Minor stroke due to large artery occlusion. When is intravenous thrombolysis not enough? Results from the SITS International Stroke Thrombolysis Register

Purpose: Beyond intravenous thrombolysis, evidence is lacking on acute treatment of minor stroke caused by large artery occlusion. To identify candidates for additional endovascular therapy, we aimed to determine the frequency of non-haemorrhagic early neurological deterioration in patients with intravenous thrombolysis-treated minor stroke caused by occlusion of large proximal and distal cerebral arteries. Secondary aims were to establish risk factors for non-haemorrhagic early neurological deterioration and report three-month outcomes in patients with and without non-haemorrhagic early neurological deterioration. Method: We analysed data from the SITS International Stroke Thrombolysis Register on 2553 patients with intravenous thrombolysis-treated minor stroke (NIH Stroke Scale scores 0–5) and available arterial occlusion data. Non-haemorrhagic early neurological deterioration was defined as an increase in NIH Stroke Scale score ≥4 at 24 h, without parenchymal hematoma on follow-up imaging within 22–36 h. Findings: The highest frequency of non-haemorrhagic early neurological deterioration was seen in 30% of patients with terminal internal carotid artery or tandem occlusions (internal carotid artery + middle cerebral artery) (adjusted odds ratio: 10.3 (95% CI 4.3–24.9), p < 0.001) and 17% in extracranial carotid occlusions (adjusted odds ratio 4.3 (2.5–7.7), p < 0.001) versus 3.1% in those with no occlusion. Proximal middle cerebral artery-M1 occlusions had non-haemorrhagic early neurological deterioration in 9% (adjusted odds ratio 2.1 (0.97–4.4), p = 0.06). Among patients with any occlusion and non-haemorrhagic early neurological deterioration, 77% were dead or dependent at three months. Conclusions: Patients with minor stroke caused by internal carotid artery occlusion, with or without tandem middle cerebral artery involvement, are at high risk of disabling deterioration, despite intravenous thrombolysis treatment. Acute vessel imaging contributes usefully even in minor stroke to identify and consider endovascular treatment, or intensive monitoring at a comprehensive stroke centre, for patients at high risk of neurological deterioration

The Main Causes of Hemorrhagic Stroke in Patients

Haemorrhagic stroke is a severe stroke subtype with high rates of morbidity and mortality. Although this condition has been recognised for a long time, the progressing haemorrhagic stroke has not received adequate attention, and it accounts for an even worse clinical outcome than the nonprogressing types of haemorrhagic stroke. In this review article, we categorised the progressing haemorrhagic stroke into acute progressing haemorrhagic stroke, subacute haemorrhagic stroke, and chronic progressing haemorrhagic stroke. Haematoma expansion, intraventricular haemorrhage, perihaematomal oedema, and inflammation, can all cause an acute progression of haemorrhagic stroke. Specific ‘second peak’ of perihaematomal oedema after intracerebral haemorrhage and ‘tension haematoma’ are the primary causes of subacute progression. For the chronic progressing haemorrhagic stroke, the occult vascular malformations, trauma, or radiologic brain surgeries can all cause a slowly expanding encapsulated haematoma. The mechanisms to each type of progressing haemorrhagic stroke is different, and the management of these three subtypes differs according to their causes and mechanisms. Conservative treatments are primarily considered in the acute progressing haemorrhagic stroke, whereas surgery is considered in the remaining two types. Haemorrhagic stroke, which accounts for 10–20 % of all of the new strokes that occur every year [8], has a 1-month mortality rate of approximately 40 % [14]. Although it has drawn the attention of researchers because of the high rates of morbidity and mortality, the outcomes and prognosis of intracranial haemorrhage have not improved significantly during the last several decades

The relation between adult height and haemorrhagic and ischaemic stroke in the Renfrew/Paisley study

Adult height is a useful marker of fetal growth, growth and nutrition in childhood and childhood infections. Studies reporting inverse associations between height and stroke therefore provide support for the hypothesis that exposures acting in early life are important determinants of risk of stroke. However, few studies have been able to examine the association between height and stroke subtype. We recently showed that height is inversely related to ischaemic stroke, but because of small numbers it was not possible to robustly analyse the association between height and haemorrhagic stroke. A Norwegian study has shown a stronger inverse association with haemorrhagic compared with ischaemic stroke, but adjustment for socioeconomic position was not possible. We recently reported a significant inverse association between height and stroke mortality in both men and women in the Renfrew/Paisley cohort. Here we examine the association between height and subtype of incident stroke in this cohort

