Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients.
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PMID:Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons. 2438 12

Spastic movement disorders show a high lifetime prevalence among patients suffering from multiple sclerosis and neuromyelitis optica. Due to the high number of factors interacting with the individual manifestations of spasticity, its symptomatic treatment affords continuous and careful balancing of therapeutic measures. A trend observed over the past few years is to base symptomatic treatment of MS on subjective assessments of functional disorders rather than on specific individual pathological signs and symptoms. This has led to a more generous and more patient-oriented perspective. Therefore, a detailed analysis, characterisation and evaluation of the individual clinical course of the disease is not only indispensable, but is actually gaining even more importance in avoiding uncontrolled polypharmacy with correspondingly increased risks for side effects.
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PMID:[Multiple sclerosis, neuromyelitis optica and spasticity: control of specific symptoms and quality of life]. 2501

Spastic hemiplegia is a common sequela of stroke. Spasticity that is not optimally reduced with systemic therapy is often treated with intramuscular botulinum toxin injections. Spastic tone can increase the difficulty of appropriately positioning the patient for botulinum toxin injections, lengthen procedure duration, and increase periprocedural pain. Our patient, a 53-year-old woman, was unable to be adequately positioned to receive botulinum toxin injections to her left upper extremity because of challenging flexion synergy posturing and related positional pain. A left interscalene brachial plexus local anesthetic block administered under ultrasound guidance was used to produce both temporary dense muscle relaxation and profound anesthesia, facilitating successful and comfortable botulinum toxin injections in this patient.
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PMID:A Novel Use of Regional Anesthesia for Spastic Hemiplegia Evaluation and Treatment: A Case Report. 2625 47

Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases.This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance.During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization.The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia.
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PMID:Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke: Case Series. 2626 68

Purpose We propose a visual myofeedback protocol as a coadjuvant therapy to standard rehabilitation of post-stroke spastic patients. We also argue in favor of the tonic stretch reflex threshold (TSRT) as a more sensitive unit for quantifying subtle changes in the spastic response that may be induced by biofeedback training. Method Sixteen volunteers with ischaemic stroke were divided into an experimental group (EG), subjected to myofeedback training in parallel with conventional physical therapy and a control group (CG), receiving only conventional physical therapy. The EG subjects underwent a six-week myofeedback training, with two sessions weekly. Both groups followed the same treatment schedule for physical therapy. The TSRTs of the volunteers' spastic muscles were assessed before the beginning of the experimental protocol and 3 weeks after it ended. Results Both groups showed some degree of improvement in the level of spasticity when the final TSRT values were compared to the initial values. However, the percentage of improvement (after-before) of the experimental group (38.59%) was significantly higher than that in the control group (18.58%). Conclusion The myofeedback training provided a significant contribution to conventional treatment, allowing for a better improvement of the spastic condition. Implications for rehabilitation Biofeedback is an effective means of improving motor control of post-stroke spastic patients. The Tonic Stretch Reflex Threshold is a more sensitive quantitative measure to assess upper-limb post-stroke spasticity. Spastic patients who participate in myofeedback training along with physical therapy can improve faster then those who participate only in traditional physical therapy rehabilitation protocols.
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PMID:Effect of myofeedback on the threshold of the stretch reflex response of post-stroke spastic patients. 2693 89

Hippotherapy is often carried out for the rehabilitation of children with Cerebral Palsy (CP), with the horse riding at a walking pace. This study aimed to explore the immediate effects of a hippotherapy protocol using a walk-trot pace on spatio-temporal gait parameters and muscle tone in children with Bilateral Spastic CP (BS-CP). Ten children diagnosed with BS-CP and 10 healthy aged-matched children (reference group) took part in this study. The children with BS-CP underwent two sessions of hippotherapy for one week of washout between them. Two protocols (lasting 30min) were applied on separate days: Protocol 1: the horse's pace was a walking pace; and Protocol 2: the horse's pace was a walk-trot pace. Children from the reference group were not subjected to treatment. A wireless inertial measurement unit measured gait spatio-temporal parameters before and after each session. The Modified Ashworth Scale was applied for muscle tone measurement of hip adductors. The participants underwent the gait assessment on a path with surface irregularities (ecological context). The comparisons between BS-CP and the reference group found differences in all spatio-temporal parameters, except for gait velocity. Within-group analysis of children with BS-CP showed that the swing phase did not change after the walk pace and after the walk-trot pace. The percentage of rolling phase and double support improved after the walk-trot. The spasticity of the hip adductors was significantly reduced as an immediate result of both protocols, but this decrease was more evident after the walk-trot. The walk-trot protocol is feasible and is able to induce an immediate effect that improves the gait spatio-temporal parameters and the hip adductors spasticity.
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PMID:Different horse's paces during hippotherapy on spatio-temporal parameters of gait in children with bilateral spastic cerebral palsy: A feasibility study. 2751 20

Individuals with cerebral palsy (CP) usually suffer from different impairments including gait impairment and spasticity. Spastic hypertonia is a defining feature of spasticity and manifests as a mechanical abnormality. The objective of this study was to determine the relationship between spastic hypertonia and gait impairments in spastic children with CP, addressing an important controversial issue. Spastic hypertonia was quantified using the pendulum test. The gait impairments were evaluated using the motion capture system in a gait laboratory. Our results showed significant correlations among gait parameters; i.e. walking speed, step length, and the pendulum test measures. This indicates that neuromuscular abnormalities are associated with spasticity and may contribute to gait impairments. The clinical implication is that the impaired gait in children with CP may be improved with the treatment of neuromuscular abnormalities.
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PMID:Pendulum test measure correlates with gait parameters in children with cerebral palsy. 2826 56

