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1.
Brain Sci ; 11(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34679356

RESUMO

During the COVID-19 pandemic and the related lockdowns, outpatient follow-up visits for patients with chronic neurological diseases have been suspended. Managing people affected by amyotrophic lateral sclerosis (ALS) has become highly complicated, leaving patients without the standard multidisciplinary follow-up. This study aimed to analyze the impact of the COVID-19 lockdown on ALS disease progression. We compared the clinical data and progression in the first year following diagnosis for patients who received ALS diagnosis during 2020 (G20, N = 34), comparing it with a group of diagnosed in 2018 (G18, N = 31). Both groups received a comparable multidisciplinary model of care in our Tertiary Expert ALS Centre, Novara, Italy. The monthly rate of ALSFRS-R decline during the lockdown was significantly increased in G20 compared to G18 (1.52 ± 2.69 vs. 0.76 ± 0.56; p-value: 0.005). In G20, 47% required non-invasive ventilation (vs. 32% of G18). Similarly, in G20, 35% of patients died vs. 19% of patients in G18 (p-value: 0.01). All results were corrected for gender, age, site of onset, and diagnostic delay. Several factors can be implicated in making ALS more severe, with a faster progression, such as reduced medical evaluations and the possibility of therapeutic changes, social isolation, and rehabilitation therapy suspension.

2.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638725

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of the corticospinal motor neurons, which ultimately leads to death. The repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) represents the most common genetic cause of ALS and it is also involved in the pathogenesis of other neurodegenerative disorders. To offer insights into C9ORF72-mediated pathogenesis, we quantitatively analyzed the proteome of patient-derived primary skin fibroblasts from ALS patients carrying the C9ORF72 mutation compared with ALS patients who tested negative for it. Differentially expressed proteins were identified, used to generate a protein-protein interaction network and subjected to a functional enrichment analysis to unveil altered molecular pathways. ALS patients were also compared with patients affected by frontotemporal dementia carrying the C9ORF72 repeat expansion. As a result, we demonstrated that the molecular pathways mainly altered in fibroblasts (e.g., protein homeostasis) mirror the alterations observed in C9ORF72-mutated neurons. Moreover, we highlighted novel molecular pathways (nuclear and mitochondrial transports, vesicle trafficking, mitochondrial bioenergetics, glucose metabolism, ER-phagosome crosstalk and Slit/Robo signaling pathway) which might be further investigated as C9ORF72-specific pathogenetic mechanisms. Data are available via ProteomeXchange with the identifier PXD023866.


Assuntos
Esclerose Amiotrófica Lateral , Proteína C9orf72 , Expansão das Repetições de DNA , Fibroblastos , Proteoma , Transdução de Sinais/genética , Pele , Adulto , Idoso , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/patologia , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma/genética , Proteoma/metabolismo , Pele/metabolismo , Pele/patologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-34355622

RESUMO

Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients' mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease onset: (1) ≤12 months; (2) ≤18 months; (3) ≤24 months; (4) ≤36 months. Date of spirometry corresponded to date of trial entry, while time interval onset-spirometry to disease duration at enrollment. Mortality rates from inclusion were computed at different time intervals. Based on progression rates, patients were stratified in slow, intermediate and fast progressors. Survival from recruitment was calculated depending on FVC, disease duration and progression rate. Results: We included 659 patients in group 1, 888 in group 2, 1019 in group 3 and 1102 in group 4. Mortality rates were higher in each group at reducing the FVC cutoff used for recruitment (p < 0.001). Median survival decreased when lowering FVC and disease duration cutoffs (p < 0.001); a higher median disease progression rate of included patients led to lower median survival from recruitment. The proportion of recruited fast progressors raised when shortening disease duration and lowering FVC cutoff. Conclusions: This is a simple model for setting eligibility criteria, based on mortality rates of patients depending on FVC and disease duration, to select the best population for RCTs, tailored to trials' primary endpoints and duration.

4.
Neurol Sci ; 42(11): 4747-4749, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34272622

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in late 2019. Researchers around the world are aggressively working to develop a vaccine. One of the vaccines approved against COVID-19 is Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19. CASE REPORT: We described a patient who developed four limb distal paraesthesia, postural instability, and facial diplegia, ten days after vaccination with ChAdOx1 nCoV-19 (ABW1277). The electrophysiological findings were compatible with acute demyelinating motor polyneuropathy (Guillain-Barrè syndrome). DISCUSSION: We therefore want to describe a temporal correlation between administration of ChAdOx1 nCoV-19 (ABW1277) vaccine and GBS without evidence of other predisposing infectious or autoimmune factors. This paper aims to highlight the importance of pharmacovigilance and subsequent reports will be needed to evaluate the possible correlation between these two events.


