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In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. The primary outcome was to interrogate the clinico-radiopathological correlates and prognostic indicators of stroke-like episode in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS). The secondary objective was to develop a multivariable prediction model to forecast stroke-like episode risk. The most common genetic cause of stroke-like episodes was the m.3243A>G variant in MT-TL1 (n = 66), followed by recessive pathogenic POLG variants (n = 22), and 11 other rarer pathogenic mitochondrial DNA variants (n = 23). The age of first stroke-like episode was available for 105 patients [mean (SD) age: 31.8 (16.1)]; a total of 35 patients (32%) presented with their first stroke-like episode ≥40 years of age. The median interval (interquartile range) between first and second stroke-like episodes was 1.33 (2.86) years; 43% of patients developed recurrent stroke-like episodes within 12 months. Clinico-radiological, electrophysiological and neuropathological findings of stroke-like episodes were consistent with the hallmarks of medically refractory epilepsy. Patients with POLG-related stroke-like episodes demonstrated more fulminant disease trajectories than cases of m.3243A>G and other mitochondrial DNA pathogenic variants, in terms of the frequency of refractory status epilepticus, rapidity of progression and overall mortality. In multivariate analysis, baseline factors of body mass index, age-adjusted blood m.3243A>G heteroplasmy, sensorineural hearing loss and serum lactate were significantly associated with risk of stroke-like episodes in patients with the m.3243A>G variant. These factors informed the development of a prediction model to assess the risk of developing stroke-like episodes that demonstrated good overall discrimination (area under the curve = 0.87, 95% CI 0.82-0.93; c-statistic = 0.89). Significant radiological and pathological features of neurodegeneration were more evident in patients harbouring pathogenic mtDNA variants compared with POLG: brain atrophy on cranial MRI (90% versus 44%, P < 0.001) and reduced mean brain weight (SD) [1044 g (148) versus 1304 g (142), P = 0.005]. Our findings highlight the often idiosyncratic clinical, radiological and EEG characteristics of mitochondrial stroke-like episodes. Early recognition of seizures and aggressive instigation of treatment may help circumvent or slow neuronal loss and abate increasing disease burden. The risk-prediction model for the m.3243A>G variant can help inform more tailored genetic counselling and prognostication in routine clinical practice.
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Síndrome MELAS , Doenças Mitocondriais , Acidente Vascular Cerebral , Adulto , DNA Mitocondrial/genética , Humanos , Síndrome MELAS/genética , Doenças Mitocondriais/complicações , Doenças Mitocondriais/genética , Mutação , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/genéticaRESUMO
Background: Entering neurosurgical training in the United Kingdom demands extensive prior commitment and achievement, despite little to no exposure to the specialty in medical school. Conferences run by student "neuro-societies" offer a means to bridge this gap. This paper describes one student-led neuro-society's experience of curating a 1-day national neurosurgical conference supported by our neurosurgical department. Methods: A pre-and post-conference survey was distributed to attendees to ascertain baseline opinions and conference impact using a five-point Likert Scale, and free text questions explored medical students' opinions of neurosurgery and neurosurgical training. The conference offered four lectures and three workshops; the latter provided practical skills and networking opportunities. There were also 11 posters displayed throughout the day. Results: 47 medical students participated in our study. Post-conference, participants were more likely to understand what a neurosurgical career involves and how to secure training. They also reported increased knowledge about neurosurgery research, electives, audits, and project opportunities. Respondents enjoyed the workshops provided and suggested the inclusion of more female speakers in future. Conclusion: Neurosurgical conferences organized by student neuro-societies successfully address the gap between a lack of neurosurgery exposure and a competitive training selection. These events give medical students an initial understanding of a neurosurgical career through lectures and practical workshops; attendees also gain insight into attaining relevant achievements and have an opportunity to present research. Student neuro-society-organized conferences have the potential to be adopted internationally and used as a tool to educate on a global level and greatly aid medical students who are aspiring neurosurgeons.
