Sequence variants in muscle tissue-related genes may determine the severity of muscle contractures in cerebral palsy.

Muscle contractures are a common complication to cerebral palsy (CP). The purpose of this study was to evaluate whether individuals with CP carry specific gene variants of important structural genes that might explain the severity of muscle contractures. Next-generation-sequencing (NGS) of 96 candidate genes associated with muscle structure and metabolism were analyzed in 43 individuals with CP (Gross Motor Function classification system [GMFCS] I, n=10; GMFCS II, n=14; GMFCS III, n=19) and four control participants. In silico analysis of the identified variants was performed. The variants were classified into four categories ranging from likely benign (VUS0) to highly likely functional effect (VUS3). All individuals with CP were classified and grouped according to their GMFCS level: Statistical comparisons were made between GMFCS groups. Kruskal-Wallis tests showed significantly more VUS2 variants in the genes COL4 (GMFCS I-III; 1, 1, 5, respectively [p < .04]), COL5 (GMFCS I-III; 1, 1, 5 [p < .04]), COL6 (GMFCS I-III; 0, 4, 7 [p < .003]), and COL9 (GMFCS I-III; 1, 1, 5 [p < .04]), in individuals with CP within GMFCS Level III when compared to the other GMFCS levels. Furthermore, significantly more VUS3 variants in COL6 (GMFCS I-III; 0, 5, 2 [p < .01]) and COL7 (GMFCS I-III; 0, 3, 0 [p < .04]) were identified in the GMFCS II level when compared to the other GMFCS levels. The present results highlight several candidate gene variants in different collagen types with likely functional effects in individuals with CP.

Impaired Ability to Suppress Excitability of Antagonist Motoneurons at Onset of Dorsiflexion in Adults with Cerebral Palsy.

We recently showed that impaired gait function in adults with cerebral palsy (CP) is associated with reduced rate of force development in ankle dorsiflexors. Here, we explore potential mechanisms. We investigated the suppression of antagonist excitability, calculated as the amount of soleus H-reflex depression at the onset of ankle dorsiflexion compared to rest, in 24 adults with CP (34.3 years, range 18-57; GMFCS 1.95, range 1-3) and 15 healthy, age-matched controls. Furthermore, the central common drive to dorsiflexor motoneurons during a static contraction in the two groups was examined by coherence analyses. The H-reflex was significantly reduced by 37% at the onset of dorsiflexion compared to rest in healthy adults (P < 0.001) but unchanged in adults with CP (P = 0.91). Also, the adults with CP had significantly less coherence. These findings suggest that the ability to suppress antagonist motoneuronal excitability at movement onset is impaired and that the central common drive during static contractions is reduced in adults with CP.

Spasticity in adults with cerebral palsy and multiple sclerosis measured by objective clinically applicable technique.

OBJECTIVE: The present study evaluated ankle stiffness in adults with and without neurological disorders and investigated the accuracy and reproducibility of a clinically applicable method using a dynamometer. METHODS: Measurements were obtained from 8 healthy subjects (age 39.3), 9 subjects with spastic cerebral palsy (CP) (age 39.8) and 8 subjects with multiple sclerosis (MS) (age 49.9). Slow and fast dorsiflexion stretches of the ankle joint were performed to evaluate passive muscle-tendon-joint stiffness, reflex mediated stiffness and range of movement (ROM), respectively. Intra/inter-rater reliability for passive and reflex mediated ankle muscle stiffness was assessed for all groups. RESULTS: Subjects with CP and MS showed significantly larger values of passive stiffness in the triceps surae muscle tendon complex and smaller ROM compared to healthy individuals, while no significant difference in reflex mediated stiffness. Measurements of passive muscle-tendon-joint stiffness and reflex mediated stiffness showed good to excellent inter- and intra-rater reliability (ICC: 0.62-0.91) in all groups. CONCLUSION: Increased stiffness was found in subjects with CP and MS with a clinically applicable method that provides valid and reproducible measurement of passive ankle muscle-tendon-joint stiffness and reflex mediated stiffness. SIGNIFICANCE: The present technique may provide important supplementary information for the clinician.

Contribution of sensory feedback to plantar flexor muscle activation during push-off in adults with cerebral palsy.

Exaggerated sensory activity has been assumed to contribute to functional impairment following lesion of the central motor pathway. However, recent studies have suggested that sensory contribution to muscle activity during gait is reduced in stroke patients and children with cerebral palsy (CP). We investigated whether this also occurs in CP adults and whether daily treadmill training is accompanied by alterations in sensory contribution to muscle activity. Seventeen adults with CP and 12 uninjured individuals participated. The participants walked on a treadmill while a robotized ankle-foot orthosis applied unload perturbations at the ankle, thereby removing sensory feedback naturally activated during push-off. Reduction of electromyographic (EMG) activity in the soleus muscle caused by unloads was compared and related to kinematics and ankle joint stiffness measurements. Similar measures were obtained after 6 wk of gait training. We found that sensory contribution to soleus EMG activation was reduced in CP adults compared with uninjured adults. The lowest contribution of sensory feedback was found in participants with lowest maximal gait speed. This was related to increased ankle plantar flexor stiffness. Six weeks of gait training did not alter the contribution of sensory feedback. We conclude that exaggerated sensory activity is unlikely to contribute to impaired gait in CP adults, because sensory contribution to muscle activity during gait was reduced compared with in uninjured individuals. Increased passive stiffness around the ankle joint is likely to diminish sensory feedback during gait so that a larger part of plantar flexor muscle activity must be generated by descending motor commands.NEW & NOTEWORTHY Findings suggest that adults with cerebral palsy have less contribution of sensory feedback to ongoing soleus muscle activation during push-off than uninjured individuals. Increased passive stiffness around the ankle joint is likely to diminish sensory feedback during gait, and/or sensory feedback is less integrated with central motor commands in the activation of spinal motor neurons. Consequently, muscle activation must to a larger extent rely on descending drive, which is already decreased because of the cerebral lesion.