Assuntos
COVID-19 , Paralisia Facial , Síndrome de Guillain-Barré , Vacinas , Vacinas contra COVID-19 , Humanos , SARS-CoV-2
5.
Neurosci Biobehav Rev ; 127: 958-978, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153344

RESUMO

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. The aim of this manuscript is to summarize the recent advances regarding the immune system involvement in ALS, with particular attention to clinical translation. We focus on the potential pathophysiologic mechanism of the immune system in ALS, discussing local and systemic factors (blood, cerebrospinal fluid, and microbiota) that influence ALS onset and progression in animal models and people. We also explore the potential of Positron Emission Tomography to detect neuroinflammation in vivo, and discuss ongoing clinical trials of therapies targeting the immune system. With validation in human patients, new evidence in this emerging field will serve to identify novel therapeutic targets and provide realistic hope for personalized treatment strategies.


Assuntos
Esclerose Amiotrófica Lateral , Doenças Neurodegenerativas , Animais , Humanos , Sistema Imunitário , Tomografia por Emissão de Pósitrons
6.
Artigo em Inglês | MEDLINE | ID: mdl-34151660

RESUMO

Objective: To assess amyotrophic lateral sclerosis (ALS) prevalence and to analyze how this estimate vary according to the historical depth of data collection. Methods: Data from the PARALS register have been used. Crude prevalence ratio was estimated on 31 December 2015 for the period 2015-2013 and then repeated extending the time interval by 3 years each time. For each time interval, prevalence ratio was calculated globally and stratified by sex, age at diagnosis, and phenotype. Prevalence was also calculated considering patients who underwent tracheostomy during the same study period. Results: Prevalence ratios increased proportionally to the length of the time period considered, ranging from 6 (95% CI 5.3-6.7) for a 3-year period to 12.1 (95% CI 11.1-13.1) per 100,000 population for a 21-year period. Prevalence ratio increase was inversely proportional to age at diagnosis, being null in the >85 years class and maximal in the 25-35 age class (+1700%). Among phenotypes, predominant UMN showed the highest increase (from 0.5, 95% CI 0.3-0.8, to 2.1, 95% CI 1.7 - 2.6, +320%). Discussion: Because of the variability of ALS survival, prevalence ratio strongly depends on the length of the follow-up period. A 12-year period should be sufficient to get a reliable estimate of ALS prevalence including long-survival patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33771057

RESUMO

Objective: This study characterized two patient-reported outcome measures (PROMs): a patient-facing adaptation of the revised amyotrophic lateral sclerosis (ALS) Functional Rating Scale ("self-entry ALSFRS-R") and the Activities-specific Balance Confidence (ABC) Scale. Methods: ALS patients presenting to clinic completed PROMs that included (1) the self-entry ALSFRS-R, (2) the Activities-specific Balance Confidence Scale (ABC Scale), and (3) a question about falls. PROM data were compared to one another and to the traditional ALSFRS-R collected by trained evaluators in clinic ("standard ALSFRS-R"). Results: Over the data collection period, 449 ALS patients completed at least one of the three PROMs. Self-entry vs. standard ALSFRS-R total scores (n = 183) had high agreement (intraclass correlation (ICC)=0.81, 95% CI = 0.67, 0.88). Self-entry ALSFRS-R total scores were significantly higher than standard ALSFRS-R total scores (2.3 points, p < 0.001). In a subset of participants who contributed data at two timepoints, the average ALSFRS-R decline was not significantly different between methods (n = 49). ABC scores correlated highly with self-entry and standard ALSFRS-R Gross Motor subdomain scores (Pearson's r = 0.72, p < 0.001 and Pearson's r = 0.76, p < 0.001, respectively; n = 130). ABC score was negatively correlated with the number of reported falls within the last month (Spearman's r=-0.40; p < 0.001; n = 130). A 10-point decrease in ABC score increased odds of a reported fall by 16%. Conclusions: In a multidisciplinary clinic setting, self-entry and standard ALSFRS-R scores were similar, but not interchangeable. Self-entry scores were higher than standard ALSFRS-R scores but declined at a similar rate to the standard ALSFRS-R. ABC scores correlated with self-reported fall history and thus may provide useful data for clinical care.


Assuntos
Esclerose Amiotrófica Lateral , Instituições de Assistência Ambulatorial , Esclerose Amiotrófica Lateral/diagnóstico , Progressão da Doença , Humanos , Medidas de Resultados Relatados pelo Paciente , Autorrelato
8.
Neurol Sci ; 42(6): 2211-2222, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33772353

RESUMO

BACKGROUND AND AIM: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. CONCLUSIONS: To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.


