Cryptogenic Stroke

Introduction: To emphasize the importance of this kind of stroke, to focus on secondary stroke prevention and to recognize that the etiology of stroke is fundamental for proper prevention. In this chapter, the history of this stroke subtype is described and its actual specific denomination: embolic stroke undetermined source (ESUS)

Traumatic spinal cord injury: current concepts and treatment update

Spinal cord injury (SCI) affects 1.3 million North Americans, with more than half occurring after trauma. In Brazil, few studies have evaluated the epidemiology of SCI with an estimated incidence of 16 to 26 per million per year. The final extent of the spinal cord damage results from primary and secondary mechanisms that start at the moment of the injury and go on for days, and even weeks, after the event. There is convincing evidence that hypotension contributes to secondary injury after acute SCI. Surgical decompression aims at relieving mechanical pressure on the microvascular circulation, therefore reducing hypoxia and ischemia. The role of methylprednisolone as a therapeutic option is still a matter of debate, however most guidelines do not recommend its regular use. Neuroprotective therapies aiming to reduce further injury have been studied and many others are underway. Neuroregenerative therapies are being extensively investigated, with cell based therapy being very promising.Univ Fed Sao Paulo, Dept Neurol & Neurocirurgia, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Neurol & Neurocirurgia, Sao Paulo, SP, BrazilWeb of Scienc

Revisão da distribuição do vite-vite-de-cabeça-cinza Hylophilus pectoralis (Passeriformes: Vireonidae), com notificação de sua ocorrência no Triângulo Mineiro e noroeste de São Paulo

The Ashy-headed Greenlet has a spotty distribution over a broad area in Amazonia, both north and south of the Solimões-Amazonas river. It is mostly found second-growth, forest edge and water-edge habitats, including mangroves and gallery and varzea forests. The species also occurs in the Pantanal, the Chiquitano Forests, and in the Cerrado of central and northeastern Brazil, including the Brazilian states of Goiás, Maranhão and Piauí. This paper presents new records extending its distribution to the south, including southwest Minas Gerais (the "Triângulo Mineiro" region), southern Goiás, northwest São Paulo and eastern Mato Grosso do Sul, suggesting a recent colonization of those regions parallel to the one shown by the closely related H. thoracicus in southeastern Brazil

Síncope de Causa Indefinida e Seus Desafios Diagnósticos

A síncope, caracterizada pela perda súbita e transitória da consciência, apresenta-se como um desafio diagnóstico, especialmente quando sua origem permanece indefinida. Este estudo abordou uma paciente idosa que experimentou síncope sem causa definida, destacando a complexidade do fenômeno. A literatura médica reconhece a diversidade de etiologias possíveis, desde distúrbios cardíacos até condições neurológicas e metabólicas, acrescentando uma camada de complexidade ao diagnóstico. A metodologia adotada foi qualitativa, concentrando-se na avaliação de uma paciente hospitalizada por meio de parâmetros observacionais e exames de imagem. A paciente, R.C.D, de 65 anos, apresentou síncope súbita após cirurgia de catarata, sendo diagnosticada com hemorragia subaracnóidea traumática e fratura cervical C5. Após imobilização e monitoramento, a paciente apresentou recuperação favorável, mas surgiram queixas de tontura e problemas de memória anterógrada. A investigação revelou inconsistências nos resultados dos exames, atribuídas à agitação psicomotora durante a captura de imagens. O envelhecimento foi destacado como fator contribuinte, impactando a resposta cardiovascular ao ortostatismo e tornando os idosos mais suscetíveis a eventos sincopais. As considerações finais enfatizam a necessidade de uma investigação detalhada e contínua para determinar as causas subjacentes da síncope em idosos, especialmente diante da complexidade do caso apresentado. A correlação entre eventos e sintomas prévios, juntamente com uma interpretação clínica cautelosa, foi ressaltada como crucial. A inconsistência nos resultados sublinha a importância de uma abordagem sistêmica e destaca a necessidade de intervenções futuras orientadas pelos achados da investigação

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe