Publications by authors named "Jose M Ferro"

173 Publications

Undergraduate neurology teaching: Comparison of an inpatient versus outpatient clinical setting.

Authors:
Isabel Pavão Martins Ana Catarina Fonseca José M Ferro

Eur J Neurol 2021 Apr 5. Epub 2021 Apr 5.

Department of Clinical Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

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http://dx.doi.org/10.1111/ene.14858DOI Listing
April 2021

Cerebral Venous Thrombosis in Sub-Saharan Africa: A Systematic Review.

Authors:
Yanina Baduro José M Ferro

J Stroke Cerebrovasc Dis 2021 Jun 31;30(6):105712. Epub 2021 Mar 31.

Serviço de Neurologia, Departamento de Neurociências e Saúde Mental, Hospital Santa Maria- CHULN, Lisboa, Portugal; Faculdade de Medicina, Universidade de Lisboa. Electronic address:

Background: The clinical epidemiology of cerebral venous thrombosis (CVT) in Sub-Saharan Africa is unknown. Such information may be relevant for service planning, prevention and for adapting existing CVT management guidelines to that zone of the World.

Aims: Systematic review to describe the demography, associated conditions, clinical and neuroimaging features, treatment and outcome of CVT in Sub-Saharan Africa.

Summary Of Review: We searched MEDLINE, Cochrane Database of Systematic Reviews, clinicaltrials.gov and reference lists of included studies for studies reporting original data on CVT in sub-Saharan Africa. We included 20 observational studies describing 287 CVT patients, 11 case reports (13 patients) and 9 case series (274 patients). All studies had a high risk of bias. In case series 58.6 % of the patients were female, the most common associated condition was infection (63.1%), followed by oral contraceptives (7.3%), pregnancy/puerperium (6.2 %), and prothrombotic conditions (2.2%). CT was the most common method to diagnose CVT (85%). Ninety-nine percent (101/102) of patients reported in case series after the year 2000 were anticoagulated. In case series, 21/210 with information (10 %) patients died in the acute phase, while 60/129 with information (46.5%) recovered without sequels.

Conclusions: The low number of reported CVT cases from Sub-Saharan Africa suggests that CVT is either infrequent, not diagnosed or not reported. Infection is the most common risk factor. Most CVT cases were confirmed by CT alone. Almost all patients reported after year 2000 received anticoagulation. Death rate was higher than in high income countries.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105712DOI Listing
June 2021

Neurology of inflammatory bowel disease.

Authors:
José M Ferro Miguel Oliveira Santos

J Neurol Sci 2021 05 27;424:117426. Epub 2021 Mar 27.

Serviço de Neurologia, Department of Neurological Sciences and Mental Health, Hospital de Santa Maria - CHULN, Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions affecting the digestive system, comprising two main distinctive entities, ulcerative colitis (UC) and Crohn's disease (CD). Besides gastrointestinal manifestations, IBD causes extraintestinal manifestations in the central and peripheral nervous system. The incidence of neurological complications in IBD ranges from 0.25% to 47.5%. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, but dysfunction of the brain-gut axis, arterial and venous thromboembolism, infections, nutritional deficiencies and side-effects of medications (steroids, metronidazole, sulfasalazine, anti-TNF-α, anti-integrin antibodies) are other contributory mechanisms. Patients with IBD have an increased risk of arterial and venous stroke, mainly during periods of exacerbations. Vasculitis is extremely rare. There is a bidirectional association between multiple sclerosis and IBD, with a relative risk for comorbidity of 1.54, being 1.53 for the risk of multiple sclerosis in IBD and 1.55 for the risk of IBD in multiple sclerosis patients. Anti-TNF-α therapy is contraindicated in the treatment of patients who have both IBD and multiple sclerosis. Demyelinating disorders can also be a rare complication of anti-TNF-α therapy. Optic neuritis, transverse myelitis, progressive myelopathy, central nervous system infections, epilepsy and encephalopathy are among other uncommon neurological complications. Peripheral nervous system manifestations include peripheral neuropathy, either demyelination and axonal, myasthenia gravis and polymyositis/dermatomyositis and localized forms of myositis.
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http://dx.doi.org/10.1016/j.jns.2021.117426DOI Listing
May 2021

Matrix Metalloproteinase-9 Levels are Associated with Brain Lesion and Persistent Venous Occlusion in Patients with Cerebral Venous Thrombosis.

Authors:
Diana Aguiar de Sousa Maria Conceição Pereira-Santos Ana Serra-Caetano Lia Lucas Neto Ana Luísa Sousa Denis Gabriel Manuel Correia Raquel Gil-Gouveia Renato Oliveira Sara Penas Mariana Carvalho Dias Manuel A Correia Marta Carvalho Ana E Sousa Patrícia Canhão José M Ferro

Thromb Haemost 2021 Mar 23. Epub 2021 Mar 23.

Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria/CHULN, Universidade de Lisboa, Lisbon, Portugal.

Background:  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  = 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,  = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 ( = 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,  = 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.
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http://dx.doi.org/10.1055/s-0041-1726094DOI Listing
March 2021

Recanalization after cerebral venous thrombosis. A randomized controlled trial of the safety and efficacy of dabigatran etexilate versus dose-adjusted warfarin in patients with cerebral venous and dural sinus thrombosis.

Authors:
José M Ferro Martin Bendszus Olav Jansen Jonathan M Coutinho Francesco Dentali Adam Kobayashi Diana Aguiar de Sousa Lia L Neto Corinna Miede Jorge Caria Holger Huisman Hans-Christoph Diener

Int J Stroke 2021 Apr 4:17474930211006303. Epub 2021 Apr 4.

Faculty of Medicine, University Duisburg-Essen, Essen, Germany.

Background: The effect of different anticoagulants on recanalization after cerebral venous thrombosis has not been studied in a randomized controlled trial.

Methods: RE-SPECT CVT (ClinicalTrials.gov number: NCT02913326) was a Phase III, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded endpoint adjudication. Acute cerebral venous thrombosis patients were allocated to dabigatran 150 mg twice daily, or dose-adjusted warfarin, for 24 weeks, after 5-15 days' treatment with unfractionated or low-molecular-weight heparin. A standardized magnetic resonance protocol including arterial spin labeling, three-dimensional time-of-flight venography, and three-dimensional contrast-enhanced magnetic resonance angiography was obtained at the end of the treatment period. Cerebral venous recanalization at six months was assessed by two blinded adjudicators, using the difference in a score of occluded sinuses and veins (predefined secondary efficacy endpoint) and in the modified Qureshi scale (additional endpoint), between baseline and the end of the treatment.

