Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period

Testa, D.; Lovati, Roberta; Ferrarini, Massimo; Salmoiraghi, Fabrizio; Filippini, Graziella

doi:10.1080/14660820410021311

Cited by 114 publications

(78 citation statements)

References 30 publications

(26 reference statements)

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“…A population-based cohort study is less likely to be biased, but it is difficult to achieve the same level of clinical detail and sample size required for analysis of the natural history of relatively uncommon subgroups such as the FA and FL syndromes. 23,24 Nonetheless, median survival from symptom onset in the bulbar and limb onset ALS groups in our study is comparable to that found in previous large clinicbased cohort studies 6,31,32 and in large population registry studies, 4,5 making it unlikely that we have overestimated survival. In the future, large populationbased samples comprising detailed and standardized phenotypic information will be required to validate or modify our conclusions.…”

Section: Resultssupporting

confidence: 76%

Natural history and clinical features of the flail arm and flail leg ALS variants

Wijesekera¹,

Mathers²,

Talman³

et al. 2009

Neurology

222

201

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Objective: We sought to define the significance of brachial amyotrophic diplegia (flail arm syndrome [FA]) and the pseudopolyneuritic variant (flail leg syndrome [FL]) of amyotrophic lateral sclerosis (ALS; motor neuron disease). Methods:We analyzed survival in clinic cohorts in London, UK (1,188 cases), and Melbourne, Australia (432 cases). Survival from disease onset was analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results:In the London cohort, the FA syndrome represented 11% and the FL syndrome 6% of the sample. Median survival was 35 months for limb onset and 27 months for bulbar onset ALS, whereas this was 61 months for FA syndrome (p Ͻ 0.001) and 69 months for FL syndrome (p Ͻ 0.001). Five-year survival in this cohort was 8.8% for bulbar onset, 20% for limb onset, 52% for FA syndrome, and 64% for FL syndrome. The ratio of men to women was 4:1 in the FA group compared to 2:1 in other limb onset cases. Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS. In the Melbourne cohort, median survival for limb onset ALS was 31 months, bulbar onset 27 months, FA syndrome 66 months (p Ͻ 0.001), and FL syndrome 71 months (p ϭ 0.001). Amyotrophic lateral sclerosis (ALS) comprises several clinical phenotypes united by a common cellular and molecular pathology. Conclusions:1 The three main clinical categories defined by Aran, Charcot, Duchenne, and others in the 19th century and which were subsequently shown to have both diagnostic and prognostic significance were progressive bulbar palsy (bulbar onset ALS), classic limb onset (Charcot) ALS, and a lower motor neuron form termed progressive muscular atrophy (PMA).2-5 Prognostic factors in these forms of ALS have been delineated through clinic and population-based studies. 6,7 Bulbar onset tends to have a worse prognosis than limb onset, and both forms have a worse prognosis than PMA.2,4-7 However, these three phenotypic categories do not fully capture the spectrum of clinical heterogeneity in ALS. This heterogeneity may contribute to diagnostic error and delay, and with the advent of large-scale whole genome studies that have the potential to identify genetic variants influencing both risk and phenotype,

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Section: Resultssupporting

confidence: 76%

Natural history and clinical features of the flail arm and flail leg ALS variants

Wijesekera¹,

Mathers²,

Talman³

et al. 2009

Neurology

222

201

View full text Add to dashboard Cite

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“…Using the PRO-ACT database allowed for validation of these findings; for example, site of onset has been shown to affect the slope of ALSFRS and overall survival time [33][34][35][36][37][38][39][40][41], with bulbar onset leading to poor prognosis compared with limb onset. Similarly, age of onset was predictive of prognosis (with poorer prognosis for patients with an later disease onset [34][35][36][37][38][39][40][41][42][43][44]). Other factors connected to prognosis in previous reports included body mass index or absolute weight [42,45]; cognitive functioning [46]; level of uric acid [42,47]; and levels of albumin and creatinine [48,49].…”

Section: Understanding Als Clinical Manifestationmentioning

confidence: 99%

Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS?

et al. 2015

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Advancing research and clinical care, and conducting successful and cost-effective clinical trials requires characterizing a given patient population. To gather a sufficiently large cohort of patients in rare diseases such as amyotrophic lateral sclerosis (ALS), we developed the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) platform. The PRO-ACT database currently consists of >8600 ALS patient records from 17 completed clinical trials, and more trials are being incorporated. The database was launched in an open-access mode in December 2012; since then, >400 researchers from >40 countries have requested the data. This review gives an overview on the research enabled by this resource, through several examples of research already carried out with the goal of improving patient care and understanding the disease. These examples include predicting ALS progression, the simulation of future ALS clinical trials, the verification of previously proposed predictive features, the discovery of novel predictors of ALS progression and survival, the newly identified stratification of patients based on their disease progression profiles, and the development of tools for better clinical trial recruitment and monitoring. Results from these approaches clearly demonstrate the value of large datasets for developing a better understanding of ALS natural history, prognostic factors, patient stratification, and more. The increasing use by the community suggests that further analyses of the PRO-ACT database will continue to reveal more information about this disease that has for so long defied our understanding.

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“…Индивидуальное течение болезни может быть крайне вариабельным и трудно прогнозируемым, несмотря на разработку в последние годы ряда относительно точных предиктивных моде-лей [44]. После постановки диагноза >1 года живут 76 % пациентов, >5 лет -24 %, >10 лет -11 % [45]. Выявлены несколько мутаций, ассоциированных с медленным (например, Asp90Ala в гене СОД1) или, напротив, быстрым (Ala4Val в гене СОД1) прогресси-рованием болезни [16].…”

Section: Exclusion Criteriaunclassified

Amyotrophic lateral sclerosis: Clinical heterogeneity and approaches to classification

Bakulin¹,

Zakroishchikova²,

Супонева³

et al. 2017

Neuromuscular Diseases

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Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period

Cited by 114 publications

References 30 publications

Natural history and clinical features of the flail arm and flail leg ALS variants

Natural history and clinical features of the flail arm and flail leg ALS variants

Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS?

Amyotrophic lateral sclerosis: Clinical heterogeneity and approaches to classification

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