Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

Mandrioli, Jessica; Malerba, Sara Angela; Beghi, Ettore; Fini, Nicola; Fasano, Antonio; Zucchi, Elisabetta; Pasqua, Silvia De; Guidi, Carlo; Terlizzi, Emilio; Sette, Elisabetta; Ravasio, Alessandro; Casmiro, Mario; Salvi, Fabrizio; Liguori, Rocco; Zinno, Lucia; Handouk, Yasmin; Rizzi, Romana; Borghi, Annamaria; Rinaldi, Rita; Medici, D.; Santangelo, Mario; Granieri, Enrico; Mussuto, V.; Aiello, Marina; Ferro, Salvatore; Vinceti, Marco

doi:10.1007/s00415-018-8778-y

Cited by 29 publications

(29 citation statements)

References 42 publications

(65 reference statements)

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“…Of note is also that in our population the C9orf72 expansion was associated with lower odds of spinal onset, NIV, hypertension, and psychiatric diseases. This evidence was not unexpected with regard to the lower odds of association between the C9orf72 expansion and spinal onset and NIV, in consideration of the above discussed higher odds of association between the C9orf72 expansion and bulbar onset, among possible onsets, and given the higher association between the C9orf72 expansion and dementia, proven to induce less adherence and compliance to treatments, including NIV (Govaarts et al, 2016; Mandrioli et al, 2018b).…”

Section: Discussionmentioning

confidence: 81%

Comparative Analysis of C9orf72 and Sporadic Disease in a Large Multicenter ALS Population: The Effect of Male Sex on Survival of C9orf72 Positive Patients

et al. 2019

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We investigated whether the C9orf72 repeat expansion is associated with specific clinical features, comorbidities, and prognosis in patients with amyotrophic lateral sclerosis (ALS). A cohort of 1417 ALS patients, diagnosed between January 1, 2009 and December 31, 2013 by 13 Italian ALS Referral Centers, was screened for the C9orf72 repeat expansion, and the analyses were performed comparing patients carrying this expansion (ALS-C9Pos) to those negative for this and other explored ALS-related mutations (ALS without genetic mutations, ALSwoGM). Compared to the ALSwoGM group, ALS-C9Pos patients ( n = 84) were younger at disease onset, at the first clinical observation and at diagnosis ( p < 0.001). After correcting for these differences, we found that ALS-C9Pos patients had higher odds of bulbar onset, diagnosis of frontotemporal dementia (FTD) and family history of ALS, FTD, and Alzheimer's disease and had lower odds of spinal onset, non-invasive ventilation, hypertension and psychiatric diseases than ALSwoGM patients. Among these variables, those related to shorter survival time were: bulbar onset, presence of FTD, hypertension, psychiatric disease, and family history of ALS ( p < 0.05). Cox proportional hazards regression multivariate analysis suggested that carrying the C9orf72 repeat expansion was an independent factor negatively impacting on survival time in men (HR 1.58, 95% CI 1.07–2.33, p = 0.021), but not in women ( p > 0.05) as well as in the whole sample ( p > 0.05). When compared to ALSwoGM, ALS-C9Pos showed an earlier disease onset, no significant diagnostic delay and a higher odds of bulbar onset, FTD and family history of ALS and dementia. Moreover, male sex drove the negative effect of expanded variant on survival, confirming the hypothesis that sex is likely to be a crucial factor in the biology of C9orf72 -related disease.

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Section: Discussionmentioning

confidence: 81%

Comparative Analysis of C9orf72 and Sporadic Disease in a Large Multicenter ALS Population: The Effect of Male Sex on Survival of C9orf72 Positive Patients

et al. 2019

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“…Current and past use of riluzole was associated with longer time to hospice referral. This could be due to participants choosing more aggressive treatments aimed at prolonging survival, which delay their entry into hospice, which has been seen in other registry studies (39,40). All study participants were alive so we were unable to estimate any differences in survival.…”

Section: Discussionmentioning

confidence: 98%

Clinical characteristics of a large cohort of US participants enrolled in the National Amyotrophic Lateral Sclerosis (ALS) Registry, 2010–2015

