Irene Oude Lansink

DUTCH SUMMARY (Translated)

Spinal muscular atrophy (SMA) is a rare, severe, and hereditary muscle disease. In the Netherlands, 15–20 children are born each year with a predisposition for this condition, and there are estimated to be between 450 and 700 people with SMA. SMA is characterized by the degeneration of motor neurons in the anterior horn of the spinal cord, leading to muscle thinning ('atrophy') and a decrease in muscle strength, primarily affecting postural muscles and muscles in the proximal limbs. During the course of the disease, reduced mobility of specific joints, known as contractures, often develops. Literature indicates that contractures frequently lead to pain and limitations in daily functioning.

The severity of SMA varies widely, captured by clinical classifications (types 0–4). The past decade has seen significant changes in SMA treatment. Since 2017, three pharmacological therapies have become available (Spinraza®, Evrysdi®, and Zolgensma®), which have positively impacted survival and motor function. Since 2022, newborn screening in the Netherlands has enabled earlier treatment, improving prospects.

Contractures are the most common orthopedic complications in SMA. Despite limited scientific evidence for specific treatments, international guidelines (2018) recommend stretching, orthoses, and standing frames to maintain muscle length. However, knowledge gaps remain regarding their pathogenesis and the impact of treatment in the era of new medications.

Thesis Aim
This thesis investigates various aspects of contractures within the changing context of SMA treatment. Part one focuses on the impact of contractures on daily life and the perspectives of rehabilitation physicians. Part two examines the longitudinal course of joint mobility, muscle strength, and agonist-antagonist imbalance in children treated early (before 18 months of age).

Part 1: Impact and Management
Chapter 2 describes the experiences of wheelchair-bound adolescents and young adults (AYA). They often find muscle weakness more hindering than contractures and have adapted over time. Meaningful and realistic treatment goals are essential; for instance, wearing regular shoes is a major priority. standing frames often evoked negative feelings when perceived as unrealistic. Physiotherapy is valued, while orthoses are often seen as burdensome. Chapter 3 [numbered as 4 in summary] explores Dutch rehabilitation physicians' perspectives, highlighting the challenges of clinical decision-making in a changing landscape and emphasizing personalized, goal-oriented care using the ICF framework. Chapter 4 [numbered as 3 in summary] discusses parental experiences during the COVID-19 pandemic, showing that protection of the child's health was the central focus.

Part 2: Joint Mobility in the Era of DMTs
Chapter 5 shows that in young children treated early, wrist and elbow range of motion remained stable, while knee extension showed a slow annual decline of 3 degrees. Chapter 6 investigates muscle strength imbalances. While muscle strength improved for both flexors and extensors, no direct correlation was found between strength changes and range of motion, though high imbalance ratios may contribute to gradual knee extension loss.

Conclusion
Chapter 7 summarizes the findings. Joint mobility decline in the elbow and wrist appears reduced in treated children compared to historical untreated cohorts. However, the risk of knee extension limitations persists. The study emphasizes the importance of continuous, high-quality contracture care and aligning personalized goals with children and their parents.