Limited value of ultrasound assessment in patients with poor outcome after carpal tunnel release surgerys

[EN] OBJECTIVE: To determine the value of ultrasonography in the assessment of patients with idiopathic carpal tunnel syndrome (CTS) and poor outcome after carpal tunnel release. METHODS: A total of 88 consecutive patients with CTS (104 hands) underwent open surgical release of the median nerve. Ultrasound (US) examination was performed blind to any patient's data. The median nerve area at tunnel inlet and outlet, the retinaculum distance, and the flattening ratio were measured. The main outcome variable was the patient's overall satisfaction using a five-point Likert scale (1 = worse, 2 = no change, 3 = slightly better, 4 = much better, 5 = cured) at 3 months postoperatively. Pre- and postoperative ultrasonographic findings in relation to clinical outcome were analysed. RESULTS: Improvement (scores 4 or 5 on the Likert scale) was recorded in 75 hands (72%). After carpal tunnel release, the cross-sectional area at tunnel inlet decreased from a mean of 14.2 to 13.3 mm2 in the group with clinical improvement and also from a mean of 12.5 to 11.6 mm2 in the group with no change or slight improvement. No significant changes in the cross-sectional area at tunnel outlet, retinaculum distance, and flattening ratio were observed. CONCLUSION: Reduction of the median nerve cross-sectional area at tunnel inlet at 3 months after carpal tunnel release was similar in patients reporting cure or great improvement and in those with slight or no improvement. Ultrasonography is of limited value in assessment of patients with poor outcome after median nerve release.

Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

Non invasive assessment of right ventricle in patients with operated tetralogy of Fallot

The objective of this study was to evaluate right ventricular function in patients with right ventricular volume overload in patients with (tetralogy of Fallot, and pulmonary atresia + VSD ) underwent corrective surgery; with echocardiography measure that can be easily applied; and to study the relationship between ProBNP and the contractile function of the right ventricle, dilated right atrium, and the consequences of pulmonary insufficiency . Methods: The study included 50 patients (50% males, mean age 30.64 ± 13.30 years) with prior cardiac surgical intervention of TDF (90%) or pulmonary atresia + VSD (10%). (49 pz) have performed a cardiac MRI and clinical evaluation, (47 pz) echocardiogram, (48 pz) ECG, (34 pz) a cardiopulmonary exercise testing, (29 pz) a dosage of ProBNP. Results: The S-wave velocity (p <0.0001), the TAPSE (p <0.0001) correlated significantly with RVEF estimated by cardiac MRI. The VO2 max was 27.93 ± 12.91 ml / kg / min, 15% of patients had VE/VCO2 The peak> 35. ProBNP correlated positively and significantly with the area of the right atrium (p = 0.0001), and negative and significant with VO2 max (p = 0.04). Those who have increased pulmonary insufficiency (PVR fraction> 30%) have a significantly increased RVED volume (p = 0.01), reduced VO2 max (p = 0.04), and lower ejection fraction of LV (p = 0.02) than the group of patients with PVR ≤ 30. Conclusion: The TAPSE and S-wave velocity are fundamental and may become the technique of choice for routine assessment of RV systolic function in adult patients with TOF. The monitoring of the Pro BNP is probably a choice, given the simplicity and their information that correlate with the test cardiopulmonary. In view of the ventricular-ventricular interaction, so measures to maintain or restore the functioning of the pulmonary valve could preserve biventricular function.

Variability analysis of discrete event series and wavefront patterns in surface electrocardiogram: contributions to psychophysiological and clinical research

