Cerebellar Repetitive Transcranial Magnetic Stimulation Research Articles

Cerebellar rTMS for Enhancing Coordination in Patients with Multiple Sclerosis: A Narrative Review

Purpose of Review: Cerebellar repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential therapeutic intervention for neurological disorders. Recently, there has been growing interest in its use to improve coordination in patients with multiple sclerosis (PwMS). This review aims to examine and discuss the current evidence on the effectiveness of cerebellar rTMS in enhancing motor coordination in individuals with MS. Methods: A comprehensive search of Science Direct, PubMed, and Google Scholar was conducted using keywords such as multiple sclerosis, cerebellar repetitive transcranial magnetic stimulation, coordination, and neurorehabilitation. Articles published from January 2012 to July 2024 were included, and only English-language studies were reviewed. Unpublished manuscripts, conference abstracts, and studies not involving larger scientific investigations were excluded. Results: The findings suggest that cerebellar rTMS, when combined with conventional rehabilitation methods, has the potential to improve coordination in PwMS. However, the available evidence is limited, and larger, more rigorous studies are needed to confirm these findings and establish standardized treatment protocols. Conclusion: Current literature indicates that cerebellar rTMS holds promise as a supplementary intervention for improving coordination in PwMS. Further high-quality trials are required to support its clinical application and to better understand the underlying mechanisms.

Effects of cerebellar repetitive transcranial magnetic stimulation plus physiotherapy in spinocerebellar ataxias - A randomized clinical trial.

In absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols. In this randomized sham controlled clinical trial, patients were assigned to verum (n = 15) or sham (n = 18) cerebellar transcranial magnetic stimulation. To yield best possible treatment effects, both intervention groups received intensified physiotherapy for the duration of the study. Ataxia severity was reduced by 1.6 points on the Scale for assessment and Rating of Ataxia among patients in the verum group (p < 0.001). Clinical improvement was significantly larger in the verum group, compared to the sham group (p < 0.01). The treatment effect was mainly carried by improved appendicular coordination. Patients in the verum group also significantly improved in the 8 Meter Walk Test (p < 0.05) and PATA rate (p < 0.01). Cerebellar rTMS ameliorates ataxia severity in patient with spinocerebellar ataxia. Condensing treatment duration to only 5 days without reduction of treatment effects facilitates applicability and therefore broadens availability to larger patient populations.

Cerebellar repetitive transcranial magnetic stimulation has no effect on contraction-induced facilitation of corticospinal excitability.

This study aimed to investigate whether the cerebellum contributes to contraction-induced facilitation (CIF) of contralateral corticospinal excitability. To this end, repetitive cerebellar transcranial magnetic stimulation (TMS) was used to test whether it modulates CIF. Overall, 20 healthy young individuals participated in the study. Single-pulse TMS was applied to the left primary motor cortex to induce motor-evoked potentials (MEP) on electromyography of the right first dorsal interosseous (FDI) muscle to test corticospinal excitability. This measurement was conducted during contraction (10% maximum voluntary contraction [MVC]) and rest (0% MVC) of the FDI muscle. CIF, cerebellar brain inhibition (CBI), cortical silent period (cSP), and resting motor threshold (rMT) were measured before and after low-frequency repetitive TMS (crTMS) of the right cerebellum to downregulate cerebellar output. The CIF (contraction/rest of the MEP), CBI (conditioned/unconditioned MEP) during contraction, cSP, and rMT were not affected by crTMS. At rest, CBI was decreased. These findings indicated that the primary motor cortex function for the increase in corticospinal excitability was not affected by crTMS. This study contributes to our understanding of the role of the cerebellum in motor control. Additionally, it may inform decision-making for the site of cerebellar ataxia treatment using non-invasive brain stimulation.

C-STIM: Protocol for a randomized, single-blind, crossover study of cerebellar repetitive transcranial magnetic stimulation (rTMS) for postural instability in people with progressive supranuclear palsy (PSP)

BackgroundMethods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP. MethodsThirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis. DiscussionThe C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

Effect of cerebellar transcranial magnetic stimulation with double-cone coil on dysphagia after subacute infratentorial stroke: A randomized, single-blinded, controlled trial

BackgroundA 10-Hz cerebellar repetitive transcranial magnetic stimulation (rTMS) could increase corticobulbar tract excitability in healthy individuals. However, its clinical efficacy for poststroke dysphagia (PSD) remains unclear. ObjectiveTo investigate the effectiveness of 10-Hz cerebellar rTMS in PSD patients with infratentorial stroke (IS). MethodsIn this single-blinded, randomized controlled trial, 42 PSD patients with subacute IS were allocated to three groups: bilateral cerebellar rTMS (biCRB-rTMS), unilateral cerebellar rTMS (uniCRB-rTMS), or sham-rTMS. The stimulation parameters were 5 trains of 50 stimuli at 10 Hz with an interval of 10 s at 90% of the thenar resting motor threshold (RMT). The Functional Oral Intake Scale (FOIS) was assessed at T0 (baseline), T1 (day 0 after intervention), and T2 (day 14 after intervention), whereas the Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and neurophysiological parameters were evaluated at T0 and T1. ResultsSignificant time and intervention interaction effects were observed for the FOIS score (F = 3.045, p = 0.022). The changes in the FOIS scores at T1 and T2 were both significantly higher in the biCRB-rTMS group than in the sham-rTMS group (p < 0.05). The uniCRB-rTMS and biCRB-rTMS groups demonstrated greater changes in the DOSS and PAS at T1, compared with the sham-rTMS group (p < 0.05). Bilateral corticobulbar tract excitability partly increased in the biCRB-rTMS and uniCRB-rTMS groups at T1, compared with T0. The percent changes in corticobulbar tract excitability parameters at T1 showed no difference among three groups. ConclusionsA 10-Hz bilateral cerebellar rTMS is a promising, noninvasive treatment for subacute infratentorial PSD.

Effects of bilateral cerebellar repetitive transcranial magnetic stimulation in poststroke dysphagia: A randomized sham-controlled trial.

Although increasing evidence indicates that cerebellar repetitive transcranial magnetic stimulation (rTMS) may be beneficial in the treatment of dysphagia, its clinical efficacy is still uncertain. To evaluate the effect of high-frequency cerebellar rTMS on poststroke dysphagia. This was a randomized, sham-controlled, double-blind trial. A total of eighty-four study participants were randomly assigned into the cerebellum and control groups. The cerebellum group received bilateral 10 Hz rTMS treatment of the pharyngeal motor area of the cerebellum. The control group was administered with sham rTMS of the pharyngeal motor area of the cerebellum. All patients underwent the same conventional swallowing rehabilitation training after the intervention 5 days a week for a total of 10 days. Assessment of swallowing function was done before treatment (baseline), after treatment (2 weeks), and during follow-up (2 weeks after treatment) using the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and the Penetration-Aspiration Scale (PAS). The interaction between time and intervention had a significant effect on PAS (P < 0.001) and FEDSS (P < 0.001). Compared to the control group, the cerebellum group exhibited significantly improved clinical swallowing function scores (PAS: P = 0.007, FEDSS: P = 0.002). Bilateral cerebellar rTMS is a potential new neurorehabilitation technique for post-stroke dysphagia. Studies should aim at investigating the therapeutic mechanism of cerebellar rTMS and improve this technique.

Effect of Low Frequency Cerebellar Repetitive Transcranial Magnetic Stimulation on Balance Impairment in Patients With Cerebral Infarction.

