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ADRIANO FERRARI

Docente a contratto
Dipartimento Chirurgico,Medico,Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa - Sede Arcispedale Santa Maria Nuova

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Pubblicazioni

2021 - Can a pathological model improve the abilities of the paretic hand in hemiplegic children? the PAM-AOT study protocol of a randomised controlled trial [Articolo su rivista]
Verzelloni, J.; Errante, A.; Beccani, L.; Filippi, M.; Bressi, B.; Cavuto, S.; Ziccarelli, S.; Bozzetti, F.; Costi, S.; Pineschi, E.; Fogassi, L.; Ferrari, A.
abstract

Introduction Action Observation Treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by subsequent repetition. In children with unilateral cerebral palsy (UCP), it improves upper limb function in daily activities. The standard paradigm of AOT requires the observation of healthy models; however, it has been demonstrated that the mirror neuron system of children with UCP is more activated by observation of pathological models, showing a similar motor repertoire, than by the healthy model, suggesting that AOT based on pathological models is superior to the standard paradigm of AOT in the functional rehabilitation of the affected upper limb of children with UCP. Methods and analysis This protocol describes an active two-arm randomised controlled evaluator-blinded trial. Twenty-six children with UCP will participate in 3 weeks of intensive AOT: the experimental group will observe a pathological model, while the control group will observe a typically developed model. The primary outcome is the spontaneous use of the paretic hand, measured with the Assisting Hand Assessment. Secondary outcome measures are the Melbourne Assessment of Unilateral Upper Limb Function, the ABILHAND-Kids and the Activities Scale for Kids-performance. Assessments will be performed at baseline (T0), at the end of intensive AOT (T1), at 8-12 weeks (T2) and at 24-28 weeks (T3) after the end of intensive AOT. Ethics and dissemination The trial was approved by the Area Vasta Emilia Nord Ethics Committee (AVEN prot. n. 133117, 29 November 2018), and it was prospectively registered on ClinicalTrials.gov. The results will be submitted for publication to a peer-reviewed journal, discussed with parents of children participating in the trial and disseminated at suitable conferences. Trial registration number NCT04088994; Pre-results.

2020 - Are perceptual disorder signs in diplegic cerebral palsied children stable over time? A retrospective cohort analysis [Articolo su rivista]
Alboresi, Silvia; Sghedoni, Alice; Borelli, Giulia; Costi, Stefania; Beccani, Laura; Neviani, Rita; Ferrari, Adriano
abstract

A group of diplegic cerebral palsied (CP) children presents six precise signs that can be easily observed during clinical examinations, physiotherapy sessions and everyday activities. These signs are: startle reaction, upper limbs in startle position, averted-eye gaze, grimaces, eye blinking and posture freezing.

2020 - Assessment of Physical Function in Children with Cerebral Palsy: Convergent Validity between the Gross Motor Function Measure and the Activities Scale for Kids [Poster]
Costi, S; Alboresi, S; Mecugni, D; Ferrari, A; Boggiani, E; Bressi, B; Paltrinieri, S
abstract

Physical function is crucial to participation in life activities and must always be accurately assessed in children with cerebral palsy (CP)1. The Activities Scale for Kids performance (ASKp) is currently used for this purpose, but its psychometric properties have not yet been completely verified in children with CP2, the principal cause of disability in industrialized countries3. Recently, the reliability of the Italian version of the scale was confirmed in this population and initial proof of validity was collected. However, there is no gold standard that can serve as a criterion. We verified the ASKp convergent validity with respect to the Gross Motor Function Measure-66 (GMFM-66), the gold standard in the assessment of gross motor abilities in this population

2020 - Cross-cultural validation of Activities Scale for Kids: the performance of healthy Italian children [Articolo su rivista]
Costi, S.; Bressi, B.; Cavuto, S.; Braglia, L.; Ferrari, A.; Pelosin, E.
abstract

BACKGROUND: The assessment of physical performance is a key element in the rehabilitation of individuals with disabilities, and understanding patients' perception of their abilities is of foremost importance for the success of the whole process. The Activities Scale for Kids performance (ASKp) is one of the few reliable and responsive outcome measures that allows children and adolescents to accurately report their physical functioning in typical activities for this age. The performance version of the ASKp has recently been translated and culturally adapted to the Italian context. METHODS: This cross-sectional study was implemented to describe the ASKp score distribution in a population of Italian school aged individuals. RESULTS: A population of 209 Italian children with a mean age of 10.96 years (SD 2.92, range 5-15) participated in this study during the academic year 2017/18. The ASKp score ranged from 52.58 to 100, with a mean value of 89.07 points (SD 10.57). Scores greater than 90 were attained for 57.4% of participants, confirming the ceiling effect of this assessment tool when administered in healthy children (95% CI: 50.4-64.2%). The ASKp was able to differentiate between different levels of physical performance according to different developmental ages (P<0.001), and it confirmed the ability to distinguish between children with typical development and those with disability (P<0.001). CONCLUSIONS: The results of this study provide the first evidence of construct validity of the Italian version of the ASKp. These results will help clinicians to interpret ASKp scores of children with musculoskeletal limitations.

2019 - Evaluation of hand function in patients with unilateral cerebral palsy who underwent multilevel functional surgery: a retrospective observational study [Articolo su rivista]
Cristella, Giovanna; Filippi, Maria C; Mori, Maurizio; Alboresi, Silvia; Ferrari, Adriano
abstract

Hemiplegia is the most common form of Cerebral Palsy. Upper Limb is generally more affected than lower one. In fact, hemiplegic children can spontaneously acquire standing and walking ability, while manipulation remains uncertain, with severe limitations in activity and participation, which define child's functional status (International Classification of Functioning - ICF). Several non-surgical tools are currently available to approach upper limb impairments. Studies regarding upper limb multilevel surgery in Hemiplegic Cerebral Palsy are relatively few and inhomogeneous.

2019 - Explicit Motor Imagery for Grasping Actions in Children With Spastic Unilateral Cerebral Palsy [Articolo su rivista]
Errante, Antonino; Bozzetti, Francesca; Sghedoni, Silvia; Bressi, Barbara; Costi, Stefania; Crisi, Girolamo; Ferrari, Adriano; Fogassi, Leonardo
abstract

Background: Motor Imagery (MI) refers to mental simulation of a motor action without producing any overt movement. Previous studies showed that children with Unilateral Cerebral Palsy (UCP) are impaired in implicit MI, as demonstrated by the performance of Hand Laterality Judgment tasks. The aim of this study was to examine the specificity of explicit MI deficits in UCP children.Methods: A group of UCP children (n = 10; aged 9-14) performed a mental chronometry task consisting in grasping an object and placing it into a container, or in imagining to perform the same action. As control, a group of typically developing (TD) children, matched by age, performed the same task. Movement durations for executed and imagined trials were recorded. A subgroup of 7 UCP children and 10 TD children also underwent a session of functional MRI to examine the activation of parieto-frontal areas typically associated to MI processes, during the imagination of reaching-grasping actions performed with the paretic hand.Results: Behavioral results revealed the existence of a correlation between executed and imaginedmovement durations both in TD and UCP groups. Moreover, the regression analysis in TD children showed that higher scores in mental chronometry tasks were positively correlated to increased bilateral activation of the intraparietal sulcus (IPS), superior parietal lobule (SPL), and dorsal premotor (PMd) cortex. A similar analysis revealed in the UCP group a positive correlation between a higher score in the mental chronometry task and bilateral activations of IPS, and to activation of contralesional, right PMd, and putamen during imagination of grasping movements.Conclusions: These results provide new insights on the relationship between MI capacity and motor deficits in UCP children, suggesting the possibility of the use of explicit MI training to improve patient's upper limb motor functions.

2019 - From movement to action: A new framework for cerebral palsy [Articolo su rivista]
Ferrari, A.
abstract

The interpretation of cerebral palsy (CP) is closely linked to points of view that are no longer acceptable: 1) the idea that it is primarily a motor problem (posture and movement disorder); 2) the idea that it is only a central (cerebral) pathology; 3) the idea that it is a non-progressive disease (fixed encephalopathy). Actually, the problems that contribute to producing the CP clinical picture are several and complex. First of all, building of the action, starting from subject motivation, through motor imagery and subsequent project elaboration. Sequentially, executive planning, disorder often hidden under the most remarkable alteration of motor patterns and muscle tone. finally, realization, conditioned by the idea that the locomotor apparatus is only and always the victim of an incapable central nervous system. little known and very neglected perceptive components can contribute to compromising subject motor control. The influences that primitive changes of musculoskeletal system, often depending on site, nature, size and time of the lesion, exert on the possible choices of the central nervous system are often overlooked. Peripheral structures can in fact modify considerably the expression of palsy (understood as the form of adaptive functions) primitively. At least six different sources of error can be identified in the cerebral palsied child. For a rehabilitative intervention with greater possibilities of effectiveness, it is necessary to recognize and evaluate each of them. Especially as regards the prevention of secondary deformities, the responsibility attributed to physiotherapy must be re-evaluated.

2019 - Gait-Based Diplegia Classification Using LSMT Networks [Articolo su rivista]
Ferrari, Alberto; Bergamini, Luca; Guerzoni, Giorgio; Calderara, Simone; Bicocchi, Nicola; Vitetta, Giorgio; Borghi, Corrado; Neviani, Rita; Ferrari, Adriano
abstract

Diplegia is a specific subcategory of the wide spectrum of motion disorders gathered under the name of cerebral palsy. Recent works proposed to use gait analysis for diplegia classification paving the way for automated analysis. A clinically established gait-based classification system divides diplegic patients into 4 main forms, each one associated with a peculiar walking pattern. In this work, we apply two different deep learning techniques, namely, multilayer perceptron and recurrent neural networks, to automatically classify children into the 4 clinical forms. For the analysis, we used a dataset comprising gait data of 174 patients collected by means of an optoelectronic system. The measurements describing walking patterns have been processed to extract 27 angular parameters and then used to train both kinds of neural networks. Classification results are comparable with those provided by experts in 3 out of 4 forms.

2019 - Mirror Neuron System Activation in Children With Unilateral Cerebral Palsy During Observation of Actions Performed by a Pathological Model [Articolo su rivista]
Errante, Antonino; Di Cesare, Giuseppe; Pinardi, Chiara; Fasano, Fabrizio; Sghedoni, Silvia; Costi, Stefania; Ferrari, Adriano; Fogassi, Leonardo
abstract

Recent evidence suggested that Action Observation Therapy (AOT), based on observation of actions followed by immediate reproduction, could be a useful rehabilitative strategy for promoting functional recovery of children affected by unilateral cerebral palsy (UCP). AOT most likely exploits properties of the parieto-premotor mirror neuron system (MNS). This is more intensely activated when participants observe actions belonging to their own motor repertoire.

2019 - Spinal bracing and lung function in type-2 spinal muscular atrophy [Articolo su rivista]
Di Pede, Chiara; Salamon, Eleonora; Motta, Matteo; Agosto, Caterina; Benini, Franca; Ferrari, Adriano
abstract

Respiratory muscle weakness associated with scoliosis in type-2 spinal muscular atrophy (SMA) leads to respiratory impairment. Spinal brace, generally utilized to slow scoliosis progression and support sitting, could worsen lung function and hamper cough maneuvers.

2018 - A proposito di percezione [Capitolo/Saggio]
Ferrari, Adriano
abstract

148 pagine 13x20 cm 15,00 € acquista €15,00 Quant.: Ambrogio Cozzi, Franco Lolli L’umano fuori asse La disabilità intellettiva nella teoria e nella pratica psicoanalitica Per quanto si cerchi spesso di inquadrarlo in una logica di tipo meramente funzionale, l’handicap psichico o mentale, soprattutto quello grave, non può fare a meno di rivelarsi allo sguardo e alla sensibilità di chi vi si accosta come una ferita profonda, insanabile, al cuore stesso dell’essere del singolo individuo. La donna e l’uomo che, come si usa dire, sono portatori di un handicap appaiono schiacciati da un fardello troppo gravoso da sostenere senza che la soggettività ne sia fortemente compromessa e invalidata. […] Affrontare la questione della disabilità intellettiva orientati da una riflessione psicoanalitica vuol dire porsi un interrogativo fondamentale – generalmente eluso – sull’esistenza dell’inconscio (o, per essere più precisi, sulle forme particolari che esso può assumere) in persone che sono, in maniera più o meno grave, compromesse dal punto di vista intellettivo e cognitivo. […] La disabilità intellettiva ci obbliga a fare i conti con una condizione dell’umano che è, assai spesso, ritenuta ai limiti dell’umanità stessa: includere queste esistenze speciali e bizzarre nel registro dell’umano è il nostro compito. Humana materia è il titolo che abbiamo voluto attribuire a questa collana proprio per ribadire che, per quanto gravi le condizioni del disabile intellettivo possano essere (o apparire), è di materia umana che egli è fatto, di materia significante, di materia sensibile alla parola, di materia plasmata dal linguaggio.

2018 - Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration [Articolo su rivista]
Carnevale, Gianluca; Pisciotta, Alessandra; Riccio, Massimo; Bertoni, Laura; DE BIASI, Sara; Gibellini, Lara; Zordani, Alessio; Cavallini, Gian Maria; LA SALA, Giovanni Battista; Bruzzesi, Giacomo; Ferrari, Adriano; Cossarizza, Andrea; DE POL, Anto
abstract

Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional defects. The application of stem cells able to differentiate in Schwann cell-like cells in vitro and in vivo, could represent an attractive therapeutic approach for the treatment of nerve injuries. Further, stem cells sources sharing the same embryological origin as Schwann cells might be considered a suitable tool. The aim of this study was to demonstrate the ability of a neuroectodermal subpopulation of human STRO-1(+) /c-Kit(+) /CD34(+) DPSCs, expressing P75(NTR) , nestin and SOX-10, to differentiate into Schwann cell-like cells in vitro and to promote axonal regeneration in vivo, which led to functional recovery as measured by sustained gait improvement, in animal rat model of peripheral nerve injury. Transplanted human dental pulp stem cells (hDPSCs) engrafted into sciatic nerve defect, as revealed by the positive staining against human nuclei, showed the expression of typical Schwann cells markers, S100b and, noteworthy, a significant number of myelinated axons was detected. Moreover, hDPSCs promoted axonal regeneration from proximal to distal stumps 1 month after transplantation. This study demonstrates that STRO-1(+) /c-Kit(+) /CD34(+) hDPSCs, associated with neural crest derivation, represent a promising source of stem cells for the treatment of demyelinating disorders and might provide a valid alternative tool for future clinical applications to achieve functional recovery after injury or peripheral neuropathies besides minimizing ethical issues. Copyright © 2016 John Wiley & Sons, Ltd.

2018 - Pharmacological differences and clinical implications of various botulinum toxin preparations: A critical appraisal [Articolo su rivista]
Ferrari, A.; Manca, M.; Tugnoli, V.; Pini, L. A.
abstract

Three different type A botulinum neurotoxins (BoNTAs) — onabotulinumtoxinA, abobotulinumtoxinA and incobotulinumtoxinA) — are currently marketed in Europe to treat several conditions. Differences between BoNTA preparations, which depend on their specific biotypes and manufacturing processes, lead to clinically relevant pharmacotherapeutic dissimilarities. All three available products are separately recognized and reviewed in American Academy of Neurology guidelines. The neurotoxin load/100U is likewise different among the different BoNTAs, with the result that the specific potency of the 150kD BoNTA neurotoxin is calculated as 137 units/ng for onabotulinumtoxinA, 154 units/ng for abobotulinumtoxinA, and 227 units/ng for incobotulinumtoxinA. It is important for clinicians to have all three BoNTAs available in order to choose the most suitable preparation for the specific indication in the single patient. Commercially available BoNTAs must be recognized as different from one another, and therefore as non-interchangeable. The essential experience of the clinician is of the utmost importance in choosing the most appropriate treatment.

2018 - Reorganization of the Action Observation Network and Sensory-Motor System in Children with Unilateral Cerebral Palsy: An fMRI Study [Articolo su rivista]
Sgandurra, Giuseppina; Biagi, Laura; Fogassi, Leonardo; Sicola, Elisa; Ferrari, Adriano; Guzzetta, Andrea; Tosetti, Michela; Cioni, Giovanni
abstract

Little is known about the action observation network (AON) in children with unilateral cerebral palsy (UCP). Using fMRI, we aimed to explore AON and sensory-motor network (SMN) in UCP children and compare them to typically developed (TD) children and analyse the relationship between AON (re-)organization and several neurophysiological and clinical measures. Twelve UCP children were assessed with clinical scales and transcranial magnetic stimulation (TMS). For the fMRI study, they underwent a paradigm based on observation of complex and simple object-manipulation tasks executed by dominant and nondominant hand. Moreover, UCP and TD children carried out a further fMRI session to explore SMN in both an active motor and passive sensory task. AON in the UCP group showed higher lateralization, negatively related to performances on clinical scales, and had greater activation of unaffected hemisphere as compared to the bilateral representation in the TD group. In addition, a good congruence was found between bilateral or contralateral activation of AON and activation of SMN and TMS data. These findings indicate that our paradigm might be useful in exploring AON and the response to therapy in UCP subjects.

