Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

Studies on the impact of assistive communication devices on the quality of life of patients with amyotrophic lateral sclerosis

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2016Amyotrophic Lateral Sclerosis (ALS) is a progressive neuromuscular disease with rapid and generalized degeneration of motor neurons. Patients with ALS experiment a relentless decline in functions that affect performance of most activities of daily living (ADL), such as speaking, eating, walking or writing. For this reason, dependence on caregivers grows as the disease progresses. Management of the respiratory system is one of the main concerns of medical support, since respiratory failure is the most common cause of death in ALS. Due to increasing muscle weakness, most patients experience dramatic decrease of speech intelligibility and difficulties in using upper limbs (UL) for writing. There is growing evidence that mild cognitive impairment is common in ALS, but most patients are self-conscious of their difficulties in communicating and, in very severe stages, locked-in syndrome can occur. When no other resources than speech and writing are used to assist communication, patients are deprived of expressing needs or feelings, making decisions and keeping social relationships. Further, caregivers feel increased dependence due to difficulties in communication with others and get frustrated about difficulties in understanding partners’ needs. Support for communication is then very important to improve quality of life of both patients and caregivers; however, this has been poorly investigated in ALS. Assistive communication devices (ACD) can support patients by providing a diversity of tools for communication, as they progressively lose speech. ALS, in common with other degenerative conditions, introduces an additional challenge for the field of ACD: as the disease progresses, technologies must adapt to different conditions of the user. In early stages, patients may need speech synthesis in a mobile device, if dysarthria is one of the initial symptoms, or keyboard modifications, as weakness in UL increases. When upper limbs’ dysfunction is high, different input technologies may be adapted to capture voluntary control (for example, eye-tracking devices). Despite the enormous advances in the field of Assistive Technologies, in the last decade, difficulties in clinical support for the use of assistive communication devices (ACD) persist. Among the main reasons for these difficulties are lack of assessment tools to evaluate communication needs and determine proper input devices and to indicate changes over disease progression, and absence of clinical evidence that ACD has relevant impact on the quality of life of affected patients. For this set of reasons, support with communication tools is delayed to stages where patients are severely disabled. Often in these stages, patients face additional clinical complications and increased dependence on their caregivers’ decisions, which increase the difficulty in adaptation to new communication tools. This thesis addresses the role of assistive technologies in the quality of life of early-affected patients with ALS. Also, it includes the study of assessment tools that can improve longitudinal evaluation of communication needs of patients with ALS. We longitudinally evaluated a group of 30 patients with bulbar-onset ALS and 17 caregivers, during 2 to 29 months. Patients were assessed during their regular clinical appointments, in the Hospital de Santa Maria-Centro Hospitalar Lisboa_Norte. Evaluation of patients was based on validated instruments for assessing the Quality of Life (QoL) of patients and caregivers, and on methodologies for recording communication and measuring its performance (including speech, handwriting and typing). We tested the impact of early support with ACD on the QoL of patients with ALS, using a randomized, prospective, longitudinal design. Patients were able to learn and improve their skills to use communication tools based on electronic assistive devices. We found a positive impact of ACD in psychological and wellbeing domains of quality of life in patients, as well as in the support and psychological domains in caregivers. We also studied performance of communication (words per minute) using UL. Performance in handwriting may decline faster than performance in typing, supporting the idea that the use of touchscreen-based ACD supports communication for longer than handwriting. From longitudinal recordings of speech and typing activity we could observe that ACD can support tools to detect early markers of bulbar and UL dysfunction in ALS. Methodologies that were used in this research for recording and assessing function in communication can be replicated in the home environment and form part of the original contributions of this research. Implementation of remote monitoring tools in daily use of ACD, based on these methodologies, is discussed. Considering those patients who receive late support for the use of ACD, lack of time or daily support to learn how to control complex input devices may hinder its use. We developed a novel device to explore the detection and control of various residual movements, based on sensors of accelerometry, electromyography and force, as input signals for communication. The aim of this input device was to develop a tool to explore new communication channels in patients with generalized muscle weakness. This research contributed with novel tools from the Engineering field to the study of assistive communication in patients with ALS. Methodologies that were developed in this work can be further applied to the study of the impact of ACD in other neurodegenerative diseases that affect speech and motor control of UL