The surface electrocardiogram (ECG) is an established diagnostic tool for the detection of abnormalities in the electrical activity of the heart. The interest of the ECG, however, extends beyond the diagnostic purpose. In recent years, studies in cognitive psychophysiology have related heart rate variability (HRV) to memory performance and mental workload. The aim of this thesis was to analyze the variability of surface ECG derived rhythms, at two different time scales: the discrete-event time scale, typical of beat-related features (Objective I), and the “continuous” time scale of separated sources in the ECG (Objective II), in selected scenarios relevant to psychophysiological and clinical research, respectively. Objective I) Joint time-frequency and non-linear analysis of HRV was carried out, with the goal of assessing psychophysiological workload (PPW) in response to working memory engaging tasks. Results from fourteen healthy young subjects suggest the potential use of the proposed indices in discriminating PPW levels in response to varying memory-search task difficulty. Objective II) A novel source-cancellation method based on morphology clustering was proposed for the estimation of the atrial wavefront in atrial fibrillation (AF) from body surface potential maps. Strong direct correlation between spectral concentration (SC) of atrial wavefront and temporal variability of the spectral distribution was shown in persistent AF patients, suggesting that with higher SC, shorter observation time is required to collect spectral distribution, from which the fibrillatory rate is estimated. This could be time and cost effective in clinical decision-making. The results held for reduced leads sets, suggesting that a simplified setup could also be considered, further reducing the costs. In designing the methods of this thesis, an online signal processing approach was kept, with the goal of contributing to real-world applicability. An algorithm for automatic assessment of ambulatory ECG quality, and an automatic ECG delineation algorithm were designed and validated.

Spinal cord injury: assessment of autonomic state-dependent control of cardiovascular system and body core temperature

Spinal cord injury (SCI) results not only in paralysis; but it is also associated with a range of autonomic dysregulation that can interfere with cardiovascular, bladder, bowel, temperature, and sexual function. The entity of the autonomic dysfunction is related to the level and severity of injury to descending autonomic (sympathetic) pathways. For many years there was limited awareness of these issues and the attention given to them by the scientific and medical community was scarce. Yet, even if a new system to document the impact of SCI on autonomic function has recently been proposed, the current standard of assessment of SCI (American Spinal Injury Association (ASIA) examination) evaluates motor and sensory pathways, but not severity of injury to autonomic pathways. Beside the severe impact on quality of life, autonomic dysfunction in persons with SCI is associated with increased risk of cardiovascular disease and mortality. Therefore, obtaining information regarding autonomic function in persons with SCI is pivotal and clinical examinations and laboratory evaluations to detect the presence of autonomic dysfunction and quantitate its severity are mandatory. Furthermore, previous studies demonstrated that there is an intimate relationship between the autonomic nervous system and sleep from anatomical, physiological, and neurochemical points of view. Although, even if previous epidemiological studies demonstrated that sleep problems are common in spinal cord injury (SCI), so far only limited polysomnographic (PSG) data are available. Finally, until now, circadian and state dependent autonomic regulation of blood pressure (BP), heart rate (HR) and body core temperature (BcT) were never assessed in SCI patients. Aim of the current study was to establish the association between the autonomic control of the cardiovascular function and thermoregulation, sleep parameters and increased cardiovascular risk in SCI patients.

Assessment of Daily Life Mobility Levels using Wearable Inertial Sensors and Minimun Measured Input Models

Tracking activities during daily life and assessing movement parameters is essential for complementing the information gathered in confined environments such as clinical and physical activity laboratories for the assessment of mobility. Inertial measurement units (IMUs) are used as to monitor the motion of human movement for prolonged periods of time and without space limitations. The focus in this study was to provide a robust, low-cost and an unobtrusive solution for evaluating human motion using a single IMU. First part of the study focused on monitoring and classification of the daily life activities. A simple method that analyses the variations in signal was developed to distinguish two types of activity intervals: active and inactive. Neural classifier was used to classify active intervals; the angle with respect to gravity was used to classify inactive intervals. Second part of the study focused on extraction of gait parameters using a single inertial measurement unit (IMU) attached to the pelvis. Two complementary methods were proposed for gait parameters estimation. First method was a wavelet based method developed for the estimation of gait events. Second method was developed for estimating step and stride length during level walking using the estimations of the previous method. A special integration algorithm was extended to operate on each gait cycle using a specially designed Kalman filter. The developed methods were also applied on various scenarios. Activity monitoring method was used in a PRIN’07 project to assess the mobility levels of individuals living in a urban area. The same method was applied on volleyball players to analyze the fitness levels of them by monitoring their daily life activities. The methods proposed in these studies provided a simple, unobtrusive and low-cost solution for monitoring and assessing activities outside of controlled environments.

