TY  - JOUR
AU  - de Boer, Eva M J
AU  - de Vries, Bálint S
AU  - Van Hecke, Wim
AU  - Mühlebner, Angelika
AU  - Vincken, Koen L
AU  - Mol, Christian P
AU  - van Rheenen, Wouter
AU  - Westeneng, Henk-Jan
AU  - Veldink, Jan H
AU  - Höglinger, Günter U
AU  - Morris, Huw R
AU  - Litvan, Irene
AU  - Raaphorst, Joost
AU  - Ticozzi, Nicola
AU  - Corcia, Philippe
AU  - Vandenberghe, Wim
AU  - Pijnenburg, Yolande A L
AU  - Seelaar, Harro
AU  - Ingre, Caroline
AU  - Van Damme, Philip
AU  - van den Berg, Leonard H
AU  - van de Warrenburg, Bart P C
AU  - van Es, Michael A
TI  - Diagnosing primary lateral sclerosis: a clinico-pathological study.
JO  - Journal of neurology
VL  - 272
IS  - 1
SN  - 0367-004X
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2024-01417
SP  - 46
PY  - 2025
AB  - 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.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.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
KW  - Humans
KW  - Male
KW  - Aged
KW  - Female
KW  - Middle Aged
KW  - Motor Neuron Disease: diagnosis
KW  - Motor Neuron Disease: pathology
KW  - Autopsy
KW  - Amyotrophic Lateral Sclerosis: diagnosis
KW  - Amyotrophic Lateral Sclerosis: pathology
KW  - Amyotrophic Lateral Sclerosis: genetics
KW  - Diagnosis, Differential
KW  - Aged, 80 and over
KW  - Brain: pathology
KW  - Brain: diagnostic imaging
KW  - DNA-Binding Proteins
KW  - Amyotrophic lateral sclerosis (Other)
KW  - Neuropathology (Other)
KW  - Primary lateral sclerosis (Other)
KW  - TDP-43 (Other)
KW  - Tau (Other)
KW  - TARDBP protein, human (NLM Chemicals)
KW  - DNA-Binding Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39666071
DO  - DOI:10.1007/s00415-024-12816-0
UR  - https://pub.dzne.de/record/273943
ER  -