Browsing by Author "Kaya Keles, Cemre Su"

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Open Access
Botulinum toxin intervention in cerebral palsy-induced spasticity management : projected and contradictory effects on skeletal muscles
(2022) Kaya Keles, Cemre Su; Ates, Filiz
Spasticity, following the neurological disorder of cerebral palsy (CP), describes a pathological condition, the central feature of which is involuntary and prolonged muscle contraction. The persistent resistance of spastic muscles to stretching is often followed by structural and mechanical changes in musculature. This leads to functional limitations at the respective joint. Focal injection of botulinum toxin type-A (BTX-A) is effectively used to manage spasticity and improve the quality of life of the patients. By blocking acetylcholine release at the neuromuscular junction and causing temporary muscle paralysis, BTX-A aims to reduce spasticity and hereby improve joint function. However, recent studies have indicated some contradictory effects such as increased muscle stiffness or a narrower range of active force production. The potential of these toxin- and atrophy-related alterations in worsening the condition of spastic muscles that are already subjected to changes should be further investigated and quantified. By focusing on the effects of BTX-A on muscle biomechanics and overall function in children with CP, this review deals with which of these goals have been achieved and to what extent, and what can await us in the future.
Open Access
Development and preclinical testing of a novel neurodenervant in the rat : C3 transferase mitigates botulinum toxin’s adverse effects on muscle mechanics
(2025) Kaya Keles, Cemre Su; Akdeniz Dogan, Zeynep D.; Yucesoy, Can A.
Spasticity, characterized by elevated muscle tone, is commonly managed with botulinum toxin type A (BTX-A). However, BTX-A can paradoxically increase passive muscle forces, narrow muscles’ length range of force exertion (lrange), and elevate extracellular matrix (ECM) stiffness. C3 transferase, known to inhibit myofibroblast and fascial tissue contractility, may counteract ECM stiffening. This study investigated whether combining BTX-A with C3 transferase reduces active forces without altering passive forces or lrange. Additionally, we examined the isolated effects of C3 transferase on muscle levels. Male Wistar rats received injections into the tibialis anterior (TA): Control (n = 7, saline) and C3 + BTX-A (n = 7, 2.5 µg C3 + 0.1U BTX-A). TA forces were measured one month post-injection, and isolated C3 transferase effects were assessed in separate groups (Control and C3, n = 6 each). Active forces were 43.5% lower in the C3 + BTX-A group compared to the Control group. No differences between groups in passive forces (p = 0.33) or lrange (p = 0.19) were observed. C3 transferase alone had no significant effect on relative muscle mass (p = 0.298) or collagen content (p = 0.093). Supplementing BTX-A with C3 transferase eliminates BTX-A’s adverse effects at the muscle level. C3 transferase alone causes no atrophy or collagen increase, which are key factors in BTX-A-induced ECM stiffening. This novel neurodenervant formula shows promise for advancing spasticity management.
Open Access
How mechanics of individual muscle-tendon units define knee and ankle joint function in health and cerebral palsy : a narrative review
(2023) Kaya Keles, Cemre Su; Ates, Filiz
This study reviews the relationship between muscle-tendon biomechanics and joint function, with a particular focus on how cerebral palsy (CP) affects this relationship. In healthy individuals, muscle size is a critical determinant of strength, with muscle volume, cross-sectional area, and moment arm correlating with knee and ankle joint torque for different isometric/isokinetic contractions. However, in CP, impaired muscle growth contributes to joint pathophysiology even though only a limited number of studies have investigated the impact of deficits in muscle size on pathological joint function. As muscles are the primary factors determining joint torque, in this review two main approaches used for muscle force quantification are discussed. The direct quantification of individual muscle forces from their relevant tendons through intraoperative approaches holds a high potential for characterizing healthy and diseased muscles but poses challenges due to the invasive nature of the technique. On the other hand, musculoskeletal models, using an inverse dynamic approach, can predict muscle forces, but rely on several assumptions and have inherent limitations. Neither technique has become established in routine clinical practice. Nevertheless, identifying the relative contribution of each muscle to the overall joint moment would be key for diagnosis and formulating efficient treatment strategies for patients with CP. This review emphasizes the necessity of implementing the intraoperative approach into general surgical practice, particularly for joint correction operations in diverse patient groups. Obtaining in vivo data directly would enhance musculoskeletal models, providing more accurate force estimations. This integrated approach can improve the clinicians’ decision-making process and advance treatment strategies by predicting changes at the muscle and joint levels before interventions, thus, holding the potential to significantly enhance clinical outcomes.