From inverted pendulum to N-link chain: inertial sensors-based assessment of movement kinematics and dynamics for functional evaluation and rehabilitation

Despite several clinical tests that have been developed to qualitatively describe complex motor tasks by functional testing, these methods often depend on clinicians' interpretation, experience and training, which make the assessment results inconsistent, without the precision required to objectively assess the effect of the rehabilitative intervention. A more detailed characterization is required to fully capture the various aspects of motor control and performance during complex movements of lower and upper limbs. The need for cost-effective and clinically applicable instrumented tests would enable quantitative assessment of performance on a subject-specific basis, overcoming the limitations due to the lack of objectiveness related to individual judgment, and possibly disclosing subtle alterations that are not clearly visible to the observer. Postural motion measurements at additional locations, such as lower and upper limbs and trunk, may be necessary in order to obtain information about the inter-segmental coordination during different functional tests involved in clinical practice. With these considerations in mind, this Thesis aims: i) to suggest a novel quantitative assessment tool for the kinematics and dynamics evaluation of a multi-link kinematic chain during several functional motor tasks (i.e. squat, sit-to-stand, postural sway), using one single-axis accelerometer per segment, ii) to present a novel quantitative technique for the upper limb joint kinematics estimation, considering a 3-link kinematic chain during the Fugl-Meyer Motor Assessment and using one inertial measurement unit per segment. The suggested methods could have several positive feedbacks from clinical practice. The use of objective biomechanical measurements, provided by inertial sensor-based technique, may help clinicians to: i) objectively track changes in motor ability, ii) provide timely feedback about the effectiveness of administered rehabilitation interventions, iii) enable intervention strategies to be modified or changed if found to be ineffective, and iv) speed up the experimental sessions when several subjects are asked to perform different functional tests.

The impact of cardiac rehabilitation on lifestyles, psychological correlates and the clinical course of cardiac disease

Objectives: The aim of this research was to evaluate the impact of Cardiac Rehabilitation (CR) on risky lifestyles, quality of life, psychopathology, psychological distress and well-being, considering the potential moderating role of depression, anxiety and psychosomatic syndromes on lifestyles modification. The influence of CR on cardiac morbidity and mortality was also evaluated. Methods: The experimental group (N=108), undergoing CR, was compared to a control group (N=85) of patients affected by cardiovascular diseases, not undergoing CR, at baseline and at 1-month, 6- and 12-months follow-ups. The assessment included: the Structured Clinical Interview for DSM-IV, the structured interview based on Diagnostic Criteria for Psychosomatic Research (DCPR), GOSPEL questionnaire on lifestyles, Pittsburgh Sleep Quality Index, Morisky Medication Adherence Scale, MOS 36-Item Short Form Health Survey, Symptom Questionnaire, Psychological Well-Being Scale and 14-items Type D Scale. Results: Compared to the control group, CR was associated to: maintenance of the level of physical activity, improvement of correct dietary behaviors and stress management, enhancement of quality of life and sleep; reduction of the most frequently observed psychiatric diagnoses and psychosomatic syndromes at baseline. On the contrary, CR was not found to be associated with: healthy dietary habits, weight loss and improvement on medications adherence. In addition, there were no relevant effects on sub-clinical psychological distress and well-being, except for personal growth and purpose in life (PWB). Also, CR did not seem to play a protective role against cardiac recurrences. The presence of psychosomatic syndromes and depressive disorders was a mediating factor on the modification of specific lifestyles. Conclusions: The findings highlight the need of a psychosomatic assessment and an evaluation of psychological sub-clinical symptomatology in cardiac rehabilitation, in order to identify and address specific factors potentially associated with the clinical course of the heart disease.

Automatic risk evaluation in elderly patients based on Autonomic Nervous System assessment

Dysfunction of Autonomic Nervous System (ANS) is a typical feature of chronic heart failure and other cardiovascular disease. As a simple non-invasive technology, heart rate variability (HRV) analysis provides reliable information on autonomic modulation of heart rate. The aim of this thesis was to research and develop automatic methods based on ANS assessment for evaluation of risk in cardiac patients. Several features selection and machine learning algorithms have been combined to achieve the goals. Automatic assessment of disease severity in Congestive Heart Failure (CHF) patients: a completely automatic method, based on long-term HRV was proposed in order to automatically assess the severity of CHF, achieving a sensitivity rate of 93% and a specificity rate of 64% in discriminating severe versus mild patients. Automatic identification of hypertensive patients at high risk of vascular events: a completely automatic system was proposed in order to identify hypertensive patients at higher risk to develop vascular events in the 12 months following the electrocardiographic recordings, achieving a sensitivity rate of 71% and a specificity rate of 86% in identifying high-risk subjects among hypertensive patients. Automatic identification of hypertensive patients with history of fall: it was explored whether an automatic identification of fallers among hypertensive patients based on HRV was feasible. The results obtained in this thesis could have implications both in clinical practice and in clinical research. The system has been designed and developed in order to be clinically feasible. Moreover, since 5-minute ECG recording is inexpensive, easy to assess, and non-invasive, future research will focus on the clinical applicability of the system as a screening tool in non-specialized ambulatories, in order to identify high-risk patients to be shortlisted for more complex investigations.

