On muscle spindles, dystonia and botulinum toxin

Abstract

Dystonia may produce co-contractions and constant strain in numerous muscle fibers, including those of the muscle spindles. As proprioceptors, muscle spindles detect dynamic or static changes in muscle length and their afferent projections to the spinal cord play a central role in control of antagonistic muscles. Their parallel arrangement with extrafusal muscle fibers and association with the earlier recruited oxidative motor units allow them to conveniently sample the activity of all motor units and effectively modulate movement. At the same time, fusimotor muscle spindle innervation contracts the striated polar portions of the intrafusal muscle fibers and prevents their slackening during extrafusal muscle contractions. Botulinum toxin remains the most efficient therapy of dystonia. Its muscular mechanism of action is hinged on cholinergic blockade not only of extrafusal, but also of intrafusal muscle fibers. Besides being a targeted muscular therapy, the alteration of the corresponding sensory input following an effect of botulinum toxin on the intrafusal muscle fibers is pivotal in modulating loss of pre-synaptic inhibition in dystonia, including suppression of the tonic vibration reflex. Whether or not trans-synaptic botulinum toxin migration occurs, a modification of the central motor programming is bound to happen in dystonia, with botulinum toxin acting either as another 'sensory trick' or as a form of 'short-term plasticity'. Knowledge of the muscle spindle anatomy and function is key to unify our understanding of abnormal movements and of effects of botulinum toxin therapy. Thus, in dystonia, overactivity of muscles and increased spindle sensitivity are germane to botulinum toxin targets of action.

Botulinum A Toxin Intravesical Injections in the Treatment of Refractory Overactive Bladder in Patients with Parkinson's Disease

“…It is well known that BoNT/A induces striated muscle denervation and weakness lasting about 3-4 months (Hamjian et al, 1994;Schiavo et al, 1994). In striated muscle it has been observed that the neurotoxin not only modulates extra-fusal component but also influences the altered muscle spindle afferent input (Abbruzzese et al, 2006;Currà & Berardelli, 2009;Rosales & Dressler, 2010;Trompetto et al, 2008). In detrusor smooth muscle the effects of BoNT/A injection last longer than in striated muscle.…”

Botulinum toxin type A in motor nervous system: unexplained observations and new challenges

“…However, the beneficial duration of action of BoNT/A on spastic or involuntary contractions does not necessarily concur or follow the muscle-relaxing effects, suggesting a more complex mechanism of action (Rosales and Dressler, 2010;Kaňovský and Rosales, 2011;Mazzocchio and Caleo 2015 ). One of the suggested mechanisms of action is modification of stretch reflex by toxin's indirect action on firing of muscle spindle afferents which provide proprioceptive control for the muscle length and tension (Rosales and Dressler, 2010;Kaňovský and Rosales, 2011). This is based on only few experimental studies assessing the BoNT/A effects on muscle spindles.…”

Dystonia, Spasticity and Botulinum Toxin Therapy: Rationale, Evidences and Clinical Context

“…BoNT is a safe and targeted treatment approach suited for focal dystonia where certain muscles are clearly involved during co-contraction and in which injections can be modified for the changing dystonia patterns, including segmental and overflow muscles involved (4,13,26). Depending upon factors such as muscle bulk, severity of muscle spasm and whether one may want/avoid contiguous muscles in a clinical context, BoNT-A in dystonia may be tailored in certain instances.…”

“…Whereas, in dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol could best be applied, since spread may be desirable for very large muscles, when multipoint muscle injections is utilized (36). In view of its "dual effects" on the extrafusal and intrafusal muscles, the clinical benefit in practice may "outstrip" the weakness induced by the BoNT (4,39) . Interestingly in cervical dystonia, discrepant and time-related effects vary between relief of muscle hypertonus, associated pain and head posture (31) .…”

“…Recently, the scope of spasticity has been broadened in its definition as a disordered sensori-motor control resulting from an upper motor neuron (UMN) lesion presenting as intermittent or sustained involuntary activation of muscles (1)(2) . Although their etiopathogenesis differ, both conditions overlap as regard the following: [a] occurrence of muscle co-contractions; [b] Overactivity involves not only extrafusal but also intrafusal muscles (3)(4) [c] Intrinsic muscle changes in size and visceco-elastic properties (5-6); [d] contractures if left unattended (7);[e] muscular spread in synergy, "overflow" and compensatory muscles; [f ] loss of dexterity; [g] occurrence of pain to varying degrees; [h] secondary bone and joint abnormalities; [i] may lead to "compensatory circuitry changes" at segmental and suprasegmental levels (4) ; [j] May lead to posturing and cosmesis issues, and [k] hygiene, quality of life and social impact . Another common thread between dystonia and spasticity is the reduction in muscle tone following botulinum neurotoxin therapy (BoNT), and effectively addressing the disordered sensori-motor control in both conditions.…”