The following papers by Richard Lieber (Skeletal Muscle as an Actuator), Thomas Roberts (Elastic Mechanisms and Muscle Function), Silvia Blemker (Skeletal Muscle has a Mind of its Own: a Computational Framework to Model the Complex Process of Muscle Adaptation) and Sabrina Lee (Muscle Properties of Spastic Muscle (Stroke and CP) are summaries of their representative contributions for the session on skeletal muscle mechanics, energetics and plasticity at the 2016 Biomechanics and Neural Control of Movement Conference (BANCOM 2016). Dr. Lieber revisits the topic of sarcomere length as a fundamental property of skeletal muscle contraction. Specifically, problems associated with sarcomere length non-uniformity and the role of sarcomerogenesis in diseases such as cerebral palsy are critically discussed. Dr. Roberts then makes us aware of the (often neglected) role of the passive tissues in muscles and discusses the properties of parallel elasticity and series elasticity, and their role in muscle function. Specifically, he identifies the merits of analyzing muscle deformations in three dimensions (rather than just two), because of the potential decoupling of the parallel elastic element length from the contractile element length, and reviews the associated implications for the architectural gear ratio of skeletal muscle contraction. Dr. Blemker then tackles muscle adaptation using a novel way of looking at adaptive processes and what might drive adaptation. She argues that cells do not have pre-programmed behaviors that are controlled by the nervous system. Rather, the adaptive responses of muscle fibers are determined by sub-cellular signaling pathways that are affected by mechanical and biochemical stimuli; an exciting framework with lots of potential. Finally, Dr. Lee takes on the challenging task of determining human muscle properties in vivo. She identifies the dilemma of how we can demonstrate the effectiveness of a treatment, specifically in cases of muscle spasticity following stroke or in children with cerebral palsy. She then discusses the merits of ultrasound based elastography, and the clinical possibilities this technique might hold. Overall, we are treated to a vast array of basic and clinical problems in skeletal muscle mechanics and physiology, with some solutions, and many suggestions for future research.
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PMID:Skeletal muscle mechanics, energetics and plasticity. 2905 12

In this review, we will work around two simple definitions of two different entities, which most often co-exist in patients with lesions to central motor pathways: Spasticity is "Enhanced excitability of velocity-dependent responses to phasic stretch at rest", which will not be the subject of this review, while Spastic dystonia is tonic, chronic, involuntary muscle contraction in the absence of any stretch or any voluntary command (Gracies, 2005). Spastic dystonia is a much less well understood entity that will be the subject this review. Denny-Brown (1966) observed involuntary sustained muscle activity in monkeys with lesions restricted to the motor cortices . He further observed that such involuntary muscle activity persisted following abolition of sensory input to the spinal cord and concluded that a central mechanism rather than exaggerated stretch reflex activity had to be involved. He coined the term spastic dystonia to describe this involuntary tonic activity in the context of otherwise exaggerated stretch reflexes. Sustained involuntary muscle activity in the absence of any stretch or any voluntary command contributes to burdensome and disabling body deformities in patients with spastic paresis. Yet, little has been done since Denny-Brown's studies to determine the pathophysiology of this non- stretch or effort related sustained involuntary muscle activity following motor lesions and there is a clear need for research studies in order to improve current therapy. The purpose of the present review is to discuss some of the possible mechanisms that may be involved in the hope that this may guide future research. We discuss the existence of persistent inward currents in spinal motoneurones and present the evidence that the channels involved may be upregulated following central motor lesions. We also discuss a possible contribution from alterations in synaptic inputs from surviving or abnormally branched sensory and descending fibres leading to over-activity and lack of motor coordination. We finally discuss evidence of alterations in motor cortical representational maps and basal ganglia lesions.
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PMID:On Denny-Brown's 'spastic dystonia' - What is it and what causes it? 2916 22

Aberrant vestibular nuclear function is proposed to be a principle driver of limb muscle spasticity after stroke. We sought to determine whether altered cortical modulation of descending vestibulospinal pathways post-stroke could impact the excitability of biceps brachii motoneurons. Twelve chronic hemispheric stroke survivors aged 46-68 years were enrolled. Sound evoked biceps myogenic potentials (SEBMPs) were recorded from the spastic and contralateral biceps muscles using surface EMG electrodes. We assessed the impact of descending vestibulospinal pathways on biceps muscle activity and evaluated the relationship between vestibular function and the severity of spasticity. Spastic SEBMP responses were recorded in 11/12 subjects. Almost 60% of stroke subjects showed evoked responses solely on the spastic side. These data strongly support the idea that vestibular drive is asymmetrically distributed to biceps motoneuron pools in hemiparetic spastic stroke survivors. This abnormal vestibular drive is very likely to be a factor mediating the striking differences in motoneuron excitability between the clinically affected and clinically spared sides. This study extends our previous observations on vestibular nuclear changes following hemispheric stroke and potentially sheds light on the underlying mechanisms of post-stroke spasticity.
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PMID:Sound-Evoked Biceps Myogenic Potentials Reflect Asymmetric Vestibular Drive to Spastic Muscles in Chronic Hemiparetic Stroke Survivors. 2917 45


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