FM-CUN-Artigos em Revistas Internacionais
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- Sighs during sleep in multiple system atrophyPublication . Parreira, Sara; Antunes, Francisco; Coelho, Miguel; Bentes, Carla; Peralta, AnaSighs are physiological phenomena and may occasionally occur during sleep in healthy young adults. Although inspiratory sighs are considered a diagnostic red flag for the parkinsonian form of multiple system atrophy (MSA), its frequency and characteristics are unclear. We aimed to define sigh frequency during sleep recordings in patients with MSA compared to Parkinson's disease (PD) patients, as well as evaluate possible associated breathing disorders or autonomic changes. We analyzed 9 polysomnography's from patients with MSA and 9 from matched PD patients. The proportion of MSA patients (both MSA-P and MSA-C) with sleep-related sighs was significantly higher than that of PD patients, and these occurred predominantly in stages N1 and N2. The median sigh index in sleep and wakefulness were also significantly higher in MSA, although with a significant inter-subject variability. Higher sigh indexes were not associated to other breathing disturbances or with longer disease duration. In MSA, 12% of sighs were associated with oxygen desaturation, while none of the events in PD patients presented with significant changes in oxygen saturation. Respiratory events followed 45% of sighs in MSA, predominantly central sleep apneas, and 29% of sighs in PD, predominantly hypopneas. Our data suggests that high sigh frequencies during sleep should also be considered a red flag for MSA, and future studies should aim to determine whether increased sighing frequency during sleep is specific for this disorder.
- Leaving no stone unturned: the search for stroke associated with atrial fibrillationPublication . Fonseca, Ana CatarinaThe diagnosis of paroxysmal atrial fibrillation (AF) continues to be a main priority in stroke patients. After the clinical trials that evaluated anticoagulation versus antiplatelet treatment in patients with embolic stroke of undetermined source (ESUS) showed that there is no benefit of anticoagulation in the absence of a diagnosis of AF, diagnosing paroxysmal AF continues to be an essential part of the etiological investigation of stroke patients. However, finding paroxysmal AF may be challenging.
- European stroke organization interim expert opinion on cerebral venous thrombosis occurring after SARS-CoV-2 vaccinationPublication . Ferro, José; de Sousa, Diana Aguiar; Coutinho, Jonathan M.; Martinelli, IdaSevere cases of cerebral venous thrombosis (CVT) with thrombocytopenia and anti-platelet factor 4 (PF4) antibodies occurring after adenoviral vector anti-SARS-CoV-2 vaccines have been recently reported. We aim to present a guidance document on the diagnosis and treatment of patients presenting with CVT after vaccination against SARS-CoV-2 infection. We reviewed the available evidence which consists on case reports, small case series, expert opinion and analogy with heparin-induced thrombocytopenia (HIT) management. Because of the low level of evidence, this is an interim document, based only on expert opinion consensus. In patients presenting with CVT after being vaccinated against SARS-CoV-2 infection, if there is thrombocytopenia a reliable HIT PF4 Antibody ELISA test should be performed, to confirm vaccine-induced immune thrombotic thrombocytopenia (VITT). In patients with CVT and thrombocytopenia, in whom VITT is suspected or confirmed, heparin (unfractionated or low molecular weight) should be avoided and non-heparin anticoagulants are preferred. If possible, platelet transfusions should be avoided. If the diagnosis of VITT is confirmed or suspected, early intravenous immunoglobulins are indicated. This expert opinion is supported by low quality evidence. It should be periodically updated, or changed to a formal guideline, as new and higher quality evidence is eventually produced. Because of their potential unfavourable clinical course, patients developing symptoms and signs suggestive of CVT after being vaccinated against SARS-CoV-2 virus should undergo urgent clinical and neuroimaging evaluation. In cases of suspected or confirmed VITT, non-heparin anticoagulants should be used, platelet transfusions avoided and intravenous immunoglobulin started early.
- Matrix Metalloproteinase-9 levels are associated with brain lesion and persistent venous occlusion in patients with cerebral venous thrombosisPublication . de Sousa, Diana Aguiar; Pereira Santos, Maria Conceição; Serra-Caetano, Ana; Lucas Neto, Lia; Sousa, Ana Luísa; Gabriel, Denis; Correia, Manuel; Gil-Gouveia, Raquel; Oliveira, Renato; Penas, Sara; Carvalho Dias, Mariana; Correia, Manuel A.; Carvalho, Marta; Sousa, Ana E.; Canhão, Patrícia; Ferro, JoséBackground: Elucidating mechanisms of brain damage in cerebral venous thrombosis (CVT) would be instrumental to develop targeted therapies and improve prognosis prediction. Matrix metalloproteinase-9 (MMP-9), a gelatinase that degrades major components of the basal lamina, has been associated to blood-brain barrier disruption. We aimed to assess, in patients with CVT, the temporal change in serum concentrations of MMP-9 and its association with key imaging and clinical outcomes. Methods: Pathophysiology of Venous Infarction-PRediction of InfarctiOn and RecanalIzaTion in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Serial collection of peripheral blood samples performed on day 1, 3, and 8, and standardized magnetic resonance imaging on day 1, 8, and 90. MMP-9 was quantified using enzyme-linked immunosorbent assay in 59 patients and 22 healthy controls. Primary outcomes were parenchymal brain lesion, early evolution of brain lesion, early recanalization, and functional outcome on day 90. Results: CVT patients with parenchymal brain lesion had higher baseline concentrations of MMP-9 compared with controls (adjusted p = 0.001). The area under receiver operating characteristic curve value for MMP-9 for predicting brain lesion was 0.71 (95% confidence interval [CI]: 0.57-0.85, p = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 (p = 0.021). Higher MMP-9 on day 8 was associated with persistent venous occlusion (odds ratio: 1.20 [per 20 ng/mL], 95% CI: 1.02-1.43, p = 0.030). Conclusion: We report a novel relationship among MMP-9, parenchymal brain damage, and early venous recanalization, suggesting that circulating MMP-9 is a dynamic marker of brain tissue damage in patients with CVT.