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BACKGROUND AND PURPOSE: Iodinated contrast is increasingly used in CT perfusion or angiographic examinations in acute stroke. Increased risk of intracranial hemorrhage (ICH) complicating microcatheter contrast injections has recently been reported in the second Interventional Management of Stroke (IMS 2) trial with contrast toxicity potentially contributory. METHODS: We reviewed clinical and radiological data on all patients treated with intravenous alteplase at a single center between May 2003 and November 2008. RESULTS: Of 312 patients treated with intravenous alteplase, 69 (22.1%) received intravenous iodinated contrast in volumes between 50 and 150 mL. Incidence of symptomatic ICH defined as per European Cooperative Acute Stroke Study 2 was 16 of 312 (5.1%; 95% CI, 2.7% to 7.6%); among patients not given contrast, it was 12 of 243 (4.9%; 2.2% to 7.7%) compared with 4 of 69 (5.8%; 0.3% to 11.3%) in those given contrast. Incidence of symptomatic ICH defined as per Safe Implementation of Thrombolysis in Stroke-MOnitoring Study (SITS-MOST) criteria was 12 of 312 (3.9%; 1.7% to 6%), 9 of 243 (3.7%; 1.3% to 6%) among those not given contrast, and 3 of 69 (4.4%; 95% CI, -0.5% to 9.2%) among those given contrast. Patients with symptomatic ICH were older, had higher pretreatment National Institutes of Health Stroke Scale, and blood glucose than those without symptomatic ICH. In logistic regression analysis, pretreatment blood glucose was the only significant predictor of symptomatic ICH by either definition (OR, 1.23; 95% CI, 1.03 to 1.48 per mmol/L increment; P=0.024). Contrast administration or dose was not associated with symptomatic ICH. CONCLUSIONS: Intravenous iodinated contrast in doses typically required for CT angiography and perfusion imaging was not associated with symptomatic intracranial hemorrhage in patients treated with alteplase.
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Angiografia Cerebral/efeitos adversos , Meios de Contraste/efeitos adversos , Hemorragias Intracranianas/etiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores Etários , Idoso , Meios de Contraste/administração & dosagem , Feminino , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: Mechanisms of early neurologic deterioration after treatment with intravenous, recombinant, tissue-type plasminogen activator (IV rt-PA) include symptomatic intracerebral hemorrhage (SICH) and early recurrent ischemic stroke. We observed a number of cases of acute deterioration due to recurrent ischemic events. METHODS: We undertook a single-center, retrospective analysis of consecutive acute stroke patients treated with IV rt-PA between January 2006 and December 2008 to define the incidence of early neurologic deterioration (>or=4-point drop on the National Institutes of Health Stroke Scale within 72 hours) and its mechanism. Deterioration was attributed to SICH when associated with a PH1 or PH2 hemorrhage on postdeterioration computed tomography scans, to recurrent ischemic stroke when there was clinical and radiologic evidence of a new territorial infarction or new vessel occlusion, and otherwise to evolution of the incident stroke. RESULTS: Of 228 consecutive IV rt-PA-treated patients, 34 (15%) developed early neurologic deterioration, 18 (8%) secondary to incident strokes 10 (4.4%) due to SICH, and 6 (2.6%) due to early recurrent ischemic events, which were significantly associated with atrial fibrillation (present in 5 of 6 patients; 4 paroxysmal, 1 permanent). In 4 patients, sudden clinical deterioration developed during or shortly after IV rt-PA infusion, and in 2, deterioration developed 3 days later. All died 2 days to 2 weeks later. The single case without atrial fibrillation had a recurrent, contralateral, middle cerebral artery stroke during IV rt-PA infusion and multiple high-signal emboli detected by transcranial Doppler. Early recurrent ischemic stroke accounted for 5 of 12 (42%) cases of early neurologic deterioration in patients with atrial fibrillation. CONCLUSIONS: In this single-center series, the incidence of early recurrent ischemic stroke after IV rt-PA was 2.6% and was associated with previous atrial fibrillation.