To investigate the effect of low frequency cerebellar repetitive transcranial magnetic stimulation (rTMS) on balance impairment in patients with cerebral infarction. Thirty-two patients were randomly divided into two groups: rTMS group (n=16) and control (n=16). In the rTMS group, treatment was performed five times per week for 2 weeks (10 sessions), and in the control group, a sham coil was used with the sound and sensation of scalp similar to the rTMS coil. Patients in both groups underwent a conventional rehabilitation program. Berg Balance Scale (BBS) was used as the primary outcome measurement. Timed Up and Go test (TUG), 10-m walk test (10mWT), and Activity-specific Balance Confidence scale (ABC) were used as the secondary outcome measurement. All scales were measured at baseline (T0), after 10 sessions of rTMS (T1), and at 4 weeks after treatment completion (T2) by therapists with over 5 years of clinical experience. There were significant improvements between T0 and T1, and between T0 and T2, for all assessed items in the rTMS group. Whereas there were significant improvements between T0 and T1, and between T0 and T2, for the BBS and 10mWT in the control group. TUG (-4.87±5.05 vs. -0.50±2.97 seconds) and ABC score (8.10±8.33 vs. 0.16±0.97) were observed significant differences in comparison of the changes from T0 to T1 between the two group. BBS score (4.40±3.66 vs. 1.88±3.14), TUG (-4.87±4.56 vs. -0.62±2.96 seconds) and ABC score (8.22±7.70 vs. -0.09±0.86) differed significantly from T0 to T2 between the two groups. Our findings suggest that low-frequency cerebellar rTMS is helpful for improving balance in patients with cerebral infarction, and maybe a beneficial treatment for these patients.

Cerebellar repetitive transcranial magnetic stimulation modulates the motor learning of visually guided voluntary postural control task

We investigated whether vermal cerebellar low-frequency repetitive transcranial magnetic stimulation (crTMS) affects motor learning of visually guided postural tracking training (VTT) using foot center of pressure (COP) as well as the stability and sensory contribution of upright standing. Twenty-one healthy volunteers participated (10 in the sham-crTMS group and 11 in the active-crTMS group). For VTT, participants stood on the force plate 1.5 m from the monitor on which the COP and target moved in a circle. Participants tracked the target with their own COP for 1 min, and 10 VTT sessions were conducted. The tracking error (TE) was compared between trials. Active- or sham-crTMS sessions were conducted prior to VTT. At baseline (before crTMS), pre-VTT (after crTMS), and post-VTT, the COP trajectory during upright static standing under four conditions (eyes, open/closed; surface, hard/rubber) was recorded. Comparison of the length of the COP trajectory or path and sensory-contribution-rate showed no significant difference between baseline and pre- and post-VTT. There was a significant decrease in TE in the sham-crTMS but not in the active-crTMS group. VTT and crTMS did not immediately affect the stability and sensory contribution of upright standing; however, crTMS immediately affected motor learning. The vermal cerebellum may contribute to motor learning of voluntary postural control.

Baseline Cerebro-Cerebellar Functional Connectivity in Afferent and Efferent Pathways Reveal Dissociable Improvements in Visuomotor Learning.

Visuomotor coordination is a complex process involving several brain regions, primarily the cerebellum and motor cortex. Studies have shown inconsistent resting-state functional magnetic resonance imaging (rsfMRI) results in the cerebellar cortex and dentate nucleus of the cerebro-cerebellar connections. Echoing anatomical pathways, these two different cerebellar regions are differentially responsible for afferent and efferent cerebro-cerebellar functional connections. The aim of this study was to measure the baseline resting-state functional connectivity of different cerebellar afferent and efferent pathways and to investigate their relationship to visuomotor learning abilities. We used different cerebellar repetitive transcranial magnetic stimulation (rTMS) frequencies before a pursuit rotor task to influence visuomotor performance. Thirty-eight right-handed participants were included and randomly assigned to three different rTMS frequency groups (1 Hz, 10 Hz and sham) and underwent baseline rsfMRI and pursuit rotor task assessments. We report that greater baseline functional connectivity in the afferent cerebro-cerebellar pathways was associated with greater accuracy improvements. Interestingly, lower baseline functional connectivity in the efferent dentato-thalamo-cortical pathways was associated with greater stability in visuomotor performance, possibly associated with the inhibitory role of the dentate nucleus and caused a reduction in the efferent functional connectivity. The functional dissociation of the cerebellar cortex and dentate nucleus and their connections, suggests that distinct mechanisms in the cerebellum regarding visuomotor learning, which should be investigated in future research.