- Patent foramen ovale and strokePublication . Miranda, Bruno; Fonseca, Ana Catarina; Ferro, JoséA patent foramen ovale (PFO) is a highly prevalent finding in cryptogenic ischaemic stroke, particularly in young adults. A common challenge in clinical practice is to distinguish between incidental and pathogenic PFO. Some clinical features and tools such as the Risk of Paradoxical Embolism score may help determining the probability of a stroke-related PFO. Nonetheless, the best therapeutic option to reduce stroke recurrence after a cryptogenic stroke with PFO has been a matter of debate for a long time. We review the mechanisms of stroke-related PFO, together with its clinical features and diagnostic criteria. In addition, we focus on the methodological details and results from new studies in the field of secondary prevention. In contrast to prior evidence, the data from three recent clinical trials and an updated meta-analysis favour PFO closure over medical treatment after cryptogenic stroke/TIA for the prevention of stroke recurrence. The PFO closure device procedure is not associated with higher mortality or cardiovascular events, except for a small increase in the occurrence of transient atrial fibrillation. Furthermore, the benefit of PFO closure was higher among those with atrial septal aneurysm and PFO with large right-to-left shunt. Future studies should address pending issues such as the option for anticoagulants or antiplatelet in patients not undergoing closure, the duration of antiplatelet treatment after PFO closure and the role of PFO closure in patients older than 60.
- Patients with undetermined stroke have increased atrial fibrosis : a cardiac magnetic resonance imaging studyPublication . Fonseca, Ana Catarina; Alves, Pedro; Inácio, Nuno; Marto, João Pedro; Viana-Baptista, Miguel; Melo, Teresa Pinho e; Ferro, José; Almeida, Ana G.Background and Purpose—Some patients with ischemic strokes that are currently classified as having an undetermined cause may have structural or functional changes of the left atrium (LA) and left atrial appendage, which increase their risk of thromboembolism. We compared the LA and left atrial appendage of patients with different ischemic stroke causes using cardiac magnetic resonance imaging. Methods—We prospectively included a consecutive sample of ischemic stroke patients. Patients with structural changes on echocardiography currently considered as causal for stroke in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification were excluded. A 3-T cardiac magnetic resonance imaging was performed. Results—One hundred and eleven patients were evaluated. Patients with an undetermined cause had a higher percentage of LA fibrosis (P=0.03) than patients with other stroke causes and lower, although not statistically significant, values of LA ejection fraction. Patients with atrial fibrillation and undetermined stroke cause showed a similar value of atrial fibrosis. Conclusions—The LA phenotype that was found in patients with undetermined cause supports the hypothesis that an atrial disease may be associated with stroke.
- Impact of physical activity in vascular cognitive impairment (AFIVASC) : study protocol for a randomised controlled trialPublication . Verdelho, Ana; Madureira, Sofia; Correia, Manuel; Ferro, José Manuel; Rodrigues, Mário; Pereira, Manuel Gonçalves; Gonçalves, Mafalda; Santos, Ana Catarina; Vilela, Pedro; Bárrios, Helena; Borges, Mariana; Santa-Clara, HelenaBackground: Cognitive impairment and cerebrovascular pathology are both frequent with ageing. Cognitive impairment due to vascular pathology of the brain, termed vascular cognitive impairment (VCI), is one of the most frequent causes of cognitive impairment in elderly subjects. Thus far, VCI has no specific pharmacological treatment. Recent observational studies have suggested a protective effect of physical activity in cognition, but adequate randomised controlled trials (RCT) are lacking. Methods: AFIVASC is a multi-centre randomised controlled trial, with a 6-month intervention treatment and an additional follow-up of 6 months, that aims to estimate the impact of 6 months of moderate intensity physical activity on cognition (the primary outcome) at 6 and 12 months in subjects with VCI. Participants are community dwellers with criteria for VCI without dementia or who have had previous stroke or transient ischaemic attack (TIA). Patients may be self-referred or referred from a medical appointment. After confirming the inclusion criteria, a run-in period of 1 month is conducted to access adherence; only after that are subjects randomly assigned (using a computerised program blinded to clinical details) to two groups (intervention group and best practice usual care group). The intervention consists of three physical activity sessions of 60 min each (two supervised and one unsupervised) per week. The primary outcome is measured by the presence or absence of decline in cognitive status. Secondary outcomes include changes in neuro-cognitive measures, quality of life, and functional and motor status. Primary and secondary outcomes are evaluated at 6 and 12 months by investigators blinded to both intervention and randomisation. A required sample size of 280 subjects was estimated. Statistical analyses will include regression analysis with repeated measures. The study was approved by the Ethics Committee for Health of Centro Hospitalar de Lisboa Norte (ref. no. 1063/13) and by the Ethics Committee for Health of Centro Hospitalar do Porto CHP (ref. no. 2016.055(049-DEFI/048-CES)). Discussion: We aim to show whether or not moderate physical activity has a beneficial impact on cognition, quality of life, motor, and functional status in people with vascular cognitive impairment, and to generate new insights on the applicability of implementing physical activity in this specific population.
