Intracerebral haemorrhage Qureshi, Adnan I, Dr; Mendelow, A David, FRCS; Hanley, Daniel F, MD
Lancet,
05/2009, Volume:
373, Issue:
9675
Journal Article
Peer reviewed
Open access
Summary Intracerebral haemorrhage is an important public health problem leading to high rates of death and disability in adults. Although the number of hospital admissions for intracerebral ...haemorrhage has increased worldwide in the past 10 years, mortality has not fallen. Results of clinical trials and observational studies suggest that coordinated primary and specialty care is associated with lower mortality than is typical community practice. Development of treatment goals for critical care, and new sequences of care and specialty practice can improve outcome after intracerebral haemorrhage. Specific treatment approaches include early diagnosis and haemostasis, aggressive management of blood pressure, open surgical and minimally invasive surgical techniques to remove clot, techniques to remove intraventricular blood, and management of intracranial pressure. These approaches improve clinical management of patients with intracerebral haemorrhage and promise to reduce mortality and increase functional survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This review focuses on the emerging principles of intracerebral hemorrhage (ICH) management, emphasizing the natural history and treatment of intraventricular hemorrhage. The translational and ...clinical findings from recent randomized clinical trials are defined and discussed. Summary of Review- Brain hemorrhage is the most severe of the major stroke subtypes. Extension of the hemorrhage into the ventricles (a 40% occurrence) can happen early or late in the sequence of events. Epidemiological data demonstrate the amount of blood in the ventricles relates directly to the degree of injury and likelihood of survival. Secondary tissue injury processes related to intraventricular bleeding can be reversed by removal of clot in animals. Specific benefits of removal include limitation of inflammation, edema, and cell death, as well as restoration of cerebral spinal fluid flow, intracranial pressure homeostasis, improved consciousness, and shortening of intensive care unit stay. Limited clinical knowledge exists about the benefits of intraventricular hemorrhage (IVH) removal in humans, because organized attempts to remove blood have not been undertaken in large clinical trials on a generalized scale. New tools to evaluate the volume and location of IVH and to test the benefits/risks of removal have been used in the clinical domain. Initial efforts are encouraging that increased survival and functional improvement can be achieved. Little controversy exists regarding the need to scientifically investigate treatment of this severity factor.
Animal models demonstrate clot removal can improve the acute and long-term consequences of intraventricular extension from intracerebral hemorrhage by using minimally invasive techniques coupled to recombinant tissue plasminogen activator-mediated clot lysis. The most recent human clinical trials show that severity of initial injury and the long-term consequences of blood extending into the ventricles are clearly related to the amount of bleeding into the ventricular system. The failure of the last 2 pivotal brain hemorrhage randomized control trials may well relate to the consequences of intraventricular bleeding. Small proof of concept studies, meta-analyses, and preliminary pharmacokinetics studies support the idea of positive shifts in mortality and morbidity, if this 1 critical disease severity factor, IVH, is properly addressed. Understanding clinical methods for the removal of IVH is required if survival and long-term functional outcome of brain hemorrhage is to improve worldwide.
Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse outcomes. Therapeutic ...interventions in acute ICH have continued to emerge with focus on arresting hemorrhage expansion, clot volume reduction of both intraventricular and parenchymal hematomas, and targeting perihematomal edema and inflammation. Large randomized controlled trials addressing the effectiveness of rapid blood pressure lowering, hemostatic therapy with platelet transfusion, and other clotting complexes and hematoma volume reduction using minimally invasive techniques have impacted clinical guidelines. We review the recent evolution in the management of acute spontaneous ICH, discussing which interventions have been shown to be safe and which may potentially improve outcomes.
Summary Background Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by ...thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18–80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov , number NCT00224770. Findings Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four 9·5%, 95% CI 2·7–22.6 vs eight 14·8%, 6·6–27·1, p=0·542), 7 day mortality (zero 0%, 0–8·4 vs one 1·9%, 0·1–9·9, p=0·562), symptomatic bleeding (one 2·4%, 0·1–12·6 vs five 9·3%, 3·1–20·3, p=0·226), and brain bacterial infections (one 2·4%, 0·1–12·6 vs zero 0%, 0–6·6, p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 22·2%; 95% CI 12·0–35·6 vs three 7·1%; 1·5–19·5; p=0·051). Interpretation MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. Funding National Institute of Neurological Disorders and Stroke, Genentech, and Codman.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this randomized trial involving patients with intracerebral hemorrhage, intensive reduction in systolic blood pressure to a target of 110 to 139 mm Hg did not result in a lower rate of death or ...disability than standard reduction to a target of 140 to 179 mm Hg.
An acute hypertensive response in patients with intracerebral hemorrhage is common
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and may be associated with hematoma expansion and increased mortality.
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The second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial
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(INTERACT2) included patients with spontaneous intracerebral hemorrhage who had a systolic blood pressure of 150 to 220 mm Hg within 6 hours after symptom onset. The rate of death or disability among patients randomly assigned to intensive reduction in the systolic blood-pressure level, with a target systolic blood pressure of less than 140 mm Hg within 1 hour, was nonsignificantly lower than the rate among those . . .
