or next generation sequencing with a myopathy panel. Aside from clinical features, SERCA activity measurement and SERCA1 western blot can assist in proving the pathogenicity of novel ATP2A1 mutations. Finally, patients with Brody disease may be at risk for malignant hyperthermia-like episodes, and therefore appropriate perioperative measures are recommended. This study will help improve understanding and recognition of Brody disease as a distinct myopathy in the broader field of calcium-related myopathies.

Background and ObjectivesGuidelines 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.MethodsWe 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.ResultsWe 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.DiscussionYoung 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.

Importance Stroke remains the second leading cause of death worldwide. Approximately 10% to 15% of all strokes occur in young adults. Information on prognosis and mortality specifically in young adults is limited. Objective To determine short- and long-term mortality risk after stroke in young adults, according to age, sex, and stroke subtype; time trends in mortality; and causes of death. Design, Setting, and Participants Registry- and population-based study in the Netherlands of 15 527 patients aged 18 to 49 years with first stroke between 1998 and 2010, and follow-up until January 1, 2017. Patients and outcomes were identified through linkage of the national Hospital Discharge Registry, national Cause of Death Registry, and the Dutch Population Register. Exposures First stroke occurring at age 18 to 49 years, documented using International Classification of Diseases, Ninth Revision , and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision , codes for ischemic stroke, intracerebral hemorrhage, and stroke not otherwise specified. Main Outcomes and Measures Primary outcome was all-cause cumulative mortality in 30-day survivors at end of follow-up, stratified by age, sex, and stroke subtype, and compared with all-cause cumulative mortality in the general population. Results The study population included 15 527 patients with stroke (median age, 44 years [interquartile range, 38-47 years]; 53.3% women). At end of follow-up, a total of 3540 cumulative deaths had occurred, including 1776 deaths within 30 days after stroke and 1764 deaths (23.2%) during a median duration of follow-up of 9.3 years (interquartile range, 5.9-13.1 years). The 15-year mortality in 30-day survivors was 17.0% (95% CI, 16.2%-17.9%). The standardized mortality rate compared with the general population was 5.1 (95% CI, 4.7-5.4) for ischemic stroke (observed mortality rate 12.0/1000 person-years [95% CI, 11.2-12.9/1000 person-years]; expected rate, 2.4/1000 person-years; excess rate, 9.6/1000 person-years) and the standardized mortality rate for intracerebral hemorrhage was 8.4 (95% CI, 7.4-9.3; observed rate, 18.7/1000 person-years [95% CI, 16.7-21.0/1000 person-years]; expected rate, 2.2/1000 person-years; excess rate, 16.4/1000 person-years). Conclusions and Relevance Among young adults aged 18 to 49 years in the Netherlands who were 30-day survivors of first stroke, mortality risk compared with the general population remained elevated up to 15 years later.

Item does not contain fulltext

Introduction Intracerebral haemorrhage (ICH) in young adults is rare but has devastating consequences. We investigated long-term mortality rates, causes of death and predictors of long-term mortality in young spontaneous ICH survivors. Patients and methods We included consecutive patients aged 18–55 years from the Prognosis of Intracerebral Haemorrhage cohort (PITCH), a prospective observational cohort of patients admitted to Lille University Hospital (2004–2009), who survived at least 30 days after spontaneous ICH. We studied long-term mortality with Kaplan-Meier analyses, collected causes of death, performed uni-/multivariable Cox-regression analyses for the association of baseline characteristics with long-term mortality. Results Of 560 patients enrolled in the PITCH, 75 patients (75% men) met our inclusion criteria (median age 50 years, interquartile range [IQR] 44–53 years). During a median follow-up of 8.2 years (IQR 5.0–10.1), 26 patients died (35%), with a standardized mortality ratio of 13.0 (95% confidence interval [95% CI] 8.5–18.0) compared to peers from the general population. Causes of death were vascular in 7 (27%) patients, non-vascular in 13 (50%) and unknown in 6 (23%). Global cerebral atrophy (hazard ratio [HR] 3.0, 95% CI 1.1–8.6), modified Rankin Score >2 before ICH (HR 3.4, 95% CI 1.0–11.0), and excessive alcohol consumption (HR 3.3, 95% CI 1.1–10.2) were independently associated with long-term mortality. Discussion We found a 13-fold higher mortality risk for young ICH survivors compared to the general French population. Predictors of long-term mortality were pre-existing conditions, not ICH-characteristics. Conclusion Young ICH survivors remain at increased mortality risk of vascular and non-vascular death for years after ICH.

