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Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of the same disease spectrum. While thalamic–cerebellar degeneration has been observed in C9orf72 expansion carriers, the exact subregions involved across the clinical phenotypes of the ALS–FTD spectrum remain unclear. Us...

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Autores principales: Bocchetta, Martina, Todd, Emily G., Tse, Nga Yan, Devenney, Emma M., Tu, Sicong, Caga, Jashelle, Hodges, John R., Halliday, Glenda M., Irish, Muireann, Piguet, Olivier, Kiernan, Matthew C., Rohrer, Jonathan D., Ahmed, Rebekah M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945983/
https://www.ncbi.nlm.nih.gov/pubmed/35326292
http://dx.doi.org/10.3390/brainsci12030336
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author Bocchetta, Martina
Todd, Emily G.
Tse, Nga Yan
Devenney, Emma M.
Tu, Sicong
Caga, Jashelle
Hodges, John R.
Halliday, Glenda M.
Irish, Muireann
Piguet, Olivier
Kiernan, Matthew C.
Rohrer, Jonathan D.
Ahmed, Rebekah M.
author_facet Bocchetta, Martina
Todd, Emily G.
Tse, Nga Yan
Devenney, Emma M.
Tu, Sicong
Caga, Jashelle
Hodges, John R.
Halliday, Glenda M.
Irish, Muireann
Piguet, Olivier
Kiernan, Matthew C.
Rohrer, Jonathan D.
Ahmed, Rebekah M.
author_sort Bocchetta, Martina
collection PubMed
description Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of the same disease spectrum. While thalamic–cerebellar degeneration has been observed in C9orf72 expansion carriers, the exact subregions involved across the clinical phenotypes of the ALS–FTD spectrum remain unclear. Using MRIs from 58 bvFTD, 41 ALS–FTD and 52 ALS patients compared to 57 controls, we aimed to delineate thalamic and cerebellar subregional changes across the ALS–FTD spectrum and to contrast these profiles between cases with and without C9orf72 expansions. Thalamic involvement was evident across all ALS–FTD clinical phenotypes, with the laterodorsal nucleus commonly affected across all groups (values below the 2.5th control percentile). The mediodorsal nucleus was disproportionately affected in bvFTD and ALS–FTD but not in ALS. Cerebellar changes were only observed in bvFTD and ALS–FTD predominantly in the superior–posterior region. Comparison of genetic versus sporadic cases revealed significantly lower volumes exclusively in the pulvinar in C9orf72 expansion carriers compared to non-carriers, irrespective of clinical syndrome. Overall, bvFTD showed significant correlations between thalamic subregions, level of cognitive dysfunction and severity of behavioural symptoms. Notably, strong associations were evident between mediodorsal nucleus atrophy and severity of behavioural changes in C9orf72-bvFTD (r = −0.9, p < 0.0005). Our findings reveal distinct thalamic and cerebellar atrophy profiles across the ALS–FTD spectrum, with differential impacts on behaviour and cognition, and point to a unique contribution of C9orf72 expansions in the clinical profiles of these patients.
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spelling pubmed-89459832022-03-25 Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72 Bocchetta, Martina Todd, Emily G. Tse, Nga Yan Devenney, Emma M. Tu, Sicong Caga, Jashelle Hodges, John R. Halliday, Glenda M. Irish, Muireann Piguet, Olivier Kiernan, Matthew C. Rohrer, Jonathan D. Ahmed, Rebekah M. Brain Sci Article Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of the same disease spectrum. While thalamic–cerebellar degeneration has been observed in C9orf72 expansion carriers, the exact subregions involved across the clinical phenotypes of the ALS–FTD spectrum remain unclear. Using MRIs from 58 bvFTD, 41 ALS–FTD and 52 ALS patients compared to 57 controls, we aimed to delineate thalamic and cerebellar subregional changes across the ALS–FTD spectrum and to contrast these profiles between cases with and without C9orf72 expansions. Thalamic involvement was evident across all ALS–FTD clinical phenotypes, with the laterodorsal nucleus commonly affected across all groups (values below the 2.5th control percentile). The mediodorsal nucleus was disproportionately affected in bvFTD and ALS–FTD but not in ALS. Cerebellar changes were only observed in bvFTD and ALS–FTD predominantly in the superior–posterior region. Comparison of genetic versus sporadic cases revealed significantly lower volumes exclusively in the pulvinar in C9orf72 expansion carriers compared to non-carriers, irrespective of clinical syndrome. Overall, bvFTD showed significant correlations between thalamic subregions, level of cognitive dysfunction and severity of behavioural symptoms. Notably, strong associations were evident between mediodorsal nucleus atrophy and severity of behavioural changes in C9orf72-bvFTD (r = −0.9, p < 0.0005). Our findings reveal distinct thalamic and cerebellar atrophy profiles across the ALS–FTD spectrum, with differential impacts on behaviour and cognition, and point to a unique contribution of C9orf72 expansions in the clinical profiles of these patients. MDPI 2022-03-01 /pmc/articles/PMC8945983/ /pubmed/35326292 http://dx.doi.org/10.3390/brainsci12030336 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bocchetta, Martina
Todd, Emily G.
Tse, Nga Yan
Devenney, Emma M.
Tu, Sicong
Caga, Jashelle
Hodges, John R.
Halliday, Glenda M.
Irish, Muireann
Piguet, Olivier
Kiernan, Matthew C.
Rohrer, Jonathan D.
Ahmed, Rebekah M.
Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72
title Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72
title_full Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72
title_fullStr Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72
title_full_unstemmed Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72
title_short Thalamic and Cerebellar Regional Involvement across the ALS–FTD Spectrum and the Effect of C9orf72
title_sort thalamic and cerebellar regional involvement across the als–ftd spectrum and the effect of c9orf72
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945983/
https://www.ncbi.nlm.nih.gov/pubmed/35326292
http://dx.doi.org/10.3390/brainsci12030336
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