The relation between cholesterol and haemorrhagic or ischaemic stroke in the Renfrew/Paisley study

Studies have found little association between cholesterol and overall stroke risk, but this could be attributable to different relations for haemorrhagic and ischaemic stroke. Stroke mortality data from prospective studies cannot usually be divided into stroke subtypes. We have therefore analysed stroke based on hospital admissions, obtained by computerised linkage with acute hospital discharges in Scotland for a large prospective cohort study

The Genetics of Primary Haemorrhagic Stroke, Subarachnoid Haemorrhage and Ruptured Intracranial Aneurysms in Adults

Background: The genetic basis of haemorrhagic stroke has proved difficult to unravel, partly hampered by the small numbers of subjects in any single study. A meta-analysis of all candidate gene association studies of haemorrhagic stroke (including ruptured subarachnoid haemorrhage and amyloid angiopathy-related haemorrhage) was performed, allowing more reliable estimates of risk.Methods: A systematic review and meta-analysis of all genetic studies in haemorrhagic stroke was conducted. Electronic databases were searched until and including March 2007 for any candidate gene in haemorrhagic stroke. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models.Results: Our meta-analyses included 6,359 cases and 13,805 controls derived from 55 case-control studies, which included 12 genes (13 polymorphisms). Statistically significant associations with haemorrhagic stroke were identified for those homozygous for the ACE/I allele (OR, 1.48; 95% CI, 1.20-1.83; p = 0.0003) and for the 5G allele in the SERPINE1 4G/5G polymorphism (OR, 1.42; 95% CI, 1.03-1.96; p = 0.03). In addition, both epsilon 2 and epsilon 4 alleles of APOE were significantly associated with lobar haemorrhage (OR, 1.81; 95% CI, 1.26-2.62; p = 0.002 and OR, 1.49; 95% 1.08-2.05; p = 0.01 respectively). Furthermore, a significant protective association against haemorrhagic stroke was found for the factor V Leiden mutation (OR, 0.30; 95% CI, 0.10-0.87; p = 0.03).Conclusion: Our data suggests a genetic contribution to some types of haemorrhagic stroke, with no overall responsible single gene but rather supporting a polygenic aetiology. However, the evidence base is smaller compared to ischaemic stroke. Importantly, for several alleles previously found to be associated with protection from ischaemic stroke, there was a trend towards an increased risk of haemorrhagic stroke

Algoritma stroke Gadjah Mada Penyusunan dan validasi untuk membedakan stroke perdarahan intraserebral dengan stroke iskemik akut atau stroke infark.

ABSTRACT A prospective study on 229 acute stroke patients was conducted to develop a Gadjah Mada Stroke Algorithm (GMSA). This algorithm was proposed as a clinical strategy for distinguishing intracerebral haemorrhage from acute ischaemic or infarction stroke after onset of stroke in 3 hospitals in Yogyakarta from 16th December 1989 until 15th November 1991. The following investigations have been made: (a) interobserver reliability for questionnaire and clinical examination of stroke patients, (b) interobserver reliability in the interpretation of CT-Scans of stroke patients, (c) validity of every clinical symptom against CT-Scans to define intracerebral haemorrhagic stroke, and (d) validity of seven multiple parallel tests against CT-Scans to define intracerebral haemorrhagic stroke. The GMSA was developed by one of seven multiparallel tests which has the highest validity. A multivariate statistical analysis and validate study showed that decreasing consciousness, headache, and Babinski\u27s reflex at the onset are significantly related to intracerebral haemorrhagic stroke. This study showed that the GMSA was reliable and valid for distinguishing intracerebral haemorrhagic stroke from acute ischaemic or infarction stroke. Key words: Gadjah Mada stroke algorithm - diagnostic test - intracerebral haemorrhagic stroke Suatu penelitian prospektif dilakukan pada 229 penderita stroke akut untuk membuat Algoritma Stroke Gadjah Mada (ASGM) sebagai suatu strategi klinik untuk membedakan stroke perdarahan intraserebral dengan stroke iskemik akut atau stroke infark dari 16 Desember 1989 sampai dengan 15 November 1991. Termasuk dalam investigasi tersebut adalah: (a) reliabilitas penilaian pemeriksaan CT-Scan dari penderita stroke, (c) validitas untuk setiap gejala klinis untuk menentukan stroke, perdarahan intraserebral dengan CT-Scan. ASGM ditentukan dari salah satu hasil validitas tes multiparalel yang tertinggi. Dari analisis multivariabel dan uji validisasi menunjukkan penurunan kesadaran, nyeri kepala, dan refleks Babinski pada waktu saat serangan signifikan berhubungan dengan stroke perdarahan intraserebral. Penelitianan ini menunjukkan ASGM adalah reliabel dan valid untuk membedakan stroke perdarahan intraserebral dengan stroke iskemik akut stroke atau stroke infark

