BACKGROUND:Respiratory failure is the main cause of death in Amyotrophic lateral sclerosis (ALS), in which the physiological sigh reflex is impaired due to inspiratory muscle weakness. Aim of this study is to assess the tolerability, safety, and effectiveness of adding a sigh cycle to non-invasive mechanical ventilation (NIMV) settings in ALS patients. METHODS:In this randomized, blind-controlled proof-of concept study, 44 consecutive ALS patients with indication for NIMV were randomized to: Group I: NIMV with Sigh cycles; Group II: NIMV without Sigh. The primary outcome was the reduction in the Oxygen Desaturation Index (ODI); secondary outcomes included: Overnight Oximetry (OvOx), Arterial blood gas (ABG), and Visual Analog Scale (VAS; 0-10) scores to assess sleep quality, symptom intensity, mask interface, and NIMV tolerance. Assessments were conducted at baseline, after NIMV adaptation (T1) and at 1-month follow-up (T2). RESULTS:The Sigh cycle was safe and well tolerated. No significant group differences were observed at T1 or T2 in the primary outcome ODI (median ΔODI: Group A:-4.2; Group B:-4.6: p = 0.54), as well as in the OvOx parameters and pO2 and pCO2 ABG values. At T2, secondary analysis showed a significant difference in HCO₃- in favor of the Sigh arm (ΔHCO3 -: -1.60 vs. 1.35 mmol/L, p = 0.042). Exploratory Cox-regression models suggested a potential independent effect of SIGH on survival. CONCLUSIONS:Sigh is safe, well tolerated in ALS patients. Although this study did not reach the primary outcome, we also cannot rule out that sigh doesn't benefit the patient.

IntroductionPercutaneous endoscopic gastrostomy (PEG) is commonly used to manage dysphagia and nutritional failure, which are among the most frequent and severe complications of amyotrophic lateral sclerosis (ALS). While several studies assessed PEG indications, outcomes, and prognostic factors, there is no evidence regarding ALS patients’ perspectives and health-related quality of life (HRQoL) associated with PEG.MethodsThis study included 48 consecutive ALS patients. At the 1-month follow-up after PEG, patients and their caregivers completed a PEG satisfaction questionnaire regarding their decision to proceed with the PEG-tube placement. HRQoL was assessed using the Gastrointestinal Quality of Life Index (GIQLI) and the Short Form-36 (SF-36).ResultsIn total, 77.1% of patients and 88.9% of caregivers confirmed that they would prefer to have a PEG tube placed again if required (p > 0.001); 93.8% of patients felt that PEG made feeding easier, exerting a positive effect on overall wellbeing (83.3%) and increasing survival rates (93.8%) (p > 0.001); 54.2% felt that PEG was cosmetically acceptable. Consistent positive rates were reported by caregivers. The GIQLI digestion subscale values significantly improved from baseline (28.3; SD = 6.6) to discharge (30.97, SD = 5.84) and were maintained at 1-month follow-up (30.21, SD = 6.7; p = 0.014). Conversely, in follow-up assessments, we observed a significant reduction in the SF-36 physical component summary (PCS) subscale (baseline = 33.3; 1-month follow-up = 28.61; p = 0.032), which was accompanied by a significant worsening in the GIQLI physical dimension subscale (baseline = 9.63; 1-month follow-up = 7.38; p = 0.044).DiscussionThis study provides preliminary evidence that ALS patients have a positive perspective on PEG positioning, which may also have a beneficial effect on HRQoL related to gastrointestinal function.

