Understanding skeletal muscle in cerebral palsy: a path to personalized medicine?

Abstract

Until recently, there has been little interest in understanding the intrinsic features associated with the pathomorphology of skeletal muscle in cerebral palsy (CP). Coupled with emerging evidence that challenges the role of spasticity as a determinant of gross motor function and in the development of fixed muscle contractures, it has become increasingly important to further elucidate the underlying mechanisms responsible for muscle alterations in CP. This knowledge can help clinicians to understand and apply treatment modalities that take these aspects into account. Thus, the inherent heterogeneity of the CP phenotype allows for the potential of personalized medicine through the understanding of muscle pathomorphology on an individual basis and tailoring treatment approaches accordingly. This review aims to summarize recent developments in the understanding of CP muscle and their relationship to musculoskeletal manifestations, in addition to proposing a treatment paradigm that incorporates this new knowledge.

Use of Shear Wave Elastography in Pediatric Musculoskeletal Disorders

“…In CP, spasticity caused by an upper motor neuron lesion often leads to muscle weakness, muscle stiffness, and contractures, which eventually restrict general mobility [16]. Recent studies have emphasized the increased intensity of the connective tissue and extracellular matrix in spastic muscles, indicating that muscle stiffness may be a critical factor in the worsening of motor disorder over time in children with CP [17,18]. These research findings may explain our clinical observations that many children with CP have an increase in muscle stiffness and a decrease in joint range of motion and in the efficiency of walking as they age into adolescence and adulthood.…”

Adult stem cell characterization from theMedial GastrocnemiusandSemitendinosusmuscles in early development of cerebral palsy pathology

“…Treatment mainly consists of management of the symptoms at the muscle level, including physiotherapy, orthoses, Botulinum Neurotoxin A (BoNT) injections and orthopaedic surgery 4,7 . However, knowledge on the effects of treatment on CP muscle morphology is incomplete and totally lacking on cellular level 4 . Hence, there is much interest in better understanding the underlying pathomorphology of skeletal muscles in patients with CP and thereby as well the effects of treatment 3 .…”

“…Yet, these longitudinal data are clinically relevant. For example, muscle imaging and animal studies highlighted that BoNT injections that are planned to reduce spasticity may induce atrophy and increase the fibro/fatty content in the muscle 4,33,34 . Though, the effects of BoNT on microscopical level or on the stem cells of the muscle are much less studied, but are required for optimizing treatment.…”

Surgical Strategies and Perioperative Considerations for Cervical Deformity With Cerebral Palsy: A Comprehensive Review of the Literature

“…1,[8][9][10][11] In addition, static anatomical factors (i.e., bones or ligaments) can result in problems with stenosis, and dynamic factors (i.e., nerves or muscles) are related to problems of incoordination. 6,10,[12][13][14][15][16] Since the cervical spine has a wide range of motion and complex functions, these factors can generate a wide range of disorders and alignment pathologies necessitating surgical treatment. 3,6,7 Although cervical spine deformities in CP have unique characteristics and substantially impact patients' quality of life, few comprehensive studies have focused on CD in patients with CP (CDCP).…”

“…Accelerated degeneration and continuous motion in the cervical spine eventually result in CM, which can further complicate a patient’s already compromised neurological function and severely limit their autonomy [ 1 , 8 - 11 ]. In addition, static anatomical factors (i.e., bones or ligaments) can result in problems with stenosis, and dynamic factors (i.e., nerves or muscles) are related to problems of incoordination [ 6 , 10 , 12 - 16 ]. Since the cervical spine has a wide range of motion and complex functions, these factors can generate a wide range of disorders and alignment pathologies necessitating surgical treatment [ 3 , 6 , 7 ].…”