The Effect of Cerebellar Repetitive Transcranial Magnetic Stimulation on Dysphagia due to Posterior Circulation Stroke, a Randomized Controlled Trial Protocol

Introduction: Cerebellum might be active during the task of swallowing. Little is known whether cerebellar repetitive transcranial magnetic stimulation (rTMS) could improve post-stroke dysphagia (PSD) due to occlusion in the posterior circulation. This paper describes the rationale and design of a randomized controlled trial that aims to determine the effect of cerebellar rTMS on dysphagia due to posterior circulation stroke. Methods and Analysis: Thirty patients with PSD due to occlusion in the posterior circulation will be randomly divided to receive real (n = 20) or sham (n = 10) cerebellar rTMS. Patients in the real rTMS group will receive 250 pulses rTMS at a low intensity with 10 Hz frequency for 10 days (five consecutive days per week). The severity of dysphagia will be assessed with videofluoroscopic swallowing study (VFSS) using the Rosenbek penetration aspiration scale (PAS), the pharyngeal constriction ratio (PCR), and the dysphagia outcome and severity scale (DOSS) before and immediately after the last session and then again after 1 and 3 months. The functional magnetic resonance imaging (fMRI) will be assessed before and after the last session and then again after 1 month and 3 months. The primary outcome is the improvement of swallowing function determined by PAS, PCR, and DOSS. The secondary outcomes include changes in brain connectivity network detected using fMRI. Discussion: This study will determine whether cerebellar rTMS improves dysphagia due to posterior circulation stroke in Chinese patients. Our findings will contribute to a new approach for swallowing function recovery after posterior circulation stroke.

Cerebellar Repetitive Transcranial Magnetic Stimulation and Noisy Galvanic Vestibular Stimulation Change Vestibulospinal Function.

BackgroundThe cerebellum strongly contributes to vestibulospinal function, and the modulation of vestibulospinal function is important for rehabilitation. As transcranial magnetic stimulation (TMS) and electrical stimulation may induce functional changes in neural systems, we investigated whether cerebellar repetitive TMS (crTMS) and noisy galvanic vestibular stimulation (nGVS) could modulate vestibulospinal response excitability. We also sought to determine whether crTMS could influence the effect of nGVS.MethodsFifty-nine healthy adults were recruited; 28 were randomly allocated to a real-crTMS group and 31 to a sham-crTMS group. The crTMS was conducted using 900 pulses at 1 Hz, while the participants were in a static position. After the crTMS, each participant was allocated to either a real-nGVS group or sham-nGVS group, and nGVS was delivered (15 min., 1 mA; 0.1–640 Hz) while patients were in a static position. The H-reflex ratio (with/without bilateral bipolar square wave pulse GVS), which reflects vestibulospinal excitability, was measured at pre-crTMS, post-crTMS, and post-nGVS.ResultsWe found that crTMS alone and nGVS alone have no effect on H-reflex ratio but that the effect of nGVS was obtained after crTMS.ConclusioncrTMS and nGVS appear to act as neuromodulators of vestibulospinal function.

The effects of unilateral and bilateral cerebellar rTMS on human pharyngeal motor cortical activity and swallowing behavior

The cerebellum is recognised to bilaterally modulate sensorimotor function and has recently been shown to play a role in swallowing. Unilateral cerebellar repetitive trans-cranial magnetic stimulation (rTMS) excites corticobulbar motor pathways to the pharynx but the effects of bilateral versus unilateral cerebellar rTMS on these pathways are unknown. In this three-part cross-over study, healthy participants (n = 13) were randomly allocated to receive unilateral or bilateral 10 Hz cerebellar rTMS. Participants were intubated with pharyngeal electromyography and/or manometry catheters for motor evoked potentials (MEPs) and pressure recordings. In part 1 of the study, single pulse TMS was used to measure baseline motor cortical pharyngeal MEP (PMEP) and hemispheric cerebellar MEP (CMEP) amplitudes, before cerebellar rTMS was administered. Repeat measures of PMEP amplitude were performed at 15-min intervals for an hour post unilateral and bilateral rTMS. Thereafter, in two further studies, a cortical ‘virtual lesion’ (V/L) was applied prior to cerebellar rTMS with pre and post PMEPs (part 2) and measurements of swallowing accuracy (part 3) using a behavioural task. Compared to baseline, unilateral and bilateral cerebellar rTMS provoked increases in pharyngeal cortical excitation (P = 0.028, 0.0005, respectively). Bilateral rTMS was significantly more effective than unilateral in causing cortical excitation (P = 0.0005) and in reversing the suppressive neurological (P = 0.0005) and behavioural (P = 0.0005) effects of a cortical V/L. Our findings suggest bilateral cerebellar rTMS has greater facilitatory effects on corticobulbar motor pathways to the pharynx than unilateral stimulation with the potential to be a more effective clinical therapy if its effects are reproduced in populations with neurogenic dysphagia.

