A treatment of precision Electroceuticals: fatigue relief in Multiple Sclerosis with personalized home-neuromodulation

In my thesis, we start with a general overview of electroceuticals, the treatment of diseases using electrical signals (PART I, Chapter 1). We then turn to the concept of personalized electroceuticals introducing Faremus, a tDCS treatment against fatigue in multiple sclerosis (MS). Faremus is first personalized by targeting whole-body primary somatosensory area (S1) which is hypoexcitable in MS fatigued patients (PART I, Chapter 2). Further personalization is at individual level with the S1 electrode shaped on the MRI derived individual cortical folding. An option to enhance electroceuticals tools emerges exploiting the electrical patterns of our brain (i.e., the neurodynamics), sustained by the recursive feedback-synchrony-plasticity principle. By studying the EEG patterns through the fractal dimension, we suggest that each area has its own specific neurodymanics. From this idea derives the intervention we called transcranial individual neurodynamics current stimulation (tIDS). Indeed, we realized that if we deliver through the transcranial stimulator electrodes a current that mimics the electrical pattern generated by a target region, we can more effectively modify its activity (Part I, Chapter 3). On the strength of our findings, we matured further steps in the direction of the realization of a therapeutical service. We realized a quantitative review of randomized controlled trials with tDCS in no-structural diseases. The results of the meta-analysis indicated that tDCS treatment for fatigue in MS ranked between moderately and highly recommendable under the guidelines of international authorities and that the recommended montage was the one of Faremus. A second important step towards establishing an electroceutical service was to test a home version of our Faremus. All patients reported excellent values of safety, acceptance and absence of side effects of home treatment which efficacy was above 30% as observed in clinical settings (PART II, Chapter 4). In the direction of the device engineering and commercialization, we set up devoted meetings with the enterprise Igea (PART II, Chapter 5). To further ameliorating and personalizing our treatment, we improved knowledge on fatigue’s mechanisms and Faremus effects. We tested whether the treatment modifies the cortico-muscular-coherence – CMC - (PART III, Chapter 6), which was previously observed to be altered in MS fatigued patients. We confirmed the hypothesis observing normalization by Faremus. These interactions led us to deepen understanding of the phenomena underlying cortico-muscular synchronization. In healthy volunteers, we tested CMC sensitivity to visual feedback and handedness of two synchronization measures: CMC and Normalized compression distance (NCD). Whereas CMC resulted to be only sensitive to visual feedback manipulation, NCD was sensitive also to handedness (PART III, Chapter 7) From this work we can conclude that i) fatigue in MS emerges as a functional alteration of sensorimotor and motor pathways that can surely benefit from electroceutical intervention ii) the treatment Faremus is between moderately and highly recommendable under the indications of the international authorities and confirms its efficacy also in home environment iii) the study of the nervous system and its communication with the muscle effectors, can be enriched by measures that take into account the complexity and non-stationarity of the neural activity.