Results: Of 120 cerebral venous thrombosis patients randomized, venous recanalization could be evaluated in 108 (55 allocated to dabigatran and 53 to warfarin, 1 patient had a missing occlusion score at baseline). No patient worsened in the score of occluded cerebral veins and sinuses, while 33 (60%) on dabigatran and 35 (67%) on warfarin improved. The mean score change from baseline in the occlusion score was similar in the two treatment groups (dabigatran -0.8, SD 0.78; warfarin -1.0, SD 0.92). In the modified Qureshi score, full recanalization was adjudicated in 24 (44%) and 19 (36%), and partial recanalization in 23 (42%) and 26 (49%) patients in the dabigatran and warfarin arms, respectively. No statistically significant treatment difference in the modified Qureshi score could be detected ( = 0.44).

Conclusion: The majority of patients with cerebral venous thrombosis, anticoagulated with either dabigatran or warfarin for six months, showed partial or complete recanalization of occluded sinuses and veins at the end of the treatment. Trial registry name: ClinicalTrials.gov URL: https://clinicaltrials.gov Registration number: NCT02913326.
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http://dx.doi.org/10.1177/17474930211006303DOI Listing
April 2021

Neurological complications of cardiomyopathies.

Authors:
Ana Catarina Fonseca Ana G Almeida Miguel Oliveira Santos José M Ferro

Handb Clin Neurol 2021 ;177:91-109

Neurology Service, Hospital Santa Maria, Centro Hospitalar Lisboa Norte and Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Electronic address:

There is a multifaceted relationship between the cardiomyopathies and a wide spectrum of neurological disorders. Severe acute neurological events, such as a status epilepticus and aneurysmal subarachnoid hemorrhage, may result in an acute cardiomyopathy the likes of Takotsubo cardiomyopathy. Conversely, the cardiomyopathies may result in a wide array of neurological disorders. Diagnosis of a cardiomyopathy may have already been established at the time of the index neurological event, or the neurological event may have prompted subsequent cardiac investigations, which ultimately lead to the diagnosis of a cardiomyopathy. The cardiomyopathies belong to one of the many phenotypes of complex genetic diseases or syndromes, which may also involve the central or peripheral nervous systems. A number of exogenous agents or risk factors such as diphtheria, alcohol, and several viruses may result in secondary cardiomyopathies accompanied by several neurological manifestations. A variety of neuromuscular disorders, such as myotonic dystrophy or amyloidosis, may demonstrate cardiac involvement during their clinical course. Furthermore, a number of genetic cardiomyopathies phenotypically incorporate during their clinical evolution, a gamut of neurological manifestations, usually neuromuscular in nature. Likewise, neurological complications may be the result of diagnostic procedures or medications for the cardiomyopathies and vice versa. Neurological manifestations of the cardiomyopathies are broad and include, among others, transient ischemic attacks, ischemic strokes, intracranial hemorrhages, syncope, muscle weakness and atrophy, myotonia, cramps, ataxia, seizures, intellectual developmental disorder, cognitive impairment, dementia, oculomotor palsies, deafness, retinal involvement, and headaches.
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http://dx.doi.org/10.1016/B978-0-12-819814-8.00001-9DOI Listing
January 2021

Cerebrovascular manifestations in hematological diseases: an update.

Authors:
José M Ferro Joana Infante

J Neurol 2021 Feb 13. Epub 2021 Feb 13.

Serviço de Hematologia e Transplantação de Medula, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.

Patients with hematological diseases often experience cerebrovascular complications including ischemic stroke, intracerebral and subarachnoid hemorrhage, microbleeds, posterior reversible encephalopathy syndrome, and dural sinus and cerebral vein thrombosis (CVT). In this update, we will review recent advances in the management of cerebrovascular diseases in the context of myeloproliferative neoplasms, leukemias, lymphomas, multiple myeloma, POEMS, paroxysmal nocturnal hemoglobinuria (PNH), thrombotic thrombocytopenic purpura (TTP), and sickle-cell disease. In acute ischemic stroke associated with hematological diseases, thrombectomy can in general be applied if there is a large vessel occlusion. Intravenous thrombolysis can be used in myeloproliferative neoplasms and sickle-cell anemia, but in other diseases, a case-by-case evaluation of the bleeding risks is mandatory. Patients with sickle-cell disease and acute stroke need very often to be transfused. In PNH, acute ischemic stroke patients must be anticoagulated. Most patients with CVT can be treated with low-molecular weight heparin (LMWH) acutely, even those with leukemias. Prevention of recurrence of cerebral thrombotic events depends on the control of the underlying disease, combined in some conditions with antithrombotic drugs. The recent introduction of specific monoclonal antibodies in the treatment of PHN and TTP has dramatically reduced the risk of arterial and venous thrombosis.
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http://dx.doi.org/10.1007/s00415-021-10441-9DOI Listing
February 2021

Cardiovascular magnetic resonance imaging and its role in the investigation of stroke: an update.

Authors:
Ana Catarina Fonseca José M Ferro Ana G Almeida

J Neurol 2021 Jan 13. Epub 2021 Jan 13.

Department of Cardiology, Hospital de Santa Maria, CCUL, University of Lisboa, Lisbon, Portugal.

Recent advances in complementary diagnostic exams have helped to clarify stroke etiology, not only by helping to confirm established stroke causes but also by unveiling new possible stroke mechanisms. Etiological investigation for cardioembolic stroke has benefited in the last years from information provided by studies analysing serum biomarkers, heart rhythm monitoring and imaging methods like cardiovascular magnetic resonance (CMR) imaging. CMR has been particularly important for the characterization of possible new cardioembolic stroke mechanisms including atrial cardiomyopathy, silent myocardial infarction and cardiomyopathies.
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http://dx.doi.org/10.1007/s00415-020-10393-6DOI Listing
January 2021

Undergraduate neurology teaching: Comparison of an inpatient versus outpatient clinical setting.

Authors:
Isabel Pavão Martins Ana Catarina Fonseca Luísa Pires José M Ferro

Eur J Neurol 2021 Apr 30;28(4):1108-1112. Epub 2020 Dec 30.

Department of Clinical Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

Background: Neurology is often perceived as a difficult discipline by medical students, yet it is an essential part of medical training. While the most common disorders of the nervous system can be observed in the outpatient setting, positive neurological signs are more likely to be found in neurology wards. We aimed to compare the impact of a neurology outpatient versus inpatient rotation setting on the grades obtained by medical students as a proxy measure of the learning outcomes.

Methods: We compared the results obtained by fourth year medical students in practical (OSCE) and multiple choice question (MCQ) exams in neurology, between students whose main (total of 24 h contact) teaching allocation was either the outpatient or inpatient setting, controlling for students' gender, teacher, academic year and student' previous achievement (measured by their scores on practical evaluation).

