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. 2021 Apr 12;10(8):1623.
doi: 10.3390/jcm10081623.

Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis-A Retrospective Cohort Study

Maria Viktoria Requardt  1 , Dennis Görlich  2 , Torsten Grehl  3 , Matthias Boentert  1   4
Affiliations

Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis-A Retrospective Cohort Study

Maria Viktoria Requardt et al. J Clin Med. .

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is ultimately fatal but characterized by substantial phenotypic heterogeneity, which is known to impact long-term course and survival. This study investigated clinical determinants of disease progression and outcome in a large cohort of patients with ALS.

Methods: Retrospective analysis included comprehensive data from 625 patients who attended a tertiary ALS centre at least twice. Patients were stratified according to five distinct clinical phenotypes: classical ALS; bulbar ALS; ALS with frontotemporal dementia (ALS-FTD); upper motor neuron predominant (UMNP); and lower motor neuron predominant (LMNP).

Results: This study confirmed higher age at symptom onset, shorter latency to diagnosis and more rapid decline in the revised ALS Functional Rating Scale sum score as predictors of poor prognosis. Hazard ratios for shorter survival were higher in patients with ALS-FTD versus classical ALS, and in patients with versus without chronic obstructive pulmonary disease (COPD). Mean survival was longest in the UMNP phenotype group.

Conclusions: This study confirmed established predictors of shorter survival in ALS and showed that concomitant COPD in particular relates to poor outcome.

Keywords: amyotrophic lateral sclerosis; disease progression; phenotypes; prognostic factors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of clinical phenotypes. UMNP = upper motor neuron predominant; LMNP = lower motor neuron predominant; ALS-FTD = ALS with frontotemporal dementia.
Figure 2
Figure 2
Distribution of ALS phenotypes according to disease progression rate as reflected by (a), ALSFRS-R early slope, and (b), ALSFRS-R late slope. ALS = amyotrophic lateral sclerosis; ALSFRS-R = revised ALS Functional Rating Scale; ALS-FTD = ALS with frontotemporal dementia; LMNP = lower motor neuron predominant; UMNP = upper motor neuron predominant.
Figure 3
Figure 3
Kaplan–Meier survival curves according to (a) age at symptom onset; (b) clinical phenotype; (c) comorbid COPD; (d) ALSFRS-R early slope. ALSFRS-R = revised ALS Functional Rating Scale; ALS-FTD = ALS with frontotemporal dementia; COPD = chronic obstructive pulmonary disease; LMNP = lower motor neuron predominant; UMNP = upper motor neuron predominant. p values refer to the overall pooled log-rank (Mantel Cox) test.
See this image and copyright information in PMC

References

    1. Hardiman O., Al-Chalabi A., Chio A., Corr E.M., Logroscino G., Robberecht W., Shaw P.J., Simmons Z., Berg L.H.V.D. Amyotrophic lateral sclerosis. Nat. Rev. Dis. Prim. 2017;3:17071. doi: 10.1038/nrdp.2017.71. - DOI - PubMed
    1. Al-Chalabi A., Hardiman O., Kiernan M.C., Chiò A., Rix-Brooks B., Berg L.H.V.D. Amyotrophic lateral sclerosis: Moving towards a new classification system. Lancet Neurol. 2016;15:1182–1194. doi: 10.1016/S1474-4422(16)30199-5. - DOI - PubMed
    1. Spataro R., Re M.L., Piccoli T., Piccoli F., La Bella V. Causes and place of death in Italian patients with amyotrophic lateral sclerosis. Acta Neurol. Scand. 2010;122:217–223. doi: 10.1111/j.1600-0404.2009.01290.x. - DOI - PubMed
    1. Rosenbohm A., The ALS Registry Study Group. Peter R.S., Erhardt S., Lulé D., Rothenbacher D., Ludolph A.C., Nagel G. Epidemiology of amyotrophic lateral sclerosis in Southern Germany. J. Neurol. 2017;264:749–757. doi: 10.1007/s00415-017-8413-3. - DOI - PubMed
    1. Georgoulopoulou E., Fini N., Vinceti M., Monelli M., Vacondio P., Bianconi G., Sola P., Nichelli P., Mandrioli J. The impact of clinical factors, riluzole and therapeutic interventions on ALS survival: A population based study in Modena, Italy. Amyotroph. Lateral Scler. Front. Degener. 2013;14:338–345. doi: 10.3109/21678421.2013.763281. - DOI - PubMed