Epidural Spinal Cord Stimulation improves gait kinematics in people with Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by a spectrum of motor impairments, ranging from infantile onset of severe muscle weakness with respiratory failure to later onset of milder limb weakness and walking impairments (SMA type 3 or 4). While there are pharmaceutical therapies available that can slow the progression of the disease, they do not effectively improve motor deficits, leaving SMA patients significantly impaired. Hence, there is a critical need to develop new combination treatments aimed to improve motor neuron function. Previous experiments conducted in a mouse model have shown that the motor deficit observed in SMA cannot be solely ascribed to spinal motoneurons loss. Instead, these deficits are associated with a decrease in the firing rate of the surviving motoneurons.This decline in firing rate is due to maladaptive changes in ion channels produced by an insufficient synaptic drive from sensory afferents. Notably, these sensory afferents can be directly stimulated via targeted epidural Spinal Cord Stimulation (SCS). ???? Thus, we hypothesized that SCS will lead to two significant results: 1. The immediate reduction of motor deficits by increasing the synaptic input from sensory afference and so the firing rate of motoneurons. 2. The generation of long-term potentiation of the SMA-affected sensory-motor synapses which could revert the maladaptive changes in ion channels, thereby improving motor deficits over the long term.?? As part of an ongoing clinical study (NCT05430113) investigating the safety and effectiveness of SCS in individuals with type 3 SMA, we temporarily implanted bilateral linear leads at the lumbar level in three participants. This study focuses on assessing the impact of SCS on locomotion. As part of my thesis, I conducted comprehensive 3D limb kinematic analyses during overground locomotion tasks. For all participants, I evaluated gait quality variables such as step length, step height, and gait velocity, under both stimulation on and stimulation of condition. Additionally, I examined changes in the Range of Motion (ROM) of the hip and knee joints throughout the duration of the study. Finally, a statistical technique known as principal component analysis was used to identify differences in gait patterns resulting from the treatment. The preliminary findings suggest that SCS induces changes in the gait kinematics, which align with improvements in their motor deficits. Indeed, all subjects showed higher values for all of the gait variables, which led to a substantial improvement in the quality of the gait. An increase in joint ROM, particularly for the most impaired participant, was also identified, suggesting that SCS has the potential to improve gait kinematics.