- Treatment variations in cerebral venous thrombosis : an international surveyPublication . Coutinho, J. M.; Seelig, R.; Bousser, M.-G.; Canhão, P.; Ferro, J. M.; Stam, J.Introduction A variety of therapies are available to treat cerebral venous thrombosis (CVT), but evidence supporting the efficacy of most therapies is scarce. Heparin is considered the primary therapy [1] , but there is no consensus whether to use unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The ‘European Federation of Neurological Societies’ (EFNS) guideline recommends LMWH because of practical advantages and based upon data from randomized trials in leg-vein thrombosis [2] . In the ‘International Study on Cerebral Vein and Dural Sinus Thrombosis’ (ISCVT), however, UFH was used in the majority of patients [3] . Endovascular thrombolysis is generally reserved for severe cases, but no randomized trials have been performed [4] . The use of prophylactic anti-epileptic drugs (AED) in CVT is controversial [5, 6] . We hypothesized that considerable variations in treatment for CVT may exist among physicians. The aim of the present study is to determine how physicians worldwide treat CVT, using an online survey that was distributed among physicians with an interest in CVT.
- A study of suicidal thoughts in acute stroke patientsPublication . Santos, Catarina Oliveira; Caeiro, Lara; Ferro, José; Figueira, Maria LuísaBACKGROUND: In previous studies, suicidal thoughts in stroke patients were related to depression and recurrent stroke. The aim of this study was to describe the presence and correlates of suicidal thoughts in acute stroke patients. METHODS: We assessed the presence of suicidal thoughts in a sample of 177 consecutive acute stroke patients (≤4 days), using the item "suicidal thoughts" of the Montgomery and Asberg Depression Rating Scale. RESULTS: Fifteen percent of acute stroke patients had suicidal thoughts, 22% of them with explicit plans to complete suicide. Suicidal thoughts were more frequent in patients with a lower educational level (Chi-square 4.69; P = .05), previous mood disorder (Chi-square 12.80; P = .001), diabetes (Chi-square 5.48; P = .04), and acute depression (Chi-square 16.59; P = .001). In logistic regression, a lower educational level (odds ratio [OR] 5.13; 95% confidence interval [CI] 0.80-33.29), diabetes (OR 3.15; 95% CI 0.81-12.28), a previous mood disorder (OR 4.22; 95% CI 1.12-15.86), and depression (OR 7.82; 95% CI 1.58-38.71) were independent factors predicting suicidal thoughts (R(2) = 0.39%). The 23 depressed acute stroke patients with suicidal thoughts were similar in demographic, clinical, and lesion variables, and were similar in profile of depression to the 63 patients with depression but without suicidal thoughts, except for a higher frequency of a previous mood disorder in the former group (Chi-square 7.87; P = .01). CONCLUSIONS: Suicidal thoughts may develop shortly after the onset of acute stroke, especially in patients with a lower educational level, a previous mood disorder, and those who developed depressive symptoms in the acute phase of stroke. The high frequency of suicidal thoughts makes the assessment of suicidal behavior in patients with acute stroke an important clinical issue.
- Aetiological diagnosis of ischaemic stroke in young adultsPublication . Ferro, José; Massaro, Ayrton R.; Mas, Jean-LouisDespite improvements in diagnosis and treatment, ischaemic stroke in young adults remains a catastrophic event from the patients’ perspective. Stroke can cause death, disability, and hamper quality of life. For the neurologist treating a young adult with suspected ischaemic stroke, the diagnostic challenge is to identify its cause. Contemporary neuroimaging of the brain and its vessels, and a comprehensive cardiac assessment, will enable identifi cation of the most frequent causes of stroke in this age group: cardioembolism and arterial dissection. Specifi c diagnostic tests for the many other rare causes of ischaemic stroke in young adults (angiography, CSF examination, screening for vasculitis and thrombophilia, genetic testing, and ophthalmological examination) should be guided by suspected clinical fi ndings or by the high prevalence of diseases associated with stroke in some countries.