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Threshold tracking transcranial magnetic stimulation and neurofilament light chain as diagnostic aids in ALS

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Title: Threshold tracking transcranial magnetic stimulation and neurofilament light chain as diagnostic aids in ALS
Authors: Anna B. Jacobsen, Hugh Bostock, James Howells, Bülent Cengiz, Gintaute Samusyte, Martin Koltzenburg, Hossein Pia, Anders Fuglsang‐Frederiksen, Jakob Blicher, Izabella Obál, Henning Andersen, Hatice Tankisi
Source: Ann Clin Transl Neurol
Annals of Clinical and Translational Neurology, Vol 11, Iss 7, Pp 1887-1896 (2024)
Jacobsen, A B, Bostock, H, Howells, J, Cengiz, B, Samusyte, G, Koltzenburg, M, Pia, H, Fuglsang-Frederiksen, A, Blicher, J, Obál, I, Andersen, H & Tankisi, H 2024, 'Threshold tracking transcranial magnetic stimulation and neurofilament light chain as diagnostic aids in ALS', Annals of clinical and translational neurology, vol. 11, no. 7, pp. 1887-1896. https://doi.org/10.1002/acn3.52095
Jacobsen, A B, Bostock, H, Howells, J, Cengiz, B, Samusyte, G, Koltzenburg, M, Pia, H, Fuglsang-Frederiksen, A, Blicher, J, Obál, I, Andersen, H & Tankisi, H 2024, 'Threshold tracking transcranial magnetic stimulation and neurofilament light chain as diagnostic aids in ALS', Annals of Clinical and Translational Neurology, vol. 11, no. 7, pp. 1887-1896. https://doi.org/10.1002/acn3.52095
Publisher Information: Wiley, 2024.
Publication Year: 2024
Subject Terms: Male, Electromyography, Amyotrophic Lateral Sclerosis, Neurosciences. Biological psychiatry. Neuropsychiatry, Middle Aged, Evoked Potentials, Motor, Transcranial Magnetic Stimulation, Transcranial Magnetic Stimulation/methods, 3. Good health, Neurofilament Proteins, Amyotrophic Lateral Sclerosis/diagnosis, Humans, Female, Neurology. Diseases of the nervous system, RC346-429, Evoked Potentials, Motor/physiology, Biomarkers, RC321-571, Research Article, Aged
Description: ObjectiveThere is a need for sensitive biomarkers in amyotrophic lateral sclerosis (ALS), to enable earlier diagnosis and to help assess potential treatments. The main objective of this study was to compare two potential biomarkers, threshold‐tracking short‐interval cortical inhibition (T‐SICI), which has shown promise as a diagnostic aid, and neurofilament light chains (NfL).MethodsNinety‐seven patients with ALS (mean age 67.1 ± 11.5 years) and 53 ALS mimics (aged 62.4 ± 12.9) were included. Mean disease duration was 14 months ±14.1. Patients were evaluated with revised ALS functional rating score (ALSFRS‐R), Penn upper motor neuron score (UMNS), muscle strength using the Medical Research Council (MRC) score and examined with T‐SICI, quantitative electromyography (EMG), and NfL measured in spinal fluid.ResultsNfL increased with increasing UMNS (rho = 0.45, p = 8.2 × 10−6) whereas T‐SICI at 2.5 ms paradoxically increased toward normal values (rho = 0.53, p = 1.9 × 10−7). However, these two measures were uncorrelated. Discrimination between ALS patients and mimics was best for NfL (area under ROC curve 0.842, sensitivity 84.9%, specificity 83.5%), compared with T‐SICI (0.675, 39.6%, 91.8%). For the patients with no UMN signs, NfL also discriminated best (0.884, 89.3%, 82.6%), compared with T‐SICI (0.811, 71.4%, 82.6%). However, when combining NfL and T‐SICI, higher AUCs of 0.854 and 0.922 and specificities of 93.8 and 100 were found when considering all patients and patients with no UMN signs, respectively.InterpretationBoth T‐SICI and NfL correlated with UMN involvement and combined, they provided a strong discrimination between ALS patients and ALS mimics.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 2328-9503
DOI: 10.1002/acn3.52095
Access URL: https://pubmed.ncbi.nlm.nih.gov/38894662
https://doaj.org/article/071fbef2b98843f8b72ce2530f44a535
https://vbn.aau.dk/da/publications/f0b08b5f-8f98-4779-a5fe-27a86bed3022
http://www.scopus.com/inward/record.url?scp=85196302127&partnerID=8YFLogxK
https://doi.org/10.1002/acn3.52095
https://vbn.aau.dk/ws/files/741326506/Jacobsen_et_al._2024_._Threshold_tracking_transcranial_magnetic_stimulation_and_neurofilament_light_chain_as_diagnostic_aids_in_ALS.pdf
https://pure.au.dk/portal/en/publications/0e9c6ad5-596e-4544-9722-1ab8427600ad
http://www.scopus.com/inward/record.url?scp=85196302127&partnerID=8YFLogxK
https://doi.org/10.1002/acn3.52095
Rights: CC BY
Accession Number: edsair.doi.dedup.....e3b62d92d85477656d8ddc3828d408f6
Database: OpenAIRE
Description
Abstract:ObjectiveThere is a need for sensitive biomarkers in amyotrophic lateral sclerosis (ALS), to enable earlier diagnosis and to help assess potential treatments. The main objective of this study was to compare two potential biomarkers, threshold‐tracking short‐interval cortical inhibition (T‐SICI), which has shown promise as a diagnostic aid, and neurofilament light chains (NfL).MethodsNinety‐seven patients with ALS (mean age 67.1 ± 11.5 years) and 53 ALS mimics (aged 62.4 ± 12.9) were included. Mean disease duration was 14 months ±14.1. Patients were evaluated with revised ALS functional rating score (ALSFRS‐R), Penn upper motor neuron score (UMNS), muscle strength using the Medical Research Council (MRC) score and examined with T‐SICI, quantitative electromyography (EMG), and NfL measured in spinal fluid.ResultsNfL increased with increasing UMNS (rho = 0.45, p = 8.2 × 10−6) whereas T‐SICI at 2.5 ms paradoxically increased toward normal values (rho = 0.53, p = 1.9 × 10−7). However, these two measures were uncorrelated. Discrimination between ALS patients and mimics was best for NfL (area under ROC curve 0.842, sensitivity 84.9%, specificity 83.5%), compared with T‐SICI (0.675, 39.6%, 91.8%). For the patients with no UMN signs, NfL also discriminated best (0.884, 89.3%, 82.6%), compared with T‐SICI (0.811, 71.4%, 82.6%). However, when combining NfL and T‐SICI, higher AUCs of 0.854 and 0.922 and specificities of 93.8 and 100 were found when considering all patients and patients with no UMN signs, respectively.InterpretationBoth T‐SICI and NfL correlated with UMN involvement and combined, they provided a strong discrimination between ALS patients and ALS mimics.
ISSN:23289503
DOI:10.1002/acn3.52095