Results: A total of 1127 students were included, of whom 644 (57.14%) were allocated mainly to the neurology ward and 483 (42.86%) to the outpatient clinic. Students assigned to the ward obtained significantly higher grades in the OSCE and MCQ exams than those placed in the outpatient clinic. Teaching setting was an independent predictor of both classifications after adjustment.

Conclusions: The teaching setting had a significant impact on the learning outcomes. This may be due to a higher likelihood of observing abnormal neurological signs or to more student-centered teaching on the ward. These results highlight the importance of a balanced distribution of students by different clinical settings.
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http://dx.doi.org/10.1111/ene.14677DOI Listing
April 2021

Author response: Undetermined stroke genesis and hidden cardiomyopathies determined by cardiac magnetic resonance.

Authors:
Ana Catarina Fonseca José M Ferro

Neurology 2020 11;95(20):941

(Lisbon).

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http://dx.doi.org/10.1212/WNL.0000000000010981DOI Listing
November 2020

N-Terminal Pro-B-Type Natriuretic Peptide Levels in Parkinson's Disease.

Authors:
Mariana Alves Daniel Caldeira Sofia Reimão José M Ferro Joaquim J Ferreira

Mov Disord 2020 10;35(10):1886-1887

Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal.

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http://dx.doi.org/10.1002/mds.28276DOI Listing
October 2020

Five-Year Prognosis After TIA or Minor Ischemic Stroke in Asian and Non-Asian Populations.

Authors:
Takao Hoshino Shinichiro Uchiyama Lawrence K S Wong Kazuo Kitagawa Hugo Charles Julien Labreuche Philippa C Lavallée Gregory W Albers Louis R Caplan Geoffrey A Donnan José M Ferro Michael G Hennerici Carlos Molina Peter M Rothwell P Gabriel Steg Pierre-Jean Touboul Éric Vicaut Pierre Amarenco

Neurology 2021 01 12;96(1):e54-e66. Epub 2020 Oct 12.

From the Department of Neurology and Stroke Center (T.H., H.C., J.L., P.C.L., P.-J.T., P.A.), Bichat Hospital, AP-HP and INSERM LVTS-U1148, DHU FIRE, Université Paris-Diderot, Sorbonne-Paris Cité, France; Center for Brain and Cerebral Vessels (S.U.), Sanno Hospital and Sanno Medical Center, International University of Health and Welfare, Tokyo, Japan; Department of Medicine and Therapeutics (L.K.S.W.), Chinese University of Hong Kong, Prince of Wales Hospital; Department of Neurology (T.H., K.K.), Tokyo Women's Medical University, Japan; Université Lille (J.L.), Centre Hospitalier Universitaire Lille, Équipe d'Accueil 2694-Santé Publique: Épidémiologie et Qualité des Soins, Lille, France; Stanford Stroke Center (G.W.A.), Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA; Cerebrovascular Disease Service (L.R.C.), Beth Israel Deaconess Medical Center, Harvard University, Boston, MA; Melbourne Brain Centre (G.A.D.), Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Department of Neurosciences (J.M.F.), Service of Neurology, Hospital Santa Maria, University of Lisbon, Portugal; Department of Neurology (M.G.H.), Universitäts Medizin Mannheim, Heidelberg University, Germany; Stroke Unit, Department of Neurology (C.M.), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Spain; Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK; Department of Cardiology (P.G.S.), Bichat Hospital, AP-HP, Paris, France; National Heart and Lung Institute Imperial College (P.G.S.), Institute of Cardiovascular Medicine and Science Royal Brompton Hospital, London, UK; Department of Biostatistics (É.V.), Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital, AP-HP, Paris, France.

Objective: To determine long-term vascular outcomes of Asian patients who experienced TIA or minor ischemic stroke and to compare the outcomes of Asian patients with those of non-Asian patients, in the context of modern guideline-based prevention strategies.

Methods: This is a subanalysis of the TIAregistry.org project, in which 3,847 patients (882 from Asian and 2,965 from non-Asian countries) with a recent TIA or minor ischemic stroke were assessed and treated by specialists at 42 dedicated units from 14 countries and followed for 5 years. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome.

Results: No differences were observed in the 5-year risk of the primary outcome (14.0% vs 11.7%; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88-1.37; = 0.41) and stroke (10.7% vs 8.5%; HR, 1.17; 95% CI, 0.90-1.51; = 0.24) between Asian and non-Asian patients. Asian participants were at higher risk of intracranial hemorrhage (1.8% vs 0.8%; HR, 2.23; 95% CI, 1.09-4.57; = 0.029). Multivariable analysis showed that the presence of multiple acute infarctions on initial brain imaging was an independent predictor of primary outcome and modified Rankin Scale score of >1 in both Asian (HR, 1.91; 95% CI, 1.11-3.29; = 0.020) and non-Asian (HR, 1.39; 95% CI, 1.02-1.90; = 0.037) patients.

Conclusion: The long-term risk of vascular events in Asian patients was as low as that in non-Asian patients, while Asian participants had a 2.2-fold higher intracranial hemorrhage risk. Multiple acute infarctions were independently associated with future disability in both groups.

Classification Of Evidence: This study provides Class I evidence that among people who experienced TIA or minor stroke, Asian patients have a similar 5-year risk of cardiovascular death, stroke, and acute coronary syndrome as non-Asian patients.
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http://dx.doi.org/10.1212/WNL.0000000000010995DOI Listing
January 2021

Endovascular Treatment for Cerebral Venous Thrombosis.

Authors:
Jonathan M Coutinho Jose M Ferro Jan Stam

World Neurosurg 2020 12 28;144:194-195. Epub 2020 Sep 28.

Department of Neurology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.wneu.2020.09.119DOI Listing
December 2020

Dural Arteriovenous Fistulae After Cerebral Venous Thrombosis.

Authors:
José M Ferro Jonathan M Coutinho Olav Jansen Martin Bendszus Francesco Dentali Adam Kobayashi Bas van der Veen Corinna Miede Jorge Caria Holger Huisman Hans-Christoph Diener

Stroke 2020 11 25;51(11):3344-3347. Epub 2020 Sep 25.

Faculty of Medicine, University Duisburg-Essen, Germany (H.-C.D.).

Background And Purpose: This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate with dose-adjusted warfarin (RE-SPECT CVT [A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis]), who had systematic follow-up magnetic resonance (MR) imaging.

Methods: RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial.

Results: We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up.

