Upper motor neuron dysfunction is associated with the presence of behavioural impairment in patients with amyotrophic lateral sclerosis

Abstract

Background and purpose: Increasing evidence shows that approximately half of patients with amyotrophic lateral sclerosis (ALS) display cognitive (ALSci) or behavioural (ALSbi) impairment, or both (ALScbi). The aim of our study was to assess whether the burden of upper and lower motor neuron involvement is associated with the presence of cognitive and behavioural impairment. Methods: A single-centre retrospective cohort of 110 Italian ALS patients was evaluated to assess correlations between motor and cognitive/behavioural phenotypes. Upper motor neuron regional involvement was measured with the Penn Upper Motor Neuron Score (PUMNS), whilst lower motor neuron signs were assessed using the Lower Motor Neuron Score. The Edinburgh Cognitive and Behavioural ALS Screen-Italian version and the Frontal Behaviour Inventory were administered to evaluate patients' cognitive and behavioural profiles. Results:The PUMNS at first visit was significantly higher in behaviourally impaired ALS patients (ALSbi and ALScbi) compared to behaviourally unimpaired individuals (ALS and ALSci) (9.9 vs. 6.9, p = 0.014). Concerning the different Frontal Behaviour Inventory subdomains, higher PUMNS correlated with the presence of apathy, emotive indifference, inflexibility, inattention, perseveration and aggressiveness. Conclusion:To our knowledge, this is the first study showing that a clinical prominent upper motor neuron dysfunction is associated with a more significant behavioural impairment in ALS patients, suggesting the hypothesis of a preferential spreading of the pathology from the motor cortex to the ventromedial prefrontal and orbitofrontal cortex in this group of patients.

Primary progressive aphasia and motor neuron disease: A review

“…As to patients primarily diagnosed with FTD, such findings are unsurprising: indeed, it is unlikely that, in the presence of such a cortical pathology, UMNs are less involved than LMNs ( McKenna et al, 2021 ). Conversely, as to primarily MND patients, these results align with recent evidence on extra-motor cortical burden being greater when UMNs are involved ( Poletti et al, 2021 ; Sbrollini et al, 2021 ; Aiello et al, 2022 ; Maranzano et al, 2022 ).…”

Cognition and motor phenotypes in ALS: a retrospective study

“…A number of limitations should be however listed. First, the present study did not include specific measures of upper vs. lower motor neuron involvement, at variance with the recent report by Maranzano et al [13], who nonetheless came to similar conclusions.…”

“…Nevertheless, few studies have to date focused on exploring cognition across different motor phenotypes of ALS [13], notwithstanding the prognostic relevance of cognitive assessment in this population [14]. Such investigations Edoardo Nicolò Aiello and Debora Pain contributed equally.…”

Serum levels of glial fibrillary acidic protein in patients with amyotrophic lateral sclerosis

“… 23 with a modification consisting in adding one point each for LMN signs in the bulbar and thoracic regions. 24 Clinical measures of UMN and LMN dysfunction were complemented by parameters derived from neurophysiological investigations –needle electromyography (EMG) and transcranial magnetic stimulation (TMS)–, namely semiquantitative indices of active and chronic limb denervation, central motor conduction time and cortical silent period. Disease stage was defined according to both King's 25 and Milano‐Torino Staging (MiToS) 26 systems.…”