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Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Intravenous thrombolysis significantly improves the chance of independent recovery from ischaemic stroke but its benefit is strongly time dependent: present evidence supports effectiveness when delivered up to 4.5 h after symptom onset but the chance of recovery is twice as great when it is given within 90 min compared with 3-4.5 h. Delivery of treatment to a high proportion of patients is possible but requires clinicians to optimise systems for patient transfer, clinical and radiological assessment. A high proportion of patients with stroke already present to UK hospitals within the treatment time window even without specific public awareness or prehospital triage. Establishing a service requires dialogue with all those involved in the patient pathway, including ambulance dispatchers, paramedics, emergency department staff, radiology and colleagues in acute medicine. Most acute stroke teams cross traditional medical disciplines. Thrombolysis should ideally be delivered within an integrated service that seamlessly includes acute stroke unit care and rehabilitation.
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Serviços de Saúde , Acidente Vascular Cerebral/terapia , Terapia Trombolítica , Doença Aguda , Atenção à Saúde , Medicina Baseada em Evidências , Serviços de Saúde/economia , Humanos , Equipe de Assistência ao Paciente , Acidente Vascular Cerebral/economia , Terapia Trombolítica/economiaRESUMO
BACKGROUND AND PURPOSE: Early ischemic changes on noncontrast CT in acute stroke include both hypoattenuation and brain swelling, which may have different pathophysiological significance. METHODS: Noncontrast CT and CT perfusion brain scans from patients with suspected acute stroke <6 hours after onset were reviewed. Five raters independently scored noncontrast CTs blind to clinical data using the Alberta Stroke Program Early CT Score (ASPECTS). Each ASPECTS region was scored as hypodense or swollen. A separate reviewer measured time to peak and cerebral blood volume in each ASPECTS region on CT perfusion. Time to peak and cerebral blood volume were compared for each region categorized as normal, hypodense, or isodense and swollen. RESULTS: Scans of 32 subjects a median 155 minutes after onset yielded 228 regions with both CT perfusion and noncontrast CT data. Isodense swelling was associated with significantly higher cerebral blood volume (P=0.016) and with penumbral perfusion (posttest:pretest likelihood ratio 1.44 [95% CI: 0.68 to 2.90]), whereas hypodensity was associated with more severe time to peak delay and with core perfusion (likelihood ratio 3.47 [95% CI: 1.87 to 6.34]). Neither isodense swelling nor hypodensity was sensitive for prediction of perfusion pattern, but appearances were highly specific (87.2% and 91.0% for penumbra and core, respectively). Intrarater agreement was good or excellent, but interrater agreement for both hypodensity and swelling was poor. CONCLUSIONS: Regions exhibiting hypoattenuation are likely to represent the infarct core, whereas regions that are isodense and swollen have increased cerebral blood volume and are more likely to signify penumbral perfusion. Although noncontrast CT is not sensitive for detection of core and penumbra, appearances are specific. Some information on tissue viability can therefore be obtained from noncontrast CT.
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Isquemia Encefálica/patologia , Acidente Vascular Cerebral/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico , Isquemia Encefálica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnósticoRESUMO
BACKGROUND AND PURPOSE: The mechanisms of perihematomal injury in primary intracerebral hemorrhage (ICH) are incompletely understood. An MRI study was designed to elucidate the nature of edema and blood flow changes after ICH. METHODS: Perihematomal blood flow and edema were studied prospectively with perfusion-weighted MRI (PWI) and diffusion-weighted MRI in 21 ICH patients. MRI and computed tomography (CT) images were coregistered to ensure perfusion and diffusion changes were outside of the hematoma. Edema volumes were measured on T2-weighted images. Apparent diffusion coefficient (ADC) values of the edematous regions were calculated. RESULTS: Mean patient age was 64.2 years (45 to 89), and median National Institutes of Health stroke scale score was 12 (3 to 24). Median time to MRI was 21 hours (4.5 to 110). Average hematoma volume on CT was 26.1 (4 to 84) mL. PWI demonstrated perihematomal relative mean transit time (rMTT) was significantly correlated with hematoma volume (r=0.60; P=0.004) but not edema volume. Perihematomal oligemia (rMTT >2 s) was present in patients with hematoma volumes of >15 mL (average rMTT 4.6+/-2.0 s). Perihematomal edema was present in all patients. ADC values within this region (1178+/-213x10(-6) mm2/s) were increased 29% relative to contralateral homologous regions. Increases in perihematomal ADC predicted edema volume (r=0.54; P=0.012) and this was confirmed with multivariate analysis. CONCLUSIONS: Acute perihematomal oligemia occurs in acute ICH but is not associated with MRI markers of ischemia and is unrelated to edema formation. Increased rates of water diffusion in the perihematomal region independently predict edema volume, suggesting the latter is plasma derived.
