So they know nothing and suggest future studies because this study wasn't good enough.
Relationship between intensity and recovery in post-stroke rehabilitation: a retrospective analysis
INTRODUCTION
Work in animal models suggests high intensity rehabilitation-based training
that starts soon after stroke is the most
effective approach to promote recovery.1
In humans, the interaction between treatment onset and intensity remains unclear.2
It has been suggested that reducing daily
treatment duration below 3hours at
the acute and subacute stages leads to
a poorer prognosis,3
while there may
also be an upper bound beyond which
high-intensity motor rehabilitation at the
acute stage might lead to unwanted side
effects.4
Designing optimal rehabilitation
treatment programmes for stroke patients
will not be possible until we understand
‘how much’, ‘when’ and ‘what’ treatment
should be delivered.2
In this retrospective
analysis, we assessed patients’ responsiveness to high-intensity and low-intensity
rehabilitation protocols across different
stages of chronicity post-stroke to address
the ‘how much’ and ‘when’ questions.
PATIENTS AND METHODS
The Queen Square Upper Limb Neurorehabilitation (QSUL)5
and the Rehabilitation Gaming System (RGS)6
datasets
comprise a cohort of 455 individuals with
upper-limb hemiparesis treated between
2008 and 2018 at different stages of chronicity post-stroke (subacute <6 months,
early chronic 6–18 months, late chronic
18 months to 4 years and beyond 4y >4
years).7
The QSUL programme delivered
a 3-week high-intensity rehabilitation
programme (high-intensity conventional
treatment (H-CT), 6hours daily, 5days per
week, 90 hours in total) based on a combination of conventional therapies (n=224).
The RGS cohort (n=231) followed a
3–12weeks low-intensity treatment
programme (20–30min/session, 3–5days
a week, 7.5–30hours in total) consisting
of either conventional treatment (lowintensity conventional treatment (L-CT),
n=69, 30%) or computer-based embodied
goal-oriented rehabilitation in virtual
reality that was automatically adjusted to
the patient’s performance (low-intensity
RGS-based neurorehabilitation (L-RGS),
n=162, 70%). Participants underwent
assessment with the upper extremity
section of the Fugl-Meyer (UE-FM) scale
at baseline, end of treatment (weeks 3–6)
and 6–24 weeks after discharge (longterm follow-up). The details of the assessment have been reported previously.5 6 To
compare the recovery metrics from both
datasets, we calculated the improvement
rate per week of treatment normalised
for the within-subject recovery potential or normalised recovery rate.6
This
metric captures an improvement measure
normalised to the total amount that each
patient could potentially reach given
their baseline score, in this case, on the
UE-FM and allows the assessment of the
responsiveness to treatment. We used the
long-term follow-up assessment, where
no treatment was given, as our control
measurement (no treatment group),
for which we calculated the normalised
recovery rate from the end of treatment.
Data were analysed in MATLAB 2019b
(The MathWorks) and Python V.3.6
(Python Software Foundation), using the
Data Analysis with Bootstrap-coupled
ESTimation libraries. In our analysis, we
considered a p value <0.05 as significant.
RESULTS
Across the two cohorts, a total of 455
patients were included in the analysis. At
the start of treatment, the H-CT was more
severely impaired as measured with UE-FM
(UE-FM score; H-CT: mean 27±13SD;
L-CT: mean 37±16SD; L-RGS: mean
36±14SD; p<0.05, one-way Analysis of
Variance ANOVA), younger (age; H-CT:
mean 49±15SD; L-CT: mean 61±11SD;
L-RGS: mean 63±12SD; p<0.001, oneway ANOVA) and more chronic (days
since stroke; H-CT: mean 1288±1602SD;
L-CT: mean 697±928SD; L-RGS:
mean 806±1003SD; p<0.01, one-way
ANOVA) than the L-CT and L-RGS
groups (detailed post hoc analysis in Ward
et al5
and Ballester et al6
).
