Surround inhibition in dystonia; a TMS study in patients with writers cramp.

There are currently 6000 patients in the Netherlands diagnosed with a primary
focal dystonia. A well recognized form of dystonia is writer*s cramp. Writer*s
cramp is a focal hand dystonia where symptoms occur only during writing and not
during other motor tasks, the trigger of this movement disorder is therefore
specific.

We observe an overflow of muscle activation in patients with a task-specif
dystonia. There is a complex organization in the motor system that channels the
spatiotemporal commands necessary for a writing task and surround inhibition is
a physiological mechanism to focus this neural activity. Surround inhibition
(SI) aids the execution of movements in the central nervous system by
facilitating the neurons of active muscles conducting the movement and
inhibiting the neurons of competing surrounding muscles. The basal ganglia
could possibly have a key role in the neurophysiology of this aspect of motor
control.
It remains however incompletely understood how surround inhibition is generated
and in which way it is relevant for the overflow of muscle activation seen in
patients with writer*s cramp. In this study we therefore set out to further
explore surround inhibition.

There are at present no good treatment options for patients with writer*s cramp
and new therapeutic options should therefore thoroughly be investigated.
Previous research has shown that modulation of the premotorcortex by rTMS
improves symptoms of writer*s cramp. The rationale for the clinical improvement
in dystonia after inhibitory rTMS over the premotor cortex remains however
unidentified.
The aim of this study is therefore not only to expand the current knowledge
about the pathophysiology of writer*s cramp but to also investigate the
foundation of this neuromodulatory intervention.

There is a complex organization in the motor system that channels the
spatiotemporal commands necessary for a writing task and surround inhibition is
a physiological mechanism to focus this neural activity. Surround inhibition
(SI) aids the execution of movements in the central nervous system by
facilitating the neurons of active muscles conducting the movement and
inhibiting the neurons of competing surrounding muscles. The basal ganglia
could possibly have a key role in the neurophysiology of this aspect of motor
control.
It remains however incompletely understood how surround inhibition is generated
and in which way it is relevant for the overflow of muscle activation seen in
patients with writer*s cramp. In this study we therefore set out to further
explore surround inhibition.

Transcranial Magnetic Stimulation (TMS) is the fundamental technique for this
study. TMS is a non invasive technique that provides the opportunity to measure
and modulate cortical excitability by means of a magnetic coil.
We will apply repetitive TMS to modulate the excitability of the premotor
cortex in patients with writer*s cramp as this method has been shown to improve
writer*s cramp in former studies. The objective of this study will be to
expand these previous studies by investigating a possible improvement of
surround inhibition and to thereby see whether a dysfunctional surround
inhibition can be considered causal for the dystonic movement in writer*s
cramp.

The main question that we want to answer by this study is if an improvement of
writer*s cramp, evoked by rTMS over the premotor cortex, does indeed aid a
normalization of surround inhibition and to thereby see whether a dysfunctional
surround inhibition can be considered causal for the dystonic movement in
writerscramp.
Primary measurements are therefore measurements of surround inhibtion (measured
by the making of a simple hand movement after an auditory cue) and writing
before and after repetitive TMS over the premotor cortex. We will record the
cortical excitability profile of these patients in addition.

TMS is currently a frequent applied method in neuroscience. Our department is
well experienced in TMS research. Important is identification of
contra-indications for his method. With TMS the main contraindication is
epilepsy, risks are minimal with the greatest risk being occurrence of an
epileptic insult. There is however worldwide regular appliance of TMS and the
latest recorded epileptic insult dates from 1998. Dystonia is an infrequent
movement disorder and we therefore ask relative small groups of patients and
controls to participate. Patients and controls will be invited to the hospital
on a single occasion where the research project will take place in
approximately 60-90 minutes. The research question is relevant and a
significant gain in the understanding of writer*s cramp can be obtained. The
benefit of this study outweighs therefore the effort taken by the
participants.