Op-brai140322 1..5

Sir, There has been a growing interest in the role of the cerebellum in primary dystonia. Although this role is not yet fully understood (Sadnicka et al., 2012), an elegant paper by Hubsch et al. (2013) in Brain showed that in writer’s cramp, a form of task-specific primary hand dystonia, the cerebellum has lost its ability to modulate sensorimotor plasticity of the motor cortex. As part of their study, they used the paired-associative stimulation protocol, a transcranial magnetic stimulation-based intervention to induce motor cortex plasticity, combined with either intermittent or continuous theta burst stimulation (TBS) over the cerebellum. Neither form of cerebellar TBS induced any change of the paired-associative stimulation effect in patients with writer’s cramp as opposed to control subjects. The authors hypothesized that this suggests that the cerebellum has lost its effect on some relevant sensorimotor integrative functions and/or that the continuously hyperactive state of the cerebellum renders it refractory to TBS. We wish to build on this by sharing our results of a cerebellar, single session TBS intervention study in patients with writer’s cramp, specifically designed to address the question whether such an intervention has any effect on dystonia severity and writing performance. The reason for this was that, based on the growing body of evidence of this role of the cerebellum in dystonia, many have already speculated on the cerebellum being a putative target for neuromodulatory interventions in dystonia. More specifically, the quite robust finding of cerebellar hyperactivity in dystonia led to the idea that applying transcranial cerebellar inhibition might have therapeutic effects. Ten patients (nine right-handed and one left-handed) with writer’s cramp were included. All but one received both continuous TBS and sham TBS with an interval of 3 months, to exclude any carryover effect. The subjects were randomized between the two groups: first continuous TBS or first sham TBS. One patient only received the real stimulation. Two healthy individuals were asked to perform the same tasks as the writer’s cramp group, mainly to see whether our kinematic writing analyses indeed detected the expected baseline abnormalities in the patients with writer’s cramp. Transcranial magnetic stimulation was delivered through a C-B60 figure-8 coil (MagVenture) connected to a Magpro-X-100 stimulator. First, the active motor threshold was determined over the hotspot, the optimal site of the magnetic coil for eliciting motor evoked potentials, in the right first dorsal interosseus muscle (or left in the one patient with left-sided writer’s cramp). Active motor threshold was defined as the minimum stimulator intensity required to obtain motor evoked potentials with an amplitude of at least 200mV in at least 5 of 10 trails while the subject maintained a low-level tonic contraction (10% of maximal voluntary contraction) in right first dorsal interosseus. We used the continuous TBS protocol, which has been proven to effectively suppress the cerebellum activity. Continuous TBS was applied at 80% of the active motor threshold over doi:10.1093/brain/awu321 BRAIN 2014: Page 1 of 5 | e1