Comment
Virtual reality versus reality in post-stroke rehabilitation
Published Online Virtual reality has become popular in some rehabilitation
June 27, 2016
http://dx.doi.org/10.1016/
settings as a means of engaging patients with motor
S1474-4422(16)30126-0 impairment after stroke in their own recovery. The
See Articles page 1019 underlying premise is that the engaged patient will
more likely participate in task-specific behaviour
and achieve one of the most important objectives
in recovery: repetition. Although small studies have
suggested the potential benefit of using virtual reality
in stroke rehabilitation, methodological issues with
respect to what constituted the control group have been
a substantial limitation.1 In these studies, comparisons
were made between virtual reality with conventional
rehabilitation versus conventional rehabilitation alone.
The confound in this design is that patients receiving
both virtual reality and conventional rehabilitation
receive more overall therapy time than those receiving
conventional rehabilitation alone. Thus, the effect seen
might be explained by any intervention that increases
repetitive activities rather than a specific property of
virtual reality. In stroke rehabilitation, this phenomenon
has been borne out in randomised trials that compared
intervention strategies that were not superior to active
controls, but were superior to an inactive group.2–4
In the The Lancet Neurology, Gustavo Sapsonik and
colleagues5 report the results of the EVREST trial, a
detailed, elegant study that included simple recreational
activities such as playing cards, bingo, Jenga, or a ball
game as part of the control intervention, attempting
to eliminate the issue of repetition dosing. Among
141 stroke patients with upper extremity weakness,
enrolled within 3 months of stroke onset, who
were assigned to non-immersive virtual reality with
conventional rehabilitation or recreational activity
with conventional rehabilitation, the total duration of
treatment over the course of 2 weeks was similar in both
groups (528 min vs 541 min, respectively, p=0·60). The
primary outcome measure, the total time to complete
the Wolf Motor Function Test (WMFT) at the end of the
intervention period, was improved by about the same in
both groups (decrease in median time from 43·7 s [IQR
26·1–68·0] to 29·7 s [21·4–45·2], 32·0% reduction for
VRWii vs 38·0 s [IQR 28·0–64·1] to 27·1 s [21·2–45·5],
28·7% reduction for recreational activity), with no
difference in serious adverse events between groups.
Effects were generally sustained after an additional
996
4 weeks in both groups and no significant differences
were seen in global measures of function or quality of
life. The authors appropriately conclude that the specific
type of activity used in post-stroke rehabilitation might
not be so relevant as long as it is task-specific and of
sufficient duration. Given the low cost of recreational
therapies worldwide, they suggest the use of these
interventions on a global scale.
Critics of the study could argue that the method of
virtual reality used, a Wii gaming machine, defined as
non-immersive virtual reality, was not truly similar
to hospital-based systems, defined as immersive. In
response to that concern, the authors report a high
compliance rate with virtual reality training in EVREST
(86%), which suggests that patients were engaged,
irrespective of the technology’s level of immersion. One
other potential criticism is the lack of a study group
with conventional rehabilitation alone, of similar total
duration of treatment over 2 weeks as virtual reality
and recreational activity. This comparison could be
made in future studies but, given the reimbursement
pressures to reduce the total duration of conventional
rehabilitation, it is unlikely that health insurers will be
easily convinced that more treatment is better with this
type of intervention.
Whether additional total duration of therapy with any
of these interventions would further improve outcomes
is another important research question in stroke
rehabilitation. The EXCITE study found that in patients
who had a stroke 3–9 months earlier, constraint-induced
movement therapy done up to 6 h per day for 14 days
significantly improved upper extremity function at
12 months, compared with conventional rehabilitation.6
The total duration of treatment was much longer in the
intervention and control groups in the EXCITE trial than
in the EVREST trial, possibly accounting for some of the
difference in outcomes between groups. By contrast, the
AVERT study showed that an average of 31 min per day
of therapy for 14 days started at an average of 18·5 h
after stroke was actually deleterious to patient recovery,
compared with an average of 10 min of therapy per day
for 14 days started at an average of 22·4 h after stroke.7
Together, these results suggest that there might indeed
be a U-shaped curve with respect to total therapy time
and recovery of function. Additionally, because of
www.thelancet.com/neurology Vol 15 September 2016

reduced neuroregenerative capabilities in old patients,
the optimum therapy duration might also vary with
patient age, which also requires further evidence.
EVREST is an important study because it shows that
easily accessible, low-cost interventions are as useful
as less accessible, higher cost ones. As the mountain
of evidence grows regarding the types and doses of
treatments for rehabilitation after stroke, so too will the
percentage of patients with improved outcomes.
