Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum

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• dc.contributor.author Carbayo, Álvaro
• dc.contributor.author Rubio Pérez, Miguel Angel
• dc.contributor.author Rojas-García, Ricard
• dc.date.accessioned 2024-10-07T06:28:01Z
• dc.date.available 2024-10-07T06:28:01Z
• dc.date.issued 2024
• dc.description.abstract Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease (MND) that shares a common clinical, genetic and pathologic spectrum with frontotemporal dementia (FTD). It is highly heterogeneous in its presentation and features. Up to 50% of patients with MND develop cognitive-behavioural symptoms during the course of the disease, meeting criteria for FTD in 10%-15% of cases. In the absence of a precise biomarker, neuropathology is still a valuable tool to understand disease nosology, reach a definite diagnostic confirmation and help define specific subgroups of patients with common phenotypic, genetic and biomarker profiles. However, few neuropathological series have been published, and the frequency of frontotemporal lobar degeneration (FTLD) in MND is difficult to estimate. In this work we describe a large clinicopathological series of MND patients, analysing the frequency of concurrent FTLD changes and trying to define specific subgroups of patients based on their clinical, genetic and pathological characteristics. We performed an observational, retrospective, multicentre case study. We included all cases meeting neuropathological criteria for MND from the Neurological Tissue Bank of the FRCB-IDIBAPS-Hospital Clínic Barcelona Biobank between 1994 and 2022, regardless of their last clinical diagnosis. While brain donation is encouraged in all patients, it is performed in very few, and representativeness of the cohort might not be precise for all patients with MND. We retrospectively reviewed clinical and neuropathological data and describe the main clinical, genetic and pathogenic features, comparing neuropathologic groups between MND with and without FTLD changes and aiming to define specific subgroups. We included brain samples from 124 patients, 44 of whom (35.5%) had FTLD neuropathologic features (i.e. FTLD-MND). Pathologic TDP-43 aggregates were present in 93.6% of the cohort and were more extensive (higher Brettschneider stage) in those with concurrent FTLD (P < 0.001). Motor symptom onset was more frequent in the bulbar region in FTLD-MND cases than in those with isolated MND (P = 0.023), with no differences in survival. We observed a better clinicopathological correlation in the MND group than in the FTLD-MND group (93.8% versus 61.4%; P < 0.001). Pathogenic genetic variants were more common in the FTLD-MND group, especially C9orf72. We describe a frequency of FTLD of 35.5% in our series of neuropathologically confirmed cases of MND. The FTLD-MND spectrum is highly heterogeneous in all aspects, especially in patients with FTLD, in whom it is particularly difficult to define specific subgroups. In the absence of definite biomarkers, neuropathology remains a valuable tool for a definite diagnosis, increasing our knowledge in disease nosology.
• dc.format.mimetype application/pdf
• dc.identifier.citation Carbayo Á, Borrego-Écija S, Turon-Sans J, Cortés-Vicente E, Molina-Porcel L, Gascón-Bayarri J, et al. Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum. Brain. 2024 Jul 5;147(7):2357-67. DOI: 10.1093/brain/awae011
• dc.identifier.doi http://dx.doi.org/10.1093/brain/awae011
• dc.identifier.issn 0006-8950
• dc.identifier.uri http://hdl.handle.net/10230/61322
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Brain. 2024 Jul 5;147(7):2357-67
• dc.rights © The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Amyotrophic lateral sclerosis
• dc.subject.keyword Frontotemporal dementia
• dc.subject.keyword Motor neuron disease
• dc.subject.keyword Neuropathology
• dc.title Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion