Human recombinant hyaluronidase injections for upper limb muscle stiffness in individuals with cerebral injury: A case series

Raghavan, Preeti; Lu, Ying; Mirchandani, Mona; Stecco, Antonio

doi:10.1016/j.jbmt.2018.09.049

Cited by 6 publications

(12 citation statements)

References 47 publications

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“…The observation of increased corneal stromal stiffness following HAse injection in normal rabbit contrasts with a recent clinical study whereby injection of HAse reduced the stiffness of muscle tissue in patients with upper limb spasticity. 29 Muscle stiffness in spasticity is defined by resistance of muscle to passive movement and is a disorder in individuals affected by neurologic injury of cerebral and spinal origin. 29 Furthermore, our data also call into question the widely held belief that HAse softens tissues to reduce scarring and increases drug penetration.…”

Section: Discussionmentioning

confidence: 99%

“…29 Muscle stiffness in spasticity is defined by resistance of muscle to passive movement and is a disorder in individuals affected by neurologic injury of cerebral and spinal origin. 29 Furthermore, our data also call into question the widely held belief that HAse softens tissues to reduce scarring and increases drug penetration. 15,16,30 These observations suggest that the function of HAse may be tissue and disease specific as well as dependent on the endogenous amount of HA and other GAG substrates expressed in the tissue.…”

Section: Discussionmentioning

confidence: 99%

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Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma

Kim

Jalilian

Thomasy

et al. 2020

Trans. Vis. Sci. Tech.

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Glycosaminoglycans (GAGs) are important components of the corneal stroma, and their spatiotemporal arrangement regulates the organization of collagen fibrils and maintains corneal transparency. This study was undertaken to determine the consequences of hyaluronidase (HAse) injected into the corneal stroma on stromal stiffness and ultrastructure. Methods: Equal volumes of HAse or balanced salt solution (vehicle) were injected intrastromally into the corneas of New Zealand white rabbits. Ophthalmic examination and multimodal imaging techniques, including Fourier-domain optical coherence tomography and in vivo confocal microscopy (IVCM), were performed at multiple time points to evaluate the impact of HAse treatment in vivo. Atomic force microscopy and transmission electron microscopy (TEM) were used to measure corneal stiffness and collagen's interfibrillar spacing, respectively. Results: Central corneal thickness progressively decreased after HAse injection, reaching its lowest value at day 7, and then returned to normal by day 42. The HAse did not impact the corneal endothelium but transiently altered keratocyte morphology at days 1 and 7, as measured by IVCM. HAse-injected corneas became stiffer by day 1 postinjection, were stiffest at day 7, and returned to preinjection values by day 90. Changes in stromal stiffness correlated with decreased interfibrillar spacing as measured by TEM. Conclusions: Degradation of GAGs by HAse decreases the corneal thickness and increases stromal stiffness through increased packing of the collagen fibrils in a timedependent manner. Translational Relevance: Intrastromal HAse injection appears relatively safe in the normal cornea, but its impact on corneal biomechanics and structure under pathologic conditions requires further study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma

Kim

Jalilian

Thomasy

et al. 2020

Trans. Vis. Sci. Tech.

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“…Subjects with stroke were assessed on clinical metrics which included measurement of upper limb motor impairment using the Fugl-Meyer Scale (FMS), 22 strength testing using the Manual Muscle Test (MMT), 23 active range of motion (AROM) measured by video motion analysis using Dartfish, 24-26 and muscle stiffness or the resistance to passive joint movement measured using the Modified Ashworth Scale (MAS). 27…”

Section: Methodsmentioning

confidence: 99%

The Role of Robotic Path Assistance and Weight Support in Facilitating 3D Movements in Individuals With Poststroke Hemiparesis

Raghavan

Bilaloglu

Ali

et al. 2020

Neurorehabil Neural Repair

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Background. High-intensity repetitive training is challenging to provide poststroke. Robotic approaches can facilitate such training by unweighting the limb and/or by improving trajectory control, but the extent to which these types of assistance are necessary is not known. Objective. The purpose of this study was to examine the extent to which robotic path assistance and/or weight support facilitate repetitive 3D movements in high functioning and low functioning subjects with poststroke arm motor impairment relative to healthy controls. Methods. Seven healthy controls and 18 subjects with chronic poststroke right-sided hemiparesis performed 300 repetitions of a 3D circle-drawing task using a 3D Cable-driven Arm Exoskeleton (CAREX) robot. Subjects performed 100 repetitions each with path assistance alone, weight support alone, and path assistance plus weight support in a random order over a single session. Kinematic data from the task were used to compute the normalized error and speed as well as the speed-error relationship. Results. Low functioning stroke subjects (Fugl-Meyer Scale score = 16.6 ± 6.5) showed the lowest error with path assistance plus weight support, whereas high functioning stroke subjects (Fugl-Meyer Scale score = 59.6 ± 6.8) moved faster with path assistance alone. When both speed and error were considered together, low functioning subjects significantly reduced their error and increased their speed but showed no difference across the robotic conditions. Conclusions. Robotic assistance can facilitate repetitive task performance in individuals with severe arm motor impairment, but path assistance provides little advantage over weight support alone. Future studies focusing on antigravity arm movement control are warranted poststroke.

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“…Studies in animal models of contracture have provided evidence that hyaluronan accumulation in the ECM may alter the viscoelastic properties of muscle, contributing to contracture . Results were presented from a preliminary study of treatment with intramuscular hyaluronidase, an enzyme that degrades ECM hyaluronan in patients with upper limb muscle stiffness and spasticity after cerebral injury who were at risk of developing contractures. In this study, researchers demonstrated reduced muscle stiffness and increased passive and active joint movement, which persisted 3 to 5 months after treatment.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Conference report on contractures in musculoskeletal and neurological conditions

et al. 2020

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Limb contractures are debilitating complications associated with various muscle and nervous system disorders. This report summarizes presentations at a conference at the Shirley Ryan AbilityLab in Chicago, Illinois, on April 19-20, 2018, involving researchers and physicians from diverse disciplines who convened to discuss current clinical and preclinical understanding of contractures in Duchenne muscular dystrophy, stroke, cerebral palsy, and other conditions. Presenters described changes in muscle architecture, activation, extracellular matrix, satellite cells, and muscle fiber sarcomeric structure that accompany or predispose muscles to contracture. Participants identified ongoing and future research directions that may lead to understanding of the intersecting factors that trigger contractures. These include additional studies of changes in muscle, tendon, joint, and neuronal tissues during contracture development with imaging, molecular, and physiologic approaches. Participants identified the requirement for

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Human recombinant hyaluronidase injections for upper limb muscle stiffness in individuals with cerebral injury: A case series

Cited by 6 publications

References 47 publications

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma

The Role of Robotic Path Assistance and Weight Support in Facilitating 3D Movements in Individuals With Poststroke Hemiparesis

Conference report on contractures in musculoskeletal and neurological conditions

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