2018 - Tele-UPCAT: Study protocol of a randomised controlled trial of a home-based Tele-monitored UPper limb Children Action observation Training for participants with unilateral cerebral palsy [Articolo su rivista]
Sgandurra, G.; Cecchi, F.; Beani, E.; Mannari, I.; Maselli, M.; Falotico, F. P.; Inguaggiato, E.; Perazza, S.; Sicola, E.; Feys, H.; Klingels, K.; Ferrari, A.; Dario, P.; Boyd, R. N.; Cioni, G.
abstract

Introduction A new rehabilitative approach, called UPper Limb Children Action Observation Training (UPCAT), based on the principles of action observation training (AOT), has provided promising results for upper limb rehabilitation in children with unilateral cerebral palsy (UCP). This study will investigate if a new information and communication technology platform, named Tele-UPCAT, is able to deliver AOT in a home setting and will test its efficacy on children and young people with UCP. Methods and analysis A randomised, allocation concealed (waitlist control) and evaluator-blinded clinical trial with two investigative arms will be carried out. The experimental group will perform AOT at home for 3 weeks using a customised Tele-UPCAT system where they will watch video sequences of goal-directed actions and then complete the motor training of the same actions. The control group will receive usual care for 3 weeks, which may include upper limb training. They will be offered AOT at home after 3 weeks. Twenty-four children with UCP will be recruited for 12 participants per group. The primary outcome will be measured using Assisting Hand Assessment. The Melbourne Assessment 2, ABILHAND, Participation and Environment Measure-Children and Youth and Cerebral Palsy Quality of Life Questionnaire will be included as secondary measures. Quantitative measures from sensorised objects and participants worn Actigraphs GXT3+ will be analysed. The assessment points will be the week before (T0) and after (T1) the period of AOT/standard care. Further assessments will be at T1 plus, the week after the AOT period for the waitlist group and at 8 weeks (T2) and 24 weeks (T3) after AOT training. Ethics and dissemination The trial has been approved by the Tuscany Paediatric Ethics Committee (169/2016). Publication of all outcomes will be in peer-reviewed journals and conference presentations. trial registration NCT03094455.

2018 - What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation [Articolo su rivista]
Castelnuovo, Gianluca; Giusti, Emanuele Maria; Manzoni, Gian Mauro; Saviola, Donatella; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Maria Spatola, Chiara Anna; Rossi, Alessandro; Varallo, Giorgia; Novelli, Margherita; Villa, Valentina; Luzzati, Francesca; Cottini, Andrea; Lai, Carlo; Volpato, Eleonora; Cavalera, Cesare; Pagnini, Francesco; Tesio, Valentina; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Seitanidis, Ionathan; Ventura, Giuseppe; Capodaglio, Paolo; D'Aniello, Guido Edoardo; Scarpina, Federica; Brioschi, Andrea; Bigoni, Matteo; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Di Lernia, Daniele; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan; Wiederhold, Brenda Kay; Gaudio, Santino; Jackson, Jeffrey B.; Tamburin, Stefano; Benedetti, Fabrizio; Agostini, Michela; Alfonsi, Enrico; Aloisi, Anna Maria; Alvisi, Elena; Aprile, Irene; Armando, Michela; Avenali, Micol; Azicnuda, Eva; Barale, Francesco; Bartolo, Michelangelo; Bergamaschi, Roberto; Berlangieri, Mariangela; Berlincioni, Vanna; Berliocchi, Laura; Berra, Eliana; Berto, Giulia; Bonadiman, Silvia; Bonazza, Sara; Bressi, Federica; Brugnera, Annalisa; Brunelli, Stefano; Buzzi, Maria Gabriella; Cacciatori, Carlo; Calvo, Andrea; Cantarella, Cristina; Caraceni, Augusto; Carone, Roberto; Carraro, Elena; Casale, Roberto; Castellazzi, Paola; Castino, Adele; Cerbo, Rosanna; Chiò, Adriano; Ciotti, Cristina; Cisari, Carlo; Coraci, Daniele; Dalla Toffola, Elena; Defazio, Giovanni; De Icco, Roberto; Del Carro, Ubaldo; Dell'Isola, Andrea; De Tanti, Antonio; D'Ippolito, Mariagrazia; Fazzi, Elisa; Ferrari, Adriano; Ferrari, Sergio; Ferraro, Francesco; Formaglio, Fabio; Formisano, Rita; Franzoni, Simone; Gajofatto, Francesca; Gandolfi, Marialuisa; Gardella, Barbara; Geppetti, Pierangelo; Giammò, Alessandro; Gimigliano, Raffaele; Greco, Elena; Ieraci, Valentina; Invernizzi, Marco; Jacopetti, Marco; La Cesa, Silvia; Lobba, Davide; Magrinelli, Francesca; Mandrini, Silvia; Manera, Umberto; Marchettini, Paolo; Marchioni, Enrico; Mariotto, Sara; Martinuzzi, Andrea; Masciullo, Marella; Mezzarobba, Susanna; Miotti, Danilo; Modenese, Angela; Molinari, Marco; Monaco, Salvatore; Morone, Giovanni; Nappi, Rossella; Negrini, Stefano; Pace, Andrea; Padua, Luca; Pagliano, Emanuela; Palmerini, Valerio; Pazzaglia, Costanza; Pecchioli, Cristiano; Picelli, Alessandro; Porro, Carlo Adolfo; Porru, Daniele; Romano, Marcello; Roncari, Laura; Rosa, Riccardo; Saccavini, Marsilio; Sacerdote, Paola; Schenone, Angelo; Schweiger, Vittorio; Scivoletto, Giorgio; Smania, Nicola; Solaro, Claudio; Spallone, Vincenza; Springhetti, Isabella; Tassorelli, Cristina; Tinazzi, Michele; Togni, Rossella; Torre, Monica; Traballesi, Marco; Tramontano, Marco; Truini, Andrea; Tugnoli, Valeria; Turolla, Andrea; Vallies, Gabriella; Verzini, Elisabetta; Vottero, Mario; Zerbinati, Paolo
abstract

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy.

2016 - L'arto superiore nella paralisi cerebrale infantile: Aspetti clinici e possibilità terapeutiche [Monografia/Trattato scientifico]
Ferrari, Adriano; Benedetti, Maria Grazia; Mori, Maurizio; Albores, Silvia
abstract

Un sottotitolo onesto per questo libro, come per quasi tutti gli altri miei lavori, avrebbe potuto essere “appunti di viaggio”. Un viaggio professionale durato tanti anni e compiuto in compagnia di compagni fedeli, medici, terapisti e tecnici, esplorando un ambito, quello della paralisi cerebrale infantile, allo stesso tempo semplice, per essere quotidianamente sotto gli occhi di tutti, data l’elevata incidenza di questa patologia, e complesso, per la continua trasformazione dei suoi aspetti clinici (il changing panorama), prodotta dalle mutate modalità di assistenza alla gravidanza, al parto ed al neonato. Un’esplorazione iniziata con strumenti semplici, la sola capacità di osservare, e con incerte mappe concettuali quali l’ambito dei riflessi e quello dei pattern posturo-motori, sostenuta strada facendo dai progressi compiuti dalle neuroscienze nello studio del controllo motorio e progressivamente documentata dalle neuroimmagini, per comprendere la fisiopatologia del danno e capire come affrontarne le conseguenze sul piano funzionale, ed estesa progressivamente dal dominio della motricità verso altre importanti dimensioni come la percezione, la modalità di apprendimento e l’identità del bambino disabile. Come ogni viaggiatore ho cercato presso altri “cultori della materia” possibili indicazioni per sapere quale fosse la direzione migliore da prendere. Adriano Milani Comparetti, per il suo modello di interpretazione della interazione competitiva fra pattern motori primari, e Giorgio Sabbadini, per aver fatto luce sulle dimensioni nascoste della paralisi (la disprassia), sono stati guide assolutamente preziose. Strada facendo ho incontrato altri viaggiatori che come me cercavano una possibile via per la rieducazione del bambino con paralisi cerebrale infantile. L’incontro con due di loro, Michele Bottos e Marcello Mario Pierro, è stato determinante per il mio procedere, poiché entrambi mi hanno generosamente aiutato a considerare anche altri differenti angoli visivi, frutto della loro personale esperienza. Confrontandoli e coniugandoli con il mio, assieme abbiamo potuto dare profondità ad una mappa concettuale che abbiamo continuato a disegnare, almeno fino a quando la vita lo ha concesso loro. Al ritorno da ognuno dei miei viaggi nel mondo della paralisi cerebrale infantile, all’atto di trasferire in forma scritta le idee e le esperienze maturate, mi aspettava puntuale un lettore attento, benevolo ma rigoroso, pronto a sottolineare i pregi del lavoro compiuto, ma altrettanto determinato a metterne in luce ogni contraddizione o lacuna: era Silvano Boccardi. Questo libro esce senza la sua correzione discreta, ma determinante. Per quanto sono stato capace di fare, ho cercato di tener conto di quanto Silvano mi ha insegnato in termini di metodologia, coerenza ed onestà intellettuale. Spero di esserci riuscito. Ho ricordato i grandi maestri e i compagni di viaggio che mi hanno lasciato. Altri per fortuna sono saldamente al mio fianco come Giovanni Cioni, che ringrazio non solo per la presentazione di questo libro, ma per il sostegno costante fornito al mio tentativo di dare un razionale all’intervento terapeutico che fosse al tempo coerente con le conoscenze più aggiornate della neurofisiopatologia del danno cerebrale. Da molti anni i nostri due gruppi di lavoro si muovono assieme, condividendo idee e prassi operative, sostenendosi reciprocamente nell’attività clinica ed integrandosi in quella della ricerca applicata e traslazionale. La considerazione finale, certo la più importante, è per i tanti allievi che in questi anni hanno voluto conoscere il pensiero e le esperienze nel mio gruppo. A loro è destinato questo libro. In esso troveranno le cose che abbiamo capito sull’attività dell’arto superiore del bambino con paralisi cerebrale infantile. Quelle che non abbiamo ancora capito sono molte di più, ma siamo certi che alcuni di loro sapranno proseguire questo viaggio ver

2016 - Modulating the motor system by action observation in right Hemiplegic Cerebral Palsy: an fMRI study [Abstract in Atti di Convegno]
Errante, A; Di Cesare, G; Fasano, F; Costi, Stefania; Sghedoni, S; Bressi, B; Volpe, V; Ferrari, Adriano; Fogassi, Leonardo
abstract

Cerebral Palsy (CP) is a major cause of motor disability in children. Among CP children, approximately one third is affected by Hemiplegic Cerebral Palsy (HCP), resulting in abnormal motor function of one body side. In recent years, it hab been suggested that the systematic use of observation of goal-directed actions followed by their execution (Action Observation Treatment, AOT) may become a rehabilitative strategy that improves the process of functional recovery in patients with stroke, Parkinson Disease and in orthopedic patients. AOT has been found effective also in HCP children.

2016 - Optimized Cryopreservation and Banking of Human Bone-Marrow Fragments and Stem Cells [Articolo su rivista]
Carnevale, Gianluca; Pisciotta, Alessandra; Riccio, Massimo; De Biasi, Sara; Gibellini, Lara; Ferrari, Adriano; La Sala, Giovanni Battista; Bruzzesi, Giacomo; Cossarizza, Andrea; De Pol, Anto
abstract

Adult mesenchymal stem cells are a promising source for cell therapies and tissue engineering applications. Current procedures for banking of human bone-marrow mesenchymal stem cells (hBM-MSCs) require cell isolation and expansion, and thus the use of large amounts of animal sera. However, animal-derived culture supplements have the potential to trigger infections and severe immune reactions. The aim of this study was to investigate an optimized method for cryopreservation of human bone-marrow fragments for application in cell banking procedures where stem-cell expansion and use are not immediately needed. Whole trabecular fragments enclosing the bone marrow were stored in liquid nitrogen for 1 year in a cryoprotective solution containing a low concentration of dimethyl sulfoxide and a high concentration of human serum (HuS). After thawing, the isolation, colony-forming-unit ability, proliferation, morphology, stemness-related marker expression, cell senescence, apoptosis, and multi-lineage differentiation potential of hBM-MSCs were tested in media containing HuS compared with hBM-MSCs isolated from fresh fragments. Human BM-MSCs isolated from cryopreserved fragments expressed MSC markers until later passages, had a good proliferation rate, and exhibited the capacity to differentiate toward osteogenic, adipogenic, and myogenic lineages similar to hBM-MSCs isolated from fresh fragments. Moreover, the cryopreservation method did not induce cell senescence or cell death. These results imply that minimal processing may be adequate for the banking of tissue samples with no requirement for the immediate isolation and use of hBM-MSCs, thus limiting cost and the risk of contamination, and facilitating banking for clinical use. Furthermore, the use of HuS for cryopreservation and expansion/differentiation has the potential for clinical application in compliance with good manufacturing practice standards.

2016 - Psychological considerations in the assessment and treatment of pain in neurorehabilitation and psychological factors predictive of therapeutic response: Evidence and recommendations from the Italian consensus conference on pain in neurorehabilitation [Articolo su rivista]
Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano; Agostini, Michela; Alfonsi, Enrico; Aloisi, Anna Maria; Alvisi, Elena; Aprile, Irene; Armando, Michela; Avenali, Micol; Azicnuda, Eva; Barale, Francesco; Bartolo, Michelangelo; Bergamaschi, Roberto; Berlangieri, Mariangela; Berlincioni, Vanna; Berliocchi, Laura; Berra, Eliana; Berto, Giulia; Bonadiman, Silvia; Bonazza, Sara; Bressi, Federica; Brugnera, Annalisa; Brunelli, Stefano; Buzzi, Maria Gabriella; Cacciatori, Carlo; Calvo, Andrea; Cantarella, Cristina; Caraceni, Augusto; Carone, Roberto; Carraro, Elena; Casale, Roberto; Castellazzi, Paola; Castino, Adele; Cerbo, Rosanna; Chiò, Adriano; Ciotti, Cristina; Cisari, Carlo; Coraci, Daniele; Toffola, Elena Dalla; Defazio, Giovanni; De Icco, Roberto; Del Carro, Ubaldo; Dell'Isola, Andrea; De Tanti, Antonio; D'Ippolito, Mariagrazia; Fazzi, Elisa; Ferrari, Adriano; Ferrari, Sergio; Ferraro, Francesco; Formaglio, Fabio; Formisano, Rita; Franzoni, Simone; Gajofatto, Francesca; Gandolfi, Marialuisa; Gardella, Barbara; Geppetti, Pierangelo; Giammò, Alessandro; Gimigliano, Raffaele; Greco, Elena; Ieraci, Valentina; Invernizzi, Marco; Jacopetti, Marco; La Cesa, Silvia; Lobba, Davide; Magrinelli, Francesca; Mandrini, Silvia; Manera, Umberto; Marchettini, Paolo; Marchioni, Enrico; Mariotto, Sara; Martinuzzi, Andrea; Masciullo, Marella; Mezzarobba, Susanna; Miotti, Danilo; Modenese, Angela; Molinari, Marco; Monaco, Salvatore; Morone, Giovanni; Nappi, Rossella; Negrini, Stefano; Pace, Andrea; Padua, Luca; Pagliano, Emanuela; Palmerini, Valerio; Pazzaglia, Costanza; Pecchioli, Cristiano; Picelli, Alessandro; Porro, Carlo Adolfo; Porru, Daniele; Romano, Marcello; Roncari, Laura; Rosa, Riccardo; Saccavini, Marsilio; Sacerdote, Paola; Schenone, Angelo; Schweiger, Vittorio; Scivoletto, Giorgio; Smania, Nicola; Solaro, Claudio; Spallone, Vincenza; Springhetti, Isabella; Tassorelli, Cristina; Tinazzi, Michele; Togni, Rossella; Torre, Monica; Traballesi, Marco; Tramontano, Marco; Truini, Andrea; Tugnoli, Valeria; Turolla, Andrea; Vallies, Gabriella; Verzini, Elisabetta; Vottero, Mario; Zerbinati, Paolo
abstract

Background: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. Objectives: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies, and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies, and psychological interventions. Finally, sense of presence was found to be related to the effectiveness of virtual reality as a distraction tool. Conclusions: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition. These factors also predict the therapeutic response to the neurorehabilitative interventions.

