Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?

Daniele Belvisi,Sebastiano Giuseppe Crisafulli,Patrizia Pantano,Matteo Tartaglia,Giorgio Leodori,Gabriele Pasqua,Giovanna Borriello,Valeria Zuccoli,Alfredo Berardelli,Viola Baione,Antonio Ianniello,Carlo Pozzilli,Antonella Conte

doi:10.3390/biomedicines10020231

Abstract

Secondary progressive multiple sclerosis (SPMS) subtype is retrospectively diagnosed, and biomarkers of the SPMS are not available. We aimed to identify possible neurophysiological markers exploring grey matter structures that could be used in clinical practice to better identify SPMS. Fifty-five people with MS and 31 healthy controls underwent a transcranial magnetic stimulation protocol to test intracortical interneuron excitability in the primary motor cortex and somatosensory temporal discrimination threshold (STDT) to test sensory function encoded in cortical and deep grey matter nuclei. A logistic regression model was used to identify a combined neurophysiological index associated with the SP subtype. We observed that short intracortical inhibition (SICI) and STDT were the only variables that differentiated the RR from the SP subtype. The logistic regression model provided a formula to compute the probability of a subject being assigned to an SP subtype based on age and combined SICI and STDT values. While only STDT correlated with disability level at baseline evaluation, both SICI and STDT were associated with disability at follow-up. SICI and STDT abnormalities reflect age-dependent grey matter neurodegenerative processes that likely play a role in SPMS pathophysiology and may represent easily accessible neurophysiological biomarkers for the SPMS subtype.

Highlights

Single- and paired-pulse transcranial magnetic stimulation (TMS) assessment showed that people with MS (pwMS) had a significantly lower short intracortical inhibition (SICI) than healthy controls (HCs)
somatosensory temporal discrimination threshold (STDT) values significantly differed between the groups, being higher in pwMS than in HCs (Table 3)
We observed that both SICI and STDT values at baseline we ciated with Expanded Disability Status Scale (EDSS) scores at follow-up, suggesting that the neurophysiolog cortical and subcortical structures

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) and is one of the leading causes of disability in young adults [1]. MS is clinically characterized by different phases and clinical subtypes, with relapsing-remitting multiple sclerosis (RRMS) being the most common clinical variant. RRMS is characterized by relapses of acute neurological symptoms that end with partial or complete remission [2]. During the course of the disease, people with MS (pwMS) may show a gradual and irreversible worsening of neurological disability that can emerge as progression from RRMS to secondary progressive multiple sclerosis (SPMS) [3]. Identification of the SPMS subtype is challenging since SPMS conversion is Biomedicines 2022, 10, 231.

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Methods

Conclusion