Is fatigue an unbreakable limit or a malleable barrier in neurorehabilitation?

Post-stroke fatigue (PSF) is one of the most debilitating symptoms for stroke survivors, but also one of the least understood. According to Kuppuswamy et al. (2023), fatigue is not simply a sensation of tiredness; it is a complex and multifaceted phenomenon involving physical, cognitive, emotional, and perceptual processes, often resistant to rest.

At the CEN - Centro Europeo de Neurociencias CENNEURO , we have adopted a radically different approach compared to conventional practice. While standard therapies are often limited to 45-60 minutes out of fear of exacerbating fatigue, our intensive therapies—spanning from 2 to 6 hours daily—not only address fatigue but use it as an opportunity to personalize interventions and optimize recovery.

How do we understand fatigue? The model proposed by Kuppuswamy and colleagues serves as a valuable guide for analyzing and treating PSF. They categorize the contributing factors into three types: predisposing, precipitating, and perpetuating.

1. Predisposing factors: Who is more vulnerable?

Predisposing factors are those that make a person more likely to experience PSF, even before the stroke occurs. These include:

• History of chronic fatigue: Individuals with prior conditions such as chronic fatigue syndrome, multiple sclerosis, or depression may be at higher risk of developing PSF.
• Genetics and inflammation: Genetic variants affecting inflammatory responses, such as polymorphisms in cytokine-related genes (e.g., IL1RN), can predispose individuals to greater sensitivity to fatigue.
• Cardiovascular and metabolic factors: Conditions like diabetes, hypertension, and obesity—affecting energy metabolism and systemic inflammation—are important contributors.

In our experience, understanding these backgrounds helps us anticipate which patients may need a slower progression or a more tailored approach to managing fatigue.

2. Precipitating factors: What triggers fatigue?

PSF can be triggered directly by biological and physiological events occurring during and after a stroke:

• Acute inflammation: The immediate inflammatory response to stroke can persist over time, affecting both brain function and energy metabolism.
• Dopaminergic dysfunction: Reduced activity in dopaminergic pathways, crucial for motivation and effort perception, is a key trigger for fatigue.
• Alterations in neural networks: Structural and functional damage in sensorimotor and prefrontal networks can increase the perceived effort required to perform even previously automatic tasks.

How do we address these triggers? At CEN, we manage these factors with specific strategies, such as adjusting task difficulty, incorporating regular breaks, and exploring innovative approaches like neuromodulation when clinically indicated to support recovery.

3. Perpetuating factors: Why does fatigue persist?

Perpetuating factors maintain or exacerbate fatigue over the long term, often beyond the initial recovery period. These include:

• Comorbidities: Depression, anxiety, chronic pain, and sleep disorders often coexist with PSF, amplifying its effects.
• Metabolic and nutritional conditions: Malnutrition, vitamin deficiencies, and circadian rhythm disruptions can perpetuate fatigue.
• Physical deconditioning: Lack of physical activity after a stroke contributes to muscle atrophy and reduced aerobic capacity, feeding a cycle of fatigue.
• Psychosocial factors: A lack of social support, reduced expectations, and fear of relapse can negatively influence the perception of available energy.

In our intensive therapies, we meticulously identify and manage these factors. For example, we work closely with nutritionists and sleep specialists, monitor medication side effects, and focus on patient motivation to break this cycle.

A critical look at conventional rehabilitation

Traditional approaches, with brief 45-60 minute sessions, often assume that fatigue is an unbreakable limit. However, our experience suggests otherwise: with proper planning and a progressive approach, many patients can tolerate—and even benefit from—more intensive therapies.

In our 2-6 hour sessions, we design:

• Individualized progression: We tailor the duration and intensity of tasks based on each patient’s tolerance.
• Strategic rest periods: Breaks are not mere interruptions but an active tool for maintaining energy balance.
• Complementary interventions: From sleep management to nutrition and pharmacotherapy, every aspect contributes to optimizing performance and mitigating fatigue.

Breaking boundaries

Fatigue is real, but it is not necessarily an unbreakable barrier. It is a multifactorial phenomenon that, far from being an excuse to reduce intensity, should invite us to design smarter and more personalized therapies. As Kuppuswamy’s model shows, fatigue is not the end but a starting point to rethink what is possible in neurocognitive rehabilitation.

Is it time to challenge rehabilitation paradigms? At CEN, we believe so. And our daily experience shows us that with the right strategies, patients can achieve more than they imagine.

I’d love to hear your thoughts and experiences. How do you address fatigue in your practice?

This post is based on the article: "Mechanisms of Post-Stroke Fatigue: A Follow-Up From the Third Stroke Recovery and Rehabilitation Roundtable" https://pmc.ncbi.nlm.nih.gov/articles/PMC10798014/