2016 - Psychological treatments and psychotherapies in the neurorehabilitation of pain: Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation [Articolo su rivista]
Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano; Agostini, Michela; Alfonsi, Enrico; Aloisi, Anna Maria; Alvisi, Elena; Aprile, Irene; Armando, Michela; Avenali, Micol; Azicnuda, Eva; Barale, Francesco; Bartolo, Michelangelo; Bergamaschi, Roberto; Berlangieri, Mariangela; Berlincioni, Vanna; Berliocchi, Laura; Berra, Eliana; Berto, Giulia; Bonadiman, Silvia; Bonazza, Sara; Bressi, Federica; Brugnera, Annalisa; Brunelli, Stefano; Buzzi, Maria Gabriella; Cacciatori, Carlo; Calvo, Andrea; Cantarella, Cristina; Caraceni, Augusto; Carone, Roberto; Carraro, Elena; Casale, Roberto; Castellazzi, Paola; Castino, Adele; Cerbo, Rosanna; Chi�, Adriano; Ciotti, Cristina; Cisari, Carlo; Coraci, Daniele; Toffola, Elena Dalla; Defazio, Giovanni; De Icco, Roberto; Del Carro, Ubaldo; Dell'Isola, Andrea; De Tanti, Antonio; D'Ippolito, Mariagrazia; Fazzi, Elisa; Ferrari, Adriano; Ferrari, Sergio; Ferraro, Francesco; Formaglio, Fabio; Formisano, Rita; Franzoni, Simone; Gajofatto, Francesca; Gandolfi, Marialuisa; Gardella, Barbara; Geppetti, Pierangelo; Giamm�, Alessandro; Gimigliano, Raffaele; Greco, Elena; Ieraci, Valentina; Invernizzi, Marco; Jacopetti, Marco; La Cesa, Silvia; Lobba, Davide; Magrinelli, Francesca; Mandrini, Silvia; Manera, Umberto; Marchettini, Paolo; Marchioni, Enrico; Mariotto, Sara; Martinuzzi, Andrea; Masciullo, Marella; Mezzarobba, Susanna; Miotti, Danilo; Modenese, Angela; Molinari, Marco; Monaco, Salvatore; Morone, Giovanni; Nappi, Rossella; Negrini, Stefano; Pace, Andrea; Padua, Luca; Pagliano, Emanuela; Palmerini, Valerio; Pazzaglia, Costanza; Pecchioli, Cristiano; Picelli, Alessandro; Porro, Carlo Adolfo; Porru, Daniele; Romano, Marcello; Roncari, Laura; Rosa, Riccardo; Saccavini, Marsilio; Sacerdote, Paola; Schenone, Angelo; Schweiger, Vittorio; Scivoletto, Giorgio; Smania, Nicola; Solaro, Claudio; Spallone, Vincenza; Springhetti, Isabella; Tassorelli, Cristina; Tinazzi, Michele; Togni, Rossella; Torre, Monica; Traballesi, Marco; Tramontano, Marco; Truini, Andrea; Tugnoli, Valeria; Turolla, Andrea; Vallies, Gabriella; Verzini, Elisabetta; Vottero, Mario; Zerbinati, Paolo
abstract

Background: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. Objectives: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. Methods: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. Results: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. Conclusions: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper.

2016 - Recommendations for the rehabilitation of children with cerebral palsy [Articolo su rivista]
Ferrari, Adriano
abstract

The SINPIA-SIMPER (Italian Society of Child and Adolescent Neuropsychiatry Italian Society of Physical Medicine and Rehabilitation) Intersociety Commission was set up in December 2000 and is composed of members from both scientific societies, who are experts in the field of rehabilitation of patients with cerebral palsy (CP). In accordance with the indications of the Italian Health Ministry's Planning Department, in 1999 this Commission was entrusted with the task of drawing up "Guidelines for the Rehabilitation of Children Affected by Cerebral Palsy", and to successively revise and update it every five years. The present document is a summary of the latest update, drawn up through meetings of the Intersociety Commission, held in 2012 and 2013, and discussed and approved at the annual SINPIA-SIMFER meeting held in Brindisi in October 2013. The current version of the Recommendations extends and updates the previous one, also addressing new areas of intervention and adding some in-depth analysis. The document as a whole is not so much a proposal for treatment updated on the basis of advancing knowledge in the field of rehabilitation of CP, as a presentation of the method that should be applied by professionals seeking to define the most appropriate intervention and treatment strategies. The text is the offspring of a process of careful exchanges, which have been conducted in a collegial and collaborative fashion among professionals working in different fields (rehabilitation medicine and child neuropsyehiatry) and in healthcare settings at different levels (ranging from first-level local settings to third-level national ones) and of different types (affiliated outpatient clinics and centers, local health authorities, hospitals, "IRCCS" research hospitals, universities).

2015 - Gait analysis contribution to problems identification and surgical planning in CP patients: An agreement study [Articolo su rivista]
Ferrari, A.; Brunner, R.; Faccioli, S.; Reverberi, S.; Benedetti, M. G.
abstract

Background. Previous studies have demonstrated that the use of gait analysis (GA) modifies decision making and changes planned surgical treatment, confirming some clinical indications or defining alternative choices, excluding or delaying already planned surgery in children with cerebral palsy (CP). Aim. To assess the difference in defining functional problems and treatment relevance using clinical assessment or gait analysis in CP children. Design. The study has been designed for assessing the rate of agreement on muscle-skeletal diagnosis, and on surgical recommendations in diplegic CP patients, when decided by two different blinded clinicians based on a) clinical assessment, and b) GA in addition to clinical assessment. Population. Twenty-five diplegic children who have been evaluated by GA before surgery and at a follow up of at least 6 months. Methods. Two separate lists of problems and consequent surgical interventions were outlined for all the patients by two blinded experts from clinical and GA assessment. The two sets of nominal-scale ratings for all patients of the two groups were statistically evaluated for agreement. Results. A fair and a slight agreement was found respectively between the two sets of problems and the two sets of surgical plans. Main differences in problems identified were relative to the presence of generalized spasticity and bony deformities as detected by means of GA instead of local problems and soft tissues spasticity/retraction clinically identified. As a consequence, by means of GA, surgery was indicated only in 65% of patients. Conclusion. The availability of a GA laboratory helps in diagnostic reasoning in CP children indicated for surgery. Low agreement found appears to be a result of a different clinical approach of the surgeons. Clinical Rehabilitation Impact. The use of GA in the analysis of motor problems in CP children provides a basis for an objective reasoning for clinical decision making and for assessing functional outcome. Further efforts are required to build a body of knowledge about a consensus on the identification of walking problems in CP children.

2015 - Human dental pulp stem cells (hDPSCs): isolation, enrichment and comparative differentiation of two sub-populations [Articolo su rivista]
Pisciotta, Alessandra; Carnevale, Gianluca; Meloni, Simona; Riccio, Massimo; De Biasi, Sara; Gibellini, Lara; Ferrari, Adriano; Bruzzesi, Giacomo; De Pol, Anto
abstract

Human dental pulp represents a suitable alternative source of stem cells for the purpose of cell-based therapies in regenerative medicine, because it is relatively easy to obtain it, using low invasive procedures. This study characterized and compared two subpopulations of adult stem cells derived from human dental pulp (hDPSCs). Human DPSCs, formerly immune-selected for STRO-1 and c-Kit, were separated for negativity and positivity to CD34 expression respectively, and evaluated for cell proliferation, stemness maintenance, cell senescence and multipotency.

2015 - Neural crest derived niche of human dental pulp stem cells promotes peripheral nerve regeneration and remyelination in animal model of critical sized sciatic nerve injury [Articolo su rivista]
Carnevale, Gianluca; Pisciotta, Alessandra; DE BIASI, Sara; Gibellini, Lara; Cossarizza, Andrea; Bruzzesi, Giacomo; Ferrari, Adriano; DE POL, Anto
abstract

ABSTRACT Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional defects. The use of stem cells, easily accessible, capable of rapid expansion in culture as well as fully integrate into the host tissue and capable to differentiate in myelinating cells of the peripheral nervous system, represent an attractive therapeutic approach for the treatment of nerve injuries. Farther, stem cells sources sharing the same embryological origin of Schwann cells, might be considered a suitable tool. The aim of this study was to demonstrate the ability of a neuroectodermal sub-population of STRO-1+/c-Kit+/CD34+ hDPSCs (1, 2), most of which being positive for neural crest (P75NTR) and neural progenitor cells (nestin) markers, to differentiate into Schwann cells-like cells in vitro and to promote axonal regeneration in vivo. As a matter of fact, following culture in appropriate induction medium, STRO-1+/c-Kit+/CD34+ hDPSCs were able to commit towards Schwann cells express- ing P75NTR, GFAP and S100b. After transplantation in animal model of sciatic nerve defect, hDPSCs promoted axonal regeneration from proximal to distal stumps, providing guidance to newly formed myelinated nerve fibers, which led to functional recovery as measured by sustained gait improvement. Particularly, transplanted hDP- SCs engrafted into critical sized sciatic nerve defect, as revealed by the positive stain- ing against human nuclei, showed the expression of typical Schwann cells markers, S100b and GFAP. In conclusion this study demonstrates that STRO-1+/c-Kit+/CD34+ hDPSCs, associated to neural crest derivation, represent a promising source of stem cells for the treatment of demyelinating disorders and might provide a valid alternative tool for future clinical applications to achieve functional recovery after injury or peripheral neuropathies besides minimizing ethical issues.

2015 - Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice [Articolo su rivista]
Pisciotta, Alessandra; Riccio, Massimo; Carnevale, Gianluca; Lu, Aiping; DE BIASI, Sara; Gibellini, Lara; LA SALA, Giovanni Battista; Bruzzesi, Giacomo; Ferrari, Adriano; Huard, Johnny; DE POL, Anto
abstract

Introduction: Duchenne muscular dystrophy (DMD), caused by a lack of the functional structural protein dystrophin, leads to severe muscle degeneration where the patients are typically wheelchair-bound and die in their mid-twenties from cardiac or respiratory failure or both. The aim of this study was to investigate the potential of human dental pulp stem cells (hDPSCs) and human amniotic fluid stem cells (hAFSCs) to differentiate toward a skeletal myogenic lineage using several different protocols in order to determine the optimal conditions for achieving myogenic commitment and to subsequently evaluate their contribution in the improvement of the pathological features associated with dystrophic skeletal muscle when intramuscularly injected into mdx/SCID mice, an immune-compromised animal model of DMD. Methods: Human DPSCs and AFSCs were differentiated toward myogenic lineage in vitro through the direct co-culture with a myogenic cell line (C2C12 cells) and through a preliminary demethylation treatment with 5-Aza-2′-deoxycytidine (5-Aza), respectively. The commitment and differentiation of both hDPSCs and hAFSCs were evaluated by immunofluorescence and Western blot analysis. Subsequently, hDPSCs and hAFSCs, preliminarily demethylated and pre-differentiated toward a myogenic lineage for 2 weeks, were injected into the dystrophic gastrocnemius muscles of mdx/SCID mice. After 1, 2, and 4 weeks, the gastrocnemius muscles were taken for immunofluorescence and histological analyses. Results: Both populations of cells engrafted within the host muscle of mdx/SCID mice and through a paracrine effect promoted angiogenesis and reduced fibrosis, which eventually led to an improvement of the histopathology of the dystrophic muscle. Conclusion: This study shows that hAFSCs and hDPSCs represent potential sources of stem cells for translational strategies to improve the histopathology and potentially alleviate the muscle weakness in patients with DMD.

2015 - “Validazione trans-culturale della scala di valutazione Activities Scale for Kids performance (ASKp): stima dell'affidabilità della versione italiana nella popolazione con PCI”. [Poster]
Bruzzi, Elena; Costi, Stefania; Signorelli, Chiara; Cristina Filippi, Maria; Alboresi, Silvia; Ferrari, Adriano
abstract

La paralisi cerebrale infantile (PCI) è la più comune causa di disabilità dell’infanzia; i bambini con PCI sperimentano spesso difficoltà nelle ADL e il miglioramento della perfomance in questi compiti diviene un aspetto prioritario dell’intervento riabilitativo. Al fine di individuare obiettivi di trattamento appropriati e misurare gli effetti del proprio intervento, gli operatori della riabilitazione devono disporre di strumenti di valutazione validi nel contesto di applicazione. Nell’ambito della riabilitazione pediatrica sono state sviluppate numerose scale di valutazione, la maggior parte delle quali non sono formalmente tradotte e validate nel contesto italiano; una di queste è la Activities Scale for Kids (ASKp) che, ad oggi, è l’unico questionario di autovalutazione in abito pediatrico creato per indagare la percezione che il bambino ha in merito alla sua disabilità o limitazione nelle ADL; la validità della ASKp nella sua versione originale, in lingua inglese, è stata testata attraverso opportuni studi su bambini con disabilità di natura muscolo-scheletrica conseguente a varie patologie. Essa non è mai stata validata nella popolazione di bambini con PCI. Lo scopo di questo studio è quello di testare la versione italiana culturalmente adattata della scala ASKp nella popolazione con PCI. MATERIALI E METODI In questo studio con disegno trasversale viene testata l’affidabilità della ASKp attraverso la sua somministrazione ad un campione di bambini e adolescenti italiani, tra i 5 e i 15 anni, nelle diverse forme cliniche di emiplegia e di diplegia dovute a PCI. Trattandosi di una scala autosomministrata, sono esclusi i bambini e gli adolescenti con ritardo mentale moderato o grave. RISULTATI Ad oggi sono stati inclusi nello studio 83 bambini e adolescenti (47 maschi e 36 femmine), con un’età media di 10 anni e 6 mesi, nella maggior parte diplegici (49 pazienti). Nell’89% dei casi il livello cognitivo dei bambini è risultato nella norma. Un quarto dei pazienti necessita di ausili per spostarsi all’esterno, mentre una proporzione quasi analoga necessita di ausili per spostarsi intra–extramoenia. Il punteggio minimo ottenuto nella ASKp è 26, quello massimo 100 e il punteggio medio 78,4. L’affidabilità, testata tramite l’α di Cronbach, è pari a 0.93 (IC 0.90-0.96). La ASKp si è dimostrata in grado di discriminare livelli diversi di autonomia tra pazienti con livello cognitivo nella norma e pazienti con lieve ritardo mentale e tra pazienti che utilizzano ausili per spostarsi negli ambienti chiusi e pazienti che non li utilizzano o vi fanno ricorso solo per gli spostamenti in spazi aperti. I risultati parziali ad oggi ottenuti non ci hanno permesso di rilevare altre capacità discriminative. CONCLUSIONI La misura della performance dei bambini con PCI nelle attività quotidiane è un outcome importante per il team riabilitativo, che può indirizzare il team verso obiettivi concreti e funzionali. È fondamentale avere a disposizione scale di valutazione delle ADL robuste e focalizzate sui bambini. La versione italiana della ASKp è affidabile nella popolazione con PCI.

2014 - A randomized trial of upper limb botulimun toxin versus placebo injection, combined with physiotherapy, in children with hemiplegia [Articolo su rivista]
Ferrari, Adriano; Alboresi, Silvia
abstract

The main goal of this study was to investigate the efficacy of Botulinum Toxin A (BoNT-A), combined with an individualized intensive physiotherapy/orthoses treatment, in improving upper limb activity and competence in daily activity in children with hemiplegia, and to compare its effectiveness with that of non-pharmacological instruments. It was a Randomized Clinical Trial of 27 children with spastic hemiplegic cerebral palsy, outpatients of two high speciality Centres for child rehabilitation. Each child was assigned by simple randomization to experimental group (BoNT-A) or control group (placebo). Assisting Hand Assessment (AHA) was chosen as primary outcome measure; other measures were selected according to ICF dimensions. Participants were assessed at baseline (T0), at T1, T2, T3 (1-3-6 months after injection, respectively). Every patient was given a specific physiotherapeutic treatment, consisting of individualized goal directed exercises, task oriented activities, daily stretching manoeuvres, functional and/or static orthoses. BoNT-A group showed a significant increase of AHA raw scores at T2, compared to control group (T2-T0: p= .025) and functional goals achievement (GAS) was also slightly better in the same group (p= .033). Other measures indicated some improvement in both groups, without significant intergroup differences. Children with intermediate severity of hand function at House scale for upper limb impairment seem to have a better benefit from BoNT-A protocol. BoNT-A was effective in improving manipulation in the activity domain, in association with individualized goal-directed physiotherapy and orthoses; the combined treatment is recommended. The study brings more evidence for the efficacy of a combined treatment botulinum toxin injection-physiotherapy-orthoses, and it gives some suggestions for candidate selection and individualized treatment. © 2014 Elsevier Ltd.