Cerebellum-mediated trainability of eye and head movements for dynamic gazing.

ObjectiveTo investigate whether gaze stabilization exercises (GSEs) improve eye and head movements and whether low-frequency cerebellar repetitive transcranial magnetic stimulation (rTMS) inhibits GSE trainability.Methods25 healthy adults (real rTMS, n = 12; sham rTMS, n = 13) were recruited. Real or sham rTMS was performed for 15 min (1 Hz, 900 stimulations). The center of the butterfly coil was set 1 cm below the inion in the real rTMS. Following stimulation, 10 trials of 1 min of a GSE were conducted at 1 min intervals. In the GSE, the subjects were instructed to stand upright and horizontally rotate their heads according to a beeping sound corresponding to 2 Hz and with a gaze point ahead of them. Electrooculograms were used to estimate the horizontal gaze direction of the right eye, and gyroscopic measurements were performed to estimate the horizontal head angular velocity during the GSE trials. The percentage change from the first trial of motion range of the eye and head was calculated for each measurement. The percent change of the eye/head range ratio was calculated to assess the synchronous changes of the eye and head movements as the exercise increased.ResultsBayesian two-way analysis of variance showed that cerebellar rTMS affected the eye motion range and eye/head range ratio. A post hoc comparison (Bayesian t-test) showed evidence that the eye motion range and eye/head range ratio were reduced in the fifth, sixth, and seventh trials compared with the first trial sham stimulation condition.ConclusionsGSEs can modulate eye movements with respect to head movements, and the cerebellum may be associated with eye–head coordination trainability for dynamic gazing during head movements.

Cerebellar repetitive transcranial magnetic stimulation (rTMS) for essential tremor: A double-blind, sham-controlled, crossover, add-on clinical trial

BackgroundThere is controversial evidence about the effect of cerebellar low-frequency stimulation in patients with essential tremor (ET). ObjectivesIn this study we assessed safety and effectiveness of 1 Hz (low-frequency) cerebellar repetitive transcranial magnetic stimulation (rTMS) on tremor severity in patients with essential tremor in a sham-controlled crossover trial. MethodsA total of 23 patients assigned into two groups to receive either sham (n = 10) or rTMS (n = 13) treatment, with crossing over after a two-month washout period. Intervention consisted of 900 pulses of 1 Hz rTMS at 90% resting motor threshold or the same protocol of sham stimulation over each cerebellar hemisphere for 5 consecutive days. Tremor severity was assessed by Fahn-Tolosa-Marin (FTM) scale at baseline and at days 5, 12 and 30 after intervention. The FTM consists of 3 subscales including tremor severity rating, performance of motor tasks, and functional disability. Carry-over and treatment effects were analyzed using independent samples t-test. ResultsThere was no significant improvement in the total FTM scores in rTMS compared to the sham stimulation on day 5 (p = 0.132), day 12 (p = 0.574), or day 30 (p = 0.382). Similarly, FTM subscales, including tremor severity rating, motor tasks, and functional disability did not improve significantly after rTMS treatment. Mild headache and local pain were the most frequent adverse events. ConclusionAlthough cerebellar rTMS seems to have acceptable safety when used in ET patients, this study could not prove any efficacy for it in reduction of tremor in these patients. Larger studies are needed to evaluate efficacy of this therapeutic intervention and to provide evidence about the optimal stimulation parameters.