A care bundle is a small but crucial set of treatments that, when implemented together, can improve outcomes.1 Acute spontaneous intracerebral haemorrhage has few effective treatments and ...intracerebral haemorrhage-specific recommendations for care bundles.2,3 In clinical practice, intracerebral haemorrhage is often approached with negativity.4 Moreover, the synergistic benefits of specialised nursing care, neurointensive and neurosurgical care, blood pressure control, reversal of coagulopathy, and other interventions have not been ascertained.5 In The Lancet, Lu Ma and colleagues6 report the results of INTERACT3, a cluster randomised, pragmatic, multicentre, blinded endpoint, stepped wedge controlled trial performed in 144 hospitals in ten predominantly low-income and middle-income countries to investigate the efficacy and safety of a care bundle incorporating early intensive blood pressure lowering and management protocols for hyperglycaemia, pyrexia, and abnormal anticoagulation in patients with intracerebral haemorrhage presenting within 6 h of symptom onset. The percentage of patients with the early withdrawal of active life support was minimal (<1%), but patient location after hospital admission might have been a bias since intensive care unit admission was 5% higher in the care bundle group than the usual care group, as was the use of intravenous blood pressure lowering treatments on days 2–7, typically an intensive care unit intervention. ...the absence of level 1 evidence for all bundle components might affect acceptance, especially for blood pressure control, where guidelines have differed.6–8 INTERACT 3 is promising, demonstrating that an intracerebral haemorrhage care bundle focused on physiological control interventions, whether synergistic or not, might promote better outcomes in hospitals where care has not previously optimised sustained interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although intracerebral hemorrhage (ICH) is a devastating disease worldwide, the pathologic changes in ultrastructure during the acute and chronic phases of ICH are poorly described. In this study, ...transmission electron microscopy was used to examine the ultrastructure of ICH-induced pathology. ICH was induced in mice by an intrastriatal injection of collagenase. Pathologic changes were observed in the acute (3 days), subacute (6 days), and chronic (28 days) phases. Compared with sham animals, we observed various types of cell death in the injured striatum during the acute phase of ICH, including necrosis, ferroptosis, and autophagy. Different degrees of axon degeneration in the striatum were seen in the acute phase, and axonal demyelination was observed in the ipsilateral striatum and corpus callosum at late time points. In addition, phagocytes, resident microglia, and infiltrating monocyte-macrophages were present around red blood cells and degenerating neurons and were observed to engulf red blood cells and other debris. Many synapses appeared abnormal or were lost. This systematic analysis of the pathologic changes in ultrastructure after ICH in mice provides information that will be valuable for future ICH pathology studies.
Objectives
Dizziness and vertigo account for about 4 million emergency department (ED) visits annually in the United States, and some 160,000 to 240,000 (4% to 6%) have cerebrovascular causes. Stroke ...diagnosis in ED patients with vertigo/dizziness is challenging because the majority have no obvious focal neurologic signs at initial presentation. The authors sought to compare the accuracy of two previously published approaches purported to be useful in bedside screening for possible stroke in dizziness: a clinical decision rule (head impulse, nystagmus type, test of skew HINTS) and a risk stratification rule (age, blood pressure, clinical features, duration of symptoms, diabetes ABCD2).
Methods
This was a cross‐sectional study of high‐risk patients (more than one stroke risk factor) with acute vestibular syndrome (AVS; acute, persistent vertigo or dizziness with nystagmus, plus nausea or vomiting, head motion intolerance, and new gait unsteadiness) at a single academic center. All underwent neurootologic examination, neuroimaging (97.4% by magnetic resonance imaging MRI), and follow‐up. ABCD2 risk scores (0–7 points), using the recommended cutoff of ≥4 for stroke, were compared to a three‐component eye movement battery (HINTS). Sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR–) were assessed for stroke and other central causes, and the results were stratified by age. False‐negative initial neuroimaging was also assessed.
Results
A total of 190 adult AVS patients were assessed (1999–2012). Median age was 60.5 years (range = 18 to 92 years; interquartile range IQR = 52.0 to 70.0 years); 60.5% were men. Final diagnoses were vestibular neuritis (34.7%), posterior fossa stroke (59.5% 105 infarctions, eight hemorrhages), and other central causes (5.8%). Median ABCD2 was 4.0 (range = 2 to 7; IQR = 3.0 to 4.0). ABCD2 ≥ 4 for stroke had sensitivity of 61.1%, specificity of 62.3%, LR+ of 1.62, and LR– of 0.62; sensitivity was lower for those younger than 60 years old (28.9%). HINTS stroke sensitivity was 96.5%, specificity was 84.4%, LR+ was 6.19, and LR– was 0.04 and did not vary by age. For any central lesion, sensitivity was 96.8%, specificity was 98.5%, LR+ was 63.9, and LR– was 0.03 for HINTS, and sensitivity was 99.2%, specificity was 97.0%, LR+ was 32.7, and LR– was 0.01 for HINTS “plus” (any new hearing loss added to HINTS). Initial MRIs were falsely negative in 15 of 105 (14.3%) infarctions; all but one was obtained before 48 hours after onset, and all were confirmed by delayed MRI.
