Jitter's Recording in a Spastic Muscle Treated by Botulinum Toxin

Stroke is a frequent, serious and disabling condition. Spasticity interferes with the classic motor pattern and reflects reflex motor activities normally inhibited by the central nervous system. This term most frequently refers to a disorder that causes a speed increase dependent on the tonic stretching reflex associated with an increase of tendon reflexes. About 30% of patients are affected and this can occur in the short, medium and long term after stroke. It would seem that, the more serious the initial motor and sensory impairments, the more likely it is to develop a pattern of spasticity. The most classic upper limb (UL) pattern is that of an internal adductum rotation of the shoulder coupled to a flessum of the elbow, wrist and fingers. Approximately 79% of spastic patients on UL have an elbow flessum, involving at different degrees the elbow flexor muscles (anterior brachialis, biceps brachialis). Spasticity and its neuro-orthopedic impact, together with muscle atrophy, joint contracture, pain resulting from the shortening of muscle fibres and ligaments, significantly impede the progression of rehabilitation, social reintegration, the pursuit of daily living activities and quality of life.

Recommended management of spasticity after stroke involves multidisciplinary rehabilitation programs associated with botulinum toxin A (BTA) treatment. Despite this, the dose injected into this muscle is ultimately more dependent on the experience, feelings and habits of the referring physician. Some studies provide a safe framework for increasing doses, but treatment failure by shortness of breath in initially responding patients is still possible.

BTA by blocking the neuromuscular junction (NMJ) is a source of denervation in muscle fiber (MF), which causes the activation of a serine protease, urokinase. This degrades the components of the basal muscle blade, causing the nerve endings to bud. The term sprouting refers to the phenomenon of collateral reinnervation by adjacent fibres from nodal (Ranvier nodes), terminal and ultra-terminal sites, making it possible to temporarily ensure the function of parental synapses paralysed by BTA. Thus, initially, between 3 and 7 days, nodal regrowth is responsible for the development of so-called "immature" NMJs. Then, secondarily, between 4 to 8 weeks, the original synapse begins its recovery through the development of terminal reinnervations, parallel to the regression of nodal regrowth. This explains clinically the increase in remote spasticity of treatment and structural changes in motor units (MU), usually observed after about 12 weeks. Compared to healthy (or naive) muscles in this treatment, BTA-induced muscles develop amyelin-like nerve fibers with more collateral and are characterized by the appearance of non-collateral or nodal reinnervations. Any motor unit (MU) is normally made up of MF of the same type. The addition of adjacent denervated MFs leads to a restructuring of the UM, which led to its functional modification.

Although it is widely accepted that the effect of BTA is temporary and reversible and that functional muscle recovery is thus allowed through the restoration of NMJ, remodelling, and induced myogenesis; some studies show that its effects persist at a distance from the injection. Indeed, whether directly after injection, several months or even a year later, there are changes in the conformation of synaptic gutters (length, width, depths and areas), with an increase in the number of nicotine receptors for Ach (ACHR) and finally a development of continuous nodal reinnervations over time. At present, histological studies are the only ones that have shown this. All the changes observed are not associated with an effective neuromuscular transmission (NMT), which is only guaranteed by the restoration of the original, much more progressive synapse. In most cases, it's estimated that NMJ is still under impregnation with BTA and therefore incompletely restored at a time when it is usual to repeat this treatment. This explains why, in clinical practice, the chemo-denervation process does not always seem entirely anatomically reversible. At present it is not clear which mechanisms are involved: insufficient contact between reinnervations and denervated MF, failure of the stimulation system or failure of Schwann's peri-synaptic cells.

The effects of BTA are still incompletely understood. Histological, molecular, biochemical and genetic analyses explain the phenomena linking denervation to muscle remodelling, with a description of muscle atrophy, a change in sarcomer structure, an increase in intramuscular lipid cells, inflammatory cells, or collagen content, responsible for a reduction in contractile tissue and therefore in the number of motor end plate (MEP). Unfortunately, these histological data cannot be extrapolated to humans or used repeatedly for follow-up. Currently, it is not known whether healthy muscles in animal models behave in the same way as human spastic muscles, nor how to study the latter in clinical routine.