PT  - JOURNAL ARTICLE
AU  - Tilsley, Penelope
AU  - Moutiez, Antoine
AU  - Brodovitch, Alexandre
AU  - Mendili, Mohamed Mounir El
AU  - Testud, Benoit
AU  - Zaaraoui, Wafaa
AU  - Verschueren, Annie
AU  - Attarian, Shahram
AU  - Guye, Maxime
AU  - Boucraut, José
AU  - Grapperon, Aude-Marie
AU  - Stellmann, Jan-Patrick
TI  - Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis
AID  - 10.3174/ajnr.A8154
DP  - 2024 Apr 01
TA  - American Journal of Neuroradiology
PG  - 494--503
VI  - 45
IP  - 4
4099  - http://www.ajnr.org/content/45/4/494.short
4100  - http://www.ajnr.org/content/45/4/494.full
SO  - Am. J. Neuroradiol.2024 Apr 01; 45
AB  - BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving rapid motor neuron degeneration leading to brain, primarily precentral, atrophy. Neurofilament light chains are a robust prognostic biomarker highly specific to ALS, yet associations between neurofilament light chains and MR imaging outcomes are not well-understood. We investigated the role of neurofilament light chains as mediators among neuroradiologic assessments, precentral neurodegeneration, and disability in ALS.MATERIALS AND METHODS: We retrospectively analyzed a prospective cohort of 29 patients with ALS (mean age, 56 [SD, 12] years; 18 men) and 36 controls (mean age, 49 [SD, 11] years; 18 men). Patients underwent 3T (n = 19) or 7T (n = 10) MR imaging, serum (n = 23) and CSF (n = 15) neurofilament light chains, and clinical (n = 29) and electrophysiologic (n = 27) assessments. The control group had equivalent 3T (n = 25) or 7T (n = 11) MR imaging. Two trained neuroradiologists performed blinded qualitative assessments of MR imaging anomalies (n = 29 patients, n = 36 controls). Associations between precentral cortical thickness and neurofilament light chains and clinical and electrophysiologic data were analyzed.RESULTS: We observed extensive cortical thinning in patients compared with controls. MR imaging analyses showed significant associations between precentral cortical thickness and bulbar or arm impairment following distributions corresponding to the motor homunculus. Finally, uncorrected results showed positive interactions among precentral cortical thickness, serum neurofilament light chains, and electrophysiologic outcomes. Qualitative MR imaging anomalies including global atrophy (P = .003) and FLAIR corticospinal tract hypersignal anomalies (P = .033), correlated positively with serum neurofilament light chains.CONCLUSIONS: Serum neurofilament light chains may be an important mediator between clinical symptoms and neuronal loss according to cortical thickness. Furthermore, MR imaging anomalies might have underestimated prognostic value because they seem to indicate higher serum neurofilament light chain levels.ALSamyotrophic lateral sclerosisALSFRS-Rrevised ALS Functional Rating ScaleCMAPcompound muscle action potentialCSTcorticospinal tractGLMgeneral linear modelLMNlower motor neuronMEPmotor-evoked potentialMNIMontreal Neurological InstituteNfLneurofilament light chainsTMStranscranial magnetic stimulationUMNupper motor neuron