Amyotrophic lateral sclerosis regional progression intervals change according to time of involvement of different body regions

Abstract

Background and purpose:The prediction of disease course is one of the main targets of amyotrophic lateral sclerosis (ALS) research, particularly considering its wide phenotypic heterogeneity. Despite many attempts to classify patients into prognostic categories according to the different spreading patterns at diagnosis, a precise regional progression rate and the time of involvement of each region has yet to be clarified. The aim of our study was to evaluate the functional decline in different body regions according to their time of involvement during disease course. Methods:In a population-based dataset of ALS patients, we analysed the functional decline in different body regions according to time and order of regional involvement.We calculated the regional progression intervals (RPIs) between initial involvement and severe functional impairment using the ALS Functional Rating Scale revised (ALSFRS-r) subscores for the bulbar, upper limb, lower limb and respiratory/thoracic regions. Timeto-event analyses, adjusted for age, sex, ALSFRS-r pre-slope (ΔALSFRS-R), cognitive status, and mutational status were performed. Results:The duration of RPI differed significantly among ALS phenotypes, with the RPI of the first region involved being significantly longer than the RPIs of regions involved later.Cox proportional hazard models showed that in fact a longer time between disease onset and initial regional involvement was related to a reduced duration of the RPI duration in each different body region (bulbar region: hazard ratio [HR] 1.11, 95% confidence interval [

Structural and Functional Brain Network Connectivity at Different King's Stages in Patients With Amyotrophic Lateral Sclerosis

“… 33 However, only some of these reports also showed a concomitant correlation of MRI features with clinical measures of functional impairment. 30 , 31 Considering the great prognostic importance of the cumulative number of body regions involved and regional progression time intervals shown by recent epidemiologic studies, 34 , 35 the assessment of advanced network-based techniques in our study bridges a gap between the neuroimaging and clinical fields, supporting the use of MRI structural connectomics as a biomarker of progressing neurodegeneration in ALS that might allow a better stratification of patients into upcoming treatment trials.…”

Calculated Maximal Volume Ventilation (cMVV) as a Marker of Early Respiratory Failure in Amyotrophic Lateral Sclerosis (ALS)

“…We also evaluated, in a separate analysis, the data of the first ABGs and PFTs performed simultaneously during the respiratory workup, using another dataset already published [12]. This dataset also reported the nearest ALSFRS-R performed, and we derived from it data on respiratory symptoms (by using ALSFRS-R item 10 and 11) and bulbar dysfunction, defining bulbar involvement when the sum of items 1, 2, and 3 resulted in a value < 12 [2]. Patients with severe pulmonary, metabolic, and kidney diseases and those with signs of uncompensated acidosis/alkalosis (ABGs pH < 7.35 and > 7.45) were excluded.…”

“…Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), a family of neurodegenerative diseases characterized by the progressive loss of bulbar, limbs, and respiratory muscles [1]. Among the different body regions involved in the degeneration of motor neurons, the thoracic/respiratory muscles are often considered to be one of the last types to become involved [2], and only 1% of patients have a respiratory onset phenotype [3].…”