Personalized Medicine for Parkinson's Disease

Personalized medicine for Parkinson’s disease is a growing and emerging concept in light of recent recognition that Parkinson’s is a syndromic condition affecting multiple neurotransmitter systems, as well as brain and extracranial structures. The clinical expression is, thus, heterogeneous, and presentation age can range from the 30s to the 90s, with PD in older patients being associated with significant neuropathological comorbidity as well, involving not just misfolded alpha synuclein deposition but also amyloid and tau. Traditional and largely guideline-driven “one size fits all” management strategies adopted in clinical practice are, therefore, often inadequate in holistic management of a patient, particularly when aspects of motor and nonmotor symptoms are taken into consideration. In this supplement of JPM, we present a selection of papers which address several possible strands of personalized medicine in PD, ranging from genomic precision medicine to digital “checklists” to ensure delivery of holistic personalized medicine involving nonpharmacological strategies, as well. We are soliciting any papers addressing biomarkers, genetics and pharmacogenetics, treatment or complementary therapies for personalized or individualized treatment for PD

Assessing residual neck mobility when wearing a cervical orthosis: an application in patients with Motor Neurone Disease

Severe weakness of the neck extensor muscles has been observed in neuromuscular pathologies, such as motor neurone disease (MND). This condition reduces the ability to perform daily activities and communicate, leading to the adoption of a cervical orthosis. However, commercially available devices are designed to immobilize the neck, which makes them uncomfortable and strenuous to wear for a long time. The lack of a device specifically designed for those patients led to the development of the Sheffield Support Snood (SSS) which enables to adjust the support given to the head, according to the task performed and to the disease progression. The following step toward the SSS commercialisation and adoption was an objective evaluation of its performance and the assessment with the end users, which was the aim of this thesis. To this purpose, an experimental protocol designed to quantitatively assess neck mobility when wearing cervical orthoses, has been developed. This protocol and the associated signal processing techniques proved to be suitable for the assessment of neck mobility through the measurement of head movements, both in laboratory and clinical settings. After having quantitatively assessed head movement limitation in MND patients, filling an existing gap in the current literature, the effects of the SSS were tested. Compared to controls, patients presented an overall impaired ability to perform head movements in terms of reduced velocity (mean values between 27% and 41% lower in movements performed reaching the maximum range of motion and between 34% and 48% lower in movements performed reaching the maximum angular velocity), reduced smoothness (mean values between 21% and 44% lower in movements performed reaching the maximum range of motion) and increased presence of coupled movements (mean values between 37% and 58% higher in movements performed reaching the maximum range of motion and between 44% and 53% in movements performed reaching the maximum angular velocity). The SSS was effective in facilitating the head movements in MND patients. Among those 9 individuals that were fitted with anterior or anterior plus lateral supports 5 of them had a reduced presence on coupled movements in at least one of the movements performed. However, a proper fitting of the orthosis appeared crucial and in the future it should be based on a quantitative approach similar to the one developed in this thesis. This study paved the way for improvements in the SSS design and for future quantitative assessment of the characteristics of motor control and movement strategies in MND patients and of how these change when using a device aiming at compensating for functional impairments

PRELIMINARY FINDINGS OF A POTENZIATED PIEZOSURGERGICAL DEVICE AT THE RABBIT SKULL

The number of available ultrasonic osteotomes has remarkably increased. In vitro and in vivo studies have revealed differences between conventional osteotomes, such as rotating or sawing devices, and ultrasound-supported osteotomes (Piezosurgery®) regarding the micromorphology and roughness values of osteotomized bone surfaces. Objective: the present study compares the micro-morphologies and roughness values of osteotomized bone surfaces after the application of rotating and sawing devices, Piezosurgery Medical® and Piezosurgery Medical New Generation Powerful Handpiece. Methods: Fresh, standard-sized bony samples were taken from a rabbit skull using the following osteotomes: rotating and sawing devices, Piezosurgery Medical® and a Piezosurgery Medical New Generation Powerful Handpiece. The required duration of time for each osteotomy was recorded. Micromorphologies and roughness values to characterize the bone surfaces following the different osteotomy methods were described. The prepared surfaces were examined via light microscopy, environmental surface electron microscopy (ESEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy. The selective cutting of mineralized tissues while preserving adjacent soft tissue (dura mater and nervous tissue) was studied. Bone necrosis of the osteotomy sites and the vitality of the osteocytes near the sectional plane were investigated, as well as the proportion of apoptosis or cell degeneration. Results and Conclusions: The potential positive effects on bone healing and reossification associated with different devices were evaluated and the comparative analysis among the different devices used was performed, in order to determine the best osteotomes to be employed during cranio-facial surgery

Program with last minute abstracts of the Padua Days on Muscle and Mobility Medicine, 27 February – 2 March, 2024 (2024Pdm3)