Raymond

Oskarsson

Mehta

et al. 2019

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Background: Amyotrophic lateral sclerosis (ALS) is a progressive fatal disease with a varying range of clinical characteristics. Objective: To describe the clinical characteristics in a large cohort of ALS participants enrolled in the National ALS Registry. Methods: Data from ALS participants who completed the Registry's online clinical survey module during 2010-2015 were analyzed to determine characteristics, such as site of onset, associated symptoms, time of symptom onset to diagnosis, time of diagnosis to hospice referral, and pharmacological and non-pharmacological interventions. Results: Of the 1758 participants who completed the survey, 60.9% were male, 62.1% were 50-69 years old, and 95.5% white. Approximately, 72.0% reported initial limb weakness onset of disease, followed by bulbar (22.1%), and trunk/global onset (6.1%). Other symptoms ever experienced included cramps (56.7%), fasciculations (56.3%), and dysarthria (33.0%). The median time between an increase of muscle cramps until an ALS diagnosis was 12 months; limb onset participants had cramps longer preceding diagnosis versus those with bulbar onset. The most frequent interventions used included riluzole (48.3% currently using), wheelchairs/scooters (32.8%), and noninvasive breathing equipment (30.0%). Participants with trunk/global onset were referred to hospice almost four times earlier than others. Conclusions: These data show how ALS clinical characteristics differ widely in a large cohort of participants preceding diagnosis and reflect variations in disease onset, progression, and prognosis. Better characterization of symptom onset may assist clinicians in diagnosing ALS sooner, which could lead to earlier therapeutic interventions.

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“…Riluzole was given infrequently in the old register. There is evidence that it slows disease in randomized trials and reduces risk of death in disease registers (23). There was no suggestion that Riluzole use was skewed to individuals who were progressing less quickly.…”

Section: Discussionmentioning

confidence: 99%

Improved survival and 30-day mortality after gastrostomy in Scottish motor neurone disease patients: evidence from a national retrospective cohort study using STROBE criteria

Gorrie

Chandran

Colville

et al. 2019

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Objectives: Defining historical changes and outcomes in the use of gastrostomy in the management of Scottish MND patients. Methods: The 1989-1998 and 2015-2016 Scottish national MND cohorts were used to examine the frequency, timing, and survival related to gastrostomy. The cohorts were censored for survival analysis. Results: There were 261 cases, 119 (46%) from the new register (2015-2016) and 142 (54%) from the old register (1989-1999). Percutaneous endoscopic gastrostomy (PEG) tubes were used exclusively in the old register vs. the new register where PEG (45%), Radiologically inserted gastrostomy (RIG) (44%) and a small number of peroral image-guided gastrostomy (PIGG) tubes (11%), p < 0.01 were used. Odds of 30-d mortality in the old register were 2.8 times that in the new register, p < 0.01. Median survival time from gastrostomy was significantly higher in the new register, 2.7 months, p < 0.05. Median survival time from onset was also higher in the new register but non-significant, 3.2 months, p ¼ 0.30. Multivariate analysis identified age at onset (hazard ratio [HR] 1.02 p ¼ 0.01), time from onset to diagnosis (HR 0.74 p < 0.01), subtype of onset (HR 1.52 p ¼ 0.01), with gastrostomy and Riluzole interacting as variables that predict risk of death. Conclusions: Gastrostomy use has increased with techniques changing over time. It is safer and survival time has increased post gastrostomy. Being older and diagnosed more quickly increases risk of death whilst taking Riluzole combined with gastrostomy reduced risk of death. Survival from onset has not significantly changed in Scottish MND patients having gastrostomy.

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Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

Abstract: Independently from other prognostic factors, patients who received riluzole for a longer period of time survived longer, but further population based studies are needed to verify if long-tem use of riluzole prolongs survival.

Cited by 29 publications

References 42 publications

Comparative Analysis of C9orf72 and Sporadic Disease in a Large Multicenter ALS Population: The Effect of Male Sex on Survival of C9orf72 Positive Patients

Comparative Analysis of C9orf72 and Sporadic Disease in a Large Multicenter ALS Population: The Effect of Male Sex on Survival of C9orf72 Positive Patients

Clinical characteristics of a large cohort of US participants enrolled in the National Amyotrophic Lateral Sclerosis (ALS) Registry, 2010–2015

Improved survival and 30-day mortality after gastrostomy in Scottish motor neurone disease patients: evidence from a national retrospective cohort study using STROBE criteria

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