All groups that received treatment
showed significant improvements (all treatment groups UE-FM; mean 5±5SD; no
treatment group UE-FM: mean 0±1SD; p
value <0.001, two-sided Mann-Whitney
test). We observed that this improvement
was proportional to training intensity,
that is, the high-intensity group showed
higher responsiveness to treatment at
all measurement points as compared to
both low-intensity groups (difference in
responsiveness between H-CT and L-CT/
L-RGS; mean 4±1SE for subacute; mean
5±1SE for early chronic; mean 5±1SE
for late chronic; mean 6±1SE for beyond
4y; p<0.001, two-sided Mann-Whitney
test) representing a clinically meaningful
change for the non-subacute patients.8
The
analysis of the effect of chronicity showed
a consistent decrease in responsiveness to
the three types of treatment (figure 1A).
Patients who started treatment in the
subacute phase (<6 months) showed the
largest improvement in comparison to
patients at chronic stages for both highintensity (the mean differences in responsiveness between subacute and all other
chronicity groups ranged from −1 to −3;
all p<0.01, two-sided Mann-Whitney test)
and low-intensity treatments (the mean
differences in responsiveness between
subacute and all other chronicity groups
ranged from −3 to −4; all p<0.01, twosided Mann-Whitney test) as shown in
figure 1B. The decrease of responsiveness
extended beyond the subacute phase and
was invariant to training intensity, that is,
those who started low-intensity treatment
earlier at the chronic stage (6–18 months)
also displayed higher gains as compared
to those who started later (difference in
responsiveness between early and late
chronic; mean 1±0SE; p<0.05, twosided Mann-Whitney test). Interestingly,
a late start did not attenuate the patient’s
responsiveness to the high-intensity
programme (difference in responsiveness between early and late chronic;
mean 1±1SE; p=0.38, two-sided MannWhitney test).
DISCUSSION
In this retrospective analysis, we showed
that, in both the QSUL and the RGS
cohorts, responsiveness to treatment was
present at practically all stages post-stroke,
demonstrating a gradually declining
impact with chronicity and modulation of
the responsiveness by the intensity of the
intervention. Our findings also support
an early rehabilitation start regardless of
intensity (ie, at the subacute stage). Beyond
this general effect, the high-intensity
approach showed a consistent higher
impact over low-intensity rehabilitation
protocols (L-RGS and L-CT) at all stages
post-stroke. Indeed, the advantageous
impact of high-intensity rehabilitation on
recovery may compensate for a late start.
For instance, patients who underwent
high-intensity training displayed enhanced
responsiveness even when treatment was
delivered with a 2-year delay compared
with low-intensity interventions. Notice,
however, that the difference in intensity
between the two rehabilitation approaches
was prominent. While the QSUL
programme consisted of 6hours daily, the
low-intensity group underwent 0.5–1hour
daily training for only 3days a week. The
lack of proportionality between the groups suggests a non-linear interaction between
treatment type, intensity, chronicity and
responsiveness.9
This analysis lacks a
control group receiving no rehabilitation
treatment at early stages post-stroke; thus,
we cannot rule out the effect of standard
treatment on the patients’ responsiveness
to additional treatments. Future studies
should investigate and model these relationships to unmask the precise type and
intensity of treatment to promote recovery
at each stage post-stroke. Altogether, these
findings suggest that current stroke guidelines must be revised to incorporate highintensity rehabilitation protocols across
the entire continuum of chronicity.10
Currently, patients obtain only 22 min
of treatment,11 with less treatment time
at later phases post-stroke. Most importantly, we need to find effective solutions
to deliver individualised high-intensity
rehabilitation protocols. The increase in
stroke survivors and the associated burden
poses a challenge for the limited resources
of our current healthcare system and asks
for the translation of effective principles
of neurorehabilitation to scalable technologies to deliver sustainable long-term care
addressing the socioeconomic burden of
stroke.