2014 - Effectiveness of standing frame on constipation in children with cerebral palsy: a single-subject study [Articolo su rivista]
Rivi, Elena; Filippi, Mariacristina; Fornasari, Elisa; Mascia, Maria Teresa; Ferrari, Adriano; Costi, Stefania
abstract

Children with cerebral palsy (CP) and quadriplegia or severe diplegia suffer from highly reduced mobility and consequent constipation. Clinicians recommend standing frames to exercise the support reaction in this population, sharing the opinion that the upright position may facilitate intestinal transit, although no evidence supports this assumption. We conducted this study to determine the effects of the standing frame on spontaneous evacuation in children with CP. Moreover, we studied its effects on the frequency of induction of evacuation, the characteristics of the stool and the pain suffered by the child due to constipation and/or evacuation. We implemented a single-subject research design in one chronically constipated child with CP and quadriplegia, Gross Motor Function Classification System Level V. To monitor the effects of the standing frame, we measured the outcome of interest throughout the study using a daily diary and the Bristol Stool Scale. This study was approved by the local Ethics Committee. This study has several limitation; primarily, the use of a single-subject research design only makes possible the visual analysis of data obtained from a unique patient. So, by themselves, data obtained do not allow us any generalization for the target population. Future research should verify our results collecting more data and also investigating the effect of the standing-frame on respiratory functions. Although the standing frame did not affect the frequency of evacuations or the characteristics of the stool, its employment reduced the inductions of evacuation and the related pain suffered by the child. However, this study has several limitations, such as the lack of generalization due to the fact that we studied a unique patient and the overall brevity of the study due to external circumstances. Therefore, we suggest future research to verify our results, also investigating the effect of the standing frame on respiratory functions. Relevance to clinical practice. The standing frame may positively influence the management of constipation of these children, possibly improving their quality of life.

2014 - La fisioterapia nella paralisi cerebrale infantile. La funzione cammino. [Monografia/Trattato scientifico]
Borelli, G.; Neviani, R.; Sghedoni, A.; Ovi, A.; Ferrari, Adriano
abstract

Questo volume riassume i principali elementi relativi alla funzione cammino nel bambino sano (sviluppo della funzione, meccanismi neurofisiologici e aspetti biomeccanici), prerequisiti fondamentali per poter comprendere i disturbi del cammino nel bambino affetto da paralisi cerebrale infantile (PCI). Vengono trattati i segni clinici tipici manifestati nel cammino dai bambini con PCI, la modalità per valutarli e interpretarli al fine di comprendere l’inquadramento diagnostico e prognostico relativo alla funzione in esame. Successivamente, vengono presentati gli ausili e le ortesi, e la loro possibile funzione all’interno del progetto riabilitativo. Il volume si conclude con una sezione di casi clinici, che descrive il processo di costruzione della seduta fisioterapica e le modalità di svolgimento attraverso esempi concreti di setting, esercizi terapeutici e proposte di compiti finalizzati. Il testo, rivolto principalmente ai fisioterapisti e ai terapisti della neuro-psicomotricità dell’età evolutiva e agli allievi delle lauree di I e II livello dell’area della riabilitazione, potrà destare interesse anche in altri professionisti come i tecnici ortopedici e i terapisti occupazionali.

2014 - New definitions of 6 clinical signs of perceptual disorder in children with cerebral palsy: an observational study through reliability measures [Articolo su rivista]
Ferrari, Adriano
abstract

BACKGROUND: Recently authors have begun to emphasize the non-motor aspects of Cerebral Palsy and their influence on motor control and recovery prognosis. Much has been written about single clinical signs (i.e., startle reaction) but so far no definitions of the six perceptual signs presented in this study have appeared in literature. AIM: This study defines 6 signs (startle reaction, upper limbs in startle position, frequent eye blinking, posture freezing, averted eye gaze, grimacing) suggestive of perceptual disorders in children with cerebral palsy and measures agreement on sign recognition among independent observers and consistency of opinions over time. DESIGN: Observational study with both cross-sectional and prospective components. SETTING: Fifty-six videos presented to observers in random order. Videos were taken from 19 children with a bilateral form of cerebral palsy referred to the Children Rehabilitation Unit in Reggio Emilia. PARTICIPANTS: Thirty-five rehabilitation professionals from all over Italy: 9 doctors and 26 physiotherapists. METHODS: Measure of agreement among 35 independent observers was compiled from a sample of 56 videos. Interobserver reliability was determined using the K index of Fleiss and reliability intra-observer was calculated by the Spearman correlation index between ranks (rho - ρ). Percentage of agreement between observers and Gold Standard was used as criterion validity. RESULTS: Interobserver reliability was moderate for startle reaction, upper limb in startle position, adverted eye gaze and eye-blinking and fair for posture freezing and grimacing. Intraobserver reliability remained consistent over time. Criterion validity revealed very high agreement between independent observer evaluation and gold standard. CONCLUSIONS: Semiotics of perceptual disorders can be used as a specific and sensitive instrument in order to identify a new class of patients within existing heterogeneous clinical types of bilateral cerebral palsy forms and could help clinicians in identifying functional prognosis. CLINICAL REHABILITATION IMPACT: To provide clinicians with a definition of 6 clinical signs found in children with cerebral palsy in routine rehabilitation settings. Future research should explore the link between these signs and motor prognosis (i.e., time to independent walking).

2013 - AFO orthoses in children with CP: the effectiveness is associated with the gait pattern. [Abstract in Rivista]
Ferrari, Adriano; Costi, Stefania
abstract

Despite the AFO orthoses for children with CP are a widely used tool, their effectiveness has not yet been clearly demonstrated by experimental evidence, both for what concerns the effects on the walking pattern, and for what regards the aspects of activity and performance [1]. In the literature, the majority of the studies that evaluates the effectiveness of orthoses does not divide the children according to the pattern of movement, and bases the evaluation on uniform targets for all. The present work, dividing the patients into 4 forms (where the patients are more skilled from 1st to 4th form, Ferrari et al. [2]), tested the effectiveness of orthoses, demonstrating the need for an individualized approach based on the walking pattern of each single patient.

2013 - Ferutinin promotes proliferation and osteoblastic differentiation in human amniotic fluid and dental pulp stem cells. [Articolo su rivista]
Zavatti, Manuela; Resca, Elisa; Bertoni, Laura; Maraldi, Tullia; Guida, Marianna; Carnevale, Gianluca; Ferrari, Adriano; DE POL, Anto
abstract

The phytoestrogen Ferutinin plays an important role in prevention of osteoporosis caused by ovariectomy-induced estrogen deficiency in rats, but there is no evidence of its effect on osteoblastic differentiation in vitro. In this study we investigated the effect of Ferutinin on proliferation and osteoblastic differentiation of two different human stem cells populations, one derived from the amniotic fluid (AFSCs) and the other from the dental pulp (DPSCs).AFSCs and DPSCs were cultured in a differentiation medium for 14 or 21days with or without the addition of Ferutinin at a concentration ranging from 10(-11) to 10(-4)M. 17β-Estradiol was used as a positive drug at 10(-8)M. Cell proliferation and expression of specific osteoblast phenotype markers were analyzed.MTT assay revealed that Ferutinin, at concentrations of 10(-8) and 10(-9)M, enhanced proliferation of both AFSCs and DPSCs after 72h of exposure. Moreover, in both stem cell populations, Ferutinin treatment induced greater expression of the osteoblast phenotype markers osteocalcin (OCN), osteopontin (OPN), collagen I, RUNX-2 and osterix (OSX), increased calcium deposition and osteocalcin secretion in the culture medium compared to controls. These effects were more pronounced after 14days of culture in both populations.The enhancing capabilities on proliferation and osteoblastic differentiation displayed by the phytoestrogen Ferutinin make this compound an interesting candidate to promote bone formation in vivo.

2013 - In vitro differentiation into insulin-producing β-cells of stem cells isolated from human amniotic fluid and dental pulp. [Articolo su rivista]
Carnevale, Gianluca; Riccio, Massimo; Pisciotta, Alessandra; Beretti, Francesca; Maraldi, Tullia; Zavatti, Manuela; Cavallini, Gian Maria; LA SALA, Giovanni Battista; Ferrari, Adriano; DE POL, Anto
abstract

AIM: To investigate the ability of human amniotic fluid stem cells and human dental pulp stem cells to differentiate into insulin-producing cells. METHODS: Human amniotic fluid stem cells and human dental pulp stem cells were induced to differentiate into pancreatic β-cells by a multistep protocol. Islet-like structures were assessed in differentiated human amniotic fluid stem cells and human dental pulp stem cells after 21 days of culture by dithizone staining. Pancreatic and duodenal homebox-1, insulin and Glut-2 expression were detected by immunofluorescence and confocal microscopy. Insulin secreted from differentiated cells was tested with SELDI-TOF MS and by enzyme-linked immunosorbent assay. RESULTS: Human amniotic fluid stem cells and human dental pulp stem cells, after 7 days of differentiation started to form islet-like structures that became evident after 14 days of induction. SELDI-TOF MS analysis, revealed the presence of insulin in the media of differentiated cells at day 14, further confirmed by enzyme-linked immunosorbent assay after 7, 14 and 21 days. Both stem cell types expressed, after differentiation, pancreatic and duodenal homebox-1, insulin and Glut-2 and were positively stained by dithizone. Either the cytosol to nucleus translocation of pancreatic and duodenal homebox-1, either the expression of insulin, are regulated by glucose concentration changes. Day 21 islet-like structures derived from both human amniotic fluid stem cells and human dental pulp stem cell release insulin in a glucose-dependent manner. CONCLUSION: The present study demonstrates the ability of human amniotic fluid stem cells and human dental pulp stem cell to differentiate into insulin-producing cells, offering a non-pancreatic, low-invasive source of cells for islet regeneration.

2013 - L’arto inferiore nella Paralisi Cerebrale Infantile. Semeiotica e chirurgia funzionale. [Monografia/Trattato scientifico]
Ferrari, Adriano; Reverberi, Sandro; Benedetti M., Grazia
abstract

Partendo dall'analisi del segno il testo affronta i principali difetti (impairment) che possono interessare l'arto inferiore nel bambino affetto da paralisi cerebrale infantile. Per ciascuna delle tre principali stazioni di movimento (piede, ginocchio e anca) vengono considerate le possibili cause del segno, le manovre di semeiotica clinica e strumentale (gait analysis) in grado di evidenziarle, le proposte di chirurgia funzionale più praticate capaci di modificarle. Per ciascun intervento chirurgico viene fornita una descrizione sintetica della procedura e dei tempi di interdizione dal carico, il protocollo di addestramento fisioterapico nell'immediato postoperatorio e quello da seguire dalla ripresa del carico in poi. Il testo è correlato da una ricca iconografia e da una bibliografia aggiornata. Un glossario ragionato permette di conoscere il significato dei principali termini utilizzati. Un capitolo conclusivo analizza le strategie dell'approccio chirurgico nelle principali forme di paralisi cerebrale infantile.

2013 - Randomized Trial of Observation and Execution of Upper Extremity Actions Versus Action Alone in Children With Unilateral Cerebral Palsy. [Articolo su rivista]
Sgandurra, G1; Ferrari, Adriano; Cossu, G.; Guzzetta, A.; Fogassi, L.; Cioni, G.
abstract

BACKGROUND: The properties of the mirror neuron system suggest a new type of upper limb (UL) rehabilitation in children with unilateral cerebral palsy (UCP), based on observation of action therapy followed by execution of a variety of observed movements (AOT). OBJECTIVE: We tested the effects of AOT in the Upper Limb Children Action Observation Training (UP-CAT) trial. METHODS: In a randomized, evaluator-blinded, block-designed trial, 24 UCP children with mild to moderate hand impairment were assigned to 2 groups. The experimental group observed, 1 hour per day for 3 consecutive weeks, video sequences of unimanual or bimanual goal-directed actions and subsequently executed observed actions with the hemiparetic UL or both ULs. The control group performed the same actions in the same order as the experimental sample, but had watched computer games. The Assisting Hand Assessment (AHA) scale was the primary outcome measure; the Melbourne assessment and ABILHAND-Kids were secondary ones. Outcomes were assessed at 1 week (T1), 8 weeks (T2), and 24 weeks (T3) after the end of the training. RESULTS: The experimental group improved more (P = .008) in score changes for the AHA at the primary endpoints T1 (P = .008), T2 (P = .019), and T3 (P = .049). No between-group significant changes were found for ABILHAND-Kids or Melbourne assessment. CONCLUSIONS: UP-CAT improved daily UL activities in UCP children, suggesting a new rehabilitation approach based on a neurophysiological model of motor learning.

2012 - Core elements of physiotherapy in cerebral palsy children: proposal for a trial checklist. [Articolo su rivista]
Meghi, P; Rossetti, L; Corrado, C; Maran, E; Arosio, N; Ferrari, Adriano
abstract

BACKGROUND: Currently international literature describes physiotherapy in cerebral palsy (CP) children only in generic terms (traditional / standard / background / routine).AIM: The aim of this study is to create a checklist capable of describing the different modalities employed in physiotherapeutic treatment by means of a non-bias, common, universal, standardised language.DESIGN: A preliminary checklist was outlined by a group of physiotherapists specialised in child rehabilitation.SETTING: For its experimentation, several physiotherapists from various paediatric units from all over Italy with different methodological approaches and backgrounds, were involved.METHODS: Using the interpretative model, proposed by Ferrari et al., and through collective analysis and discussion of clinical videos, the core elements were progressively selected and codified. A reliability study was then carried out by eight expert physiotherapists using an inter-rate agreement model.RESULTS: The checklist analyses therapeutic proposals of CP rehabilitation through the description of settings, exercises and facilitations and consists of items and variables which codify all possible physiotherapeutic interventions. It is accompanied by written explanations, demonstrative videos, caregiver interviews and descriptions of applied environmental adaptations. All checklist items obtained a high level of agreement (according to Cohen's kappa coefficient), revealing that the checklist is clearly and easily interpretable.CONCLUSION: The checklist should facilitate interaction and communication between specialists and families, and lead to comparable research studies and scientific advances. CLINICAL REHABILITATION IMPACT: The main value is to be able to correlate therapeutic results with core elements of adopted physiotherapy.

2012 - Effectiveness of AFO orthoses in children affected by cerebral palsy: Clinical evaluation does not always define patient satisfaction [Abstract in Rivista]
Ferrari, Adriano; Neviani, R.; Borghi, C; Costi, Stefania
abstract

Orthoses represent one of the tools most frequently used for the rehabilitation course of children affected by cerebral palsy (CP). A number of studies tried to evaluate the effectiveness of orthoses [1]. At present time no homogeneous results were found, both for what concerns their impact on the motor performance, and, mainly, for what concerns their effect in the fields of activities and participation [2]. These fields are still now very slightly explored. As indicated by [2], it is therefore necessary to deeper explore these issues in order to improve the rehabilitation care.

2012 - Fibroin scaffold repairs critical-size bone defects in vivo supported by human amniotic fluid and dental pulp stem cells. [Articolo su rivista]
Riccio, Massimo; Maraldi, Tullia; Pisciotta, Alessandra; LA SALA, Giovanni Battista; Ferrari, Adriano; G., Bruzzesi; A., Motta; C., Migliaresi; DE POL, Anto
abstract

The main aim of this study was the comparative evaluation of fibroin scaffolds combined with human stem cells, such as dental pulp stem cells (hDPSCs) and amniotic fluid stem cells (hAFSCs), used to repair critical-size cranial bone defects in immunocompromised rats. Two symmetric full-thickness cranial defects on each parietal region of rats have been replenished with silk fibroin scaffolds with or without preseeded stem cells addressed toward osteogenic lineage in vitro. Animals were euthanized after 4 weeks postoperatively and cranial tissue samples were taken for histological analysis. The presence of human cells in the new-formed bone was confirmed by confocal analysis with an antibody directed to a human mitochondrial protein. Fibroin scaffolds induced mature bone formation and defect correction, with higher bone amount produced by hAFSC-seeded scaffolds. Our findings demonstrated the strong potential of stem cells/fibroin bioengineered constructs for correcting large cranial defects in animal model and is likely a promising approach for the reconstruction of human large skeletal defects in craniofacial surgery.

