The study aims to investigate the impact that the set of factors to which a post-stroke person is exposed during daily life can have on their health. The study will examine the totality of conditions, known as the "exposome," which include biological, environmental, social, and lifestyle factors.

The exposome represents the complex set of environmental conditions to which an individual is exposed throughout their entire life, including factors such as light, atmospheric pollutants, diet, lifestyles, stress, and interpersonal relationships that are closely correlated with the environmental context and the social network in which and with which the person lives (e.g., rural/metropolitan context, presence or absence of a caregiver) (D'Errico et al., 2023).

The WHO evaluates health in bio-psycho-social terms to arrive at the concept of human functioning and "lived health" (Bickenbach et al., 2023), meaning the ability to carry out daily activities and social participation with the best possible personal and environmental interaction. Studies correlating the exposome with human functioning outcomes in post-stroke patients are extremely limited to date. Indeed, most clinical scales assess the motor, cognitive, and relational abilities of the individual and their impact on quality of life, but the socio-environmental interactions of the individual (e.g., sociodemographic, psychological factors, and living environment) are not systematically included in the analysis (Fahey et al., 2018).

Among the elements of the exposome to be considered, the dual patient-caregiver relationship plays an absolutely central role, as does the environmental context in which patient and caregiver express relationships and activities through which they give form and meaning to emotions, intentions, and resulting actions that shape behaviors and lifestyles.

For all these reasons, it is necessary to redefine multifactorial outcome measures that quantify and qualify relevant aspects of the exposome in an integrated way.

Urbanization and the varying geographical context of residence also carry significant weight in the exposome. "Rural" settings generally allow for greater experience of biodiversity with natural environments and greater exposure to natural light, positively influencing circadian rhythms with antidepressant effects potentially comparable to pharmacological treatments (Burgess et al., 2010). Equally important are contexts that facilitate social relationships, with the potential to significantly and positively influence the psychological well-being of individuals and their perceived sense of happiness (Beccetti et al., 2023). "Metropolitan" contexts, on the other hand, are characterized by environmental situations that may include sources of light pollution, which is associated with a higher risk of psychiatric disorders (Nature 2023, editorial), reduced air quality - associated with obesity and metabolic problems in children (Maitre et al., 2022) - as well as other environmental constraints such as architectural barriers and a fragmented human relational fabric that lead to restrictions or impoverishment of social participation.

Unfavorable environmental conditions can also negatively influence mechanisms of inflammation and systemic immunity (Vieujean S., 2022). Numerous data show that inflammation affects the nervous system both indirectly and through the disruption of slow-wave sleep phases (Gerhard et al., 2000; Block et al., 2005), with consequent alterations in brain plasticity (Facchin et al., 2020) and functional recovery. The combined analysis of inflammation and EEG in post-stroke patients can provide fundamental data for better understanding the role played by the environment in the reconfiguration of functional networks. In particular, inflammasomes, the Natural Killer immune response, cortisol, melatonin, and catecholamine concentrations, neurotrophic factors in peripheral extracellular vesicles of astrocytic origin (ADEVs), single nucleotide polymorphisms (SNPs), and microRNAs can provide information individually or in combination with EEG-based slow-wave sleep detection.

These findings suggest that the exposome and biodiversity may have a determining impact through components that can influence human functioning, with evident potential consequences for the lived health conditions of post-stroke individuals and their caregivers. Biodiversity, which can also be expressed through varied multisensory stimulation, can induce changes in the lifestyle of the individual and their immediate social network, consequently modifying human functioning and creating the bio-psycho-social conditions essential for maintaining and enhancing the results achieved through rehabilitation processes in stroke patients.

In particular, correlations between exposure to both natural and artificial light and modifications in neurophysiological, functional, and biological responses - investigated in numerous studies - suggest its prominent role in both the internal and external exposome (McGlashan et al., 2021; Sabbah et al., 2022).

The limitations of existing studies and the limited exploration of the impact the exposome may have on rehabilitation outcomes in post-stroke patients define an important scientific context to be systematically explored, in order to create new models for evaluating the health status derived from integrated multimodal rehabilitation processes. The challenges that future research will need to address are: i) the adoption of an interdisciplinary approach; ii) the introduction of multifactorial bio-psycho-social analyses; iii) the study of heterogeneous patient populations across the lifespan, with specific reference to developmental age; iv) the inclusion, recognition, and analysis of the role and lived experience of caregivers.

Inclusion Criteria:

• Subjects with Cerebral Stroke, both ischemic and hemorrhagic, in either pediatric or adult age;
• Age > 5 years
• Absence of ongoing clinical acute conditions
• Able to provide written informed consent to participate in the study if of legal age, or consent from a legal representative if a minor
• Absence of major psychiatric disorders associated with the disability condition

Exclusion Criteria:

• Inability to provide informed consent
• Presence of other neurological conditions (e.g. Multiple Sclerosis, Parkinson's Disease…)
• Presence of ongoing clinical acute conditions
• Presence of major psychiatric disorders associated with the disability condition

post-stroke patients