Conclusions: Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02913326.
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http://dx.doi.org/10.1161/STROKEAHA.120.031235DOI Listing
November 2020

Late seizures in cerebral venous thrombosis.

Authors:
Mayte Sánchez van Kammen Erik Lindgren Suzanne M Silvis Sini Hiltunen Mirjam Rachel Heldner Fabiola Serrano Johan Zelano Susanna M Zuurbier Maryam Mansour Diana Aguiar de Sousa Patrícia Canhão Saleem Al-Asady Esme Ekizoglu Petra Redfors Nilufer Yesilot Masoud Ghiasian Miguel A Barboza Valentina Arnao Paolo Aridon Martin N M Punter José M Ferro Antonio Arauz Turgut Tatlisumak Marcel Arnold Jukka Putaala Katarina Jood Jonathan M Coutinho

Neurology 2020 09 5;95(12):e1716-e1723. Epub 2020 Aug 5.

From the Department of Neurology (M.S.v.K., S.M.S., S.M.Z., J.M.C.), Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Clinical Neuroscience (E.L., J.Z., P.R., T.T., K.J.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (E.L., J.Z., P.R., T.T., K.J.), Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurology (S.H., T.T., J.P.), Helsinki University Hospital and University of Helsinki, Finland; Department of Neurology (M.R.H., M.A.), Inselspital, Bern University Hospital and University of Bern, Switzerland; National Institute of Neurology and Neurosurgery Manuel Velasco Suarez (F.S., A.A.), Mexico City, Mexico; Sina Hospital (M.M., M.G.), Hamadan University of Medical Science, Iran; Department of Neurosciences and Mental Health (Neurology) (D.A.d.S., P.C., J.M.F.), Hospital de Santa Maria/CHULN; University of Lisbon (D.A.d.S., P.C., J.M.F.), Portugal; Manchester Centre for Clinical Neurosciences (S.A.-A., M.N.M.P.), Salford Royal NHS Foundation Trust, UK; Department of Neurology (E.E., N.Y.), Istanbul Faculty of Medicine, Istanbul University, Turkey; Neurosciences Department (M.A.B.), Hospital Dr. R.A. Calderón Guardia, CCSS, San José, Costa Rica; and Department of Biomedicine, Neuroscience and Advanced Diagnostics (V.A., P.A.), University of Palermo, Italy.

Objective: To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT.

Methods: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS.

Results: We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS.

Conclusion: During a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS.
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http://dx.doi.org/10.1212/WNL.0000000000010576DOI Listing
September 2020

Acute symptomatic seizures in cerebral venous thrombosis.

Authors:
Erik Lindgren Suzanne M Silvis Sini Hiltunen Mirjam R Heldner Fabiola Serrano Michele de Scisco Johan Zelano Susanna M Zuurbier Mayte Sánchez van Kammen Maryam Mansour Diana Aguiar de Sousa Sara Penas Saleem Al-Asady Esme Ekizoglu Petra Redfors Awet Ahmed Nilufer Yesilot Masoud Ghiasian Miguel A Barboza Valencia Arnao Paolo Aridon Martin N M Punter José M Ferro Timothy Kleinig Antonio Arauz Turgut Tatlisumak Marcel Arnold Jukka Putaala Jonathan M Coutinho Katarina Jood

Neurology 2020 09 5;95(12):e1706-e1715. Epub 2020 Aug 5.

From the Department of Clinical Neuroscience (E.L., J.Z., P.R., A. Ahmed, T.T., K.J.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (E.L., J.Z., P.R., A. Ahmed, T.T., K.J.), Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurology (S.M.S., S.M.Z., M.S.v.K., J.M.C.), Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Neurology (S.H., T.T., J.P.), Helsinki University Hospital and University of Helsinki, Finland; Department of Neurology (M.R.H., M.A.), Inselspital, Bern University Hospital and University of Bern, Switzerland; National Institute of Neurology and Neurosurgery Manuel Velasco Suarez (F.S., A. Arauz), Mexico City, Mexico; Department of Neurology (M.d.S., T.K.), Royal Adelaide Hospitals and Department of Medicine, University of Adelaide, SA, Australia; Sina Hospital (M.M., M.G.), Hamadan University of Medical Science, Iran; Department of Neurosciences and Mental Health (Neurology) (D.A.d.S., J.M.F.), Hospital de Santa Maria/CHULN; University of Lisbon (D.A.d.S., J.M.F.); Faculdade de Medicina (S.P.), Universidade de Lisboa, Lisbon, Portugal; Manchester Centre for Clinical Neurosciences (S.A.-A., M.N.M.P.), Salford Royal NHS Foundation Trust, UK; Department of Neurology (E.E., N.Y.), Istanbul Faculty of Medicine, Istanbul University, Turkey; Neurosciences Department (M.A.B.), Hospital Dr. R.A. Calderón Guardia, CCSS, San José, Costa Rica; and Department of Biomedicine (V.A., P.A.), Neuroscience and Advanced Diagnostics, University of Palermo, Italy.

Objective: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium.

Methods: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression.

Results: Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome.

Conclusion: ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.
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http://dx.doi.org/10.1212/WNL.0000000000010577DOI Listing
September 2020

Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial.

Authors:
Jonathan M Coutinho Susanna M Zuurbier Marie-Germaine Bousser Xunming Ji Patricia Canhão Yvo B Roos Isabelle Crassard Ana Paiva Nunes Maarten Uyttenboogaart Jian Chen Bart J Emmer Stefan D Roosendaal Emmanuel Houdart Jim A Reekers René van den Berg Rob J de Haan Charles B Majoie José M Ferro Jan Stam

JAMA Neurol 2020 08;77(8):966-973

Department of Neurology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.

Importance: To date, only uncontrolled studies have evaluated the efficacy and safety of endovascular treatment (EVT) in patients with cerebral venous thrombosis (CVT), leading to the lack of recommendations on EVT for CVT.

Objective: To evaluate the efficacy and safety of EVT in patients with a severe form of CVT.

Design, Setting, And Participants: TO-ACT (Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis) was a multicenter, open-label, blinded end point, randomized clinical trial conducted in 8 hospitals in 3 countries (the Netherlands, China, and Portugal). Patients were recruited from September 2011 to October 2016, and follow-up began in March 2012 and was completed in December 2017. Adult patients with radiologically confirmed CVT who had at least 1 risk factor for a poor outcome (mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system) were included. Data were analyzed according to the intention-to-treat principle from March 2018 to February 2019. The trial was halted after the first interim analysis for reasons of futility.