2012 - Human serum promotes osteogenic differentiation of Human Dental Pulp Stem Cells in vitro and in vivo. [Articolo su rivista]
Pisciotta, Alessandra; Riccio, Massimo; Carnevale, Gianluca; Beretti, Francesca; Gibellini, Lara; Maraldi, Tullia; Cavallini, Gian Maria; Ferrari, Adriano; Bruzzesi, G; DE POL, Anto
abstract

Human dental pulp is a promising alternative source of stem cells for cell-based tissue engineering in regenerative medicine, for the easily recruitment with low invasivity for the patient and for the self-renewal and differentiation potential of cells. So far, in vitro culture of mesenchymal stem cells is usually based on supplementing culture and differentiation media with foetal calf serum (FCS). FCS is known to contain a great quantity of growth factors, and thus to promote cell attachment on plastic surface as well as expansion and differentiation. Nevertheless, FCS as an animal origin supplement may represent a potential means for disease transmission besides leading to a xenogenic immune response. Therefore, a significant interest is focused on investigating alternative supplements, in order to obtain a sufficient cell number for clinical application, avoiding the inconvenients of FCS use. In our study we have demonstrated that human serum (HS) is a suitable alternative to FCS, indeed its addition to culture medium induces a high hDPSCs proliferation rate and improves the in vitro osteogenic differentiation. Furthermore, hDPSCs-collagen constructs, pre-differentiated with HS-medium in vitro for 10 days, when implanted in immunocompromised rats, are able to restore critical size parietal bone defects. Therefore these data indicate that HS is a valid substitute for FCS to culture and differentiate in vitro hDPSCs in order to obtain a successful bone regeneration in vivo.

2012 - Malattie neuromuscolari dell'età evolutiva: clinica e riabilitazione [Monografia/Trattato scientifico]
Ferrari, Adriano; Lodesani, Manuela
abstract

malattie neuromuscolari dell'età evolutiva: clinica e riabilitazione

2012 - Myelomeningocele and pregnancy: a case report and review of the literature. [Articolo su rivista]
Blasi, I; Ferrari, Adriano; Comitini, G; Vinci, V; Abrate, M; LA SALA, Giovanni Battista
abstract

The improvement of antenatal management and surgical techniques has greatly increased the survival rate of infants with spina bifida. More of these women are reaching adulthood and reproductive age and therefore could become pregnant. Pregnancy complications depend on the kind of spina bifida and subject's condition.We report a case of woman with a severe kyphoscoliosis, that progressively affects lung capacity until 32 weeks of gestation, when she underwent caesarean section.These patients deserve careful obstetric care, genetic counselling and urological, obstetric, neurological and anaesthetic management.

2012 - Spina bifida: clinica e riabilitazione [Capitolo/Saggio]
Ferrari, Adriano; Lodesani, Manuela
abstract

spina bifida: clinica e riabilitazione

2011 - Al-Awadi-Raas-Rothschild (limb/pelvis/uterus-hypoplasia/aplasia) syndrome and WNT7A mutations: genetic homogeneity and nosological delineation. [Articolo su rivista]
Garavelli, L; Wischmeijer, A; Rosato, S; Gelmini, C; Reverberi, S; Sassi, S; Ferrari, Adriano; Mari, F; Zabel, B; Lausch, E; Unger, S; Superti Furga, A.
abstract

The Al-Awadi-Raas-Rothschild syndrome (AARRS; OMIM 276820) and the Fuhrmann syndrome (FS; OMIM 228930) are distinct limb malformation disorders comprising different degrees of limb aplasia or hypoplasia. In 2006, Woods et al. found different recessive WNT7A mutations in one family segregating the AARRS phenotype and in a second family with FS. To explain the common genetic basis for the two clinically distinct disorders, functional studies were done showing that partial loss of WNT7A function resulted in FS, while complete loss of WNT7A function resulted in the more severe phenotype of AARRS. In spite of the elucidation of the molecular basis of AARRS, there remains to this day considerable diagnostic confusion that has culminated in the lumping of Schinzel phocomelia syndrome with AARRS; however, this phocomelic limb defect is quite different in its clinical aspect and pathogenesis from the limb findings of AARRS. Here, we report on a child with the AARRS phenotype and homozygosity for a non-conservative E72K mutation in WNT7A, underline the homogeneity of the WNT7A-associated AARRS phenotype, and propose differential diagnostic criteria for the AARRS reflecting the roles of WNT7A in limb development. © 2010 Wiley-Liss, Inc.

2011 - Combinare tossica botulina, fisioterapia e ortesi nel trattamento della mano plegica del bambino. Può un RCT sostenere l'efficacia? [Articolo su rivista]
Muzzini, S.; Borelli, G.; Maoret, A. R.; Filippi, Mc; Sassi, S.; . Paolicelli, P. B.; Cioni, G.; Ferrari, Adriano
abstract

La terapia con tossina botulinica nel trattamento dell’arto superiore del bambino emiplegico si è mostrata efficace nel modificare le componenti strutturali e segmentarie ma non esiste per ora una sufficiente evidenza sulla incisività rispetto alle dimensioni funzionali dell’activity e delle autonomie della vita quotidiana. Abbiamo effettuato un RCT per verificare i cambiamenti indotti nelle diverse dimensioni ICF dal trattamento combinato tossina-fisioterapia-ortesi ed esplorare quanto dei risultati ottenuti fosse attribuibile all’azione della tossina e quanto al trattamento fisioterapico individualizzato combinato. Riportiamo qui alcune riflessioni critiche sulla metodologia scelta e sulle possibili ricadute in termini di risultato.

2011 - Equinus foot classification in cerebral palsy: an agreement study between clinical and gait analysis assessment. [Articolo su rivista]
Benedetti, Mg; D'Apote, G; Faccioli, S; Costi, Stefania; Ferrari, Adriano
abstract

BACKGROUND: Excessive ankle plantar flexion (equinus foot) is a common problem in cerebral palsy (CP) and several treatment options can be considered depending on the equinus type. Few attempts have been made to classify different forms of equinus foot for specific treatment.AIM: This study is aimed at defining equinus foot types in CP patients according to the Ferrari classification, integrating clinical and instrumental assessments. The hypothesis is that clinical differentiation of equinus foot can be evidenced by recurrent anomalies identifiable through gait analysis (GA), which can make the assessment, usually based only on clinician semeiotics, more objective.DESIGN: Clinical and instrumental assessments were performed separately by a senior CP physiatrist and a senior GA physiatrist, the latter was blind to the clinical diagnosis of equinus type.SETTING: OutpatientsPOPULATION: Twenty patients, 16 diplegics and 4 hemiplegics (mean age 11 years, SD 4 years 11 months).METHODS: Clinical assessment by means of Modified Ashworth Scale, Gross Motor Function Measure (GMFM), Observational Gait Analysis (OGA), and measurement of lower limb muscle strength by dynamometer were used to classify the equinus type. Gait analysis assessed the kinematics and EMG of affected lower limbs.RESULTS: Ten different equinus types were identified. Since various forms of equinus can be present in the same patient, we were able to classify a total of 61 types of equinus in 36 feet. Substantial agreement was found between Clinical and Gait Analysis equinus assignment matched in 50 out of 61 types (Index of agreement with Fleiss' Kappa 79.3 % ). In some case only Gait Analysis was able to identify the equinus type, while in others it did not confirm clinical assignment.CONCLUSION: Gait analysis is able to distinguish different equinus types according to Ferrari classification, making the clinical decision less arbitrary. CLINICAL REHABILITATION IMPACT: Correct objective diagnosis of equinus foot in CP patients is of paramount importance when choosing suitable rehabilitative interventions.

2011 - Human amniotic fluid stem cells seeded in fibroin scaffold produce in vivo mineralized matrix. [Articolo su rivista]
Maraldi, Tullia; Riccio, Massimo; Resca, Elisa; Pisciotta, Alessandra; LA SALA, Giovanni Battista; Ferrari, Adriano; Bruzzesi, G; Motta, A; Migliaresi, C; Marzona, Laura; DE POL, Anto
abstract

This study investigated the potential of amniotic fluid stem cells (AFSCs) to synthesize mineralized extracellular matrix (ECM) within different porous scaffolds of collagen, poly-D,L-lactic acid (PDLLA), and silk fibroin. The AFSCs were initially differentiated by using an osteogenic medium in two-dimensional culture, and expression of specific bone proteins and the physiologic mineral production by the AFSCs were analyzed. In particular, during differentiation process, AFSCs expressed proteins like Runt-related transcription factor 2 (Runx2), Osterix, Osteopontin, and Osteocalcin with a sequential expression, analogous to those occurring during osteoblast differentiation, and produced extracellular calcium stores. AFSCs were then cultured on three-dimensional (3D) scaffolds and evaluated for their ability to differentiate into osteoblastic cells in vivo. Stem cells were cultured in vitro for 1 week in collagen, fibroin, and PDLLA scaffolds. The effect of predifferentiation of the stem cells in scaffolds on the subsequent bone formation in vivo was determined in a rat subcutaneous model. With the addition of a third dimension, osteogenic differentiation and mineralized ECM production by AFSCs were significantly higher. This study demonstrated the strong potential of AFSCs to produce 3D mineralized bioengineered constructs in vivo and suggests that fibroin may be an effective scaffold material for functional repair of critical size bone defects.

2011 - Il contributo delle scienze umane nella formazione delle professioni sanitarie della riabilitazione [Articolo su rivista]
Ferrari, Adriano; Mamoli, Vittoria
abstract

Il contributo delle scienze umane nella formazione delle professioni sanitarie della riabilitazioneL'articolo è una dissertazione sul ruolo delle medical humanities nella formazione del professionista della riabilitazione.Partendo dalla definizione della presa in cura e presa in carico del paziente, gli autori illustrano l'esperienza maturata nel Corso di Laurea in Fisioterapia dell'Università di Modena e Reggio Emilia nell'insegnamento delle scienze umane.

2011 - Il metodo Doman [Articolo su rivista]
Ferrari, Adriano; Alboresi, Silvia
abstract

Nel panorama della riabilitazione infantile, il metodo Doman ha occupato e continua ad occupare un ruolo di primo piano. Le ragioni di questo successo sono legate soprattutto ai messaggi che Doman ha saputo indirizzare ai genitori ai quali ha parlato apertamente di possibilità di miglioramento, se non di piena guarigione. Per giudicare onestamente la veridicità delle affermazioni di Doman, è giusto confrontarle con quanto le neuroscienze sostenevano ai tempi in cui Doman scriveva le sue proposte. Molte ricerche avvenute all’epoca o successivamente hanno confutato le affermazioni di Doman sulla quantità e qualità del recupero, dimostrandone l’infondatezza dei presupposti e delle procedure. Poche sono state le voci a favore e tutte su settori limitati del linguaggio. Le famiglie che nonostante i tanti giudizi negativi espressi sul metodo volessero praticare comunque la cura Doman, attratte per lo più dalla concretezza dei percorsi terapeutici in termini di quantità, progressione e durata, riceverebbero risposte economiche difformi nelle diverse regioni italiane per una differente legislazione regionale

2011 - Individualized intensive physiotherapy-orthosis treatment in hand functional recovery of children with spastic hemiplegia after botulinum toxin injection [Abstract in Rivista]
Ferrari, Adriano; Maoret, A. R.; Filippi, Mc; Beccani, L.; Bassi, B; Muzzini, S.
abstract

Background: The 2010 Cochrane review regarding Botulinum Toxin A (BoNT-A) upper limb injections in children with CP, underlined the need to better define the associated physiotherapy treatment. Through an RCT involving 24 children with hemiplegic CP, an attempt was made to define the physiotherapy protocol. The results confirmed the determinant role of intensive individualized goaldirected physiotherapy in activity domain improvement. Objective: To define precise criteria for individualized physiotherapy planning and a functional exercise inventory after BONT-A injections. Method: After BONT-A injection an individualized physiotherapy programme was created for each child considering not only injected muscles and functional goals but also motor learning capacity and modifiability, pointing, reaching, grasping, manipulating, releasing strategies, sensoryperceptual disorders, bottom-up components, cognitive level, age, sex and personality. Physiotherapeutic treatment consisted of everyday stretching maneuvers, therapeutic exercises and activities organized in three 45 minute weekly sessions, for 24 weeks. Functional individualized goals were established with family and child. The treatment was combined with nighttime positional splints and daytime functional orthoses aimed at facilitating grasping and handling. The therapeutic approach was specific timed to BONT-A action. During the first month therapists focused on segmental treatment such as stretching, with simple unimanual or bimanual exercises; both transitive and intransitive tasks were proposed, aimed at activating muscles antagonistic to injected ones. From the second to the sixth post-injection month increasing complex functional activities, bimanual and unimanual tasks, with or without functional orthoses were utilized. Either motor tasks, requiring previously selective then sequential executive control, or perception oriented tasks were considered. Setting was particularly important in guiding and supporting activities, every exercise was incorporated into a game or routine activity. Toys, common objects or specifically constructed items were used. Repetition was often needed to fix newly learned abilities, but each exercise was slightly modified every few repetitions in order to maintain interest, limit frustration and improve generalization. Family cooperation helped transfer exercised abilities to daily life. Video recording and testing before, during and after treatment were performed. Conclusion:Functional intensive individualized child-focused approach, combining physiotherapy and orthoses, is effective in improving manipulation after botulinum injection. Positive standardized test results (AHA, Abilhand-kids, Shuee, soon to be released data) are encouraging. This approach is limited by the time required for preparing individualized treatments and personalizing settings.

2011 - L'evoluzione dei principi ispiratori della riabilitazione infantile a partire dalle posizioni concettuali di Adriano Milani Comparetti [Articolo su rivista]
Ferrari, Adriano
abstract

Vengono analizzati i progressi della Riabilitazione in campo infantile degli ultimi venticinque anni partendo dalle scelte indicate da Adriano Milani Comparetti. I temi affrontati riguardano la progettazione in condizione isorisorse, la presa in cura e la presa in carico, la specificità e la globalità, l’intensività dell’intervento terapeutico, la natura dell’esercizio e la sua relazione con lo sviluppo normale, i percorsi di apprendimento del paziente, la relazione con la famiglia, il rapporto tra medici e terapisti e tra terapisti e bambini, i disturbi della relazione, la formazione dell’operatore ed, infine, il delicato tema dei metodi di trattamento verso la metodologia.

2011 - Neuroni Mirror e riabilitazione in età evolutiva [Articolo su rivista]
Ferrari, Adriano
abstract

Un bambino con paralisi cerebrale infantile (PCI) su tre è affetto da emiplegia. Tradizionalmente questi pazienti ricevono fisioterapia e terapia occupazionale al fine di incentivare al massimo le loro capacità residue. La recente scoperta dei neuroni mirror ha permesso di aprire nuove frontiere nel campo della neuro riabilitazione. I neuroni specchio sono stati scoperti per la prima volta nella corteccia premotoria del macaco. Esistono evidenze sperimentali secondo cui le aree motorie si attivano sia quando viene eseguito un atto motorio finalizzato, sia quando l’azione è semplicemente osservata o mentalmente rievocata. Anche nell’uomo è stata dimostrata un’attivazione delle stesse aree motorie sia durante l’osservazione di atti motori finalizzati che durante l’esecuzione delle stesse azioni, e questo in modo somatotopicamente organizzato. L’osservazione e l’imitazione motoria rappresentano un tipo di approccio riabilitativo che agisce sulla riorganizzazione dei circuiti neuronali, impiegando sia meccanismi diretti che indiretti. Partendo da questi presupposti abbiamo pensato di sottoporre un gruppo di pazienti a un training standardizzato che prevedeva l’osservazione e la riproduzione di atti motori ecologici, uni e bimanuali a complessità crescente, per un periodo di tempo limitato. La probabile efficacia del trattamento, associata al suo approccio ecologico, alla relativa facilità nel metterlo in atto e alla limitata durata temporale potrebbe rappresentare un punto di partenza favorevole affinché tale metodica possa, eventualmente, diffondersi nella pratica clinica.

2011 - Presentazione della serie di contributi dedicati alla riabilitazione in età evolutiva [Articolo su rivista]
Ferrari, Adriano
abstract

Presentazione della serie di contributi dedicati alla riabilitazione in età evolutiva.

