The relation between macro- and microscopic muscular alterations of the medial gastrocnemius in children with spastic cerebral palsy.

Children with spastic cerebral palsy (CP) exhibit muscle growth deficits, secondary to the pathological neural input to the muscular system caused by the primary brain lesion. As a result, their medial gastrocnemius is commonly affected and is characterized by macro- and microscopic muscular alterations. At the macroscopic level, the muscle volume (MV), anatomical cross-sectional area of the muscle belly (Belly-CSA), muscle belly length (ML), and the intrinsic muscle quality are reduced. At the microscopic level, the cross-sectional area of the muscle fiber (Fiber-CSA) is characterized by an increased within-patient variability (coefficient of variation), the fiber type proportion is altered, and capillarization is reduced. However, the relationship between the macro- and microscopic muscle characteristics remains unclear, and understanding these connections could offer valuable insights into muscle growth deficits and the potential impact of interventions in children with CP. To address this, the present cross-sectional study examined both macro- and microscopic parameters of the medial gastrocnemius in a single cohort of young ambulant children with CP and age-matched typically developing (TD) peers, and investigated how deficits in macroscopic muscle size correlate with alterations at the microscopic level. A group of 46 children with CP (median age 5.4 [3.3] years) and a control group of 34 TD children (median age 6.3 [3.4] years), who had data on microscopic muscular properties (defined through the histological analyses of muscle biopsies), as well as macroscopic muscle properties (defined by 3D freehand ultrasound) were included. We defined Pearson's or Spearman's correlations, depending on the data distribution. The macroscopic muscle size parameters (MV, Belly-CSA, ML) showed significant moderate correlations (0.504-0.592) with the microscopic average Fiber-CSA in TD and CP. To eliminate the common effect of anthropometric growth at the macro- as well as microscopic level, the data were expressed as deficits (i.e., z-scores from normative centile curves or means) or were normalized to body size parameters. A significant but low correlation was found between the z-scores of MV with the z-scores of the Fiber-CSA (r = 0.420, p = 0.006). The normalized muscle parameters also showed only low correlations between the macro- and microscopic muscle size parameters, namely between Belly-CSA and Fiber-CSA, both in the TD (r = 0.408, p = 0.023) and the CP (ρ = 0.329, p = 0.041) group. Explorations between macroscopic muscle parameters and other microscopic muscle parameters (capillary density, capillary to fiber ratio, and fiber type proportion) revealed no or only low correlations. These findings emphasize that muscle growth deficits in children with CP are not simply a direct consequence of macroscopic muscle size reductions, but rather involve a complex interaction between macro- and microscopic alterations. Understanding these relationships could provide critical insights into the mechanisms of muscle impairment and help guide more targeted interventions to improve muscle function and growth in this population.