Objective To unveil clinical features, comorbidities, disease progression and prognostic factors in a population-based cohort of ALS patients carrying C9ORF72 expansion (C9 + ALS). Methods This is a retrospective observational study on ALS patients residing in Emilia Romagna and Piedmont-Valle D'Aosta regions whose data are available through population based registers. We analysed patients who underwent genetic testing, focusing on C9 + ALS subgroup. Results Among 2204 genotyped patients of the two registers, 150 were C9 + ALS. In comparison with patients without mutation, a higher proportion of family history (12.85 vs 68%, p < 0.001) and frontotemporal dementia (3.93% vs 10.67%, p < 0.001) was detected in C9 + ALS. C9 + ALS presented a faster disease progression as measured by monthly decline in ALS Functional Rating Scale-Revised (1.86 +/- 3.30 vs 1.45 +/- 2.35, p < 0.01) and in forced vital capacity (5.90 +/- 5.24 vs 2.97 +/- 3.47, p < 0.01), a shorter diagnostic delay (8.93 +/- 6.74 vs 12.68 +/- 12.86 months, p < 0.01) and earlier onset (58.91 +/- 9.02 vs 65.04 +/- 11.55 years, p < 0.01). Consistently, they reached death or tracheostomy earlier than other patients (31 vs 37 months, HR = 1.52, 95% C.I. 1.27-1.82, p < 0.001). With respect to other genotyped patients, C9 + ALS patients did not present a significantly higher prevalence of concomitant diseases. Independent prognostic factors of survival of C9 + ALS included sex, age, progression rate, presence of frontotemporal dementia and thyroid disorders, with the latter being associated with prolonged ALS survival (43 vs 29 months, HR = 0.42, 95% C.I. 0.24-0.74, p = 0.003). Conclusion Even in the context of a more aggressive disease, C9 + ALS had a longer survival in presence of thyroid disorders. This finding may suggest protective pathogenic pathways in C9 + ALS to be explored, looking for therapeutic strategies to slow disease course.

Factors predicting disease progression in C9ORF72 ALS patients / Mandrioli, Jessica; Zucchi, Elisabetta; Martinelli, Ilaria; Van der Most, Laura; Gianferrari, Giulia; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Tupler, Rossella; Vinceti, Marco; Chiò, Adriano; Calvo, Andrea. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - 270:2(2023), pp. 877-890. [10.1007/s00415-022-11426-y]

Factors predicting disease progression in C9ORF72 ALS patients

Mandrioli, Jessica;Zucchi, Elisabetta;Martinelli, Ilaria;Van der Most, Laura;Gianferrari, Giulia;Simonini, Cecilia;Tupler, Rossella;Vinceti, Marco;
2023

Abstract

Objective To unveil clinical features, comorbidities, disease progression and prognostic factors in a population-based cohort of ALS patients carrying C9ORF72 expansion (C9 + ALS). Methods This is a retrospective observational study on ALS patients residing in Emilia Romagna and Piedmont-Valle D'Aosta regions whose data are available through population based registers. We analysed patients who underwent genetic testing, focusing on C9 + ALS subgroup. Results Among 2204 genotyped patients of the two registers, 150 were C9 + ALS. In comparison with patients without mutation, a higher proportion of family history (12.85 vs 68%, p < 0.001) and frontotemporal dementia (3.93% vs 10.67%, p < 0.001) was detected in C9 + ALS. C9 + ALS presented a faster disease progression as measured by monthly decline in ALS Functional Rating Scale-Revised (1.86 +/- 3.30 vs 1.45 +/- 2.35, p < 0.01) and in forced vital capacity (5.90 +/- 5.24 vs 2.97 +/- 3.47, p < 0.01), a shorter diagnostic delay (8.93 +/- 6.74 vs 12.68 +/- 12.86 months, p < 0.01) and earlier onset (58.91 +/- 9.02 vs 65.04 +/- 11.55 years, p < 0.01). Consistently, they reached death or tracheostomy earlier than other patients (31 vs 37 months, HR = 1.52, 95% C.I. 1.27-1.82, p < 0.001). With respect to other genotyped patients, C9 + ALS patients did not present a significantly higher prevalence of concomitant diseases. Independent prognostic factors of survival of C9 + ALS included sex, age, progression rate, presence of frontotemporal dementia and thyroid disorders, with the latter being associated with prolonged ALS survival (43 vs 29 months, HR = 0.42, 95% C.I. 0.24-0.74, p = 0.003). Conclusion Even in the context of a more aggressive disease, C9 + ALS had a longer survival in presence of thyroid disorders. This finding may suggest protective pathogenic pathways in C9 + ALS to be explored, looking for therapeutic strategies to slow disease course.
2023
25-ott-2022
270
2
877
890
Factors predicting disease progression in C9ORF72 ALS patients / Mandrioli, Jessica; Zucchi, Elisabetta; Martinelli, Ilaria; Van der Most, Laura; Gianferrari, Giulia; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Tupler, Rossella; Vinceti, Marco; Chiò, Adriano; Calvo, Andrea. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - 270:2(2023), pp. 877-890. [10.1007/s00415-022-11426-y]
Mandrioli, Jessica; Zucchi, Elisabetta; Martinelli, Ilaria; Van der Most, Laura; Gianferrari, Giulia; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Tupler, Rossella; Vinceti, Marco; Chiò, Adriano; Calvo, Andrea
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1320191
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