2011 - UPCAT: disegno di uno studio sull'efficacia dell'osservazione dell'azione nella riabilitazione del bambino con emiplegia [Articolo su rivista]
Ferrari, Adriano; Sgandurra, G.; Burzi, V.; Parente, E.; Di Gioia, C.; Cioni, G.
abstract

La realizzazione con successo di uno studio clinico randomizzato controllato (RCT), che rappresenta il gold standard nella valutazione di nuovi interventi terapeutici e riabilitativi, è possibile se viene costruito preventivamente un disegno dello studio basato su rigorosi principi scientifici. Il Consolidated Standard of Reporting Trials (CONSORT) è stato ideato per definire una serie di punti essenziali da seguire per redigere un RCT e, quindi, fornisce indirettamente i criteri essenziali richiesti che devono essere valutati a priori durante la fase di definizione dello studio. Occorre, infatti, che all’inizio il ricercatore clinico pianifichi tutte le varie fasi dello studio, decida le modalità più appropriate con cui eseguirlo e preveda le eventuali difficoltà in modo tale da ridurre al minimo i possibili bias. Elementi quali la definizione della numerosità del campione e la scelta delle misure di outcome primarie e secondarie sono requisiti fondamentali nella costruzione di un RCT. Nel contempo la definizione della modalità di randomizzazione, di allocazione e di blinding dello studio sono indispensabili affinché il trial possa scientificamente essere definito un RCT valido. Questo lavoro presenta il processo di scelta del disegno di studio, secondo le modalità previste dal CONSORT, per il progetto multicentrico denominato UPCAT (Upper Limb Children Action observation Therapy), un RCT destinato a valutare l’efficacia di un modello riabilitativo fondato sulla recente scoperta del sistema mirror, per la riabilitazione dell’arto superiore in bambini con emiplegia. Verrà dimostrato come è possibile, una volta disegnato ad hoc lo studio e le modalità di intervento, condurre e portare a termine tutte le varie fasi previste.

2011 - Upper limb children action-observation training (UP-CAT) study: design of a randomised clinical trial for children with hemiplegia [Abstract in Rivista]
Ferrari, Adriano; Sgandurra, G.; Sicola, E.; Di Pietro, R.; Burzi, V.; Filippi, M. C.; Parente, E.; Di Gioia, C.; Fogassi, L.; Cioni, G.
abstract

Objective: The purpose of the present study was to design and test a Randomised Clinical Trial (RCT) for evaluating the efficacy of action-observation therapy in improving the upper limb (UL) activity in children with hemiplegia. Background: Rehabilitation for children with hemiplegia to improve function in the impaired UL uses a wide range of intervention programs; researches using adequately powered RCTs, rigorous methodology and valid outcome measures are essential, to provide the highest level support of therapy effectiveness. Design/Methods: The trial was designed according to Consolidated Standards of Reporting Trials (CONSORT) Statement. It was a randomised, evaluator-blinded, matchpair group trial. Children were randomised within pairs to either experimental or control group. The experimental group performed an Action–Observation Therapy based on watching video sequences of goal actions, chosen according to their UL functional level, combined with motor training with their hemiplegic UL. The control group performed the same tailored actions after watching computer games. A carefully revision of psychometric properties (e.g. small detectable differences) of UL outcome measures for hemiplegic children was performed. Assisting Hand Assessment was chosen as primary measure and based on its power calculation a sample size of 12 matched pairs was established. Moreover, Melbourne and ABILHAND-Kids were included as secondary measures. The time line of assessments was T0 (on the week preceding the onset of the treatment), T1 and T2 (on the week and 8 weeks after the end of the treatment, respectively). Results: We were able to perform children recruitment and testing in the 24 consecutive children according to above experimental planning. The two experimental and control groups differ only for the type of observation but the performed actions were similar so that the changes induced by observation should be measured. Conclusions: To provide reliable results of program rehabilitation effectiveness it is essential to design RCT studies according to CONSORT guidelines.

2011 - Upper limb children action-observation training (UP-CAT): a randomised controlled trial in Hemiplegic Cerebral Palsy [Articolo su rivista]
G., Sgandurra; Ferrari, Adriano; G., Cossu; A., Guzzetta; L., Biagi; M., Tosetti; L., Fogassi; G., Cioni
abstract

BACKGROUND: Rehabilitation for children with hemiplegic cerebral palsy (HCP) aimed to improve function of the impaired upper limb (UL) uses a wide range of intervention programs. A new rehabilitative approach, called Action-Observation Therapy, based on the recent discovery of mirror neurons, has been used in adult stroke but not in children. The purpose of the present study is to design a randomised controlled trial (RCT) for evaluating the efficacy of Action-Observation Therapy in improving UL activity in children with HCP.METHODS/DESIGN: The trial is designed according to CONSORT Statement. It is a randomised, evaluator-blinded, match-pair group trial. Children with HCP will be randomised within pairs to either experimental or control group. The experimental group will perform an Action-Observation Therapy, called UP-CAT (Upper Limb-Children Action-Observation Training) in which they will watch video sequences showing goal-directed actions, chosen according to children UL functional level, combined with motor training with their hemiplegic UL. The control group will perform the same tailored actions after watching computer games. A careful revision of psychometric properties of UL outcome measures for children with hemiplegia was performed. Assisting Hand Assessment was chosen as primary measure and, based on its calculation power, a sample size of 12 matched pairs was established. Moreover, Melbourne and ABILHAND-Kids were included as secondary measures. The time line of assessments will be T0 (in the week preceding the onset of the treatment), T1 and T2 (in the week after the end of the treatment and 8 weeks later, respectively). A further assessment will be performed at T3 (24 weeks after T1), to evaluate the retention of effects. In a subgroup of children enrolled in both groups functional Magnetic Resonance Imaging, exploring the mirror system and sensory-motor function, will be performed at T0, T1 and T2.DISCUSSION: The paper aims to describe the methodology of a RCT for evaluating the efficacy of Action-Observation Therapy in improving UL activity in children with hemiplegia. This study will be the first to test this new type of treatment in childhood. The paper presents the theoretical background, study hypotheses, outcome measures and trial methodology.

2010 - Dysperceptive forms [Capitolo/Saggio]
Alboresi, Silvia; Ferrari, Adriano; Ferrari, Alberto
abstract

In over thirty years of clinical observation of cerebral palsied (CP) children, especially among premature babies with bilateral motor damage, we have repeatedly found a group of patients with a unique combination of clinical characteristics which, we believe, could represent a specific group within the CP categorization. For convenience, we have termed them dysperceptive and we have been studying their behavior in a fairly large group of patients in order to see if some phenomena, unmistakably observed in single cases, were recognizable, also in different degrees, in larger groups. We have maintained the term perceptual disturbance or dysperception for the first and most interesting hypothesis that the errors performed by these children could happen during the collection, interpretation, and re-elaboration of information, especially of the sense of movement, even if other fascinating theories can be found especially in the field of psychology. These complex behaviors, for example fear, can be observed during clinical examination or physiotherapeutic treatments. In addition, parents and older children often describe some specific situations, which are recurrent and typical, that take place in everyday life in different settings (at school, on holiday, with friends, etc.), often underlining the limitations produced by these phenomena regarding motor independence and quality of life. These signs can be observed in CP children with diverse motor damage (diplegia, tetraplegia, but not hemiplegia) and at different development levels. In order to explore consistency and recurrence of the more important or frequent dysperceptive signs, describe them in detail and collect evidence by suitable instruments, we have been and are still employing video recording sessions (natural history of these signs). © 2010 Springer-Verlag Milan.

2010 - Guide to the interpretation of cerebral palsy [Capitolo/Saggio]
Ferrari, Adriano; Alboresi, Silvia
abstract

The term cerebral palsy in English, paralisi cerebrale infantile in Italian, infirmité motrice cérébrale in French, paralisis cerebral in Spanish and Zerebral Bewegung Störung in German de fines a persistent but not unchangeable disorder of posture and motion, due to an organic and not progressive alteration of the cerebral function, determined by preperi- and post natal causes, before its growth and development are completed (Bax, 1964; Spastic Society Berlin, 1966, Edinburgh, 1969). © 2010 Springer-Verlag Milan.

2010 - Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures [Articolo su rivista]
Riccio, Massimo; Resca, Elisa; Maraldi, Tullia; Pisciotta, Alessandra; Ferrari, Adriano; Bruzzesi, G; DE POL, Anto
abstract

The aim of this study was to characterize the in vitro osteogenic differentiation of dental pulp stem cells (DPSCs) in 2D cultures and 3D biomaterials. DPSCs, separated from dental pulp by enzymatic digestion, and isolated by magnetic cell sorting were differentiated toward osteogenic lineage on 2D surface by using an osteogenic medium. During the differentiation process, DPSCs express specific bone proteins like Runx-2, Osx, OPN and OCN with a sequential expression, analogous to those occurring during osteoblast differentiation, and produce extracellular calcium deposits. In order to differentiate cells in a 3D space that mimes the physiological environment, DPSCs were cultured in two distinct bioscaffolds, MatrigelTM and Collagen sponge. With the addition of a third dimension, osteogenic differentiation and mineralized extracellular matrix production significantly improved. In particular, in MatrigelTM DPSCs differentiated with osteoblast/osteocyte characteristics and connected by gap junction, and therefore formed calcified nodules with a 3D intercellular network. Furthermore, DPSCs differentiated in collagen sponge actively secrete human type I collagen micro-fibrils and form calcified matrix containing trabecular-like structures. These neo-formed DPSCs-scaffold devices may be used in regenerative surgical applications in order to resolve pathologies and traumas characterized by critical size bone defects.

2010 - Mirroring ed apprendimento [Relazione in Atti di Convegno]
Ferrari, Adriano
abstract

l'autore descrive i meccanismi attraverso i quali i neuroni mirror potrebbero influenzare l'apprendimento motorio anche dopo lesione del SNC

2010 - Outcome evaluation of surgery treatment by means of gait analysis in children with cerebral palsy: the normality pattern is not an effective term of comparison [Abstract in Atti di Convegno]
Neviani, R.; Costi, Stefania; Borghi, C.; Ferrari, Adriano; Faccioli, S.; Ferrari, A.
abstract

INTRODUCTION: Among the treatments available for the rehabilitation of the alterations of walking in children affected by Cerebral Palsy (CP), multilevel surgery is one of the most effective and used solutions despite its irreversible nature. Increasingly literature provides evidences of the large benefits afforded by Gait Analysis (GA) in the process of surgery decision making and in the choice of the most appropriate surgery tecnique [1]. However, besides the diagnostic process, GA can be used in order to measure accurately and effectively the outcome of the treatment [1]. The aim of the present study is to demonstrate how deviations in the kinematic pattern of walking provoked by a surgery treatment can determine i) an improvement in the motor performance and ii) an increase in the autonomy level in action, also when they vary in the opposite direction with respect to the normal pattern.METHODS: 15 dipelgic children with purely spastic forms of CP (age range 7 – 17 years) classified in one of the four forms of diplegia proposed by [2] and addressed by a clinical examination to undergo a functional surgery treatment on the lower limbs, participated in the study. The aim of the surgery treatment was to improve the motor performance and the autonomy level in walking. The treatments adopdet included tendon and muscolar lengthenings, and interventions of skeleton correction. The motor performance exhibited by the subjects was measured both by means of the Gross Motor Function Measure 88 (GMFM) by using merely the dimension D and E [3], and of GA, the day before (session PRE) and after six months (session POST) the surgery intervention. The kinematic of at least three gait cycles for each limb was acquired through the protocol Total3DGait [4] by means of an 8 cameras Vicon MX+ system (Vicon Motion System, UK). The 9 kinematic variables relative to the sagittal, frontal and transverse plane rotations of the hip, knee and ankle and the 4 relative to the rotations on the sagittal and frontal plane of the segments pelvis and trunk obtained during the PRE and POST sessions were compared with respect to the normality bands [4]. In particular, for each of the 13 kinematic variables considered, set of 3 mean waveforms were computed from the gait cycles acquired in the two sessions PRE and POST and from the normality bands. For each subject, the approach of the 13 mean waveforms of the POST session towards the normality, with respect to the ones of the session PRE, was computed in terms of offset (Off) and Range of Movement (ROM). In particular, positive values of Off and ROM indicate an approach of the POST mean waveforms to the normal ones in the absolute and range terms. RESULTS: The GMFM values obtained were positive in 13 cases over 15, with a percentage mean value of 3.4 and a standard deviation of 6.1. The following table reports the mean and the standard deviation values relative to Off and ROM obtained from the 13 kinematics variable considered for each of the 15 subjects enrolled. p1p2p3p4p5p6p7p8p9p10p11p12p13p14p15ROMmean-0.3-1.60.4-0.70.22.11.3-0.5-0.31.8-0.50.8-0.91.50.2sd3.36.64.09.04.25.76.12.56.43.73.65.54.62.74.3Offmean0.3-2.00.20.9-0.33.3-0.60.53.23.72.6-0.11.11.4-0.2sd5.85.16.44.95.98.25.53.08.414.96.95.47.66.24.1Table 1: mean and standard deviations (sd) values obtained for Off and ROM over the 13 kinematics variables considered for the 15 subjects (p1 – p15).DISCUSSION: The GMFM data obtained revealed an improvement in the autonomy level in action in 13 cases over 15. On the contrary, the elevated values of the standard deviations together with mean values close to 0 of Off and ROM parameters, demonstrate that the kinematic waveforms obtained in the POST session did not approach the normality pattern homogeneously among the different joints of a single subject. Therefore, the comparison of the GA data with respect to the normality bands was not effective in the asses

2010 - Proposta di esame PiTrAv per valutare le competenze professionalizzanti nel CL in Fisioterapia: la prospettiva di studenti e tutor clinici. [Abstract in Rivista]
Costi, Stefania; Sandra Bassi, Pt; Maria Pia Padalino, Pt; Luisa Montanari, Pt; Elena Ferrari, Pt; Marco Altimani, Ptstudent; Ferrari, Adriano
abstract

Nel CL in Fisioterapia (CLF) l’esame di tirocinio del III anno deve garantire la competenza professionale.[1] Presso il CLF del nostro Ateneo applichiamo una modalità di esame finale di tirocinio definita PiTrAv. L’acronimo sintetizza le sue tre fasi: Pianificazione, Trattamento, AutoValutazione. Esso valuta l’abilità di risoluzione di un problema clinico e le abilità gestuali e relazionali che gli studenti adottano per risolvere efficacemente un problema in situazione reale. L’indagine qualitativa ha lo scopo di evidenziare le opinioni dei tutor clinici e degli studenti partecipanti all’esame per verificarne la validità “di facciata” in qualità di esame abilitante alla professione fisioterapista. MATERIALI E METODISono stati auto-somministrati dei questionari individuali, anonimi, a risposta aperta breve rivolti agli studenti e ai tutor clinici-valutatori nell’esame PiTrAV. La somministrazione è avvenuta prima della comunicazione agli studenti del voto ottenuto. Le risposte ai questionari sono state analizzate da due fisioterapisti indipendenti, ricorrendo ad un terzo parere in caso di disaccordo. RISULTATIStudenti: PiTrAv è stato giudicato completo e globale, facendo emergere competenze professionali di ragionamento clinico e presa in carico del paziente e rendendo evidenti le competenze mancanti. Le criticità sollevate riguardano l’elevato stress percepito e la emotività vissuta nella situazione. I tempi di esame sono stati giudicati da molti studenti inadeguati per esprimere pienamente le competenze professionali e le abilità di ragionamento clinico. Tutor clinici: PiTrAv è stato giudicato in grado di far emergere competenze professionalizzanti di presa in carico, di ragionamento clinico e relazionali. Le criticità evidenziate riguardano la mancanza di un livello accettabile di performance oggettivo, univoco e condiviso, la durata complessiva dell’esame e l’ingente impegno organizzativo. CONCLUSIONIPiTrAV sembra essere un valido strumento per certificare l’acquisizione di abilità professionalizzanti degli studenti fisioterapisti. Esso misura l’abilità di integrazione delle conoscenze teoriche e tecnico-comportamentali, finalizzata a risolvere problemi attraverso il ragionamento clinico.

