#3090 Different measures of behavioural involvement in amyotrophic lateral sclerosis yield varying rates of behavioural change

2021 ◽  
Vol 92 (8) ◽  
pp. A12.1-A12
Author(s):  
Lyndsay Didcote ◽  
Silia Vitoratou ◽  
Ammar Al-Chalabi ◽  
Laura H Goldstein
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Behavioural Change ◽  
Screening Tools ◽  
Complete Agreement ◽  
Spearman Correlation ◽  
Healthcare Provision ◽  
Cognitive Behavioural ◽  
Moderate Range ◽  
Lateral Sclerosis

Objectives/AimsAmyotrophic Lateral Sclerosis (ALS), also known as Motor Neuron Disease (MND), is a progressive and life-limiting neurodegenerative disease which can involve behavioural change. There are five commonly reported disease-specific screening tools of behavioural change but it is not clear how they differ in applicability. This study therefore set out to investigate the extent to which these measures similarly identify impairment by examining i) intercorrelations between scores on the measures completed about the same people with ALS, and ii) the percentage of people with ALS characterised as impaired on each measure.MethodsThe behavioural component of the ALS-Cognitive Behavioural Screen (ALS-CBS-b), behavioural component of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS-b), ALS-Frontotemporal Dementia Questionnaire (ALS-FTD-Q), Beaumont Behavioural Inventory (BBI), and MND Behavioural Instrument (MiND-B) were all completed by 35 carers of people with ALS. Total scores for each measure underwent Spearman correlation analysis. Classifications of impairment (for behavioural impairment or ALS-FTD) were determined using published cut-offs and agreement between measures was determined by calculating Cohens kappa coefficients.ResultsThe behavioural measures were significantly intercorrelated (p<0.05 in all cases) but with differing strengths of association. The association between the ALS-CBS-b and ALS-FTD-Q was weak to moderate (r=0.41) while other associations between the ALS-FTD-Q, MiND-B, BBI, and ALS-CBS-b were moderate to strong (0.53-0.75). While the ECAS-b was moderately associated with the BBI (r=0.53), the ECAS-b was only weakly to moderately associated with the ALS-CBS-b, MiND-B and ALS-FTD-Q (0.36-0.48). The association between ALS-CBS-b and ALS-FTD-Q scores (r=0.41) was similarly in the weak to moderate range. The ECAS-b and ALS-CBS-b had the weakest intercorrelation (r=0.36). Percentages of the sample classified with behavioural involvement by the measures ranged between 20.0% (ALS-FTD-Q) and 74.3% (MiND-B). Percentages of the sample classified with ALS-FTD by the measures ranged between 2.9% (ECAS-b) and 20% (ALS-CBS-b). Agreement of classification between measures (Cohens kappa) was mostly fair to moderate (0.21-0.57) although generally better for classifications of ALS-FTD than for milder behavioural involvement. Between the ECAS-b and BBI there was complete agreement on the classification of ALS-FTD (k = 1.0).ConclusionsExisting measures of behavioural change in people with ALS may yield very differing conclusions and cannot be assumed to be interchangeable. Variability in the detection of impairment between measures may result from differing item content, behaviours sampled or cut-off scores for impairment. This inconsistency between measures may lead to inappropriate healthcare provision and discrepancies in research conclusions.FundingMND Association

scholarly journals A systematic review of non-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis

2021 ◽  
Author(s):  
Emily Beswick ◽  
Deborah Forbes ◽  
Zack Hassan ◽  
Charis Wong ◽  
Judith Newton ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Sleep Disturbances ◽  
Neuropsychiatric Symptoms ◽  
Behavioural Change ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Behavioural Changes ◽  
Non Motor Symptoms ◽  
Lateral Sclerosis

Abstract Background Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva. Aim/hypothesis We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments. Methods We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. Results 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms. Conclusions Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs. PROPSERO registration CRD42020223648.

scholarly journals Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis

2015 ◽  
Vol 33 (4) ◽  
pp. 735-748 ◽  
Author(s):  
Jeffrey M. Statland ◽  
Richard J. Barohn ◽  
April L. McVey ◽  
Jonathan S. Katz ◽  
Mazen M. Dimachkie
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Clinical Diagnosis ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Lateral Sclerosis

Cortical correlates of behavioural change in amyotrophic lateral sclerosis

2018 ◽  
Vol 90 (4) ◽  
pp. 380-386 ◽  
Author(s):  
Monica Consonni ◽  
Stefano F Cappa ◽  
Eleonora Dalla Bella ◽  
Valeria Elisa Contarino ◽  
Giuseppe Lauria
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Orbitofrontal Cortex ◽  
Behavioural Change ◽  
Principal Component ◽  
Behavioural Changes ◽  
The Core ◽  
Behavioural Profile ◽  
The Right ◽  
Item Scale ◽  
Lateral Sclerosis

BackgroundBehavioural changes in amyotrophic lateral sclerosis (ALS) are heterogeneous. The study aim was to identify the behavioural profiles of non-demented patients with ALS and their neuroimaging correlates and to elucidate if they are comparable to those reported in studies of the behavioural-variant of frontotemporal dementia (bvFTD).MethodsBehavioural changes of 102 non-demented patients with ALS were assessed through the Frontal Behavioural Inventory (FBI), a 24-item scale assessing different behavioural modifications, mainly chosen from the core clinical features of FTD. Principal component analysis (PCA) was used to detect distinct clusters of behavioural changes based on FBI subscores. The cortical thinning related to each behavioural profile was analysed in 29 patients with ALS. Cronbach’s α was used to test the reliability of bvFTD-related FBI clustering in our cohort.ResultsSixty patients with ALS had FBI score≥1. PCA identified three phenotypic clusters loading on disinhibited/hostile, dysexecutive and apathetic FBI subscores. Imaging analyses revealed that the thinning of bilateral orbitofrontal cortex was related to apathy, the right frontotemporal and cingular cortex to the disinhibited/hostile profile and the left precuneus cortex to the dysexecutive behaviours. The bvFTD-associated aggressive profile reliably applied to our cohort.ConclusionsIn non-demented patients with ALS, different behavioural profiles could be identified. The right frontotemporal and cingular cortex thinning was the hallmark of the behavioural profile mostly overlapping that described in bvFTD. Our findings provide the unbiased identification of determinants relevant for a novel stratification of patients with ALS based on their behavioural impairment, which might be useful as proxy of cognitive decline.

scholarly journals Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis

2020 ◽  
Vol 91 (12) ◽  
pp. 1304-1311 ◽  
Author(s):  
Jennifer A Saxon ◽  
Jennifer C Thompson ◽  
Jennifer M Harris ◽  
Anna M Richardson ◽  
Tobias Langheinrich ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Frontotemporal Dementia ◽  
Neuropsychological Testing ◽  
Behavioural Change ◽  
Repeat Expansion ◽  
Phenotypic Differences ◽  
Prospective Comparative Study ◽  
Precise Relationship ◽  
The Relationship ◽  
Lateral Sclerosis

ObjectiveThe precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be an oversimplification. Direct comparisons between patients who have behavioural variant FTD (bvFTD) with and without ALS are rare. This prospective comparative study aimed to determine whether there are phenotypic differences in cognition and behaviour between patients with FTD-ALS and bvFTD alone.MethodsPatients with bvFTD or FTD-ALS and healthy controls underwent neuropsychological testing, focusing on language, executive functions and social cognition. Behavioural change was measured through caregiver interview. Blood samples were screened for known FTD genes.Results23 bvFTD, 20 FTD-ALS and 30 controls participated. On cognitive tests, highly significant differences were elicited between patients and controls, confirming the tests’ sensitivities to FTD. bvFTD and FTD-ALS groups performed similarly, although with slightly greater difficulty in patients with ALS-FTD on category fluency and a sentence-ordering task that assesses grammar production. Patients with bvFTD demonstrated more widespread behavioural change, with more frequent disinhibition, impulsivity, loss of empathy and repetitive behaviours. Behaviour in FTD-ALS was dominated by apathy. The C9ORF72 repeat expansion was associated with poorer performance on language-related tasks.ConclusionsDifferences were elicited in cognition and behaviour between bvFTD and FTD-ALS, and patients carrying the C9ORF72 repeat expansion. The findings, which raise the possibility of phenotypic variation between bvFTD and FTD-ALS, have clinical implications for early detection of FTD-ALS and theoretical implications for the nature of the relationship between FTD and ALS.

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