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Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/patologia , Hemorragia Cerebral/patologia , Imagem de Difusão por Ressonância Magnética , Hematoma/etiologia , Hematoma/patologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Plasma/metabolismoRESUMO
BACKGROUND AND PURPOSE: Acute poststroke hyperglycemia has been associated with larger infarct volumes and a cortical location, regardless of diabetes status. Stress hyperglycemia has been attributed to activation of the hypothalamic-pituitary-adrenal axis but never a specific cortical location. We tested the hypothesis that damage to the insular cortex, a site with autonomic connectivity, results in hyperglycemia reflecting sympathoadrenal dysregulation. METHODS: Diffusion-weighted MRI, glycosylated hemoglobin (HbA1c), and blood glucose measurements were obtained in 31 patients within 24 hours of ischemic stroke onset. Acute diffusion-weighted imaging (DWI) lesion volumes were measured, and involvement of the insular cortex was assessed on T2-weighted images. RESULTS: Median admission glucose was significantly higher in patients with insular cortical ischemia (8.6 mmol/L; n=14) compared with those without (6.5 mmol/L; n=17; P=0.006). Multivariate linear regression demonstrated that insular cortical ischemia was a significant independent predictor of glucose level (P=0.001), as was pre-existing diabetes mellitus (P=0.008). After controlling for the effect of insular cortical ischemia, DWI lesion volume was not associated with higher glucose levels (P=0.849). There was no association between HbA1c and glucose level (P=0.737). CONCLUSIONS: Despite the small sample size, insular cortical ischemia appeared to be associated with the production of poststroke hyperglycemia. This relationship is independent of pre-existing glycemic status and infarct volume. Neuroendocrine dysregulation after insular ischemia may be 1 aspect of a more generalized acute stress response. Future studies of poststroke hyperglycemia should account for the effect of insular cortical ischemia.
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Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Hiperglicemia/etiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Isquemia Encefálica/patologia , Imagem de Difusão por Ressonância Magnética , Hemoglobinas Glicadas/metabolismo , Humanos , Infarto da Artéria Cerebral Anterior/sangue , Infarto da Artéria Cerebral Anterior/complicações , Infarto da Artéria Cerebral Anterior/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND PURPOSE: The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. METHODS: Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. RESULTS: Interrater reliability was measured with the kappa statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (kappa(w)=0.78); 1 rater assigned significantly lower grades than the other (P=0.048). On the structured interview, the overall agreement between raters was 78% (kappa(w)=0.93), and there was no overall difference between raters in grades assigned (P=0.17). Rankin grades from the conventional assessment and the structured interview were highly correlated, but there was significantly less disagreement between raters when the structured interview was used (P=0.004). CONCLUSIONS: Variability and bias between raters in assigning patients to Rankin grades may be reduced by use of a structured interview. Use of a structured interview for the scale could potentially improve the quality of results from clinical studies in stroke.
