Reperfusion therapy for acute ischemic stroke: where are we in 2023? / Terapia de reperfusão para o acidente vascular isquêmico agudo: onde estamos em 2023?

Abstract Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Resumo Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Neurological implications of SARS-CoV-2 infection: review of literature / Implicações neurológicas da infecção por SARS-CoV-2: revisão da literatura

The infection caused by the new coronavirus had its first case described in December 2019, in Wuhan, China, and reached a pandemic status in March 2020. Since then, knowledge about the different aspects of this infection has evolved, as well as increased reports concerning related neurological manifestations. Thus, the neurologist assumes a fundamental role in the care of these patients, who may have a clinical phenotype that goes beyond respiratory aspects. In the present study, we highlight the data available in the literature so far regarding the main neurological implications related to COVID-19 infection, in addition to calling attention for some aspects related to patients with previous neurological diseases who contract this infection.

A infecção causada pelo novo Coronavírus teve seu primeiro caso descrito em dezembro de 2019, em Wuhan, China e alcançou o status de pandemia em março de 2020. Desde então, o conhecimento sobre os diferentes aspectos da referida infecção evolui assim como aumentam relatos de manifestações neurológicas relacionadas. Assim, o neurologista assume papel fundamental na assistência desses pacientes, que podem ter um fenótipo clínico que ultrapassa os aspectos respiratórios. No presente estudo, destacamos os dados disponíveis na literatura até o presente momento no tocante às principais implicações neurológicas relacionadas à infecção pelo COVID-19, além de destacar alguns aspectos relativos aos pacientes com doenças neurológicas prévias que contraem a referida infecção.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke.

These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke / Diretrizes brasileiras para o tratamento endovascular de pacientes com acidente vascular cerebral isquêmico agudo

ABSTRACT These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

RESUMO Estas diretrizes são o resultado de um esforço conjunto de membros da Sociedade Brasileira de Doenças Cerebrovasculares (SBDCV), Departamento científico de Doenças Cerebrovasculares da Academia Brasileira de Neurologia (ABN), Rede Brasil AVC (RBAVC) e da Sociedade Brasileira de Neurorradiologia Diagnóstica e Terapêutica (SBNR). Membros destas 4 entidades participaram de fórum de discussões por internet de temas pré-definidos, seguidos de encontros de videoconferência para discussão de pontos controversos e das recomendações, em busca de um consenso final. Estas diretrizes tem seu foco sobre as implicações dos recentes ensaios clínicos de tratamento endovascular do acidente vascular cerebral (AVC) isquêmico agudo relacionado a oclusão de artérias proximais. O texto final foi elaborado para servir de orientação no manejo destes pacientes AVC isquêmico pelos diferentes profissionais de saúde, gestores de saúde pública e de saúde complementar no Brasil.

Migraine patients should be cautiously followed for risk factors leading to cardiovascular disease.

Migraine and ischemic strokes are two of the most prevalent diseases worldwide. Besides having a coincident symptomatology, for long researchers have been searching for a possible causal relation between these diseases. Current evidence based on data suggest that patients with aura migraine could have a doubled risk of developing an ischemic stroke, when compared to the rest of the population. At the same time, migraine sufferers apparently have higher incidences of risk factors for cardiovascular events. The aim of this review was not only to dissect some of the more compelling evidence based on data regarding this association, but also to discuss the possible clinical and therapeutic implications.

Migraine patients should be cautiously followed for risk factors leading to cardiovascular disease / Pacientes com migrânea devem ser acompanhados com cuidado com relação aos fatores de risco para doenças cardiovasculares

Migraine and ischemic strokes are two of the most prevalent diseases worldwide. Besides having a coincident symptomatology, for long researchers have been searching for a possible causal relation between these diseases. Current evidence based on data suggest that patients with aura migraine could have a doubled risk of developing an ischemic stroke, when compared to the rest of the population. At the same time, migraine sufferers apparently have higher incidences of risk factors for cardiovascular events. The aim of this review was not only to dissect some of the more compelling evidence based on data regarding this association, but also to discuss the possible clinical and therapeutic implications.

