Pediatric Neuromuscular Disorders



Pediatric Neuromuscular Disorders


Colyn Watkins, MD

Benjamin J. Shore, MD, MPH, FRCSC


Dr. Shore or an immediate family member serves as a board member, owner, officer, or committee member of American Academy for Cerebral Palsy and Developmental Medicine and Pediatric Orthopaedic Society of North America. Neither Dr. Watkins nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter.





Introduction

Remarkable advances in pediatric healthcare over the past several decades have enabled children with complex chronic conditions to live longer. Complex chronic neurologic conditions in children encompass static, progressive, central, and peripheral neurologic diseases including, but not limited to, cerebral palsy, leukodystrophy, muscular dystrophy, spinal muscular atrophy, and spina bifida. Although etiology, natural history, and treatment requirements vary in these children, certain commonalities exist in terms of their musculoskeletal manifestations and orthopaedic pathologies. In all of these conditions, a combination of muscular imbalance, weakness, and altered underlying tone results in diminished initial function, delayed motor milestones, subsequent contracture development, eventual torsional abnormalities leading to gait disturbances, hip subluxation, and scoliosis. Recent medical advances and targeted gene therapy have demonstrated tremendous promise in decreasing the burden of disease and subsequently increasing life expectancy. The orthopaedic surgeon must be up to date on the orthopaedic interventions required to improve quality of life, function, and participation.


Cerebral Palsy


Background

Cerebral palsy is the most common cause of physical disability affecting children in developed countries.1 It is an umbrella term for a group of heterogeneous conditions in terms of etiology, brain pathology, and clinical features. Cerebral palsy is a static encephalopathy, but the musculoskeletal pathology is progressive. Children with cerebral palsy have complex needs and are usually treated by a multidisciplinary team. In a classic study, the term tenotomy was popularized to correct deformity in cerebral palsy, and the link was identified between brain injury and deformity, thus bridging the gap between neurology and orthopaedics.2

The development of gross motor function in children with cerebral palsy can be described by a series of curves that were derived from longitudinal measurements of gross motor function, using the Gross Motor Function Measure.3 The curves show rapid acquisition of gross motor function in infants, with a progressive separation of the curves especially between the ages of
2 and 4 years. The curves plateau between the ages of 3 and 6 years. The five gross motor curves constitute the five levels of the Gross Motor Function Classification System (GMFCS)4 (Figure 1). Children classified as GMFCS I-III are considered to be independently ambulatory, whereas children classified as GMFCS IV-V primarily use a wheelchair for mobility and function. Therefore, treatment is dichotomized according to gross motor function. The goal of medical and surgical treatment for ambulatory children and adults classified as GMFCS I-III is to improve gait efficiency, participation, and community mobility; treatment goals for those classified as GMFCS IV and V include improving seating balance or tolerance, standing ability, and assistance with activities of daily living. Orthopaedic management includes tone management, surgery, physical and occupational therapy, and brace treatment.


Tone Management

Spasticity is common in individuals with cerebral palsy and is the result of a lesion affecting the pyramidal system, which causes a velocity-dependent increase in muscle tone with increased spastic tonic stretch reflexes. Spasticity is often associated with premature birth and the characteristic lesion of periventricular leukomalacia on MRI.5 Untreated spasticity can lead to discomfort, decreased range of motion, subsequent contracture development, and ultimate torsional abnormalities. The newborn child with cerebral palsy does not have contractures or lower limb deformities, and most do not show signs of spasticity.5 With time, spasticity develops, activity levels remain low, the growth of muscle-tendon units lags behind bone growth, and contractures develop. An important therapeutic window exists for spasticity management before the development of fixed contractures. Spasticity management can be classified as focal or generalized, whereas the intervention effect is either temporary or permanent. Oral baclofen provides generalized temporary spasticity management, whereas botulinum toxin A injections provide a more focal temporary intervention. In comparison, selective dorsal rhizotomy (SDR) represents the most permanent example of global spasticity reduction. Often children require a combination of focal and generalized therapy to achieve optimal tone reduction.

Botulinum toxin A helps provide muscle relaxation by selectively blocking the release of acetylcholine at the neuromuscular junction. There is strong evidence that injection of botulinum toxin A results in a reduction in muscle stiffness as measured by the Modified Ashworth Scale and a reduction in spasticity, as measured by the Modified Tardieu Scale. Unfortunately, a change in the Modified Ashworth Scale or Modified Tardieu Scale does not result in a predictable improvement in more meaningful outcome measures such as Gross Motor Function Measure, gait, activity, or participation. The paradox of clinical trials of botulinum toxin A is strong evidence for improvement in surrogate outcomes (Modified Ashworth Scale and Modified Tardieu Scale) and weak evidence or no evidence for improvement in clinically relevant outcomes.6 In the past decade, a large body of work has been performed in animals and humans investigating the effects of botulinum toxin A injections. Injection of botulinum toxin A in animal models is followed by acute muscle atrophy, replacement of contractile elements of muscle with fat, and upregulation of molecular pathways leading to fibrosis.7 Injection of botulinum toxin A may have adverse effects in the muscle injected that may not be fully reversible, such as persistent atrophy, fatty infiltration, and fibrosis.7 Careful consideration of the risks and benefits of botulinum toxin A injection must be considered, and recommendations for application will continue to evolve.

