In this month’s issue of the International Journal of Stroke
(IJS), we have a focus on stroke recovery and rehabilitation, covering
both the third international Stroke Recovery and Rehabilitation
Roundtable (SRRR3) consensus statements and recent related work
published in the journal. The recommendations of SRRR3 were officially
launched at the 2023 World Stroke Congress in Toronto, Canada.
The roundtables are an initiative of the International Stroke Recovery and Rehabilitation Alliance (ISRRA).
1
This third roundtable effort builds on the first and second SRRR
initiatives to address new areas where consensus was needed to support
progress in the field of stroke recovery and rehabilitation. The first
roundtable covered definitions,
2 biomarkers,
3 standardized measurement of sensorimotor recovery,
4 preclinical and clinical alignment,
5 and monitoring and reporting of stroke recovery research.
6 The second addressed consensus concerning trial development,
7 cognition,
8 translation into clinical practice,
9 and standardized measurement of quality of movement.
10 The third roundtable focused on control comparator trial design,
11 fatigue,
12 non-invasive brain stimulation,
13 and standardized measurement of balance and mobility.
14
A global initiative and undertaking, SRRR3 included over 50 experts
from more than 20 countries around the world. Each SRRR3 taskforce topic
for consensus will be discussed in turn and linked to recent studies in
the journal.
Control comparator selection is
a critical trial design issue. The benefit of an experimental
intervention is established relative to a prespecified comparator. Poor
selection can diminish the effect observable. To improve preclinical and
clinical control comparator decision-making during trial development,
this taskforce
11 developed the CONtrol DeSIGN (CONSIGN) decision support tool (
https://www.redcap.link/SRRR-CONSIGN).
This tool was designed to address common control design challenges
faced by trialists. These included selecting an appropriate type of
control, managing threats to internal validity, and understanding the
content of the control and how it differs from the experimental
intervention. There is no one-size-fits-all control comparator design.
Recent stroke recovery and rehabilitation studies published in the IJS
demonstrate the breadth of controls used.
15–17 This taskforce did define each type of control and when it is useful; it is a handy reference table for all trialists.
The global pooled prevalence of fatigue after stroke is 46.9% (95% confidence interval = 43.4–50.8%).
18
Despite the high burden of fatigue, progress in the field has been
hampered by inconsistent definitions, outcome measures, and trial
findings. The multidisciplinary fatigue taskforce
12
produced a roadmap for future research. They presented a consensus
definition, “a feeling of exhaustion, weariness or lack of energy that
can be overwhelming, and which can involve physical, emotional,
cognitive and perceptual contributors, which is not relieved by rest and
affects a person’s daily life,” and tackled four priority areas: (1)
best measurement tools for research, (2) clinical identification of
fatigue and potentially modifiable causes, (3) promising interventions
and recommendations for future trials, and (4) possible biological
mechanisms of fatigue. The taskforce recommended outcome measures to use
in studies of post-stroke fatigue, screening of all stroke patients
using a new Stroke Fatigue Clinical Assessment Tool, highlighted
priority therapies to examine for future research, and priority areas
for understanding the biology of post-stroke fatigue. Some priorities
for intervention development and testing (e.g. pharmacological
interventions
19 and exercise
20) and understanding biology (e.g. neuroimaging correlates
21) align with recent IJS papers.
Another
taskforce was established to develop consensus recommendations to
identify and address outstanding translational bench-bedside barriers
and provide a roadmap for the use of transcranial magnetic stimulation
and transcranial Direct Current Stimulation for stroke recovery and
rehabilitation.
13
Recommendations highlight an urgent need for an increased understanding
of non-invasive brain stimulation mechanisms, improved methodological
rigor in both preclinical and clinical non-invasive brain stimulation
studies, standardization of outcome measures, increased clinical
relevance in preclinical animal models, and greater optimization and
individualization of non-invasive brain stimulation protocols. To
facilitate the implementation of these recommendations, the expert panel
developed a new SRRR3 Unified Non-Invasive Brain Stimulation Research
Checklist.
Although prospective
epidemiological studies are lacking, mobility problems are experienced
by 80% of stroke survivors. After 3 months, 40% of initially
non-ambulatory stroke survivors are either unable to walk or dependent
on assistance of a person, whereas 30–80% experience a fall within the
first 4 years post-stroke.
22
The present consensus recommendations established a standardized set of
clinical measurement instruments for investigating lower limb motor
function, sitting- and standing-balance, and mobility. These can be
considered with other work regarding measurement of physical activity
post-stroke.
23
Testing protocols were added to this roundtable to ensure the same
clinical tests were implemented consistently. Furthermore, how to define
the underlying constructs and which baseline characteristics to assess
were recommended at timepoints in line with previous recommendations.
2
Finally, kinetic and kinematic metrics, including their equipment, were
recommended to monitor recovery of quality of movement during standing
and walking post-stroke. The recommendations serve to support
harmonization of data collection, which will improve the comparability
between studies and support establishment of big balance and mobility
data sets post-stroke. Only then phenotyping recoverers and
non-recoverers of lower limb recovery
24–26 and identifying responders of a therapy
22 may give more robust answers in the future.
The
completed roundtables add to the growing library of roundtable
recommendations that can (and are) being used to guide the stroke
recovery and rehabilitation research. The themes to date have spanned
harmonization of terminology and outcomes, clinical trial design and
conduct, and neglected domains of cognition and fatigue, with a
cross-cutting theme of preclinical–clinical alignment as many
roundtables have approached their taskforce by integrating knowledge and
skills across the translational pipeline. Increasingly, consensus
efforts are shaping the focus and methods of recovery and rehabilitation
research. Our hope is that research funders and research teams pay
attention to the priority targets and methodological rigor that is
called for in these statements and that international collaboration
drives new discoveries that benefit the millions of survivors each year
who are impacted by stroke.
Kathryn S Hayward
The University of Melbourne, Melbourne, VIC, Australia
Email: Kate.hayward@unimelb.edu.au
Julie Bernhardt
The Florey, Melbourne, VIC, Australia
Gert Kwakkel
Amsterdam University Medical Centre, Amsterdam, The Netherlands
