Деонтологические аспекты бокового амиотрофического склероза

One of the significant problems in deontology is the degree of awareness of terminally ill patients regarding the diagnosis and prognosis of their disease. This topic is complex and relevant, it touches ethical and psychological, legal and medical aspects. The article discusses the positive and negative aspects of fully informing patients  with amyotrophic lateral sclerosis about the fatal diagnosis. There are 2  clinical cases reflecting different approaches of this complex issue: full awareness and concealment of the diagnosis.Одна из значимых проблем в деонтологии – степень осведомленности неизлечимых больных о своем диагнозе. Данная тема сложна и актуальна, она затрагивает вопросы этики, психологии,  правовые и медицинские аспекты. В статье обсуждаются положительные и отрицательные  стороны полного информирования пациентов о заболевании боковым амиотрофическим  склерозом и его фатальном исходе. Приведены 2 клинических случая, отражающие разные  подходы к этому сложному вопросу: полная информированность в отношении болезни и  утаивание диагноза, которые демонстрируют преимущества принципа открытости между врачом и пациенто

Боковой амиотрофический склероз: механизмы патогенеза и новые подходы к фармакотерапии (обзор литературы)

Amyotrophic lateral sclerosis is a neurodegenerative disease, resulting in the loss of self-service and death of the middle-aged and elderly people. In the last 2 decades, significant progress has been made in the study of the pathogenesis of this disease. Two known drugs (riluzole and edaravone) have been approved by the Food and Drug Administration for treatment of amyotrophic lateral sclerosis. The efficacy of these drugs is extremely low, so clinical trials of new drugs are ongoing all over the world. This review discusses the current achievements and future directions of therapy of this disease.Боковой амиотрофический склероз – тяжелое нейродегенеративное заболевание, обусловленное поражением двигательных нейронов головного и спинного мозга и приводящее к тяжелой инвалидизации и смерти через 3–5 лет с момента его дебюта. В последние 2 десятилетия достигнут значительный прогресс в изучении патогенетических механизмов развития данного заболевания. Рилузол и эдаравон, одобренные Управлением по контролю за качеством пищевых продуктов и лекарственных препаратов (Food and Drug Administration) в 2003 и 2017 гг. для лечения бокового амиотрофического склероза, оказались недостаточно эффективны, поэтому продолжается поиск новых препаратов. В статье обсуждаются современные достижения и некоторые перспективные направления патогенетической терапии бокового амиотрофического склероза

ТРУДНОСТИ ДИАГНОСТИКИ БОКОВОГО АМИОТРОФИЧЕСКОГО СКЛЕРОЗА У ВИЧ-ИНФИЦИРОВАННОГО ПАЦИЕНТА

We described a case of amyotrophic lateral sclerosis (ALS) with comorbid HIV infection. The diagnosis was confirmed by genetic tests. The difficulty of the differential diagnosis between amyotrophic lateral sclerosis and HIV-associated ALS syndrome is discussed.Описан случай развития бокового амиотрофического склероза (БАС) на фоне ВИЧ-инфекции, подтвержденный данными молекулярно-генетического исследования. Обсуждается сложность дифференциальной диагностики между классическим БАС и БАС-подобным синдромом у ВИЧ-инфицированного пациента

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 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

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 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

Amyotrophic lateral sclerosis: pathogenetic mechanisms and new approaches to pharmacotherapy (literature review)

Amyotrophic lateral sclerosis is a neurodegenerative disease, resulting in the loss of self-service and death of the middle-aged and elderly people. In the last 2 decades, significant progress has been made in the study of the pathogenesis of this disease. Two known drugs (riluzole and edaravone) have been approved by the Food and Drug Administration for treatment of amyotrophic lateral sclerosis. The efficacy of these drugs is extremely low, so clinical trials of new drugs are ongoing all over the world. This review discusses the current achievements and future directions of therapy of this disease

Deontological aspects of the amyotrophic lateral sclerosis

One of the significant problems in deontology is the degree of awareness of terminally ill patients regarding the diagnosis and prognosis of their disease. This topic is complex and relevant, it touches ethical and psychological, legal and medical aspects. The article discusses the positive and negative aspects of fully informing patients  with amyotrophic lateral sclerosis about the fatal diagnosis. There are 2  clinical cases reflecting different approaches of this complex issue: full awareness and concealment of the diagnosis

Difficulties in diagnosing amyotrophic lateral sclerosis in a HIV-Positive Patient

We described a case of amyotrophic lateral sclerosis (ALS) with comorbid HIV infection. The diagnosis was confirmed by genetic tests. The difficulty of the differential diagnosis between amyotrophic lateral sclerosis and HIV-associated ALS syndrome is discussed

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 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

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

Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00973-1, published online 6 December 2021. In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article