Stefano Masiero

University of Padova, Padua, Veneto, Italy

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Publications (63)107.29 Total impact

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    ABSTRACT: Background Spinal cord injury (SCI) is a severe neurological disorder associated not only with ongoing medical complications but also with a significant loss of mobility and participation. The introduction of robotic technologies to recover lower limb function has been greatly employed in the rehabilitative practice. The aim of this preliminary report were to evaluate the efficacy, the feasibility and the changes in the mobility and in the de-adaptations of a new rehabilitative protocol for EKSO™ a robotic exoskeleton device in subjects with SCI disease with an impairment of lower limbs assessed by gait analysis and clinical outcomes. Method This is a pilot single case experimental A-B (pre-post) design study. Three cognitively intact voluntary participants with SCI and gait disorders were admitted. All subjects were submitted to a training program of robot walking sessions for 45 min daily over 20 sessions. The spatiotemporal parameters at the beginning (T0) and at the end of treatment (T1) were recorded. Other clinical assessments (6 min walking test and Timed Up and Go test) were acquired at T0 and T1. Results Robot training were feasible and acceptable and all participants completed the training sessions. All subjects showed improvements in gait spatiotemporal indexes (Mean velocity, Cadence, Step length and Step width) and in 6 min Walking Test (T0 versus T1). Conclusions Robot training is a feasible form of rehabilitation for people with SCI. Further investigation regarding long term effectiveness of robot training in time is necessary. Trial registration ClinicalTrials.gov NCT02065830.
    Preview · Article · Dec 2016 · BMC Neurology
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    ABSTRACT: We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board. Six non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials. No increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease. We describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material. EudraCT:2009-014484-39 .
    Full-text · Article · Dec 2015 · Journal of Translational Medicine
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    ABSTRACT: Prevalence of oropharyngeal dysphagia among the elderly is high, but underestimated and underdiagnosed. It may give raise to relevant complications impacting on morbidity, hospital length of stay and health care costs. Dysphagia evaluation and management is a multidisciplinary task; it includes a detailed history taking, clinical and instrumental exams, and identification of the risk of aspiration. Long-standing individual abilities and impairments determine the goals of an ad hoc rehabilitation program. Currently there are no standard algorithmic approaches for the management of dysphagia in the elderly. Education of health professionals on early diagnosis and improvement of therapeutic strategies are mainstays to allow maximal recovery potential in this population. This narrative review summarizes the current rehabilitation approaches for dysphagia in the elderly. The aim is to inform the treating health care professionals, whether caring physician, physical medicine doctor, speech/swallowing therapist or nurse, on the state-of-the-art and stimulate discussion in the scientific community.
    No preview · Article · Nov 2015 · Aging - Clinical and Experimental Research
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    ABSTRACT: Background: Addiction is associated with dorso-lateral prefrontal cortex (DLPFC) dysfunction and altered brain-oscillations. High frequency repetitive transcranial magnetic stimulation (HFrTMS) over DLPFC reportedly reduces drug craving. Its effects on neuropsychological, behavioural and neurophysiological are unclear. Methods: We assessed psychological, behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification. Participants were randomized to active HFrTMS (10Hz, 100% motor threshold) or sham. Immediately before the first and after the last session, 32-channels EEG was recorded and alcohol craving Visual Analogue Scale, Symptom Check List-90-R, Numeric Stroop task and Go/No-go task administered. Tests were repeated at 1-month follow-up. Results: 17 subjects (mean age 44.7 years, 4 F) were assessed. Active rTMS subjects performed better at Stroop test at end of treatment (p=0.036) and follow up (p=0.004) and at Go-NoGo at end of treatment (p=0.05) and follow up (p=0.015). Depressive symptoms decreased at end of active treatment (p=0.036). Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham (p=0.026). No significant modifications over time or group emerged for craving and number of drinks at follow up. Conclusion: 4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms. An overall reduction of faster EEG frequencies was observed. Nonetheless, this schedule is ineffective in reducing craving and alcohol intake.
