Phd in MORPHOGENESIS AND TISSUE ENGINEERING

Thesis title: Non motor neuron involvement in ALS

Background: Amyotrophic lateral sclerosis (ALS) is considered the main model for motor neuron disease. Increasing evidences highlight non motor neuron involvement in ALS, such as a cognitive and sensory fibres impairment. Aim of this project was to demonstrate the involvement of sensory-motor networks in ALS and the possibility to modulate them through the skin tactile stimulation. Second aim of the project was to describe kinematic patterns of finger tapping in an ALS sample, looking for extrapyramidal features and relationships between neurophysiological and kinematic parameters. Material and methods: for the first aim of the project, PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. To demonstrate a possible modulation of sensory-motor networks through skin stimulation, 15 healthy subjects underwent to the same PAS protocol administered to the ALS cohort; the same healthy subjects underwent to the PAS protocol following a 10-minutes skin stimulation, in a different day. Differences between the trend of MEP amplitude after PAS in the two sessions were analysed. For the second aim of the project, 14 ALS patients underwent a complete neurophysiological (motor NCS from ulnar and median nerves, repetitive nerve stimulation -RNS-, needle EMG from FDI, central motor conduction time -CMCT- from ADM and FDI) and kinematic assessment during a 15-seconds finger tapping trial (total number of movement, coefficient of variation -CV-, amplitude, amplitude slope, velocity and velocity slope were detected), compared to the data from healthy controls. Results: In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 compared to the baseline. In ALS patients, a significant increase in MEP amplitude was also observed after 60 minutes, thus demonstrating NMDA-mediated enhanced facilitatory plasticity. In the healthy volunteers’ cohort, skin stimulation significantly enhanced the MEP amplitude increase after PAS at T30 and showed a trend to significancy at T60 (p=0.07), thus demonstrating an increased sensory-motor networks excitability. In the kinematic study, ALS patients showed a reduction in the total number of movement and angular velocity compared to healthy controls, with an increased CV, demonstrating a low rhythmic movement. Nevertheless, amplitude, amplitude slope and velocity slope did not differ from healthy control sample, thus demonstrating a different behaviour from Parkinson patients. Finally, the reduction in the number of movement correlated with cMAP amplitude from median nerve and denervation from FDI, while the angular velocity correlated with cMAP amplitude from ulnar nerve and denervation from FDI, thus underlining a key-role for peripheral nervous system in determining these kinematic features. Conclusions: this project demonstrated an involvement of sensory-motor networks in ALS; the same networks can be hyper-excited by sensory skin stimulation, that should be avoided in ALS rehabilitation. No extrapyramidal feature can be described in the kinematic study, which demonstrated a slow and arhythmic finger tapping, which mainly correlated to peripheral nervous system involvement.