Il trattamento ortodontico nei bambini con particolari necessità sanitarie (SHCN): una valutazione della durata e del risultato clinico utilizzando l'indice PAR (Peer Assessment Rating), la componente DHC (Dental Health Component) e la componente AC (Aesthetic Component) dell'indice IOTN (Orthodontic Treatment Need Index)

Obbiettivo: Valutazione delle eventuali differenze nel trattamento ortodontico di un gruppo di bambini con particolari necessità sanitarie (SHCN) rispetto ad un gruppo di bambini non diagnosticati con SHCN. Materiali e Metodi: Il gruppo campione (SHCN) è costituito da 50 bambini con SHCN. Il gruppo di controllo (NO SHCN) è costituito da 50 bambini non diagnosticati con SHCN pienamente corrispondenti per età, genere e tipo di apparecchio ortodontico utilizzato con i pazienti del gruppo di studio. I dati riguardanti i gruppi SHCN e NO SHCN sono stati analizzati in modo retrospettivo, valutando: - il punteggio pre- e post-trattamento e la riduzione finale dei valori dell'indice PAR (Peer Assessment Rating), della componente DHC (Dental Health Component) e della componente AC (Aesthetic Component) dell'indice IOTN (Orthodontic Treatment Need Index), - il numero di appuntamenti, - il numero di sedute semplici e complesse, - la durata complessiva del trattamento, - l'età all’inizio ed alla fine della terapia. Risultati: Non sono state rilevate differenze statisticamente significative tra i due gruppi per quanto concerne il numero di appuntamenti, la durata complessiva del trattamento, l'età all’inizio ed alla fine della terapia ortodontica (valori del p-value:0.682, 0.458, 0.535, 0.675). Sono state rilevate differenze statisticamente significative tra i due gruppi per quanto riguarda i punteggi dell’indice PAR, delle componenti DHC e AC dello IOTN pre- e post-trattamento, il numero di sedute semplici e complesse (valori del p-value:0.030, 0.000, 0.020, 0.023, 0.000, 0.000, 0.043, 0.037). Per quanto concerne la riduzione finale del valore dell’indice PAR, della componente DHC e di quella AC dello IOTN non sono state riscontrate differenze statisticamente significative tra i due gruppi (valori del p-value:0.060, 0.765, 0.825). Conclusioni: Lo studio incoraggia gli ortodontisti a trattare i bambini con SHCN nell'obiettivo di migliorarne la qualità di vita, pur evidenziando la necessità di un maggior numero di sedute complesse.

Cognitive and behavioural assessment of parkinsonian syndromes at onset: a longitudinal study

Background: cognitive impairment is one of the non motor features widely descripted in parkinsonian syndrome, it has been related to the motor characteristics of the parkinsonian syndrome, associated with neuropsychiatric dysfunction and the characteristic sleep and autonomic features. It has been shown to be highly prevalent at all disease stages and to contribute significantly to disability. Objectives: aim of this study is to evaluate longitudinally the cognitive and behavioral characteristics of patients with a parkinsonian syndrome at onset; to describe the cognitive and behavioral characteristics of each parkinsonian syndrome; to define in PD patients at onset the presence of MCI or Parkinson disease dementia; to correlate the cognitive and behavioral characteristics with the features of the parkinsonian syndrome and with the associated sleep and autonomic features. Results: we recruited 55 patients, 22 did not present cognitive impairment both at T0 and at T1. 18 patients presented a progression of cognitive impairment. Progressive cognitively impaired patients were older and presented the worst motor phenotype. Progression of cognitive impairment was not associated to sleep and autonomic features. Conclusion: the evaluation of cognitive impairment could not be useful as a predictor of a correct diagnosis but each non motor domain will help to clarify and characterize the motor syndrome. The diagnosis of parkinsonian disorders lies in building a clinical profile in conjunction with other clinical characteristics such as mode of presentation, disease progression, response to medications, sleep and autonomic features.