Contains fulltext : 238502.pdf (Publisher’s version ) (Open Access) Stroke is a leading cause of disability and the second most common cause of death worldwide. Increasing evidence suggests that air pollution is an emerging risk factor for stroke. Over the past decades, air pollution levels have continuously increased and are now estimated to be responsible for 14% of all stroke-associated deaths. Interpretation of previous literature is difficult because stroke was usually not distinguished as ischaemic or haemorrhagic, nor by cause. This Review summarises the evidence on the association between air pollution and the different causes of ischaemic stroke and haemorrhagic stroke, to clarify which people are most at risk. The risk for ischaemic stroke is increased after short-term or long-term exposure to air pollution. This effect is most pronounced in people with cardiovascular burden and stroke due to large artery disease or small vessel disease. Short-term exposure to air pollution increases the risk of intracerebral haemorrhage, a subtype of haemorrhagic stroke, whereas the effects of long-term exposure are less clear. Limitations of the current evidence are that studies are prone to misclassification of exposure, often rely on administrative data, and have insufficient clinical detail. In this Review, we provide an outlook on new research opportunities, such as those provided by the decreased levels of air pollution due to the current COVID-19 pandemic.

Introduction The aim of this study was to determine the risk of recurrent intracerebral haemorrhage (ICH), ischaemic stroke, all stroke, any vascular event and all-cause mortality in 30-day survivors of ICH, according to age and sex. Patients and methods We linked national hospital discharge, population and cause of death registers to obtain a cohort of Dutch 30-day survivors of ICH from 1998 to 2010. We calculated cumulative incidences of recurrent ICH, ischaemic stroke, all stroke and composite vascular outcome, adjusted for competing risk of death and all-cause mortality. Additionally, we compared survival with the general population. Results We included 19,444 ICH-survivors (52% male; median age 72 years, interquartile range 61–79; 78,654 patient-years of follow-up). First-year cumulative incidence of recurrent ICH ranged from 1.5% (95% confidence interval 0.9–2.3; men 35–54 years) to 2.4% (2.0–2.9; women 75–94 years). Depending on age and sex, 10-year risk of recurrent ICH ranged from 3.7% (2.6–5.1; men 35–54 years) to 8.1% (6.9–9.4; women 55–74 years); ischaemic stroke 2.6% to 7.0%, of all stroke 9.9% to 26.2% and of any vascular event 15.0% to 40.4%. Ten-year mortality ranged from 16.7% (35–54 years) to 90.0% (75–94 years). Relative survival was lower in all age-groups of both sexes, ranging from 0.83 (0.80–0.87) in 35- to 54-year-old men to 0.28 (0.24–0.32) in 75- to 94-year-old women. Discussion ICH-survivors are at high risk of recurrent ICH, of ischaemic stroke and other vascular events, and have a sustained reduced survival rate compared to the general population. Conclusion The high risk of recurrent ICH, other vascular events and prolonged reduced survival-rates warrant clinical trials to determine optimal secondary prevention treatment after ICH.

ObjectiveTo investigate incidence of stroke and its subtypes in young adults, according to sex and age, and to study trends over time.MethodsWe established a nationwide cohort through linkage of national registries (hospital discharge, cause of death, and population register) with patients aged 18–50 years and those ≥50 years with first-ever ischemic stroke, intracerebral hemorrhage, or unspecified stroke, using ICD-9/ICD-10 codes between 1998 and 2010 in the Netherlands. Outcomes were yearly incidence of stroke stratified by age, sex, and stroke subtype, its changes over time, and comparison of incidence in patients 18–50 years to patients ≥50 years.ResultsWe identified 15,257 patients (53% women; mean age 41.8 years). Incidence increased exponentially with age (R2 = 0.99) and was higher for women than men, most prominently in the youngest patients (18–44 years). The relative proportion of ischemic stroke increased with age (18–24 years: 38.3%; 44–49 years: 56.5%), whereas the relative proportion of intracerebral hemorrhage decreased (18–24 years: 34.0%; 44–49 years: 18.3%). Incidence of any stroke in young adults increased (1998: 14.0/100,000 person-years: 2010: 17.2; +23%; p < 0.001), driven by an increase in those aged over 35 years and ischemic stroke incidence (46%), whereas incidence decreased in those ≥50 years (329.1%–292.2%; −11%; p = 0.009).ConclusionsIncidence of any stroke in the young increases with age in patients over 35, is higher in women than men aged 18–44 years, and has increased by 23% in one decade, through an increase in ischemic stroke. Incidence of intracerebral hemorrhage is comparable for women and men and remained stable over time.