Conclusions
HINTS substantially outperforms ABCD2 for stroke diagnosis in ED patients with AVS. It also outperforms MRI obtained within the first 2 days after symptom onset. While HINTS testing has traditionally been performed by specialists, methods for empowering emergency physicians (EPs) to leverage this approach for stroke screening in dizziness should be investigated.
Resumen
Objetivos
El mareo y el vértigo contabilizan aproximadamente 4 millones de visitas anuales a los servicios de urgencias (SU) en Estados Unidos, y de 160.000 a 240.000 (4% al 6%) tienen un origen cerebrovascular. El diagnóstico de ictus en los pacientes con vértigo o mareo es complejo debido a que la mayoría no tienen signos de focalidad neurológica evidentes en la atención inicial. Los autores comparan la certeza de dos aproximaciones previamente publicadas que resultaron ser de utilidad en el cribaje a pie de cama del posible ictus en el mareo: una regla de decisión clínica HINTS: Head Impulse (impulso de la cabeza), Nystagmus (nistagmo), Test of Skew (test de la desviación), y una regla de estratificación del riesgo ABCD2: Age (edad), Blood pressure (presión arterial), Clinical features (hallazgos clínicos), Duration of symptoms (duración de los síntomas), Diabetes (diabetes).
Metodología
Estudio transversal de pacientes de alto riesgo (más de un factor de riesgo de ictus) con síndrome vestibular agudo (SVA) (mareo o vértigo agudo persistente con nistagmo, más náuseas o vómitos; intolerancia a la movilización de la cabeza; e inestabilidad de la marcha aparecidos de novo) realizado en un único centro universitario. Se llevó a cabo en todos los pacientes una exploración neurootológica, de neuroimagen (97,4% mediante resonancia magnética RM) y de seguimiento. Las puntuaciones de riesgo ABCD2 (0–7 puntos), usando el punto de corte recomendado ≥ 4 para ictus, se compararon con una batería de movimiento ocular de tres componentes (HINTS). Se evaluaron la sensibilidad, la especificidad y las razones de probabilidad positiva y negativa (RPP y RPN) para ictus y otras causas centrales, y los resultados se estratificaron por edad. También se evaluaron los falsos negativos iniciales de la neuroimagen (RM).
Resultados
Se evaluaron 190 pacientes adultos con SVA (1999–2012). La mediana de edad fue de 60,5 años (rango 18 a 92 años; RIC 52,0 a 70,0 años); un 60,5% fueron hombres. Los diagnósticos finales fueron neuritis vestibular (34,7%), ictus de fosa posterior (59,5% 105 infartos, 8 hemorragias) y otras causas centrales (5,8%). La mediana de ABCD2 fue 4,0 (rango 2 a 7; RIC 3,0 a 4,0). ABCD2 ≥4 para ictus tuvo una sensibilidad de un 61,1%, una especificidad de un 62,3%, una RPP de 1,62, y una RPN de 0,62; la sensibilidad fue menor para aquéllos que eran más jóvenes de 60 años (28,9%). La sensibilidad para el ictus del HINTS fue de un 96,5%, la especificidad de un 84,4%, la RPP de 6,19 y la RPN de 0,04, y no se modificó por la edad. Para cualquier lesión central, la sensibilidad fue de un 96,8%, la especificidad de un 98,5%, la RPP de 63,9 y la RPN de 0,03 para el HINTS; y la sensibilidad de un 99,2%, la especificidad de un 97,0%, la RPP de 32,7 y la RPN de 0,01 para HINTS+ (cualquier nueva pérdida de audición añadida al HINTS). Las RM iniciales fueron falsamente negativas en 15 de 105 (14,3%) infartos, todas salvo una fueron hechas antes de las 48 horas del inicio de la clínica, y todos fueron confirmados por una RM diferida.
Conclusiones
El HINTS mejora sustancialmente el ABCD2 para el diagnóstico de ictus en los pacientes con SVA en el SU. También supera a la RM obtenida en los primeros dos días tras el inicio de los síntomas. Dado que el test de HINTS se ha realizado tradicionalmente por especialistas, se deberían investigar métodos que permitan a los urgenciólogos hacer uso de esta aproximación para el cribado de ictus en el mareo.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•We evaluated outcomes of ICH that affect right-hemispheric structures in mice.•ICH was induced in ventricle, cortex, hippocampus, and striatum.•Motor, cognitive, and emotion-related behaviors were ...evaluated.•Brain damage and behavioral deficits after ICH differed by brain region affected.•This study will help to inform future preclinical studies of ICH outcomes.
Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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