Dataset Information

Muscle paresis and passive stiffness: key determinants in limiting function in Hereditary and Sporadic Spastic Paraparesis.

ABSTRACT:

Background

People with Hereditary and Sporadic Spastic Parapresis (SP) walk with a stiff legged gait characterised by a lack of knee flexion.

Objective

We investigated the relationship between lower limb strength and stiffness and knee flexion during swing phase while walking in 20 people with SP and 18 matched controls.

Methods

Maximal isometric strength was measured using a dynamometer. Passive stiffness and spasticity was assessed during motor-driven slow (5°/s) and fast (60°/s) stretches at the ankle and knee while the subject was relaxed or preactivating the muscle. Walking was assessed using 3D motion analysis.

Results

Isometric muscle strength was decreased in people with SP with over a 50% reduction in strength being found in the ankle dorsiflexors. Passive stiffness, assessed during slow stretches, was 35% higher in the plantarflexors in people with SP (P<0.05). Faster stretches induced large stretch evoked muscle activity and over a 110% increase in stiffness at the ankle and knee in people with SP reflecting the presence of spasticity (P<0.05). However, stretch reflex size and stiffness was similar between the groups following identical stretches of the pre-activated muscle (P>0.05). Lower knee flexion during swing phase was associated with reduced knee flexion velocity at the end of stance phase which in turn was associated with reduced plantarflexor strength and increased passive stiffness in the knee extensors.

Conclusions

The relative importance of muscle paresis and passive stiffness in limiting walking in SP suggests that these impairments should be the target of future therapies.

SUBMITTER: Marsden J

PROVIDER: S-EPMC3657152 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Muscle paresis and passive stiffness: key determinants in limiting function in Hereditary and Sporadic Spastic Paraparesis.

Marsden Jon J Ramdharry Gita G Stevenson Valerie V Thompson Alan A

Gait & posture 20111101 2

<h4>Background</h4>People with Hereditary and Sporadic Spastic Parapresis (SP) walk with a stiff legged gait characterised by a lack of knee flexion.<h4>Objective</h4>We investigated the relationship between lower limb strength and stiffness and knee flexion during swing phase while walking in 20 people with SP and 18 matched controls.<h4>Methods</h4>Maximal isometric strength was measured using a dynamometer. Passive stiffness and spasticity was assessed during motor-driven slow (5°/s) and fast ...[more]

PMID: 22050971

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Project description:Hereditary spastic paraparesis type 15 is a recessive complicated form of the disease clinically characterized by slowly progressive spastic paraparesis and mental deterioration with onset between the first and second decade of life. Thinning of corpus callosum is the neuroradiological distinctive sign frequently associated with white matter abnormalities. The causative gene, ZFYVE26, encodes a large protein of 2539 amino acid residues, termed spastizin, containing three recognizable domains: a zinc finger, a leucine zipper and a FYVE domain. Spastizin protein has a diffuse cytoplasmic distribution and co-localizes partially with early endosomes, the endoplasmic reticulum, microtubules and vesicles involved in protein trafficking. In addition, spastizin localizes to the mid-body during the final step of mitosis and contributes to successful cytokinesis. Spastizin interacts with Beclin 1, a protein required for cytokinesis and autophagy, which is the major lysosome-mediated degradation process in the cell. In view of the Beclin 1-spastizin interaction, we investigated the possible role of spastizin in autophagy. We carried out this analysis by using lymphoblast and fibroblast cells derived from four different spastizin mutated patients (p.I508N, p.L243P, p.R1209fsX, p.S1312X) and from control subjects. Of note, the truncating p.R1209fsX and p.S1312X mutations lead to loss of spastizin protein. The results obtained indicate that spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation. In cells lacking spastizin or with mutated forms of the protein, spastizin interaction with Beclin 1 is lost although the formation of the Beclin 1-UVRAG-Rubicon complex can still be observed. However, in these cells we demonstrate an impairment of autophagosome maturation and an accumulation of immature autophagosomes. Autophagy defects with autophagosome accumulation can be observed also in neuronal cells upon spastizin silencing. These results indicate that autophagy is a central process in the pathogenesis of complicated forms of hereditary spastic paraparesis with thin corpus callosum.

Dataset Information

Muscle paresis and passive stiffness: key determinants in limiting function in Hereditary and Sporadic Spastic Paraparesis.

Background

Objective

Methods

Results

Conclusions

Publications

Muscle paresis and passive stiffness: key determinants in limiting function in Hereditary and Sporadic Spastic Paraparesis.

Similar Datasets

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