RESUMEN
Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.
Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/genética , MutaciónRESUMEN
Amyotrophic lateral sclerosis (ALS) is a rare fatal motor neuron disease. Although many potential mechanisms have been proposed, the pathophysiology of the disease remains unknown. Currently available treatments can only delay the progression of the disease and prolong life expectancy by a few months. There is still no definitive cure for ALS, and the development of new treatments is limited by a lack of understanding of the underlying biological processes that trigger and promote neurodegeneration. Several scientific results suggest a neurovascular impairment in ALS providing perspectives for the development of new biomarkers and treatments. In this article, we performed a systematic review using PRISMA guidelines including PubMed, EmBase, GoogleScholar, and Web of Science Core Collection to analyze the scientific literature published between 2000 and 2021 discussing the neurocardiovascular involvement and ophthalmologic abnormalities in ALS. In total, 122 articles were included to establish this systematic review. Indeed, microvascular pathology seems to be involved in ALS, affecting all the neurovascular unit components. Retinal changes have also been recently highlighted without significant alteration of the visual pathways. Despite the peripheral location of the retina, it is considered as an extension of the central nervous system (CNS) as it displays similarities to the brain, the inner blood-retinal barrier, and the blood-brain barrier. This suggests that the eye could be considered as a 'window' into the brain in many CNS disorders. Thus, studying ocular manifestations of brain pathologies seems very promising in understanding neurodegenerative disorders, mainly ALS. Optical coherence tomography angiography (OCT-A) could therefore be a powerful approach for exploration of retinal microvascularization allowing to obtain new diagnostic and prognostic biomarkers of ALS.
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Esclerosis Amiotrófica Lateral , Microvasos , Vasos Retinianos , Tomografía de Coherencia Óptica , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/fisiopatología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/fisiopatología , Humanos , Microvasos/diagnóstico por imagen , Microvasos/fisiopatología , Angiografía/métodos , Movimientos SacádicosRESUMEN
AIMS: Histological analysis of brain tissue samples provides valuable information about the pathological processes leading to common neurodegenerative disorders. In this context, the development of novel high-resolution imaging approaches is a current challenge in neuroscience. METHODS: To this end, we used a recent super-resolution imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyse human brain sections. We combined STORM cell imaging protocols with neuropathological techniques to image cryopreserved brain samples from control subjects and patients with neurodegenerative diseases. RESULTS: This approach allowed us to perform 2D-, 3D- and two-colour-STORM in neocortex, white matter and brainstem samples. STORM proved to be particularly effective at visualizing the organization of dense protein inclusions and we imaged with a <50 nm resolution pathological aggregates within the central nervous system of patients with Alzheimer's disease, Parkinson's disease, Lewy body dementia and fronto-temporal lobar degeneration. Aggregated Aß branches appeared reticulated and cross-linked in the extracellular matrix, with widths from 60 to 240 nm. Intraneuronal Tau and TDP-43 inclusions were denser, with a honeycomb pattern in the soma and a filamentous organization in the axons. Finally, STORM imaging of α-synuclein pathology revealed the internal organization of Lewy bodies that could not be observed by conventional fluorescence microscopy. CONCLUSIONS: STORM imaging of human brain samples opens further gates to a more comprehensive understanding of common neurological disorders. The convenience of this technique should open a straightforward extension of its application for super-resolution imaging of the human brain, with promising avenues to current challenges in neuroscience.
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Enfermedad de Alzheimer/patología , Encéfalo/patología , Microscopía , Enfermedad de Parkinson/patología , Humanos , Cuerpos de Inclusión/patología , Cuerpos de Lewy/patología , Enfermedad por Cuerpos de Lewy/patología , Masculino , Neuronas/patología , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismoAsunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis por Herpes Simple/diagnóstico , Complicaciones Infecciosas del Embarazo/diagnóstico , Corticoesteroides/uso terapéutico , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis por Herpes Simple/tratamiento farmacológico , Encefalitis por Herpes Simple/inmunología , Femenino , Herpes Simple/complicaciones , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Herpes Simple/inmunología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Paresia/diagnóstico , Paresia/tratamiento farmacológico , Paresia/etiología , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/patología , Segundo Trimestre del EmbarazoAsunto(s)
Enfermedad por Depósito de Glucógeno de Tipo IIb/diagnóstico , Enfermedad por Depósito de Glucógeno de Tipo IIb/genética , No Compactación Aislada del Miocardio Ventricular/diagnóstico , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Mutación , Miotonía/diagnóstico , Enfermedad por Depósito de Glucógeno de Tipo IIb/complicaciones , Enfermedad por Depósito de Glucógeno de Tipo IIb/fisiopatología , Humanos , No Compactación Aislada del Miocardio Ventricular/complicaciones , No Compactación Aislada del Miocardio Ventricular/genética , Masculino , Miotonía/complicaciones , Miotonía/genética , Linaje , Fenotipo , Adulto JovenRESUMEN
BACKGROUND: There have been dramatic changes in neurology over the past decade; these advances require a constant adaptation of residents' theoretical and practical training. The French Association of Neurology Residents and the College of Neurology Teachers conducted a national survey to assess the French neurology residents' satisfaction about their training. METHODS: A 16-item questionnaire was sent via e-mail to French neurology residents completing training in 2014. Data were collected and processed anonymously. RESULTS: Of eligible respondents, 126 returned the survey, representing approximately 40% of all the French neurology residents. Most residents (78%) rated their clinical training favorably. Seventy-two percent reported good to excellent quality teaching of neurology courses from their faculty. However, many residents (40%) felt insufficient their doctoral thesis supervision. All residents intended to enter fellowship training after their residency, and most of them (68%) planned to practice in a medical center. CONCLUSION: French neurology residents seemed satisfied with the structure and quality of their training program. However, efforts are required to improve management of the doctoral thesis and make private practice more attractive and accessible during the residency. In the future, similar surveys should be scheduled to regularly assess neurology residents' satisfaction and the impact of the forthcoming national and European reforms.
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Internado y Residencia , Neurología/educación , Adulto , Actitud del Personal de Salud , Selección de Profesión , Curriculum , Docentes , Becas , Femenino , Francia , Geografía , Humanos , Internado y Residencia/organización & administración , Internado y Residencia/normas , Masculino , Encuestas y CuestionariosRESUMEN
Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes.