Diagnosing primary lateral sclerosis: a clinico-pathological study.

Autor: de Boer EMJ; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands., de Vries BS; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands., Van Hecke W; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands., Mühlebner A; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands., Vincken KL; Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands., Mol CP; Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands., van Rheenen W; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands., Westeneng HJ; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands., Veldink JH; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands., Höglinger GU; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Morris HR; Department of Clinical and Movement Neurosciences, University College London, London, UK., Litvan I; Department of Neurosciences, UC San Diego, La Jolla, CA, USA., Raaphorst J; Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Ticozzi N; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy., Corcia P; Service de Neurologie, CHRU Bretonneau, Tours, France., Vandenberghe W; Department of Neurology, University Hospitals Leuven, Louvain, Belgium., Pijnenburg YAL; Department of Neurology, Alzheimer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands., Seelaar H; Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands., Ingre C; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden., Van Damme P; Department of Neurology, University Hospitals Leuven, Louvain, Belgium.; Laboratory of Neurobiology, Department of Neuroscience, KU Leuven and Center for Brain and Disease Research, VIB, Louvain, Belgium., van den Berg LH; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands., van de Warrenburg BPC; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson and Movement Disorders, Radboud University Medical Center, Nijmegen, The Netherlands., van Es MA; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. m.a.vanes@umcutrecht.nl.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Dec 12; Vol. 272 (1), pp. 46. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1007/s00415-024-12816-0
Abstrakt: Background:  Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration, diagnosed clinically due to the absence of a (neuropathological) gold standard. Post-mortem studies, particularly TDP-43 pathology analysis, are limited.
Methods: This study reports on 5 cases in which the diagnostic criteria for PLS were met, but in which neuropathology findings showed (partially) conflicting results. These discrepancies prompted us to perform a clinico-pathology study focussing on diagnostic challenges and accuracy in PLS. To this end, all cases were reviewed by an international panel of 11 experts using an e-module and structured questionnaires.
Results: Autopsy exhibited neuropathological findings consistent with amyotrophic lateral sclerosis (ALS) in one case, while two cases exhibited similar, but more limited lower motor neuron involvement, hinting at PLS or ALS overlap. Another case displayed tau-pathology indicative of progressive supranuclear palsy. The final case displayed extensive myelin loss without a proteinopathy or a clear diagnosis. The expert panel identified 24 different ancillary investigations lacking across cases (e.g. genetic testing, DAT scans, neuropsychological evaluation), listed 28 differential diagnoses, and identified 13 different conditions as the most likely diagnosis. Autopsy results led panel members to change their final diagnosis in 42% of the cases.
Conclusions: This study underscores the diagnostic challenges posed by diverse underlying pathologies resulting in upper motor neuron phenotypes. Despite adhering to the same diagnostic criteria, consensus amongst experts was limited. Ensuring the diagnostic consistency is crucial for advancing understanding and treatment of PLS. Explicit guidelines for excluding potential mimics along with a neuropathological gold standard are imperative.
Competing Interests: Declarations. Conflicts of interest: E.M.J. de Boer: reports no disclosures relevant to the manuscript. B.S. de Vries: reports no disclosures relevant to the manuscript. W. van Hecke: reports no disclosures relevant to the manuscript. A. Mühlebner: reports no disclosures relevant to the manuscript. K.L. Vincken: reports no disclosures relevant to the manuscript. C.P. Mol: reports no disclosures relevant to the manuscript. W. van Rheenen: reports no disclosures relevant to the manuscript. H-J Westeneng: reports no disclosures relevant to the manuscript. J.H. Veldink: reports to have sponsored research agreements with Biogen and Astra Zeneca. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement n° 772376 – EScORIAL. G.U. Höglinger: reports no disclosures relevant to the manuscript. H.R. Morris: reports no disclosures relevant to the manuscript. I. Litvan: reports no disclosures relevant to the manuscript. J. Raaphorst: reports no disclosures relevant to the manuscript. N. Ticozzi: reports no disclosures relevant to the manuscript. P. Corcia: reports no disclosures relevant to the manuscript. W. Vandenberghe: reports no disclosures relevant to the manuscript. Y.A.L. Pijnenburg: reports no disclosures relevant to the manuscript. H. Seelaar: reports no disclosures relevant to the manuscript. C. Ingre: reports no disclosures relevant to the manuscript. P. Van Damme: reports no disclosures relevant to the manuscript. L.H. van den Berg: declares fees to his institution from Biogen, Wave, Amylyx, Ferrer, and Cytokinetics for being on a scientific advisory board; fees to his institution from Amylyx for a lecture; an unrestricted educational grant from Takeda; and is the Chair of ENCALS and TRICALS. B.P.C. van de Warrenburg: reports no disclosures relevant to the manuscript. M.A. van Es: has consulted for Biogen, and has received travel grants from Shire (formerly Baxalta), performed work as a medical monitor for Ferrer (NCT05178810) with fees going to his institution. MAvE receives funding support from the Netherlands Organization for Health Research and Development (Vidi scheme), The Thierry Latran Foundation, the Motor Neurone Disease Association, FIGHT-MND and the ALS Foundation Netherlands. He is also a member of the European Reference Network for Rare Neuromuscular Diseases (ERN-NMD).
(© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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