Migrânea e acidentes vasculares cerebrais isquêmicos (AVCI) são duas das doenças de maior prevalência em todo o mundo. Além de apresentarem alguns sintomas em comum, há muito tempo pesquisadores procuram investigar uma relação causal entre as duas. As informações atuais baseadas em evidência sugerem que pacientes com migrânea com aura podem ter um risco duas vezes maior de desenvolver AVCI, quando comparados com o restante da população. Ao mesmo tempo, aqueles sofrem de migrânea possuem aparentemente maior incidência de fatores de risco para eventos cardiovasculares. O objetivo desta revisão foi não apenas avaliar grande parte das mais importantes e convincentes evidências científicas sobre esta associação, mas também discutir suas possíveis implicações clínicas e terapêuticas.

Brazilian guidelines for the application of transcranial ultrasound as a diagnostic test for the confirmation of brain death.

Neurosonological studies, specifically transcranial Doppler (TCD) and transcranial color-coded duplex (TCCD), have high level of specificity and sensitivity and they are used as complementary tests for the diagnosis of brain death (BD). A group of experts, from the Neurosonology Department of the Brazilian Academy of Neurology, created a task force to determine the criteria for the following aspects of diagnosing BD in Brazil: the reliability of TCD methodology; the reliability of TCCD methodology; neurosonology training and skills; the diagnosis of encephalic circulatory arrest; and exam documentation for BD. The results of this meeting are presented in the current paper.

Brazilian guidelines for the application of transcranial ultrasound as a diagnostic test for the confirmation of brain death / Diretrizes brasileiras para o uso do ultrassom transcraniano como teste diagnóstico de confirmação de morte cerebral

Neurosonological studies, specifically transcranial Doppler (TCD) and transcranial color-coded duplex (TCCD), have high level of specificity and sensitivity and they are used as complementary tests for the diagnosis of brain death (BD). A group of experts, from the Neurosonology Department of the Brazilian Academy of Neurology, created a task force to determine the criteria for the following aspects of diagnosing BD in Brazil: the reliability of TCD methodology; the reliability of TCCD methodology; neurosonology training and skills; the diagnosis of encephalic circulatory arrest; and exam documentation for BD. The results of this meeting are presented in the current paper.

Estudos neurossonológicos, especialmente o Doppler transcraniano (DTC) e o duplex transcraniano codificado a cores (DTCC), apresentam elevados níveis de especificidade e sensibilidade quando utilizados como exames complementares no diagnóstico de morte encefálica (ME). Um grupo de peritos do Departamento Científico de Doppler transcraniano da Academia Brasileira de Neurologia criou uma força-tarefa de forma a determinar os critérios neurossonológicos para os seguintes aspectos no diagnóstico de ME no Brasil: metodologia do DTC; metodologia do DTCC; treinamento e habilidades em Neurossonologia; diagnóstico de parada circulatória encefálica e documentação do exame para a ME. Os resultados deste encontro foram apresentados neste artigo.

Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke.

Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS <8, modified Rankin Scale scores of 0-1 in patients with NIHSS 8-14, or modified Rankin Scale scores 0-2 in patients with NIHSS >14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.

Treatment of vascular dementia. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology / Tratamento da demência vascular. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

Scientific Department of Cognitive Neurology and Aging of ABN had a consensus meeting to write recommendations on treatment of vascular dementia, there was no previous issue. This disease has numerous particularities and can be considered a preventable dementia. Prevention treatment is primary care of vascular risk factors or a secondary prevention of factors that could cause recurrence of ischemic or hemorrhagic brain modifications. In these guidelines we suggested only symptomatic treatment, pharmacologic or non-pharmacologic. We have reviewed current publications on MEDLINE (PubMed), LILACS e Cochrane Library databases. Recommendations are concern to the following factors and their prevention evidences, association, or treatment of vascular dementia: physical activity, tobacco use, diet and food supplements, arterial hypertension, diabetes mellitus, obesity, statins, cardiac failure, atrial fibrillation, antithrombotics, sleep apnea, carotid revascularization, symptomatic pharmacological treatment.

O DC de Neurologia Cognitiva e do Envelhecimento da ABN reuniu-se para escrever recomendações para o tratamento da demência vascular, uma vez que não havia nenhuma recomendação neste sentido. Esta doença tem inúmeras particularidades e pode ser considerada uma das demências que pode ser prevenida. O tratamento para sua prevenção é o de cuidados primários para os fatores de risco vasculares, ou a prevenção secundária dos fatores que levam a recorrência de alterações isquêmicas ou hemorrágicas cerebrais. Nestas recomendações sugerimos apenas o tratamento sintomático, medicamentoso ou não. Baseamo-nos nas evidências disponíveis, através da revisão das publicações nas bases MEDLINE (PubMed), LILACS e Cochrane Library. As recomendações dizem respeito aos seguintes fatores e suas evidências na prevenção, associação ou tratamento da demência vascular: atividade física, álcool, tabagismo, dieta e suplementos, hipertensão arterial, diabetes mellitus, obesidade, estatinas, insuficiência cardíaca, fibrilação atrial, antiagregantes, apneia do sono, revascularização carotídea e tratamento farmacológico sintomático.

Tratamento da demência vascular / Treatment of vascular dementia

O DC de Neurologia Cognitiva e do Envelhecimento da ABN reuniu-se para escrever recomendações para o tratamento da demência vascular, uma vez que não havia nenhuma recomendação neste sentido. Esta doença tem inúmeras particularidades e pode ser considerada uma das demências que pode ser prevenida. O tratamento para sua prevenção é o de cuidados primários para os fatores de risco vasculares, ou a prevenção secundária dos fatores que levam a recorrência de alterações isquêmicas ou hemorrágicas cerebrais. Nestas recomendações sugerimos apenas o tratamento sintomático, medicamentoso ou não. Baseamo-nos nas evidências disponíveis, através da revisão das publicações nas bases MEDLINE (PubMed), LILACS e Cochrane Library. Foram analisados artigos relacionados exclusivamente à demência vascular. As recomendações dizem respeito aos seguintes fatores e suas evidências na prevenção, associação ou tratamento da demência vascular: atividade física, álcool, tabagismo, dieta e suplementos, hipertensão arterial, diabetes mellitus, obesidade, estatinas, insuficiência cardíaca, fibrilação atrial, antiagregantes, apneia do sono, revascularização carotídea e tratamento farmacológico sintomático.

Patent foramen ovale in trigeminal autonomic cephalalgias and hemicrania continua: a non-specific pathophysiological occurrence?

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54% vs. 25%, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.

Patent foramen ovale in trigeminal autonomic cephalalgias and hemicrania continua: a non-specific pathophysiological occurrence? / Foramen oval patente em cefaleias trigêmino-autonômicas e hemicrania contínua: uma ocorrência fisiopatológica não específica?

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54 percent vs. 25 percent, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.

O forame oval patente (FOP), uma anormalidade cardíaca relativamente comum em adultos, tem sido associado à enxaqueca, mas raramente às cefaléias trigêmino-autonômicas (TACs). Utilizamos o Doppler transcraniano (DTC) para detecção de shunt direito-esquerdo (SDE) em 24 pacientes com cefaléia em salvas (CS), sete com hemicrania paroxística (HP), dois com hemicrania continua (HC) e um com SUNCT; alem de 34 controles. O SDE foi mais frequente nos pacientes com CS do que nos controles (54 por cento vs. 25 por cento p=0,03), particularmente acima de 50 anos. No grupo HP+HC+SUNCT, o SDE foi encontrado em seis pacientes e dois controles (p=0,08). O hábito de fumar, bem como sonolência excessiva diurna foram mais frequentes em paciente com CS. O FOP pode ter importância inespecífica na fisiopatologia das TACs e HC, na dependência da susceptibilidade individual a fatores desencadeantes.

Benign monomelic amyotrophy with proximal upper limb involvement: case report.

Monomelic amyotrophy (MA) is a rare condition in which neurogenic amyotrophy is restricted to an upper or lower limb. Usually sporadic, it usually has an insidious onset with a mean evolution of 2 to 4 years following first clinical manifestations, which is, in turned, followed by stabilization. We report a case of 20-years-old man who presented slowly progressive amyotrophy associated with proximal paresis of the right upper limb, which was followed by clinical stabilization 4 years later. Eletroneuromyography revealed denervation along with myofasciculations in various muscle groups of the right upper limb. We call attention to this rare location of MA, as well as describe some theories concerning its pathophysiology .