Interventions: Patients were randomized to receive either EVT with standard medical care (intervention group) or guideline-based standard medical care only (control group). The EVT consisted of mechanical thrombectomy, local intrasinus application of alteplase or urokinase, or a combination of both strategies. Patients in the intervention group underwent EVT as soon as possible but no later than 24 hours after randomization.

Main Outcomes And Measures: Primary end point was the proportion of patients with a good outcome at 12 months (recovered without a disability; modified Rankin Scale [mRS] score of 0-1). Secondary end points were the proportion of patients with an mRS score of 0 to 1 at 6 months and an mRS score of 0 to 2 at 6 and 12 months, outcome on the mRS across the ordinal continuum at 12 months, recanalization rate, and surgical interventions in relation to CVT. Safety end points included symptomatic intracranial hemorrhage.

Results: Of the 67 patients enrolled and randomized, 33 (49%) were randomized to the intervention group and 34 (51%) were randomized to the control group. Patients in the intervention group vs those in the control group were slightly older (median [interquartile range (IQR)] age, 43 [33-50] years vs 38 [23-48] years) and comprised fewer women (23 women [70%] vs 27 women [79%]). The median (IQR) baseline National Institutes of Health Stroke Scale score was 12 (7-20) in the EVT group and 12 (5-20) in the standard care group. At the 12-month follow-up, 22 intervention patients (67%) had an mRS score of 0 to 1 compared with 23 control patients (68%) (relative risk ratio, 0.99; 95% CI, 0.71-1.38). Mortality was not statistically significantly higher in the EVT group (12% [n = 4] vs 3% [n = 1]; P = .20). The frequency of symptomatic intracerebral hemorrhage was not statistically significantly lower in the intervention group (3% [n = 1] vs 9% [n = 3]; P = .61).

Conclusions And Relevance: The TO-ACT trial showed that EVT with standard medical care did not appear to improve functional outcome of patients with CVT. Given the small sample size, the possibility exists that future studies will demonstrate better recovery rates after EVT for this patient population.

Trial Registration: ClinicalTrials.gov Identifier: NCT01204333.
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http://dx.doi.org/10.1001/jamaneurol.2020.1022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235912PMC
August 2020

Response to the Letter by Ajay K Mishra and Co-workers Commenting on "Safety and Efficacy of Thrombolysis and Mechanical Thrombectomy in Infective Endocarditis".

Authors:
Sofia Bettencourt José M Ferro

J Stroke Cerebrovasc Dis 2020 06 20;29(6):104791. Epub 2020 Mar 20.

Hospital de Santa Maria, Neurology, Serviço de Neurologia, Portugal.

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104791DOI Listing
June 2020

Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation.

Authors:
Diana Aguiar de Sousa Lia Lucas Neto Antonio Arauz Ana Luísa Sousa Denis Gabriel Manuel Correia Raquel Gil-Gouveia Sara Penas Mariana Carvalho Dias Manuel A Correia Marta Carvalho Patrícia Canhão José M Ferro

Stroke 2020 04 2;51(4):1174-1181. Epub 2020 Mar 2.

From the Department of Neurosciences and Mental Health (Neurology), Hospital Santa Maria/CHULN, University of Lisbon, Portugal (D.A.d.S., M.C.D., P.C., J.M.F.).

Background and Purpose- The hypothesis that venous recanalization prevents progression of venous infarction is not established in patients with cerebral venous thrombosis (CVT). Evidence is also scarce on the association between residual symptoms, particularly headache, and the recanalization grade. We aimed to assess, in patients with CVT treated with standard anticoagulation, (1) the rate of early venous recanalization, (2) whether lack of early recanalization was predictor of parenchymal brain lesion progression, and (3) the prevalence and features of persistent headache according to the recanalization grade achieved. Methods- PRIORITy-CVT (Pathophysiology of Venous Infarction - Prediction of Infarction and Recanalization in CVT) was a multicenter, prospective, cohort study including patients with newly diagnosed CVT. Standardized magnetic resonance imaging was performed at inclusion (≤24 hours of therapeutic anticoagulation), days 8 and 90. Potential imaging predictors of recanalization were predefined and analyzed at each anatomical segment. Primary outcomes were rate of early recanalization and brain lesion progression at day 8. Secondary outcomes were headache (days 8 and 90) and functional outcome (modified Rankin Scale at days 8 and 90). Results- Sixty eight patients with CVT were included, of whom 30 (44%) had parenchymal lesions. At the early follow-up (n=63; 8±2 days), 68% (n=43) of patients had partial recanalization and 6% (n=4) full recanalization. Early recanalization was associated both with early regression (=0.03) and lower risk of enlargement of nonhemorrhagic lesions (=0.02). Lesions showing diffusion restriction (n=12) were fully reversible in 66% of cases, particularly in patients showing early venous recanalization. Evidence of new or enlarged hemorrhagic lesions, headache at days 8 and 90, and unfavorable functional outcome at days 8 and 90 were not significantly different in patients achieving recanalization. Conclusions- Venous recanalization started within the first 8 days of therapeutic anticoagulation in most patients with CVT and was associated with early regression of nonhemorrhagic lesions, including venous infarction. There was an association between persistent venous occlusion at day 8 and enlargement of nonhemorrhagic lesions.
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http://dx.doi.org/10.1161/STROKEAHA.119.028532DOI Listing
April 2020

Acute Ischemic Stroke Treatment in Infective Endocarditis: Systematic Review.

Authors:
Sofia Bettencourt José M Ferro

J Stroke Cerebrovasc Dis 2020 Apr 3;29(4):104598. Epub 2020 Feb 3.

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Department of Neurosciences and Mental Health, Serviço de Neurologia, Hospital Santa Maria/Centro Hospitalar Lisboa Norte, Lisboa, Portugal.

Background: Ischemic stroke is a frequent neurologic complication of infective endocarditis. This systematic review aims to evaluate the efficacy and safety of thrombectomy in comparison to thrombolysis and to combined treatment in patients with infective endocarditis associated acute ischemic stroke.

Methods: A systematic literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review included case reports, cases series, cross-sectional studies, case control studies, randomized controlled trials or nonrandomized controlled trials, which reported the treatment of endocarditis-related acute ischemic stroke with mechanical thrombectomy, intravenous or intra-arterial thrombolysis in adult patients.

Data Sources: Scielo, b-on, Pubmed and Cochrane, from inception to April 2019. Reference lists were also checked. We compared the efficacy (independence, neurological improvement) and safety (intracranial bleeding, death) of acute ischemic stroke treatment with thrombolysis, thrombectomy and combined therapy.

