In this case, TMS over the motor cortex and the cerebellum had an immediate and cumulative effect not just for ataxia, but also for diplopia. To the best of our knowledge, this is the first report in which TMS improved diplopia in a SCA6 patient.
Especially, diplopia improved immediately after localized, one-side (right side), stimulation (with a Figure-8 coil) over the motor cortex. In addition, the intensity of the stimulation over the cerebellum was comparatively weak compared to previous reports [4,5,6] and the patient was conscious of the improvement immediately after stimulation of the motor cortex. Therefore, we considered that the improvement was mainly due to stimulation over the motor cortex.
In this case, since vertical misalignment (especially for the upper-right gaze) and the upper-right diplopia spot tended to remain after stimulation, we considered that this ophthalmoparesis was the main cause of diplopia. To detect changes associated with this ophthalmoparesis objectively, we used a Hess chart examination and video recordings before and after TMS. However, we could not identify any significant changes. It is possible that the oculomotor changes were too small to be identified with these instruments or the improvement of diplopia may have been due to some cause other than oculomotor changes.
Several possible mechanisms could account for this diplopia-improvement with TMS. First, we can speculate that the excitability of the cerebellum changed with TMS over the motor cortex, which might induce oculomotor changes. Previous studies have shown that there are neural networks between the cerebral cortex and the cerebellum [9, 10], and that TMS over the motor cortex increases bilateral cerebellar blood flow [11, 12]. Increased blood flow may be associated with the excitability of the cerebellum. Since the cerebellum has efferent fibers to the vestibular nucleus (part of the neural integrator) which is connected to the oculomotor nucleus , the increased cerebellar excitability might regulate these connections and lead to some oculomotor improvement. The incidence of ophthalmoparesis in SCA6 patients has been reported to range from less than 10% to about 50% [1, 14]. In a prospective multicenter study, the frequency of ophthalmoparesis in SCA6 patients with diplopia was lower than those in other SCAs; 43% of SCA6 patients had diplopia, and 4 and 14% of these patients showed horizontal and vertical ophthalmoparesis, respectively . These results suggest that, in addition to ophthalmoparesis, diplopia may be related to other oculomotor disorders, particularly in SCA6 patients. In SCA6 patients, gaze-evoked nystagmus (GEN), dysmetric saccade (hyper > hypo), smooth pursuit, square-wave jerks, and other forms of nystagmus (rebound, periodic alternating, and downbeat nystagmus) have been reported [1,2,3, 9, 14]. Among these disorders, our patient had GEN, hypermetric saccade, smooth pursuit disorder, and rebound nystagmus. Since diplopia appeared with lateral eye fixation in this case, GEN was a plausible cause. Since nystagmus could induce diplopia  as well as oscillopsia, the improvement of GEN might lead to the improvement of diplopia. However, we could not detect a change in GEN with our video recordings. Although we did not detect changes in GEN objectively with our limited instruments, we might have been able to detect changes if we had assessed oculomotor movement in detail with the use of electrooculograms, nystagmography, 3D eye-tracking, etc.
Second, the frontal eye field (FEF) might have been stimulated in this patient. The FEF projects to the superior colliculus in the midbrain, where ocular movement signals are assumed to be integrated . Since the FEF is believed to be relatively close to the primary motor cortex , the stimulus might have spread there and indirectly affected ocular movement and gazes. Interestingly, TMS over the FEF has been reported to facilitate saccades and visual cognition [16, 18]. It is possible that these factors might have contributed to the improvement of diplopia.
Third, previous studies have shown that a complicated brain network (including the frontal, parietal, occipital, and temporal lobules) is related to binocular fusion . The stimulus could have affected this network, and the change in binocular fusion (especially in sensory fusion) might have induced the improvement in diplopia. For a more detailed assessment of fusion, the Worth Four Dot test and Titmus stereo test should have been done.
In the current case, the cause of diplopia was not detected with our limited instruments, and the improvement in diplopia was based on a subjective and quantitative evaluation. It would have been better if we could clarify the cause of diplopia and demonstrate that diplopia had indeed improved by an objective and qualitative evaluation.