Analysis of the presence of the hyaluronic acid inside the deep fasciae and in the muscles

Recent works have demonstrated that the deep fascia is a multilayer structure, formed by different layers of collagen fibers and loose connective tissue (LCT). The aim of this work was to study the layers of LCT inside the deep fasciae, and in particular to evaluate the presence of Hyaluronic acid (HA). Three fresh not embalmed cadavers were studied. Samples of the deep fascia together with the underlying muscles were taken from the neck over the SCOM, from the abdomen over the rectus muscle and from the thigh over the sartorius muscle. Samples were stained with hematoxylin-eosin, azan-Mallory, Alcian blue and a biotinylated HA-binding protein that has high specificity for HA. At the microscopic evaluation, the deep fascia was formed of two or three layers of parallel collagen fibre bundles, densely packaged. Each collagen layer presented a mean thickness (± SD) of 277.6 ± 86.1 µm. Between the different layers, a thin layer of loose connective tissue could be recognized, having mean thickness 43 ± 12 µm. Staining with the Alcian Blue and with the highly specific HA-binding peptide documented a layer of hyaluronan between fascia and muscle and inside deep fascia, in particular inside the loose connective tissue separating the fibrous sub-layer of the fascia. In some samples, some fibroblast-like cells that stained very well at the Alcian Blue stain were observed. It was postulated that these were specialized cells for the biosynthesis of the HA-rich matrix, that we’ll call “fasciacyte”. This means that the fascia thus provides an extracellular matrix that is a gliding lubricant over muscle, permitting the free contraction of muscles, but also a unique matrix for its repair and regeneration. Besides, the HA inside the deep fascia facilitates the free sliding of two adjacent fibrous fascial layers, guaranteed the normal functionality of the deep fascia. If the HA assumes a more packed conformation, or more generally if the loose connective tissue inside the fascia alters its density, the behavior of the whole deep fascia and of the underlying muscle could be compromised. This could be at the origin of many myofascial pains

The possible use of ultrasonography for the diagnosis of myofascial neck pain

A definitive diagnosis of chronic neck pain (CNP) is sometimes not possible. The aim of this study was to understand the possible role of the deep fasciae in CNP and the utility of the ultrasonography in the diagnosis of myofascial neck pain. The morphometric and clinical data of 25 healthy subjects and 28 patients with CNP were compared. For all subjects, the active and passive cervical Range Of Motion (ROM) was analysed and the Neck Pain Disability Questionnaire (NDPQ) was administered. The fascial thickness of the sternal ending of the sternocleidomastoid and medial scalene muscles was also analysed by ultrasonography. There were significant differences between healthy subjects in the thickness of the upper side of the sternocleidomastoid fascia and the lower and upper sides of the right scalene fascia. Analysis of the thickness of the sub-layers showed a significant increase of the loose connective tissue inside the fascia, rather than of the fibrous sublayers. The data support the hypothesis that the loose connective tissue inside the fasciae plays a significant role in the pathogenesis of CNP. In particular, the value of 0.15 cm of the SCM fascia was considered as a cut-off value which allows the clinician to make a diagnosis of myofascial disease in a subject with CNP. The variation of thickness of the fascia correlated with the increase in quantity of the loose connective tissue but not with dense connective tissue, and probably more specifically with hyaluronan

Fascial Manipulation® for chronic aspecific low back pain: a single blinded randomized controlled trial [version 2; referees: 2 approved]

Background: The therapeutic approach to chronic aspecific low back pain (CALBP) has to consider the multifactorial aetiology of the disorder. International guidelines do not agree on unequivocal treatment indications. Recommendations for fascial therapy are few and of low level evidence but several studies indicate strong correlations between fascial thickness and low back pain. This study aims at comparing the effectiveness of Fascial Manipulation® associated with a physiotherapy program following guidelines for CALBP compared to a physiotherapy program alone. Methods: 24 subjects were randomized into two groups, both received eight treatments over 4 weeks. Outcomes were measured at baseline, at the end of therapy and at a 1 month and a 3 months follow-up. Pain was measured with the visual analogue scale (VAS) and the brief pain inventory (BPI), function with the Rolland-Morris disability questionnaire (RMDQ), state of well-being with the short-form 36 health-survey (SF-36). The mean clinical important difference (MCID) was also measured. Results: Patients receiving Fascial Manipulation® showed statistically and clinically significant improvements at the end of care for all outcomes, in the short (RMDQ, VAS, BPI) and medium term for VAS and BPI compared to manual therapy. The MCID show significant improvements in the means and percentage of subjects in groups in all outcomes post-treatment, in the short and medium term. Conclusion: Fascial tissues were implicated in the aetiology of CALBP and treatment led to decreased symptomatic, improved functional and perceived well-being outcomes that were of greater amplitude compared to manual therapy alone

Human neural stem cell transplantation in ALS: initial results from a phase I trial

We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanit\ue0 and the competent Ethics Committees and was monitored by an external Safety Board

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Ultrasound imaging and Fascial Manipulation® for rigid retinacula in two cases of complex regional pain syndrome

: Complex regional Pain Syndrome (CRPS) is a complex disease with articulate impact on the quality of life and its management is challenging. Ultrasound imaging can identify/assess different musculoskeletal structures that might have role in its pathogenesis. We present two cases of CRSP in whom B-mode ultrasonography and sonoelastography showed rigid retinacula associated with the symptomatology. Both patients were also/successfully treated with Fascial Manipulation®

Ialuronidasi per la rigidità muscolare nella spasticità Hyaluronidase for muscle stiffness in spasticity

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.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

Ialuronidasi per la rigidità muscolare nella spasticità Hyaluronidase for muscle stiffness in spasticity

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.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

Poster 258: A New Treatment for the Ankle Sprain Outcomes

Objective: The authors want to evaluate if specific alterations of ankle retinacula can be evidenced in patients with functional ankle instability (3 months) and if treatment focused on the fascia could restore normal function to the retinacula. Design: An in vivo radiologic study by MRI was performed on 20 patients to evaluate possible damage to the ankle retinacula. Setting: In those subjects (11 cases) with an evident alteration of at least one of the retinacula, static posturography was quantitatively measured and painful symptoms were recorded using a specific questionnaire. Interventions: These subjects were treated by the same practitioner, according to the methodology of Fascial Manipulation for 3 treatment sessions. Main Outcome Measures: Evaluation with static posturography and the questionnaire was repeated after treatment and at the 1, 3, 6 months. Results:: By MRI, the retinacula were clearly visible and easily evaluated. They appeared as low signal intensity bands with a mean thickness of 1 mm. In all patients, 4 types of retinacular alterations were identified. After treatment, a mean pain reduction of 32.2% was recorded (mean value of VAS prior: 41/100; after 3: 8.8/100), together with a good recovery of movement. The initial benefit was generally maintained (mean value of VAS: 13/100) at a short-term follow-up. Static posturography showed a significant difference (P.05) in sway path between the first and the last evaluation: initial mean sway path (msp) was 7.9 mm/sec and final msp was 6.9 mm/sec, coinciding with patients\u2019 reports of an improved sense of balance. Conclusions: Retinacula could be seen as a specialization of the fascia for local, spatial proprioception of foot and ankle movements. Their damage, during ankle sprains, could modify the lines of forces within the fascia of the foot and leg, altering the role of the fascial system in peripheral control of articular motility. Restoring normal tension to the fascia could improve proprioceptive activity of receptors