Neurophysiological Assessment in Patients With Multiple Sclerosis

Summary

Main aim of this study will be the evaluation of the neurophysiological techniques of Transcranial Magnetic Stimulation (TMS) via electroencephalography (EEG) co-registration (TMS-EEG) with the study of TEPs (TEP: transcranial evoked potentials) as surrogates of white matter and grey matter functional integrity in patients with Multiple Sclerosis (MS). Data will be compared with those obtained from a group of healthy control subjects. Secondary aim will be the longitudinal evaluation of these neurophysiological parameters in MS patients during routine clinical and radiological evaluations, performed according to clinical practice, for 12 months.

To this aim a longitudinal multicenter study will be carried out, interventional (for neurophysiological techniques) and observational (for clinical and radiological evaluations), which involves the enrollment of 64 patients diagnosed with MS. Patients will keep their usual therapeutic regimen and their usual clinical-radiological checks according to clinical practice. The control group will consist of 64 healthy subjects, enrolled with prior written informed consent, age and sex-matched with MS patients and selected among the caregivers of the patients. Healthy subjects will only undergo neurophysiological assessment at baseline.

The neurophysiological evaluation will include the study of the propagation of potentials induced by stimulation. This method allows the study of cortical responses in terms of time domain and frequency, obtaining a measurement of interhemispheric connectivity and of microstructural and functional integrity of white matter. In the same way, these methods allow the assessment of grey matter integrity through the study of intracortical excitability.

Conditions

• Multiple Sclerosis
• Demyelinating Disease
• Inflammatory Disease

Interventions

OTHER

Neurophysiological assessment

EMG will be recorded from the Abductor pollicis brevis muscle (APB) with surface electrodes. EEG will be recorded with a 32-channel elastic cap via a TMS compatible system. TMS will be performed using a Magstim 200 stimulator with a 90 mm figure-of-eight coil localized on motor and non-motor areas using a neuronavigation system together with an optical tracking system. Coordinates for neuronavigation will be calculated in the MNI space and fit of each participant's anatomical MRI. Three minutes of continuous-EEG will be recorded with subjects at rest. Single-pulse neuronavigated TMS (sp-TMS) will be delivered at rest below the resting motor threshold intensity (RMT) over the APB hotspot on M1 during concurrent EEG recording. In a final block, the subject will maintain a voluntary muscle contraction (50% of the maximal voluntary contraction) of the left APB, and sp-TMS will be delivered at 130% RMT over the ipsilateral APB hotspot in order to record the lpSP.

OTHER

clinical assessment

Clinical evaluation, performed at each time point, will include: * The assessment of clinical disability using EDSS score * The multiple sclerosis functional composite (MSFC), a three-part quantitative objective measure of neurologic function, measuring lower limbs (timed 25-foot walk \[T25FW\]), upper limbs (nine-hole peg test \[9HPT\]) and cognitive (three-second paced auditory serial addition test \[PASAT3\]) function. In order to reduce inter-rater variability, the same physician/technician with adequate training will administer all three tests. The patient should feel comfortable with the situation. Examiner should explain the instructions in a professional but friendly way and let the patient ask any questions before starting the tests. Examiner should write down the test results, as well as any situation that disturbs the performance of patient. Examiner should not provide direct feedback to the patient about his/her performance

Sponsors & Collaborators

• University of Roma La Sapienza

  lead OTHER

Principal Investigators

• Diego Centonze, MD, PhD · Unit of Neurology, IRCCS Neuromed, Pozzilli, IS

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-10-31

Primary Completion

2023-07-01

Completion

2023-09-01