Assessment of gait spatio-temporal parameters in neurological disorders using wearable inertial sensors

Movement analysis carried out in laboratory settings is a powerful, but costly solution since it requires dedicated instrumentation, space and personnel. Recently, new technologies such as the magnetic and inertial measurement units (MIMU) are becoming widely accepted as tools for the assessment of human motion in clinical and research settings. They are relatively easy-to-use and potentially suitable for estimating gait kinematic features, including spatio-temporal parameters. The objective of this thesis regards the development and testing in clinical contexts of robust MIMUs based methods for assessing gait spatio-temporal parameters applicable across a number of different pathological gait patterns. First, considering the need of a solution the least obtrusive as possible, the validity of the single unit based approach was explored. A comparative evaluation of the performance of various methods reported in the literature for estimating gait temporal parameters using a single unit attached to the trunk first in normal gait and then in different pathological gait conditions was performed. Then, the second part of the research headed towards the development of new methods for estimating gait spatio-temporal parameters using shank worn MIMUs on different pathological subjects groups. In addition to the conventional gait parameters, new methods for estimating the changes of the direction of progression were explored. Finally, a new hardware solution and relevant methodology for estimating inter-feet distance during walking was proposed. Results of the technical validation of the proposed methods at different walking speeds and along different paths against a gold standard were reported and showed that the use of two MIMUs attached to the lower limbs associated with a robust method guarantee a much higher accuracy in determining gait spatio-temporal parameters. In conclusion, the proposed methods could be reliably applied to various abnormal gaits obtaining in some cases a comparable level of accuracy with respect to normal gait.

Clinical applicability of an US model to calculate the head blood outflow through collateral vessels.

Le vene giugulari interne sembrano essere la via principale attraverso cui il sangue defluisce dal cervello verso il cuore, quando siamo in posizione supina. Nel 2008 il professor Paolo Zamboni ha scoperto che una diminuzione dell'attività giugulare può portare allo sviluppo di una condizione emodinamica chiamata CCSVI. Questa può causare ipossia, ritardi nella perfusione cerebrale e riduzione del drenaggio dei cataboliti, oltre ad un'attivazione infiammatoria delle piccole vene e dei tessuti vicini. Questa condizione è stata da subito associata alla sclerosi multipla e su questo argomento si sono dibattuti molti gruppi di ricerca. Inoltre, altre patologie sembrano essere associate alla CCSVI, come il morbo di Parkinson, l'Alzheimer e la sindrome di Meniere. Proprio quest'ultima è uno degli argomenti che attualmente interessa di più il gruppo di lavoro in cui mi sono inserita. Questa patologia comporta problemi uditivi, come sordità e tinnito, vertigini e nausea. Il gruppo Vascolar Disease Center (VDC) dell'Università di Ferrara ha previsto per l'anno 2015 uno studio multicentrico, in cui si cercherà di verificare la correlazione tra CCSVI e sindrome di Meniere. La mia tesi fa parte di un studio preliminare a quello multicentrico. All'inizio del lavoro mi sono dedicata ad un'analisi critica di un modello emodinamico per la quantificazione dei flussi sanguigni: il modello BMC, pubblicato nel 2013 dal gruppo VDC, effettuando in parallelo una ricerca bibliografica sullo stato dell'arte in materia. In seguito ho cominciato a studiare off-line diversi studi patologici e fisiologici, in modo da prendere confidenza con gli strumenti e con le metodologie da utilizzare. Sono stata poi coinvolta dal gruppo VDC per partecipare attivamente al miglioramento del protocollo legato al modello BMC. Infine ho analizzato, con due metodologie differenti, 35 studi effettuati su pazienti otorinolaringoiatrici. Con i risultati ottenuti ho potuto effettuare diverse analisi statistiche al fine di verificare l'equivalenza delle due metodologie. L'obiettivo ultimo era quello di stabilire quale delle due fosse la tecnica migliore da utilizzare, successivamente, nello studio multicentrico.

Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials

BACKGROUND: Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. METHODS: An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. RESULTS: Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. CONCLUSION: Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.