BACKGROUND AND PURPOSE:The use of multiple tests, including spirometry, arterial blood gas (ABG) analysis and overnight oximetry (OvOx), is highly recommended to monitor the respiratory function of patients with motor neuron disease (MND). In this study, we propose a composite score to simplify the respiratory management of MND patients and better stratify their prognosis. MATERIALS AND METHODS:We screened the clinical charts of 471 non-ventilated MND patients referred to the Neuro-rehabilitation Unit of the San Raffaele Scientific Institute of Milan (January 2001-December 2019), collecting spirometric, ABG and OvOx parameters. To evaluate the prognostic role of each measurement, univariate Cox regression for death/tracheostomy was performed, and the variables associated with survival were selected to design a scoring system. Univariate and multivariate Cox regression analyses were then carried out to evaluate the prognostic role of the score. Finally, results were replicated in an independent cohort from the Turin ALS Center. RESULTS:The study population included 450 patients. Six measurements were found to be significantly associated with survival and were selected to design a scoring system (maximum score = 8 points). Kaplan-Meier analysis showed significant stratification of survival and time to non-invasive mechanical ventilation adaptation according to score values, and multivariate analysis confirmed the independent effect of the respiratory score on survival of each cohort. CONCLUSION:Forced vital capacity, ABG and OvOx parameters provide complementary information for the respiratory management and prognosis of MND patients and the combination of these parameters into a single score might help neurologists predict prognosis and guide decisions on the timing of the implementation of different diagnostic or therapeutic approaches.

Both motor imagery and action observation have been shown to play a role in learning or re-learning complex motor tasks. According to a well accepted view they share a common neurophysiological basis in the mirror neuron system. Neurons within this system discharge when individuals perform a specific action and when they look at another individual performing the same or a motorically related action. In the present paper, after a short review of literature on the role of action observation and motor imagery in motor learning, we report the results of a kinematics study where we directly compared motor imagery and action observation in learning a novel complex motor task. This involved movement of the right hand and foot in the same angular direction (in-phase movement), while at the same time moving the left hand and foot in an opposite angular direction (anti-phase movement), all at a frequency of 1 Hz. Motor learning was assessed through kinematics recording of wrists and ankles. The results showed that action observation is better than motor imagery as a strategy for learning a novel complex motor task, at least in the fast early phase of motor learning. We forward that these results may have important implications in educational activities, sport training and neurorehabilitation.

Kinematic and functional magnetic resonance imaging were combined to investigate how movement complexity (in-phase vs. anti-phase) and rate (maximum rate vs. 1 Hz) influence the brain sensorimotor network of relapsing- remitting fatigued (F) and notfatigued (NF) MS patients during the performance of coordinated hand and foot movements.Kinematic measures did not differ between F and NF patients. Task and disease showed an interaction in the right precuneus and posterior lobe of the cerebellum during in-phase/anti-phase conditions and in the right precuneus and posterior and anterior lobes of the cerebellum during maximum vs. 1 Hz rate. Task, disease and fatigue showed an interaction in the right precentral gyrus, the left postcentral gyrus, the left SII, the right precuneus, the right basal ganglia, the left lingual gyrus, and the posterior lobe of the cerebellum, bilaterally, during in-phase/ anti-phase conditions and the left postcentral gyrus, the left SII, the right anterior lobe of the cerebellum, and the posterior lobe of the cerebellum, bilaterally during maximum vs. 1 Hz rate.Investigations of motor task performance in MS patients require careful control of several variables, including task complexity, movement rate, and the presence of "subtle" clinical disturbances, such as fatigue, which might be underestimated at a standard neurological assessment.

Behavioral studies have provided important insights into the mechanisms governing interlimb coordination. In this study, we combined kinematic and functional magnetic resonance imaging (fMRI) analysis to investigate the brain cortical and subcortical areas involved in interlimb coordination and the influence of direction of movement and of body segment position on the activity of those areas. Fifteen right-handed healthy subjects were studied while performing cyclic in-phase and antiphase hand and foot movements with the dominant, right limbs, with the upper limb positioned either prone or supine, and in front or behind with respect to the trunk. When contrasting antiphase to in-phase movements, fMRI analysis demonstrated an increased recruitment of a widespread sensorimotor network (including regions in the frontal and parietal lobes, bilaterally, the cingulated motor area, the thalami, the visual cortex, and the cerebellum) considered to function in motor, sensory, and multimodal integration processing. When contrasting the anterior to the posterior position of the upper limb with respect to the trunk, we found different recruitment patterns in the frontal and parietal regions as well as the preferential recruitment of the basal ganglia, the insula, and the cerebellum during the first condition and of regions located in the temporal lobes during the second one. Different brain areas are engaged at a different extent during interlimb coordination. In addition to the relative difficulty of the movement, the different cognitive and sensorial loads needed to control and perform the motor act might be responsible for these findings.