Relation between number of siblings and adult mortality and stroke risk: 25 year follow up of men in the Collaborative study

<b>Study objective</b>: To investigate the relation between number of siblings, mortality risk, and stroke risk. <b>Design</b>: Prospective cohort study. <b>Setting</b>: 27 workplaces in Scotland. <b>Participants</b>: 5765 employed men aged 35–64 from a variety of different workplaces, screened between 1970 and 1973. <b>Main results</b>: There were strong relationships between number of siblings and socioeconomic variables and also with adult behavioural measures. Men with greater numbers of siblings had an increased risk of dying of all causes, coronary heart disease, lung cancer, stomach cancer, and respiratory disease over a 25 year follow up period. Adjustment for risk factors could explain these associations, excepting stomach cancer mortality. With the definition of stroke as either a hospital admission for stroke or death from stroke, there was a strong relation between number of siblings and haemorrhagic stroke, but not ischaemic stroke. <b>Conclusions</b>: Number of siblings is strongly related to mortality risk, but as it is also related to many risk factors, adjustment for these can generally explain the relation with mortality. The exceptions are stomach cancer mortality and haemorrhagic stroke, which are known to be related to deprivation in childhood, and, in the case of stomach cancer to childhood infection

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke:an individual patient data meta-analysis of randomised controlled trials

SummaryBackgroundMany international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke.MethodsWe obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome “dead or dependent” in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis.FindingsPatients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59–0·67) and for haemorrhagic events was 0·60 (0·55–0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events.InterpretationThere was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised.FundingMRC

Dietary fibre intake and risk of ischaemic and haemorrhagic stroke in the UK Women’s Cohort Study

BACKGROUND: Stroke risk is modifiable through many risk factors, one being healthy dietary habits. Fibre intake was associated with a reduced stroke risk in recent meta-analyses; however, data were contributed by relatively few studies, and few examined different stroke types. METHODS: A total of 27 373 disease-free women were followed up for 14.4 years. Diet was assessed with a 217-item food frequency questionnaire and stroke cases were identified using English Hospital Episode Statistics and mortality records. Survival analysis was applied to assess the risk of total, ischaemic or haemorrhagic stroke in relation to fibre intake. RESULTS: A total of 135 haemorrhagic and 184 ischaemic stroke cases were identified in addition to 138 cases where the stroke type was unknown or not recorded. Greater intake of total fibre, higher fibre density and greater soluble fibre, insoluble fibre and fibre from cereals were associated with a significantly lower risk for total stroke. For total stroke, the hazard ratio per 6 g/day total fibre intake was 0.89 (95% confidence intervals: 0.81–0.99). Different findings were observed for haemorrhagic and ischaemic stroke in healthy-weight or overweight women. Total fibre, insoluble fibre and cereal fibre were inversely associated with haemorrhagic stroke risk in overweight/obese participants, and in healthy-weight women greater cereal fibre was associated with a lower ischaemic stroke risk. In non-hypertensive women, higher fibre density was associated with lower ischaemic stroke risk. CONCLUSIONS: Greater total fibre and fibre from cereals are associated with a lower stroke risk, and associations were more consistent with ischaemic stroke. The different observations by stroke type, body mass index group or hypertensive status indicates potentially different mechanisms

Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments. Graphical Abstract