    Full-text · Article · Nov 2015 · Drug and alcohol dependence
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    ABSTRACT: Hemodilution during cardiopulmonary bypass (CPB) is widely used to decrease transfusion and improve microcirculation but has drawbacks, such as diminished hemoblogin levels. Among others, reduced brain oxygenation accounts for neurological adverse outcomes after CPB. The aim of the present study was to ascertain if and how continuous electroencephalogram (EEG) during CPB is affected by hematocrit level and what should be the minimum value to avoid significant frequency band shifts on the EEG. A comparative study design was used with 16 subjects undergoing elective mitral valve repair/replacement. EEG was continuously recorded during the surgical procedure (from anesthesia induction to 20 min after CPB end). Data were marked at relevant time points (T0 : before CPB start; T1 : after 30 min from CPB beginning; T2 : at CPB end), and the following 2 min EEG analyzed with a fast Fourier transform to obtain relative power for delta, theta, alpha, and beta bands. A general linear model for repeated measure was used to study interactions of time (T0 , T1 , and T2 ), EEG frequency band, and topographical distribution. The relative powers for each electrode were calculated and represented using topographic maps. Power spectrum differences between time points (T2 -T1 ; T2 -T0 ;T1 -T0 ) were calculated for each electrode, and differences >10%, considered indicative of neuronal sufferance, were included in further analysis. Cutoff hemoglobin values that maximize the proportion of correctly classified EEG band shifts were obtained by previous definition were obtained. At T2 , diffuse EEG slowing in delta and theta bands was detected; a minor slowing over anterior regions was evident at T1 for the theta band. Decrements in EEG power greater than 10% were detected only for the delta band at T2 . Hemoglobin concentration levels at which no slowing increase was evident were 9.4 mg/dL (Ht: 28.2%) at T1 and 9.2 mg/dL (Ht: 27.6%) at T2 . EEG burst-suppression pattern related to a lesser degree of slowing at T2 . In conclusion, we propose hemoglobin cutoff levels that prevent EEG slowing indicative of neuronal sufferance. In addition, burst-suppression EEG patterns offer higher central nervous system protection as measured on EEG. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
    No preview · Article · Jul 2015 · Artificial Organs
  • Paolo Manganotti · M Acler · Stefano Masiero · A Del Felice
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    ABSTRACT: Rehabilitation programs, to be efficiently tailored, need clear prognostic markers. In acute stroke, neurophysiological measures, such as motor evoked potentials (MEPs), have been proposed, although with discordant results. The aim of this study was to identify a reliable neurophysiological measure of recovery in acute poststroke individuals by combining MEPs and the N100 component of transcranial magnetic stimulationevoked potentials (TEPs). Nine acute post-stroke subjects were included. Clinical evaluation performed in the first week after the event included administration of the European Stroke Scale and Barthel Index and recording of MEPs and TEPs; administration of the clinical scales was repeated after one and three months. The presence/absence of MEPs and TEPs showed correlations with motor outcome. Individuals with a poorer outcome showed absence of both MEPs and TEPs; absence of MEPs alone was related to a partial recovery. Given the results of this exploratory study, further investigation is needed to define the accuracy of combined use of MEPs and TEPs as an approach for predicting motor recovery after acute stroke.
    No preview · Article · Jun 2015
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    Full-text · Conference Paper · Mar 2015
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    ABSTRACT: Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI) patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES). Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb). Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest that the MHCemb positive muscle fibers we observe result from the activation, proliferation and fusion of satellite cells, the myogenic precursors present under the basal lamina of the muscle fibers. Using morphological features and molecular biomarkers, we show that severely atrophic muscle fibers, with a peculiar cluster reorganization of myonuclei, are present in rodent muscleseven-months after neurectomy and in human muscles 30-months after complete Conus-Cauda Equina Syndrome and that these are structurally distinct from early myotubes. Beyond reviewing evidence from rodent and human studies, we add some ultrastructural evidence of muscle fiber regeneration in long-term denervated human muscles and discuss the options to substantially increase the regenerative potential of severely denervated human muscles not having been treated with h-bFES. Some of the mandatory procedures, are ready to be translated from animal experiments to clinical studies to meet the needs of persons with longterm irreversible muscle denervation. An European Project, the trial Rise4EU (Rise for You, a personalized treatment for recovery of function of denervated muscle in long-term stable SCI) will hopefully follow
    Full-text · Article · Feb 2015 · European Journal of Translational Myology
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    ABSTRACT: Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · Brain Stimulation
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    ABSTRACT: We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board. Six non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials. No increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease. We describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material. Trial registration
    Full-text · Article · Jan 2015 · Journal of Translational Medicine
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    ABSTRACT: Objective: To discover the anatomist who first identified the upper oesophageal sphincter. Method: The authors searched dozens of antique anatomy textbooks kept in the old section of the 'Vincenzo Pinali' Medical Library of Padua University, looking for descriptions of the upper oesophageal sphincter. Results: The oesophageal sphincter was drawn correctly only in 1601, by Julius Casserius, in the book De vocis auditusque organis historia anatomica… (which translates as 'An Anatomical History on the Organs of Voice and Hearing …'), and was properly described by Antonio Maria Valsalva in 1704 in the book De aure humana tractatus… ('Treatise on the Human Ear …'). Conclusion: Anatomists Casserius and Valsalva can be considered the discoverers of the 'oesophageal sphincter'.
