Histological analysis of the semitendinosus muscle in young children with cerebral palsy compared to age matched typically developing children.

Abstract

Cerebral palsy (CP) is a neurological disorder caused by a non-progressive lesion in the developing fetal or infant brain associated with structural muscle alterations. Despite its relevant function in walking, the semitendinosus (ST) structure has been poorly investigated in CP, especially in (very) young children, although this could help determine early events and whether these alterations differ between age groups. This study aimed at defining the histological characteristics of the ST muscle in very young (preschool age group: 3-5 years old) and young (school age group: 6-9 years old) ambulant children with CP, in comparison to age-matched typically developing (TD) children. Microbiopsies of ST were collected in 37 children with CP and 33 TD children (preschool: 15 CP, 9 TD; school age: 22 CP, 24 TD). Muscle cross-sections were immunostained with (1) myosin heavy chain (MHC-I, MHC-IIa, and MHC-IIx) to determine fiber cross-sectional area (absolute: afCSA and normalized to total lower leg length: nfCSA), fiber proportion, (2) CD31 combined with MHC to assess capillary density, capillary to fiber ratio, capillary domain, and heterogeneity index, and (3) Pax7 to quantify the number of satellite cells. fCSA intrasubject variation was determined by coefficient of variation (CV). None of the parameters were altered in the preschool age CP compared to TD, except for larger type I afCSA in girls compared to boys. For the school-age group, type IIx afCSA (+21%, p = 0.019), nfCSA of all fibers (+48%, p = 0.03), and type IIa (+32%, p = 0.019) were larger in CP, and type IIx proportion was higher (+91%, p = 0.016) compared to TD. There was also an increased CV (all fibers: +30%, p = 0.005; type I: +32%, p < 0.001; IIa: +38%, p = 0.025). Satellite cell number and capillarization remained unaltered. These results indicate that the ST appears unaffected in very young ambulant CP children, but alterations develop with age.