Cerebellar repetitive transcranial magnetic stimulation restores pharyngeal brain activity and swallowing behaviour after disruption by a cortical virtual lesion.

Key points Despite evidence that the human cerebellum has an important role in swallowing neurophysiology, the effects of cerebellar stimulation on swallowing in the disrupted brain have not been explored.In this study, for the first time, the application of cerebellar neurostimulation is characterized in a human model of disrupted swallowing (using a cortical virtual lesion).It is demonstrated that cerebellar stimulation can reverse the suppressed activity in the cortical swallowing system and restore swallowing function in a challenging behavioural task, suggesting the findings may have important therapeutic implications. Repetitive transcranial magnetic stimulation (rTMS) can alter neuronal activity within the brain with therapeutic potential. Low frequency stimulation to the ‘dominant’ cortical swallowing projection induces a ‘virtual‐lesion’ transiently suppressing cortical excitability and disrupting swallowing behaviour. Here, we compared the ability of ipsi‐lesional, contra‐lesional and sham cerebellar rTMS to reverse the effects of a ‘virtual‐lesion’ in health. Two groups of healthy participants (n = 15/group) were intubated with pharyngeal catheters. Baseline pharyngeal motor evoked potentials (PMEPs) and swallowing performance (reaction task) were measured. Participants received 10 min of 1 Hz rTMS to the pharyngeal motor cortex which elicited the largest PMEPs to suppress cortical activity and disrupt swallowing behaviour. Over six visits, participants were randomized to receive 250 pulses of 10 Hz cerebellar rTMS to the ipsi‐lesional side, contra‐lesional side or sham while assessing PMEP amplitude or swallowing performance for an hour afterwards. Compared to sham, active cerebellar rTMS, whether administered ipsi‐lesionally (P = 0.011) or contra‐lesionally (P = 0.005), reversed the inhibitory effects of the cortical ‘virtual‐lesion’ on PMEPs and swallowing accuracy (ipsi‐lesional, P < 0.001, contra‐lesional, P < 0.001). Cerebellar rTMS was able to reverse the disruptive effects of a ‘virtual lesion’. These findings provide evidence for developing cerebellar rTMS into a treatment for post‐stroke dysphagia.

Cerebellar repetitive transcranial magnetic stimulation for patients with essential tremor

IntroductionThe possibility of repetitive transcranial magnetic stimulation (rTMS) as an alternative therapy for essential tremor (ET) patients has emerged. However, its effect on medicated ET patients is lacking. The aim of this pilot study was to investigate the effect of cerebellar low-frequency rTMS as an “add-on” treatment. MethodsIn this single-blinded, randomized, sham-controlled pilot study, patients with ET were randomized into two groups, one receiving real-rTMS and the other sham-rTMS. For 5 days, 1200 stimulations per day were applied to the bilateral cerebellar hemispheres at an intensity of 90% of the resting motor threshold (RMT) with a frequency of 1-Hz. Motor evoked potentials (MEPs) and the Fahn-Tolosa-Marin tremor rating scales (TRS) were measured before, immediately, and 4 weeks after the completion of the rTMS procedures. All patients continued taking medications during all procedures. ResultsAmong 22 patients, 12 and 10 patients were randomized into the real- and sham-rTMS groups, respectively. Repeated analysis of variance (ANOVA) measurements showed that the total TRS, TRS-A and B were changed both in real and sham-rTMS groups without interaction between time and group. TRS-C and MEPs, were not significantly changed at each follow-up point in either the real or sham-rTMS sessions. ConclusionWe conclude that cerebellar low-frequency rTMS is safe, but has no significant effect as an “add-on” therapy in patients with ET.