    No preview · Article · Oct 2014 · The Journal of Laryngology & Otology
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    ABSTRACT: Action observation activates the same motor areas as those involved in the performance of the observed actions and promotes functional recovery following stroke. Movement observation is now considered a promising tool for motor rehabilitation, by allowing patients to train their motor functions when voluntary movement is partially impaired. We asked chronic-stroke patients, affected by either left (LHD) or right hemisphere (RHD) lesions, to observe either a left or right hand, while grasping a small target (eliciting a precision grip) or a large target (eliciting a whole hand grasp directed towards a target object). To better understand the effects of action observation on damaged motor circuits, we used transcranial magnetic stimulation (TMS) to induce motor evoked potentials (MEP) from two muscles of the unaffected hand in 10 completely hemiplegic participants. Results revealed that LHD patients showed MEP facilitation on the right (contralesional) M1 during action observation of hand-object interactions. In contrast, results showed no facilitation of the left (contralesional) M1 in RHD patients. Our results confirm that action observation might have a positive influence on the recovery of motor functions after stroke. Activating the motor system by means of action observation might provide a mechanism for improving function, at least in LHD patients.
    Full-text · Article · Apr 2014
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    Full-text · Article · Mar 2014 · European Journal of Translational Myology
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    ABSTRACT: Steroidogenic enzymes autoantibodies (SEAbs) are frequently present and are markers of autoimmune premature ovarian failure (POF) in females with autoimmune Addison's disease (AAD). The prevalence and the significance of SEAbs in males with AAD have not been yet defined. We studied the prevalence of SEAbs in a large cohort of males with AAD and assessed the relationship between SEAbs positivity and testicular function. 154 males with AAD (mean age 34yrs) were studied. SEAbs included autoantibodies to: steroid-producing-cells (StCA), detected by immunofluorescence; steroid 17α-hydroxylase (17α-OHAbs) and side-chain-cleavage enzyme (SCCAbs) measured by immunoprecipitation assays. Gonadal function was evaluated by measuring follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex-hormone-binding-globulin (SHGB), anti-Müllerian hormone (AMH), inhibin-B (I-B). 26 males, 10 SEAbs(+) and 16 SEAbs(-) were followed-up for a mean period of 7.6 years to assess the behavior of SEAbs and testicular function. SEAbs were found in 24.7% of males with AAD with the highest frequency in patients with APS-1. The levels of reproductive hormones in 30 SEAbs(+) males were in the normal range according to age and were not significantly different compared to 55 SEAbs(-) males (p>0.05). During follow-up, both SEAbs(+) and SEAbs(-) patients maintained normal testicular function. SEAbs were found with high frequency in males with AAD, however were not associated with testicular failure. This study suggests that the diagnostic value of SEAbs in males with AAD differs compared to females and this may be related to the immuno-privileged status of the testis.
    No preview · Article · Feb 2014 · Clinical & Experimental Immunology

  • No preview · Conference Paper · Nov 2013
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    ABSTRACT: Permanent denervated muscles were evaluated by ultra sound (US) to monitor changes in morphology, thickness, contraction-relaxation kinetics and perfusion. In a case of monolateral lesion of the sciatic nerve (due to a surgical neurotomy during the removal of hyperplastic lifenodes in the pelvis) morphology and ultrasonographic structure of the denervated muscles changed during a period of electro stimulation from a pattern typical of complete denervation-induced muscle atrophy to a pattern which might be considered "normal" when detected in an old patient. Despite the higher than normal energy of the delivered electrical stimuli of Vienna home-based Functional Electrical Stimulation (h-b FES) the muscles shown electromyografic and ultrasonographyc signs of re-innervation during the years of training.
    Full-text · Article · Sep 2013 · Biomedizinische Technik/Biomedical Engineering
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    ABSTRACT: This is a single case report about the possibility to recover tetanic contractility in a peripherally denervated and atrophic tibialis anterior muscle (TA). We performed a first electrostimulation test (ET1) to assess the muscular reactivity to electrical stimulation and measured TA thickness by US. Based on the parameters obtained during ET1, we suggested home-based surface electrostimulation training for 2 months and then we performed a second electrostimulation test (ET2). In ET2 there was an evident reduction of the impulse length necessary to evoke a twitch response, reflecting the fact that there was a recovered excitability of the muscle. Lowering duration of the impulse it could possible to use a higher frequency of stimulation to obtain tetanic contractility, that could represent the best muscular training to avoid atrophy and to use electrical stimulation as walking aid in peripheral denervation.