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Atividades Cotidianas/classificação , Avaliação da Deficiência , Entrevistas como Assunto/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Reabilitação do Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Acidente Vascular Cerebral/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity. Animal studies suggest that infarct expansion may be responsible. The influence of persisting hyperglycemia after stroke has not previously been examined. We measured the blood glucose profile after acute ischemic stroke and correlated it with infarct volume changes using T2- and diffusion-weighted MRI. METHODS: We recruited 25 subjects within 24 hours of ischemic stroke symptoms. Continuous glucose monitoring was performed with a glucose monitoring device (CGMS), and 4-hour capillary glucose levels (BGL) were measured for 72 hours after admission. MRI and clinical assessments were performed at acute (median, 15 hours), subacute (median, 5 days), and outcome (median, 85 days) time points. RESULTS: Mean CGMS glucose and mean BGL glucose correlated with infarct volume change between acute and subacute diffusion-weighted MRI (r>or=0.60, P<0.01), acute and outcome MRI (r=0.56, P=0.01), outcome National Institutes of Health Stroke Scale (NIHSS; r>or=0.53, P<0.02), and outcome modified Rankin Scale (mRS; r>or=0.53, P=0.02). Acute and final infarct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose >or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels >or=7 mmol/L were independently associated with increased final infarct volume change. CONCLUSIONS: Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.
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Isquemia Encefálica/fisiopatologia , Infarto Cerebral/diagnóstico , Hiperglicemia/diagnóstico , Hiperglicemia/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Doença Aguda , Idoso , Glicemia , Isquemia Encefálica/complicações , Isquemia Encefálica/terapia , Infarto Cerebral/etiologia , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Fibrinolíticos/administração & dosagem , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/complicações , Hiperglicemia/terapia , Monitorização Fisiológica , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Regressão , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do TratamentoRESUMO
Diabetes mellitus is a complex metabolic syndrome with significant effects on the systemic and cerebral vasculature. The incidence and severity of ischaemic stroke are increased by the presence of diabetes, and outcome from stroke is poorer. More than one third of patients admitted with acute stroke are hyperglycaemic at presentation. Reasons for the altered prognosis in diabetes associated stroke are multifactorial. A direct influence of hyperglycaemia at the time of ischaemia is likely to be important. The use of novel methods to delineate stroke topography and pathophysiology such as MR spectroscopy, diffusion and perfusion weighted MRI appear helpful in delineating the effects of hyperglycaemia on stroke pathophysiology. Randomised clinical trials to determine optimal management for patients with hyperglycaemia following stroke are ongoing. Such trials will determine if aggressive control of acute hyperglycaemia following stroke has similar benefits to that observed following acute myocardial infarction. Clinicians responsible for stroke patients should be aware of the importance of adequate glycaemic control in both primary and secondary prevention of stroke.
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Diabetes Mellitus/epidemiologia , Hiperglicemia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Diabetes Mellitus/terapia , Humanos , Hiperglicemia/terapia , Incidência , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Post-stroke hyperglycaemia (PSH) is associated with higher mortality and dependence, but further data on predictors of PSH and its evolution over time are required. We examined the prevalence, predictors, and prognosis of acute PSH using data from well-characterised clinical trials in the VISTA database. METHODS: Data were extracted for individual participants enrolled <24 h after stroke with ≥1 blood glucose readings documented. PSH was defined as glucose >7.0 mmol/l. Outcome measures were: (1) prevalence of PSH; (2) predictors of PSH by binary logistic regression; (3) mortality, and (4) favourable functional outcome [modified Rankin Scale (mRS) score <2] at day 90. RESULTS: For 2,649 subjects treated at a median 5.5 h after admission, PSH was present in 1,126 (42.6%, 95% CI 40.7-44.5) on admission and within the first 48 h in 1,421 (53.7%, 95% CI 51.8-55.6). PSH developed between 24 and 48 h in 19.4% (95% CI 17.5-21.4) of initially normoglycaemic subjects. Admission and 48-hour PSH were predicted predominantly by a history of diabetes (for admission PSH: OR 7.40, 95% CI 5.60-9.79) and less clearly by stroke severity. Favourable outcome (mRS <2) at day 90 was less likely with PSH within the first 48 h, advanced age, and higher NIHSS score, and more likely with recombinant tissue plasminogen activator treatment. CONCLUSIONS: Over 40% of ischaemic stroke patients are hyperglycaemic on admission, and 20% of those who are initially normoglycaemic develop hyperglycaemia within 48 h. Diabetes is the strongest predictor of acute hyperglycaemia. Hyperglycaemia within the first 48 h is independently associated with higher mortality and poorer functional outcome, with an absolute increase of 12.9%.
