Fatigue in Cerebral Palsy: An EEG- and FDG-PET-based Study of Brain Activity and Its Correlation With Fatigue.

1.1. Cerebral palsy: epidemiology and symptomatology

Cerebral palsy (CP) is a neurodevelopmental disorder with a prevalence of 0.2-0.5% (Oskoui et al., 2013; McGuire et al., 2019; McIntyre et al., 2022). In most cases, the condition is apparent from early life and affects motor activity. Three phenotypes of CP are recognized according to motor disability:

spastic CP, dyskinetic CP, and atactic CP (Bekteshi et al., 2023). These variants are considered to arise from pathology affecting the corticofugal tracts, the basal ganglia, and the cerebellum, respectively.

CP is classified into 5 categories, depending on the severity of motor dysfunction (Piscitelli et al., 2021). The Gross Motor Function Classification System (GMFCS) level I means that the patient can move, walk stairs, and run and jump without any form of aid. GMFCS level II means that the patient moves with some difficulty, cannot run or jump, and need to hold a rail when walking stairs. GMFCS level III means that the patient needs a hand-held aid (stick, crutches) and needs a wheelchair for longer distances GMFCS level IV means that the patient has limited ability to move autonomously and uses a wheelchair. GMFCS level V means that the patient usually uses a wheelchair. CP has, in most cases in which a cause can be identified, a genetic background, often a de novo mutation, whereas a perinatal condition (birth asphyxia, neonatal brain infection) is a minor cause of CP (Gonzalez-Mantilla et al., 2023; Janzing et al., 2024).

1.2 Comorbidities in CP: fatigue, pain, intellectual disability, and epilepsy Fatigue is common among CP patients, affecting approximately 40% (Jacobson et al., 2020). Fatigue in CP is commonly interpreted as muscle fatigue related to the motor impairment of CP (Brunton and Rice, 2012; Puce et al., 2021). There is a growing understanding that mental fatigue is an important aspect of CP (Puce et al., 2021); however, a recent review found no valid instrument for measuring mental fatigue in CP (Dutia et al., 2024), pointing to an important obstacle in fatigue research in CP.