Assuntos
Esclerose Amiotrófica Lateral , Disfunção Cognitiva , Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/diagnóstico , Humanos , Estudos Longitudinais , Testes Neuropsicológicos
9.
Brain Sci ; 11(2)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668641

RESUMO

Telehealth, by definition, is distributing health-related services while using electronic technologies. This narrative Review describes the technological health services (telemedicine and telemonitoring) for delivering care in neurodegenerative diseases, Alzheimer's disease, Parkinson's Disease, and amyotrophic lateral Sclerosis, among others. This paper aims to illustrate this approach's primary experience and application, highlighting the strengths and weaknesses, with the goal of understanding which could be the most useful application for each one, in order to facilitate telehealth improvement and use in standard clinical practice. We also described the potential role of the COVID-19 pandemic to speed up this service's use, avoiding a sudden interruption of medical care.

11.
Neurogenetics ; 22(1): 65-70, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471268

RESUMO

Primary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.


Assuntos
Encefalopatias/genética , Mutação/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Idoso , Encéfalo/metabolismo , Encéfalo/patologia , Encefalopatias/diagnóstico , Encefalopatias/patologia , Éxons/genética , Feminino , Humanos , Linhagem , Fenótipo
12.
NeuroRehabilitation ; 48(1): 49-57, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33386822

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons. The current practice of caring for patients affected by ALS involves a multidisciplinary team without any indication about oral health care. OBJECTIVE: We sought to investigate the functional status and oral health in patients with ALS to define a specific multidisciplinary management. METHODS: In this cross-sectional study, we included patients affected by ALS, evaluating their functional status, using the Revised ALS Functional Rating Scale (ALSFRS-R) and their oral health status through specific parameters, including Brief Oral Health Status Examination (BOHSE), Winkel Tongue Coating Index (WTCI), and Oral Food Debris Index (OFDI). RESULTS: All 37 patients (mean age: 61.19±11.56 years) showed a poor oral status, independent from the functional status and strictly correlated to the severity of sialorrhea (p = 0.01). OFDI index was negatively correlated with the ALSFRS-R upper limb (p = 0.03). Patients with bulbar onset had significantly lower ability to perform adequate tongue movements in terms of protrusion (p = 0.006) and lateralization (p < 0.001). Significant negative correlations between survival rate and BOHSE (p = 0.03) was found. CONCLUSIONS: Taken together, our findings showed that a poor oral health status might be correlated to a worse functional status and survival time. Thus, an adequate oral health care and rehabilitation should be considered as crucial in the multidisciplinary management of patients with ALS.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Progressão da Doença , Estado Funcional , Saúde Bucal/tendências , Idoso , Esclerose Amiotrófica Lateral/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extremidade Superior/fisiopatologia
13.
Acta Neurol Scand ; 143(5): 489-496, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33185886

RESUMO

BACKGROUND AND OBJECTIVE: Specialized multidisciplinary ALS care has been shown to extend survival and improve patient's and caregiver's quality of life. During the COVID-19 pandemic, the management of patients suddenly changed and telemedicine has been proven to be as effective as outpatient care. We elaborate the experience with Telemedicine of a Tertiary ALS Center from an Italian geographical area with high infectious risk during the COVID-19 pandemic. METHODS: 19 patients were evaluated in telemedicine by a multidisciplinary team including a neurologist (clinical evaluation, intercurrent events, and drug prescriptions); a dietician (diet and weight monitoring); a psychologist (psychological assessment and support); and a physiotherapist (physiotherapy treatment and device prescription). Telemedicine was performed using the online platform "IoMT Connected Care Platform (Ticuro Reply)." RESULTS: All patients reported a positive perception of talking face to face with healthcare professionals and were satisfied with how the team understood their problems. During video televisits, there was a change in the patient's medication regimen in 11/19; 2/19 required pneumological evaluation and started NIV; and 9/16 patients required prescription of devices. The mean monthly decline of ALSFRS-R before televisit was 0.88 (SD 1.17) and during televisit of 0.49 (SD 0.75). Bodyweight and daily caloric content remain stable. Reduction in HADS scores and stability in ALSAQ-40 were observed. DISCUSSION: Our study positively reproduced the multidisciplinary approach currently used with ALS patients, trying to stabilize the functional and metabolic status and improving the psychological one. Future directions include a personalized telemedicine program according to the patient's needs.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/terapia , COVID-19/epidemiologia , Pandemias , Satisfação do Paciente , Telemedicina/métodos , Adulto , Esclerose Amiotrófica Lateral/psicologia , COVID-19/psicologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/normas , Qualidade de Vida/psicologia , Telemedicina/normas
14.
Eur J Phys Rehabil Med ; 57(1): 78-84, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32744050