Treadmill training with an incline reduces ankle joint stiffness and improves active range of movement during gait in adults with cerebral palsy.

PURPOSE: We investigated if 30 min of daily treadmill training with an incline for 6 weeks would reduce ankle joint stiffness and improve active range of movement in adults with cerebral palsy (CP). METHODS: The study was designed as a randomized controlled clinical trial including 32 adults with CP (GMFCS 1-3) aged 38.1 SD 12 years. The training group (n = 16) performed uphill treadmill training at home daily for 30 min for 6 weeks in addition to their usual activities. Passive and reflex mediated stiffness and range of motion (ROM) of the ankle joint, kinematic and functional measures of gait were obtained before and after the intervention/control period. Intervention subjects trained 31.4 SD 10.1 days for 29.0 SD 2.3 min (total) 15.2 h. RESULTS: Passive ankle joint stiffness was reduced (F = 5.1; p = 0.031), maximal gait speed increased (F = 42.8, p < 0.001), amplitude of toe lift prior to heel strike increased (F = 5.3, p < 0.03) and ankle angle at heel strike was decreased (F = 12.5; p < 0.001) significant in the training group as compared to controls. CONCLUSION: Daily treadmill training with an incline for 6 weeks reduces ankle joint stiffness and increases active ROM during gait in adults with CP. Intensive gait training may thus be beneficial in preventing and reducing contractures and help to maintain functional gait ability in adults with CP. Implications for rehabilitation Uphill gait training is an effective way to reduce ankle joint stiffness in adult with contractures. 6 weeks of daily uphill gait training improves functional gait parameters such as gait speed and dorsal flexion during gait in adults with cerebral palsy.

Explosive Resistance Training Increases Rate of Force Development in Ankle Dorsiflexors and Gait Function in Adults With Cerebral Palsy.

Kirk, H, Geertsen, SS, Lorentzen, J, Krarup, KB, Bandholm, T, and Nielsen, JB. Explosive resistance training increases rate of force development in ankle dorsiflexors and gait function in adults with cerebral palsy. J Strength Cond Res 30(10): 2749-2760, 2016-Alterations in passive elastic properties of muscles and reduced ability to quickly generate muscle force contribute to impaired gait function in adults with cerebral palsy (CP). In this study, we investigated whether 12 weeks of explosive and progressive heavy-resistance training (PRT) increases rate of force development of ankle dorsiflexors (RFDdf), improves gait function, and affects passive ankle joint stiffness in adults with CP. Thirty-five adults (age: 36.5; range: 18-59 years) with CP were nonrandomly assigned to a PRT or nontraining control (CON) group in this explorative trial. The PRT group trained ankle dorsiflexion, plantarflexion, leg press, hamstring curls, abdominal curls, and back extension 3 days per week for 12 weeks, with 3 sets per exercise and progressing during the training period from 12 to 6 repetition maximums. RFDdf, 3-dimensional gait analysis, functional performance, and ankle joint passive and reflex-mediated muscle stiffness were evaluated before and after. RFDdf increased significantly after PRT compared to CON. PRT also caused a significant increase in toe lift late in swing and a significantly more dorsiflexed ankle joint at ground contact and during stance. The increased toe-lift amplitude was correlated to the increased RFDdf (r = 0.73). No other between-group differences were observed. These findings suggest that explosive PRT may increase RFDdf and facilitate larger range of movement in the ankle joint during gait. Explosive PRT should be tested in clinical practice as part of a long-term training program for adults with CP.

Impaired gait function in adults with cerebral palsy is associated with reduced rapid force generation and increased passive stiffness.

OBJECTIVE: It is still not clarified whether spasticity contributes to impairments of gait function. Here we compared biomechanical measures of muscle weakness and stiffness of ankle muscles to impairments of gait function in adults with cerebral palsy (CP). METHODS: Twenty-four adults with CP (mean age 34.3, range 18-57 years) and fifteen healthy age-matched controls were biomechanically measured for passive and reflex-mediated stiffness of the ankle plantarflexors at rest, maximal voluntary plantarflexion and dorsiflexion effort (MVCpf,df) and rate of force development (RFDpf,df). Kinematic analysis of the ankle joint during treadmill walking was obtained by 3-D motion analysis. RESULTS: Passive stiffness was significantly increased in adults with CP compared to controls. Passive stiffness and RFDdf were correlated to reduced toe lift. RFDpf provided the best correlation to push-off velocity, range of movement in the ankle joint and gait speed. Reflex-mediated stiffness was not correlated to any parameters of impaired gait. CONCLUSIONS: Impaired gait function in adults with CP is associated with reduced RFD and increased passive stiffness of ankle muscles. SIGNIFICANCE: These findings suggest that reduced rapid force generation and increased passive stiffness of ankle muscles rather than increased reflex-mediated stiffness (spasticity) likely contributes to impaired gait function in adults with CP.