Abstract WP195: Cerebellar Magnetic Stimulation for Long-Lasting Dizziness After Brainstem Stroke

Introduction: Brainstem stroke sometimes causes long-lasting dizziness. A cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been postulated as a mechanism of dizziness in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for long-lasting post-brainstem stroke dizziness. Methods: We first applied cerebellar rTMS in healthy volunteers (n=11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, we enrolled 11 patients with long-lasting post-brainstem stroke dizziness (lateral medullary infarction, 9; lateral pontine infarction, 1; and lateral pontine hemorrhage, 1), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. Results: After rTMS, DHI scores were significantly reduced with disappearance or attenuation of the ipsilesional nystagmus characteristic of the long-lasting post-brainstem stroke dizziness. Reduction in the absolute VOR gain was also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem, measured in 4 patients, was increased. However, the effects of cerebellar rTMS did not always persist. Conclusion: Our study showed the potential efficacy of cerebellar rTMS for treatment of long-lasting post-brainstem stroke dizziness. Further large-scale randomized studies are warranted to confirm our findings.

Effects of cerebellar magnetic stimulation on chronic post-lateral medullary infarction dizziness: A proof-of-principle cohort study

Background and purposeLateral medullary infarction (LMI) sometimes causes long-lasting dizziness. Although the precise mechanism of chronic post-LMI dizziness is unknown, a cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been reported in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for chronic post-LMI dizziness. MethodsWe first applied cerebellar rTMS in healthy volunteers (n = 11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, between September and December 2015, we enrolled six patients (aged≥20 years) with chronic post-LMI dizziness (duration≥6 months), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for up to 25 months for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. ResultsFour of the six patients completed the study without complications. After rTMS, DHI scores were reduced (mean pre-rTMS DHI score minus post-rTMS DHI score was 13.0 [P = 0.036]) with disappearance of the ipsilesional nystagmus characteristic of the post-LMI dizziness. Reduction in the absolute VOR gain (mean pre- rTMS gain minus post-rTMS gain in the ipsilesional direction was 0.135 [P = 0.036] and that in the contralesional direction was 0.137 [P = 0.031]) were also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem was increased in four of five patients. The effects of cerebellar rTMS did not always persist, and three of four patients elected to undergo more than one rTMS series. The repeat cerebellar rTMS treatments had same beneficial effects. ConclusionOur study showed, for the first time, the potential efficacy of cerebellar rTMS for treatment of chronic post-LMI dizziness. The short duration of the cerebellar rTMS effects can be compensated for by repeating the rTMS treatment every few months. Further large-scale randomized studies are warranted to confirm our findings.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation

This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

F149. Low-frequency repetitive transcranial cerebellar magnetic stimulation as an ‘Add-On’ therapy in patients with essential tremor

Introduction ET is a common movement disorder. It is not life threatening, but it can significantly impair patients’ activities of daily living. Beta-blockers and primidone have been used as the treatment of choice for patients with ET. However, up to 50% of ET patients report that they are not satisfied with the improvement of tremor symptoms by these medications. We investigated effect of cerebellar low-frequency repetitive transcranial magnetic stimulation (rTMS) as an ‘add-on’ treatment on patients with Essential tremor (ET). Methods This was a single-center, prospective, sham-controlled and single-blinded study. Fourteen ET patients participated. ET was diagnosed when the patient had bilateral postural or kinetic tremor of the arms, no dystonia and no possibility of drug-induced secondary tremor. In addition, we included subjects in this study only if they had residual significant tremor despite beta-blockers and other drugs as symptomatic management. Subjects were randomized into a group receiving real-rTMS and another group receiving sham-rTMS. rTMS was applied over each side of the cerebellum in turn. The order of the stimulation to each side was randomly assigned. For 5 days, 600 stimulations a day were applied with an intensity of 90% of the resting motor threshold (RMT) with 1-Hz frequency. Clinical tremor rating scale (CTRS) was measured before, a week and 5 weeks after starting day of the rTMS procedure. Results Eight and 6 patients were randomized to the groups of real and sham-rTMS, respectively. The mean age, symptoms duration and baseline CTRS scores were comparable. ANOVA analysis showed that all three parts (A, B and C) of CTRS were not different before, a week and 5 weeks after starting rTMS procedure both in real and sham-rTMS groups. There were no adverse events including headache, dizziness, syncope and seizure. Conclusion Cerebellar low-frequency rTMS is safe but not effective as an ‘add-on’ therapy in patients with ET.