Brian Silver
Rhode Island Hospital, Providence, RI, USA
Brian_Silver@brown.edu
I report personal fees for stroke outcomes adjudication in the Women’s Health
Initiative and SOCRATES studies, personal fees from expert review for
medicolegal cases related to stroke, salary as a Joint Commission stroke surveyor,
and personal fees for chapters written in Ebix, Medlink, and Medscape.
The pros and cons of intravenous thrombolysis in stroke
Intravenous thrombolysis with alteplase is an emergency
treatment aiming at early recanalisation of the occluded
cerebral artery and reperfusion of the ischaemic brain
tissue.1–3 Occlusion of any part of the brain supplying
arteries, including the large cerebral arteries and small
intracerebral arterioles, can be the cause of an ischaemic
stroke leading to various neurological deficits. Typically,
alteplase is administered within 4·5 h of symptom onset,
and the earlier it is given, the more effective it is.4 Young
age, low National Institutes of Health Stroke Scale score
at onset, effective recanalisation, and early neurological
improvement are predictors of favourable outcome
at 3 months.5–7 However, alteplase can only be applied
after an intracranial haemorrhage has been ruled out.
As alteplase might not recanalise the occluded cerebral
artery, thrombectomy is used in many stroke centres.
Otherwise, the patient is likely to develop a severe brain
infarction, which can become life threatening within the
first few days after stroke. Also, the patient might have
an intracerebral haemorrhage after thrombolysis, which
is often fatal within the first few days after stroke.4
After emergency treatment, the patient requires
dedicated treatment, which is best provided in a stroke
unit. This standard care aims to monitor and adjust vital
variables, to initiate secondary prophylaxis according
to the cerebrovascular, cardiac, or coagulatory cause of
the individual patient’s stroke, and to rehabilitate the
www.thelancet.com/neurology Vol 15 September 2016
Comment
1 Lohse KR, Hilderman CG, Cheung KL, Tatla S, Van der Loos HF. Virtual reality
therapy for adults post-stroke: a systematic review and meta-analysis
exploring virtual environments and commercial games in therapy.
PloS ONE 2014; 9: e93318.
2 Lo AC, Guarino PD, Richards LG, et al. Robot-assisted therapy for long-term
upper-limb impairment after stroke. N Engl J Med 2010; 362: 1772–83.
3 Duncan PW, Sullivan KJ, Behrman AL, et al. Body-weight-supported
treadmill rehabilitation after stroke. N Engl J Med 2011; 364: 2026–36.
4 Dromerick AW, Lang CE, Birkenmeier RL, et al. Very early constraint-induced
movement during stroke rehabilitation (VECTORS): a single-center RCT.
Neurology 2009; 73: 195–201.
5 Saposnik G, Cohen LG, Mamdani M, et al, for Stroke Outcomes Research
Canada. Efficacy and safety of non-immersive virtual reality exercising in
stroke rehabilitation (EVREST): a randomised, multicentre, single-blind,
controlled trial. Lancet Neurol 2016; published online June 27. http://dx.doi.
org/10.1016/S1474-4422(16)30121-1.
6 Wolf SL, Winstein CJ, Miller JP, et al. Effect of constraint-induced
movement therapy on upper extremity function 3 to 9 months after
stroke: the EXCITE randomized clinical trial. JAMA 2006; 296: 2095–104.
7 Bernhardt J, Langhorne P, Lindley RI, et al. Efficacy and safety of very early
mobilisation within 24 h of stroke onset (AVERT): a randomised controlled
trial. Lancet 2015; 386: 46–55.
patient. However, to what extent initial treatment with Published Online
July 19, 2016
alteplase also pertains to the long-term prognosis of http://dx.doi.org/10.1016/
ischaemic stroke is unknown. S1474-4422(16)30159-4
In The Lancet Neurology, Eivind Berge and colleagues8 See Articles page 1028
report the effect of alteplase on stroke survival of up to
3 years from the Third International Stroke Trial (IST-3).
This large, randomised, controlled, open-label trial
included 3035 participants, and 1948 patients were
followed up with use of national death registries in the
UK and Scandinavia. More patients given alteplase died
within 7 days (99 [10%] of 967) than did those who
received standard care only (65 [7%] of 979) owing
to intracranial haemorrhage and malignant brain
infarction. Thereafter, fewer patients given alteplase
and standard care died than did those given standard
care alone (354 [41%] of 868 vs 429 [47%] of 914;
p=0·007), which was not due to patients’ age, stroke
severity, or time lag until treatment. These data are
important and in line with a nationwide follow-up
study in Denmark,9 providing a solid basis in favour of
an effective treatment for a devastating neurological
emergency. Although alteplase has the potential to
harm the individual patient, it has been shown to be
cost-effective over the patient’s lifetime.10
However, two important issues for this trial deserve
further consideration. First, similar to a previous
report from the IST-3 group,11 risk of death in patients
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