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Hyperglycaemia following acute stroke is both common and prolonged, regardless of diabetes status. A substantial body of evidence, derived from animal and human literature, has demonstrated that post-stroke hyperglycaemia has a deleterious effect upon clinical and radiological stroke outcomes. Whether intensive glycaemic manipulation positively influences the fate of ischaemic tissue remains to be shown. This article provides an overview of the prevalence, aetiology, and mechanisms of tissue injury arising as a result of post-stroke hyperglycaemia, as well as exploring the evidence from glucose-lowering treatment trials to date. Additionally, novel insights into post-stroke hyperglycaemia derived from continuous glucose monitoring are discussed. Stroke is a leading cause of death worldwide and the commonest cause of long-term disability amongst adults. Increasing evidence suggests that disordered physiological variables following acute ischaemic stroke adversely affect outcomes. Of these, post-stroke hyperglycaemia (PSH) is the most frequently recognised abnormality and is documented in up to 50% of patients at the time of stroke presentation. Importantly, a significant proportion of hyperglycaemic acute stroke patients (approximately 50%) have undiagnosed disorders of glucose metabolism, including diabetes. Animal and human data have repeatedly demonstrated that PSH negatively impacts upon the fate of ischaemic brain tissue, with greater infarct growth, higher mortality and more severe disability being consistent findings amongst hyperglycaemic stroke subjects. For these reasons, PSH represents an attractive physiological target for acute stroke therapies with potential application across broad time windows, stroke subtypes and stroke severity. In addition to providing an overview of the adverse effects of hyperglycaemia following acute ischaemic stroke, this article aims to summarise the evidence from current glucose-lowering treatment trials as well as exploring continuous glucose monitoring and the implications for future glycaemic manipulation.
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Glicemia/análise , Isquemia Encefálica/sangue , Hiperglicemia/sangue , Monitorização Ambulatorial/métodos , Adulto , Animais , Glicemia/metabolismo , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Pessoas com Deficiência , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/fisiopatologia , Modelos Animais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND: Intravenous alteplase is licensed for treatment of ischaemic stroke within 3 h of onset. Up to one-third of patients in the UK present to hospital within this time window but few are treated. AIMS: To examine the effect of a stroke thrombolysis protocol on service provision for an acute stroke service in the UK, jointly run by Neurology and Medicine for the Elderly providing a comprehensive stroke service to a local population of 370,000. DESIGN: Prospective observational study. METHODS: Data collected prospectively for all thrombolysis referrals over a 12-month period beginning July 2004. RESULTS: One hundred and eighty-eight patients were referred for potential thrombolysis, 129 transferred, 102 had an ischaemic stroke and 49 received intravenous thrombolysis. Referral rates from primary care and accident and emergency increased after guideline dissemination. Forty-three percent of the 49 patients treated with intravenous rt-PA achieved independence (modified Rankin Scale score 0-2) at 3months. CONCLUSION: A high proportion of ischaemic stroke patients can be treated with alteplase within 3 h of onset with organized hospital services and dissemination of a simple referral protocol to local primary and secondary care services.
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Fibrinolíticos/uso terapêutico , Encaminhamento e Consulta , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/normas , Ativador de Plasminogênio Tecidual/uso terapêutico , Métodos Epidemiológicos , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Acidente Vascular Cerebral/complicações , Terapia Trombolítica/estatística & dados numéricos , Fatores de Tempo , Resultado do TratamentoRESUMO
Basilar artery occlusion is assumed to carry a grave prognosis, with mortality rates of up to 90%. Diagnosis is often delayed, or even missed, as a result of the variety of clinical presentations seen with this condition. The pathogenesis of occlusion can be secondary to both local atherothrombosis or cardioembolism. The use of noninvasive imaging such as magnetic resonance imaging and computed tomography angiography has improved recognition of clinical syndromes associated with occlusion. Although no randomized studies have been performed, recanalization of the vascular occlusion, particularly with thrombolytic agents, appears to result in improved outcomes in selected patients. However, the optimum timing for therapy is unclear, and reperfusion therapy may need to be combined with definitive vascular treatment of underlying vascular stenosis. Increasing awareness of this condition may reveal the natural history to be more diverse than previously recognized.