During the 2023 Padua Days on Muscle and Mobility Medicine the 2024 meeting was scheduled from 28 February to 2 March 2024 (2024Pdm3). During autumn 2023 the program was expanded with Scientific Sessions which will take place over five days (in 2024 this includes February 29), starting from the afternoon of 27 February 2024 in the Conference Rooms of the Hotel Petrarca, Thermae of Euganean Hills (Padua), Italy. As per consolidated tradition, the second day will take place in Padua, for the occasion in the Sala San Luca of the Monastery of Santa Giustina in Prato della Valle, Padua, Italy. Confirming the attractiveness of the Padua Days on Muscle and Mobility Medicine, over 100 titles were accepted until 15 December 2023 (many more than expected), forcing the organization of parallel sessions on both 1 and 2 March 2024. The five days will include lectures and oral presentations of scientists and clinicians from Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Denmark, Egypt, France, Germany, Iceland, Ireland, Italy, Romania, Russia, Slovenia, Switzerland, UK and USA. Only Australia, China, India and Japan are missing from this edition. But we are confident that authors from those countries who publish articles in the PAGEpress: European Journal of Translational Myology (EJTM: 2022 ESCI Clarivate's Impact Factor: 2.2; SCOPUS Cite Score: 3.2) will decide to join us in the coming years. Together with the program established by 31 January 2024, the abstracts will circulate during the meeting only in the electronic version of the EJTM Issue 34 (1) 2024. See you soon in person at the Hotel Petrarca in Montegrotto Terme, Padua, for the inauguration scheduled the afternoon of 27 February 2024 or on-line for free via Zoom. Send us your email address if you are not traditional participants listed in Pdm3 and EJTM address books

A novel optogenetics-based therapy for obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is characterised by repeat upper airway narrowing and/or collapse during sleep. Many patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel, optogenetics-based therapy, that enables light-stimulation induced upper airway dilator muscle contractions to maintain airway patency. The primary aims of this thesis were to determine feasibility in a rodent model of OSA, and identify effective optogenetic constructs for activating upper airway muscles. Chapters 2 and 3 outline the development of a novel construct for the expression of light-sensitive proteins (opsins) in upper airway muscles, comparing two promotors and two recombinant adeno-associated virus capsids (rAAV) for optogenetic gene transfer. Results show that a muscle-specific promotor (tMCK) was superior to a non-specific promotor (CAG). With tMCK, opsin expression in the tongue was 470% greater (p=0.013, RM-ANOVA), brainstem expression was abolished, and light stimulation facilitated a 66% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA (p<0.001, linear mixed model) (Chapter 2). Moreover, a novel, highly myotropic rAAV serotype, AAVMYO, was superior to a wild-type serotype, AAV9. The AAVMYO serotype driven by tMCK facilitated a further increase in muscle activity with light stimulation to 194% of that recorded during unstimulated breaths (p<0.001, linear mixed model) (Chapter 3). Finally, ultrasound imaging confirmed that the optimised construct was able to generate effective light-induced muscle contractions and airway dilation (Chapter 4). A secondary aim was to advance preclinical trials for the proposed therapy. To this end, a surgical protocol for chronic implantation of light delivery hardware and recording electrodes in rodents was developed (Chapter 5). The final protocol will allow us to determine the effects of acute and chronic light stimulation on opsin-expressing upper airway muscles during natural sleep. In summary, Chapters 2 to 4 provide proof-of-concept for a non-invasive optogenetics-based OSA therapy. The combination of a muscle-specific promotor and a muscle-specific viral vector presents a novel and highly effective method of inducing light sensitivity into skeletal muscle and facilitating light-evoked airway dilation. Finally, Chapter 5 commences the development of a surgical protocol that will aid ongoing preclinical trials

Recent Advances in Minimally Invasive Surgery

Minimally invasive surgery has become a common term in visceral as well as gynecologic surgery. It has almost evolved into its own surgical speciality over the past 20 years. Today, being firmly established in every subspeciality of visceral surgery, it is now no longer a distinct skillset, but a fixed part of the armamentarium of surgical options available. In every indication, the advantages of a minimally invasive approach include reduced intraoperative blood loss, less postoperative pain, and shorter rehabilitation times, as well as a marked reduction of overall and surgical postoperative morbidity. In the advent of modern oncologic treatment algorithms, these effects not only lower the immediate impact that an operation has on the patient, but also become important key steps in reducing the side-effects of surgery. Thus, they enable surgery to become a module in modern multi-disciplinary cancer treatment, which blends into multimodular treatment options at different times and prolongs and widens the possibilities available to cancer patients. In this quickly changing environment, the requirement to learn and refine not only open surgical but also different minimally invasive techniques on high levels deeply impact modern surgical training pathways. The use of modern elearning tools and new and praxis-based surgical training possibilities have been readily integrated into modern surgical education,which persists throughout the whole surgical career of modern gynecologic and visceral surgery specialists