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| Home > Articles > Published articles > Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum |
(Institut de Recerca Sant Pau) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut de Recerca Sant Pau) (Universitat Autònoma de Barcelona. Departament de Medicina) (Hospital Clínic i Provincial de Barcelona) (Hospital Universitari de Bellvitge) (Hospital del Mar (Barcelona, Catalunya)) (GMA Clinic, Neurology Department, European Reference Network On Rare Neuromuscular Diseases (ERN EURO-NMD), Barcelona) (Hospital Universitari Vall d'Hebron) (Hospital Universitari Vall d'Hebron) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Universitat Internacional de Catalunya. Ace Alzheimer Center Barcelona) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya)) (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya)) (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya)) (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya)) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Hospital Clínic i Provincial de Barcelona)| Date: | 2024 |
| 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. |
| Grants: | Instituto de Salud Carlos III PI19/01543 Instituto de Salud Carlos III PI23/00845 Instituto de Salud Carlos III CM21/00057 Instituto de Salud Carlos III CM21/00101 Instituto de Salud Carlos III PI21/00791 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Amyotrophic lateral sclerosis ; Motor neuron disease ; Frontotemporal dementia ; Neuropathology |
| Published in: | Brain, Vol. 147, Núm. 7 (july 2024) , p. 2357-2367, ISSN 1460-2156 |