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Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/terapia , Insuficiência Vertebrobasilar/diagnóstico , Insuficiência Vertebrobasilar/terapia , Arteriopatias Oclusivas/etiologia , Diagnóstico Diferencial , Humanos , Prognóstico , Insuficiência Vertebrobasilar/etiologiaRESUMO
Controversy exists whether acute hyperglycemia is causally associated with worse stroke outcome or simply reflects a more severe stroke. In reversible ischemia models, hyperglycemia is associated with lactic acidosis and conversion of penumbral tissue to infarction. However, the relationship between hyperglycemia, lactic acidosis, and stroke outcome has not been explored in humans. Sixty-three acute stroke patients were prospectively evaluated with serial diffusion-weighted and perfusion-weighted magnetic resonance imaging and acute blood glucose measurements. Patients with hypoperfused at-risk tissue were identified by acute perfusion-diffusion lesion mismatch. As a substudy, acute and subacute magnetic resonance spectroscopy was performed in the 33 most recent patients to assess the relationship between acute blood glucose and lactate production in the ischemic region. In 40 of 63 patients with acute perfusion-diffusion mismatch, acute hyperglycemia was correlated with reduced salvage of mismatch tissue from infarction, greater final infarct size, and worse functional outcome. These correlations were independent of baseline stroke severity, lesion size, and diabetic status. Furthermore, higher acute blood glucose in patients with perfusion-diffusion mismatch was associated with greater acute-subacute lactate production, which, in turn, was independently associated with reduced salvage of mismatch tissue. In contrast, acute blood glucose levels in nonmismatch patients did not independently correlate with outcome measures, nor was there any acute-subacute increase in lactate in this group. Acute hyperglycemia increases brain lactate production and facilitates conversion of hypoperfused at-risk tissue into infarction, which may adversely affect stroke outcome. These findings support the need for randomized controlled trials of aggressive glycemic control in acute stroke.
Assuntos
Hiperglicemia/sangue , Hiperglicemia/patologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia , Doença Aguda , Idoso , Glicemia/metabolismo , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Humanos , Hiperglicemia/complicações , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Análise de Regressão , Acidente Vascular Cerebral/complicaçõesRESUMO
OBJECTIVE: To report initial experience with the use of intravenous tissue plasminogen activator (tPA) to treat acute ischaemic stroke at an Australian tertiary-care hospital. DESIGN: Retrospective audit of computerised hospital stroke database. PARTICIPANTS AND SETTING: All patients with acute ischaemic stroke treated with intravenous tPA between April 1999 and July 2002 at the Royal Melbourne Hospital, VIC. MAIN OUTCOME MEASURES: Times from stroke onset to arrival at the emergency department (ED) and treatment; rates of symptomatic intracerebral haemorrhage (ICH); clinical outcome at three months; and violations of treatment protocol. RESULTS: Of 932 patients admitted with ischaemic stroke, 30 were treated with intravenous tPA. Median time from stroke onset to tPA treatment was 2 h 48 min, and median door-to-needle time was 1 h 49 min. Door-to-needle time improved in the last 12 months of the audit, with four of 15 patients achieving the recommended 60 min. Eleven patients (37%) had excellent clinical outcomes at three-month follow-up (modified Rankin score, 0-1), and 15 (50%) were functionally independent (score, 0-2). Mortality rate was 10%, similar to that of all ischaemic stroke patients during the audit period. Two patients (7%) had symptomatic ICH. Treatment deviated from protocol in seven patients (23%), five of whom received tPA over three hours after stroke onset. CONCLUSION: Rates of favourable outcomes and symptomatic ICH at our hospital were similar to those achieved in international phase III and IV trials in specialised centres.