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Stecco, Antonio (2016) Ialuronidasi per la rigidità muscolare nella spasticità Hyaluronidase for muscle stiffness in spasticity. [Tesi di dottorato]

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Abstract (inglese)

Background: Spasticity is a common neurological impairment after injury to the central nervous system, but the neural and biomechanical contributions to it are still poorly understood. Histopathological studies have demonstrated a generalized increase in extracellular connective tissue in spastic muscles, which can decrease its compliance, and reduce the threshold for stimulation of the spindle receptors. Here we propose and provide preliminary evidence for a novel hypothesis for exacerbation of spasticity in an immobilized limb - the hyaluronan hypothesis. We hypothesize that the extracellular connective tissue, which is composed chiefly of hyaluronan, becomes hyper-viscous and stiff in an immobilized limb due to its non-Newtonian properties.
Methods: In this case series, we assessed the safety, tolerability, and efficacy of human recombinant hyaluronidase, which hydrolyzes hyaluronan, in combination with saline in restoring tissue compliance. Twenty-one individuals, with moderate-severe upper limb spasticity affecting more than one joint, received multiple intramuscular injections of hyaluronidase-saline. Adverse effects were monitored over 15 weeks. The Modified Ashworth Scale (MAS) assessed reduction in spasticity while active and passive range of motion was assessed using quantitative video analysis of upper limb movement.
Findings: 21 participants were included. The procedure was well tolerated. Extensive safety monitoring in all patients revealed no clinically significant adverse events at 15 weeks. Treatment seemed to be effective at reducing spasticity in all twenty-one participants who received the injections (p<0.05 in 16 evaluation over 24 in passive ROM and 17 over 24 in active ROM). The measures of motor function (MAS) showed still improvement at 15 months (p=.000).
Interpretations: Subcutaneous administration of hyaluronidase-saline in a multiple sites was fairly safe and well tolerated in adult patients with spasticity; however, these results must be viewed as preliminary until data from blinded, controlled clinical trials are available.

Abstract (italiano)

Introduzione: La spasticità è un danno neurologico comune conseguente ad una lesione al sistema nervoso centrale, ma i contributi neurali e biomeccanici ad esso correlati sono ancora poco conosciuta. Studi istopatologici hanno dimostrato un aumento generalizzato nel tessuto connettivo extracellulare nei muscoli spastici, che può diminuire la sua funzionalità e ridurre la soglia per la stimolazione dei fusi neuromuscolari. Con questo lavoro proponiamo e forniamo le prove preliminari per una nuova ipotesi per l'esacerbazione della spasticità in un arto immobilizzato: l'ipotesi ialuronato. Si Ipotizza che il tessuto connettivo extracellulare, che è composto principalmente da ialuronato, diventi iper-viscoso e rigido in un arto immobilizzato grazie alle sue proprietà non-Newtoniane.
Metodi: In questo case series, è stata valutata la sicurezza, tollerabilità e efficacia della ialuronidasi ricombinante umana, che idrolizza lo ialuronato, in combinazione con una soluzione salina per ripristinare la funzionalità dei tessuti. Ventuno persone fisiche, con moderata-grave spasticità degli arti superiori in più di una articolazione, hanno ricevuto multiple iniezioni intramuscolari di ialuronidasi-salina. Gli effetti avversi sono stati monitorati per 15 settimane. La Modified Ashworth Scale (MAS) ha valutato la riduzione della spasticità mentre la l’escursione articolare di movimento attiva e passiva è stata valutata mediante analisi quantitativa del movimento dell'arto (ROM) superiore tramite video.
Risultati: 21 partecipanti sono stati inclusi. La procedura è stata ben tollerata. Il monitoraggio estensivo sulla sicurezza dei pazienti non ha rivelato eventi avversi clinicamente significativi a 15 settimane. Il trattamento è risultato efficace nel ridurre la spasticità in tutti i ventuno partecipanti che hanno ricevuto le iniezioni (p <0.05 di 16 valutazione su 24 nella ROM passivo e 17 su 24 nel ROM attivo). Le misure di funzione motoria (MAS) hanno mostrato un mantenimento del miglioramento a 15 mesi (p = 0,000).
Conclusioni: La somministrazione di ialuronidasi-salina in più siti è risultata sicura e ben tollerata in pazienti adulti con spasticità; tuttavia, questi risultati devono essere visti come preliminari fino a quando ulteriori studi clinici controllati in cieco non saranno disponibili.

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Tipo di EPrint:Tesi di dottorato
Relatore:Zaccaria, Marco - Ermolao, Andrea
Dottorato (corsi e scuole):Ciclo 28 > Scuole 28 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > SCIENZE GERIATRICHE ED EMATOLOGICHE E FISIOPATOLOGIA CLINICA
Data di deposito della tesi:07 Gennaio 2016
Anno di Pubblicazione:06 Gennaio 2016
Informazioni aggiuntive:The research was performed in collaboration with Prof Preeti Raghavan: Director of Motor Recovery Lab, New York University Langone Medical Center We thanks the Hospital for Joint Disease for the collaboration
Parole chiave (italiano / inglese):Hyaluronidase; muscle stiffness; spasticity; fascia
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/09 Medicina interna
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:9017
Depositato il:06 Ott 2016 17:52
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