Stefano Masiero

This position document has been developed by the Dysphagia Working Group, a committee of members from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society, and invited experts. It consists of 12 sections that cover all aspects of clinical management of oropharyngeal dysphagia (OD) related to geriatric medicine and discusses prevalence, quality of life, and legal and ethical issues, as well as health economics and social burden. OD constitutes impaired or uncomfortable transit of food or liquids from the oral cavity to the esophagus, and it is included in the World Health Organization's classification of diseases. It can cause severe complications such as malnutrition, dehydration, respiratory infections, aspiration pneumonia, and increased readmissions, institutionalization, and morbimortality. OD is a prevalent and serious problem among all phenotypes of older patients as oropharyngeal swallow response is impaired in older people and can cause aspiration. Despite its prevalence and severity, OD is still underdiagnosed and untreated in many medical centers. There are several validated clinical and instrumental methods (videofluoroscopy and fiberoptic endoscopic evaluation of swallowing) to diagnose OD, and treatment is mainly based on compensatory measures, although new treatments to stimulate the oropharyngeal swallow response are under research. OD matches the definition of a geriatric syndrome as it is highly prevalent among older people, is caused by multiple factors, is associated with several comorbidities and poor prognosis, and needs a multidimensional approach to be treated. OD should be given more importance and attention and thus be included in all standard screening protocols, treated, and regularly monitored to prevent its main complications. More research is needed to develop and standardize new treatments and management protocols for older patients with OD, which is a challenging mission for our societies.

This paper presents the development of and clinical tests on NeReBot (NEuroREhabilitation roBOT): a three degrees-of-freedom (DoF), wire-driven robot for poststroke upper-limb rehabilitation. Basically, the robot consists of a set of three wires independently driven by three electric motors. The wires are connected to the patient's upper limb by means of a splint and are supported by a transportable frame, located above the patient. By controlling wire length, rehabilitation treatment (based on the passive or active-assistive spatial motion of the limb) can be delivered over a wide working space. The arm trajectory is set by the therapist through a very simple teaching-by-showing procedure, enabling most common "hands on" therapy exercises to be reproduced by the robot. Compared to other rehabilitation robots, NeReBot offers the advantages of a low-cost mechanical structure, intrinsically safe treatment thanks to the use of wires, high acceptability by the patient, who does not feel constrained by an "industrial-like" robot, transportability (it can be easily placed aside a hospital bed and/or a wheelchair), and a good trade-off between low number of DoF and spatial performance. These features and the very encouraging results of the first clinical trials make the NeReBot a good candidate for adoption in the rehabilitation treatment of subacute stroke survivors. Clinical trials were performed with a 12-patient experimental group and a 12-patient control group. Resulted that the patients who received robotic therapy in addition to conventional therapy showed greater reductions in motor impairment (in terms of Medical Research Council score, the upper limb subsection of the Fugl-Meyer score, and the Motor Status Score) and improvements in functional abilities (as measured by the Functional Independence Measure and its motor component). No adverse effects occurred and the robotic approach was very well accepted. According to these results, the NeReBot therapy may efficaciously complement standard poststroke multidisciplinary rehabilitation and offer novel therapeutic strategies for neurological rehabilitation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: EudraCT:2009-014484-39 .