2010 - Severe scoliosis in neurodevelopmental disabilities: clinical signs and therapeutic proposals. [Articolo su rivista]
Ferrari, Adriano; Ferrara, C; Balugani, M; Sassi, S.
abstract

AbstractScoliosis is an important cause of disability in childhood, due to its incidence and limitation on ability. In neurodevelopmental disabilities, scoliosis worsens the already limited functional capacities of the child and can thwart abilities partially recovered through rehabilitation. In celebral palsied children (CP), scoliosis is considered a consequence of damage to the central nervous system or a complication of a peripheral impairment, in particular, through obliquity of pelvis, of the unilateral dislocation of hip. In order to explain the scoliosis of central origin, primitive and pathological reflexes, reactions or automatisms must be taken into account, especially the asymmetrical ones. This contradicts the absence of scoliosis in hemiplegia. On the contrary, symmetrical patterns should act as protective factors. However, the greater incidence of scoliosis in tetraplegia than in dipegia does not confirm this idea. Scoliosis is secondary when it is linked to an unilateral hip dislocation for side of convexity, proximity, measure and timing sequence. In childhood neuromuscular diseases (NMD), scoliosis is the unavoidable consequence of muscle weakness. The only protective factor may be muscle stiffness in case of fibrotic degeneration. The main curve is reducible for longer periods, while the less reducible secondary one at cervical level can limit the correction possibilities, due to the need to keep the head aliened. In spina bifida (SB) children, lesional and supralesional scoliosis can be present. In the former, the malformative ones directly derive from the vertebrae involved in the myelomeningocele and the secondary ones develop from the unilateral hip dislocation similar to CP, or from muscular imbalance (a typical feature of SB, especially for lower lumbar levels) or from primitive skeletal malformations of pelvic girdle or lower limbs. The acquired ones are caused by muscle weakness as in NMD. In the supralesional scoliosis, the curve is the consequence of an impairment in neurological structures especially of ponto-cerebellar carrefour or of an acquired tethered cord and may affect any segment of spinal column, also above the primitive lesion level. The scoliosis in neurodevelopmental disabilities can be treated conservatively with corsets and postural systems, with limited results. or through a surgical approach, often made difficult due to the multiple impairments present in the same patient

2010 - THE ROLE OF GAIT ANALYSIS IN ESTABLISHING THE FUNCTIONAL SURGERY PROGRAM IN DIPLEGIC CP CHILDREN. [Abstract in Rivista]
Faccioli, S; Reverberi, S; Neviani, Rita; Costi, Stefania; Benedetti, MARIA GRAZIA; Giannini, S; Ferrari, Adriano
abstract

Orthoses represent one of the tools most frequently used for the rehabilitation course of children affected by cerebral palsy (CP). A number of studies tried to evaluate the effectiveness of orthoses [1]. At present time no homogeneous results were found, both for what concerns their impact on the motor performance, and, mainly, for what concerns their effect in the fields of activities and participation [2]. These fields are still now very slightly explored. As indicated by [2], it is therefore necessary to deeper explore these issues in order to improve the rehabilitation care. This study aims at verifying the effectiveness of the orthoses on motor performance, with relation to gross motor abilities and patient satisfaction.

2009 - Bioetica e riabilitazione nel bambino grave [Articolo su rivista]
Ferrari, Adriano
abstract

Bioetica e riabilitazione nel bambino grave

2009 - Concetti di riabilitazione del bambino affetto da esiti di mielomeningocele [Monografia/Trattato scientifico]
Ferrari, Adriano
abstract

Concetti di riabilitazione del bambino affetto da esiti di mielomeningocele

2009 - Concetti di riabilitazione delle malattie neuromuscolari [Monografia/Trattato scientifico]
Ferrari, Adriano
abstract

Riabilitazione nelle malattie neuromuscolari

2009 - La riabilitazione del bambino con paralisi cerebrale infantile [Articolo su rivista]
Ferrari, Adriano
abstract

La riabilitazione del bambino con paralisi cerebrale infantile

2009 - Lignes de conduite pour la rééducation de l'enfant atteint d'infirmité motrice cérébrale en Italie. Italian guidelines for rehabilitation of the cerebral palsy child [Articolo su rivista]
Ferrari, Adriano; G., Tarditi
abstract

In Italy, guidelines for care for cerebral palsy children arose from work conducted by the intersociety commission of the Italian society of physical medicine and rehabilitation (SIMFER) and the Italian society of childhood and adolescence neuropsychiatris (SINPIA) which began in 1999 and ended in 2001. the texts were approved by both societies in 2002 and accepted by Ministry of Health in june of that year. A first revision was published in 2005.

2009 - ORTESI MODULARE ASTRAGALO CALCANEARE (OMAC): STUDY OF ITS EFFICACY IN THE CORRECTION OF THE VALGUS-PRONATUS FOOT IN CHILDREN WITH CEREBRAL PALSY.  Gait & Posture 30 · October 2009  [Abstract in Rivista]
Ferrari, Adriano; Costi, Stefania; Flori, G; Neviani, Rita; Raggi, M; Cutti, A.
abstract

Ankle Foot Orthoses (AFOs) are frequently prescribed for ambulatory children with Cerebral Palsy (CP) to improve their walking pattern. In particular, AFOs are currently indicated to prevent and correct the equinus-valgus-pronatus foot deformity. However, several studies indicated that walking with AFOs impairs the second and the third rocker [1]. A new model of orthosis, named the “Ortesi Modulare Astragalo Calcaneare” (OMAC, fig 1), has been recently proposed and patented. This orthosis was designed to overcome the AFOs limitations, that is preventing the equinus-valgus-pronatus foot but preserving the second and third rocker. The purpose of this study was to assess the efficacy and the compliance of the use of the OMAC with respect the AFO in children with CP.

2009 - Paralisi Cerebrale Infantile [Monografia/Trattato scientifico]
Ferrari, Adriano
abstract

riabilitazione in età evolutiva

2009 - Predictors of successful sexual partnering of adults with Spina Bifida [Articolo su rivista]
C., Gatti; C., Del Rossi; Ferrari, Adriano; E., Casolari; G., Casadio; G., Scire
abstract

Predictors of successful sexual partnering of adults with Spina Bifida

2009 - The Sapstic Forms of Cerebral Palsy [Monografia/Trattato scientifico]
Ferrari, Adriano; G., Cioni
abstract

Guida alla valutazione delle funzioni adattive

2008 - Clinica Riabilitativa e ausili [Capitolo/Saggio]
Ferrari, Adriano
abstract

Clinica Riabilitativa e ausili

2008 - Duchenne muscle activity evaluation and muscle function preservation: is it possible a prophylactic strategy? [Articolo su rivista]
Palmieri, Beniamino; V., Sbendorio; Ferrari, Adriano; A., Pietrobelli
abstract

Duchenne muscular dystrophy yields pervasive and progressive muscle mass loss. In the current measures relating to the monitoring of disease progression the following are relevant (i): the type of scale used, (ii) the clinical significance of the attribute being measured and (iii) the mathematical properties of the data provided. The high prevalence of obesity at an early stage of this pathology could result not only from reduced physical activity, but also from low resting energy expenditure, abnormal nutrient utilization or overfeeding. This muscle weakness may be attenuated by regular low-intensity exercise. However, there is a critical lack of data to support appropriate exercise prescription. Because inappropriate activity may exacerbate the dystrophic process, a systematic analysis of muscle function to determine potential exercise load thresholds to avoid injury in dystrophic mice and dogs, and then in humans is recommended.

2008 - The term diplegia should be enhanced (I): a new rehabilitation oriented classification of cerebral palsy. [Articolo su rivista]
Ferrari, Adriano; Alboresi, Silvia; S., Muzzini; R., Pascale; S., Per azza; G., Cioni
abstract

The classification systems for cerebral palsy (CP) need to be continuously updated, according to specific aims and to significant changes observed over the years in the panorama of CP. A simplification of CP categories, abandoning the use of the term diplegia, has been recently suggested. Conversely, in this paper a new proposal for classification of CP is briefly presented, where special attention is given to diplegia which is suggested to be divided into four main clinical forms, according to the patterns of walking observable in these subjects. The proposed classification was applied to a large population of 213 subjects with diplegia, among 467 cases of CP admitted to two reference centres for this disorder. The relative incidence of the four forms is reported. The adopted classification criteria, based on a primary ability of professionals working in rehabilitation, i.e. observation capacity, makes this approach simple and easy to use at all levels of the rehabilitation services for CP.

2008 - The term diplegia should be enhanced (II): contribution to validation of the new rehabilitation oriented classification. [Articolo su rivista]
G., Cioni; M., Lodesani; M., Coluccini; S., Sassi; P. B., Paolicelli; R., Pascale; S., Perazza; Ferrari, Adriano
abstract

Recent proposals of classification for cerebral palsy (CP), mainly revised for epidemiological purposes, suggest to abandon the use of the term diplegia. Conversely, in this paper data are presented to support the proposal to maintain the distinction between spastic tetraplegia and diplegia, and to subdivide this latter according to four main clinical patterns of walking observable in these children. This proposal of classification was validated by testing a group of 467 subjects with CP, of whom 213 with diplegia and 115 with tetraplegia, consecutively admitted between January 2005 and December 2006 to two national reference centers for this disability. The results were compared with findings obtained by other methods of classifying gross and fine motor function and associated disorders. The subjects with tetraplegia strongly differ from those of diplegia, both for motor functions and for other disabilities. The four main walking patterns of spastic diplegia were easily recognizable and observers were able to assign most of the subjects to one form of the classification. Significant correlations between walking forms of diplegia and distribution of Gross Motor Function Classification System (GMFCS) levels were found. Some of the forms significantly differ also for fine motor and mental disability. These findings suggest that in clinical practice the category of diplegia not only can be kept as a separate form of CP, but it may be enhanced, through the identification of different subcategories of children, divided according to their walking patterns.

2008 - The term diplegia should be enhanced. Part III: inter-observer reliability of the new rehabilitation oriented classification. [Articolo su rivista]
R., Pascale; S., Perazza; G., Borelli; E., Bianchini; Alboresi, Silvia; Paolicelli, P. B.; Ferrari, Adriano; G., Cioni
abstract

AIM: The aim of this study was to validate a recent classification of gait in children with the spastic diplegic form of cerebral palsy (CP) by checking the reliability of different scorers in assigning subject walking performance to one of the four specific patterns described in the classification. METHODS: The gait patterns of 50 children and adolescents with CP (23 males, 27 females; age range 3-17 years) were selected among patients whose videos were stored in the archives of the Pisa and Reggio Emilia Hospitals. Only video recordings of gait with homogeneous features (duration of at least 90 s, simultaneous recordings on sagittal and frontal views, and other criteria) were taken for examination. The videos were blindly scored using an observational gait scale, at first by two of the authors of the classification system (defined as ''maximum experts''), then by ten expert observers, and finally by 206 professionals of rehabilitation after a one-day training on the classification. Cohen's kappa statistics (k) and intra class correlations (ICC) were calculated. RESULTS: Kappa and ICC indicate an almost perfect agreement both between the two maximum experts and among the ten expert observers. Good results were also obtained in the group of one-day trained scorers. Only a few cases were assigned to the ''unclassified'' category. The profession of the observer (doctor or therapist) and previous knowledge of the classification had no significant influence on reliability scores. CONCLUSION: The results suggest that the proposed classification can be reliably applied, even utilizing short video recordings, to arrange diplegic children into different patterns. Further studies are needed to validate the use of this classification system for clinical and research aims.

2007 - Appropriatezza nella riabilitazione del bambino affetto da paralisi cerebrale infantile [Articolo su rivista]
Ferrari, Adriano
abstract

Per "appropriatezza" in clinica (diagnosi, terapia, ecc.) si deve intendere la misura in cui un particolare intervento è indicato, sia efficace per la persona che lo riceve.Nella riabilitazione del bambino affetto da paralisi cerebrale infantile (PCI), il concetto di appropriatezza è sostanzialmente poggiato sull'equilibrio che si riesce a stabilire fra gli interventi terapeutici erogati dai servizi sanitari, particolarmente da quelli di riabilitazione infantile , e le richieste della famiglia, incluse, a partire da una certa età, quelle del bambino stesso.

2007 - La visita fisiatrica [Capitolo/Saggio]
Ferrari, Adriano; Lodesani, Manuela
abstract

La visita fisiatrica

2007 - L’appropriatezza in riabilitazione infantile [Articolo su rivista]
Ferrari, Adriano
abstract

Nel vasto panorama della Riabilitazione, la riabilitazione infantile, ed in particolare la riabilitazione del bambino affetto da Paralisi Cerebrale, costituisce da sempre la fucina da cui provengono la maggior parte delle proposte riabilitative che trovano poi impiego anche nel recupero e nella rieducazione funzionale delle patologie dell'adulto, neurologiche e non solo.

2006 - A proposito di appropriatezza in riabilitazione [Relazione in Atti di Convegno]
Ferrari, Adriano
abstract

Possiamo parlare di appropriatezza di quanto siamo soliti compiere nel trattamento rieducativo e nella relazione di aiuto alla persona con mielolesione soltanto se facciamo riferimento al concetto generale di contratto terapeutico.

2006 - A proposito di appropriatezza in riabilitazione [Articolo su rivista]
Ferrari, Adriano
abstract

Possiamo parlare di appropriatezza di quanto siamo soliti compiere nel trattamento rieducativo e nella relazione di aiuto alla persona con mielolesione soltanto se facciamo riferimento al concetto generale di contratto terapeutico. Contratto terapeutico è ciò che viene concordato, in maniera esplicita o più spesso implicita, con il paziente e la sua famiglia al momento della presa in carico. Questo contratto raccoglie le istanze espresse dai parenti, primo interlocutore del Servizio, e successivamente quelle del paziente stesso, che costituiscono le richieste.

2005 - Aspetti critici delle classificazioni [Capitolo/Saggio]
Ferrari, Adriano
abstract

A tutt'oggi la paralisi cerebrale infantile viene dichiarata "turba persistente della postura e del movimento". Per restare coerenti con questa definizione, l'unica possibilità per una classificazione della PCI dovrebbe essere offerta dall'analisi dei disturbi della postura e del movimento (da intendersi più propriamente nel senso cinesiologico di gesto), valutati sia in senso qualitativo (natura), sia in senso quantitativo (misura).

2005 - Classificazione cinematica [Capitolo/Saggio]
Ferrari, Adriano
abstract

La paralisi cerebrale infantile (PCI) viene tutt'ora considerata "una turba persistente ma non immutabile della postura e del movimento", accogliendo sostanzialmente come ancora valida la definizione dettata ormai 40 anni fa da Martin Bax e riconfermata per altro dallo stesso autore "A persistent disorder of movement and posture caused by non-progressive defects or lesions of the immature brain".

2005 - Condizioni per il trattamento rieducativo [Capitolo/Saggio]
Ferrari, Adriano; M., Lodesani; S., Muzzini; S., Sassi
abstract

Al momento di accogliere il bambino affetto da paralisi cerebrale infantile (PCI) e di stipulare con la sua famiglia il contatto terapeutico, il primo compito importante ed a volte più difficile che impegna il medico riabilitatore è rappresentato dalla necessità di trasformare e di trasferire il concetto di lesione, con quanto di oggettivo e di provato lo accompagna, nel concetto di paralisi, condizione soggettiva e potenziale il cui trattamento si rivela pieno di se, di ma, di forse e di però.

2005 - Considerazioni metodologiche [Capitolo/Saggio]
Ferrari, Adriano; M., Lodesani
abstract

Agli importanti miglioramenti compiuti in campo clinico per la prevenzione, la diagnosi precoce e quando possibile il trattamento, ancora contenitivo più che emendativo, delle lesioni del sistema nervoso centrale (SNC), si stanno affiancando, se pur con una latenza non sempre giustificata, altrettanti progressi nell'ambito della rieducazione del bambino affetto da paralisi cerebrale infantile (PCI).

2005 - Difetti Motori [Capitolo/Saggio]
Ferrari, Adriano
abstract

Il difeto motorio viene universalmente considerato il cuore del problema della paralisi cerebrale infantile (PCI). Pur essendo consapevoli che esso non è quasi mai il solo problema presente e a volte non è neppure il più importante, riteniamo ancora giustificato iniziare l'analisi dei disturbi presentati da questa complessa patologia partendo dalle alterazioni subite dalla postura e dal movimento.

2005 - Difetti percettivi [Capitolo/Saggio]
Ferrari, Adriano
abstract

La definizione internazionale tuttora accreditata considerata la paralisi cerebrale infantile (PCI) unicamente una turba della postura e del movimento, trascurando in modo oggi inaccettabile l'influenza esercitata dai disturbi percettivi e dai problemi cognitivi, emotivi e relazionali sulla "natura del difetto" e sulla "storia naturale" di ciascuna forma clinica.

2005 - Forme diplegiche [Capitolo/Saggio]
Ferrari, Adriano; G., Cioni
abstract

Il vocabolo "diplegia" dovrebbe significare letterarmente "una paralisi cerebrale di due arti comunque distribuita" (quindi anche l'emiplegia), ma dai lavori di Freud in avanti il termine diplegia è stato comunemente utilizzato per indicare "una paralisi cerebrale dei due lati", quindi anche la tetraplegia e la doppia emiplegia, ivi comprese le sindromi non spastiche.

