Search

Objective: To assess the determinants of amyotrophic lateral sclerosis (ALS) phenotypes in a population-based cohort., Methods: The study population included 2,839 patients with ALS diagnosed in Piemonte, Italy (1995-2015). Patients were classified according to motor (classic, bulbar, flail arm, flail leg, predominantly upper motor neuron [PUMN], respiratory) and cognitive phenotypes (normal, ALS with cognitive impairment [ALSci], ALS with behavioral impairment [ALSbi], ALSci and ALSbi combined [ALScbi], ALS-frontotemporal dementia [FTD]). Binary logistic regression analysis was adjusted for sex, age, and genetics., Results: Bulbar phenotype correlated with older age ( p < 0.0001), women were more affected than men at increasing age ( p < 0.0001), classic with younger age ( p = 0.029), men were more affected than women at increasing age ( p < 0.0001), PUMN with younger age ( p < 0.0001), flail arm with male sex ( p < 0.0001) and younger age ( p = 0.04), flail leg with male sex with increasing age ( p = 0.008), and respiratory with male sex ( p < 0.0001). C9orf72 expansions correlated with bulbar phenotype ( p < 0.0001), and were less frequent in PUMN ( p = 0.041); SOD1 mutations correlated with flail leg phenotype ( p < 0.0001), and were less frequent in bulbar ( p < 0.0001). ALS-FTD correlated with C9orf72 ( p < 0.0001) and bulbar phenotype ( p = 0.008), ALScbi with PUMN ( p = 0.014), and ALSci with older age ( p = 0.008)., Conclusions: Our data suggest that the spatial-temporal combination of motor and cognitive events leading to the onset and progression of ALS is characterized by a differential susceptibility to the pathologic process of motor and prefrontal cortices and lower motor neurons, and is influenced by age, sex, and gene variants. The identification of those factors that regulate ALS phenotype will allow us to reclassify patients into pathologically homogenous subgroups, responsive to targeted personalized therapies., (© 2020 American Academy of Neurology.)

Objective: To assess the association of the degree of severity of motor impairment to that of cognitive impairment in a large cohort of patients with amyotrophic lateral sclerosis (ALS)., Methods: This is a population-based cross-sectional study on patients with ALS incident in Piemonte, Italy, between 2007 and 2015. Cognitive status was classified according to the revised ALS-FTD Consensus Criteria. The King system and the Milano Torino Staging system (MiToS) were used for defining the severity of motor impairment., Results: Of the 797 patients included in the study, 163 (20.5%) had ALS-frontotemporal dementia (FTD), 38 (4.8%) cognitive and behavioral impairment (ALScbi), 132 (16.6%) cognitive impairment (ALSci), 63 (7.9%) behavioral impairment (ALSbi), 16 (2.0%) nonexecutive impairment, and 385 (48.2%) were cognitively normal. According to King staging, the frequency of cases with ALS-FTD progressively increased from 16.5% in stage 1-44.4% in stage 4; conversely, the frequency of ALSci, ALSbi, and ALScbi increased from King stage 1 to King stage 3 and decreased thereafter. A similar pattern was observed with the MiToS staging. ALS-FTD was more frequent in patients with bulbar involvement at time of cognitive testing. Patients with C9ORF72 expansion (n = 61) showed more severe cognitive impairment with increasing King and MiToS stages., Conclusion: Our findings suggest that ALS motor and cognitive components may worsen in parallel, and that cognitive impairment becomes more pronounced when bulbar function is involved. Our data support the hypothesis that ALS pathology disseminates in a regional ordered sequence, through a cortico-efferent spreading model., (© 2019 American Academy of Neurology.)

Objectives: Amyotrophic lateral sclerosis (ALS) is not only a motor disorder: More than 50% of patients have cognitive dysfunctions over the course of the disease. At the same time, mood disorders may also occur in ALS patients following diagnosis due to the fatal prognosis; however, little data are available on any depression beforehand. Starting from these considerations, the aim of our study was to investigate the occurrence of depression in Italian ALS patients prior to diagnosis, evaluating its prevalence in the subjects who have developed cognitive dysfunctions and in those who did not., Materials and Methods: We included 318 patients, establishing the presence of depression in the 5 years before ALS diagnosis. Patients underwent a complete battery of neuropsychological tests with the aim to evaluate the executive functions, behavior, language, and memory., Results: Before diagnosis, 40 patients with ALS had been diagnosed with depression: Among them, 29 patients had cognitive impairment over the course of the disease and only 11 did not develop any cognitive alteration (OR 1.46; 95% CI: 1.26-1.66, adjusted for sex, age, and disease phenotype, P: 0.038). Moreover, there is a significant difference in survival time between ALS patients with depression before ALS, compared to ALS patients without previous depression (P: 0.006)., Conclusions: We reported a high prevalence of depression in the past in patients with ALS and cognitive impairment, as compared to patients without cognitive deficits, showing also that patients with both had a shorter survival time. These aspects require multidisciplinary approach at disease onset., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)