Results: Through systematic review 37 articles describing 52 patients met criteria. The risk of intracranial hemorrhage was 4.14 times higher in patients treated with intravenous thrombolysis (P = .001) and 4.67 times higher in patients treated with combined treatment (P = .01). There was trend for independence (P = .09) and neurological improvement (P = .07) in favor of thrombectomy, when comparing this group to the group treated with intravenous thrombolysis.

Conclusions: With the limitation of the low quality of the available evidence, thrombectomy in infective endocarditis associated stroke appears to be safer than thrombolysis, or combined treatment. These results may be useful to guide clinical decisions, in selected patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104598DOI Listing
April 2020

Headache at the Chronic Stage of Ischemic Stroke.

Authors:
Mariana Carvalho Dias Teresa Martins Gonçalo Basílio Lia Lucas Neto Lara Caeiro José M Ferro Ana Verdelho

Headache 2020 03 5;60(3):607-614. Epub 2020 Feb 5.

Neurology Service, Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal.

Background: Headache in ischemic stroke survivors after the acute stage is incompletely described.

Objective: We aimed to prospectively describe the characteristics of headache and the predictors of headache at the chronic stage after ischemic stroke.

Methods: We conducted a prospective observational cohort study including 102 acute ischemic stroke patients admitted to a Stroke Unit. Patients were interviewed at the acute and the chronic stage (12 months after stroke). Characteristics of those headaches were collected using a previously validated headache questionnaire enabling headache classification following the International Headache Society criteria. Pre-stroke headache history was registered using the same instrument.

Results: Forty-five patients out of 89 with completed follow-up (51%) reported headache at the chronic stage. In most of the patients, headache was sporadic, mild, pressure-like, with a duration of minutes to hours, with characteristics of tension-type headache in 51% (n = 23/45). Headache was a reactivation of pre-stroke headache in 33% (n = 15/45), different from pre-stroke headache in 44% (n = 20/45), and of new-onset in 22% (n = 10/45). Only 1 patient had a new-onset headache at the acute stage that persisted with the same characteristics at the chronic stage. Pre-stroke headache (OR = 5.3; 95% CI [2.01-13.98] P = .001) and female sex (OR = 3.5; 95% CI [1.3-9.4] P = .013) predicted headache at the chronic stage after stroke, controlling for age, severity, and location of stroke.

Conclusions: Headache in ischemic stroke survivors at the chronic stage is more frequent in women and in patients with pre-stroke headache. It is most frequently a headache with different characteristics of the pre-stroke headache and only rarely a new-onset headache starting at the acute stage and persisting at the chronic stage.
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http://dx.doi.org/10.1111/head.13761DOI Listing
March 2020

Undetermined stroke genesis and hidden cardiomyopathies determined by cardiac magnetic resonance.

Authors:
Ana Catarina Fonseca João Pedro Marto Daniela Pimenta Tatiana Guimarães Pedro N Alves Nuno Inácio Miguel Viana-Baptista Teresa Pinho E Melo Fausto J Pinto José M Ferro Ana G Almeida

Neurology 2020 01 2;94(1):e107-e113. Epub 2019 Dec 2.

From the Department of Neurology (A.C.F., D.P., P.N.A., T.P.e.M., J.M.F.), Hospital de Santa Maria, Institute of Molecular Medicine, University of Lisboa; Department of Neurology (J.P.M., M.V.-B.), Hospital Egas Moniz; Department of Cardiology (T.G., F.J.P., A.G.A.), Hospital de Santa Maria, University of Lisboa; and Department of Neurology (N.I.), Hospital Beatriz Ângelo, Lisbon, Portugal.

Objective: To determine whether cardiac magnetic resonance imaging (CMR) could be useful in identifying previously undiagnosed cardiomyopathies in a cohort of patients with ischemic stroke who underwent standard etiologic investigation and to describe the type and frequency of these cardiomyopathies.

Methods: We performed a subanalysis of a previously collected prospective cohort of patients with ischemic stroke. Patients with structural changes on echocardiography that are considered causal for stroke in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification were excluded. A 3T CMR was performed. We compared the frequency of the cardiomyopathies that we found with reference values for the general population.

Results: One hundred thirty-two patients with a mean age of 68.4 years were included. In 7 patients (5.3%, 95% confidence interval 2.59%-10.54%) CMR identified cardiomyopathy. Four patients had hypertrophic cardiomyopathy, 2 had restrictive cardiomyopathy, and 1 had noncompaction cardiomyopathy. Six of these patients had been classified after standard evaluation as having undetermined stroke and 1 patient as having cardioembolic stroke (atrial fibrillation). We found a higher frequency of hypertrophic cardiomyopathy in the entire cohort and in the undetermined cause group compared to the general population (3.03% and 5.81% vs 0.2%, respectively, = 0.001 and < 0.001). The frequency of noncompaction cardiomyopathy was also higher in our cohort (0.76% vs 0.05%, respectively, < 0.001).

Conclusions: Although rare, cardiomyopathies should be considered as a possible cause of ischemic stroke classified as of undetermined etiology after standard evaluation.
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http://dx.doi.org/10.1212/WNL.0000000000008698DOI Listing
January 2020

Reperfusion therapies and poststroke seizures.

Authors:
Carla Bentes Francesco Brigo Johan Zelano José M Ferro

Epilepsy Behav 2020 03 11;104(Pt B):106524. Epub 2019 Nov 11.

Department of Neuroscience and Mental Health (Neurology), Hospital de Santa Maria, CHULN, Lisbon, Portugal; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.

Seizures are not only a frequent complication of stroke but have been associated with an unfavorable functional and vital outcome of patients who have had stroke. Facing a new paradigm of acute standard stroke care, acute symptomatic seizures in this clinical setting deserve to be rethought. Reperfusion therapies, the gold standard treatment for acute ischemic stroke, improve long-term survival and outcome of patients who have had stroke and have been associated both with clinical seizures and the occurrence of epileptiform activity in the electroencephalogram (EEG). This narrative review describes the different physiopathological mechanisms underlying the possible association between reperfusion therapies and seizures, both acute symptomatic seizures and unprovoked seizures, and the current evidence regarding the risk of poststroke seizures in treated patients. It also identifies the gaps in our knowledge to foster future studies in this field. By different mechanisms, reperfusions therapies may have opposing effects on the risk of poststroke seizures. There is a need for a better definition of the specific physiopathology of seizures in clinical practice, as many factors can be recognized. Additionally, most of the current clinical evidence refers to acute symptomatic seizures and not to unprovoked seizures or poststroke epilepsy, and our analysis does not support the existence of a strong association between thrombolysis and poststroke seizures. So far, the impact of reperfusion therapies on the frequency of poststroke seizures is unclear. To study this effect, many clinical challenges must be overcome, including a better and clear operational definition of seizures and stroke characteristics, the standard of stroke and epilepsy care and EEG monitoring, and the degree of reperfusion success. Prospective, high quality, larger, and longer follow-up multicentric studies are urgently needed. Additionally, stroke registries can also prove useful in better elucidate whether there is an association between reperfusion therapies and seizures. This article is part of the Special Issue "Seizures & Stroke".
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http://dx.doi.org/10.1016/j.yebeh.2019.106524DOI Listing
March 2020

Emotions after stroke: A narrative update.

