Behavioral changes in early ALS correlate with voxel-based morphometry and diffusion tensor imaging☆,☆☆
Introduction
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor involvement in limb, bulbar, and respiratory functions [1] and also shows symptoms involving non-motor systems [2], such as frontotemporal dysfunction (FTD) including cognitive decline [3] and behavioral impairment including personality change, apathy, disinhibition, and irritability. Moreover, there is evidence linking FTD and motor neuron disease [4], [5], [6], [7], [8].
The frontal symptoms such as apathy and disinhibition not only affect the patients' care, but also key clinical decisions, such as non-invasive positive pressure ventilation, enteral nutrition, intravenous hyperalimentation, and artificial ventilation [9]. Behavioral changes have been documented in ALS patients [10], although that study assessed the symptoms in relatively advanced stages of ALS. It is important to know whether these behavioral changes are also present during the early course of the illness, as the rapid progress of ALS impairments forces patients and their families to make key decisions during the early stage. Furthermore, behavioral symptoms that occur as early as the beginning of motor symptoms provide evidence that neuroanatomical systems related to behavioral changes are involved simultaneously with motor systems.
Reports have also demonstrated the importance of frontosubcortical circuits in determining behavior [11], [12]. However, an understanding of the neuroanatomical changes related to behavioral impairments in ALS patients is lacking. In this study, we evaluated the neurobehavioral symptoms of ALS patients and examined their neuroanatomical correlates of behavioral symptoms using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).
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Subjects
Patients participating in the study were admitted for diagnosis to the Nagoya University Hospital from May 2009 to June 2010. We enrolled 39 consecutively patients who were diagnosed as either laboratory supported, probable, or definite ALS by the EI Escorial criteria during their administration [13]. From these we selected early-stage ALS patients. The definition of early stage is difficult in ALS. Even in short duration patients, the dependent state is often associated with advanced
Results
Demographics and ALS-related variables are summarized in Table 1. The MMSE and FAB scores of ALS patients were significantly lower than those of controls (p < 0.001). The FrSBe post-illness scores were higher than the pre-illness scores, irrespective of the patients' scores for the ALSFRS-R, FVC, MMSE, and FAB. In particular, there was a significant difference between the pre- and post-illness apathy subscale FrSBe scores (Table 2), but no significant differences in either disinhibition or
Discussion
Our results demonstrated that even early ALS patients show significant increases in their FrSBe score. In particular, the apathy score showed a significant change from the pre to the post-illness stage. The apathy score was mildly but significantly changed. The score was correlated with reduced gray matter volume, decreased FA values, and increased MD values in the prefrontal lobe as demonstrated by VBM. Although the initial behavioral changes in ALS have not been fully investigated, these
Acknowledgements
This work was supported by Health and Labor Science Research Grants for Research on Measures for Intractable Diseases, and Comprehensive Research on Aging and Health by the Ministry of Health, Labor and Welfare, Japan.
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2021, CortexCitation Excerpt :A recent finding using the DAS has shown a specific association between greater patient-reported emotional apathy and poorer performance on a traditional facial emotion recognition task (Radakovic et al., 2017). The results showing carer-rated emotional apathy and decreased grey matter density in the right anterior cingulate extend previous findings implicating this region in impaired processing of negative emotions (Palmieri et al., 2010) and apathy in ALS patients without dementia (Femiano et al., 2018; Tsujimoto et al., 2011; Woolley et al., 2011). Interestingly, early changes in the frontal and cingulate regions have also been associated with apathy progression among presymptomatic carriers of FTD mutations, suggesting apathy as an early neurobehavioural marker of FTD (Malpetti et al., 2020).
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The statistical analysis with our professional affiliation is academic.
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Disclosure: All authors were supported by Health and Labor Science Research Grants for research on measures for intractable diseases and comprehensive research on Aging and Health of the Ministry of Health, Labor, and Welfare, Japan. We take full responsibility for the data, their analyses and interpretation, and the conduct of the research, and had full access to all of the data, and had the right to publish all data, separate and apart from the attitudes of the sponsor.