International Consensus Lays the Groundwork for Personalized Stroke Rehabilitation

Why do two people with apparently similar strokes recover their abilities in very different ways? This remains one of the major questions in neurorehabilitation. Dr. Israel Fernández-Cadenas, head of the Pharmacogenomics and Neurovascular Genetics Research Group, and Dr. Cristina Gallego-Fabrega, a researcher in the same group at the Sant Pau Research Institute (IR Sant Pau), have participated in an international consensus that sets priorities for addressing this question through the study of molecular biomarkers.

The document, published in the International Journal of Stroke, calls for large multicenter and longitudinal studies capable of tracking the biological changes that occur during recovery. The goal is to better understand the mechanisms of brain repair and lay the groundwork for more personalized neurorehabilitation.

The work was developed as part of the fourth Stroke Recovery and Rehabilitation Roundtable, an international initiative that brought together 17 experts from nine countries. Its recommendations aim to overcome some main current limitations in research on recovery after stroke: studies with small numbers of patients, conducted at a single center, with samples collected at only one time point and with overly broad measures of functional outcomes.

“Recovery after stroke does not depend solely on the size or location of the lesion. It involves processes such as inflammation, brain plasticity, vascular repair, and neuronal response that we still do not fully understand,” explains Dr. Israel Fernández-Cadenas. “Identifying molecular signals related to these processes can help us better understand why each person recovers differently and, in the future, design more precise treatments.”

From Predicting Outcomes to Understanding the Mechanisms of Recovery

The consensus proposes expanding the role of biomarkers. Beyond using them to estimate functional prognosis, the authors argue that they should also be used to study the cellular and molecular mechanisms that underlie spontaneous brain recovery and the response to therapeutic interventions.

This knowledge could help identify new pharmacological targets, determine whether a treatment is acting on the intended biological mechanism, and better tailor the type, timing, and dose of rehabilitation therapies.

“The goal is not to label a patient according to their possible prognosis but to understand which mechanisms are active during recovery and how we can enhance them,” says Dr. Cristina Gallego-Fabrega. “To achieve this, we need studies that follow people over time and relate their clinical progress to the biological changes that occur after stroke.”

Larger Studies and Harmonized Data

The document’s main recommendation is to promote large, multicenter, longitudinal studies that integrate clinical data, biological samples, and detailed assessments of recovery. To date, much of the research in this field has relied on small cohorts collected at a single center or using samples obtained at only one time point, making it difficult to validate findings.

The authors propose analyzing different layers of biological information, including genetics, gene activity, proteins, metabolites, and epigenetic modifications. These approaches, collectively known as "omics technologies," could make it possible to identify, in an unbiased way, molecules associated with different recovery trajectories.

The consensus identifies several candidate biomarkers that could be incorporated into future research, including neurofilament light chain, a protein associated with axonal damage; brain-derived neurotrophic factor, or BDNF, which is linked to brain plasticity; glial fibrillary acidic protein, associated with glial cells; brain-derived tau; and interleukin-6, which is linked to inflammation. However, the document emphasizes that none of these biomarkers have yet been sufficiently validated for widespread use in rehabilitation care.

“The priority is to move from isolated studies to networks capable of including a sufficient number of patients and analyzing data using comparable protocols,” says Dr. Fernández-Cadenas. “Only then will we be able to confirm which signals are truly relevant and which can be translated into clinical practice.”

Serial Samples and Specific Assessments

The document recommends prioritizing the collection of blood samples, as this is a minimally invasive, scalable option suitable for repeated analyses. To study injury and repair processes, it proposes collecting samples between 3 and 7 days, at 1 month, and at 3 months after stroke. In studies focused on a specific intervention, it recommends collecting samples before treatment begins and after the full course of sessions has been completed.

The authors also advocate combining global disability scales with function-specific assessments of areas such as movement, language, and cognition. This would make it possible to better distinguish between neurological recovery of a function and compensatory strategies that allow a person to function despite a persistent limitation.

The article also highlights the potential of emerging technologies such as extracellular vesicles originating from the central nervous system and circulating cell-free DNA. Both could make it possible to study, from a blood sample, signals more directly related to brain injury and repair, although they still require methodological validation before clinical use.

Precision Neurorehabilitation Without Limiting Access to Care

The consensus emphasizes that biomarker results should not be used to restrict access to rehabilitation or deny care to patients considered to have a poorer prognosis. Instead, their purpose should be to better understand the diversity of recovery trajectories and expand therapeutic opportunities.

To move forward, the authors propose establishing national centers for sample processing and storage, an international repository of molecular data, and multi-year funding frameworks. They also recommend harmonizing collection time points, clinical measures, and sample processing in order to facilitate comparison and validation of results across countries.

“Precision neurorehabilitation is not about reducing options, but about having more tools to offer each patient the intervention that is most likely to provide the greatest benefit,” concludes Dr. Gallego-Fabrega. “This consensus lays the groundwork for generating the evidence needed to turn that goal into a reality.”

Reference Article:

Edwardson MA, Braun RG, Aldridge CM, Akinyemi R, Engelter ST, Fernández-Cadenas I, Gallego-Fabrega C, Le Grand Q, Maguire J, Nave AH, Ratan R, Worrall BB, Xu H, Brodtmann A, Cramer SC, Hayward KS, Lindgren AG. Molecular biomarkers in stroke recovery: Consensus-based core recommendations from the fourth Stroke Recovery and Rehabilitation Roundtable. Int J Stroke 2026:17474930261475960. https://doi.org/10.1177/17474930261475960.