RESUMO

BACKGROUND: Decreased range of motion is a common secondary complication of motor neuron disease (MND) that can contribute to functional decline and decreased participation in daily activities. AIM: The purpose of this study was to develop and assess the effectiveness of educational brochures and videos aimed at improving knowledge regarding the importance of a regular stretching program. DESIGN: This was a quality improvement (QI) project. SETTING: Participants were seen in an outpatient multidisciplinary neuromuscular clinic. POPULATION: Individuals with motor neuron disease were invited to participate in this QI study. METHODS: Individuals were asked to complete surveys asking questions regarding current stretching program, pain levels, and knowledge of benefits of stretching before and after receiving the stretching brochures or videos. RESULTS: A total of 53 participants completed the pre-intervention survey, 28 in the brochure group and 25 in the video group. Of those, 86% and 88% completed the post-intervention survey in the brochure and video groups, respectively. The video group increased stretching frequency significantly more than the brochure group (2.04 and 0.62 days/week respectively, P=0.004). Significantly more participants in the video group reported usage of stretches from the educational materials on a regular basis (54% for brochure group and 86% for video group, P=0.024). CONCLUSIONS: Educational brochures and videos are two different strategies to improve knowledge of benefits of stretching for individuals with MND. Both groups increased frequency of stretching. Videos may be better able to improve frequency of stretching when compared to brochures. CLINICAL REHABILITATION IMPACT: The brochures and videos developed for this study can be used by clinicians treating individuals with MND. By improving knowledge regarding the benefits of stretching, individuals with MND may choose to prioritize stretching as a part of their routine. This in turn may help to prevent or address potential joint or muscle length issues or assist patients to incorporate preventative measures into their treatment plans.


Assuntos
Terapia por Exercício/métodos , Doença dos Neurônios Motores/fisiopatologia , Doença dos Neurônios Motores/terapia , Exercícios de Alongamento Muscular/fisiologia , Educação de Pacientes como Assunto/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Melhoria de Qualidade , Inquéritos e Questionários
15.
Neurol Sci ; 42(3): 1119-1121, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33051751

RESUMO

We found four patients with some characteristic phenotype in our ICU, characterized by focal hypotrophies of the shoulder girdle and the bilateral peroneal district and underlying critical illness neuro-myopathy. In our opinion, these hypotrophies are secondary to the prone position. Is our intention to start early treatment protocol with electrostimulation to evaluate the effectiveness in the prevention of critical illness and focal hypotrophies in ICU SARS-CoV-2 patients, to increase chances of returning to a preinfection functional status.


Assuntos
COVID-19/complicações , Doenças Musculares/virologia , Polineuropatias/virologia , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Decúbito Ventral , SARS-CoV-2
16.
Brain Sci ; 10(12)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339434

RESUMO

In amyotrophic lateral sclerosis (ALS), magnetic resonance imaging (MRI) allows investigation at the microstructural level, employing techniques able to reveal white matter changes. In the current study, a diffusion tensor imaging (DTI) analysis, with a collection of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) indexes, was performed in ALS patients to correlate geno- and phenotype features with MRI data, to investigate an in-vivo correlation of different neuropathological patterns. All patients who underwent the MR-DTI analysis were retrospectively recruited. MRI scan was collected within three months from diagnosis. FA and ADC values were collected in corpus callosum (CC), corona radiata (CR), cerebral peduncle (CR), cerebellar peduncle (CbP) and corticospinal tract at posterior limb of internal capsule (CST). DTI analysis performed in the whole ALS cohort revealed significant FA reduction and ADC increase in all selected regions, as widespread changes. Moreover, we observed a higher value of FA in rCR in bulbar patients. A positive correlation between ALS Functional Rating Scale-Revised and FA in rCP was evident. In consideration of the non-invasiveness, the reliability and the easy reproducibility of the method, we believe that brain MRI with DTI analyses may represent a valid tool usable as a diagnostic marker in ALS.