Authors:
José M Ferro Ana C Santos

Int J Stroke 2020 04 3;15(3):256-267. Epub 2019 Oct 3.

Hospital do Mar - Cuidados Especializados Lisboa, Bobadela, Portugal.

Aim: In this narrative review we aimed to describe how stroke affects emotions and update the readers on the emotional disturbances that occur after stroke.

Methods: We searched Medline from 1.1.2013 to 1.7.2019, personal files and references of selected publications. All retrieved systematic reviews and randomized controlled trials were included. Other references were selected by relevance.

Summary Of Review: The emotional response includes a reactive behavior with arousal, somatic, motivational and motor components, and a distinctive cognitive and subjective affective experience. Emotional category responses and experiences after stroke can show dissociations between the behavioral response and the cognitive and affective experiences. Emotional disturbances that often occur after stroke include fear, anger, emotional indifference, lack of understanding of other emotions, and lack of control of emotional expression. Emotional disturbances limit social reintegration of the persons with stroke and are a source of caregiver burnout. The evidence to support the management of the majority of emotional disorders in stroke survivors is currently weak and of low or very low methodologic quality. An exception are the disorders of emotional expression control where antidepressants can have a strong beneficial effect, by reducing the number and duration of the uncontrollable episodes of crying or laughing.

Conclusion: Our current knowledge of the emotional disorders that occurs in acute stroke patients and in stroke survivors is heterogeneous and limited. Joint efforts of different research approaches, methodologies and disciplines will improve our current understanding on emotional disorder after stroke and indicate rational pathways to manage them.
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http://dx.doi.org/10.1177/1747493019879662DOI Listing
April 2020

Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial.

Authors:
José M Ferro Jonathan M Coutinho Francesco Dentali Adam Kobayashi Andrey Alasheev Patrícia Canhão Denis Karpov Simon Nagel Laura Posthuma José Mário Roriz Jorge Caria Mandy Frässdorf Holger Huisman Paul Reilly Hans-Christoph Diener

JAMA Neurol 2019 Dec;76(12):1457-1465

Faculty of Medicine, University Duisburg-Essen, Essen, Germany.

Importance: Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT.

Objective: To compare the efficacy and safety of dabigatran etexilate with those of dose-adjusted warfarin in preventing recurrent VTEs in patients who have experienced a CVT.

Design, Setting, And Participants: RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach.

Interventions: Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks.

Main Outcomes And Measures: Primary outcome was a composite of patients with a new VTE (recurrent CVT, deep vein thrombosis of any limb, pulmonary embolism, and splanchnic vein thrombosis) or major bleeding during the study period. Secondary outcomes were cerebral venous recanalization and clinically relevant non-major bleeding events.

Results: In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7).

Conclusions And Relevance: This trial found that patients who had CVT anticoagulated with either dabigatran or warfarin had low risk of recurrent VTEs, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT.

Trial Registration: ClinicalTrials.gov identifier: NCT02913326.
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http://dx.doi.org/10.1001/jamaneurol.2019.2764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724157PMC
December 2019

Cerebral Venous Thrombosis: an Update.

Authors:
José M Ferro Diana Aguiar de Sousa

Curr Neurol Neurosci Rep 2019 08 23;19(10):74. Epub 2019 Aug 23.

Serviço de Neurologia, Department of Neurosciences and Mental Health, Centro Hospitalar Lisboa Norte, Instituto de Medicina Molecular, Lisbon, Portugal.

Purpose Of Review: The purpose of this update is to summarize the recent advances on the management of cerebral venous thrombosis (CVT).

Recent Findings: There is a trend in declining frequency of CVT patients presenting with focal deficits or coma and a decrease in mortality over time. Anemia and obesity were identified as risk factors for CVT. During pregnancy and puerperium, the higher risk of CVT occurs in the first months post-delivery. With appropriate management, 1/3 of comatose CVT patients can have a full recovery. The management of CVT patients includes treatment of associated conditions, anticoagulation with parenteral heparin, prevention of recurrent seizures, and decompressive neurosurgery in patients with large venous infarcts/hemorrhages with impending herniation. After the acute phase, patients should be anticoagulated for 3-12 months. Results of recently completed randomized controlled trials on endovascular treatment and comparing dabigatran with warfarin will improve the treatment of CVT.
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http://dx.doi.org/10.1007/s11910-019-0988-xDOI Listing
August 2019

Diagnostic imaging in the management of patients with possible cerebral venous thrombosis: a cost-effectiveness analysis.

Authors:
Dennis M Hedderich José M Ferro Wolfgang G Kunz

Neuroradiology 2019 Oct 10;61(10):1155-1163. Epub 2019 Jul 10.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Purpose: Imaging is crucial for management of patients with possible cerebral venous thrombosis (CVT). To evaluate the cost-effectiveness of different noninvasive imaging strategies in patients with possible CVT.

Methods: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALY) associated with the following imaging strategies: non-contrast CT (NCCT), NCCT plus CT venography (CTV), routine MRI without vascular imaging (R-MRI), and MRI with venography (MRV). The analysis was performed from a US healthcare perspective. Model input was based on best available and most recent evidence, including outcome data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Starting age was 37 years; both high and low pre-test probabilities of CVT were evaluated. Probabilistic sensitivity analyses (PSA) estimated model uncertainty.

Results: In the base-case analysis, NCCT and CTV were dominant over R-MRI and MRV. CTV led to incremental lifetime QALYs compared with NCCT (23.385 QALYs vs. 23.374 QALYs) at slightly higher lifetime costs ($5210 vs. $5057). In PSA, CTV was the strategy with the highest percentage of cost-effective iterations if willingness-to-pay (WTP) thresholds were higher than $13,750/QALY. Complying with contemporary WTP thresholds, CTV was thus identified as the most cost-effective strategy. When the pre-test probability was set to 50%, CTV was also preferred.

Conclusion: In patients at the peak age of CVT incidence yet low clinical pre-test probability, diagnostic imaging with CTV is the most cost-effective strategy.
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http://dx.doi.org/10.1007/s00234-019-02252-7DOI Listing
October 2019

Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source.

