A. Nuara

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study.

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinsons disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. OBJECTIVE To evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. METHODS Twenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. RESULTS No drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P < 0.0001). CONCLUSIONS High-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

Deep Repetitive Transcranial Magnetic Stimulation With H-coil on Lower Limb Motor Function in Chronic Stroke: A Pilot Study

OBJECTIVES To assess the efficacy of high-frequency (20 Hz) brain stimulation on lower limb motor function in subjects with chronic (> 6 mo) subcortical stroke. DESIGN Double-blind, placebo-controlled crossover study. SETTING University hospital. PARTICIPANTS Right-handed subjects (N=10) affected by a first-ever subcortical stroke in the territory of the middle cerebral artery were included in this study. INTERVENTIONS Repetitive transcranial magnetic stimulation (rTMS) was delivered with the H-coil, specifically designed to target deeper and larger brains regions. Each subject received both real and sham rTMS in a random sequence. The 2 rTMS cycles (real or sham) were composed of 11 sessions each, administered over 3 weeks and separated by a 4-week washout period. MAIN OUTCOME MEASURES Lower limb functions were assessed by the lower limb Fugl-Meyer scale, the 10-m walk test, and the 6-minute walk test before and 1 day after the end of each treatment period, as well as at a 4-week follow-up. RESULTS Real rTMS treatment was associated with a significant improvement in lower limb motor function. This effect persisted over time (follow-up) and was significantly greater than that observed with sham stimulation. A significant increase in walking speed was also found after real rTMS, but this effect did not reach statistical significance in comparison with the sham stimulation. CONCLUSIONS These data demonstrated that 3 weeks of high-frequency deep rTMS could induce long-term improvements in lower limb functions in the chronic poststroke period, lasting at least 1 month after the end of the treatment.

Excitatory Deep Transcranial Magnetic Stimulation With H-Coil Over the Right Homologous Broca’s Region Improves Naming in Chronic Post-stroke Aphasia:

Background. The role of the right hemisphere in poststroke aphasia recovery is still controversial and the effects of repetitive transcranial magnetic stimulation (rTMS) over the right homologous Broca’s region have been seldom investigated. Objective. This study aimed to compare the effect of excitatory, inhibitory, and sham rTMS delivered with H-coil over the right inferior frontal gyrus in chronic aphasic patients. Methods. Five right-handed poststroke aphasic patients underwent a picture naming task before and immediately after each of 3 sessions of rTMS: excitatory (10 Hz), inhibitory (1 Hz), and sham rTMS, in random sequence and separated by at least 1 week. Results. Only the excitatory 10-Hz stimulation was associated with a significant improvement in naming performance (P = .043) and was significantly more effective than 1-Hz rTMS (P = .043). Conclusions. A single session of excitatory deep brain rTMS over the right inferior frontal gyrus with H-coil significantly improves naming in right-handed chronic poststroke aphasic patients. This result is in line with the hypothesis of a positive, rather than detrimental, role of the right hemisphere in chronic aphasia due to a left-hemispheric stroke.

P19.19 Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied with H-coil for chronic migraine prophylaxis

Introduction: We investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on corticomotor excitability (CE), motor behavior, and mood in patients with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Repetitive TMS has not been investigated systematically in PSP or CBD patients. PSP and CBD share bradykinetic-rigid features of Parkinson’s disease. PSP and CBD show a high incidence of frontal dysfunction and depression; CBD is dominated by asymmetric limb apraxia and dystonia. Objectives: We hypothesized that rTMS over primary motor cortex (M1rTMS) would affect CE and motor behavior while rTMS over dorsolateral prefrontal cortex (DLPFC-rTMS) would affect mood. Patients were randomized to receive M1-rTMS, DLPFC-rTMS, or sham-rTMS at 90% motor threshold in 3 sessions with assessments before vs. after stimulation. 5 CBD patients received 1 Hz-rTMS (for dystonia) and 10 PSP patients received 5 Hz-rTMS (for akinesia-rigidity) over M1 contralateral to the more symptomatic limb. All patients received 5 Hz-rTMS over left DLPFC. Methods: CE was assessed with resting motor thresholds (rMT) and motor evoked potential amplitudes (MEP); motor behavior assessed with maximal (MAX) and comfortable (COM) tapping speed; mood assessed with visual analog scales. Results: (1) In PSP, 5 Hz rTMS over M1 did not improve tapping speeds, (2) rTMS over left DLPFC showed a trend towards improvement of overall wellness (p = 0.07, 2-tailed), a protocol comparable with rTMS use for depression, (3) rTMS over M1 in PSP did not significantly modify MEP amplitude. We found no significant differences in rMT in PSP patients vs healthy controls; CBD patients may have higher motor thresholds compared to healthy controls (p = 0.028), but was limited in CBD patients due to high rMT. Conclusions: These preliminary results provide support to further explore high-frequency left DLPFC rTMS for affective symptoms. Higher frequency rTMS over M1 or higher intensity stimulation may be needed to demonstrate changes in CE. Alternative strategies for addressing high rMT in CBD patients may be needed for applying rTMS.

