Mirrortherapy for improving handfunction in chronic stage after stroke: a study on its effectiveness and an fMRI evaluation of underlying cortical mechanisms.

Approximately 55% to 75% of patients that survive a stroke will experience
significant problems in the upper extremity. Because of the physical limitation
(hemiparesis, loss of muscle strength) and due to the fact that
patients tend to avoid using their affected hand in daily activities (*learned
non-use*), many patients will develop a dysfunctional arm and hand. Optimizing
upper limb functioning is therefore a central issue in many post-stroke
rehabilitation programs. Despite the common clinical knowledge that recovery of
arm function will
plateau after 6 months to 1 year, it has been demonstrated that practice
schedules may be effective even when performed in the chronic stage after
stroke (Caraugh and Kim, 2005; Barreca et al., 2003). This effectiveness
increases when treatment is task-specific (van Peppen et al. 2004) and when the
intensity of
treatment is high (Kwakkel et al. 1999).
Mirror therapy
Ramachandran first introduced mirror therapy in 1996. In mirror therapy, the
reflection of the intact arm is visually superimposed on the involved hand,
creating an illusion of normal movement of the involved hand. Using mirror
therapy in patients with phantom pain after amputation, patients reported that
they could move and relax the often-cramped phantom limb and experienced pain
relief. Soon after this first report, Altschuler (1999) reported on the
successful use of mirror therapy for training the upper extremity after stroke.
In a randomized cross-over design on chronic stroke patients, comparing 4 weeks
of mirror therapy and 4 weeks of regular exercises, it was established that
range of motion, speed, and accuracy of arm movement were more strongly
increased after the mirror therapy. Similarly, Sathian et al. (2003) found that
2 weeks of intense mirror therapy in chronic stroke resulted in a strong
recovery of grip strength and hand movement of the paretic arm. In two recent
studies, Stevens et al. reported (2003, 2004) on a small number of stroke
patients trained with mirror therapy for 3 to 4 weeks, with increases in
Fugl-Meyer scores, active ranges of motion, movement speed, and hand dexterity
after mirror therapy. Finally, in a small randomized clinical trial,
Rothangel (2004) compared mirror therapy with standard exercise therapy in 16
chronic stroke patients and found that the mirror therapy group showed larger
improvement in hand function.
While all these above-mentioned studies report positive effects of mirror
therapy in stroke, all of these studies were undersized and not sufficiently
controlled. Therefore, to establish whether mirror therapy has sufficient value
to be included in standard care for stroke patients, larger and
better-controlled outcome studies are needed with a sufficiently long-term
follow-up.
Mechanism of action of mirror therapy
Adaptive changes take place in the human brain after focal injury. How this
adaptation can be modulated is a key question in neurorehabilitation.
Functional training of the paretic hand increases somatosensory input,
improving motor function due to plasticity of the affected motor cortex.
Therapeutic exercise might be more successful if the ability of peri-infarct
and nonprimary motor regions of the affected hemisphere to respond to motor
training can be improved. For example, transcranial magnetic stimulation
synchronously applied to a human motor cortex engaged in a motor training task
enhances use-dependent plasticity (Butefisch et al 2004).
Although it is still unclear how mirror therapy fits in the model of enhancing
cortical plasticity, a number of studies have shown that mirror illusions have
measurable effects on brain activity (e.g., Fink, 1999; Garry, 2005).
Altschuler et al. (1999) hypothesized that mirror therapy provides visual input
of a normal movement of
the affected arm in stroke patients, which may substitute for a decreased or
absent proprioceptive input. Another hypothesis is that mirror therapy is a
form of visual guided motor imagery (Stevens, 2004). Motor imagery is the
mental performance of a movement without overt execution of this movement.
Extensive
clinical, neurophysiological and neuroimaging evidence demonstrates that motor
imagery involves the same neural networks as motor execution (for review, see
Mulder, 2004). Motor imagery may therefore be a useful therapeutic tool in
neurorehabilitation (Johnson-Frey, 2004). A final hypothesis concerns the
involvement of the mirror neuron system (Rosen 2005). Mirror neurons (for
review, see Rizzolatti, 2004) are bimodal visuomotor neurons that are active
during action observation, mental simulation (imagery) and action execution.
For example, it has been found that passive observation of an action
facilitates M1 excitability of
the muscles used in that specific action (Fadiga, 2004). The mirror neurons are
now generally understood to be the system that is the bases of learning new
skills by visual inspection of the skill (imitation learning; Rizzolatti,
2004). In a recent fMRI study at our department on neural activation during
mirror illusions in 18 healthy subjects, we found systematic activation in two
cortical areas, one of which is linked with the mirror neuron system (Matthys
et al., submitted). This finding suggests that mirror induced visual illusions
may provide an ideal image representation for action observation, and that the
mirror neuron system may be the core neural network associated with mirror
therapy. However, the
specific contribution of visual feedback through mirror therapy is yet
unsolved. Further knowledge of the underlying mechanism of mirror therapy will
further improve the therapeutic application of mirror illusions.

Literature
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The study objective is to evaluate, with respect to hand function, the effect
of a physical therapy program based on mirror therapy compared to conventional
physical therapy in chronic stroke patients and to improve our understanding of
the underlying cortical mechanisms of mirror therapy and to evaluate the changes
in the neural activation during hand movements after 6 weeks of mirror therapy
or regular physical therapy.

The aim of the addendum is to further validate the Stroke-ULAM, one of the
measurement tools used in the main study. In a group of healthy volunteers the
effects of handedness on the outcome parameters of the Stroke-ULAM will be
explored. Subsequently, the use of a correction for handedness on the outcome
measures of stroke patients of the main research will be evaluated.

The effects of a 6-week mirror therapy program for chronic stroke patients
(n=2x20) will be compared to standard physical therapy in an RCT, for which
funding has been obtained from other sources. In this proposal, brain
imaging using fMRI will be performed in a subgroup of the patients involved in
the above-mentioned RCT to evaluate immediate and long-term changes in the
neural network involved in the control hand movements. In addition, the fMRI
data will be evaluated to provide further insight in the underlying cortical
mechanisms of mirror
therapy.

To carry out the addendum, 20 healthy volunteers will be recruted. They will
wear the Stroke-ULAM for one and a half day. During this period they are
instructed to carry out their daily activities as usual, only they are not
allowed to bathe or shower.

It is known from literature that the most effective therapy is the one with a
high intensity (hours a day). Since mirror therapy can also be done without
supervision of a therapist, it is a potential effective therapy. The intensity
and specific form of mirror therapy will be established in the first phase of
this project. The background will be that mirror therapy will be compared to
standard physical therapy. To avoid that a possible effect can be explained
from differences in intensity of treatment between groups, exercises and
exercise time will be equal for both groups. The intervention in the
experimental group will therefore only differ by the use of
mirror illusions. Exercises will be learned and exercise therapy will be
provided by an experienced physical therapist. However, an important part of
the intervention is that patients have to practice at home. Therefore, patients
are materially supported with a mirror and an instruction video or DVD. A diary
is used to control for exercise time per day (including the total minutes of
practice). Furthermore, patients will be personally contacted and individually
coached during the intervention period (by phone and home visit).

The healthy volunteers do not receive an intervention.

Both interventions (with and without mirror) have a low risk profile.
Complaints of ahhesive capsulitis of the shoulder joint or symptoms of shoulder
hand syndrome may increase and muscle soreness may occur.

For the healty volunteers their are no risks associated with participating.