Baclofen is an agonist at the beta subunit of gamma-aminobutyric acid on the monosynaptic and polysynaptic neurons at the spinal cord level and brain.8 Baclofen works to reduce the release of excitatory neurotransmitters in the presynaptic neurons and stimulates inhibitory neuronal signals in the postsynaptic neurons with resultant relief of spasticity. Although oral baclofen can be effective for spasticity reduction, it results in global spasticity reduction, which can lead to constipation, drooling, and decreased axial tone and head control.8

The limited solubility of baclofen when administered orally can be overcome by intrathecal administration using a programmable, battery-operated surgically implanted pump connected to a catheter and delivery system into the intrathecal space; the blood-brain barrier is bypassed and the systemic adverse effect profile is decreased. Intrathecal baclofen (ITB) pump application has been shown in a 2021 study to be effective in reducing spasticity and is most frequently used for nonambulatory children and youth with a diagnosis of cerebral palsy who experience spasticity and/or dystonia9 (Figure 2, A and B). Although invasive and without morbidity, ITB is the most effective current method available for the management of severe spasticity, dystonia, and mixed movement disorders in cerebral palsy and commonly used for patients categorized as GMFCS IV and V.10

SDR is a neurosurgical procedure in which 30% to 50% of the dorsal rootlets between L1 and S1 are transected for the permanent relief of spasticity in a

select group of children with primarily spastic diplegia (GMFCS I-III). SDR is most effective for young ambulatory children, ranging in age from 2 to 10 years.11 Although there have been a handful of case series investigating the outcome of SDR in GMFCS IV and V children, superiority compared with ITB has not been demonstrated.11 A comparison of functional outcomes 10 years after intervention found that both patients who underwent SDR and those who did not undergo SDR had significant improvement in gait pathology; however, the non-SDR group experienced significantly better gait improvement but also underwent more orthopaedic interventions than the SDR group, highlighting that different treatment courses may result in similar outcomes into young adulthood.12












Spine Surgery

Gross motor functional status is correlated with the risk of development of scoliosis, with nonambulatory children (GMFCS IV-V) being at greatest risk compared with ambulatory children who have a risk similar to that of the general population.13 The cause of scoliosis in cerebral palsy remains speculative, but spasticity, dystonia, muscle imbalance, weakness, postural impairment, and immobility have been suggested as contributing factors. Previous studies have suggested that bracing rarely prevents progression of spinal deformity for nonambulatory children categorized as GMFCS IV.14 Newer technology with compression suits with stays to provide additional truncal support has been commercially promoted for patients with scoliosis, although there is no convincing evidence to date to support effective prevention of curve progression at this time.

Typical scoliotic curves in cerebral palsy will begin to progress at the start of the preadolescent growth spurt and usually progress faster than idiopathic curves. The rate of progression accelerates when the curve reaches 40° to 50° and especially as the child enters pubertal growth. Spinal curves in cerebral palsy are more likely to continue to progress after skeletal maturity if the curve is more than 40°. In skeletally mature individuals with curves less than 50°, the progression was 0.8° per year and 1.4° per year for curves greater than 50°.15 Segmental fixation along the entire course of the spine using strong double rods is necessary to distribute the corrective forces throughout the length of the segments to be fused. The segmental anchors may be sublaminar wires, hooks, or pedicle screws, or a combination of these. Fusion should include the pelvis when pelvic obliquity exceeds 10° to 15° on an AP radiograph of the pelvis with the patient in the sitting position.16


Despite acceptable outcomes in terms of deformity correction after spinal fusion, a 2021 prospective, longitudinal study has demonstrated at 5-year follow-up that sustained improvements in health-related quality of life were noted in children who underwent hip reconstruction but not in children who underwent spinal fusion; their scores initially improved at 1 year but by 2 years returned to baseline and remained at baseline 5 years after spinal fusion.17


Hip Surveillance and Surgery

The early stage of neuromuscular hip displacement is silent, and formal screening by radiographs of the hips with careful positioning is advised. Indications for referral to hip surveillance programs are based on GMFCS level, the extent of topographic involvement, and ambulatory status.18 Untreated hip displacement and dislocation may lead to pain and functional impairment affecting the ability to sit, stand, or walk, and impaired quality of life. A 2021 prospective longitudinal study has demonstrated that for nonambulatory children with cerebral palsy who undergo hip reconstruction surgery, at 2 and 5 years after surgery there were long-lasting increases in the overall Caregiver Priorities and Child Health Index of Life with Disabilities total score and improvements in specific scores related to positioning and mobility, comfort and emotions, and health.17 A similar population-based study in adults with cerebral palsy found that 72% experienced pain when their migration percentage was greater than 30%.19

Population-based hip surveillance has demonstrated that the overall risk of hip displacement (defined as a migration percentage greater than 30%) is approximately 30%.20 Preventive surgery, defined as soft-tissue release of the adductor, gracilis, and iliopsoas muscles, is typically indicated for children with a migration percentage between 30% and 40%, and although helpful in achieving improvements in range of motion, long-term studies have demonstrated an overall survivorship of approximately 30% at 7 years, with nonambulatory children experiencing the highest revision rates.21 Osseous reconstruction is recommended for a migration percentage greater than 40%, which includes femoral varus derotational osteotomy with or without associated pelvic osteotomy. Well-performed hip reconstruction has the potential to improve Caregiver Priorities and Child Health Index of Life with Disabilities scores, which remain improved 5 years after the index procedure17 (Figure 3). For hips that present with late, painful dislocations or associated femoral head deformity, salvage surgery is indicated. A 2021 review comparing four different salvage surgical procedures found that the highest parent satisfaction was associated with a proximal femoral resection. The study authors found that steroid injections were also effective but need to be repeated and are less effective over time.22 A previous systematic review came to similar conclusions demonstrating comparable pain outcomes among salvage procedures, with patients who have had arthrodesis having greater pain and a higher complication rate.23 Ultimately there is no single optimal procedure for salvage, but hip arthrodesis should be avoided.

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May 1, 2023 | Posted by in ORTHOPEDIC | Comments Off on Pediatric Neuromuscular Disorders

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