2005 - Forme dispercettive [Capitolo/Saggio]
Ferrari, Adriano; Muzzini, M. L. O. D. E. S. A. N. I. S.; S, Sassi
abstract

Il capitolo che descrive due forme di paralisi cerebrale, ha una chiave interpretativa di tipo percettivo e non motorio.

2005 - Forme emiplegiche [Capitolo/Saggio]
Ferrari, Adriano; G., Cioni
abstract

Il vocabolo "diplegia" dovrebbe significare letteralmente "una paralisi cerebrale di due arti comunque distribuita", ma dai lavori di Freud in avanti il termine diplegia è stato comunemente utilizzato per indicare "una paralisi cerebrale dei due lati", quindi anche la tetraplegia e la doppia emiplegia, ivi comprese le sindromi non spastiche.

2005 - Forme tetraplegiche [Capitolo/Saggio]
Ferrari, Adriano; M., Lodesani; S., Muzzini; S., Sassi
abstract

La letteratura considera tetraplegie, o tetraparesi, le paralisi cerebroli infantili caratterizzate da: interessamento equivalente di tutti e quattro gli arti, crescita somatica difficoltosa, ritardo mentale spesso importante, disturbi visivi frequenti, deficit uditivi possibili,compromissione orofacciale da paralisi pseudobulbare, con conseguenti disordini della masticazione, della deglutizione, della mimica, e del linguaggio, epilessia con crisi di difficile , leucomalcia periventricolare grave come lesione cerebrale più tipica.

2005 - Guida all'interpretazione della paralisi cerebrale infantile [Capitolo/Saggio]
Ferrari, Adriano; M., Lodesani; S., Muzzini; S., Sassi
abstract

L'espressione Paralisi Cerebrale Infantile definisce una "turba persistente ma non immutabile della postura e del movimento, dovuta ad una alterazione organica e non progressiva della funzione cerebrale, per cause pre - peri - post natali, prima che se ne completi la crescita e lo sviluppo".

2005 - Guidelines for rehabilitation of children with cerebral palsy [Articolo su rivista]
Ferrari, Adriano; G., Cioni
abstract

In the last few years on the international scene, and recently in Italy too, more and more attention has been paid to direct clinical practice to higher quality and more appropriate accessibility of health services. To achieve this, it has become necessary to stimulate the use of diagnostic and therapeutic procedures based on scientific evidence. The 1998-2000 Italian National Health Programme and the subsequent Law 229-99 have suggested adopting guidelines to better match these needs. Through them, it would become possible to reach the main aim which is to insure the highest appropriateness of intervention, reducing to a minimum the variability of medical choices in assistance strategies caused by subjective interpretation and lack of knowledge. Another reason for today's interest in guidelines is linked to 2 other processes that are currently taking place in the Italian Health System: firstly institutional certification and secondly the continuous education of medical staff. The creation, use, knowledge and participation in the verifying procedures of guidelines are integral parts of both these 2 processes, which today every single medical operator must be involved in.

2005 - Le forme spastiche della paralisi cerebrale infantile. Guida all'esplorazione delle funzioni adattive [Monografia/Trattato scientifico]
Ferrari, Adriano; Cioni, G.
abstract

Nel testo vengono affrontati i principali temi connessi alla valutazione delle funzioni adattive nelle forme spastice delle PCI (la definizione di PCI e le sue modifiche negli ultimi decenni, i nuovi orientamenti classificativi, l'eziopatogenesi, le correlazioni anatomico-funzioneli, la semiotica, i cosiddetti "disturbi associati" visivi, cognitivi, della vita di relazione, ecc.).

2005 - Problemi di riabilitazione in età evolutiva [Articolo su rivista]
Ferrari, Adriano
abstract

Gli straordinari progressi compiuti in campo clinico nella prevenzione, nella diagnosi tempestiva e nel trattamento emendativo, quando possibile, delle lesioni del sistema nervoso centrale (SNC) non sono stati affiancati, fino ad ora, da equivalenti miglioramenti nel campo della rieducazione del bambino affetto da paralisi cerebrale infantile (PCI).

2005 - Ricerche e terapie di frontiera nel trattamento della spina bifida [Curatela]
Ferrari, Adriano
abstract

La Spina Bifida è una delle più complesse patologie in campo medico e chirurgico. E', infatti, al contempo una affezione congenita ed evolutiva, neurologica e ortopedica, centrale e periferica, motoria e percettiva, somatica e viscerale, organica e psicologica ecc. Per poche altre patologie del bambino come dell’adulto il trattamento rieducativo esige un approccio multiprofessionale integrato, non tanto per una scelta metodologica, quanto per una reale necessità, poiché il singolo professionista non può possedere al contempo tutte le competenze richieste per tutte le fasce di età e per tutti i problemi presenti nel singolo paziente. Il volume raccoglie i frutti di un importante appuntamento scientifico, la Prima Conferenza Internazionale «Ricerche e terapie di frontiera nel trattamento della Spina Bifida», organizzata dall’Associazione GASBI (Genitori Associati Spina Bifida), in cui i maggiori specialisti in campo nazionale e internazionale hanno messo a confronto conoscenze, esperienze, progetti, al fine di costruire un approccio il più ampio e completo possibile a questa patologia, di illustrare le strade attualmente percorribili e di individuare nuove soluzioni e risposte sempre più mirate ed efficaci. Ricerche e terapie di frontiera nel trattamento della Spina Bifida presenta, infatti, i risultati che la ricerca scientifica sta producendo a livello internazionale, con l’obiettivo di chiarire ciò che è immediatamente spendibile e ciò che invece costituisce un sicuro progresso, ma non è ancora traducibile in termini di terapia applicativa. In primo piano la terapia precoce intrauterina (chirurgia fetale), la neuroriparazione delle lesioni motorie, le protesi motorie, le protesi sensoriali, le protesi intelligenti, la terapia genetica, la ricerca sulle cause della Spina Bifida... Interventi che acquisiscono la loro pienezza solo nella prospettiva descritta da Adriano Ferrari nella sua prefazione: «ogni conquista dell’uomo non può prescindere dall’etica e soprattutto dal diritto all’autodeterminazione del singolo individuo. Ricordiamoci che la diversità, ogni diversità, è un difetto quanto un valore e che il compito del terapeuta non è concretizzare i desideri dei genitori, ma realizzare la persona con Spina Bifida con le sue differenze e con i suoi limiti, aiutandola non tanto a diventare "almeno" uguale agli altri, perché nessuno può essere uguale a nessun altro, ma a divenire ciò che vuol veramente essere, cioè pienamente se stessa». Il volume costituisce una valida opportunità di conoscenza e aggiornamento per medici, operatori sociali, psicologi, educatori, ricercatori, docenti, genitori e familiari di persone con Spina Bifida.

2004 - Linee Guida per la riabilitazione dei bambini affetti da spina bifida [Articolo su rivista]
T., Redaelli; Ferrari, Adriano; M., Cazzagon; N., Sias; G., Traditi; A., Marucco; R., Camoriano; M., Nora; V., D'Annunzio
abstract

La Società Italiana di Medicina Fisica e Riabilitazione (SIMFER), in relazione ai propri compiti statutari e sulla base di indicazioni del Dipartimento di Programmazione del Ministero della Sanità, ha dato incarico ad una commissione di Soci di elaborare ""Linee guida per la riabilitazione dei bambini affetti da spina bifida"

2004 - Movimento,percezione,partecipazione: le dimensioni dell'intervento psicomotorio nella paralisi cerebrale infantile. [Articolo su rivista]
Ferrari, Adriano
abstract

Movimento,percezione,partecipazione: le dimensioni dell'intervento psicomotorio nella paralisi cerebrale infantile.

2004 - Riflessioni quasi filosofiche intorno agli enunciati del Manifesto per la riabilitazione del bambino. [Articolo su rivista]
Ferrari, Adriano
abstract

Con un commento puntuale al "Manifesto per la riabilitazione" viene illeustrato il concetto di riabilitazione come processo complesso e globale, cioè rivolto a tutti gli aspetti dell'individuo coinvolti nella disabilità (motori, cognitivi, psichici) , teso a rpomuovere nel bambino e nella sua famiglia la migliore qualità di vita possibile.

2002 - Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: A population-based case-control study [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Nacci, G.; Pietrini, V.; Bratter, P.; Alber, D.; Ferrari, Adriano; Vescovi, L.; Guidetti, D.; Sola, P.; Malagù, S.; Aramini, C.; Vivoli, Gianfranco
abstract

We analyzed the association between the environmental exposure to trace elements and the risk of sporadic amyotrophic lateral sclerosis (ALS) in a population-based case-control study in the Emilia-Romagna region in northern Italy. We evaluated exposure to selected trace elements by measuring toenail concentrations of the same by means of inductively coupled plasma optical spectrometry and instrumental neutron activation analysis. The final number enrolled in the study was 22 patients and 40 controls. Disease progression, assessed through a clinical score, was generally unassociated with toenail trace element levels, with the exception of an inverse relation with zinc and selenium content and a direct correlation with copper concentration. In logistic regression analysis, we found no evidence of an association between ALS risk and toenail content of cadmium, lead, copper, zinc, manganese, selenium, chromium, cobalt, iron, and aluminum. This investigation does not suggest a major role in sporadic ALS etiology of environmental exposure to these trace elements, though results for zinc, selenium, and copper should be evaluated with caution due to the potentiallimitations of toenails as biomarkers of chronic exposure in patients.

2002 - Erythrocyte zinc, copper, and copper/zinc superoxide dismutase and risk of sporadic amyotrophic lateral sclerosis: a population-based case-control study. [Articolo su rivista]
Vinceti, Marco; Bergomi, Margherita; Nacci, G.; Pietrini, V.; Ferrari, Adriano; Fortini, K; Guidetti, D.; Sola, P.; Rocchi, Emilio; Mancia, D.; Vivoli, Gianfranco
abstract

We investigated through a population-based case-control study the hypothesis that disturbances in the chemistry of copper and zinc and in activity of the antioxidant enzyme copper/zinc superoxide-dismutase (SOD1) are involved in the etiopathogenesis of sporadic amyotrophic lateral sclerosis (ALS). We recruited 20 patients with sporadic ALS and 22 population controls from three northern Italian provinces, and we analyzed zinc and copper content and SOD1 activity in erythrocytes. These variables were unrelated to disease progression as evaluated through a disability score; zinc concentrations inversely correlated with copper in referents but not in patients. SOD1 activity was lower and erythrocyte zinc and copper levels were slightly higher in patients than in referents. Comparing the second to the bottom tertile of erythrocyte SOD1 activity, relative risk of ALS was 0.4 (95% confidence interval 0.1-2.0); the risk further decreased to 0.1 (95% confidence interval 0-0.9) for comparison of highest to lowest tertile (P for trend 0.027). Copper and zinc levels were not associated with disease risk. Our findings indicate that a lower SOD1 activity is associated with ALS, but we cannot be sure whether this association is a marker of causal action or is secondary to a confounder, or to disease onset itself.

2002 - Immunohistochemical study of muscle biopsy in children with cerebral palsy [Articolo su rivista]
A., Marbini; Ferrari, Adriano; G., Cioni; M. F., Bellanova; C., Fusco; F., Gemignani
abstract

Muscle biopsy was examined in 20 children with cerebral palsy, using immunohistochemical methods for marker of denervation neural cell adhesion molecules (N-CAM) in addition to standard techniques. Histological and histochemical study showed mild myopathic changes, type 1 predominance, and type 1 and type 2 hypotrophy, in accord with previous observations. Immunohistochemical study showed N-CAM expression in most biopsies (15/20), usually in scattered fibers, whereas in four patients aged less than 6 years it was expressed in grouped fibers. Our study supports the hypothesis of motor unit remodeling as a consequence of spasticity, especially in early phases of the disease.

1996 - Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: Influence of environmental exposure to lead [Articolo su rivista]
D., Guidetti; M., Bondavalli; R., Sabadini; N., Marcello; Vinceti, Marco; S., Cavalletti; A., Marbini; F., Gemignani; A., Colombo; Ferrari, Adriano; Vivoli, Gianfranco; F., Solime
abstract

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000, On December 31st, 1992, the prevalence rate was 5.4 per 100,000, In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No. 12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

1996 - Immunohistochemical localization of utrophin and other cytoskeletral proteins in skin smooth muscle in neuromuscular diseases [Articolo su rivista]
A., Marbini; F., Gemignani; M. F., Bellanova; D., Guidetti; Ferrari, Adriano
abstract

We investigated the immunohistochemical distribution of cytoskeletal proteins in smooth muscles of 15 patients with Duchenne muscular dystrophy (DMD), 8 patients with Becker muscular dystrophy (BMD), 28 patients with various neuromuscular diseases, and 2 normal controls, performing skin and muscle biopsies. Dystrophin immunostaining confirmed absent reaction in the arrector pili muscles of DMD patients, faint positive reaction in BMD patients, and strong dystrophin reaction in patients with other neuromuscular diseases and normal controls. Immunostaining of utrophin was positive with variable intensity in the arrector pili muscles in all DMD patients. In BMD patients, utrophin was faintly expressed in the arrector pili muscles in 2 cases, and negative in the other 5 patients. In the other cases of neuromuscular diseases and in normal controls, immunostaining for utrophin was negative in the arrector pili muscles. Staining of the capillary endothelial cells and muscular vessel walls was seen in normal controls, as well as in DMD, BMD, and other neuromuscular diseases. Vinculin, vimentin and desmin were expressed both in arrector pili smooth muscles and in vessel walls of patients with dystrophinopathy and other neuromuscular diseases, as well as in normal controls. Thus utrophin is normally expressed in the smooth muscle of the vessels and its expression does not vary in neuromuscular diseases. On the contrary, in the arrector pili smooth muscle utrophin is not expressed in normal controls but it is in dystrophinopathies, paralleling the findings in striated muscle, which expresses utrophin in a reciprocal manner with respect to dystrophin.

1996 - Influence of the Treadmill Speed/Slope on Quadriceps Oxygenation during dynamic Exercise [Relazione in Atti di Convegno]
V., Quaresima; A., Pizzi; R. A., De Blasi; Ferrari, Adriano; M., Ferrari
abstract

One of the main obstacles that has restricted “in vivo” studies of skeletal muscle metabolism during exercise has been the invasive nature of tissue biopsy and the high cost of phosphorus nuclear magnetic resonance equipment. Big research efforts have been recently focused on the development of non-invasive optical techniques to monitor tissue functions. Changes of cerebral and muscle oxy- and deoxy-hemoglobin ([Hb02], [Hb]) can be quantitated from near infrared spectroscopy (NIRS) measurements combining absorption and optical pathlength (Ferrari et al. 1992). NIRS has been extensively used in neuroscience to measure cerebral oxygenation, blood flow, and blood volume (Edwards et al. 1988; Wyatt et al. 1990). Some efforts have been focused also on skeletal muscle. In the last four years the aim of our group has been to explore NIRS capabilities for muscle functional monitoring. Pathlength changes in muscle have been measured on volunteers in different experimental conditions by time resolved spectroscopy (Ferrari et al. 1993) and phase modulation (Duncan et al. 1993). Muscle oxygen consumption (V02) can be measured by NIRS at rest and during isometric exercise by the application of arterial occlusion (Cheatle et al. 1991; De Blasi et al. 1993). We recently proposed a new method for the simultaneous measurement of forearm blood flow and V02 by inducing a venous occlusion (De Blasi et al. 1994)

1993 - Differences and variations in the patterns of early independent walking [Articolo su rivista]
Cioni, G; Duchini, F; Milianti, B; Paolicelli, Pb; Sicola, E; Boldrini, A; Ferrari, Adriano
abstract

The early development of walking was investigated in 25 normal fullterm and in 25 low-risk preterm infants. All subjects were videorecorded within 3-4 weeks of the beginning of independent walking and again 4 months later. Analysis of the videos was carried out according to a predetermined list of items, with a semiquantitative score for each. The results indicate wide interindividual differences in normal infants in the form of independent walking. Several items seemed to be associated in different ways in different individuals. Age of onset, as long as the corrected age was considered, did not differ between preterm and fullterm infants, neither did their walking patterns. Gait asymmetries were often observed in both groups and they were related with asymmetries observable in prewalking locomotor behaviour. Toe-strike often occurred at the beginning of walking, but not after 4 months; in preterm infants the toe strike pattern correlated significantly with certain motor characteristics observed during the first weeks of life.