‘More therapy, earlier’ didn’t boost stroke recovery

A clinical trial led by University of Auckland researchers found that high-intensity therapy for patients begun within two weeks of a stroke did not improve hand and arm recovery beyond standard care.

Targeting new treatments to promote hand and arm recovery is necessary because persistent hand weakness is known to reduce a person’s independence at six months after stroke.

The findings challenge the idea that “more therapy, earlier” will lead to better outcomes.

The ESPRESSo (Enhancing Spontaneous Recovery after Stroke) trial compared the effects of three weeks of daily high-repetition and high-intensity hand and arm therapies, starting within two weeks of stroke.

In a world-first for a rehabilitation trial, patients were selected based on a key biomarker that is linked to their potential for hand and arm recovery, despite the initial severity of their symptoms.

One group received the extra therapy by interacting with an immersive videogame-based digital platform which teases out a high volume of exploratory hand and arm movements that guide an animated dolphin, orca or other aquatic creature, through different levels of game play.

The other group received a time-matched dose of additional conventional therapy. Despite having access to an extra 90 minutes of therapy each day for 15 days, neither group did better than a cohort who received standard care alone.

“We saw substantial recovery in almost all patients, but without any benefit of having extra therapy,” says Professor Winston Byblow, the University of Auckland neuroscientist who led the study.

The extra-therapy patients improved markedly between the study onset and when the additional therapy ended, with further and smaller gains at three months (the study primary endpoint). However, the three month outcomes were the same as a previous cohort treated at the same centre, who received only standard therapy.

“Our findings suggest that early recovery after stroke is dominated by powerful biological repair processes and increasing therapy dose over and above standard care very early after stroke may not enhance those processes,” says Byblow, who is based in the School of Exercise, Sport and Rehabilitation Sciences.

Stroke recovery typically unfolds in phases. The first weeks are characterised by spontaneous biological recovery, driven by changes in brain excitability, reorganisation of neural circuits, and resolution of acute injury effects.

The ESPRESSo trial was prompted by the dramatic improvements often seen in animal studies when therapy doses and intensities are much higher than patients routinely experience.

For the patients, recovery followed a strikingly consistent pattern regardless of the therapy type or extra therapy.

“This tells us that natural biological processes dominate recovery in the early phase after stroke.

“This doesn’t mean rehabilitation isn’t important, it most certainly is, but the timing, dose, and a patient’s capacity to engage in therapy at the very early stage matter more than previously appreciated,” he says.

“It is interesting to see that extra therapy can be delivered by using digital aids that are fun, engaging and rated as enjoyable by patients, with the same outcomes achieved as conventional therapy.”

The results have important implications for how stroke rehabilitation services are organised.

Delivering intensive therapy very early after stroke is challenging, even in well resourced hospitals such as the one where the trial was conducted. Patients are often fatigued, medically unstable and juggling multiple rehabilitation priorities.

The study suggests high dose therapy may be more effective later, once patients are able to engage more fully, albeit when gains are smaller.

“We may need to explore more biological treatments early rather than pushing patients harder with activity-based therapies alone. The activity-based therapy dose can be gradually increased over time,” Byblow says.

“The biggest gains from intensive training may come after early spontaneous recovery has run its course.”

The ESPRESSo trial was a single site, randomised, assessor-blinded Phase IIa clinical trial conducted at Auckland City Hospital between 2021 and 2024.

Sixty-four stroke survivors were randomly assigned to either video game-based exploratory movement therapy or conventional therapy, alongside experienced therapists for 90 minutes per weekday over three weeks, in addition to usual care.

The study was funded by the Health Research Council of New Zealand, and the international research team included collaborators from Johns Hopkins University, New York Medical College, UCLA, the University of Adelaide, and MindMaze SA (Switzerland).