Benign monomelic amyotrophy with proximal upper limb involvement: case report

Monomelic amyotrophy (MA) is a rare condition in which neurogenic amyotrophy is restricted to an upper or lower limb. Usually sporadic, it usually has an insidious onset with a mean evolution of 2 to 4 years following first clinical manifestations, which is, in turned, followed by stabilization. We report a case of 20-years-old man who presented slowly progressive amyotrophy associated with proximal paresis of the right upper limb, which was followed by clinical stabilization 4 years later. Eletroneuromyography revealed denervation along with myofasciculations in various muscle groups of the right upper limb. We call atention to this rare location of MA, as well as describe some theories concerning its pathophysiology .

A amiotrofia monomélica é condição rara em que a amiotrofia neurogênica é restrita somente a um membro superior ou inferior. Usualmente esporádica, possui um início insidioso e evolução lenta de 2-4 anos após as primeiras manifestações, seguida por estabilização. Relatamos o caso de um homem que aos 20 anos apresentou lentamente amiotrofia e paresia proximal no membro superior direito, estabilizando-se em quatro anos. A eletroneuromiografia identificou a presença de desnervação e fasciculações em diversos músculos proximais do membro superior direito. Chamamos a atenção para esta rara localização desta entidade, assim como descrevemos algumas das hipóteses da fisiopatologia.

[Safety of intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke]. / Segurança do transplante autólogo, intra-arterial, de células mononucleares da medula óssea na fase aguda do acidente vascular cerebral isquêmico.

Stroke is the third cause of death and the leading cause of disability in adult subjects. Although stroke mortality has been declining in some countries, stroke morbidity has been increasing due to the aging of population and patients improved survival. Treatment with recombinant tissue plasminogen activator (rtPA) is successful provided it is administered within 3 hours of symptoms onset, but its use is limited to about 5% of the patients with acute ischemic stroke. Furthermore, no neuroprotective agent has yet been proven effective in human clinical trials. The development of other therapeutic strategies is, therefore, warranted. The use of stem cells in animal models has led to functional improvement following stroke. Recent publications have shown that bone marrow mononuclear cells (BM-MNC) therapy through intracoronary injection is a safe procedure in patients with acute or chronic ischemic heart disease. Based on these preliminary data, there has been growing interest in the study of BM-MNC transplantation for acute ischemic stroke. We report the first case of intra-arterial autologous BM-MNC transplantation for acute ischemic stroke.

Segurança do transplante autólogo, intra-arterial, de células mononucleares da medula óssea na fase aguda do acidente vascular cerebral isquêmico / Intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke

O acidente vascular cerebral (AVC) é a terceira causa de óbito e a principal causa de incapacidade em indivíduos adultos. Embora a mortalidade do AVC esteja diminuindo em alguns países, a morbidade tem aumentado em razão do envelhecimento da população e do aumento da sobrevida dos pacientes . O tratamento com ativador do plasminogênio tissular recombinante (rt-PA) é eficaz quando instituído em até 3 horas após o início dos sintomas², porém seu uso está limitado a cerca de 5 por cento dos pacientes na fase aguda do AVC isquêmico. Além disso, nenhum agente para neuroproteção teve sua eficácia comprovada em estudos clínicos em humanos. Portanto, outras estratégias terapêuticas precisam ser desenvolvidas. Em modelos animais, o uso de células-tronco correlacionou-se com melhora funcional após o AVC . Publicações recentes têm demonstrado a segurança do tratamento com células mononucleares da medula óssea (CMMO) injetadas via intracoronária em pacientes portadores de cardiopatia isquêmica aguda ou crônica4,5. Baseado nesses dados iniciais, há crescente interesse no estudo do transplante com CMMO na fase aguda do AVC. Relatamos o primeiro caso de transplante autólogo de CMMO via intra-arterial na fase aguda do AVC isquêmico.