Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?

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.

Neurophysiological and clinical biomarkers of secondary progressive multiple sclerosis: A cross-sectional study

“…Higher frailty levels and abnormalities in the considered neurophysiological measures may capture those neurodegenerative processes that underlie the progressive course of the disease. Abnormalities in both neurophysiological and frailty indices may depend on the involvement of gray matter ( 3 , 6 ). This conclusion is also supported by MRI evidence of higher gray matter loss in patients with SPMS as compared to those with RRMS ( 12 ).…”

“…All neurophysiological assessments were performed in a random order while patients were comfortably sitting on an armchair. The neurophysiological index was calculated for each patient using the following formula obtained in a previous work ( 3 ):…”

“…To test STDT we used procedures explained in previous studies ( 3 , 10 , 11 ). Briefly, pairs of square-wave electric stimuli were delivered with an increasing ISI of 10 ms starting from a couple of simultaneous stimuli.…”

“…The first is short intracortical inhibition (SICI), which tests inhibitory interneuron excitability in the motor cortex. The second is the somatosensory temporal discrimination threshold (STDT), which tests inhibitory interneuron excitability in the primary sensory cortex ( 3 , 4 ).…”

Multimodal diagnostics in multiple sclerosis: predicting disability and conversion from relapsing-remitting to secondary progressive disease course – protocol for systematic review and meta-analysis

“…Fourth , neurophysiological biomarkers can discriminate clinical subtypes of MS. For example, abnormalities in somatosensory temporal discrimination threshold (STDT) and short intracortical inhibition (SICI) reflect neurodegenerative processes which play an important role in SPMS pathophysiology. Compared with SICI, STDT has a higher sensitivity (94.4% vs 58.8%) and lower specificity (54.3% vs 67.9%) in differentiating MS subtypes 62. The preliminary literature analysis showed a low classification accuracy of the discussed methods.…”