Cortical Motor Circuits after Piano Training in Adulthood: Neurophysiologic Evidence

The neuronal mechanisms involved in brain plasticity after skilled motor learning are not completely understood. We aimed to study the short-term effects of keyboard training in music-naive subjects on the motor/premotor cortex activity and interhemispheric interactions, using electroencephalography and transcranial magnetic stimulation (TMS). Twelve subjects (experimental group) underwent, before and after a two week-piano training: (1) hand-motor function tests: Jamar, grip and nine-hole peg tests; (2) electroencephalography, evaluating the mu rhythm task-related desynchronization (TRD) during keyboard performance; and (3) TMS, targeting bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), to obtain duration and area of ipsilateral silent period (ISP) during simultaneous tonic contraction of APB and ADM. Data were compared with 13 controls who underwent twice these measurements, in a two-week interval, without undergoing piano training. Every subject in the experimental group improved keyboard performance and left-hand nine-hole peg test scores. Pre-training, ISP durations were asymmetrical, left being longer than right. Post-training, right ISPAPB increased, leading to symmetrical ISPAPB. Mu TRD during motor performance became more focal and had a lesser amplitude than in pre-training, due to decreased activity over ventral premotor cortices. No such changes were evidenced in controls. We demonstrated that a 10-day piano-training was associated with balanced interhemispheric interactions both at rest and during motor activation. Piano training, in a short timeframe, may reshape local and inter-hemispheric motor cortical circuits.

Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.

Anti-GAD antibody-positive myoclonic leg jerks

High levels of autoantibodies directed against glutamic acid decarboxylase (GAD) are associated with stiff-person syndrome (SPS). However, other neurological syndromes have been described in association with anti-GAD antibodies, defining a novel group of syndromes, collectively named ‘‘hyperexcitability disorders’’. Here, we describe a patient complaining for acute onset of involuntary jerk movements in his legs, associated with pathologically increased level of anti-GAD antibodies.

Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response

Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the diseases course.

P568: Multimodal evoked potentials in predicting response to immunomodulating treatment in multiple sclerosis

S.-M. Kim1, S.-Y. Park2, J.Y. Kim3, J.-J. Sung1, K.S. Park3, O. Kwon4, S.H. Kim5, J. Park5, K.-W. Lee1 1Seoul Nationl University Hospital, Neurology, Seoul, Republic of Korea; 2National cancer center, Neurology, Seoul, Republic of Korea; 3Seoul National University, Bundang Hospital, Neurology, Gyeonggi, Republic of Korea; 4Eulji General Hospital, Neurology, Seoul, Republic of Korea; 5Seoul National University Hospital, Medical Research Collaborating Center, Seoul, Republic of Korea

P569: Corticospinal reserve predicts the effect of deep repetitive brain stimulation with h-coil and neurorehabilitation on walking impairment in progressive multiple sclerosis: results from two randomized, double blind studies

S.-M. Kim1, S.-Y. Park2, J.Y. Kim3, J.-J. Sung1, K.S. Park3, O. Kwon4, S.H. Kim5, J. Park5, K.-W. Lee1 1Seoul Nationl University Hospital, Neurology, Seoul, Republic of Korea; 2National cancer center, Neurology, Seoul, Republic of Korea; 3Seoul National University, Bundang Hospital, Neurology, Gyeonggi, Republic of Korea; 4Eulji General Hospital, Neurology, Seoul, Republic of Korea; 5Seoul National University Hospital, Medical Research Collaborating Center, Seoul, Republic of Korea