Language impairment in motor neuron disease phenotypes different from classical amyotrophic lateral sclerosis: a review

Abstract

BackgroundUp to 35-40% of patients with amyotrophic lateral sclerosis (ALS) present with language deficits falling within the spectrum of frontotemporal degeneration (FTD). It is currently debated whether frontotemporal involvement occurs or not in motor neuron disease (MND) phenotypes that differ from classical ALS (i.e., both non-ALS MNDs and non-classical ALS endo-phenotypes) - this stance being supported by the notion of a common pathology underlying MNDs. To investigate whether language dysfunctions also occur in patients with different-from-classical-ALS MNDs can; a) help determine whether the MND-FTD continuum could be broadened at a neuropsychological level; b) convey relevant entailments to cognitive diagnostics in these populations.AimsThe present study thus aimed at reviewing evidence regarding language impairment in different-from-classical-ALS MND patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were consulted to implement and report the present review. Studies were included if a) language was quantitatively assessed b) in patients diagnosed with different-from-classical-ALS MND phenotypes. Studies assessing demented patients only were excluded. From an original N=1117 contributions, N=20 group studies were finally included. Secondary outcomes were taken into account for qualitatively assessing potential biases in generalizing results.Main contributionStudies were divided into those assessing predominant-upper vs. - lower MND patients (UMND/LMND). Language dysfunctions appeared to be more prevalent and severe in UMND patients. Language screeners were able to detect language deficits in both groups. Lexical-semantic deficits appeared to be highly prevalent in both groups and a selective difficulty in action-vs. object-naming was systematically detected. Morpho-syntactic deficits were seldom reported in both groups. Phonological deficits and central dysgraphic features were found in UMND patients only.ConclusionPatients with different-from-classical-ALS MND phenotypes display language deficits similar to those of classical ALS patients (as far as both prevalence and type are concerned) and thus could be validly included in the MND-FTD continuum at a neuropsychological level. A greater cortical involvement might account for language deficits being more severe in UMND patients. Consistently with guidelines for cognitive assessment in ALS patients, action-naming tasks might represent a valid and sensitive tool for assessing language in UMND/LMND patients too.

Prevalence and determinants of language impairment in non‐demented amyotrophic lateral sclerosis patients

“…Even in the face of the abovementioned considerations on the potential biases of the ECAS-Language, and consistently with earlier reports [8,9], this work appears to confirm that attention and executive functioning are strong determinants of language in nondemented ALS patients-also showing that dysexecutive features are associated with LI in this population. Nevertheless, a notable amount of variance (i.e., 46.6%) in ECAS-Language scores could not be accounted for by either executive performances or other variables, this supporting the previously acknowledged notion of LI being primary, at least to an extent, in this population [8,9] and not merely secondary to executive dysfunction [2][3][4].…”

“…Relatedly, it has to be mentioned that the present prevalence estimate is measure-dependent, thus coming with the potential biases intrinsic to the ECAS-Language. In this regard, it has been highlighted that, compared to other ECAS subscales, the ECAS-Language might suffer from a slightly poorer sensitivity [27], with such an issue having been attributed to it not optimally covering the full spectrum of LI typical of non-demented ALS patients [2][3][4]27]. Consistently, the present work highlights that the Naming and, to an even greater extent, Spelling tasks of the ECAS-Language are the major drivers of the performance on this subscale, at variance with the Comprehension task [25].…”

“…Language impairment (LI) within the spectrum of primary progressive aphasia (PPA) is typical of non‐demented amyotrophic lateral sclerosis (ALS) patients' cognitive profile [1], including phonological, lexical‐semantic and morpho‐syntactic deficits, alterations in connected speech and pragmatics [2,3], as well as dysgraphic features [4].…”

“…However, despite much being known on the semiology of LI in non-demented ALS patients [2][3][4], its epidemiology in this population is still largely obscure. Indeed, the currently accepted prevalence estimate of LI in non-demented ALS patients (i.e., ≈35%-40%) [1,7] relies on the 2013 pioneering study by Taylor et al [8], which, however, (i) addressed a relatively small sample size (N = 50) and (ii) did not include ALS-specific language measures.…”

Bulbar involvement and cognitive features in amyotrophic lateral sclerosis: a retrospective study on 347 patients

“…Remarkably, BI at testing herewith represented a risk factor only for executive dysfunction, as it did not affect either overall cognitive efficiency or other cognitive domains/functions. While this finding is consistent with previous reports on the topic, which commonly link BI to executive deficits in ALS (Schreiber et al, 2005;Sterling et al, 2010;Morimoto et al, 2012;Mannarelli et al, 2014;Burke et al, 2016), it does not align with the literature concerning the association between BI and language impairment in this population (Pinto-Grau et al, 2018;Aiello et al, 2022a,b;Sbrollini et al, 2022). This inconsistency might be due to a measure-related issue-since, as previously suggested (Aiello et al, 2022c;McMillan et al, 2022;Solca et al, 2023), the ECAS-L does not represent a comprehensive language measure in ALS.…”