Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

The association of post-stroke anhedonia with salivary cortisol levels and stroke lesion in hippocampal/parahippocampal region

Luisa Terroni,1 Edson Amaro Jr,2 Dan V Iosifescu,3 Patricia Mattos,4 Fabio I Yamamoto,5 Gisela Tinone,5 Adriana B Conforto,5 Matildes FM Sobreiro,1 Valeri D Guajardo,1 Mara Cristina S De Lucia,7 Ayrton C Moreira,6 Milberto Scaff,5 Claudia C Leite,2 Renerio Fraguas1 1Consultation-Liaison Psychiatry Group, Department and Institute of Psychiatry, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 2Department of Radiology, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 3Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; 5Department of Neurology, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 6Department of Medicine, University of São Paulo, School of Medicine, Ribeirão Preto, Brazil; 7Division of Psychology, Central Institute, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil Background: Anhedonia constitutes a coherent construct, with neural correlates and negative clinical impact, independent of depression. However, little is known about the neural correlates of anhedonia in stroke patients. In this study, we investigated the association of post-stroke anhedonia with salivary cortisol levels and stroke location and volume.Patients and methods: A psychiatrist administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to identify anhedonia in 36 inpatients, without previous depression, consecutively admitted in a neurology clinic in the first month after a first-ever ischemic stroke. Salivary cortisol levels were assessed in the morning, evening, and after a dexamethasone suppression test. We used magnetic resonance imaging and a semi-automated brain morphometry method to assess stroke location, and the MRIcro program according to the Brodmann Map to calculate the lesion volume.Results: Patients with anhedonia had significantly larger diurnal variation (P-value =0.017) and higher morning levels of salivary cortisol (1,671.9±604.0 ng/dL versus 1,103.9±821.9 ng/dL; P-value =0.022), and greater stroke lesions in the parahippocampal gyrus (Brodmann area 36) compared to those without anhedonia (10.14 voxels; standard deviation ±17.72 versus 0.86 voxels; standard deviation ±4.64; P-value =0.027). The volume of lesion in the parahippocampal gyrus (Brodmann area 36) was associated with diurnal variation of salivary cortisol levels (rho=0.845; P-value =0.034) only in anhedonic patients.Conclusion: Our findings suggest that anhedonia in stroke patients is associated with the volume of stroke lesion in the parahippocampal gyrus and with dysfunction of the hypothalamic–pituitary–adrenal axis. Keywords: anhedonia, stroke, glucocorticoids, depression, hippocampus, parahippocampa

Anticorpos antifosfolípides em 66 pacientes com infarto cerebral entre 15 e 40 anos Antiphospholipid antibodies in 66 patients with cerebral infarction between 15 and 40 years old

Os anticorpos antifosfolípides (aFLs) constituem grupo heterogêneo de imunoglobulinas que tem sido relacionado com alterações na coagulabilidade. Indivíduos com títulos elevados teriam maior probabilidade de desenvolver tromboses de repetição, tanto arterial como venosa, e por conseguinte infarto cerebral (IC). Os testes para detecção mais utilizados em estudos clínicos são o inibidor lúpico e a anticardiolipina. Têm-se relatado maiores percentuais de positividade nesses testes em pacientes jovens com IC. Neste estudo procuramos investigar a prevalência desses anticorpos em pacientes com IC entre 15 e 40 anos em nosso Serviço. Examinamos 66 pacientes para presença de aFLs e obtivemos 16,65% de resultados positivos. Confirmamos diagnóstico de síndrome do anticorpo antifosfolípide primária em três (4,55%) casos. Concluímos que a pesquisa de rotina para aFLs em pacientes jovens com IC está indicada neste grupo de pacientes, mas correlacioná-los com o episódio isquêmico nem sempre é possível.<br>The antiphospholipid antibodies (aPLs) are a heterogenous group of immunoglobulins that have been related with alterations in blood coagulability in recent years. Patients with elevated titers of these antibodies have a high probability to develop thrombotic events, including cerebral infarct (CI). The tests currently used to detect these antibodies are the lupus anticoagulant and ELISA for anticardiolipin antibodies which have a larger proportion of positivity among young patients with CI. In our study we tested 66 patients with cerebral infarcts whose ages ranged from 15 to 40 years for the presence of lupus anticoagulant and anticardiolipin antibodies. The results showed that eleven (16.65%) patients were positive for aPLs and three (4.55%) of them fulfilled the diagnostic criteria for primary antiphospholipid syndrome. These data point out to the importance of investigating aPLs in young patients with CI and its high prevalence in this group compared with healthy population

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Second asymptomatic carotid surgery trial (ACST-2) : a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable