“NUTRISTROKE”: THE ROLE OF NUTRITION AND BODY COMPOSITION IN POST-STROKE RECOVERY

Stroke represents one of the most pressing global health challenges, ranking as the second leading cause of death and the third leading cause of death and disability combined. Rehabilitation is a multidisciplinary process of care aimed at managing and reducing stroke-related impairments and optimizing functional recovery. Notably, even among patients with comparable baseline motor and cognitive function, some achieve worse outcome than others. This suggests that factors beyond initial neurological severity may influence the response of post-stroke survivors to rehabilitation treatment. Within this context, nutrition and body composition assessment emerge as crucial components in the overall picture of the patients that have to undergo rehabilitation after a stroke insult. Malnutrition is highly prevalent and clearly associated with poorer clinical and functional outcomes during the rehabilitation period. Moreover, stroke survivors frequently experience a progressive loss of muscle strength, mass and quality, leading to a condition termed stroke-related sarcopenia, which may profoundly affect the entire recovery process after a cerebrovascular event. However, until now, there has been very poor literature considering the role of malnutrition and sarcopenia affecting post stroke rehabilitation, and most studies have been conducted in Asian population, leaving Caucasian population unexplored. The “Nutritional Status in Subacute Stroke Patients Under Rehabilitation (NUTRISTROKE)” protocol is a prospective longitudinal observational, multicentric study carried out from 2020 to 2023 aimed at investigating the complex interplay between nutritional status, body composition, and functional and cognitive outcomes in subacute Italian post-stroke patients undergoing a six-week rehabilitation program. For this study, demographic and clinical data were registered, and nutritional status was evaluated by means of anthropometric and hematochemical parameters, together with body composition assessment performed with Bioelectrical Impedance Analysis (BIA), at admission to the rehabilitation center (T0) and after a six-week rehabilitation treatment (T1). BIA proved to be an easy-to-use, safe, inexpensive and non-invasive device, very suitable for the rehabilitation setting. Among the functional and cognitive outcome measures assessed within the NUTRISTROKE protocol, the modified Barthel Index (mBI), the Fugl–Meyer Assessment for the Upper Extremity (FMA-UE), and the Motricity Index for upper (MI-UE) and lower (MI-LE) extremities were evaluated at both T0 and T1 to determine, respectively, the patient’s independence in Activities of Daily Living (ADL), upper limb motor performance, and upper and lower limb muscle strength. Post-stroke patients were enrolled in two rehabilitation centers of Fondazione Don Carlo Gnocchi: “S. Maria della Provvidenza” located in Rome (RM, Italy) and the “Polo Specialistico Riabilitativo” located in Sant’Angelo dei Lombardi (AV, Italy). Patients in both centers followed the same rehabilitation protocol, consisting of both conventional and robotic interventions and underwent the same functional and clinical assessments, except for body composition analysis, which was carried out only at the Rome center. A final sample of 109 subacute post-stroke patients was evaluated across the two centers. This thesis aims to present the main findings obtained during my PhD activity conducted within the framework of this clinical study. My primary objective was to investigate the role of body composition in post-stroke recovery by examining some BIA-derived parameters that have been poorly explored or never addressed in stroke patients, and to provide novel insights into how sarcopenia, malnutrition, and dietary intake may affect rehabilitation outcomes. From these studies, five manuscripts were published in international peer reviewed journals. The first study was a preliminary analysis conducted to explore Body Cell Mass (BCM) as a potential BIA-derived biomarker of functional recovery in a group of 61 patients. BCM is a key parameter reflecting the metabolically active cellular mass of the body, which is directly involved in oxygen consumption and closely related to nutritional status. Our group found that BCM measured at admission was not only positively correlated with baseline ADL independence but was also positively associated with gains in ADL independence over the rehabilitation period, regardless of patients’ functional status at admission. These results suggest that assessing BCM at admission not only would improve the evaluation of body composition status in post-stroke patients but would also potentially predict their recovery. The second study was carried out with the aim of investigating whether segmental Phase Angle (PhA) was a more appropriate assessment tool of muscle quality in post stroke patients, who often experience hemiparesis, than the assessment of whole-body PhA. The PhA is a BIA-derived parameter computed directly from the two raw BIA parameters, Resistance (Rz) and Reactance (Xc), and is related to cellular health and muscle quality. While whole-body PhA is derived from Rz and Xc measured across the entire body, segmental PhA is evaluated separately in different body segments. This study showed that, as expected, whole-body PhA values in patients were below the normal range. From the segmental data analysis, we found that the affected hemisoma, arm and leg had considerably lower PhA values compared with the unaffected side. Furthermore, after six-week of rehabilitation, PhA values of all affected limbs improved, whereas those of the unaffected limbs and whole-body PhA did not. At both time points segmental PhA values of the affected limbs were associated with all functional outcome measures, while whole-body PhA correlated only with mBI. Thanks to these results, reported for the first time in a Caucasian population, it has become evident that segmental PhA plays a critical role, as it enables the precise monitoring of changes in muscle quality induced by rehabilitation in post-stroke patients with hemiparesis. Besides segmental PhA, another valuable tool for qualitatively assessing body composition is Bioelectrical Impedance Vector Analysis (BIVA). Despite the widespread use of BIVA in different clinical and athletic contexts, its application in subacute post-stroke patients remained unexplored. Therefore, the third study aimed to fill this gap by analyzing BIVA in patients recruited at the rehabilitation unit in Rome. The analysis revealed that most patients exhibited marked fluid overload and reduced muscle mass. BIVA also showed that patients with malnutrition and sarcopenia were characterized at admission by rightward shift of their bioimpedance vectors on the Rz-Xc graph compared to those without these conditions. Moreover, BIVA measured at admission distinguished patients who would have greater improvement from those with lower improvement in independence in Activity of Daily Living (ADL). BIVA seems to be a very easy-to-use tool that allows an immediate evaluation of hydration and nutritional status of stroke survivors, significantly complementing the traditional BIA approach. Moreover, we showed that BIVA can differentiate patients based on their functional recovery, making it a future potential prognostic tool. Another important field of investigation was examined in the fourth study, which explored, for the first time, the impact of sarcopenia, diagnosed according to the EWGSOP2 criteria, on both functional and cognitive outcomes after rehabilitation. The existing literature had focused exclusively on Asian post-stroke patients, leaving the investigations in Caucasian cohorts unexplored. Our group demonstrated that sarcopenic patients presented poorer nutritional status and lower scores in all functional and cognitive assessments at admission compared to non-sarcopenic counterparts. Moreover, although both sarcopenic and non-sarcopenic groups showed significant improvements in all assessed functional and cognitive outcomes after the rehabilitation program, individuals with sarcopenia still ended rehabilitation with worse results, particularly in terms of walking ability and independence. Specifically, fewer sarcopenic patients were able to achieve higher levels of ambulation compared with their non-sarcopenic counterparts. Furthermore, even after controlling for baseline characteristics, the sarcopenic patients exhibited lower recovery of independence in ADL the end of the rehabilitation treatment. The accurate diagnosis of sarcopenia in patients affected by stroke appears to be crucial, and greater efforts are needed in rehabilitation settings to design targeted interventions that include nutritional supervision and supplementation, as well as individualized rehabilitation programs. Besides the studies on body composition and the impact of sarcopenia on rehabilitation outcomes, another important part of my research focused on the analysis of food consumption in patients enrolled in the “NUTRISTROKE” protocol. Monitoring food consumption during post-stroke rehabilitation is both challenging and essential, as stroke-related complications may compromise adequate nutrition, highlighting the need to ensure that patients’ dietary requirements are effectively met. As defined in the protocol, the amount of food wasted at each meal—breakfast, lunch and dinner—was systematically recorded six days per week over the entire six-week rehabilitation period, resulting in a total of 108 meals evaluated for each patient. We then investigated the relationship between nutritional intake and functional recovery, considering the presence of malnutrition. We identified 105 patients (96%) at risk of malnutrition, and, according to the Global Leadership Initiative on Malnutrition (GLIM) criteria, 43 were diagnosed as malnourished, 15 of whom were severely malnourished. On average, malnourished patients wasted more food than non-malnourished patients and showed a significantly lower recovery in independence in ADL. Furthermore, linear regression analysis revealed that the recovery in ADL independence was significantly associated with the amount of wasted “second dishes”, which mainly contained protein, even after controlling for age. Therefore, the assessment of malnutrition and systematic monitoring of food intake represent key components of the nutritional evaluation of post-stroke patients, particularly given that prolonged hospitalization can negatively influence nutritional status, with direct implications for the recovery process. Taken together, all the studies included in this thesis provide strong evidence that body composition and nutritional status are key determinants of post-stroke recovery. Specifically, this work demonstrates that a comprehensive nutritional evaluation should include: (i) an appropriate assessment of body composition that considers stroke-related impairments, using not only whole-body BIA but also segmental BIA and BIVA; (ii) an accurate diagnosis of malnutrition and sarcopenia at admission to the rehabilitation center; and (iii) a simple but systematic monitoring of food intake during hospitalization. Importantly, these findings have guided the development of new research perspectives, specifically the observational study “Nutritional Status in Subacute Stroke Patients Under Rehabilitation 2.0” (NUTRISTROKE 2.0), which is currently ongoing. This protocol aims to further deepen the assessment of nutritional status in post-stroke patients undergoing rehabilitation by integrating a more detailed quantification of individual nutrient intake, an evaluation of dysphagia using a quantitative scale, and other biological analyses such as metabolomic analysis of urine samples and gut microbiota analysis. Overall, this thesis supports the importance of integrating nutritional and body composition evaluations into rehabilitation pathways to promote personalized care, enhance functional recovery, and improve the quality of life of stroke survivors.