By Judit Málly
One of the most devastating symptoms of stroke is motor deficit. It is widely believed that if there is no improvement after one year of intensive physiotherapy, the symptoms will persist for life. Now, new therapies are being developed to directly stimulate the damaged brain after a stroke in order to promote additional healing beyond that achieved by conventional physiotherapy.
Influencing the brain without surgery or anaesthetics has been a longstanding therapeutic goal and about 30 years ago a device that influenced the activity of the brain in a non-invasive way was built in the UK. Transcranial magnetic stimulation (TMS) uses a changing magnetic field which can focally stimulate any part of the cortical area of the brain.
Just as radio waves penetrate thick walls, TMS easily goes through the skull. The other method, transcranial direct current stimulation (tDCS), uses a weak direct current to stimulate the brain. In the latter method, the stimulus is not localised but spreads to the opposite hemisphere and into the deep parts of the brain. Both the synaptic and non-synaptic pathways are involved in the outcome.
At first, TMS was used as a diagnostic tool to measure the motor evoked potential (MEP) and conduction of the motor nerves in the central and peripheral regions. When the motor cortex is stimulated by TMS, a muscle contracts on the opposite side of the body and this can be assessed by electromyography. It was soon discovered that a single stimulus of TMS can decrease the reaction time in Parkinson’s disease but the effects were short-lived and that is why a single stimulus in one session cannot be used for therapy. When our group applied TMS for several days, the after effect lasted for several months beyond the stimulation period. This protocol was used to treat stroke patients.
Normally, there is a mutual inhibition between the two hemispheres of the brain, but the balance is destroyed by a stroke lesion. It means that the non-lesioned hemisphere is over activated because it receives less inhibitory effect from the lesioned hemisphere. The first therapeutic goal with repetitive transcranial magnetic stimulation (rTMS) and tDCS was to restore the balance of the interhemispheric inhibition. The repeated stimulation for a week or more changes the intracortical excitability which leads to a better outcome in patients with stroke. The reversion of the damaged interhemispheric inhibition with low- or high-frequency stimulation led to improved movement in the paretic hands. The studies using low frequency involved patients with slight disabilities and researchers observed the acceleration of movement in paretic extremities. High-frequency stimulation restored the excitability of the lesioned hemisphere and was also effective in improving the function of the paretic hand assessed by Wolf Motor Function Tests.
The most interesting result was that a new movement can be induced in a paretic hand even 10 years after a stroke with low frequency stimulation over both the non-lesioned and the lesioned hemispheres. Researchers (Hsu et al) have used a meta-analysis to compare the studies and found that the low frequency stimulation produced better and longer lasting results than the high frequency stimulation.
There is also acceptance that anodal stimulation is better than cathodal stimulation as shown by the various functional tests performed by stroke patients and the scores that show independence in daily living. It seems that both rTMS and tDCS can improve the quality of life of patients with strokes.
The basic effect of both non-invasive brain stimulations is on the neurotransmitter systems. During the learning process, the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) decreases in the cortical area as assessed by proton magnetic resonance spectroscopy. After anodal stimulation there was a decrease in the GABA concentration in the cortical area. Both types of stimulation increase the brain-derived nerve factor which is necessary for restoration processes and for the development of neuroplasticity.
The principle of non-invasive brain stimulation is based on the change of excitability of certain cortical areas but this change can last for hours or days. We cannot show the direct link between the change in neuroplasticity and the delayed development of the therapeutic effect which appears weeks or months later. In addition, the site of action of non-invasive stimulation is not clearly known but both types of stimulation prepare the lesioned brain for better outcomes. Currently, there is a general conclusion that we must introduce non-invasive brain stimulation into the daily practice of stroke treatment.
Judit Málly is head of the Institute of Neurorehabilitation, Sopron, Hungary