Authors:
Hans-Christoph Diener Ralph L Sacco J Donald Easton Christopher B Granger Richard A Bernstein Shinichiro Uchiyama Jörg Kreuzer Lisa Cronin Daniel Cotton Claudia Grauer Martina Brueckmann Marina Chernyatina Geoffrey Donnan José M Ferro Martin Grond Bernd Kallmünzer Jerzy Krupinski Byung-Chul Lee Robin Lemmens Jaime Masjuan Miroslav Odinak Jeffrey L Saver Peter D Schellinger Danilo Toni Kazunori Toyoda

N Engl J Med 2019 05;380(20):1906-1917

From the University Duisburg-Essen and University Hospital Essen, Essen (H.-C.D.), Boehringer Ingelheim Pharma GmbH K.G., Biberach (C.G.), Boehringer Ingelheim International GmbH, Ingelheim, Faculty of Medicine Mannheim of the University of Heidelberg, Mannheim (M.B.), Kreisklinikum Siegen, Siegen, and the University of Marburg, Marburg (M.G.), University Hospital Erlangen, Erlangen (B.K.), and Johannes Wesling Klinikum Minden and Ruhr University Bochum, Minden (P.D.S.) - all in Germany; Miller School of Medicine, University of Miami, Miami (R.L.S.); University of California at San Francisco, San Francisco (J.D.E.), and the Department of Neurology and Comprehensive Stroke Center, University of California at Los Angeles, Los Angeles (J.L.S.) - both in California; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (C.B.G.); Feinberg School of Medicine of Northwestern University, Chicago (R.A.B.); International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo (S.U.), and the National Cerebral and Cardiovascular Center, Osaka (K.T.) - both in Japan; Boehringer Ingelheim, Singapore, Singapore (J. Kreuzer); Boehringer Ingelheim, Burlington, ON, Canada (L.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (D.C.); City Clinical Emergency Care Hospital, Kursk (M.C.), and the Military Medical Academy, St. Petersburg (M.O.) - both in Russia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia (G.D.); Serviço de Neurologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal (J.M.F.); F. Ass. Mutua Terrassa, Terrassa (J. Krupinski), and Servicio de Neurología, Hospital Universitario Ramón y Cajal (IRYCIS), Departamento de Medicina, Universidad de Alcalá, Madrid (J.M.) - both in Spain; Hallym University Sacred Heart Hospital, Seoul, South Korea (B.-C.L.); KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology, VIB Center for Brain & Disease Research, University Hospitals Leuven, Department of Neurology, Leuven, Belgium (R.L.); and Hospital Policlinico Umberto I, Sapienza University, Rome (D.T.).

Background: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear.

Methods: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding.

Results: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively.

Conclusions: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).
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http://dx.doi.org/10.1056/NEJMoa1813959DOI Listing
May 2019

Brush Sign Is Associated With Increased Severity in Cerebral Venous Thrombosis.

Authors:
Diana Aguiar de Sousa Lia Lucas Neto Simon Jung Sara Penas Leonidas Panos Mirjam R Heldner Urs Fischer Marcel Arnold Patrícia Canhão Marwan El-Koussy José M Ferro Arsany Hakim

Stroke 2019 06 30;50(6):1574-1577. Epub 2019 Apr 30.

University Institute of Diagnostic and Interventional Neuroradiology (M.E-.K., A.H.), Inselspital University Hospital, Bern, Switzerland.

Background and Purpose- The brush sign (BS) is an abnormally accentuated signal drop of the subependymal and deep medullary veins in paramagnetic-sensitive magnetic resonance sequences, previously described in acute ischemic stroke. We aimed to describe the BS in patients with thrombosis of the cerebral veins and sinuses and explore its association with clinical severity, thrombosis extent, parenchymal brain lesion, and clinical prognosis. Methods- We assessed consecutive adult patients admitted to 2 university hospitals with diagnosis of acute thrombosis of the cerebral veins and sinuses and imaging assessment with magnetic resonance imaging, including paramagnetic-sensitive sequences. Demographics, imaging findings, clinical presentation, and functional outcome at 3 months were analyzed according to the presence of BS. Results- In 118 patients included, BS was observed in gradient-echo T2*weighted (T2*WI) in 16% and susceptibility-weighted imaging in 13% of cases. All patients with BS had thrombosis of the superior sagittal sinus, straight sinus, or deep venous system. BS was associated with ipsilateral parenchymal lesion (odds ratio, 6.4; 95% CI, 1.9-21.1; P=0.002) and higher thrombus load (median [interquartile range] 5 [4-6] versus 2 [2-4]); P<0.0001). BS was also associated with focal neurological deficits (OR 4.2; 95%CI, 1.4-12.7, P=0.01). The functional outcome at 3 months was not significantly different in patients with BS. Conclusions- BS in T2*WI and susceptibility-weighted imaging was observed in approximately one in 7 patients with acute thrombosis of the cerebral veins and sinuses. BS was significantly associated with ipsilateral parenchymal brain lesion, extent of thrombosis, and manifestation with focal neurological deficits. This suggests that BS can represent a marker of severity in thrombosis of the cerebral veins and sinuses.
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http://dx.doi.org/10.1161/STROKEAHA.119.025342DOI Listing
June 2019

Neurological Complications of Infective Endocarditis.

Authors:
Filipa Dourado Sotero Madalena Rosário Ana Catarina Fonseca José M Ferro

Curr Neurol Neurosci Rep 2019 03 30;19(5):23. Epub 2019 Mar 30.

Department of Neurosciences and Mental Health, Neurology Service, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.

Purpose Of Review: The purpose of this narrative review and update is to summarize the current knowledge and provide recent advances on the neurologic complications of infective endocarditis.

Recent Findings: Neurological complications occur in about one-fourth of patients with infective endocarditis. Brain MRI represents a major tool for the identification of asymptomatic lesions, which occur in most of the patients with infective endocarditis. The usefulness of systematic brain imaging and the preferred treatment of patients with infective endocarditis and silent brain lesions remains uncertain. The basis of treatment of infective endocarditis is early antimicrobial therapy. In stroke due to infective endocarditis, anticoagulation and thrombolysis should be avoided. Endovascular treatment can be useful for both acute septic emboli and mycotic aneurysms, but evidence is still limited. In patients with neurological complications, cardiac surgery can be safely performed early, if indicated. The optimal management of a patients with neurological complications of infective endocarditis needs an individualized case discussion and the participation of a multidisciplinary team including neurologists, cardiologists, cardiothoracic surgeons, neuroradiologists, neurosurgeons, and infectious disease specialists.
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http://dx.doi.org/10.1007/s11910-019-0935-xDOI Listing
March 2019