    Full-text · Article · Sep 2013 · Biomedizinische Technik/Biomedical Engineering
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    ABSTRACT: Addison's disease (AD) is a rare endocrine condition. we aimed to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633 Italian patients with AD followed-up since 1967. adrenal-cortex autoantibodies, presence of other autoimmune and non-autoimmune diseases, non-adrenal autoantibodies, adrenal imaging and genetic profile for HLA-DR and AIRE were analyzed. 492(77.7%) patients were found to be affected by autoimmune AD(A-AD), 57(9%) tuberculous AD, 29(4.6%) genetic-associated AD, 10(1.6%) adrenal cancer, 6(0.94%) post-surgical AD, 4(0.6%) vascular disorder related, 3(0.5%) post-infectious AD, and 32(5.1%) were defined as idiopathic. Adrenal cortex antibodies were detected in the vast majority (88-100%) of patients with recent onset A-AD, but in none of those with non-autoimmune AD. Adrenal imaging revealed normal/atrophic glands in all A-AD patients. 88% of patients with A-AD had other clinical or autoimmune diseases or were positive for non-adrenal autoantibodies. BASED ON THE COEXISTENCE OF OTHER AUTOIMMUNE DISORDERS, 65.6% OF PATIENTS WITH A-AD WERE FOUND TO HAVE TYPE 2 AUTOIMMUNE POLYENDOCRINE SYNDROME (APS-2), 14.4% APS-1 AND 8.5% APS-4. CLASS II-HLA ALLELES DRB1*03 AND *04 WAS INCREASED, AND DRB1*01,07,13 WAS REDUCED IN APS-2 PATIENTS WHEN COMPARED TO CONTROLS. 96% OF THE PATIENTS WITH APS-1 REVEALED AIRE GENE MUTATIONS.CONCLUSIONS: A-AD is the most prevalent form of adrenal insufficiency in Italy, and approximately 90% of the patients are adrenal autoantibody positive at the onset. Assessment of patients with A-AD for the presence of other autoimmune diseases should be helpful in monitoring and diagnosing APS type 1, 2 or 4 and improving patients care.
    Preview · Article · Sep 2013 · European Journal of Endocrinology
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    Full-text · Article · Aug 2013 · European Journal of Translational Myology
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    ABSTRACT: Background Ankylosing spondylitis is a major chronic rheumatic disease that predominantly affects axial joints, determining a rigid spine from the occiput to the sacrum. The dorsal hyperkyphosis may induce the patients to stand in a stooped position with consequent restriction in patients’ daily living activities. The aim of this study was to develop a method for quantitatively and objectively assessing both balance and posture and their mutual relationship in ankylosing spondylitis subjects. Methods The data of 12 healthy and 12 ankylosing spondylitis subjects (treated with anti-TNF-α stabilized), with a mean age of 51.42 and 49.42 years; mean BMI of 23.08 and 25.44 kg/m2 were collected. Subjects underwent a morphological examination of the spinal mobility by means of a pocket compass needle goniometer, together with an evaluation of both spinal and hip mobility (Bath Ankylosing Spondylitis Metrology Index), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index). Quantitative evaluation of kinematics and balance were performed through a six cameras stereophotogrammetric system and a force plate. Kinematic models together with a test for evaluating balance in different eye level conditions were developed. Head protrusion, trunk flexion-extension, pelvic tilt, hip-knee-ankle flexion-extension were evaluated during Romberg Test, together with centre of pressure parameters. Results Each subject was able to accomplish the required task. Subjects’ were comparable for demographic parameters. A significant increment was observed in ankylosing spondylitis subjects for knee joint angle with the target placed at each eye level on both sides (p < 0.042). When considering the pelvic tilt angle a statistically significant reduction was found with the target placed respectively at 10° (p = 0.034) and at 30° (p = 0.019) less than eye level. Furthermore in ankylosing spondylitis subjects both hip (p = 0.048) and ankle (p = 0.029) joints angles differs significantly. When considering the posturographic parameters significant differences were observed for ellipse, center of pressure path and mean velocity (p < 0.04). Goniometric evaluation revealed significant increment of thoracic kyphosis reduction of cervical and lumbar range of motion compared to healthy subjects. Conclusions Our findings confirm the need to investigate both balance and posture in ankylosing spondylitis subjects. This methodology could help clinicians to plan rehabilitation treatments.
    Full-text · Dataset · Jul 2013