17.
Brain Commun ; 2(2): fcaa124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134918

RESUMO

Despite wide genetic, environmental and clinical heterogeneity in amyotrophic lateral sclerosis, a rapidly fatal neurodegenerative disease targeting motoneurons, neuroinflammation is a common finding. It is marked by local glial activation, T cell infiltration and systemic immune system activation. The immune system has a prominent role in the pathogenesis of various chronic diseases, hence some of them, including some types of cancer, are successfully targeted by immunotherapeutic approaches. However, various anti-inflammatory or immunosuppressive therapies in amyotrophic lateral sclerosis have failed. This prompted increased scrutiny over the immune-mediated processes underlying amyotrophic lateral sclerosis. Perhaps the biggest conundrum is that amyotrophic lateral sclerosis pathogenesis exhibits features of three otherwise distinct immune dysfunctions-excessive inflammation, autoimmunity and inefficient immune responses. Epidemiological and genome-wide association studies show only minimal overlap between amyotrophic lateral sclerosis and autoimmune diseases, so excessive inflammation is usually thought to be secondary to protein aggregation, mitochondrial damage or other stresses. In contrast, several recently characterized amyotrophic lateral sclerosis-linked mutations, including those in TBK1, OPTN, CYLD and C9orf72, could lead to inefficient immune responses and/or damage pile-up, suggesting that an innate immunodeficiency may also be a trigger and/or modifier of this disease. In such cases, non-selective immunosuppression would further restrict neuroprotective immune responses. Here we discuss multiple layers of immune-mediated neuroprotection and neurotoxicity in amyotrophic lateral sclerosis. Particular focus is placed on individual patient mutations that directly or indirectly affect the immune system, and the mechanisms by which these mutations influence disease progression. The topic of immunity in amyotrophic lateral sclerosis is timely and relevant, because it is one of the few common and potentially malleable denominators in this heterogenous disease. Importantly, amyotrophic lateral sclerosis progression has recently been intricately linked to patient T cell and monocyte profiles, as well as polymorphisms in cytokine and chemokine receptors. For this reason, precise patient stratification based on immunophenotyping will be crucial for efficient therapies.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32915077

RESUMO

BACKGROUND AND OBJECTIVE: Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease's natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS. Methods: Clinical characteristics, electrophysiological findings, laboratory values, disease-related symptoms, and medications for symptom management were collected from PLS patients seen between 2000 and 2015. Results: The NEALS registry included data from 250 PLS patients. Median follow-up time was 3 years. The mean rate of functional decline measured by ALSFRS-R total score was -1.6 points/year (SE:0.24, n = 124); the mean annual decline in vital capacity was -3%/year (SE:0.55, n = 126). During the observational period, 18 patients died, 17 patients had a feeding tube placed and 7 required permanent assistive ventilation. Conclusions: The NEALS PLS Registry represents the largest available aggregation of longitudinal clinical data from PLS patients and provides a description of expected natural disease progression. Data from the registry will be available to the PLS community and can be leveraged to plan future clinical trials in this rare disease.


Assuntos
Esclerose Amiotrófica Lateral , Doença dos Neurônios Motores , Doenças Neurodegenerativas , Adulto , Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/epidemiologia , Humanos , Doença dos Neurônios Motores/epidemiologia , Sistema de Registros , Estudos Retrospectivos
19.
Stem Cell Res ; 47: 101924, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739880

RESUMO

Among the known causative genes of familial ALS, SOD1mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not caused by loss of its detoxifying activity but by a gain-of-function. In order to better understand the pathogenic mechanisms of SOD1 mutation, a human induced pluripotent stem cell (hiPSC) line was generated from the somatic cells of a female patient carrying a missense variation in SOD1 (L145F).

20.
BMC Med ; 18(1): 153, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32546239

RESUMO

BACKGROUND: A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression. METHODS: Fifty patients and 50 matched controls were enrolled. The microbial profile of stool samples from patients and controls was analyzed via PCR-Denaturing Gradient Gel Electrophoresis, and the main microbial groups quantified via qPCR. The whole microbiota was then analyzed via next generation sequencing after amplification of the V3-V4 region of 16S rDNA. Patients were then randomized to receive probiotic treatment or placebo and followed up for 6 months with ALSFRS-R, BMI, and FVC%. RESULTS: The results demonstrate that the gut microbiota of ALS patients is characterized by some differences with respect to controls, regardless of the disability degree. Moreover, the gut microbiota composition changes during the course of the disease as demonstrated by the significant decrease in the number of observed operational taxonomic unit during the follow-up. Interestingly, an unbalance between potentially protective microbial groups, such as Bacteroidetes, and other with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been shown. The 6-month probiotic treatment influenced the gut microbial composition; however, it did not bring the biodiversity of intestinal microbiota of patients closer to that of control subjects and no influence on the progression of the disease measured by ALSFRS-R was demonstrated. CONCLUSIONS: Our study poses the bases for larger clinical studies to characterize the microbiota changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut. TRIAL REGISTRATION: CE 107/14, approved by the Ethics Committee of the "Maggiore della Carità" University Hospital, Italy.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Adolescente , Adulto , Idoso , Animais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
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