Browsing by Author "Orlik, Benjamin"

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    Relationship of muscle morphology to hip displacement in cerebral palsy: a pilot study investigating changes intrinsic to the sarcomere
    (2019-06-21) Larkin-Kaiser, Kelly A; Howard, Jason J; Leonard, Timothy; Joumaa, Venus; Gauthier, Luke; Logan, Karl; Orlik, Benjamin; El-Hawary, Ron; Herzog, Walter
    Abstract Background Cerebral palsy (CP) is the most common cause of childhood disability, typified by a static encephalopathy with peripheral musculoskeletal manifestations—most commonly related to spasticity—that are progressive with age. Hip displacement is one of the most common manifestations, observed to lead to painful degenerative arthritis over time. Despite the key role that spasticity-related adductor muscle contractures are thought to play in the development of hip displacement in CP, basic science research in this area to date has been limited. This study was initiated to correlate hip adductor muscle changes intrinsic to the sarcomere—specifically, titin isoforms and sarcomere length—to the severity of hip displacement in children with spastic cerebral palsy. Methods Single gracilis muscle biopsies were obtained from children with CP (Gross Motor Function Classification System (GMFCS) III-V; n = 10) who underwent adductor muscle release surgery for the treatment of hip displacement. Gel electrophoresis was used to estimate titin molecular weight. Sarcomere lengths were measured from muscle fascicles using laser diffraction. The severity of hip displacement was determined by measuring by Reimers migration percentage (MP) from anteroposterior pelvic x-rays. Correlation analyses between titin, sarcomere lengths, and MP were performed. Results The mean molecular weight of titin was 3588 kDa. The mean sarcomere length was 3.51 μm. Increased MP was found to be associated with heavier isoforms of titin (R2 = 0.65, p < 0.05) and with increased sarcomere lengths (R2 = 0.65, p < 0.05). Heavier isoforms of titin were also associated with increased sarcomere lengths (R2 = 0.80, p < 0.05). Conclusions Our results suggest that both larger titin isoforms and sarcomere lengths are positively correlated with increased severity of hip displacement and may represent adaptations in response to concomitant increases in spasticity and muscle shortening. Trial registration As this study does not report the results of a health care intervention on human participants, it has not been registered.
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    Stiffness of Hip Adductor Myofibrils is decreased in Children with Spastic Cerebral Palsy
    (Elsevier, 2019-02-23) Leonard, Timothy R.; Howard, Jason J.; Larkin-Kaiser, Kelly A.; Joumaa, Venus; Logan, Karl J.; Orlik, Benjamin; El-Hawary, Ron; Gauthier, Luke E.; Herzog, Walter
    Cerebral palsy (CP) is the result of a static brain lesion which causes spasticity and muscle contracture. The source of the increased passive stiffness in patients is not understood and while whole muscle down to single muscle fibres have been investigated, the smallest functional unit of muscle (the sarcomere) has not been. Muscle biopsies (adductor longus and gracilis) from pediatric patients were obtained (CP n=9 and control n=2) and analyzed for mechanical stiffness, in-vivo sarcomere length and titin isoforms. Adductor longus muscle was the focus of this study and the results for sarcomere length showed a significant increase in length for CP (3.6µm) compared to controls (2.6µm). Passive stress at the same sarcomere length for CP compared to control was significantly lower in CP and the elastic modulus for the physiological range of muscle was lower in CP compared to control (98.2kPa and 166.1kPa, respectively). Our results show that CP muscle at its most reduced level (the myofibril) is more compliant compared to normal , which is completely opposite to what is observed at higher structural levels (single fibres, muscle fibre bundles and whole muscle). It is noteworthy that at the in vivo sarcomere length in CP, the passive forces are greater than normal, purely as a functional of these more compliant sarcomeres operating at long lengths. Titin isoforms were not different between CP and non-CP adductor longus but titin:nebulin was reduced in CP muscle, which may be due to titin loss or an over-expression of nebulin in CP muscles.